The ROTSE-III Robotic Telescope System

The observation of a prompt optical flash from GRB990123 convincingly demonstrated the value of autonomous robotic telescope systems. Pursuing a program of rapid follow-up observations of gamma-ray bursts, the Robotic Optical Transient Search Experiment (ROTSE) has developed a next-generation instrument, ROTSE-III, that will continue the search for fast optical transients. The entire system was designed as an economical robotic facility to be installed at remote sites throughout the world. There are seven major system components: optics, optical tube assembly, CCD camera, telescope mount, enclosure, environmental sensing & protection and data acquisition. Each is described in turn in the hope that the techniques developed here will be useful in similar contexts elsewhere.Comment: 19 pages, including 4 figures. To be published in PASP in January, 2003. PASP Number IP02-11

The ROTSE-IIIa Telescope System

We report on the current operating status of the ROTSE-IIIa telescope, currently undergoing testing at Los Alamos National Laboratories in New Mexico. It will be shipped to Siding Spring Observatory, Australia, in first quarter 2002. ROTSE-IIIa has been in automated observing mode since early October, 2001, after completing several weeks of calibration and check-out observations. Calibrated lists of objects in ROTSE-IIIa sky patrol data are produced routinely in an automated pipeline, and we are currently automating analysis procedures to compile these lists, eliminate false detections, and automatically identify transient and variable objects. The manual application of these procedures has already led to the detection of a nova that rose over six magnitudes in two days to a maximum detected brightness of m_R~13.9 and then faded two magnitudes in two weeks. We also readily identify variable stars, includings those suspected to be variables from the Sloan Digital Sky Survey. We report on our system to allow public monitoring of the telescope operational status in real time over the WWW.Comment: 3 pages, 4 figures, submitted for publication in the proceedings of ``Gamma-Ray Burst and Afterglow Astronomy 2001: A Workshop Celebrating the First Year of the HETE Mission'

Evidence of acclimatization or adaptation in Hawaiian corals to higher ocean temperatures

Ocean temperatures have been accelerating at an alarming rate mainly due to anthropogenic fossil fuel emissions. This has led to an increase in the severity and duration of coral bleaching events. Predicted projections for the state of reefs do not take into account the rates of adaptation or acclimatization of corals as these have not as yet been fully documented. To determine any possible changes in thermal tolerances, manipulative experiments were conducted to precisely replicate the initial, pivotal research defining threshold temperatures of corals nearly five decades ago. Statistically higher calcification rates, survivorship, and lower mortality were observed in Montipora capitata, Pocillopora damicornis, and Lobactis scutaria in the present study at 31 °C compared to the original 1970 findings. First whole colony mortality was also observed to occur sooner in 1970 than in 2017 in M. capitata (3 d vs. 15 d respectively), L. scutaria (3 d vs. 17 d), and in P. damicornis (3 d vs. 13 d). Additionally, bleaching occurred sooner in 1970 compared to the 2017 experiment across species. Irradiance was an important factor during the recovery period for mortality but did not significantly alter calcification. Mortality was decreased by 17% with a 50% reduction in irradiance during the recovery period. These findings provide the first evidence of coral acclimatization or adaptation to increasing ocean temperatures for corals collected from the same location and using close replication of the experiment conducted nearly 50 years earlier. An important factor in this increased resistance to elevated temperature may be related to removal of the discharge of treated sewage into Kāne‘ohe Bay and resulting decrease in nitrification and eutrophication. However, this level of increased temperature tolerance may not be occurring rapidly enough to escape the projected increased intensity of bleaching events, as evidenced by the recent 2014 and 2015 high coral mortality in Hawai‘i (34%) and in the tropics worldwide

Molecular Profiling Reveals Diversity of Stress Signal Transduction Cascades in Highly Penetrant Alzheimer's Disease Human Skin Fibroblasts

The serious and growing impact of the neurodegenerative disorder Alzheimer's disease (AD) as an individual and societal burden raises a number of key questions: Can a blanket test for Alzheimer's disease be devised forecasting long-term risk for acquiring this disorder? Can a unified therapy be devised to forestall the development of AD as well as improve the lot of present sufferers? Inflammatory and oxidative stresses are associated with enhanced risk for AD. Can an AD molecular signature be identified in signaling pathways for communication within and among cells during inflammatory and oxidative stress, suggesting possible biomarkers and therapeutic avenues? We postulated a unique molecular signature of dysfunctional activity profiles in AD-relevant signaling pathways in peripheral tissues, based on a gain of function in G-protein-coupled bradykinin B2 receptor (BKB2R) inflammatory stress signaling in skin fibroblasts from AD patients that results in tau protein Ser hyperphosphorylation. Such a signaling profile, routed through both phosphorylation and proteolytic cascades activated by inflammatory and oxidative stresses in highly penetrant familial monogenic forms of AD, could be informative for pathogenesis of the complex multigenic sporadic form of AD. Comparing stimulus-specific cascades of signal transduction revealed a striking diversity of molecular signaling profiles in AD human skin fibroblasts that express endogenous levels of mutant presenilins PS-1 or PS-2 or the Trisomy 21 proteome. AD fibroblasts bearing the PS-1 M146L mutation associated with highly aggressive AD displayed persistent BKB2R signaling plus decreased ERK activation by BK, correctible by gamma-secretase inhibitor Compound E. Lack of these effects in the homologous PS-2 mutant cells indicates specificity of presenilin gamma-secretase catalytic components in BK signaling biology directed toward MAPK activation. Oxidative stress revealed a JNK-dependent survival pathway in normal fibroblasts lost in PS-1 M146L fibroblasts. Complex molecular profiles of signaling dysfunction in the most putatively straightforward human cellular models of AD suggest that risk ascertainment and therapeutic interventions in AD as a whole will likely demand complex solutions

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Structural and dynamic properties that govern the stability of an engineered fibronectin type III domain

Consensus protein design is a rapid and reliable technique for the improvement of protein stability, which relies on the use of homologous protein sequences. To enhance the stability of a fibronectin type III (FN3) domain, consensus design was employed using an alignment of 2123 sequences. The resulting FN3 domain, FN3con, has unprecedented stability, with a melting temperature >100°C, a ΔG(D−N) of 15.5 kcal mol(−1) and a greatly reduced unfolding rate compared with wild-type. To determine the underlying molecular basis for stability, an X-ray crystal structure of FN3con was determined to 2.0 Å and compared with other FN3 domains of varying stabilities. The structure of FN3con reveals significantly increased salt bridge interactions that are cooperatively networked, and a highly optimized hydrophobic core. Molecular dynamics simulations of FN3con and comparison structures show the cooperative power of electrostatic and hydrophobic networks in improving FN3con stability. Taken together, our data reveal that FN3con stability does not result from a single mechanism, but rather the combination of several features and the removal of non-conserved, unfavorable interactions. The large number of sequences employed in this study has most likely enhanced the robustness of the consensus design, which is now possible due to the increased sequence availability in the post-genomic era. These studies increase our knowledge of the molecular mechanisms that govern stability and demonstrate the rising potential for enhancing stability via the consensus method