Expression of antimicrobial peptides associated with different susceptibilities to environmental chemicals in Drosophila suzukii and Drosophila melanogaster.

Drosophila suzukii is a serious agricultural pest. The evolved morphology of the female D. suzukii assists in penetrating the surface of fresh fruit and spawns eggs with its unique ovipositor. Conversely, Drosophila melanogaster, a taxonomically close species with D. suzukii, largely inhabits decaying and fermenting fruits and is consistently exposed to extensive environmental chemicals, such as 2-phenylethanol, ethanol, and acetic acid, produced by microorganisms. Considering the distinct habitats of the two flies, D. suzukii is thought to be more susceptible to environmental chemicals than D. melanogaster. We investigated the significantly higher survival rate of D. melanogaster following exposure to 2-phenylethanol, ethanol, and acetic acid. A comparison of the expression of antimicrobial peptides (AMPs) between the two flies treated with chemicals established that AMPs were generally more abundantly induced in D. melanogaster than in D. suzukii, particularly in the gut and fat body. Among the AMPs, the induction of genes (Diptericin A, Diptericin B, and Metchnikowin), which are regulated by the immune deficiency (IMD) pathway, was significantly higher than that of Drosomycin, which belongs to the Toll pathway in chemical-treated D. melanogaster. A transgenic RNAi fly (D. melanogaster) with silenced expression of AMPs and Relish, a transcription factor of the IMD pathway, exhibited significantly reduced survival rates than the control fly. Our results suggest that AMPs regulated by the IMD pathway play an important role in the chemical tolerance of D. melanogaster, and these flies are adapted to their habitats by physiological response.

Colorectal polyp prevention by daily aspirin use is abrogated among active smokers.

PURPOSE: Based on suggestive findings from a recent study of high-risk Japanese patients, we sought to determine whether the risk of colorectal polyps associated with smoking may be modified by daily use of aspirin in an analysis of a large US screening population. METHODS: This is a cross-sectional study of 2,918 consecutive colonoscopy patients at a university hospital over a 30-month period. Data were abstracted from electronic medical records. Multivariate models of polyp counts were used to examine the competing risks of smoking and aspirin use. Models were further stratified by polyp location (proximal vs. distal) and pathologic subtype (dysplastic vs. serrated). RESULTS: Incidental rate of polyps was higher among active smokers [incidence rate ratio (IRR) 1.72; 95 % confidence interval (CI) 1.46-2.02] and lower among daily aspirin users (IRR 0.73; 95 % CI 0.61-0.86) compared to those who used neither. Smoking interacts significantly with aspirin use resulting in loss of aspirin protection (IRR 1.69; 95 % CI 1.28-2.24). Stratified analyses demonstrate that aspirin specifically reduces the risk of traditional dysplastic adenomas (IRR 0.72; 95 % CI 0.61-0.86) not serrated/hyperplastic polyps (IRR 0.92; 95 % CI 0.72-1.17) and that the modification of aspirin protection by smoking is primarily observed within the distal colorectum (p < 0.03). CONCLUSIONS: We report for the first time, in a typical risk US clinical population, a lack of protective association of aspirin for polyps among active smokers. Future prospective studies are recommended to confirm this mitigating effect in order to improve the precision of the growing evidence base about the chemopreventive benefit of aspirin in colorectal cancer.

Optimal periods of exclusive breastfeeding associated with any breastfeeding duration through one year.

OBJECTIVE: To quantify optimal minimum durations of exclusive breastfeeding associated with maintenance of any breastfeeding at 15 time points during the first year of life. STUDY DESIGN: Mothers (n = 1189) from the prospective Infant Feeding Practices Study II cohort who initiated exclusive breastfeeding with healthy term infants were included. In a 80:20 split-sample validation study, receiver operating characteristic curves estimated optimal minimum durations of exclusive breastfeeding needed to predict maintenance of any breastfeeding at 15 time points during the first year (n = 951). Logistic regression estimated the predictive performance of the identified thresholds adjusted for maternal age, race, education, parity, support system, and return-to-work status. Results were validated in the remaining 20% (n = 238). RESULTS: Optimal minimum durations ranged from 4.0-17.1 weeks of exclusive breastfeeding associated with maintenance of any breastfeeding at 15 time points. All estimated threshold durations were statistically significant after adjustment. CONCLUSIONS: Using a methodological approach unique to breastfeeding duration research, the authors report optimal durations of exclusive breastfeeding associated with duration of any breastfeeding at time points throughout the first year. Perinatal clinicians, pediatricians, lactation professionals, policymakers, researchers, and families might apply these findings to achieve desirable collective breastfeeding duration outcomes.

Therapy model for advanced intracerebral B16 mouse melanoma using radiation therapy combined with immunotherapy.

A reproducible therapy model for advanced intracerebral B16 melanoma is reported. Implanted tumors (D0), suppressed by a single 15 Gy radiosurgical dose of 100 kVp X-rays (D8), were further suppressed by a single ip injection of a Treg-depleting mAb given 2 days prior to the initiation (D9) of four weekly then eight bi-monthly sc injections of GMCSF-transfected, mitotically disabled B16 cells. The trends of seven independent experiments were similar to the combined result: The median (days) [SD/total N] of survival went from 15[1.09/62] (no treatment control) to 35.8[8.8/58] (radiation therapy only) to 52.5[13.5/57] (radiation therapy plus immunotherapy). Within 2 weeks after immunization, tumors in mice receiving radiation therapy plus immunotherapy were significantly smaller than tumors in mice treated only with radiosurgery. Splenocytes and lymph node cells from immunized mice showed increased interferon γ production when cultured with syngeneic tumor cells. We suggest that our model will be useful for the development and testing of novel combination therapies for brain tumors.

Microfabrication of Microlens by Timed-Development-and-Thermal-Reflow (TDTR) Process for Projection Lithography.

This paper presents a microlens fabrication process using the timed-development-and-thermal-reflow process, which can fabricate various types of aperture geometry with a parabolic profile on a single substrate in the same batch of the process. By controlling the development time of the uncrosslinked negative photoresist, a state of partial development of the photoresist is achieved, called the timed development process. The thermal reflow process is followed after the timed development, which allows the photoresist to regain its liquid state to form a smooth meniscus trench surrounded by a crosslinked photoresist sidewall. Microlens with larger aperture size forms deeper trench with constant development time. With constant aperture size, longer developing time shows deeper meniscus trench. The depth of the meniscus trench is modeled in the relationship of the development time and aperture size. Other characteristics for the microlens including the radius of curvature, focal length, and the parabolic surface profile are modeled in the relationship of the microlens thickness and diameter. Microlens with circular, square, and hexagonal bases have been successfully fabricated and demonstrated where each geometry of the lens-bases shows different fill factors of the lens arrays. To test the fabricated lenses, a miniaturized projection lithography scheme was proposed. A centimeter-scale photomask pattern was photo-reduced using the fabricated microlens array with a ratio of 133, where the smallest linewidth was measured as 2.6 µm.

Estimating non-additive within-season temperature effects on maize yields using Bayesian approaches.

Detrimental impacts of extreme heats on the U.S. crop yields have been well-documented by a number of empirical studies. However, less have focused on within-growing season weather variation and the interaction between temperature and precipitation. The objective of this study is to emphasize the importance of disaggregating temperature exposures within growing season. To achieve our objective, we estimate the impact of within-season monthly temperature and precipitation variations on maize yields in the U.S. corn belt region. We provide a discussion on variable selection methods in the context of estimating crop yield responses to climate variables. We find that the models that utilize within-growing season monthly variations performs better compared to the models with growing season aggregated weather variables and show the strength of Bayesian estimations. We also find that the warming impacts predicted by the models that utilize within-growing season variations are smaller than the predicted impacts of the models with aggregated weather variables. The findings indicate that the temperature effects are not additive across months within growing season.

Bayesian sparse reduced rank multivariate regression.

Many modern statistical problems can be cast in the framework of multivariate regression, where the main task is to make statistical inference for a possibly sparse and low-rank coefficient matrix. The low-rank structure in the coefficient matrix is of intrinsic multivariate nature, which, when combined with sparsity, can further lift dimension reduction, conduct variable selection, and facilitate model interpretation. Using a Bayesian approach, we develop a unified sparse and low-rank multivariate regression method to both estimate the coefficient matrix and obtain its credible region for making inference. The newly developed sparse and low-rank prior for the coefficient matrix enables rank reduction, predictor selection and response selection simultaneously. We utilize the marginal likelihood to determine the regularization hyperparameter, so our method maximizes its posterior probability given the data. For theoretical aspect, the posterior consistency is established to discuss an asymptotic behavior of the proposed method. The efficacy of the proposed approach is demonstrated via simulation studies and a real application on yeast cell cycle data.