The effect of ionic redistributions on the microwave dielectric response of cytosol water upon glucose uptake.

The sensitivity of cytosol water's microwave dielectric (MD) response to D-glucose uptake in Red Blood Cells (RBCs) allows the detailed study of cellular mechanisms as a function of controlled exposures to glucose and other related analytes like electrolytes. However, the underlying mechanism behind the sensitivity to glucose exposure remains a topic of debate. In this research, we utilize MDS within the frequency range of 0.5-40 GHz to explore how ionic redistributions within the cell impact the microwave dielectric characteristics associated with D-glucose uptake in RBC suspensions. Specifically, we compare glucose uptake in RBCs exposed to the physiological concentration of Ca2+ vs. Ca-free conditions. We also investigate the potential involvement of Na+/K+ redistribution in glucose-mediated dielectric response by studying RBCs treated with a specific Na+/K+ pump inhibitor, ouabain. We present some insights into the MD response of cytosol water when exposed to Ca2+ in the absence of D-glucose. The findings from this study confirm that ion-induced alterations in bound/bulk water balance do not affect the MD response of cytosol water during glucose uptake.

Microwave Dielectric Response of Bovine Milk as Pregnancy Detection Tool in Dairy Cows.

The most reliable methods for pregnancy diagnosis in dairy herds include rectal palpation, ultrasound examination, and evaluation of plasma progesterone concentrations. However, these methods are expensive, labor-intensive, and invasive. Thus, there is a need to develop a practical, non-invasive, cost-effective method that can be implemented on the farm to detect pregnancy. This study suggests employing microwave dielectric spectroscopy (MDS, 0.5-40 GHz) as a method to evaluate reproduction events in dairy cows. The approach involves the integration of MDS data with information on milk solids to detect pregnancy and identify early embryonic loss in dairy cows. To test the ability to predict pregnancy according to these measurements, milk samples were collected from (i) pregnant and non-pregnant randomly selected cows, (ii) weekly from selected cows (n = 12) before insemination until a positive pregnancy test, and (iii) daily from selected cows (n = 10) prior to insemination until a positive pregnancy test. The results indicated that the dielectric strength of Δε and the relaxation time, τ, exhibited reduced variability in the case of a positive pregnancy diagnosis. Using principal component analysis (PCA), a clear distinction between pregnancy and nonpregnancy status was observed, with improved differentiation upon a higher sampling frequency. Additionally, a neural network machine learning technique was employed to develop a prediction algorithm with an accuracy of 73%. These findings demonstrate that MDS can be used to detect changes in milk upon pregnancy. The developed machine learning provides a broad classification that could be further enhanced with additional data.

The inhibition of glucose uptake to erythrocytes: microwave dielectric response.

Dielectric spectroscopy has been used in the study and development of non-invasive glucose monitoring (NIGM) sensors, including the range of microwave frequencies. Dielectric relaxation of red blood cell (RBC) cytosolic water in the microwave frequency band has been shown to be sensitive to variations in the glucose concentration of RBC suspensions. It has been hypothesized that this sensitivity stems from the utilization of D-glucose by RBCs. To verify this proposition, RBCs were pretreated with inhibitors of D-glucose uptake (cytochalasin B and forskolin). Then their suspensions were exposed to different D-glucose concentrations as measured by microwave dielectric spectroscopy (MDS) in the 500 MHz-40 GHz frequency band. After incubation of RBCs with either inhibitor, the dielectric response of water in the cytoplasm, and specifically its relaxation time, demonstrated minimal sensitivity to the change of D-glucose concentration in the medium. This result allows us to conclude that the sensitivity of MDS to glucose uptake is associated with variations in the balance of bulk and bound RBC cytosolic water due to intracellular D-glucose metabolism, verifying the correctness of the initial hypothesis. These findings represent a further argument to establish the dielectric response of water as a marker of glucose variation in RBCs.

The dielectric response of hydrated water as a structural signature of nanoconfined lichen melanins.

Lichens are unique symbiotic organisms from a mutually beneficial alliance of fungi and algae/cyanobacteria that successfully survive extreme temperatures and drought conditions. Most probably such extraordinary vitality of lichens is underlain by melanins, one of the main structural and chemical lichen components, and their mutual relationship with residual water. In this paper, we propose mechanisms, which allow lichens to store up the extra water in their structure. Melanins that are constituents of the cortical lichen layer and presumably contribute to unique water-lichen interactions are chosen for physical experiments in a wide temperature domain. Two melanin pigments extracted from different lichens are studied here - eumelanin from Lobaria pulmonaria and allomelanin from Cetraria islandica. To investigate the inner melanin structure and water-melanin interactions, FTIR and BDS techniques are applied. The BDS technique was used in a wide temperature region of 123-293 K for melanins with various hydration levels. The relaxation processes related to the confinement of supercooled water - in melanins are observed and discussed in details. At medium and high hydration levels, the relaxation process in two melanins of different chemical compositions and supramolecular structures exhibits a well-known crossover that was already observed in many types of confinements. The analysis of FTIR and BDS results helps to clarify the lichen-water interaction processes.

Hydration of methemoglobin studied by in silico modeling and dielectric spectroscopy.

The hemoglobin concentration of 35 g/dl of human red blood cells is close to the solubility threshold. Using microwave dielectric spectroscopy, we have assessed the amount of water associated with hydration shells of methemoglobin as a function of its concentration in the presence or absence of ions. We estimated water-hemoglobin interactions to interpret the obtained data. Within the concentration range of 5-10 g/dl of methemoglobin, ions play an important role in defining the free-to-bound water ratio competing with hemoglobin to recruit water molecules for the hydration shell. At higher concentrations, hemoglobin is a major contributor to the recruitment of water to its hydration shell. Furthermore, the amount of bound water does not change as the hemoglobin concentration is increased from 15 to 30 g/dl, remaining at the level of ∼20% of the total intracellular water pool. The theoretical evaluation of the ratio of free and bound water for the hemoglobin concentration in the absence of ions corresponds with the experimental results and shows that the methemoglobin molecule binds about 1400 water molecules. These observations suggest that within the concentration range close to the physiological one, hemoglobin molecules are so close to each other that their hydration shells interact. In this case, the orientation of the hemoglobin molecules is most likely not stochastic, but rather supports partial neutralization of positive and negative charges at the protein surface. Furthermore, deformation of the red blood cell shape results in the rearrangement of these structures.

Physiological Monitoring and Hearing Loss: Toward a More Integrated and Ecologically Validated Health Mapping.

With an ongoing shift from managing disease toward the inclusion of maintaining health and preventing disease, the world has seen the rise of increasingly sophisticated physiological monitoring and analytics. Innovations range from wearables, smartphone-based spot monitoring to highly complex noncontact, remote monitoring, utilizing different mechanisms. These tools empower the individual to better navigate their own health. They also generate powerful insights towards the detection of subclinical symptoms or processes via existing and novel digital biomarkers. In that context, a topic that is receiving increasing interest is the modulation of human physiology around an individual "baseline" in everyday life and the impact thereof on other sensorineural body functions such as hearing. More and more fully contextualized and truly long-term physiological data are becoming available that allows deeper insights into the response of the human body to our behavior, immediate environment and the understanding of how chronic conditions are evolving. Hearing loss often goes hand in hand with chronic conditions, such as diabetes, cognitive impairment, increased risk of fall, mental health, or cardiovascular risk factors. This inspires an interest to not only look at hearing impairment itself but to take a broader view, for example, to include contextualized vital signs. Interestingly, stress and its physiological implications have also been shown to be a relevant precursor to hearing loss and other chronic conditions. This article deduces the requirements for wearables and their ecosystems to detect relevant dynamics and connects that to the need for more ecologically valid data towards an integrated and more holistic mapping of hearing characteristics.

Dielectric spectra broadening as a signature for dipole-matrix interactions. V. Water in protein solutions.

In this paper, the fifth of our series focused on the dielectric spectrum symmetrical broadening of water, we consider the solutions of methemoglobin (MetHb) in pure water and in phosphate-buffered saline (PBS). The universal character of the Cole-Cole dielectric response, which reflects the interaction of water dipoles with solute molecules, was described in Paper I [E. Levy et al., J. Chem. Phys. 136, 114502 (2012)]. It enables the interpretation of the dielectric data of MetHb solutions in a unified manner using the previously developed 3D trajectory method driven by the protein concentration. It was shown that protein hydration is determined by the interaction of water dipoles with the charges and dipoles located on the rough surfaces of the protein macromolecules. In the case of the buffered solution, the transition from a dipole-charged to a dipole-dipole interaction with the protein concentration is observed {see Paper III [A. Puzenko et al., J. Chem. Phys. 137, 194502 (2012)]}. A new approach is proposed for evaluating the amount of hydration water molecules bounded to the macromolecule that takes into account the number of positive and negative charges on the protein's surface. In the case of the MetHb solution in PBS, the hydration of the solvent ions and their interaction with charges on the protein's surface are also taken into consideration. The difference in hydration between the two solutions of MetHb is discussed.

Oxygenation state of hemoglobin defines dynamics of water molecules in its vicinity.

This study focuses on assessing the possible impact of changes in hemoglobin (Hb) oxygenation on the state of water in its hydration shell as it contributes to red blood cell deformability. Microwave Dielectric Spectroscopy (MDS) was used to monitor the changes in interactions between water molecules and Hb, the number of water molecules in the protein hydration shell, and the dynamics of pre-protein water in response to the transition of Hb from the tense (T) to the relaxed (R) state, and vice versa. Measurements were performed for Hb solutions of different concentrations (5 g/dl-30 g/dl) in phosphate-buffered saline buffer. Cole-Cole parameters of the main water relaxation peak in terms of interactions of water molecules (dipole-dipole/ionic dipole) during the oxygenation-deoxygenation cycle were used to analyze the obtained data. The water mobility-represented by α as a function of ln τ-differed dramatically between the R (oxygenated) state and the T (deoxygenated) state of Hb at physiologically relevant concentrations (30 g/dl-35 g/dl or 4.5 mM-5.5 mM). At these concentrations, oxygenated hemoglobin was characterized by substantially lower mobility of water in the hydration shell, measured as an increase in relaxation time, compared to deoxyhemoglobin. This change indicated an increase in red blood cell cytosolic viscosity when cells were oxygenated and a decrease in viscosity upon deoxygenation. Information provided by MDS on the intraerythrocytic water state of intact red blood cells reflects its interaction with all of the cytosolic components, making these measurements powerful predictors of the changes in the rheological properties of red blood cells, regardless of the cause.

Water in the hydrated protein powders: Dynamic and structure.

It is not an understatement to say that the interplay between water and protein is a fundamental aspect of life. The vitality of an organism depends on the functionality of its biological machinery, and this, in turn, is mediated in water. Yet, we understand surprisingly little about the nature of the interface between bulk water and the protein. On the one hand, we know that the nature of the bulk water is dominated by the existence of H-bonding and H-bonded networks. On the other hand, the protein surface, where much of the bioactivity is centered, is a complex landscape of hydrophilic and hydrophobic elements. So how does the interface between these two entities work and how do they influence each other? The question is important because if one understands how a particular protein interface influences the dynamics of the water, it then becomes an easily accessible marker for similar behavior in other protein systems. The dielectric relaxation of hydrated proteins with different structures, lysozyme, collagen, and phycocyanin, has been reviewed in this paper. The dynamics of hydrated water was analyzed in terms of orientation and the ionic defect migration model. This approach enables to characterize the microscopic relaxation mechanism of the dynamics of hydration water on the different structures of the protein. In addition, our model is also capable of characterizing not only hydrated proteins but also polymer-water systems.

The human skin as a sub-THz receiver - Does 5G pose a danger to it or not?

In the interaction of microwave radiation and human beings, the skin is traditionally considered as just an absorbing sponge stratum filled with water. In previous works, we showed that this view is flawed when we demonstrated that the coiled portion of the sweat duct in upper skin layer is regarded as a helical antenna in the sub-THz band. Experimentally we showed that the reflectance of the human skin in the sub-THz region depends on the intensity of perspiration, i.e. sweat duct's conductivity, and correlates with levels of human stress (physical, mental and emotional). Later on, we detected circular dichroism in the reflectance from the skin, a signature of the axial mode of a helical antenna. The full ramifications of what these findings represent in the human condition are still unclear. We also revealed correlation of electrocardiography (ECG) parameters to the sub-THz reflection coefficient of human skin. In a recent work, we developed a unique simulation tool of human skin, taking into account the skin multi-layer structure together with the helical segment of the sweat duct embedded in it. The presence of the sweat duct led to a high specific absorption rate (SAR) of the skin in extremely high frequency band. In this paper, we summarize the physical evidence for this phenomenon and consider its implication for the future exploitation of the electromagnetic spectrum by wireless communication. Starting from July 2016 the US Federal Communications Commission (FCC) has adopted new rules for wireless broadband operations above 24 GHz (5 G). This trend of exploitation is predicted to expand to higher frequencies in the sub-THz region. One must consider the implications of human immersion in the electromagnetic noise, caused by devices working at the very same frequencies as those, to which the sweat duct (as a helical antenna) is most attuned. We are raising a warning flag against the unrestricted use of sub-THz technologies for communication, before the possible consequences for public health are explored.

A Study of Moisture Sorption and Dielectric Processes of Starch and Sodium Starch Glycolate : Theme: Formulation and Manufacturing of Solid Dosage Forms Guest Editors: Tony Zhou and Tonglei Li.

PURPOSE: This study explored the potential of combining the use of moisture sorption isotherms and dielectric relaxation profiles of starch and sodium starch glycolate (SSG) to probe the location of moisture in dried and hydrated samples. METHODS: Starch and SSG samples, dried and hydrated, were prepared. For hydrated samples, their moisture contents were determined. The samples were probed by dielectric spectroscopy using a frequency band of 0.1 Hz to 1 MHz to investigate their moisture-related relaxation profiles. The moisture sorption and desorption isotherms of starch and SSG were generated using a vapor sorption analyzer, and modeled using the Guggenheim-Anderson-de Boer equation. RESULTS: A clear high frequency relaxation process was detected in both dried and hydrated starches, while for dried starch, an additional slower low frequency process was also detected. The high frequency relaxation processes in hydrated and dried starches were assigned to the coupled starch-hydrated water relaxation. The low frequency relaxation in dried starch was attributed to the local chain motions of the starch backbone. No relaxation process associated with water was detected in both hydrated and dried SSG within the frequency and temperature range used in this study. The moisture sorption isotherms of SSG suggest the presence of high energy free water, which could have masked the relaxation process of the bound water during dielectric measurements. CONCLUSION: The combined study of moisture sorption isotherms and dielectric spectroscopy was shown to be beneficial and complementary in probing the effects of moisture on the relaxation processes of starch and SSG.

The low-temperature dynamic crossover in the dielectric relaxation of ice Ih.

Based on the idea of defect migration as the principal mechanism in the dielectric relaxation of ice Ih, the concept of low-temperature dynamic crossover was proposed. It is known that at high temperatures, the diffusion of Bjerrum and ionic defects is high and their movement may be considered to be independent. Simple switching between these two mechanisms leads to a dynamic crossover at ∼235 K. By introducing coupling between the Bjerrum and ionic defects, it is possible to describe the smooth bend in the relaxation time at low temperatures in ice Ih. However, because the mobility of Bjerrum orientation defects slows down at low temperatures, they may create blockages for proton hopping. The trapping of ionic defects by L-D defects for a long period of time leads to an increase in the relaxation time and causes a low-temperature crossover. This model was validated by experimental dielectric measurements using various temperature protocols.

Confined water dynamics in a hydrated photosynthetic pigment-protein complex.

Water is of fundamental importance for life. It plays a critical role in all biological systems. In phycocyanin, a pigment-protein complex, the hydration level influences its absorption spectrum. However, there is currently a gap in the understanding of how protein interfaces affect water's structure and properties. This work presents combined dielectric and calorimetric measurements of hydrated phycocyanin with different levels of hydration in a broad temperature interval. Based on the dielectric and calorimetric tests, it was shown that two types of water exist in the phycocyanin hydration shell. One is confined water localized inside the phycocyanin ring and the second is the water that is embedded in the protein structure and participates in the protein solvation. The water confined in the phycocyanin ring melts at the temperature 195 ± 3 K and plays a role in the solvation at higher temperatures. Moreover, the dynamics of all types of water was found to be effected by the presence of the ionic buffer.

The mechanism of the dielectric relaxation in water.

Although relating to the same system, the interpretations of the water spectra from Raman and Dielectric spectroscopy present independent pictures of the nature of water. We show that in the overlap region of the two methods it is possible to combine these views into a coherent concept of what drives the dynamic features of water. In this work, we develop the idea that the dielectric relaxation in water is driven by the migration of defects through the H-bond network, leading to a Debye-like peak in the lower frequencies. The deviation from the Debye law in the higher sub-THz frequencies is traced to a global fluctuation of the same H-bond network, clearly evident in the Raman Spectra. By incorporating these two views, a mathematical formalism is presented that can aptly explicate the dielectric spectra of liquid water.

The dynamic crossover in dielectric relaxation behavior of ice I(h).

The main mechanism of the dielectric relaxation process of ordinary hexagonal ice (ice Ih) and its temperature dependence remains unclear. The most interesting and as yet unexplained feature of ice is the presence of the dynamical crossover in relaxation time behavior around Tc = 230 ± 3 K. Since there are no phase transitions in the ice at this temperature (first or second order), we cannot correlate the origin of this crossover with any structural change. Here we present a model according to which the temperature of the crossover is defined by the polarization mechanism. The dielectric relaxation driven by the diffusion of L-D orientational Bjerrum defects (at high temperature, T > Tc) is transformed into a dielectric relaxation dominated by the diffusion of intrinsic ionic H3O(+)/OH(-) defects (at low temperature, T < Tc). In the framework of the model, we propose an analytical equation for the complex dielectric permittivity that takes into account the contribution of both types of defects.

The puzzling first-order phase transition in water-glycerol mixtures.

Over the last decade, discussions on a possible liquid-liquid transition (LLT) have strongly intensified. The LLT proposed by several authors focused mostly on explaining the anomalous properties of water in a deeply supercooled state. However, there have been no direct experimental observations yet of LLT in bulk water in the so-called 'no man's land', where water exists only in the crystalline states. Recently, a novel experimental strategy to detect LLT in water has been employed using water-glycerol (W-G) mixtures, because glycerol can generate a strong hindrance for water crystallization. As a result, the observed first-order phase transition at a concentration of glycerol around cg≈ 20 mol% was ascribed to the LLT. Here we show unambiguously that the first order phase transition in W-G mixtures is caused by the ice formation. We provide additional dielectric measurements, applying specific annealing temperature protocols in order to reinforce this conclusion. We also provide an explanation, why such a phase transition occurs only in the narrow glycerol concentration range. These results clearly demonstrate the danger of analysis of phase-separating liquids to gain better insights into water dynamics. These liquids have complex phase behavior that is affected by temperature, phase stability and segregation, viscosity and nucleation, and finally by crystallization, that might lead to significant misinterpretations.

Dielectric spectra broadening as a signature for dipole-matrix interaction. IV. Water in amino acids solutions.

In this paper, the fourth one of our series on the dielectric spectrum symmetrical broadening of water, we consider amino acid (AA) aqueous solutions. The developed 3D-trajectory is applied here to the variety of zwitterion amino acids representing both the hydrophobic and hydrophilic nature of their residues. The dipole moment of amino acids due to their zwitterion determines their interaction with the solvent and reflects mostly the dipole-matrix interactions described in our Paper I [E. Levy et al., J. Chem. Phys. 136, 114502 (2012)]. It is also shown that in the case of charged AAs at high concentrations, the shape of the 3D trajectory transforms to the pattern typical of the dipole-charge interactions that were described in our Paper III [A. Puzenko et al., J. Chem. Phys. 137, 194502 (2012)].

Dielectric relaxation in weakly ergodic dilute dipole systems.

We introduce a method for calculating dipole correlations in systems containing hopping processes exhibiting weak ergodicity breaking. Modeled after the original Kirkwood-Fröhlich theory, the new method provides a bridge extending Fröhlich's insights from the realm of rigid dipoles into weakly non-ergodic fluctuating virtual dipolar entities. Relevant for the investigation of any system containing transport processes, it provides a testable parameter derived primarily from the static dielectric parameters. Three examples of systems including porous silicon, porous glass, and ferroelectric crystals are brought to demonstrate the model's versatility, including direct confirmation of Fröhlich's original idea.

Hydration of AMP and ATP molecules in aqueous solution and solid films.

Water enables life and plays a critical role in biology. Considered as a versatile and adaptive component of the cell, water engages a wide range of biomolecular interactions. An organism can exist and function only if its self-assembled molecular structures are hydrated. It was shown recently that switching of AMP/ATP binding to the insulin-independent glucose transporter Human Erythrocyte Glucose Transport Protein (GLUT1) may greatly influence the ratio of bulk and bound water during regulation of glucose uptake by red blood cells. In this paper, we present the results on the hydration properties of AMP/ATP obtained by means of dielectric spectroscopy in aqueous solution and for fully ionized forms in solid amorphous films with the help of gravimetric studies.