UCLA Library

Prostate cancer growth is driven by androgen signaling using the androgen receptor (AR). Androgen deprivation therapy (ADT) is the gold standard for prostate cancer, but the majority of ADT-treated patients develop resistance, which often involves the loss of luminal lineage identity and AR-independent growth. Previous work has shown that modulating metabolism can regulate cell fate in many tissues. Therefore, it is important to understand the mechanisms behind how altered metabolism affects lineage identity and response to AR blockade, a common form of treatment for prostate cancer involving blocking AR signaling. Inhibition of mitochondrial pyruvate carrier 1, an essential metabolic enzyme, with small molecule UK5099 in mouse basalderived nonmalignant organoids blocked luminal differentiation and UK5099-treated organoids retained a basal phenotype. AR expression decreased substantially in vehicle-treated organoids, but had a more modest decrease in UK5099-treated organoids in castrated conditions. Expression of Tmprss2, an AR target gene, slightly decreased in vehicle-treated organoids, yet slightly increased with UK5099 treatment in castrated conditions. The organoid size assay was a useful tool in determining how modulating metabolism affected the impact of castration on organoid diameter in 3D ex vivo organoid culture. It shows that the number of days post-castration onset could affect the relative size of different treatment groups, but 6 days after castration vehicletreated organoids were smaller in castrated conditions than control conditions. Castrated UK5099-treated organoids, however, appeared slightly larger than the UK5099 control. An investigation into differentiation and metabolic pathways affected by UK5099-treatment revealed differential expression of phosphorylated p-65 (NFkB), changes in β-catenin nuclear translocation, and increased citrate synthase, OGDH, and MDH2 in the nucleus. This shows that UK5099 affects both differentiation and metabolism. Collectively, these results show that altering metabolism affects lineage identity and response to AR blockade. Modulation of metabolism appears to be a potential method of improving clinical outcomes for advanced prostate cancer.

Objective To investigate the estimated hearing preservation rates in patients with sporadic VS (vestibular schwannomas) after RS (retrosigmoid) surgery through a meta-analysis based on the published hearing outcomes within the current literature.

Data Sources Both the PubMed and Cochrane databases were used to identify retrospective and prospective studies which involved hearing outcomes of VS patients who underwent the RS approach. The final search was performed on November 11, 2017. The first and third authors independently reviewed the aggregated articles, and final decisions of study inclusion were dependent on consensus.

Study Selection Of 313 articles, 16 studies (5.1%) met eligibility criteria. Together, these 16 studies comprised a total of 1,249 patients with serviceable preoperative hearing in the affected ear, from whom postoperative hearing preservation could be evaluated.

Data Extraction Both preoperative and postoperative hearing grades were extracted to determine the hearing preservation rate presented in the group of patients in each article. Additionally, demographics regarding gender, age, mean tumor size, and mean FU (follow-up) time pertaining to the patients in each article were extracted as well.

Data Synthesis Study heterogeneity was quantified through computation of t²,Q, and I² statistics. A Wald-type Q statistic was used to assess statistical significance of study heterogeneity. Assessment of study bias was performed using standard funnel plot analysis and an Egger’s test for funnel plot asymmetry. Significant cross-study heterogeneity was found, with rates of hearing preservation ranging from 12-79% across studies. Aggregate hearing preservation was 23% under a fixed effects model and 37% allowing for random study effects. Clear systematic bias was also apparent, with disproportionate numbers of (mostly smaller) studies reporting hearing preservation rates markedly higher than the aggregate estimates (P< 0.0001). As expected, rates of hearing preservation were also strongly dependent on preoperative tumor size, with rates of 59%, 37%, and 11% observed for intracanalicular, small, and large (>20 mm) tumors, respectively.

Conclusions Hearing preservation rates are likely dependent on multiple factors and tumor size has a strong effect. It is critical to discuss the patient’s expectations for hearing preservation when deciding on treatment plans for VS.

Diet and exercise have been established as contributors to human health, but less is known about how they interact to impact the gut microbiota. Based on scientific literature and evolutionary evidence, a combination of a minimally-processed fiber-rich diet and regular physical activity can benefit almost everyone. Diet and exercise affect one another; eating fiber-rich foods may increase the efficiency of physical activity and performing physical activity alters hormones that regulate food intake. This review explores the mechanisms by which diet and exercise affect one another as well as how they affect SCFA production, gut microbial diversity, and gut barrier integrity.

The purpose of this report is to walk readers through the conceptual design development of an autonomous transporter that carries a golf ball and shoots it as far as possible. High and low-level design requirements are outlined to discuss intended functionality of the transporter. Preliminary design concepts are presented. An Objective Tree and a Pairwise Comparison Chart are then used to select the best concept based on desired qualities. CAD models of the chosen design are shown. Preliminary calculations for the drive and launch systems are formed and discussed to prove the robot’s ability to succeed at accomplishing the proposed task.

The number of people infected with HIV/AIDS in Russia is shocking. While the governments of many countries, including those of South Africa and India, have managed to get their HIV/AIDS epidemics under control, Russia’s continues to be one of the world’s only HIV/AIDS epidemics that is still growing. Despite this fact, Putin and his administration have done surprisingly little to combat the spread of the disease. HIV/AIDS is a highly stigmatized disease in Russia, making it particularly difficult to contain: it is associated with homosexuality, drug use, prostitution, and crime. Although many consider stigma to be an unfortunate but unavoidable byproduct of culture, this paper will argue that the stigma surrounding HIV/AIDS, particularly the stigma that associates HIV/AIDS with homosexuality, serves a political purpose to Putin, as it allows him to garner domestic popularity by protecting his citizens from the diseased and dangerous homosexual community as well as distract them from the more pressing political, social, and economic problems that currently face Russia. The consequences of Putin’s refusal to solve the HIV/AIDS crisis in Russia are far-reaching, as the HIV/AIDS epidemic in Russia is currently fueling a tuberculosis epidemic.

This research aims to survey the development and current state of Japanese taiko music in Brazil, specifically São Paulo, as a musical genre and cultural practice. Its specific goal is to exhibit hybrid samba-taiko percussion performance as a practice which provides Japanese-Brazilians with a space to express, construct, and realize their hybrid sociocultural identities in spite of the restrictive racial and musical constructs of contemporary Brazilian society.

It provides the background to this conflict of cultural identity with a historical narrative of Japanese immigration to Brazil, and a discourse on the Brazilian cultural ideology of racial democracy. This project also serves to familiarize readers with taiko as a musical genre by outlining the historical development of kumidaiko musical practice in Japan and its development in Brazil, and to define samba-taiko’s hybrid musical characteristics through an analysis of contemporary music examples. Overall this research iterates samba-taiko’s role of emerging significance to Japanese-Brazilian culture.

1871 marked a turning point in John Ruskin’s career. At that point in his career, he had become an established intellectual authority with his appointment at Oxford, Ruskin Sr. had passed away and left him both a fortune and free reign over his intellectual pursuits, and he had taken over his own publishing methods. These momentous changes helped Ruskin turn to more closely examine questions of readership and what he saw as those readers’ needs: educational reading practices in particular and better education in general. My honors thesis seeks to examine the major project John Ruskin embarked on to ameliorate the needs of his readers: Fors Clavigera: Letters to the Workmen and Labourers of Great Britain (1871-84). This project examines how Ruskin came to write Fors: the material and biographical circumstances surrounding its production, Ruskin’s authority at the time, and the implied audience he was writing for. Here I explore the letters and investigate their form, the assumptions they make regarding reading, and the confusion respecting whether their implied audience matched up with the actual one Ruskin had. The works of what scholars call the “late Ruskin” (1870-1900) are daunting because of the phenomenal quantity and the experimental nature of much of that work. But this period, I argue, is also one of Ruskin’s most important because it is the time when he finally gains intellectual independence, and uses his status as an intellectual authority to bring about social change. Francis O’Gorman writes that “[r]eaders of Victorian non-fictional prose were once encouraged to believe that John Ruskin died in 1860. Not literally, certainly, but intellectually and imaginatively (1). The present project is invested in debunking this myth in order to remind readers that the “late Ruskin” has continuously influenced not only art criticism but also publishing methods, reading practices, and socialist thought.