Activation Energies and Beyond Piskulich, Zeke A; Mesele, Oluwaseun O; Thompson, Ward H
The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory,
08/2019, Volume:
123, Issue:
33
Journal Article
Peer reviewed
Open access
Recent advances in the calculation and interpretation of the activation energy for a dynamical process are described. Specifically, new approaches that apply the fluctuation theory of statistical ...mechanics to dynamics enable the direct determination of the activation energy for an arbitrary dynamical time scale from simulations at a single temperature. This opens up significant new possibilities for understanding activated processes in cases where a traditional Arrhenius analysis is not possible. The methods also enable a rigorous decomposition of the activation energy into contributions associated with the different interactions and motions present in the system. These components can be understood in the context of Tolman’s interpretation of the activation energy. Specifically, they provide insight into how energy can be most effectively deposited to accelerate the dynamics of interest, promising important new mechanistic information for a broad range of chemical processes. The general approach can be extended beyond activation energies to the examination of non-Arrhenius behavior as well as the changes in dynamical time scales with respect to other thermodynamic variables such as pressure.
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IJS, KILJ, NUK, PNG, UL, UM
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•Juvenile and adolescent tree shrews become hyperopic in narrow-band red light.•The vitreous chamber is smaller than normal and the choroid is thicker.•Tree shrews at these ages do ...not become hyperopic in response to a plus lens.•The continuing response to red contrasts with the lack of response to a plus lens.•The emmetropization mechanism can slow eye growth in juvenile and adolescent animals.
In infant tree shrews, exposure to narrow-band long-wavelength (red) light, that stimulates long-wavelength sensitive cones almost exclusively, slows axial elongation and produces hyperopia. We asked if red light produces hyperopia in juvenile and adolescent animals, ages when plus lenses are ineffective. Animals were raised in fluorescent colony lighting (100–300 lux) until they began 13days of red-light treatment at 11 (n=5, “infant”), 35 (n=5, “juvenile”) or 95 (n=5, “adolescent”) days of visual experience (DVE). LEDs provided 527–749 lux on the cage floor. To control for the higher red illuminance, a fluorescent control group (n=5) of juvenile (35 DVE) animals was exposed to ∼975 lux. Refractions were measured daily; ocular component dimensions at the start and end of treatment and end of recovery in colony lighting. These groups were compared with normals (n=7). In red light, the refractive state of both juvenile and adolescent animals became significantly (P<0.05) hyperopic: juvenile 3.9±1.0 diopters (D, mean±SEM) vs. normal 0.8±0.1D; adolescent 1.6±0.2D vs. normal 0.4±0.1D. The fluorescent control group refractions (0.6±0.3D) were normal. In red-treated juveniles the vitreous chamber was significantly smaller than normal (P<0.05): juvenile 2.67±0.03mmvs. normal 2.75±0.02mm. The choroid was also significantly thicker: juvenile 77±4μmvs. normal 57±3μm (P<0.05). Although plus lenses do not restrain eye growth in juvenile tree shrews, the red light-induced slowed growth and hyperopia in juvenile and adolescent tree shrews demonstrates that the emmetropization mechanism is still capable of restraining eye growth at these ages.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cocaine addiction is a major public health problem that is particularly difficult to treat. Without medically proven pharmacological treatments, interventions to change the maladaptive behavior of ...addicted individuals mainly rely on psychosocial approaches. Here we report on impairment in cocaine-addicted patients to act purposefully toward a given goal and on the influence of extended training on their behavior. When patients were rewarded for their behavior, prolonged training improved their response rate toward the goal but simultaneously rendered them insensitive to the consequences of their actions. By contrast, overtraining of avoidance behavior had no effect on patient performance. Our findings illustrate the ineffectiveness of punitive approaches and highlight the potential for interventions that focus on improving goal-directed behavior and implementing more desirable habits to replace habitual drug-taking.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
Agola JO, Jim PA, Ward HH, BasuRay S, Wandinger‐Ness A. Rab GTPases as regulators of endocytosis, targets of disease and therapeutic opportunities.
Rab GTPases are well‐recognized targets in human ...disease, although are underexplored therapeutically. Elucidation of how mutant or dysregulated Rab GTPases and accessory proteins contribute to organ specific and systemic disease remains an area of intensive study and an essential foundation for effective drug targeting. Mutation of Rab GTPases or associated regulatory proteins causes numerous human genetic diseases. Cancer, neurodegeneration and diabetes represent examples of acquired human diseases resulting from the up‐ or downregulation or aberrant function of Rab GTPases. The broad range of physiologic processes and organ systems affected by altered Rab GTPase activity is based on pivotal roles in responding to cell signaling and metabolic demand through the coordinated regulation of membrane trafficking. The Rab‐regulated processes of cargo sorting, cytoskeletal translocation of vesicles and appropriate fusion with the target membranes control cell metabolism, viability, growth and differentiation. In this review, we focus on Rab GTPase roles in endocytosis to illustrate normal function and the consequences of dysregulation resulting in human disease. Selected examples are designed to illustrate how defects in Rab GTPase cascades alter endocytic trafficking that underlie neurologic, lipid storage, and metabolic bone disorders as well as cancer. Perspectives on potential therapeutic modulation of GTPase activity through small molecule interventions are provided.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The temperature derivative of the infrared (IR) spectrum of HOD/D2O is directly calculated from simulations at a single temperature using a fluctuation theory approach. It is demonstrated, on the ...basis of an energetic decomposition of the derivative, that the blue shift with increasing temperature is associated with the competition between electrostatic and Lennard-Jones interactions. The same competition gives rise, where their contributions cancel, to a near isosbestic point. The derivative is further used to define an effective internal energy (and entropy) associated with the IR spectrum, and it is shown how a van’t Hoff relation can be used to accurately predict the spectrum over a wide range of temperatures. These predictions also explain why a precise isosbestic point is not observed.
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Aims
To test whether recreational drug use (RDU) and sexualized drug use (SDU) changed in the Amsterdam area between 2008 and 2018 and quantify associations of SDU with condomless anal sex (CAS), ...recent human immunodeficiency virus (HIV) or sexually transmitted infections (STI) among human immunodeficiency virus (HIV)‐negative men who have sex with men (MSM).
Design
Open prospective cohort study.
Setting
Public Health Service of Amsterdam, the Netherlands.
Participants
A total of 976 HIV‐negative MSM, aged ≥ 18 years.
Measurements
Self‐reported RDU and sexual behaviour in the past 6 months. Laboratory‐confirmed HIV and STI (chlamydia, gonorrhoea and syphilis). We studied: any RDU; any SDU (i.e. any RDU during sex); specific SDU (i.e. use of mephedrone, methamphetamine, gamma‐hydroxybutyric acid/gamma‐butyrolactone, ketamine, amphetamine, cocaine and/or ecstasy during sex); use of individual drugs; and use of individual drugs during sex. We evaluated changes over calendar years in the proportion of individuals with these end‐points using logistic regression with generalized estimating equations (GEE) and number of drugs (using negative binomial regression with GEE), adjusted for current age, country of birth and education level.
Findings
Median age of participants in 2008 was 33.2 years (interquartile range = 27.8–40.1); 83.1% were born in the Netherlands. The proportion of any RDU increased from 67.2% in 2008 to 69.5% in 2018 adjusted odds ratio (aOR) = 1.25; 95% confidence interval (CI) = 1.03–1.51. Any SDU increased from 53.8% in 2008 to 59.8% in 2013 (aOR = 1.23; 95% CI = 1.07–1.42) and remained stable afterwards. Specific SDU increased from 25.0% in 2008 to 36.1% in 2018 (aOR = 2.10; 95% CI = 1.71–2.58). The average number of drugs used increased for those reporting any RDU, any SDU and specific SDU (all P < 0.05. Among those engaging in sex, any SDU was associated with CAS (aOR = 1.36; 95% CI = 1.19–1.55), HIV (aOR = 5.86; 95% CI = 2.39–14.4) and STI (aOR = 2.31; 95% CI = 1.95–2.73). Specific SDU was associated with CAS (aOR = 1.58; 95% CI = 1.37–1.81), HIV (aOR = 6.30; 95% CI = 3.28–12.1) and STI (aOR = 2.15; 95% CI = 1.81–2.55).
Conclusions
Among human immunodeficiency virus (HIV)‐negative men who have sex with men in Amsterdam, recreational drug use, including sexualized drug use, increased between 2008 and 2018. Sexualized drug use was strongly associated with condomless anal sex, HIV and sexually transmitted infections.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
In response to a need for a general catalog of genome variation to address the large-scale sampling designs required by association studies, gene mapping and evolutionary biology, the National Center ...for Biotechnology Information (NCBI) has established the dbSNP database S.T.Sherry, M.Ward and K.Sirotkin (1999) Genome Res., 9, 677–679. Submissions to dbSNP will be integrated with other sources of information at NCBI such as GenBank, PubMed, LocusLink and the Human Genome Project data. The complete contents of dbSNP are available to the public at website: http://www.ncbi.nlm.nih.gov/SNP. The complete contents of dbSNP can also be downloaded in multiple formats via anonymous FTP at ftp://ncbi.nlm.nih.gov/snp/.
Lung cancer is the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) lacks validated biomarkers to predict treatment response. This study investigated whether ...circulating tumor cells (CTCs) are detectable in patients with NSCLC and what their ability might be to provide prognostic information and/or early indication of patient response to conventional therapy.
In this single-center prospective study, blood samples for CTC analysis were obtained from 101 patients with previously untreated, stage III or IV NSCLC both before and after administration of one cycle of standard chemotherapy. CTCs were measured using a semiautomated, epithelial cell adhesion molecule-based immunomagnetic technique.
The number of CTCs in 7.5 mL of blood was higher in patients with stage IV NSCLC (n = 60; range, 0 to 146) compared with patients with stage IIIB (n = 27; range, 0 to 3) or IIIA disease (n = 14; no CTCs detected). In univariate analysis, progression-free survival was 6.8 v 2.4 months with P < .001, and overall survival (OS) was 8.1 v 4.3 months with P < .001 for patients with fewer than five CTCs compared with five or more CTCs before chemotherapy, respectively. In multivariate analysis, CTC number was the strongest predictor of OS (hazard ratio HR, 7.92; 95% CI, 2.85 to 22.01; P < .001), and the point estimate of the HR was increased with incorporation of a second CTC sample that was taken after one cycle of chemotherapy (HR, 15.65; 95% CI, 3.63 to 67.53; P < .001).
CTCs are detectable in patients with stage IV NSCLC and are a novel prognostic factor for this disease. Further validation is warranted before routine clinical application.
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