An Analytical Investigation of Flapping Wing Structures for Micro Air Vehicles

An analytical model of flapping wing structures for bio-inspired micro air vehicles is presented in this dissertation. Bio-inspired micro air vehicles (MAVs) are based on insects and hummingbirds. These animals have lightweight, flexible wings that undergo large deformations while flapping. Engineering studies have confirmed that deformations can increase the lift of flapping wings. Wing flexibility has been studied through experimental construction-and-evaluation methods and through computational numerical models. Between experimental and numerical methods there is a need for a simple method to model and evaluate the structural dynamics of flexible flapping wings. This dissertation's analytical model addresses this need. A time-periodic assumed-modes beam analysis of a flapping, flexible wing undergoing linear deformations is developed from a beam analysis of a helicopter blade. The resultant structural model includes bending and torsion degrees of freedom. The model is non-dimensionalized. The ratio of the system's structural natural frequency to wingbeat frequency characterizes its constant stiffness, and the amplitude of flapping motion characterizes its time-periodic stiffness. Current flapping mechanisms and MAVs are compared to biological fliers on the basis of the characteristic parameters. The beam analysis is extended to develop an plate model of a flapping wing. The time-periodic stability of the flapping wing model is assessed with Floquet analysis. A flapping-wing stability diagram is developed as a function of the characteristic parameters. The analysis indicates that time-periodic instabilities are more likely for large-amplitude, high-frequency flapping motion. Instabilities associated with the first bending mode dominate the stability diagram. Due to current limitations of flapping mechanisms, instabilities are not likely in current experiments but become more likely at the operating conditions of biological fliers. The effect of structural design parameters, including wing planform and material stiffness, are assessed with an assumed-modes aeroelastic model. Wing planforms are developed from an empirical model of biological planforms. Non-linearities are described in the effect of membrane thickness on lift generation. Structural couplings due to time-periodic stiffness are identified that can decrease lift generation at certain wingbeat frequencies

Karyotype analysis and sex determination in Australian Brush-turkeys (Alectura lathami)

Sexual differentiation across taxa may be due to genetic sex determination (GSD) and/or temperature sex determination (TSD). In many mammals, males are heterogametic (XY); whereas females are homogametic (XX). In most birds, the opposite is the case with females being heterogametic (ZW) and males the homogametic sex (ZZ). Many reptile spe- cies lack sex chromosomes, and instead, sexual differentiation is influenced by temperature with specific temperatures promoting males or females varying across species possessing this form of sexual differentiation, although TSD has recently been shown to override GSD in Australian central beaded dragons (Pogona vitticeps). There has been speculation that Australian Brush-turkeys (Alectura lathami) exhibit TSD alone and/or in combination with GSD. Thus, we sought to determine if this species possesses sex chromosomes. Blood was collected from one sexually mature female and two sexually mature males residing at Sylvan Heights Bird Park (SHBP) and shipped for karyotype analysis. Karyotype analysis revealed that contrary to speculation, Australian Brush-turkeys possess the classic avian ZW/ZZ sex chromosomes. It remains a possibility that a biased primary sex ratio of Austra- lian Brush-turkeys might be influenced by maternal condition prior to ovulation that result in her laying predominantly Z- or W-bearing eggs and/or sex-biased mortality due to higher sensitivity of one sex in environmental conditions. A better understanding of how maternal and extrinsic factors might differentially modulate ovulation of Z- or W-bearing eggs and hatching of developing chicks possessing ZW or ZZ sex chromosomes could be essential in conservation strategies used to save endangered members of Megapodiidae

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Karyotype results for Australian Brush-turkeys.

<p>G-band karyotype images without microchromosomes of A) female <i>A</i>. <i>lathami</i> demonstrating heterogametic ZW sex chromosomes and B) male <i>A</i>. <i>lathami</i> demonstrating homogametic ZZ sex chromosomes, C) G-band sex chromosomes of one female and two male <i>A</i>. <i>lathami</i>, and D) a C-band female metaphase image demonstrating weak to absent C-banding on the Z chromosome and complete C-banding on the W chromosome. For A and B, the numbers of corresponding chromosomes from the <i>G</i>. <i>gallus domesticus</i> karyotype are provided parenthetically.</p

Karyotype results for Australian Brush-turkeys.

<p>G-band karyotype images without microchromosomes of A) female <i>A</i>. <i>lathami</i> demonstrating heterogametic ZW sex chromosomes and B) male <i>A</i>. <i>lathami</i> demonstrating homogametic ZZ sex chromosomes, C) G-band sex chromosomes of one female and two male <i>A</i>. <i>lathami</i>, and D) a C-band female metaphase image demonstrating weak to absent C-banding on the Z chromosome and complete C-banding on the W chromosome. For A and B, the numbers of corresponding chromosomes from the <i>G</i>. <i>gallus domesticus</i> karyotype are provided parenthetically.</p

Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis

Cancer genome sequencing studies have identified numerous driver genes, but the relative timing of mutations in carcinogenesis remains unclear. The gradual progression from premalignant Barrett's esophagus to esophageal adenocarcinoma (EAC) provides an ideal model to study the ordering of somatic mutations. We identified recurrently mutated genes and assessed clonal structure using whole-genome sequencing and amplicon resequencing of 112 EACs. We next screened a cohort of 109 biopsies from 2 key transition points in the development of malignancy: benign metaplastic never-dysplastic Barrett's esophagus (NDBE; n = 66) and high-grade dysplasia (HGD; n = 43). Unexpectedly, the majority of recurrently mutated genes in EAC were also mutated in NDBE. Only TP53 and SMAD4 mutations occurred in a stage-specific manner, confined to HGD and EAC, respectively. Finally, we applied this knowledge to identify high-risk Barrett's esophagus in a new non-endoscopic test. In conclusion, mutations in EAC driver genes generally occur exceptionally early in disease development with profound implications for diagnostic and therapeutic strategies

Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions.

In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including &gt;25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling. We applied these methods to clinical specimens gathered from 669 patients in New York City during the first two months of the outbreak, yielding a broad molecular portrait of the emerging COVID-19 disease. We find significant enrichment of a NYC-distinctive clade of the virus (20C), as well as host responses in interferon, ACE, hematological, and olfaction pathways. In addition, we use 50,821 patient records to find that renin-angiotensin-aldosterone system inhibitors have a protective effect for severe COVID-19 outcomes, unlike similar drugs. Finally, spatial transcriptomic data from COVID-19 patient autopsy tissues reveal distinct ACE2 expression loci, with macrophage and neutrophil infiltration in the lungs. These findings can inform public health and may help develop and drive SARS-CoV-2 diagnostic, prevention, and treatment strategies