Differences in Withdrawal Symptomatology during Short-Term Smoking Abstinence in Menthol versus Non-Menthol Female Smokers

Faculty adviser: Alicia M Allen, Ph.D., M.P.H.Menthol cigarettes are popular among smokers, but menthol smokers have been shown to have a harder time quitting smoking. More severe withdrawal symptoms in menthol cigarette smokers versus non-menthol cigarette smokers may contribute to less-successful smoking cessation outcomes among menthol smokers. The purpose of this project is to examine whether menthol cigarette smokers showed more severe withdrawal symptoms, as measured by the Minnesota Withdrawal Scale (MNWS) and the Questionnaire on Smoking Urges - Brief (QSU), than non-menthol smoking counterparts during short-term smoking abstinence.This research was supported by the Undergraduate Research Opportunities Program (UROP)

Changes in skeletal collagen crosslinks and matrix hydration in high and low turnover chronic kidney disease

Chronic kidney disease (CKD) increases fracture risk. The results of this work point to changes in bone collagen and bone hydration as playing a role in bone fragility associated with CKD. INTRODUCTION: Clinical data have documented a clear increase in fracture risk associated with chronic kidney disease (CKD). Preclinical studies have shown reductions in bone mechanical properties although the tissue-level mechanisms for these differences remain unclear. The goal of this study was to assess collagen cross-links and matrix hydration, two variables known to affect mechanical properties, in animals with either high- or low-turnover CKD. METHODS: At 35 weeks of age (>75 % reduction in kidney function), the femoral diaphysis of male Cy/+ rats with high or low bone turnover rates, along with normal littermate (NL) controls, were assessed for collagen cross-links (pyridinoline (Pyd), deoxypyridinoline (Dpd), and pentosidine (PE)) using a high-performance liquid chromatography (HPLC) assay as well as pore and bound water per volume (pw and bw) using a 1H nuclear magnetic resonance (NMR) technique. Material-level biomechanical properties were calculated based on previously published whole bone mechanical tests. RESULTS: Cortical bone from animals with high-turnover disease had lower Pyd and Dpd cross-link levels (-21 % each), lower bw (-10 %), higher PE (+71 %), and higher pw (+46 %) compared to NL. Animals with low turnover had higher Dpd, PE (+71 %), and bw (+7 %) along with lower pw (-60 %) compared to NL. Both high- and low-turnover animals had reduced material-level bone toughness compared to NL animals as determined by three-point bending. CONCLUSIONS: These data document an increase in skeletal PE with advanced CKD that is independent of bone turnover rate and inversely related to decline in kidney function. Although hydration changes occur in both high- and low-turnover disease, the data suggest that nonenzymatic collagen cross-links may be a key factor in compromised mechanical properties of CKD.This work was supported by National Institutes of Health grants AR58005 (SM), DL100093 (CN), AR063157 (JSN), and the Indiana Clinical Translational Science Institute grant TR000162 (CN). The cross-link analysis is the result of work supported with resources and the use of facilities at the VA Tennessee Valley Healthcare System. All authors were involved in the design, conduct and analyses of the study. The authors would like to thank Drew Brown, Shannon Roy, and Kali O’Neill for technical assistance. We would also like to acknowledge the late Dr. Vincent H. Gattone II (1951-2013), who was instrumental in developing this animal model

Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease

Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild antiresorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole-bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared with normal controls, as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. Although it had little effect on cortical bone geometry, it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation, and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole-bone mechanical properties in CKD through its impact on skeletal material properties

Optimality of mutation and selection in germinal centers

The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis of its parameter space to look for optimal values of mutation rate, selection strength, and initial antibody-antigen binding level that maximize the affinity improvement. With these optimized parameters, the model is compatible with the experimental observations such as the ~100-fold affinity improvements, the number of mutations, the hypermutation rate, and the "all or none" phenomenon. Moreover, we study the reasons behind the optimal parameters. The optimal mutation rate, in agreement with the hypermutation rate in vivo, results from a tradeoff between accumulating enough beneficial mutations and avoiding too many deleterious or lethal mutations. The optimal selection strength evolves as a balance between the need for affinity improvement and the requirement to pass the population bottleneck. These findings point to the conclusion that germinal centers have been optimized by evolution to generate strong affinity antibodies effectively and rapidly. In addition, we study the enhancement of affinity improvement due to B cell migration between germinal centers. These results could enhance our understandings to the functions of germinal centers.Comment: 5 figures in main text, and 4 figures in Supplementary Informatio

The Type Ia Supernova Rate in Redshift 0.5--0.9 Galaxy Clusters

Supernova (SN) rates are potentially powerful diagnostics of metal enrichment and SN physics, particularly in galaxy clusters with their deep, metal-retaining potentials and relatively simple star-formation histories. We have carried out a survey for supernovae (SNe) in galaxy clusters, at a redshift range 0.5<z<0.9, using the Advanced Camera for Surveys (ACS) on the Hubble Space Telescope. We reimaged a sample of 15 clusters that were previously imaged by ACS, thus obtaining two to three epochs per cluster, in which we discovered five likely cluster SNe, six possible cluster SNe Ia, two hostless SN candidates, and several background and foreground events. Keck spectra of the host galaxies were obtained to establish cluster membership. We conducted detailed efficiency simulations, and measured the stellar luminosities of the clusters using Subaru images. We derive a cluster SN rate of 0.35 SNuB +0.17/-0.12 (statistical) \pm0.13 (classification) \pm0.01 (systematic) [where SNuB = SNe (100 yr 10^10 L_B_sun)^-1] and 0.112 SNuM +0.055/-0.039 (statistical) \pm0.042 (classification) \pm0.005 (systematic) [where SNuM = SNe (100 yr 10^10 M_sun)^-1]. As in previous measurements of cluster SN rates, the uncertainties are dominated by small-number statistics. The SN rate in this redshift bin is consistent with the SN rate in clusters at lower redshifts (to within the uncertainties), and shows that there is, at most, only a slight increase of cluster SN rate with increasing redshift. The low and fairly constant SN Ia rate out to z~1 implies that the bulk of the iron mass in clusters was already in place by z~1. The recently observed doubling of iron abundances in the intracluster medium between z=1 and 0, if real, is likely the result of redistribution of existing iron, rather than new production of iron.Comment: Accepted to ApJ. Full resolution version available at http://kicp.uchicago.edu/~kerens/HSTclusterSNe

Effects of a nanoscopic filler on the structure and dynamics of a simulated polymer melt and the relationship to ultra-thin films

We perform molecular dynamics simulations of an idealized polymer melt surrounding a nanoscopic filler particle to probe the effects of a filler on the local melt structure and dynamics. We show that the glass transition temperature $T_g$ of the melt can be shifted to either higher or lower temperatures by appropriately tuning the interactions between polymer and filler. A gradual change of the polymer dynamics approaching the filler surface causes the change in the glass transition. We also find that while the bulk structure of the polymers changes little, the polymers close to the surface tend to be elongated and flattened, independent of the type of interaction we study. Consequently, the dynamics appear strongly influenced by the interactions, while the melt structure is only altered by the geometric constraints imposed by the presence of the filler. Our findings show a strong similarity to those obtained for ultra-thin polymer films (thickness $\lesssim 100$ nm) suggesting that both ultra-thin films and filled-polymer systems might be understood in the same context

Strong Lensing Analysis of A1689 from Deep Advanced Camera Images

We analyse deep multi-colour Advanced Camera images of the largest known gravitational lens, A1689. Radial and tangential arcs delineate the critical curves in unprecedented detail and many small counter-images are found near the center of mass. We construct a flexible light deflection field to predict the appearance and positions of counter-images. The model is refined as new counter-images are identified and incorporated to improve the model, yielding a total of 106 images of 30 multiply lensed background galaxies, spanning a wide redshift range, 1.0$<$z$<$5.5. The resulting mass map is more circular in projection than the clumpy distribution of cluster galaxies and the light is more concentrated than the mass within $r<50kpc/h$. The projected mass profile flattens steadily towards the center with a shallow mean slope of $d\log\Sigma/d\log r \simeq -0.55\pm0.1$, over the observed range, r$<250kpc/h$, matching well an NFW profile, but with a relatively high concentration, $C_{vir}=8.2^{+2.1}_{-1.8}$. A softened isothermal profile ($r_{core}=20\pm2$\arcs) is not conclusively excluded, illustrating that lensing constrains only projected quantities. Regarding cosmology, we clearly detect the purely geometric increase of bend-angles with redshift. The dependence on the cosmological parameters is weak due to the proximity of A1689, $z=0.18$, constraining the locus, $\Omega_M+\Omega_{\Lambda} \leq 1.2$. This consistency with standard cosmology provides independent support for our model, because the redshift information is not required to derive an accurate mass map. Similarly, the relative fluxes of the multiple images are reproduced well by our best fitting lens model.Comment: Accepted by ApJ. For high quality figures see http://wise-obs.tau.ac.il/~kerens/A168

Mechanisms of Psychological Distress following War in the Former Yugoslavia: The Role of Interpersonal Sensitivity

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This study was funded by a grant from the European Commission, contract number INCO-CT-2004-509176. AN was supported by a Clinical Early Career Research Fellowship (113295) and a Project Grant (104288