Bimolecular recombination reactions: K-adiabatic and K-active forms of the bimolecular master equations and analytic solutions

Expressions for a K-adiabatic master equation for a bimolecular recombination rate constant k_(rec) are derived for a bimolecular reaction forming a complex with a single well or complexes with multiple well, where K is the component of the total angular momentum along the axis of least moment of inertia of the recombination product. The K-active master equation is also considered. The exact analytic solutions, i.e., the K-adiabatic and K-active steady-state population distribution function of reactive complexes, g(EJK) and g(EJ), respectively, are derived for the K-adiabatic and K-active master equation cases using properties of inhomogeneous integral equations (Fredholm type). The solutions accommodate arbitrary intermolecular energy transfer models, e.g., the single exponential, double exponential, Gaussian, step-ladder, and near-singularity models. At the high pressure limit, the k_(rec) for both the K-adiabatic and K-active master equations reduce, respectively, to the K-adiabatic and K-active bimolecular Rice–Ramsperger–Kassel–Marcus theory (high pressure limit expressions). Ozone and its formation from O + O_2 are known to exhibit an adiabatic K. The ratio of the K-adiabatic to the K-active recombination rate constants for ozone formation at the high pressure limit is calculated to be ∼0.9 at 300 K. Results on the temperature and pressure dependence of the recombination rate constants and populations of O_3 will be presented elsewhere

Integration of structural brain networks is related to openness to experience: A diffusion MRI study with CSD-based tractography

Openness to experience is one of the big five traits of personality which recently has been the subject of several studies in neuroscience due to its importance in understanding various cognitive functions. However, the neural basis of openness to experience is still unclear. Previous studies have found largely heterogeneous results, suggesting that various brain regions may be involved in openness to experience. Here we suggested that performing structural connectome analysis may shed light on the neural underpinnings of openness to experience as it provides a more comprehensive look at the brain regions that are involved in this trait. Hence, we investigated the involvement of brain network structural features in openness to experience which has not yet been explored to date. The magnetic resonance imaging (MRI) data along with the openness to experience trait score from the self-reported NEO Five-Factor Inventory of 100 healthy subjects were evaluated from Human Connectome Project (HCP). CSD-based whole-brain probabilistic tractography was performed using diffusion-weighted images as well as segmented T1-weighted images to create an adjacency matrix for each subject. Using graph theoretical analysis, we computed global efficiency (GE) and clustering coefficient (CC) which are measures of two important aspects of network organization in the brain: functional integration and functional segregation respectively. Results revealed a significant negative correlation between GE and openness to experience which means that the higher capacity of the brain in combining information from different regions may be related to lower openness to experience

^1H{^(19)F} NOE NMR Structural Signatures of the Insulin R_6 Hexamer: Evidence of a Capped HisB10 Site in Aryl- and Arylacryloyl-carboxylate Complexes

New and improved insulin: ^1H{^(19)F} NOE NMR difference spectra for CF_3-substituted aromatic carboxylates bound at the HisB10 sites of the R_6 human insulin (HI) hexamer show strong NOEs between the CF_3 groups and the LeuB6, AsnB3, and PheB1 sidechains. The NOEs and structural modeling establish that these carboxylates form closed complexes with the HisB10 site capped by the PheB1 rings

Bimolecular Recombination Reactions: K‑Adiabatic and K‑Active Forms of RRKM Theory, Nonstatistical Aspects, Low-Pressure Rates, and Time-Dependent Survival Probabilities with Application to Ozone. 2

We consider for bimolecular recombination reactions the K-adiabatic versus the K-active forms of RRKM theory, where K is the component of the total angular momentum along the axis of least moment of inertia of the recombination product. When that product is approximately a prolate symmetric top, with two moments of inertia of the product substantially larger than the third, K becomes a dynamically slowly varying quantity and the K-adiabatic form of RRKM theory is the appropriate version to use. Using classical trajectory results for the rate constant for ozone formation in the low-pressure region as an example, excellent agreement for the recombination rate constant k_(rec) with the K-adiabatic RRKM theory is observed. Use of a two transition state (inner, outer TS) formalism also obviates any need for assessing recrossings in the exit channel. In contrast, the K-active form of RRKM theory for this system disagrees with the trajectory results by a factor of about 2.5. In this study we also consider the distribution of the (E, J) resolved time-dependent survival probabilities P(E, J, t) of the intermediate O_3^* formed from O + O_2. It is calculated using classical trajectories. The initial conditions for classical trajectories were selected using action-angle variables and a total J representation for (E, J) resolved systems, as described in Part I.1 The difference between K-active and K-adiabatic treatments is reflected also in a difference of the K-active RRKM survival probability P(E, J, t) from its trajectory-based value and from its often non-single-exponential decay. It is shown analytically that k_(rec) (K-active) ≥ k_(rec) (K-adiabatic), independent of the details of the TS (e.g., variational or fixed RRKM theory, 1-TS or 2-TS). Nonstatistical effects for O_3^* formation include a small initial recrossing of the transition state, a slow (several picoseconds) equipartitioning of energy among the two O–O bonds of the newly formed O_3^*, and a small nondissociation (a quasi-periodicity) of some trajectories originating in O_3^* (∼10%) and so, by microscopic reversibility, are not accessible from O + O_2. An apparently new feature of the present results is the comparison of classical trajectories with K-adiabatic and K-active theories for rate constants of bimolecular recombinations. The quantum mechanical counterpart of classical K-adiabatic RRKM theory is also given, and its comparison with the experimental k_(rec) for O_3 is given elsewhere

High Seroprevalence of Anti-H. pylori Antibodies in Patients with Ventilator Associated Pneumonia

Background: Despite major advances in the management of ventilator-associated pneumonia, its pathogenesis is not clearly known. Recently, the role of gastric colonization has been proposed. We compared the prevalence of H. pylori by serology in patients with VAP and in control subjects to determine the role of H. pylori and gastric colonization in the pathogenesis of VAP. Methods:118 intubated and mechanically ventilated patients were included and divided into two groups; 59 subjects with VAP and 59 control patients. Results of the serologic tests, demographic characteristics and time of blood sampling were registered. Results: Mean age in seropositive patients was significantly higher. 71.2% in the VAP group and 61.01% in controls were IgG seropositive (P=0.24). IgM seropositivity was 23.73% versus 8.47% in VAPs and controls, respectively (P=0.024). By increasing the time of intubation, more patients became seropositive for IgM (Pearson’s correlation coefficient=0.4, P=0.002). Conclusion:  IgM seropositivity and serum level were significantly higher in VAP patients. Also by increasing the duration of intubation and time of sampling, serum levels and seropositivity for IgM increased significantly

Hepatic cysteine sulphinic acid decarboxylase depletion and defective taurine metabolism in a rat partial nephrectomy model of chronic kidney disease

© 2021, The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Background: Taurine depletion occurs in patients with end-stage chronic kidney disease (CKD). In contrast, in the absence of CKD, plasma taurine is reported to increase following dietary L-glutamine supplementation. This study tested the hypothesis that taurine biosynthesis decreases in a rat CKD model, but is rectified by L-glutamine supplementation. Methods: CKD was induced by partial nephrectomy in male Sprague-Dawley rats, followed 2 weeks later by 2 weeks of 12% w/w L-glutamine supplemented diet (designated NxT) or control diet (NxC). Sham-operated control rats (S) received control diet. Results: Taurine concentration in plasma, liver and skeletal muscle was not depleted, but steady-state urinary taurine excretion (a measure of whole-body taurine biosynthesis) was strongly suppressed (28.3 ± 8.7 in NxC rats versus 78.5 ± 7.6 μmol/24 h in S, P < 0.05), accompanied by reduced taurine clearance (NxC 0.14 ± 0.05 versus 0.70 ± 0.11 ml/min/Kg body weight in S, P < 0.05). Hepatic expression of mRNAs encoding key enzymes of taurine biosynthesis (cysteine sulphinic acid decarboxylase (CSAD) and cysteine dioxygenase (CDO)) showed no statistically significant response to CKD (mean relative expression of CSAD and CDO in NxC versus S was 0.91 ± 0.18 and 0.87 ± 0.14 respectively). Expression of CDO protein was also unaffected. However, CSAD protein decreased strongly in NxC livers (45.0 ± 16.8% of that in S livers, P < 0.005). L-glutamine supplementation failed to rectify taurine biosynthesis or CSAD protein expression, but worsened CKD (proteinuria in NxT 12.5 ± 1.2 versus 6.7 ± 1.5 mg/24 h in NxC, P < 0.05). Conclusion: In CKD, hepatic CSAD is depleted and taurine biosynthesis impaired. This is important in view of taurine’s reported protective effect against cardio-vascular disease - the leading cause of death in human CKD.Peer reviewe

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Mathematical Modeling of Glioblastoma Wound Healing Assay (WHA) and Radiation Response in Non-Small Cell Lung Cancer (NSCLC)

University of Minnesota Ph.D. dissertation. January 2021. Major: Mechanical Engineering. Advisor: David Odde. 1 computer file (PDF); 68 pages.Glioblastoma is a brain tumor with a poor prognosis. This disease is characterized by its inherent heterogeneity and the migratory nature of its cancer cells. Understanding the mechanics of tumor cell infiltration into healthy tissue can potentially improve prognostic outcomes. To further investigate this effect, we used a wound healing assay on compliant collagen-I-coated polyacrylamide substrates and plating of U251 glioma cell lines. We then applied a Brownian dynamics-based tumor simulator (BDTS) to use minimal input parameters to assess and compare properties of a simple wound healing experiment, i.e. single cell random motility coefficients (D) and tissue culture doubling time (p). Interestingly, we found that without adjusting for a priori assumptions on how wound closure takes place, the ensemble behavior of the wound closure rate can be simulated with single cell input data. Our experiments confirmed that cells on substrates with higher Young’s moduli tend to close the gap more rapidly as an ensemble of individual cells. This finding validates the results of our simulated scenarios. Additionally, we demonstrated that heterogeneity in motility coefficients (D) or variations in doubling time (p) does not explain wound closure rate with any degree of significance compared to an assumption of uniform D and p values. These results demonstrate the ability of single cell data to accurately predict tumor level dynamics, and further demonstrate the relative robustness with respect to cell-to-cell heterogeneity. We demonstrate the importance of considering intratumoral heterogeneity and the development of resistance during fractionated radiotherapy when the same dose of radiation is delivered for all fractions (Fractional Equivalent Dosing, FED).A mathematical model was developed with the following parameters: a starting population of 1011 non-small cell lung cancer (NSCLC) tumor cells, 48-hour doubling time, and cell death per the linear-quadratic (LQ) model with α and β values derived from RSIα/β, in a previously described gene expression based model that estimates α and β. To incorporate both inter- and intratumor radiation sensitivity, RSIα/β output for each patient sample is assumed to represent an average value in a gamma distribution with the bounds set to -50% and +50% of RSIa/b. Therefore, we assume that within a given tumor there are subpopulations that have varying radiation sensitivity parameters that are distinct from other tumor samples with a different mean RSIα/β. A simulation cohort (SC) comprised of 100 lung cancer patients with available RSIα/β (patient specific α and β values) was used to investigate 60Gy in 30 fractions with fractionally equivalent dosing (FED). A separate validation cohort (VC) of 57 lung cancer patients treated with radiation with available local control (LC), overall survival (OS), and tumor gene expression was used to clinically validate the model. Cox regression was used to test for significance to predict clinical outcomes as a continuous variable in multivariate analysis (MVA). Finally, the VC was used to compare FED schedules with various altered fractionation schema utilizing a Kruskal-Wallis test. This was examined using the end points of end of treatment log cell count (LCC) and by a parameter described as mean log kill efficiency (LKE) defined as: LCC = log10(tumorcellcount) LKE=((log10(〖〖day〗_i〗_tumorcellcount )– log10(〖〖day〗_(i+1)〗_tumorcellcount )))/(〖day〗_i_dosage) Cox regression analysis on LCC for the VC demonstrates that, after incorporation of intratumoral heterogeneity, LCC has a linear correlation with local control (p = 0.002) and overall survival (p =< 0.001). Other suggested treatment schedules labeled as High Intensity Treatment (HIT) with a total 60Gy delivered over 6 weeks have a lower mean LCC and an increased LKE compared to standard of care 60Gy delivered in FED in the VC. We find that LCC is a clinically relevant metric that is correlated with local control and overall survival in NSCLC. We conclude that 60Gy delivered over 6 weeks with altered HIT fractionation leads to an enhancement in tumor control compared to FED when intratumoral heterogeneity is considered