George Crumb’s Personal Response to the Golden Age of Social Activism: Night of the Four Moons, Black Angels, and Vox Balaenae

American composer George Crumb (b. 1929) started to garner public attention in the 1960s with a new kind of message and sound. Crumb’s approach to composition has been to exploit music as a form of communication to convey the metaphysical and the psychological through various mediums. With the social movements in the 1960s, many Americans were inspired to fight for change; as for Crumb, composing became his platform for social commentary. His approach to social activism was to express his ideas through musical dialogues and symbolism. The subtle quotations that he often borrowed from other composers are typically short in length, but their roles are significant in that they convey a deeper meaning and provide a broader context to his piece. This document aims to identify the motivations and the historical connections behind the symbolism in Crumb’s pivotal chamber works, as well as discuss his musical contributions to social activism and his intended effect. Indeed the impact may have extended beyond the average listening audience to influence future generation of composers as well. I will explore such composers who followed Crumb’s lead and utilized music as a platform for social activism. Three of Crumb’s chamber works composed between 1969 and 1971 will be examined: • Night of the Four Moons (1969) reflects Crumb’s ambivalent feelings about the Apollo 11 mission to the moon in 1969. The texts were extracted from four of Federico García Lorca’s poems. Understanding the four original poems by Lorca provides a more complete context by which to interpret the metaphors Crumb used. • Black Angels (1970) demonstrates the state of anger and darkness born by the Vietnam War. Crumb used numerology as a cohesive element, specifically the prime numbers 7 and 13 to represent the essential polarity – God versus Devil. The numerological symbolism is variously expressed in the musical structure, including phrase length, groupings of notes, time brackets, numbers of changes, and more. He also alluded to tonal music to represent the harmonious and God, and atonal to represent the current chaotic state. • Vox Balaenae (1971) is an ecological piece, which Crumb utilized the flute to suggest the sounds of a whale after being inspired by a recording of a singing humpback whale. This work provided a distinct musical voice to the world’s first anti-whaling campaign launched by the environmental non-profit organization, Greenpeace, in 1975, which eventually ignited a global “Save the Whales” movement. Additionally, the adaptation of Strauss’s Also sprach Zarathustra theme contains metaphors about the evolution of mankind. This document aims to contribute to the available knowledge concerning the interpretation of Crumb’s compositions by providing new insights to help researchers and performers attain a deeper understanding of Crumb’s chamber works that involve social change movements between 1969 and 1971

Prevalence and Correlates of Depression among Chronic Kidney Disease Patients in Taiwan

Background: Chronic kidney disease (CKD) is a progressive disease that causes a permanent impairment of renal function and premature mortality. The associated prognosis may result in serious psychological distress to the affected individual. However, there are limited data on the psychological correlates, and in particular depression, in Chinese CKD patients. This study aimed to examine the prevalence of depression, as well as the influence of other psychosocial factors on depression, among Taiwanese CKD patients. Methods: We used a cross-sectional research design to recruit 270 CKD patients who were not undergoing dialysis treatment at a hospital in southern Taiwan during 2011. The structured questionnaire used in this study gathered information on respondent demographic and disease characteristics, and information obtained from the Taiwanese Depression Questionnaire. Factors associated with depression were examined by a multiple logistic regression analysis. Results: The crude and age-standardized prevalence of depression were 22.6% and 20.6%, respectively. Those who had sleep disturbances, reported having no religious beliefs, followed no regular exercise regimen, and were diagnosed with stage III or above CKD demonstrated a significantly higher risk of depression. Conclusion: Our findings are beneficial to healthcare providers, as they identify both the prevalence of depression and several of its correlates. By identifying CKD patients with a higher risk of depression, healthcare providers may be better able to ensure the provision of appropriate rehabilitation to this population

XRCC1, but not APE1 and hOGG1 gene polymorphisms is a risk factor for pterygium.

PurposeEpidemiological evidence suggests that UV irradiation plays an important role in pterygium pathogenesis. UV irradiation can produce a wide range of DNA damage. The base excision repair (BER) pathway is considered the most important pathway involved in the repair of radiation-induced DNA damage. Based on previous studies, single-nucleotide polymorphisms (SNPs) in 8-oxoguanine glycosylase-1 (OGG1), X-ray repair cross-complementing-1 (XRCC1), and AP-endonuclease-1 (APE1) genes in the BER pathway have been found to affect the individual sensitivity to radiation exposure and induction of DNA damage. Therefore, we hypothesize that the genetic polymorphisms of these repair genes increase the risk of pterygium.MethodsXRCC1, APE1, and hOGG1 polymorphisms were studied using fluorescence-labeled Taq Man probes on 83 pterygial specimens and 206 normal controls.ResultsThere was a significant difference between the case and control groups in the XRCC1 genotype (p=0.038) but not in hOGG1 (p=0.383) and APE1 (p=0.898). The odds ratio of the XRCC1 A/G polymorphism was 2.592 (95% CI=1.225-5.484, p=0.013) and the G/G polymorphism was 1.212 (95% CI=0.914-1.607), compared to the A/A wild-type genotype. Moreover, individuals who carried at least one C-allele (A/G and G/G) had a 1.710 fold increased risk of developing pterygium compared to those who carried the A/A wild type genotype (OR=1.710; 95% CI: 1.015-2.882, p=0.044). The hOGG1 and APE1 polymorphisms did not have an increased odds ratio compared with the wild type.ConclusionsXRCC1 (Arg399 Glu) is correlated with pterygium and might become a potential marker for the prediction of pterygium susceptibility

Intraocular Pressure Changes: An Important Determinant of the Biocompatibility of Intravitreous Implants

Background: In recent years, research efforts exploring the possibility of using biomaterial nanoparticles for intravitreous drug delivery has increased significantly. However, little is known about the effect of material properties on intravitreous tissue responses. Principal Findings: To find the answer, nanoparticles made of hyaluronic acid (HA), poly (l-lactic acid) (PLLA), polystyrene (PS), and Poly N-isopropyl acrylamide (PNIPAM) were tested using intravitreous rabbit implantation model. Shortly after implantation, we found that most of the implants accumulated in the trabecular meshwork area followed by clearance from the vitreous. Interestingly, substantial reduction of intraocular pressure (IOP) was observed in eyes implanted with particles made of PS, PNIPAM and PLLA, but not HA nanoparticles and buffered salt solution control. On the other hand, based on histology, we found that the particle implantation had no influence on cornea, iris and even retina. Surprisingly, substantial CD11b+ inflammatory cells were found to accumulate in the trabecular meshwork area in some animals. In addition, there was a good relationship between recruited CD11b+ cells and IOP reduction. Conclusions: Overall, the results reveal the potential influence of nanoparticle material properties on IOP reduction and inflammatory responses in trabecular meshwork. Such interactions may be critical for the development of future ocula

Repurposing Metformin for Lung Cancer Management

In this article, we introduced the background knowledge of lung cancer management and considered repurposing old drugs to overcome therapy bottleneck. We chose metformin to prove both its antihyperglycemia and antitumor formation effects. Based on the metformin-related AMPK-dependent pathway, we tried to explore the AMPK-independent pathway in inhibition of lung tumorigenesis by metformin. Using preclinical data mining from clinical settings with a literature review, we attempted to clarify the role of metformin in lung cancer management. Additional objective and strong evidence are needed using randomized control studies to verify the benefit of metformin in clinical practice. Furthermore, we proposed two lung cancer animal models and showed the establishment processes thoroughly. We hope that these two lung cancer animal models provide a useful platform for furthering old drug repurposing as well as new drug investigations in the future

The p53-dependent apoptotic pathway of breast cancer cells (BC-M1) induced by the bis-type bioreductive compound aziridinylnaphthoquinone

INTRODUCTION: Several aziridinylbenzoquinone drugs have undergone clinical trials as potential antitumor drugs. These bioreductive compounds are designed to kill cells preferentially within the hypoxia tumor microenvironment. The bioreductive compound of bis-type naphthoquinone synthesized in our laboratory, 2-aziridin-1-yl-3-[(2-{2-[(3-aziridin-1-yl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)thio]ethoxy}ethyl)thio]naphthoquinone (AZ-1), had the most potent death effect on the breast cancer cells BC-M1 in our previous screening. In the present study, we determined that the mechanism of the death effect of BC-M1 cells induced by AZ-1 was mediated by the apoptosis pathway. METHODS: We evaluated the cytotoxicity of AZ-1 and the anti-breast cancer drugs tamoxifen and paclitaxel to BC-M1 cells and MCF-7 cells by the MTT assay and measured the apoptosis phenomena by Hoechst 33258 staining for apoptotic bodies. We also quantified the sub-G(1 )peak area and the ratio of the CH(2)/CH(3 )peak area of the cell membrane in BC-M1 cells by flow cytometry and (1)H-NMR spectra, respectively. The apoptosis-related protein expressions, including p53, p21, the RNA-relating protein T-cell restricted intracellular antigen-related protein, cyclin-dependent kinase 2 (cell cycle regulating kinase) and pro-caspase 3, were detected by western blot, and the caspase-3 enzyme activity was also quantified by an assay kit. RESULTS: AZ-1 induced two of the breast cancer cell lines, with IC(50 )= 0.51 μM in BC-M1 cells and with IC(50)= 0.57 μM in MCF-7 cells, and showed less cytotoxicity to normal fibroblast cells (skin fibroblasts) with IC(50)= 5.6 μM. There was a 10-fold difference between two breast cancer cell lines and normal fibroblasts. Of the two anti-breast cancer drugs, tamoxifen showed IC(50)= 0.12 μM to BC-M1 cells and paclitaxel had much less sensitivity than AZ-1. The expression of p53 protein increased from 0.5 to 1.0 μM AZ-1 and decreased at 2.0 μM AZ-1. The p21 protein increased from 0.5 μM AZ-1, with the highest at 2 μM AZ-1. Regarding the AZ-1 compound-induced BC-M1 cells mediating the apoptosis pathway, the apoptotic body formation, the sub-G(1 )peak area, the ratio of CH(2)/CH(3 )of phospholipids in the cell membrane and the enzyme activity of caspase-3 were all in direct proportion with the dose-dependent increase of the concentration of AZ-1. The death effect-related proteins, including T-cell restricted intracellular antigen-related protein, cyclin-dependent kinase 2, and pro-caspase-3, all dose-dependently decreased with AZ-1 concentration. CONCLUSIONS: The AZ-1-induced cell death of BC-M1 cells mediating the apoptosis pathway might be associated with p53 protein expression, and AZ-1 could have the chance to be a candidate drug for anti-breast cancer following more experimental evidence, such as animal models

Relationships between serum HER2 ECD, TIMP-1 and clinical outcomes in Taiwanese breast cancer

<p>Abstract</p> <p>Background</p> <p>Serum levels of the extracellular domain of HER2/neu (HER2 ECD) have been demonstrated to be associated with clinical outcomes. A disintegrin and metalloproteinase-10, a sheddase of HER2/neu, can drive cancer progression and its activity is inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1). However, elevated TIMP-1 expression has been associated with a poor prognosis of breast cancer. Therefore, this study was performed to explore the relationships between serum HER2 ECD, TIMP-1 and clinical outcomes.</p> <p>Methods</p> <p>One hundred and eighty-five female breast cancer patients, who received curative mastectomy without neo-adjuvant chemotherapy at Chang-Gung Memorial Hospital, were recruited with informed consent for this study. Pre-operative serum levels of HER2 ECD and TIMP-1 were measured using an enzyme-linked immunosorbent assay.</p> <p>Results</p> <p>Twenty-three cases (12.4%) were classified HER2 ECD positive. HER2 ECD positivity was significantly associated with age, lymph node involvement, histological grade, estrogen receptor status, progesterone receptor status, tissue HER2/neu overexpression, and disease-free survival (DFS). In an age, stage, ER and HER2/neu status matched subgroup (N = 41), the serum level of TIMP-1 was significantly associated with HER2 ECD positivity and DFS.</p> <p>Conclusions</p> <p>A high serum TIMP-1 was significantly associated with HER2 ECD positivity and a poorer DFS among Taiwanese primary breast cancer patients with HER2 overexpression.</p