Unequal Concentrations Research Articles

A mathematical study of the interaction between oxygen and lactate in an in vivo and in vitro tumor

Micro-environmental acidity is a common feature of the tumor. One of the causes behind tumor acidity is lactate production by hypoxic cells of the tumor. Hypoxia is a direct result of the establishment of oxygen gradients. It is commonly observed in the tumor in an in vitro experimental setup and also in vivo situation. Here, we propose a mathematical model to analyze the production of lactate by hypoxic cells, and it is used as an alternative fuel by normoxic cells in tumor tissue in vitro and in vivo conditions. Also, we study the effects of unequal oxygen concentrations at the tumor boundaries on lactate status in the tumor. The effects of necrotic core on lactate accumulation is examined. The results are in good agreement with experimental data and are in align with the theoretical findings of previous studies. The analytical results show that lactate levels are elevated in an in vivo tumor compared to that in an in vitro tumor. Also, during the onset of necrotic core formation, the effects of necrotic core on lactate levels are noticed. Knowledge of the lactate status in a patient’s tumor may be helpful in choosing the appropriate and effective medicines for cancer treatment.

Pressure and Composition Effects on a Common Nanoparticle Ligand-Solvent Pair.

The effect of pressure on the properties of nanoparticles is a growing area of investigation. These measurements are typically performed in a colloidal suspension; however, pressure-induced changes in the interactions between the nanoparticle surface and the solvent are often neglected. Here, we report vibrational spectroscopy of a common nanoparticle ligand, 1-dodecanethiol, and a common solvent, toluene, under pressure. We find that the pressure-induced phase change of the 1-dodecanethiol is altered by the presence of toluene and that change depends on the concentration of the free ligand in the solution. At near-equal concentrations, phase segregation is observed and the dodecanethiol crystallizes independently from the toluene. On the other hand, at unequal concentrations, concerted phase transitions are observed in the dodecanethiol and toluene, and a disordered conformation of dodecanethiol is maintained under much higher pressures. These results shed light on the pressure-induced changes in intermolecular interactions between nanoparticle ligands and solvents, which must be considered in the design of high-pressure investigations of colloidal nanoparticles.

Stoichiometric effect on the structural transformation and spatial variation of polyamide reverse osmosis membranes: A molecular dynamics study

Reverse osmosis based on polyamide membranes is currently the leading technology for desalination and water purification. However, the spatial variation of polyamide architecture, especially regarding stoichiometric criteria at the real reaction interface during membrane fabrication, is poorly understood. Here we conducted equilibrium molecular dynamic simulations, mimicking the practical construction of polyamide matrices using a variety of monomer component stoichiometries, to investigate resulting differences in both the morphological transformation and mass transport through the polymer network. Our simulations indicated that an equal stoichiometry of the reactive functional groups predominantly resulted in favorable polyamide matrix qualities such as a high crosslinking density, uniform pore size distribution, and adequate layer compactness. Despite the thickness-dependent water diffusion across the active layer, an analysis of polyamide membrane density revealed depth heterogeneity, particularly for membranes constructed under unequal concentrations. Consequently, uncontrollable defects are likely to be created, as evidenced by the partial penetration of Na+ across such membranes. In addition, the residual functional groups in the polyamide matrices (–COOH and –NH2) influenced the transport behavior of ions near the membrane surface. Overall, our simulations provide a visual platform for understanding the stoichiometry-induced relationship between membrane structure and performance, which may guide the future design of defect-free and scaling-resistant reverse osmosis membranes.

Study of nonmonotonic electron mobility due to influence of asymmetric structure parameters in pseudomorphic heterojunction field effect transistors

Nonmonotonic electron mobility is obtained in InxGa1-xAs/GaAs double quantum well pseudomorphic heterostructure field effect transistor by changing the structure parameters. We show that a rapid drop in mobility occurs at the point of resonance of sub-band states due to asymmetric variation of doping concentrations. The sub-band wave function distributions change significantly near the resonance and influence the sub-band mobilities through the scattering potentials, there by causing the dip in μ. The depth of nonlinearity in μ enhances by increasing the central barrier width and the difference between the well widths. On the other hand, variation of μ as a function of asymmetric change of well widths leads to a hump like raise in μ under unequal doping concentrations. Our results of nonlinear mobility can be utilized in low temperature transistor applications.

Unsymmetrical design and operation in counter-flow microfluidic fuel cell: A prospective study

Performance of counter-flow microfluidic fuel cell is severely limited by the uneven current density distribution within the electrodes. In this work, in-depth numerical investigations are performed to examine the prospects of unsymmetrical design and operation in an all-vanadium counter-flow microfluidic fuel cell with flow-through electrodes to better utilize the electrode effective zone considering the anode-cathode mismatch on the mass transfer and electrochemical kinetics. Results indicate that size and position of the electrode effective zone vary under different operation conditions. Longer electrodes are required when the electrolyte flow rate or reactant concentration decreases. Optimized cathode length is smaller than its anode counterpart due to the faster diffusion rate of the oxidant and improved electrochemical reaction rate at the cathode. Concentration-related activation loss is found to play a key role in the performance of counter-flow microfluidic fuel cells and consequently, unequal initial flow rates are preferred in the cell operation to unequal initial reactant concentrations. Catholyte flow rate could be safely reduced to half of that in the anode with 95% retention of the output current, bringing a reduction of 50% in the catholyte consumption. The present findings could provide useful guidance for the future development of counter-flow microfluidic fuel cells.

Multi-residue enantioselective analysis of chiral drugs in freshwater sediments

Pharmaceutical and illicit drugs are emerging contaminants found in the environment globally. Many are chiral and stereochemistry plays an important role on their environmental fate and effects. However, investigations at the enantiomeric level are limited, particularly for complex particulate matrices such as sediments. This is due to further sample processing requirements and a lack of suitable analytical methods. Therefore, here a new enantioselective methodology is proposed for 15 drugs in sediment. Sample treatment by accelerated solvent extraction and solid phase extraction was critical for subsequent enantioselective separations. Using liquid chromatography–tandem mass spectrometry, a Chiral-V enantioselective column enabled multi-residue separations of anti-depressants, beta-blockers, beta-agonist, anti-histamine and stimulants. Method trueness for all enantiomers was 86–121% and method quantitation limits were below 3 ng g−1 dry weight. Application of the method revealed the enantiomeric composition of fluoxetine, amphetamine, propranolol, venlafaxine and citalopram in sediment for the first time. All drugs except venlafaxine were present in non-racemic form, i.e. unequal enantiomer concentrations. This is significant considering drug toxicity towards benthic organisms could be enantiospecific.

Parameter Estimation and Covariance Matrix of the Linear Functional Relationship Model for Circular Variables with Unequal Error Concentrations

Functional relationship model is used to study the data that are subjected to errors. In this paper, we consider the linear functional relationship model with bivariate circular data where the pair of errors is with unequal concentration parameters. The parameter estimation of the model for circular data is different from linear data due to its wrapped around nature. We propose some improvements on the parameter estimation where some iterative procedures are considered. The concentration parameters are estimated based on the Bessel function. Also, we derive the corresponding covariance matrix of the model based on the Fisher Information matrix. Monte Carlo simulation studies were performed to study the suitability of the estimation method. It is found that the biasness of the estimates is small. Practical application of the method is illustrated by using real data set. Keywords: circular data; covariance matrix; Von Mises distribution; simulation study

Race, Gender, and Socioeconomic Variations in C-Reactive Protein Using the Health and Retirement Study.

To clarify the relationships among race, gender, and socioeconomic status (SES) with C-reactive protein (CRP). The present study analyzed data from 6,521 Black and White respondents aged 51 and older in the Health and Retirement Study, a nationally representative sample of midlife and older adults, to address two aims. We sought to (i) assess the independent associations between race, gender, and SES with CRP concentrations and (ii) test whether race, gender, and SES interacted to produce unequal CRP concentrations cross-sectionally and over a 4-year follow-up. The results demonstrated that race, gender, and SES were each independently associated with baseline CRP, but only SES was associated with CRP at follow-up. Furthermore, race, gender, and education interacted to produce differential CRP levels at baseline. There were incremental benefits for each additional level of education for White men and women, but the relationship between education and CRP was more complicated for Black men and women. Compared with other race/gender groups with less than high school, Black women had the highest and Black men had the lowest levels of CRP. There were no apparent benefits to CRP for Black women with college compared with Black women with high school, while Black men with less than high school and college had similar concentrations of CRP. In clarifying the complexity inherent in CRP disparities, this work contributes to a greater understanding of the biological mechanisms underlying racial disparities in leading causes of morbidity and mortality in the United States.

Reply.

Arshinoff and Modabber5 call into question two assumptions of our mathematical model describing the residence times of moxifloxacin in the anterior segment with two different intracameral injection strategies.1 The authors of the letter agree with us on the underlying principle of our publication but disagree on the volume of the anterior chamber (AC) and the half-life of antibiotics. We selected two representative mean pseudophakic AC volumes (0.19 mL and 0.33 mL), substantiated by the literature,2,3 to demonstrate the principle that injecting the same dose of antibiotics (eg, 500 μg) into ACs with varying volumes produces varying concentrations of antibiotics within the total aqueous humor volume. The larger volume of 0.33 mL of Matsuura was derived from aqueous humor sampling immediately after intracameral injection in humans, before any possible fibrosis of the capsule. Libre and Mathews4 also agree with this volume. Arshinoff and Modabber's5 estimation of 0.5 mL is based on a mean phakic AC volume in the human eye of 0.25 mL; however, measurements of the AC volume in the elderly phakic eye average only 0.15 mL.6,7 With this experimentally derived volume, Arshinoff's estimation of the mean pseudophakic aqueous volume would be 0.4 mL, close to Matsuura and Libre's reported value of 0.33 mL. The AC size is known to vary from patient to patient, which cataract surgeons recognize when operating on smaller eyes and myopic eyes with longer axial lengths and larger chambers. Therefore, attempting to replace the aqueous contents with an antibiotic solution of known concentration will achieve the more consistent final concentration of drug, irrespective of the patient's pseudophakic AC volume. This same principle would have been demonstrated had we chosen two different AC volumes. There is a wide variation in the reported half-life elimination of antibiotics in the AC. Generally speaking, interdrug variation in elimination times, especially in the eye, may be due to factors such as differences in the drug molecular size, tissue binding, active pump mechanisms, and obstructions or reductions to outflow and drug elimination. Asena obtained antibiotic half-lives between 1.2 hours and 13 hours in rabbits, depending on which time points were used8; Lipnitzki et al.9 found between 0.64 hours and 1.8 hours in rabbits. Matsuura et al.3,10 demonstrated a half-life in rabbits and humans that averaged 1.2 hours over most time points. We chose 1.2 hours as it agrees with the 1% per minute aqueous turnover rate noted by Goel et al.11 The varied measures of the intradrug half-life elimination time of moxifloxacin and other antibiotics in the AC may be due to imprecision in injection and sampling techniques, pharmacokinetics that are not single compartment, and variations in individual subject anatomy and physiology. We would caution against the speculation of postantibiotic effects in regard to half-life because efficacy should be related to the target microorganism.12 Furthermore, principles that apply to the multidose administration of antibiotics in the treatment of systemic infections should not be presumptively applied to the scenario of single-dose intraocular injection without empirical evidence. Our study used two different and substantiated aqueous volumes and demonstrated that injecting small volumes of an agent can result in unequal final drug concentrations in the AC. Given the patient-to-patient variations, the “flushing” or large-volume injection technique should offer some degree of standardization and assurance of a more uniform final drug concentration in the pseudophakic AC as compared with smaller-volume–injected aliquots, thereby minimizing the interpatient variable of AC volume differences during cataract surgery.

Berufliche und private Standortfaktoren für die Niederlassung von Hausärzten in ländlichen Räumen

The safeguarding of primary health care in rural regions is broadly discussed in science, politics and practice. Thereby the knowledge about current location factors is insufficient, because existing studies focus on professional factors or on locational imaginations of future doctors instead of analysing effective locational decisions. Thus, this study asks which professional and private location factors influence the settling decisions of general practitioners in rural regions. Therefore two regional case studies are conducted with overall 21 interviews with regional experts and newly settled doctors, working out crucial location factors. Building on that, the influence of chosen location factors for regional unequal practitioner concentrations as well as for the development of practitioner numbers are nationwide quantified by multiple regression models. The results show, that professional aspects, like economic security, close patient contacts and organisational freedom, as well as biographical relations are especially decisive criteria for the doctors’ location decisions. Furthermore, family-friendly everyday environments are very important for many of them. Other soft location factors as high standard cultural and leisure facilities are negligible. Furthermore, there is a relationship between inpatient and outpatient care. Many general practitioners worked in a regional hospital, before they switched to the ambulant sector, due to better working conditions and an easier compatibility with family life. The results point to a change of location factors, whereby further needs for research and concrete policy recommendations arise.

The isospin dependence of the nuclear force and its impact on the many-body system

A major goal of contemporary nuclear physics is to improve our knowledge of the nuclear matter equation of state. In particular, the equation of state of isospin- asymmetric matter (that is, with unequal concentrations of protons and neutrons), is not well understood, mostly due to our limited knowledge of the symmetry energy. The latter reduces the binding energy in a nucleus with unequal number of protons and neutrons, and is crucial for understanding nuclear stability. We review experimental, phenomenological, and theoretical facts about the symmetry energy. We emphasize the importance of adopting a microscopic approach towards a better understanding of this important quantity.

Improved Normalization of Systematic Biases Affecting Ion Current Measurements in Label-free Proteomics Data

Normalization is an important step in the analysis of quantitative proteomics data. If this step is ignored, systematic biases can lead to incorrect assumptions about regulation. Most statistical procedures for normalizing proteomics data have been borrowed from genomics where their development has focused on the removal of so-called 'batch effects.' In general, a typical normalization step in proteomics works under the assumption that most peptides/proteins do not change; scaling is then used to give a median log-ratio of 0. The focus of this work was to identify other factors, derived from knowledge of the variables in proteomics, which might be used to improve normalization. Here we have examined the multi-laboratory data sets from Phase I of the NCI's CPTAC program. Surprisingly, the most important bias variables affecting peptide intensities within labs were retention time and charge state. The magnitude of these observations was exaggerated in samples of unequal concentrations or "spike-in" levels, presumably because the average precursor charge for peptides with higher charge state potentials is lower at higher relative sample concentrations. These effects are consistent with reduced protonation during electrospray and demonstrate that the physical properties of the peptides themselves can serve as good reporters of systematic biases. Between labs, retention time, precursor m/z, and peptide length were most commonly the top-ranked bias variables, over the standardly used average intensity (A). A larger set of variables was then used to develop a stepwise normalization procedure. This statistical model was found to perform as well or better on the CPTAC mock biomarker data than other commonly used methods. Furthermore, the method described here does not require a priori knowledge of the systematic biases in a given data set. These improvements can be attributed to the inclusion of variables other than average intensity during normalization.

Massive Parallel Sequencing Provides New Perspectives on Bacterial Brain Abscesses

Rapid development within the field of massive parallel sequencing (MPS) is about to bring this technology within reach for diagnostic microbiology laboratories. We wanted to explore its potential for improving diagnosis and understanding of polymicrobial infections, using bacterial brain abscesses as an example. We conducted a prospective nationwide study on bacterial brain abscesses. Fifty-two surgical samples were included over a 2-year period. The samples were categorized as either spontaneous intracerebral, spontaneous subdural, or postoperative. Bacterial 16S rRNA genes were amplified directly from the specimens and sequenced using Ion Torrent technology, with an average of 500,000 reads per sample. The results were compared to those from culture- and Sanger sequencing-based diagnostics. Compared to culture, MPS allowed for triple the number of bacterial identifications. Aggregatibacter aphrophilus, Fusobacterium nucleatum, and Streptococcus intermedius or combinations of them were found in all spontaneous polymicrobial abscesses. F. nucleatum was systematically detected in samples with anaerobic flora. The increased detection rate for Actinomyces spp. and facultative Gram-negative rods further revealed several species associations. We suggest that A. aphrophilus, F. nucleatum, and S. intermedius are key pathogens for the establishment of spontaneous polymicrobial brain abscesses. In addition, F. nucleatum seems to be important for the development of anaerobic flora. MPS can accurately describe polymicrobial specimens when a sufficient number of reads is used to compensate for unequal species concentrations and principles are defined to discard contaminant bacterial DNA in the subsequent data analysis. This will contribute to our understanding of how different types of polymicrobial infections develop.

ANALYSIS OF THE SYMMETRY ENERGY IN A MICROSCOPIC APPROACH

A major goal of contemporary nuclear physics is to improve our knowledge of the nuclear matter equation of state (EoS). In particular, the EoS of isospin-asymmetric matter (that is, with unequal concentrations of protons and neutrons), is not well understood, mostly due to our limited knowledge of the symmetry energy. The latter reduces the binding energy in a nucleus with unequal number of protons and neutrons, and is crucial for understanding nuclear stability. We will review experimental, phenomenological and theoretical facts about the symmetry energy, with particular emphasis on analyzing how the various components of the nuclear force, in a microscopic model, contribute to this important quantity.

Characterization of polybacterial clinical samples using a set of group-specific broad-range primers targeting the 16S rRNA gene followed by DNA sequencing and RipSeq analysis

The standard use of a single universal broad-range PCR in direct 16S rDNA sequencing from polybacterial samples leaves the minor constituents at risk of remaining undetected because all bacterial DNA will be competing for the same reagents. In this article we introduce a set of three broad-range group-specific 16S rDNA PCRs that together cover the clinically relevant bacteria and apply them in the investigation of 25 polybacterial clinical samples. Mixed DNA chromatograms from samples containing more than one species per primer group were analysed using RipSeq Mixed (iSentio, Norway), a web-based application for the interpretation of chromatograms containing up to three different species. The group-specific PCRs reduced complexity in the resulting DNA chromatograms and made the assay more sensitive in situations with unequal species concentrations. Together this allowed for identification of a significantly higher number of bacterial species than did standard direct sequencing with a single universal primer pair and RipSeq analysis (95 vs 51). The method could improve microbiological diagnostics for important groups of patients and can be established in any laboratory with experience in direct 16S rDNA sequencing.

Pyrosequencing on templates generated by asymmetric nucleic acid sequence-based amplification (asymmetric-NASBA)

Pyrosequencing is an ideal tool for verifying the sequence of amplicons. To enable pyrosequencing on amplicons from nucleic acid sequence-based amplification (NASBA), asymmetric NASBA with unequal concentrations of T7 promoter primer and reverse transcription primer was proposed. By optimizing the ratio of two primers and the concentration of dNTPs and NTPs, the amount of single-stranded cDNA in the amplicons from asymmetric NASBA was found increased 12 times more than the conventional NASBA through the real-time detection of a molecular beacon specific to cDNA of interest. More than 20 bases have been successfully detected by pyrosequencing on amplicons from asymmetric NASBA using Human parainfluenza virus (HPIV) as an amplification template. The primary results indicate that the combination of NASBA with a pyrosequencing system is practical, and should open a new field in clinical diagnosis.

THE MICROSCOPIC APPROACH TO NUCLEAR MATTER AND NEUTRON STAR MATTER

We review a variety of theoretical and experimental investigations aimed at improving our knowledge of the nuclear matter equation of state. Of particular interest are nuclear matter extreme states in terms of density and/or isospin asymmetry. The equation of state of matter with unequal concentrations of protons and neutrons has numerous applications. These include heavy-ion collisions, the physics of rare, short-lived nuclei and, on a dramatically different scale, the physics of neutron stars. The "common denominator" among these (seemingly) very different systems is the symmetry energy, which plays a crucial role in both the formation of the neutron skin in neutron-rich nuclei and the radius of a neutron star (a system 18 orders of magnitude larger and 55 orders of magnitudes heavier). The details of the density dependence of the symmetry energy are not yet sufficiently constrained. Throughout this article, our emphasis will be on the importance of adopting a microscopic approach to the many-body problem, which we believe to be the one with true predictive power.

Eddy damped quasinormal Markovian theory for chemically reactive scalars in isotropic turbulence

The eddy damped quasinormal Markovian theory has been applied to the mixing of three scalars undergoing an isothermal, bimolecular chemical reaction of the form: A+B→C, with a reaction rate constant that is independent of the scalar concentrations. The model is an extension of the work by Vaithianathan, Ulitsky, and Collins [Proc. Combust. Inst. 29, 2139 (2002)] to allow for unequal initial molar concentrations of the reactant species and differences in the molecular diffusivities of the three scalars, thereby enabling the effect of differential diffusion to be studied. Comparisons of the model with results from direct numerical simulations are in good agreement for the low-order statistics considered here. The model also was used to explore the effect of the parameters (Reynolds number, Schmidt number, and Damköhler number) on the scalar statistics. The results show that differential diffusion effects decrease with increasing Reynolds number, as has been observed for nonreacting scalars. However, statistics involving the product species (e.g., cross correlation coefficients ρAC and ρBC) have the opposite trend with Damköhler number, which raises the question of the role of differential diffusion for the intermediate species in a turbulent flame, where the unity Lewis number assumption is often invoked on the basis of the high Reynolds number even though the Damköhler number too is quite large.

Role of Proton Gradients in the Mechanism of Osmosis

Experiments were carried out to determine whether the newly identified "exclusion zone" found adjacent to hydrophilic surfaces might play a role in osmosis. Two chambers were juxtaposed face to face, separated by a membrane made of cellulose acetate or Nafion. One chamber contained water, the other 100 mM sodium sulfate solution. Osmotically driven transmembrane fluid flow from low to high salt was observed using both membranes, in agreement with previous reports. Characteristic pH differences and potential differences between chambers were also noted. Visual examination with microsphere markers revealed extensive exclusion zones adjacent to both types of membrane. As these zones routinely generate protons in the water regions beyond, unequal proton concentrations in the respective chambers may be responsible for creating both the pH and potential gradients, which may be ultimately responsible for the osmotic drive.

Investigation of ion concentration and electric potential distributions in charged membrane/electrolyte systems

The ion concentration, electrical potential and current distributions of a membrane/electrolyte system under equilibrium conditions are investigated numerically. The membrane is modeled as an array of finite-length charged pores with uniform distributed surface charge density and in contact with single- or multi-component electrolytes in both sides of the membrane. The numerical model is verified using the theoretical results from Donnan, Nernst and the surface potentials. For cases involving equal electrolyte bulk concentrations in both sides of the membrane, it is found that the dimensionless Debye length and surface charge density characterize the ion concentration and potential distributions in the system. The electrical potential difference between the membrane and external bulk electrolyte depends on the degree of increase in counter-ion concentration inside the pore relative to the bulk electrolyte. Higher potential difference can be resulted as the dimensionless Debye length decreases or the surface charge density increases. In a membrane/multi-component system, the resulting potential difference between the membrane and external bulk electrolyte is smaller as compared with the membrane/single-component electrolyte system due to the increase in dimensionless Debye length. For systems with unequal electrolyte bulk concentrations in contact with the membrane, current flow appears in the system due to the establishment of concentration and potential gradients in the system. The current flow increases with the increase in the bulk electrolyte concentration difference. The current flow in the multi-component electrolyte system is found to be smaller than that for the single-component system due to the increase in dimensionless Debye length.