Nomadic Trails for Chamber Orchestra

Nomadic Trails for chamber orchestra (2021) is a 14-minute symphonic work in two movements scored for flute/piccolo, oboe, cor anglais, clarinet, contrabassoon/bassoon, 3 trumpets, trombone, bass trombone, 3 percussions, harp, and strings. The work is inspired by the nomadic culture of Uly Dala, the Great Steppe, and traditional Kazakh music, and, through the use of contrasting compositional approaches, addresses the issue of duality taken from the ancient Central Asian religion, Tengriism. In this orchestral work, I blend my musical language with re-constructions and re-interpretations of thematic materials from various well-known küis (solo compositions of oral tradition composed for and performed on the Kazakh instrument, Dombyra) by legendary 19th-century Küishis (composer-performers of küis), such as Kurmangazy Sagyrbaev, Dauletkerey Shigayev, and Dina Nurpeisova. I also explore how different spatial references and historical milieus of the Central Asian nomadic culture can be reflected in a composition written for Western orchestra, and investigate how extra-musical cultural referents, such as Kazakh legends, petroglyphs, and traditional ornaments, can influence the structures and textures of a musical piece. The two movements of Nomadic Trails depict scenes in two different settings: one in the wilderness, and the other in an urban domain: The first movement, “The Great Steppe,” composed in a collage-like form of mini-sections, is inspired by Kazakh legends and petroglyphs, all of which unveil the nomadic stories of the past. The 6-minute movement features melodic quotations taken from three küis: Köroğlu by Dauletkerey, and Qyzyl Qaiyn and Adai by Kurmangazy. Each of the themes in this symphonic medley appear in a kaleidoscopic manner and bring in a different mood, color, tempo and texture. Blurring the borders between abstract and concrete, “The Great Steppe” leaves space to allow the listener to create their own imaginary landscapes. The second movement, “Scenes at the Uralsk Fair,” depicts a celebration of life at a town fair. It is based on the motivic elaborations and de-constructions of thematic materials taken from the küi, Nauai / Nauysky, composed by Dina Nurpeisova, a female Küishi. The complex structure of this contrasting 8-minute movement is an amalgamation of the rondo and variations forms, which strikes a resemblance with the repetitive yet varying structures of Kazakh traditional ornaments. The movement is unified by its fast-moving tempo, syncopated rhythmic patterns and strong pulse that culminates into a whirlwind of vigorous, volcanic bursts describing the bustling atmosphere of the Kazakh town fair.AMUMusic: CompositionUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/169668/1/tsuimlm_1.pd

Design of microarray probes for virus identification and detection of emerging viruses at the genus level

BACKGROUND: Most virus detection methods are geared towards the detection of specific single viruses or just a few known targets, and lack the capability to uncover the novel viruses that cause emerging viral infections. To address this issue, we developed a computational method that identifies the conserved viral sequences at the genus level for all viral genomes available in GenBank, and established a virus probe library. The virus probes are used not only to identify known viruses but also for discerning the genera of emerging or uncharacterized ones. RESULTS: Using the microarray approach, the identity of the virus in a test sample is determined by the signals of both genus and species-specific probes. The genera of emerging and uncharacterized viruses are determined based on hybridization of the viral sequences to the conserved probes for the existing viral genera. A detection and classification procedure to determine the identity of a virus directly from detection signals results in the rapid identification of the virus. CONCLUSION: We have demonstrated the validity and feasibility of the above strategy with a small number of viral samples. The probe design algorithm can be applied to any publicly available viral sequence database. The strategy of using separate genus and species probe sets enables the use of a straightforward virus identity calculation directly based on the hybridization signals. Our virus identification strategy has great potential in the diagnosis of viral infections. The virus genus and specific probe database and the associated summary tables are available a

Women Under Kuomintang R ule Variations on the Feminine Mystique

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68360/2/10.1177_009770047500100101.pd

Pharmaceuticals in tap water: human health risk assessment and proposed monitoring framework in China

Background: Pharmaceuticals are known to contaminate tap water worldwide, but the relevant human health risks have not been assessed in China. Objectives: We monitored 32 pharmaceuticals in Chinese tap water and evaluated the life-long human health risks of exposure in order to provide information for future prioritization and risk management. Methods: We analyzed samples (n = 113) from 13 cities and compared detected concentrations with existing or newly-derived safety levels for assessing risk quotients (RQs) at different life stages, excluding the prenatal stage. Results: We detected 17 pharmaceuticals in 89% of samples, with most detectable concentrations (92%) at < 50 ng/L. Caffeine (median-maximum, nanograms per liter: 24.4-564), metronidazole (1.8-19.3), salicylic acid (16.6-41.2), clofibric acid (1.2-3.3), carbamazepine (1.3-6.7), and dimetridazole (6.9-14.7) were found in ≥ 20% of samples. Cities within the Yangtze River region and Guangzhou were regarded as contamination hot spots because of elevated levels and frequent positive detections. Of the 17 pharmaceuticals detected, 13 showed very low risk levels, but 4 (i.e., dimetridazole, thiamphenicol, sulfamethazine, and clarithromycin) were found to have at least one life-stage RQ ≥ 0.01, especially for the infant and child life stages, and should be considered of high priority for management. We propose an indicator-based monitoring framework for providing information for source identification, water treatment effectiveness, and water safety management in China. Conclusion: Chinese tap water is an additional route of human exposure to pharmaceuticals, particularly for dimetridazole, although the risk to human health is low based on current toxicity data. Pharmaceutical detection and application of the proposed monitoring framework can be used for water source protection and risk management in China and elsewhere

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Insulin-like Growth Factor Binding Protein 7 Activates the Retinoid Acid Differentiation Pathway in Acute Myeloid Leukemia Cells

Acute myeloid leukemia (AML) is characterized by the accumulation of malignant blasts with impaired transcriptional differentiation programs. Despite important advances in AML therapy, the five-year overall survival rate of AML patients remains a disappointing 30-40%. This poor prognosis is mainly caused by survival of chemotherapy resistant leukemic cells, named leukemic stem cells (LSC), re-initiating relapse. However, for AML patients with PML-RARA positive acute promyelocytic leukemia (APL), treatment with all trans retinoic acid (ATRA) results in cure rates of &gt;90%. Upon ATRA treatment, APL cells can restore transcription leading to granulocytic differentiation, and in combination with arsenic trioxide APL cells go into apoptosis. While the success of ATRA treatment has been demonstrated for APL patients, so far it has not proved effective for non-APL AML patients.Previously, we demonstrated that insulin-like growth factor binding protein 7 (IGFBP7), a negative regulator of IGF1 receptor (IGF1R) activity, induces apoptosis of AML cells and sensitizes AML cells to chemotherapy-induced cell death. Since it has been shown that IGF1R inhibitors can eliminate therapy-resistant cells by modifying their chromatin state, we hypothesized that IGFBP7 may also have the capacity to modify an epigenetic state and unlock the ATRA-driven differentiation response. To this end, we generated APL cell lines with down- or upregulated IGFBP7 levels and demonstrated that knockdown of IGFBP7 in NB4 cells blocked ATRA-induced differentiation, whereas overexpression of IGFBP7 led to an 8-fold increase in differentiation in the presence of low concentrations of ATRA, together suggesting a role for IGFBP7 in ATRA-induced differentiation in APL cells.Strategies to increase efficacy of ATRA-based therapy might also improve treatment outcomes for non-APL AML, and therefore we investigated the potential of IGFBP7 to induce susceptibility for ATRA-driven differentiation in this group. ATRA and IGFBP7 treatment of non-APL AML cell lines and primary AML cells derived from patients at diagnosis demonstrated an enhanced efficiency of the combination therapy to induce differentiation of myeloid CD45dimCD33+ AML cells (2.5-fold increase in CD11b-expression) and/or to reduce viability of AML CD45dim cells as compared to single treatments (from 30-39% to 70% reduction upon IGFBP7, ATRA or combination therapy, respectively), in 50% of tested primary AML samples, while this combination therapy did not influence normal hematopoietic cell survival. Remarkably, ATRA-IGFBP7 treatment diminished the in vivo engraftment potential of primary AML cells as compared to treatment with either drug alone in NSG mice (from 28% and 52% to 17% engraftment upon ATRA, IGFBP7 or combination therapy, respectively). Re-transplantation of human AML derived from first transplanted mice into secondary recipients demonstrated that the ATRA-IGFBP7 combination treatment also eliminated LSC more effectively (1.4-fold reduction). Together these data suggest that IGFBP7 enhances sensitivity of AML (stem) cells to ATRA, and is able to induce a transcriptional program sensitizing AML cells for ATRA-induced differentiation and cell death.To identify factors responsible for IGFBP7-induced ATRA sensitivity, we performed gene expression profiling of primary AML samples treated with IGFBP7, and identified growth factor independent protein 1 (GFI1) as one of the top down-regulated genes upon IGFBP7 stimulation. As overexpression of GFI1 in non-APL AML patient samples resulted in a &gt;2.5-fold reduction in IGFBP7-induced susceptibility to ATRA-driven differentiation, low GFI1 expression is suggested to be associated with susceptibility to ATRA in AML cells.In conclusion, our results indicate that treatment of AML patient with a combination of ATRA and IGFBP7 might be successful in preventing relapse and improving AML patient survival, which has to be confirmed in further clinical studies.Disclosures Ossenkoppele: Karyopharm: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Jazz: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Roche: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Genmab: Research Funding; Celgene: Honoraria, Research Funding; Johnson &amp; Johnson: Consultancy, Honoraria, Research Funding.↵* Asterisk with author names denotes non-ASH members

Viral infections associated with Kawasaki disease

Kawasaki disease (KD) is a disease of unknown cause. To investigate the infectious etiology of Kawasaki disease, we initiated a prospective case-control study to investigate possible links between common viral infections and Kawasaki disease. Methods: We enrolled 226 children with KD and 226 age- and sex-matched healthy children from February 2004 to March 2010. Throat and nasopharyngeal swabs were taken for both viral isolation and polymerase chain reaction (PCR) for various viruses. Results: The mean age of the 226 KD cases was 2.07 years, and the male to female ratio was 1.43 (133 boys to 93 girls). Their mean fever duration was 7.5 days with a mean peak temperature of 39.7°C. In addition to the typical symptoms of fever, neck lymphadenopathy, lip fissure and/or strawberry tongue, skin rash, nonpurulent bulbar conjunctivitis, palm/sole erythema, and induration followed by periungual desquamation, these KD cases also exhibited cough (69%), rhinorrhea (58%), and diarrhea (45%). Cases of KD had a significantly higher positive rate of viral isolation in comparison with the control group (7.5% vs. 2.2%, p = 0.02). Compared with the control group, cases of KD were more likely to have overall positive rates of viral PCR (50.4% vs. 16.4%, p < 0.001) and for various viruses including enterovirus (16.8% vs. 4.4%, p < 0.001), adenovirus (8.0% vs. 1.8%, p = 0.007), human rhinovirus (26.5% vs. 9.7%, p < 0.001), and coronavirus (7.1% vs. 0.9%, p = 0.003). Conclusion: We found that some common respiratory viruses, such as adenoviruses, enteroviruses, rhinoviruses, and coronaviruses, were associated with KD cases