Flavor decomposition of the nucleon electromagnetic form factors

Background: The spatial distribution of charge and magnetization in the proton and neutron are encoded in the nucleon electromagnetic form factors. The form factors are all approximated by a simple dipole function, normalized to the charge or magnetic moment of the nucleon. The differences between the proton and neutron form factors and the deviation of GEn from zero are sensitive to the difference between up- and down-quark contributions to the form factors. Methods: We combine recent measurements of the neutron form factors with updated extractions of the proton form factors, accounting for two-photon exchange corrections and including an estimate of the uncertainties for all of the form factors to obtain a complete set of measurements up to Q^2 approximately 4 (GeV/c)^2. We use this to extract the up- and down-quark contributions which we compare to recent fits and calculations. Results: We find a large differences between the up- and down-quark contributions to G_E and G_M, implying significant flavor dependence in the charge and magnetization distributions. The rapid falloff of the ratio GEp/GMp does not appear in the individual quark form factors, but arises from a cancellation between the up- and down-quark contributions. We see indications that the down-quark contributions to the Dirac and Pauli form factors deviate from the suggested 1/Q^4 scaling behavior suggested by a previous analysis. Finally, while recent models provide a generally good qualitative description of the data, the down-quark contribution to G_E/G_M and F_2/F_1 are not reproduced by any of the models. Finally, we note that while the inclusion of recent \gmn data from CLAS modifies the high-$Q^2$ slightly, the tension between these data and previous measurements at lower $Q^2$ has a more significant impact, suggesting the need for additional data in this region.Comment: 13 pages, 10 figures, submitted to Physical Review

Gene Silencing Agents in Breast Cancer

MicroRNAs (miRs) are a class of non-coding RNAs, approximately 20–25 nucleotides long, discovered in the nematode, Caenorhabditis elegans, in 1993. There are two primary categories of non-coding RNA (ncRNA): (1) short interfering RNAs (siRNA) and (2) microRNAs (miRs). In general, miRs control protein production via partially complementary binding of the mRNA 3′UTRs. Both siRNAs and miRNAs are critical regulators of developmental and homeostatic processes as well as disease pathogenesis. While the treatment of advanced stage breast cancer presents several challenges, the development of therapeutic resistance contributes to a high mortality rate. Dysregulation of miR expression has been implicated in progression of breast cancer disease. Moreover, miRs have been found to play a role in the development of drug resistance. In this context, one of the therapeutic potentials of miRNAs is the correlation of circulating miR levels with breast cancer progression stages and disease phenotypes. Secondly, researchers are investigating novel delivery strategies for the substitution or silencing of ncRNAs involved in the disease. This chapter describes both the general miRNA mechanism of actions and the miRNAs related to breast cancer research. It is specifically designed for breast cancer researchers with expertise in gene delivery, clinicians, and clinical translational scientists

Duplicitous Dispositions of Micro-RNAs (miRs) in Breast Cancer

In 1993, a gene silencer known as lin-4 was first discovered in Caenorhabditis elegans and demonstrated to be critical for larval development. Lin-4 belongs to a family of signaling molecules known as non-protein coding microRNAs (miRNAs) which are not only highly conserved in humans, but also involved in the fundamental processes of oncogenesis. While miRNAs are not translated to proteins themselves, they are capable of regulating the expression and translation of other genes thus affecting a multitude of biological and pathological pathways as well as those essential to the malignant landscape. The aim of this chapter is to explore the diverse roles of miRNAs in the context of breast cancer. Following a brief overview of miRNA biogenesis, this chapter covers the production of miRNAs by tumor cells and stromal cells, onco-suppressor miRNAs, use as therapeutics, contribution to therapeutic resistance, and finally their emerging role as biomarkers

The Effect of Work-Related Stress and Burnout on Nursing Performance and Job Satisfaction: a Study of Hospitals in Saudi Arabia.

Background: While there is much research on work-related stress among nurses in the literature, little attention has been focused on the effect of work-related stress and burnout on nursing performance and job satisfaction in hospitals within Saudi Arabia. In particular, studies from the western region of Saudi Arabia are lacking. Therefore, this study focuses on nurses in Jeddah, the country’s entry port and a city that regularly hosts pilgrims. Jeddah is highly multicultural, and the second largest city in Saudi Arabia with nearly 4 million people including travellers; it has the largest foreigner to citizen population ratio in Saudi Arabia, and a particularly high proportion of hospital nurses non-native to Saudi Arabia. Aim: The aim of this thesis was to identify research gaps and to contribute to existing knowledge by developing hypotheses pertaining to the level of work-related stress and burnout among hospital nurses in different hospital types in Jeddah. The study further evaluated the relationship between work-related stress and burnout, and how this related to nursing performance and job satisfaction. The analysis also examined the relationships between these variables among hospital nurses, and whether relationships are different for different hospital types. Methods: A systematic review of existing research into nursing stress in Saudi Arabia between 2003 and 2014 was carried out. From the 81 articles identified from the database search, 8 met the inclusion criteria. At the onset a pilot study was conducted was done among hospital nurses in King Abdulaziz University.Thereafter, a quantitative survey of 567 nurses derived from three large hospitals representing each sector (private, public and other governmental agency sector hospitals) was conducted. Bilingual questionnaires were used to collect quantifiable, reliable, and valid data in order to test the hypothesis derived from the pilot study.The data was analysed by quantitative research method of cross-sectional analysis and correlational study. Findings: Results showed levels of work-related stress varied among nurses depending on the type of hospital where the nurses were employed. Furthermore, there was a positive relationship between levels of work-related stress and burnout among hospital nurses working in all three types of hospitals in Saudi Arabia. However, there was a very weak relationship between work-related stress and job performance among private hospital (International Medical Center) nurses compared to the strength of this relationship observed in public hospitals. Stress was a significant predictor of burnout among nurses while burnout was the strongest descriptor of the relationship between work-related stress and job satisfaction among nurses. The analysis outcome revealed that work-related stress had the highest impact on job satisfaction, which was facilitated by burnout. Nurses working in the public (King Fahad Hospital) and university (King Abdulaziz University Hospital) hospitals reported high levels of stress and burnout, and also conveyed low levels of job performance and high levels of dissatisfaction compared with nurses working in the International Medical Center (IMC) . The type of hospital moderated the effect between burnout and job satisfaction in both King Fahad Hospital (KFH) and King Abdulaziz University Hospital (KAUH) but did not affect the International Medical Center (IMC).The relationship between stress and burnout was significantly stronger in nurses working in the IMC compared with the KFH and KAUH hospitals. However, burnout was not important in the relationship between stress and satisfaction for those who worked in IMC. Therefore, hospital type did appear to moderate the mediation effect between burnout and job satisfaction, even though, the mediation effect occurred only in KFH and KAUH hospitals but not in IMC . Conclusion: The study demonstrated that there is evidence of work-related stress among nurses in Jeddah, Saudi Arabia.Its prevalence depended on the age,experience,nationality and the employment status of the nurses. Work-related stress and burnout impacted negatively on job performance and job satisfaction in nurses in public (KFH) and university (KAUH) hospitals but not in private (IMC) hospitals.Notably,there is a mediated relationship between work-related stress and burnout and a moderated mediation difference between the type of hospitals. Both work-related stress and burnout have shown an effect on the level of job satisfaction of nurses and their job performance. In essence,measures should be taken to help alleviate work-related stress and burnout levels of nurses working in non-privately funded hospitals Saudi Arabia. This study recommends an increase hiring Saudi Arabian nurses,a review of task allocation policies for nurses,provision of targeted training for nurses,increased focused government funds allocation to healthcare,an adoption of an integrated stress prevention, intervention and management program throughout the healthcare system of Saudi Arabia

Metabolic Reprogramming of Triple-Negative Breast Cancer: The Role of miRNAs

MicroRNAs (miRNAs) are well known to influence the expression of the genes that regulate critical cellular functions. Various reports have suggested that they play critical roles in breast cancer metabolism through the regulation of various metabolic pathways, including the metabolism of glucose, lipids, glycolysis and the mitochondrial tricarboxylic acid cycle (TCA). miRNAs regulate the metabolic process by targeting key molecules (enzymes, kinases transporters) or by modifying the expression of key transcription molecules. In addition, miRNAs can indirectly regulate mRNA translation by targeting chromatin-remodeling enzymes. Furthermore, miRNAs influence the expression of both oncogenes and tumor suppressors and have a major impact on PI3K/AKT, HIF, and MYC signal transduction, which contributes to the metabolic phenotype in human cancer. Although human epidermal growth factor and endocrine therapies have been effective in treating breast cancer, for locally advanced and distant metastases mortality remains high. Drug resistance and recurrence remain major hurdles for advanced breast cancer therapy. Given the critical influence of metabolic reprogramming in the progression of neoplasm, tumorigenesis and metastasis, research should focus on novel targets of metabolic enzymes to reverse drug resistance and improve overall survival rates. Blocking the miRNAs that contribute to metabolic reprogramming or the use of exogenous miRNAs as antisense oligonucleotides, may be an effective way to treat aggressive, chemo-resistant cancers. This review summarizes current knowledge on the mechanism of action of miRNAs in altering the metabolism of cancer cells and presents possible therapeutic approaches to treating breast cancers that are resistant to current drugs

Precision Rosenbluth Measurement of the Proton Elastic Electromagnetic Form Factors and Their Ratio at Q^2 = 2.64, 3.20, and 4.10 GeV^2

Due to the inconsistency in the results of the GEp/Gmp ratio of the proton, as extracted from the Rosenbluth and recoil polarization techniques, high precision measurements of the e-p elastic scattering cross sections were made at Q^2 = 2.64, 3.20, and 4.10 GeV^2. Protons were detected, in contrast to previous measurements where the scattered electrons were detected, which dramatically decreased epsilon-dependent systematic uncertainties and corrections. A single spectrometer measured the scattered protons of interest while simultaneous measurements at Q^2 = 0.5 GeV^2 were carried out using another spectrometer which served as a luminosity monitor in order to remove any uncertainties due to beam charge and target density fluctuations. The absolute uncertainty in the measured cross sections is \approx 3% for both spectrometers and with relative uncertainties, random and slope, below 1% for the higher Q^2 protons, and below 1% random and 6% slope for the monitor spectrometer. The extracted electric and magnetic form factors were determined to 4%-7% for GEp and 1.5% for GMp. The ratio GEp/Gmp was determined to 4%-7% and showed mu_p GEp/GMp \approx 1.0. The results of this work are in agreement with the previous Rosenbluth data and inconsistent with high-Q^2 recoil polarization results, implying a systematic difference between the two techniques.Comment: Ph.D. Thesis, Northwestern University, Advisor: Ralph E. Sege