ASU Scholarship Showcase

Structural studies on living cells by conventional methods are limited to low resolution because radiation damage kills cells long before the necessary dose for high resolution can be delivered. X-ray free-electron lasers circumvent this problem by outrunning key damage processes with an ultra-short and extremely bright coherent X-ray pulse. Diffraction-before-destruction experiments provide high-resolution data from cells that are alive when the femtosecond X-ray pulse traverses the sample. This paper presents two data sets from micron-sized cyanobacteria obtained at the Linac Coherent Light Source, containing a total of 199,000 diffraction patterns. Utilizing this type of diffraction data will require the development of new analysis methods and algorithms for studying structure and structural variability in large populations of cells and to create abstract models. Such studies will allow us to understand living cells and populations of cells in new ways. New X-ray lasers, like the European XFEL, will produce billions of pulses per day, and could open new areas in structural sciences.

Gompertz’s empirical equation remains the most popular one in describing cancer cell population growth in a wide spectrum of bio-medical situations due to its good fit to data and simplicity. Many efforts were documented in the literature aimed at understanding the mechanisms that may support Gompertz’s elegant model equation. One of the most convincing efforts was carried out by Gyllenberg and Webb. They divide the cancer cell population into the proliferative cells and the quiescent cells. In their two dimensional model, the dead cells are assumed to be removed from the tumor instantly. In this paper, we modify their model by keeping track of the dead cells remaining in the tumor. We perform mathematical and computational studies on this three dimensional model and compare the model dynamics to that of the model of Gyllenberg and Webb. Our mathematical findings suggest that if an avascular tumor grows according to our three-compartment model, then as the death rate of quiescent cells decreases to zero, the percentage of proliferative cells also approaches to zero. Moreover, a slow dying quiescent population will increase the size of the tumor. On the other hand, while the tumor size does not depend on the dead cell removal rate, its early and intermediate growth stages are very sensitive to it.

Background: To determine the effects of high sucrose diets on vascular reactivity. We hypothesized that similar to high fat diets (HFD), HSD feeding would lead to increased adiposity resulting in inflammation and oxidative stress-mediated impairment of vasodilation.

Methods: Male Sprague-Dawley rats were fed control chow (Chow), HSD or HFD diets for 6 weeks. The role of inflammation and oxidative stress on impaired vasodilation were assessed in isolated mesenteric arterioles.

Results: HSD and HFD induced increased adiposity, oxidative stress and inflammation. HFD rats developed fasting hyperglycemia. Both HSD and HFD rats developed impaired glucose tolerance and hyperleptinemia. Nitric oxide (NO)-mediated vasodilation was significantly attenuated in both HSD and HFD rats but was normalized by treatment with antioxidants or anti-inflammatory drugs. Endothelial NO synthase (eNOS) protein expression was not affected by diet. Sensitivity to NO was reduced since NOS inhibition attenuated vasodilation in Chow rats but did not further impair vasodilation in HSD or HFD rats. Likewise, responsiveness to a NO donor was attenuated in both experimental groups.

Conclusions: Oxidative stress diminishes vasodilatory responsiveness in HSD and HFD rats through ROS-mediated scavenging of NO and decreased smooth muscle sensitivity to NO. Inflammation also plays a significant role in the impaired vasodilation.

Background: The National Health Interview Survey (NHIS) was used to ascertain whether increases in inadequate sleep differentially affected black and white Americans. We tested the hypothesis that prevalence estimates of inadequate sleep were consistently greater among blacks, and that temporal changes have affected these two strata differentially.

Methods: NHIS is an ongoing cross-sectional study of non-institutionalized US adults (≥18 years) providing socio-demographic, health risk, and medical factors. Sleep duration was coded as very short sleep [VSS] (<5 h), short sleep [SS] (5–6 h), or long sleep [LS] (>8 h), referenced to 7–8 h sleepers. Analyses adjusted for NHIS’ complex sampling design using SAS-callable SUDAAN.

Results: Among whites, the prevalence of VSS increased by 53 % (1.5 % to 2.3 %) from 1977 to 2009 and the prevalence of SS increased by 32 % (19.3 % to 25.4 %); prevalence of LS decreased by 30 % (11.2 % to 7.8 %). Among blacks, the prevalence of VSS increased by 21 % (3.3 % to 4.0 %) and the prevalence of SS increased by 37 % (24.6 % to 33.7 %); prevalence of LS decreased by 42 % (16.1 % to 9.4 %). Adjusted multinomial regression analysis showed that odds of reporting inadequate sleep for whites were: VSS (OR = 1.40, 95 % CI = 1.13-1.74, p < 0.001), SS (OR = 1.34, 95 % CI = 1.25-1.44, p < 0.001), and LS (OR = 0.94, 95 % CI = 0.85-1.05, NS). For blacks, estimates were: VSS (OR = 0.83, 95 % CI = 0.60-1.40, NS), SS (OR = 1.21, 95 % CI = 1.05-1.50, p < 0.001), and LS (OR = 0.84, 95 % CI = 0.64-1.08, NS).

Conclusions: Blacks and whites are characteristically different regarding the prevalence of inadequate sleep over the years. Temporal changes in estimates of inadequate sleep seem dependent upon individuals’ race/ethnicity.

Background: Androgens bind to the androgen receptor (AR) in prostate cells and are essential survival factors for healthy prostate epithelium. Most untreated prostate cancers retain some dependence upon the AR and respond, at least transiently, to androgen ablation therapy. However, the relationship between endogenous androgen levels and cancer etiology is unclear. High levels of androgens have traditionally been viewed as driving abnormal proliferation leading to cancer, but it has also been suggested that low levels of androgen could induce selective pressure for abnormal cells. We formulate a mathematical model of androgen regulated prostate growth to study the effects of abnormal androgen levels on selection for pre-malignant phenotypes in early prostate cancer development.

Results: We find that cell turnover rate increases with decreasing androgen levels, which may increase the rate of mutation and malignant evolution. We model the evolution of a heterogeneous prostate cell population using a continuous state-transition model. Using this model we study selection for AR expression under different androgen levels and find that low androgen environments, caused either by low serum testosterone or by reduced 5α-reductase activity, select more strongly for elevated AR expression than do normal environments. High androgen actually slightly reduces selective pressure for AR upregulation. Moreover, our results suggest that an aberrant androgen environment may delay progression to a malignant phenotype, but result in a more dangerous cancer should one arise.

Conclusions: The model represents a useful initial framework for understanding the role of androgens in prostate cancer etiology, and it suggests that low androgen levels can increase selection for phenotypes resistant to hormonal therapy that may also be more aggressive. Moreover, clinical treatment with 5α-reductase inhibitors such as finasteride may increase the incidence of therapy resistant cancers.

Objective: To assess the informational, educational and instrumental environments among Mexican healthcare settings for their potential to promote physical activity (PA).

Materials and Methods: The Environmental Physical Activity Assessment Tool for Healthcare Settings (EPATHS) was developed to assess the PA environments of 40 clinics/hospitals representing the three Mexican healthcare systems in Guadalajara. The EPATHS assessed the presence and quality of PA enhancing features in the informational (e.g. signage),educational (e.g. pamphlets), and instrumental (e.g. stairs)environments of included clinics/hospitals.

Results: 28 (70%) clinics/hospitals had more than one floor with stairs; 60% of these had elevators. Nearly 90% of stairs were visible, accessible and clean compared to fewer than 30% of elevators. Outdoor spaces were observed in just over half (55%) of clinics/hospitals, and most (70%) were of good quality. Only 25% clinics/hospitals had educational PA materials.

Conclusions: The PA instrumental environment of Mexican healthcare settings is encouraging. The informational and educational environments could improve.

Depression and anxiety after stroke negatively affect patient outcomes; however, health care professionals may overlook poststroke depression and anxiety while they focus on the physical disabilities of patients soon after a stroke. The purpose of this study was to investigate the prevalence and predictors of depression, anxiety, or both concurrently at one month after stroke. We conducted a cross-sectional, descriptive study in a sample of 231 hospitalized patients with ischemic stroke in Korea. Data were collected by interviews using a series of structured questionnaires in addition to clinical data retrieved from patients’ medical records. More than 70% were identified as depressed, 45.9% experienced anxiety, and 43.7% had concurrent depression and anxiety. Using a multiple logistic regression analysis, we identified anxiety as a predictor of depression; depression as a predictor of anxiety; and female sex, headaches, and swallowing difficulty as predictors of the comorbidity of depression and anxiety. Periodical screenings for poststroke depression and anxiety from an early stage in a hospital to years after stroke in a community are recommended to provide better chances for early identification of patients at risk because depression and anxiety may manifest at any stage of recovery. Special attention should be given to individuals with culture-bound somatic symptoms in addition to female patients and those who have difficulty swallowing among Korean stroke patients.

Purpose: To identify barriers and discuss strategies for recruitment of older Chinese immigrants into clinical research studies.

Methods: A systematic review was conducted using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). PubMed, WEB of Science, CINAHL Plus, and the Cochrane Central Register of Controlled Trials were searched from 2001 to 2014. Empirical studies with Chinese immigrants aged 60 or older were identified and analyzed. Numerical analysis, such as calculation of response rates as indexes for recruitment outcomes, was conducted. Content analyses for recruitment barriers were abstracted.

Results: Thirteen studies of 4753 subjects were analyzed. Response rates ranged from 39% to 99%. Recruitment barriers include younger old age (i.e., 60-70 years old), low health literacy, longer length of stay in the US, limited English speaking ability, low acculturation, time constraints, inadequate transportation, social stigma about diseases, and mistrust of researchers.

Discussion: Recruitment can be facilitated by overcoming the aforementioned barriers, which include the following strategies: 1) using convenience sampling methods, particularly personal referral; 2) using special techniques to recruit younger subgroup of Chinese elders, such as doing outreach on holidays or weekends; 3) communicating effectively using participants’ native language; 4) exercising cultural competency; 5) establishing relationships of trust with participants and community leaders; 6) answering misconceptions about clinical trials; 7) providing incentives for participation; and 8) proper selection of research and interview locations.

The aim of this study was to evaluate the effects of moderate aerobic exercise training on sleep, depression, cortisol, and markers of immune function in patients with chronic primary insomnia. Twenty-one sedentary participants (16 women aged 44.7 ± 9 years) with chronic primary insomnia completed a 4-month intervention of moderate aerobic exercise. Compared with baseline, polysomnographic data showed improvements following exercise training. Also observed were reductions in depression symptoms and plasma cortisol. Immunologic assays revealed a significant increase in plasma apolipoprotein A (140.9 ± 22 to 151.2 ± 22 mg/dL) and decreases in CD4 (915.6 ± 361 to 789.6 ± 310 mm[superscript 3]) and CD8 (532.4 ± 259 to 435.7 ± 204 mm[superscript 3]). Decreases in cortisol were significantly correlated with increases in total sleep time (r = -0.51) and REM sleep (r = -0.52). In summary, long-term moderate aerobic exercise training improved sleep, reduced depression and cortisol, and promoted significant changes in immunologic variables.

This study explores the capabilities of the Coherent X-ray Imaging Instrument at the Linac Coherent Light Source to image small biological samples. The weak signal from small samples puts a significant demand on the experiment. Aerosolized Omono River virus particles of ∼40 nm in diameter were injected into the submicrometre X-ray focus at a reduced pressure. Diffraction patterns were recorded on two area detectors. The statistical nature of the measurements from many individual particles provided information about the intensity profile of the X-ray beam, phase variations in the wavefront and the size distribution of the injected particles. The results point to a wider than expected size distribution (from ∼35 to ∼300 nm in diameter). This is likely to be owing to nonvolatile contaminants from larger droplets during aerosolization and droplet evaporation. The results suggest that the concentration of nonvolatile contaminants and the ratio between the volumes of the initial droplet and the sample particles is critical in such studies. The maximum beam intensity in the focus was found to be 1.9 × 10¹² photons per µm² per pulse. The full-width of the focus at half-maximum was estimated to be 500 nm (assuming 20% beamline transmission), and this width is larger than expected. Under these conditions, the diffraction signal from a sample-sized particle remained above the average background to a resolution of 4.25 nm. The results suggest that reducing the size of the initial droplets during aerosolization is necessary to bring small particles into the scope of detailed structural studies with X-ray lasers.