QSim, a program for NMR simulations

We present QSim, a program for simulation of NMR experiments. Pulse sequences are implemented and analyzed in QSim using a mouse driven interface. QSim can handle almost any modern NMR experiment, using multiple channels, shaped pulses, mixing, decoupling, phase-cycling and pulsed field gradients. Any number of spins with any spin quantum number can, in theory, be used in simulations. Relaxation is accounted for during all steps of pulse sequences and relaxation interference effects are supported. Chemical kinetics between any numbers of states can be simulated. Both classical and quantum mechanical calculations can be performed. The result of a simulation can be presented either as magnetization as a function of time or as a processed spectrum.     

Thermal force approach to molecular evolution

Recent experiments are discussed where temperature gradients across mesoscopic pores are shown to provide essential mechanisms for autonomous molecular evolution. On the one hand, laminar thermal convection can drive DNA replication as the molecules are continuously cycled between hot and cold regions of a chamber. On the other hand, thermophoresis can accumulate charged biopolymers in similar convection settings. The experiments show that temperature differences analogous to those across porous rocks present a robust nonequilibrium boundary condition to feed the replication and accumulation of evolving molecules. It is speculated that similar nonequilibrium conditions near porous submarine hydrothermal mounds could have triggered the origin of life. In such a scenario, the encapsulation of cells with membranes would be a later development. It is expected that detailed studies of mesoscopic boundary conditions under nonequilibrium conditions will reveal new connecting pieces in the fascinating puzzle of the origins of life.     

Energetics of an rf SQUID Coupled to Two Thermal Reservoirs

We study energetics of a Josephson tunnel junction connecting a superconducting loop pierced by an external magnetic flux (an rf SQUID) and coupled to two independent thermal reservoirs of different temperature. In the framework of the theory of quantum dissipative systems, we analyze energy currents in stationary states. The stationary energy flow can be periodically modulated by the external magnetic flux exemplifying the rf SQUID as a quantum heat interferometer. We also consider the transient regime and identify three distinct regimes: monotonic decay, damped oscillations and pulse-type behavior of energy currents. The first two regimes can be controlled by the external magnetic flux while the last regime is robust against its variation.     

Modeling Free Energy Availability from Hadean Hydrothermal Systems to the First Metabolism

Off-axis Hydrothermal Systems (HSs) are seen as the possible setting for the emergence of life. As the availability of free energy is a general requirement to drive any form of metabolism, we ask here under which conditions free energy generation by geologic processes is greatest and relate these to the conditions found at off-axis HSs. To do so, we present a conceptual model in which we explicitly capture the energetics of fluid motion and its interaction with exothermic reactions to maintain a state of chemical disequilibrium. Central to the interaction is the temperature at which the exothermic reactions take place. This temperature not only sets the equilibrium constant of the chemical reactions and thereby the distance of the actual state to chemical equilibrium, but these reactions also shape the temperature gradient that drives convection and thereby the advection of reactants to the reaction sites and the removal of the products that relate to geochemical free energy generation. What this conceptual model shows is that the positive feedback between convection and the chemical kinetics that is found at HSs favors a greater rate of free energy generation than in the absence of convection. Because of the lower temperatures and because the temperature of reactions is determined more strongly by these dynamics rather than an external heat flux, the conditions found at off-axis HSs should result in the greatest rates of geochemical free energy generation. Hence, we hypothesize from these thermodynamic considerations that off-axis HSs seem most conducive for the emergence of protometabolic pathways as these provide the greatest, abiotic generation rates of chemical free energy.     

Effects of moderate heat stress on photosynthesis: importance of thylakoid reactions, rubisco deactivation, reactive oxygen species, and thermotolerance provided by isoprene

Photosynthesis is particularly sensitive to heat stress and recent results provide important new insights into the mechanisms by which moderate heat stress reduces photosynthetic capacity. Perhaps most surprising is that there is little or no damage to photosystem II as a result of moderate heat stress even though moderate heat stress can reduce the photosynthetic rate to near zero. Moderate heat stress can stimulate dark reduction of plastoquinone and cyclic electron flow in the light. In addition, moderate heat stress may increase thylakoid leakiness. At the same time, rubisco deactivates at moderately high temperature. Relationships between effects of moderate heat on rubisco activation and thylakoid reactions are not yet clear. Reactive oxygen species such as H₂O₂ may also be important during moderate heat stress. Rubisco can make hydrogen peroxide as a result of oxygenase side reactions and H₂O₂ production by rubisco was recently shown to increase substantially with temperature. The ability to withstand moderately high temperature can be improved by altering thylakoid lipid composition or by supplying isoprene. In my opinion this indicates that thylakoid reactions are important during moderate heat stress. The deactivation of rubisco at moderately high temperature could be a parallel deleterious effect or a regulatory response to limit damage to thylakoid reactions.     

Study of thermal properties and heat-induced denaturation and aggregation of soy proteins by modulated differential scanning calorimetry

The thermal properties and heat-induced denaturation and aggregation of soy protein isolates (SPI) were studied using modulated differential scanning calorimetry (MDSC). Reversible and non-reversible heat flow signals were separated from the total heat flow signals in the thermograms. In the non-reversible profiles, two major endothermic peaks (at around 100 and 220 degrees C, respectively) associated with the loss of residual water were identified. In the reversible profiles, an exothermic peak associated with thermal aggregation was observed. Soy proteins denatured to various extents by heat treatments showed different non-reversible and reversible heat flow patterns, especially the exothermic peak. The endothermic or exothermic transition characteristics in both non-reversible and reversible signals were affected by the thermal history of the samples. The enthalpy change of the exothermic (aggregation) peak increased almost linearly with increase in relative humidity (RH) in the range between 8 and 85%. In contrast, the onset temperature of the exotherm decreased progressively with increase in RH. These results suggest that the MDSC technique could be used to study thermal properties and heat-induced denaturation/aggregation of soy proteins at low moisture contents. Associated functional properties such as water holding and hydration property can also be evaluated.     

Validation of a model describing two-dimensional heat transfer during solid-state fermentation in packed bed bioreactors

A two-dimensional heat transfer model was validated against two experimental studies from the literature which describe the growth of Aspergillus niger during solid-state fermentation in packed bed bioreactors. With the same set of model parameters, the two-dimensional model was able to describe both radial temperature gradients, which dominated in one of the studies, and axial temperature gradients, which dominated in the other study. The sensitivity of the model predictions to the characteristics of the substrate and the microbe were explored. The temperatures reached in the column are most sensitive to parameters which affect the peak heat load, including the substrate packing density, the maximum specific growth rate, and the maximum biomass concentration. Even though the bed is assumed to be aerated with saturated air, the increase in temperature with bed height increases the water-carrying capacity of the air and therefore enables evaporation to contribute significantly to cooling. The model suggests that evaporation can remove as much as 78% of the heat from the bed during times of peak heat generation. Our model provides a tool which can guide the design and operation of packed bed bioreactors. However, further improvements are necessary to do this effectively, the most important of which is the incorporation of a water balance.     

Quantum corrections to the particle distribution function and reaction rates in dense media

Quantum mechanics predicts the existence of power-law tails in the momentum distribution function of particles in dense media even under conditions of thermodynamic equilibrium. The generalized expressions allowing for the effect of the medium density show that quantum corrections lead to a sharp increase in the reaction rates of threshold exothermic processes (such as fusion and chemical reactions and vibrational-translational relaxation). The accompanying modification of the distribution function changes the wings of the emission and absorption lines. The profiles of the absorption lines in dense gaseous media are shown to be asymmetric with respect to the line center.     

Calorimetric detection of curvature strain in phospholipid bilayers.

Phospholipids in biological membranes are arranged as bilayers. When constrained to pack into planar bilayers, certain phospholipids will form unstable structures as a consequence of their molecular shape and noncovalent bonding. This produces curvature strain which may provide energy for certain membrane processes. We demonstrate that an exothermic process associated with the relief of curvature strain can be detected calorimetrically. The enthalpy for the incorporation of a few percent lysophosphatidylcholine into large unilamellar vesicles of monomethyldioleoylphosphatidylethanolamine at pH 7.4 is exothermic but it is endothermic for stable bilayers such as this same lipid at pH 9 or dioleoylphosphatidylcholine at pH 7.4 or 9. The addition of lysophosphatidylcholine to monomethyldioleoylphosphatidylethanolamine at pH 7.4 is exothermic only for the addition of the first few percent of lysophosphatidylcholine and then it becomes endothermic. The size of the exothermic heat change is sensitive to changes in temperature, while the endothermic processes are relatively temperature-insensitive. The exothermic heat is also larger when 1 or 2 mol % of diolein is incorporated into vesicles of monomethyldioleoylphosphatidylethanolamine. These results are all consistent with the exothermic process corresponding to the relief of curvature strain in bilayers having a tendency to convert to the hexagonal phase. It provides a demonstration that considerable energy may be released upon the incorporation of certain molecules into membranes which have a low radius of spontaneous curvature.     

The potential for establishment of axial temperature profiles during solid-state fermentation in rotating drum bioreactors

The mixing and heat transfer phenomena within rotating drum bioreactors (RDBs) used for solid-state fermentation processes are poorly studied. The potential for the establishment of axial temperature gradients within the substrate bed was explored using a heat transfer model. For growth of Aspergillus oryzae on wheat bran within a 24 L RDB with air at a superficial velocity of 0.0023 m s(-1) and 15% relative humidity, the model predicts an axial gradient between the air inlet and outlet of 2 degrees C during rapid growth, compared to experimental axial temperature gradients of between 1 and 4 degrees C. Undesirably high temperatures occur throughout the bed under these operating conditions, but the model predicts that good temperature control can be achieved using humid air (90% relative humidity) at superficial velocities of 1 m s(-1) for a 204 L RDB. For a 2200 L RDB, good temperature control is predicted with superficial velocities as low as 0.4 m s(-1) with the airflow being switched from 90% to 15% relative humidity whenever the temperature at the outlet end of the drum exceeds the optimal temperature for growth. This work suggests that significant axial temperature gradients can arise in those RDBs that lack provision for axial mixing. It is therefore advisable to use angled lifters within RDBs to promote axial mixing.     

Thermally driven fission of protocells

We propose a simple mechanism for the self-replication of protocells. Our main hypothesis is that the amphiphilic molecules composing the membrane bilayer are synthesized inside the protocell through exothermic chemical reactions. The slow increase of the inner temperature forces the hottest molecules to move from the inner leaflet to the outer leaflet of the bilayer. Because of this outward translocation flow, the outer leaflet grows faster than the inner leaflet. This differential growth increases the mean curvature and amplifies any local shrinking of the protocell until it splits in two. The proposed model, based on mere laws of physics, is a step in the study of the origin of life, as well as a clue for a better understanding of cell proliferation in cancer.     

Thermodynamics in the present progressive mode and its role in the context of the origin of life.

The origin and evolution of biological organizations proceeding on Earth are put in a nonequilibrium thermodynamic framework within a cosmological context. The dynamic process responsible for chemical evolution leading to the origin of biological being depends upon consumer-dominating thermodynamics, in which the heat sink is taken to be active in extracting heat energy from a body at a higher temperature. Consumer-dominating thermodynamics follows from the fact that when a small hot body contacts a cold heat sink, it decreases the temperature at the possible fastest rate. The fastest temperature drop, when applied to chemical products being synthesized through the energy supplied from an external heat source, is selective in keeping only those products that can decrease the temperature at the fastest rate among the available alternatives. Synthesis of small organic molecules in the small ice grains in interstellar diffuse clouds irradiated by ultraviolet radiation is a representative case of consumer-dominating thermodynamics, in which diffuse clouds serve as cold heat sinks in the cosmological context. Another case of consumer-dominating thermodynamics predominant on Earth especially in the perspective of the origin and evolution of life is with submarine hydrothermal vents, in which the surrounding cold seawater constantly serves as the cold heat sink.     

Simple chemical tools to expand the range of proteomics applications

Proteomics is an expanding technology with potential applications in many research fields. Even though many research groups do not have direct access to its main analytical technique, mass spectrometry, they can interact with proteomics core facilities to incorporate this technology into their projects. Protein identification is the analysis most frequently performed in core facilities and is, probably, the most robust procedure. Here we discuss a few chemical reactions that are easily implemented within the conventional protein identification workflow. Chemical modification of proteins with N-hydroxysuccinimide esters, 4-sulfophenyl isothiocyanate, O-methylisourea or through β-elimination/Michael addition can be easily performed in any laboratory. The reactions are quite specific with almost no side reactions. These chemical tools increase considerably the number of applications and have been applied to characterize protein-protein interactions, to determine the N-terminal residues of proteins, to identify proteins with non-sequenced genomes or to locate phosphorylated and O-glycosylated.     

Hydrothermal Reactions of Pyruvic Acid: Synthesis,Selection, and Self-Assembly of Amphiphilic Molecules

Selection and self-assembly of organic compounds in aqueous phases must have been a primary process leading to emergent molecular complexity and ultimately to the origin of life. Facile reactions of pyruvic acid under hydrothermal conditions produce a complex mixture of larger organic molecules, some of which are amphiphiles that readily self-assemble into cell-sized vesicular structures. Chemical characterization of major components of this mixture reveals similarities to the suite of organic compounds present in the Murchison carbonaceous chondrite, some of whose molecules also self-assemble into membranous vesicles. Physical properties of the products are thus relevant to understanding the prebiotic emergence of molecular complexity. These results suggest that a robust family of prebiotic reaction pathways produces similar products over a range of geochemical and astrochemical environments.     

Simulation and investigation of quantum dot effects as internal heat-generator source in breast tumor site

The Pennes bio-heat transfer equation, which introduces the exchange magnitude of heat transfer between tissue and blood, is often used to solve the temperature distribution for thermal imaging and sensing. Near-infrared light has the ability to be used as a non-invasive means of diagnostic imaging within the woman's breast. Due to the diffusive nature of light in different tissue, computational model-based methods are required for functional imaging within the breast. In this article, the time-dependent bio-heat transfer is solved by a numerical method. In our model, the heat generation source (intrinsic and extrinsic) involves laser, metabolism, and quantum dot that the metabolism and heat generated by QDs are considered as intrinsic. We supposed the injected quantum dots would target the tumor site by a passive targeting process and then by interaction of laser radiation and quantum dot, the photoluminescence of quantum dot is converted to heat in the tumor site. The extra generated heat can impact on the extracted heat profile. One of the important applications of this research has led to a sensitivity improvement of the imaging system, which is potentially useful in the diagnosis and detection of breast cancer.     

Thermodynamics of the binding of human apolipoprotein A-I to dimyristoylphosphatidylglycerol

The interaction of human serum apolipoprotein A-I with dimyristoylphosphatidylglycerol was analyzed by isothermal titration calorimetry. Binding of the apolipoprotein A-I to large unilamellar vesicles of dimyristoylphosphatidylglycerol, a negatively charged phospholipid, is characterized by thermodynamic parameters which are invariant over the 30-40 degrees C temperature range. The enthalpy change resulting from the first additions of lipid are positive and decline in magnitude with subsequent additions of lipid. After several additions of lipid, the sign of the enthalpy changes to negative and then reaches a constant value/injection. This exothermic process is larger and opposite in sign to the heat of dilution. Similar behavior is also observed when the lipid is in the form of a dispersion in distilled water. Only a non-saturable exothermic process is observed at 30 degrees C with large unilamellar vesicles of the zwitterionic lipid, dimyristoylphosphatidylcholine. The beginning of an exothermic process can also be observed prior to the larger endotherm in the first injections of large unilamellar vesicles of dimyristoylphosphatidylglycerol into the protein. We analyze the enthalpy changes for the reaction of dimyristoylphosphatidylglycerol with the protein as arising from two distinct processes, one endothermic and the other exothermic. The binding isotherms for the high affinity binding of the apolipoprotein A-I to large unilammelar vesicles of dimyristoylphosphatidylglycerol, over the temperature range 30-40 degrees C, gave an enthalpy change of 1.43 +/- 0.07 kcal/mol of protein and a free energy change of -5.91 +/- 0.04 kcal/mol of protein for the binding of the protein to a cluster of 25 +/- 2 lipid molecules. Thus this reaction is entropically driven.     

Energy Transduction Inside of Amphiphilic Vesicles: Encapsulation of Photochemically Active Semiconducting Particles

Amphiphilic bilayer membrane structures (vesicles) have been postulated to have been abiotically formed and spontaneously assemble on the prebiotic Earth, providing compartmentalization for the origin of life. These vesicles are similar to modern cellular membranes and can serve to contain water-soluble species, concentrate species, and have the potential to catalyze reactions. The origin of the use of photochemical energy in metabolism (i.e. energy transduction) is one of the central issues in the origin of life. This includes such questions as how energy transduction may have occurred before complex enzymatic systems, such as required by contemporary photosynthesis, had developed and how simple a photochemical system is possible. It has been postulated that vesicle structures developed the ability to capture and transduce light, providing energy for reactions. It has also been shown that pH gradients across the membrane surface can be photochemically created, but coupling these to drive chemical reactions has been difficult. Colloidal semiconducting mineral particles are known to photochemically drive redox chemistry. We propose that encapsulation of these particles has the potential to provide a source of energy transduction inside vesicles, and thereby drive protocellular chemistry, and represents a model system for early photosynthesis. In our experiments we show that TiO₂ particles, in the ~20 nm size range, can be incorporated into vesicles and retain their photoactivity through the dehydration/rehydration cycles that have been shown to concentrate species inside a vesicle.     

Noise reduction in the intracellular pom1p gradient by a dynamic clustering mechanism

Chemical gradients can generate pattern formation in biological systems. In the fission yeast Schizosaccharomyces pombe, a cortical gradient of pom1p (a DYRK-type protein kinase) functions to position sites of cytokinesis and cell polarity and to control cell length. Here, using quantitative imaging, fluorescence correlation spectroscopy, and mathematical modeling, we study how its gradient distribution is formed. Pom1p gradients exhibit large cell-to-cell variability, as well as dynamic fluctuations in each individual gradient. Our data lead to a two-state model for gradient formation in which pom1p molecules associate with the plasma membrane at cell tips and then diffuse on the membrane while aggregating into and fragmenting from clusters, before disassociating from the membrane. In contrast to a classical one-component gradient, this two-state gradient buffers against cell-to-cell variations in protein concentration. This buffering mechanism, together with time averaging to reduce intrinsic noise, allows the pom1p gradient to specify positional information in a robust manner.     

Experimental study on characteristic of bioheat transfer and numerical simulation for the temperature fields in transverse and longitudinal sections of pig tongue

The influence factors of the tongue tissue structure on the temperature fields are importantly laid on the diameters and positions of arteries. Then temperature fields of certain sections are simulated by the finite element method (FEM). The results show that temperature gradients of the tongue in length are wider than in depth as a result of the specific vascularity. Thereby the relationship between temperature fields of tongue surface and those in transverse and longitudinal sections can be developed. This work will be further referential to study on the characteristics of heat transfer in human tongue, and will promote the development of bioheat transfer science.     

Equipment-Free Incubation of Recombinase Polymerase Amplification Reactions Using Body Heat

The development of isothermal amplification platforms for nucleic acid detection has the potential to increase access to molecular diagnostics in low resource settings; however, simple, low-cost methods for heating samples are required to perform reactions. In this study, we demonstrated that human body heat may be harnessed to incubate recombinase polymerase amplification (RPA) reactions for isothermal amplification of HIV-1 DNA. After measuring the temperature of mock reactions at 4 body locations, the axilla was chosen as the ideal site for comfortable, convenient incubation. Using commonly available materials, 3 methods for securing RPA reactions to the body were characterized. Finally, RPA reactions were incubated using body heat while control RPA reactions were incubated in a heat block. At room temperature, all reactions with 10 copies of HIV-1 DNA and 90% of reactions with 100 copies of HIV-1 DNA tested positive when incubated with body heat. In a cold room with an ambient temperature of 10 degrees Celsius, all reactions containing 10 copies or 100 copies of HIV-1 DNA tested positive when incubated with body heat. These results suggest that human body heat may provide an extremely low-cost solution for incubating RPA reactions in low resource settings.