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Rock debris covers ~30% of glacier ablation areas in the Central Himalaya and modifies the impact of atmospheric conditions on mass balance. The thermal properties of supraglacial debris are diurnally variable but remain poorly constrained for monsoon-influenced glaciers over the timescale of the ablation season. We measured vertical debris profile temperatures at 12 sites on four glaciers in the Everest region with debris thickness ranging from 0.08 to 2.8 m. Typically, the length of the ice ablation season beneath supraglacial debris was 160 days (15 May to 22 October)—a month longer than the monsoon season. Debris temperature gradients were approximately linear (r2 > 0.83), measured as −40°C m–1 where debris was up to 0.1 m thick, −20°C m–1 for debris 0.1–0.5 m thick, and −4°C m–1 for debris greater than 0.5 m thick. Our results demonstrate that the influence of supraglacial debris on the temperature of the underlying ice surface, and therefore melt, is stable at a seasonal timescale and can be estimated from near-surface temperature. These results have the potential to greatly improve the representation of ablation in calculations of debris-covered glacier mass balance and projections of their response to climate change.
The bio-synthesis of pyoverdine (PVD) in Pseudomonas aeruginosa involves multiple enzymatic steps including the action of non-ribosomal peptide synthetases (NRPSs). One hallmark of NRPS is their ability to make usage of non-proteinogenic amino-acids synthesized by co-expressed accessory enzymes. It is generally proposed that different enzymes of a secondary metabolic pathway assemble into large supra-molecular complexes. However, evidence for the assembly of sequential enzymes in the cellular context is sparse. Here, we used in cellulo single-molecule tracking and Förster resonance energy transfer measured by fluorescence lifetime microscopy (FRET-FLIM) to explore the spatial partitioning of the ornithine hydroxylase PvdA and its interactions with NRPS. We found PvdA was mostly diffusing bound to large complexes in the cytoplasm with a small exchangeable trapped fraction. FRET-FLIM clearly showed that PvdA is physically interacting with PvdJ, PvdI, PvdL, and PvdD, the four NRPS involved in the PVD pathway in Pseudomonas aeruginosa PAO1. The binding modes of PvdA were strikingly different according to the NRPS it is interacting with, suggesting that PvdA binding sites have co-evolved with the enzymatic active sites of NRPS. Our data provide evidence for strongly organized multi-enzymatic complexes responsible for the bio-synthesis of PVD and illustrate how binding sites have evolved to finely control the co-localization of sequential enzymes and promote metabolic pathway efficiency.
Using the recently developed techniques of electron tomography, we have explored the first stages of disfiguring formation of zinc soaps in modern oil paintings. The formation of complexes of zinc ions with fatty acids in paint layers is a major threat to the stability and appearance of many late 19th and early 20th century oil paintings. Moreover, the occurrence of zinc soaps in oil paintings leading to defects is disturbingly common, but the chemical reactions and migration mechanisms leading to large zinc soap aggregates or zones remain poorly understood. State-of-the-art scanning (SEM) and transmission (TEM) electron microscopy techniques, primarily developed for biological specimens, have enabled us to visualize the earliest stages of crystalline zinc soap growth in a reconstructed zinc white (ZnO) oil paint sample. In situ sectioning techniques and sequential imaging within the SEM allowed three-dimensional tomographic reconstruction of sample morphology. Improvements in the detection and discrimination of backscattered electrons enabled us to identify local precipitation processes with small atomic number contrast. The SEM images were correlated to low-dose and high-sensitivity TEM images, with high-resolution tomography providing unprecedented insight into the structure of nucleating zinc soaps at the molecular level. The correlative approach applied here to study phase separation, and crystallization processes specific to a problem in art conservation creates possibilities for visualization of phase formation in a wide range of soft materials.
Objectives: Glioblastoma is a lethal disease in the elderly population. We aimed to evaluate disease and treatment outcomes in the oldest-old patients. Methods: Patients >80 years old with histologically confirmed glioblastoma treated between 2004 and 2009 were identified. We included patients managed with best supportive care (BSC), temozolomide (TMZ) alone, radiotherapy (RT) alone, or concomitantly with TMZ (CRT). Survival outcomes were analyzed using the Kaplan–Meier method. Results: Ultimately, 48 patients were analyzed. Median age and Eastern Cooperative Oncology Group (ECOG) Performance Status were 82 years and 2, respectively. The median Age-Adjusted Charlson Index (AAC) was 6. Gross total and subtotal resections were performed in 16.7% and 18.8% of patients, respectively. Biopsy followed by RT alone was the treatment modality for 23/48 (47.9%), while 17/48 (35.4%) received surgery followed by RT alone or CRT. A total of 8 (16.7%) were managed with BSC after biopsy. Median overall survival (OS) and progression-free survival (PFS) were 4.1 (95% confidence interval [95% CI] 3.3-4.9) and 2.7 (95% CI 1.5-3.9) months, respectively. Improved median OS was observed in those treated with surgical resection followed by RT alone or CRT (7.1 months), compared to biopsy followed by RT alone (4.2 months) or BSC (2.0 months; p=0.002). Surgical resection, age≤85, and AAC<6 were associated with better OS (p=0.032, p=0.031, and p=0.02, respectively). Cause of death was neurological progression in 56% of cases. RT was well-tolerated. Conclusions: PFS and OS outcomes remain poor in the oldest-old patients (>80 years old). Younger age, lower AAC, surgical resection, and adjuvant treatment were associated with improved OS.
The state is central to social scientific and historical inquiry today, reflecting its importance in domestic and international affairs. States kill, coerce, fight, torture, and incarcerate, yet they also nurture, protect, educate, redistribute, and invest. It is precisely because of the complexity and wide-ranging impacts of states that research on them has proliferated and diversified. Yet, too many scholars inhabit separate academic silos, and theorizing of states has become dispersed and disjointed. This book aims to bridge some of the many gaps between scholarly endeavors, bringing together scholars from a diverse array of disciplines and perspectives who study states and empires. The book offers not only a sample of cutting-edge research that can serve as models and directions for future work, but an original conceptualization and theorization of states, their origins and evolution, and their effects.
The U.K. 1.2 metre Schmidt Telescope acquired its first full aperture objective prism in 1975. This was a very low dispersion prism (2400 Å/mm at 4300 Å) which has been found to be particularly useful in searching for faint QSO’s.
EPA has conducted several ex post assessments of regulatory compliance costs, with the ultimate goal of identifying ways to improve ex ante cost estimation. The work to date has culminated in four case studies that examine five regulations using a common conceptual framework. The standardized framework provides a systematic way to investigate key drivers of compliance costs to see if judgments can be made about why and how ex ante and ex post estimates of costs differ. In addition to describing this conceptual framework, we describe the criteria used to select the rules to be analyzed, summarize the main hypotheses for why ex ante and ex post cost estimates may differ and discuss some of the challenges encountered in conducting these ex post analyses.