Evolutionary Reduction of the First Thoracic Limb in Butterflies

Members of the diverse butterfly families Nymphalidae (brush-footed butterflies) and Riodinidae (metalmarks) have reduced first thoracic limbs and only use two pairs of legs for walking. In order to address questions about the detailed morphology and evolutionary origins of these reduced limbs, the three thoracic limbs of 13 species of butterflies representing all six butterfly families were examined and measured, and ancestral limb sizes were reconstructed for males and females separately. Differences in limb size across butterflies involve changes in limb segment size rather than number of limb segments. Reduction of the first limb in both nymphalids and riodinids appears particularly extensive in the femur, but the evolution of these reduced limbs is suggested to be a convergent evolutionary event. Possible developmental differences as well as ecological factors driving the evolution of reduced limbs are discussed

Sub-micrometer epitaxial Josephson junctions for quantum circuits

We present a fabrication scheme and testing results for epitaxial sub-micrometer Josephson junctions. The junctions are made using a high-temperature (1170 K) "via process" yielding junctions as small as 0.8 mu m in diameter by use of optical lithography. Sapphire (Al2O3) tunnel-barriers are grown on an epitaxial Re/Ti multilayer base-electrode. We have fabricated devices with both Re and Al top electrodes. While room-temperature (295 K) resistance versus area data are favorable for both types of top electrodes, the low-temperature (50 mK) data show that junctions with the Al top electrode have a much higher subgap resistance. The microwave loss properties of the junctions have been measured by use of superconducting Josephson junction qubits. The results show that high subgap resistance correlates to improved qubit performance

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.

BackgroundThe large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).MethodsPROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3 years or until death or study withdrawal.ResultsIn 2011-2017, 1976 patients were followed for 46.6 months (median). The median age was 72 years, and the baseline median prostate-specific antigen level was 15.0 ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7 months (95% confidence interval [CI], 28.6-32.2 months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7 months (95% CI, 39.4-46.2 months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.ConclusionsPROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings

Disturbance distance: quantifying forests' vulnerability to disturbance under current and future conditions

Disturbances, both natural and anthropogenic, are critical determinants of forest structure, function, and distribution. The vulnerability of forests to potential changes in disturbance rates remains largely unknown. Here, we developed a framework for quantifying and mapping the vulnerability of forests to changes in disturbance rates. By comparing recent estimates of observed forest disturbance rates over a sample of contiguous US forests to modeled rates of disturbance resulting in forest loss, a novel index of vulnerability, Disturbance Distance, was produced. Sample results indicate that 20% of current US forestland could be lost if disturbance rates were to double, with southwestern forests showing highest vulnerability. Under a future climate scenario, the majority of US forests showed capabilities of withstanding higher rates of disturbance then under the current climate scenario, which may buffer some impacts of intensified forest disturbanceinfo:eu-repo/semantics/publishedVersio

Infrared skin damage thresholds from 1940-nm continuous-wave laser exposures

A series of experiments are conducted in vivo using Yucatan mini-pigs (Sus scrofa domestica) to determine thermal damage thresholds to the skin from 1940-nm continuous-wave thulium fiber laser irradiation. Experiments employ exposure durations from 10 ms to 10 s and beam diameters of approximately 4.8 to 18 mm. Thermal imagery data provide a time-dependent surface temperature response from the laser. A damage endpoint of minimally visible effect is employed to determine threshold for damage at 1 and 24 h postexposure. Predicted thermal response and damage thresholds are compared with a numerical model of optical-thermal interaction. Results are compared with current exposure limits for laser safety. It is concluded that exposure limits should be based on data representative of large-beam exposures, where effects of radial diffusion are minimized for longer-duration damage threshold

Individual epigenetic status of the pathogenic D4Z4 macrosatellite correlates with disease in facioscapulohumeral muscular dystrophy

BACKGROUND: Both forms of facioscapulohumeral muscular dystrophy (FSHD) are associated with aberrant epigenetic regulation of the chromosome 4q35 D4Z4 macrosatellite. Chromatin changes due to large deletions of heterochromatin (FSHD1) or mutations in chromatin regulatory proteins (FSHD2) lead to relaxation of epigenetic repression and increased expression of the deleterious double homeobox 4 (DUX4) gene encoded within the distal D4Z4 repeat. However, many individuals with the genetic requirements for FSHD remain asymptomatic throughout their lives. Here we investigated family cohorts of FSHD1 individuals who were either affected (manifesting) or without any discernible weakness (nonmanifesting/asymptomatic) and their unaffected family members to determine if individual epigenetic status and stability of repression at the contracted 4q35 D4Z4 array in myocytes correlates with FSHD disease. RESULTS: Family cohorts were analyzed for DNA methylation on the distal pathogenic 4q35 D4Z4 repeat on permissive A-type subtelomeres. We found DNA hypomethylation in FSHD1-affected subjects, hypermethylation in healthy controls, and distinctly intermediate levels of methylation in nonmanifesting subjects. We next tested if these differences in DNA methylation had functional relevance by assaying DUX4-fl expression and the stability of epigenetic repression of DUX4-fl in myogenic cells. Treatment with drugs that alter epigenetic status revealed that healthy cells were refractory to treatment, maintaining stable repression of DUX4, while FSHD1-affected cells were highly responsive to treatment and thus epigenetically poised to express DUX4. Myocytes from nonmanifesting subjects had significantly higher levels of DNA methylation and were more resistant to DUX4 activation in response to epigenetic drug treatment than cells from FSHD1-affected first-degree relatives containing the same contraction, indicating that the epigenetic status of the contracted D4Z4 array is reflective of disease. CONCLUSIONS: The epigenetic status of the distal 4qA D4Z4 repeat correlates with FSHD disease; FSHD-affected subjects have hypomethylation, healthy unaffected subjects have hypermethylation, and nonmanifesting subjects have characteristically intermediate methylation. Thus, analysis of DNA methylation at the distal D4Z4 repeat could be used as a diagnostic indicator of developing clinical FSHD. In addition, the stability of epigenetic repression upstream of DUX4 expression is a key regulator of disease and a viable therapeutic target