Evolution of topography in glaciated mountain ranges

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Earth, Atmospheric, and Planetary Sciences, 2002.Includes bibliographical references.This thesis examines the response of alpine landscapes to the onset of glaciation. The basic approach is to compare fluvial and glacial landscapes, since it is the change from the former to the latter that accompanies climatic cooling. This allows a detailed evaluation of hypotheses relating climate change to tectonic processes in glaciated mountain belts. Fieldwork was carried out in the eastern Sierra Nevada, California, and the Sangre de Cristo Range, Colorado, alongside digital elevation model analyses in the western US, the Southern Alps of New Zealand, and the Himalaya of northwestern Pakistan. The evidence presented here suggests that the so-called "chicken-and-egg" hypothesis is overstated in its appeal to glacial erosion as a major source of relief production and subsequent peak uplift. Glaciers in the eastern Sierra Nevada and the western Sangre de Cristos have redistributed relief, but have produced only modest relief by enlarging drainage basins at the expense of low-relieftopography. Glaciers have lowered valley floors and ridgelines by similar amounts, limiting the amount of "missing mass" that can be generated, and causing a decrease in drainage basin relief.(cont.) The principal response of glaciated landscapes to rapid rock uplift is the development of towering cirque headwalls. This represents considerable relief production, but is not caused by glacial erosion alone. Large valley glaciers can maintain their low gradient regardless of uplift rate, which supports the "glacial buzzsaw" hypothesis. However, the inability of glaciers to erode steep hillslopes as rapidly can cause mean elevations to rise. Cosmogenic isotope dating is used to show that (i) where plucking is active, the last major glaciation removed sufficient material to reset the cosmogenic clock; and (ii) former glacial valley floors now stranded near the crest of the Sierra Nevada are at varying stages of abandonment, suggesting a cycle of drainage reorganisation and relief inversion due to glacial erosion similar to that observed in river networks. Glaciated landscapes are quite distinct from their fluvial counterparts in both landforms and processes. Given the scarcity of purely fluvial, active mountain ranges, it is essential that glacial erosion be considered amongst the processes sculpting active orogenic belts.by Simon H. Brocklehurst.Ph.D

Glacial erosion and relief production in the Eastern Sierra

Abstract The proposal that climate change can drive the uplift of mountain summits hinges on the requirement that glacial erosion significantly enhances the relief of a previously fluvially sculpted mountain range. We have tested this hypothesis through a systematic investigation of neighbouring glaciated and nonglaciated drainage basins on the eastern side of the Sierra Nevada, CA. We present a simple, objective method for investigating the relief structure of a drainage basin, which shows noticeable differences in the spatial distribution of relief between nonglaciated and glaciated basins. Glaciated basins on the eastern side of the Sierra Nevada have only f80 m greater mean geophysical relief than nonglaciated basins. This ''extra'' relief, though, is attributable principally to the larger size of the glaciated basins, as geophysical relief generally increases with basin size. The glaciers on this side of the range were only responsible for relief production if they substantially increased headward erosion rates into low relief topography, such as an elevated plateau, and thus enlarged previously fluvial basins. We carried out a preliminary morphometric analysis to elucidate the importance of this effect and found that the glaciers of the eastern Sierra Nevada may have eroded headward at considerably faster rates than rivers, but only when they were not obstructed from doing so by either competing larger glaciers in adjacent valleys or transfluent ice at the head of the basin. Our results also suggest that, in temperate regions, alpine glaciers are capable of eroding downward at faster rates than rivers above the equilibrium line altitude (ELA). Although we can rule out significant peak uplift in response to local relief production, in the special case of the Sierra Nevada the concentration of mass removal above the ELA could have contributed to flexural uplift at the edge of a tilting block.

Robust methods for purification of histones from cultured mammalian cells with the preservation of their native modifications

Post-translational modifications (PTMs) of histones play a role in modifying chromatin structure for DNA-templated processes in the eukaryotic nucleus, such as transcription, replication, recombination and repair; thus, histone PTMs are considered major players in the epigenetic control of these processes. Linking specific histone PTMs to gene expression is an arduous task requiring large amounts of highly purified and natively modified histones to be analyzed by various techniques. We have developed robust and complementary procedures, which use strong protein denaturing conditions and yield highly purified core and linker histones from unsynchronized proliferating, M-phase arrested and butyrate-treated cells, fully preserving their native PTMs without using enzyme inhibitors. Cell hypotonic swelling and lysis, nuclei isolation/washing and chromatin solubilization under mild conditions are bypassed to avoid compromising the integrity of histone native PTMs. As controls for our procedures, we tested the most widely used conventional methodologies and demonstrated that they indeed lead to drastic histone dephosphorylation. Additionally, we have developed methods for preserving acid-labile histone modifications by performing non-acid extractions to obtain highly purified H3 and H4. Importantly, isolation of histones H3, H4 and H2A/H2B is achieved without the use of HPLC. Functional supercoiling assays reveal that both hyper- and hypo-phosphorylated histones can be efficiently assembled into polynucleosomes. Notably, the preservation of fully phosphorylated mitotic histones and their assembly into polynucleosomes should open new avenues to investigate an important but overlooked question: the impact of mitotic phosphorylation in chromatin structure and function

Chemical Magnetoreception: Bird Cryptochrome 1a Is Excited by Blue Light and Forms Long-Lived Radical-Pairs

Cryptochromes (Cry) have been suggested to form the basis of light-dependent magnetic compass orientation in birds. However, to function as magnetic compass sensors, the cryptochromes of migratory birds must possess a number of key biophysical characteristics. Most importantly, absorption of blue light must produce radical pairs with lifetimes longer than about a microsecond. Cryptochrome 1a (gwCry1a) and the photolyase-homology-region of Cry1 (gwCry1-PHR) from the migratory garden warbler were recombinantly expressed and purified from a baculovirus/Sf9 cell expression system. Transient absorption measurements show that these flavoproteins are indeed excited by light in the blue spectral range leading to the formation of radicals with millisecond lifetimes. These biophysical characteristics suggest that gwCry1a is ideally suited as a primary light-mediated, radical-pair-based magnetic compass receptor

Effect of Sanitation on Soil-Transmitted Helminth Infection: Systematic Review and Meta-Analysis

A systematic review and meta-analysis by Kathrin Ziegelbauer and colleagues finds that sanitation is associated with a reduced risk of transmission of helminthiases to humans

Clinical Use and Therapeutic Potential of IVIG/SCIG, Plasma-Derived IgA or IgM, and Other Alternative Immunoglobulin Preparations

Intravenous and subcutaneous immunoglobulin preparations, consisting of IgG class antibodies, are increasingly used to treat a broad range of pathological conditions, including humoral immune deficiencies, as well as acute and chronic inflammatory or autoimmune disorders. A plethora of Fab- or Fc-mediated immune regulatory mechanisms has been described that might act separately or in concert, depending on pathogenesis or stage of clinical condition. Attempts have been undertaken to improve the efficacy of polyclonal IgG preparations, including the identification of relevant subfractions, mild chemical modification of molecules, or modification of carbohydrate side chains. Furthermore, plasma-derived IgA or IgM preparations may exhibit characteristics that might be exploited therapeutically. The need for improved treatment strategies without increase in plasma demand is a goal and might be achieved by more optimal use of plasma-derived proteins, including the IgA and the IgM fractions. This article provides an overview on the current knowledge and future strategies to improve the efficacy of regular IgG preparations and discusses the potential of human plasma-derived IgA, IgM, and preparations composed of mixtures of IgG, IgA, and IgM

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Protein kinase C and clostridial neurotoxins affect discrete and related steps in the secretory pathway

1. The effects on catecholamine secretion of activation of protein kinase C and clostridial neurotoxins were examined in digitonin-permeabilized bovine adrenal chromaffin cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44281/1/10571_2004_Article_BF00711564.pd

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks