Pore fluid constraints on deep ocean temperature and salinity during the Last Glacial Maximum

Pore water records of δ^(18)O and [Cl] from ODP Site 1063A on the Bermuda Rise constrain the change in seawater δ^(18)O and salinity from the Last Glacial Maximum (LGM) to the Holocene to be 0.75±0.05‰ and 2.5±0.1% respectively. Coupled with a measured benthic foraminiferal δ^(18)O change, this result means that bottom waters were 4.6±0.8°C cooler than the Holocene at the LGM and therefore at or near the seawater freezing point. Coupled δ^(18)O and chlorinity results give an extrapolated mean ocean LGM to Holocene change in δ^(18)O of 0.95±0.09‰. These data also constrain the past southern source deep‐water salinity to be 35.76±0.04 psu, which is within error of the mean deep ocean value for this time

Law Reform in Estonia: The Role of Georgetown University Law Center

On June 19, 1992, we and seven other members of the Georgetown University Law Center community landed in Tallinn, the capital of Estonia, to help the Estonian government draft laws to support a market economy. Our group consisted of six students, two professors, and an alumnus. The country to which we had come had declared its independence from the Soviet Union less than one year before. After fifty years of imposed communism, the Estonian leaders wanted to understand and adopt the basic foundations for a Western legal system that would support democratic and market institutions

Identification of prodromal presentations of Parkinson's disease among primary care outpatients in Germany

Background: This study aimed to identify clinical features that predate the diagnosis of PD in a primary care setting. Methods: This retrospective case-control study was based on data from the Disease Analyzer database (IQVIA) and included 17,702 patients with Parkinson's disease and 17,702 non-PD controls matched for age, sex, and index year. We analyzed the prevalence of 15 defined diagnoses and symptoms documented within 2 years, ≥2 to <5, and ≥5 to <10 years prior to the index date in patients with and without PD. Logistic regression analyses were conducted to assess the association between PD and the predefined diagnoses. Results: The prevalence of motor, neuropsychiatric and autonomic features was higher in those with a later diagnosis of Parkinson's disease than controls for all three periods except for rigidity in the ≥2 to <5 and ≥5 to <10-year periods and erectile dysfunction in the most recent period before diagnosis. The clinical presentation recorded in the greatest percentage of patients was depression, followed by dizziness, insomnia, and constipation, but these were also common in the control population. The odds ratios were highest for increase in tremor, followed by balance impairment and memory problems, particularly in the latest period before diagnosis, and by constipation particularly in the earliest period examined. Conclusion: The prodromal features of PD could be identified in this large primary care database in Germany with similar results to those found in previous database studies despite differences in methodologies and systems

Current concepts and controversies in the pathogenesis of Parkinson’s disease dementia and Dementia with Lewy Bodies

Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) are relentlessly progressive neurodegenerative disorders that are likely to represent two ends of a disease spectrum. It is well established that both are characterised pathologically by widespread cortical Lewy body deposition. However, until recently, the pathophysiological mechanisms leading to neuronal damage were not known. It was also not understood why some cells are particularly vulnerable in PDD/DLB, nor why some individuals show more aggressive and rapid dementia than others. Recent studies using animal and cell models as well as human post-mortem analyses have provided important insights into these questions. Here, we review recent developments in the pathophysiology in PDD/DLB. Specifically, we examine the role of pathological proteins other than α-synuclein, consider particular morphological and physiological features that confer vulnerabilities on some neurons rather than others, and finally examine genetic factors that may explain some of the heterogeneity between individuals with PDD/DLB

Macromodel-based simulation and measurement of the dynamic pull-in of viscously damped RF-MEMS switches

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Finite size corrections to random Boolean networks

Since their introduction, Boolean networks have been traditionally studied in view of their rich dynamical behavior under different update protocols and for their qualitative analogy with cell regulatory networks. More recently, tools borrowed from statistical physics of disordered systems and from computer science have provided a more complete characterization of their equilibrium behavior. However, the largest part of the results have been obtained in the thermodynamic limit, which is often far from being reached when dealing with realistic instances of the problem. The numerical analysis presented here aims at comparing - for a specific family of models - the outcomes given by the heuristic belief propagation algorithm with those given by exhaustive enumeration. In the second part of the paper some analytical considerations on the validity of the annealed approximation are discussed.Comment: Minor correction

Repositioning the Catalytic Triad Aspartic Acid of Haloalkane Dehalogenase: Effects on Stability, Kinetics, and Structure

Haloalkane dehalogenase (DhlA) catalyzes the hydrolysis of haloalkanes via an alkyl-enzyme intermediate. The covalent intermediate, which is formed by nucleophilic substitution with Asp124, is hydrolyzed by a water molecule that is activated by His289. The role of Asp260, which is the third member of the catalytic triad, was studied by site-directed mutagenesis. Mutation of Asp260 to asparagine resulted in a catalytically inactive D260N mutant, which demonstrates that the triad acid Asp260 is essential for dehalogenase activity. Furthermore, Asp260 has an important structural role, since the D260N enzyme accumulated mainly in inclusion bodies during expression, and neither substrate nor product could bind in the active-site cavity. Activity for brominated substrates was restored to D260N by replacing Asn148 with an aspartic or glutamic acid. Both double mutants D260N+N148D and D260N+N148E had a 10-fold reduced kcat and 40-fold higher Km values for 1,2-dibromoethane compared to the wild-type enzyme. Pre-steady-state kinetic analysis of the D260N+N148E double mutant showed that the decrease in kcat was mainly caused by a 220-fold reduction of the rate of carbon-bromine bond cleavage and a 10-fold decrease in the rate of hydrolysis of the alkyl-enzyme intermediate. On the other hand, bromide was released 12-fold faster and via a different pathway than in the wild-type enzyme. Molecular modeling of the mutant showed that Glu148 indeed could take over the interaction with His289 and that there was a change in charge distribution in the tunnel region that connects the active site with the solvent. On the basis of primary structure similarity between DhlA and other α/β-hydrolase fold dehalogenases, we propose that a conserved acidic residue at the equivalent position of Asn148 in DhlA is the third catalytic triad residue in the latter enzymes.

The energy penalty of post-combustion CO2 capture & storage and its implications for retrofitting the U.S. installed base

A review of the literature has found a factor of 4 spread in the estimated values of the energy penalty for post-combustion capture and storage of CO2 from pulverized-coal (PC) fired power plants. We elucidate the cause of that spread by deriving an analytic relationship for the energy penalty from thermodynamic principles and by identifying which variables are most difficult to constrain. We define the energy penalty for CCS to be the fraction of fuel that must be dedicated to CCS for a fixed quantity of work output. That penalty can manifest itself as either the additional fuel required to maintain a power plant's output or the loss of output for a constant fuel input. Of the 17 parameters that constitute the energy penalty, only the fraction of available waste heat that is recovered for use and the 2nd-law separation efficiency are poorly constrained. We provide an absolute lower bound for the energy penalty of ~11%, and we demonstrate to what degree increasing the fraction of available-waste-heat recovery can reduce the energy penalty from the higher values reported. It is further argued that an energy penalty of ~40% will be easily achieved while one of ~29% represents a decent target value. Furthermore, we analyze the distribution of PC plants in the U.S. and calculate a distribution for the additional fuel required to operate all these plants with CO2 capture and storage (CCS).Earth and Planetary SciencesEngineering and Applied Science

Screening and Counseling Practices Reported by Obstetrician–Gynecologists for Patients With Hepatitis C Virus Infection

Background: Obstetrician—gynecologists are important providers of primary health care to women, and the hepatitis C virus (HCV) infection screening practices and recommendations provided by obstetrician—gynecologists for HCV-infected patients are unknown. Methods: We surveyed American College of Obstetricians and Gynecologists (ACOG) Fellows, including 413 Fellows who were participating in the Collaborative Ambulatory Research Network (CARN) and 650 randomly sampled Fellows, about HCV screening and counseling practices. Results: In total, 74% of CARN members and 44% of non-CARN members responded. Demographics and practice structure were similar between the two groups. More than 80% of providers routinely collected drug use and blood transfusion histories from their patients. Of the respondents, 49% always screened for HCV infection when patients had a history of injection drug use, and 35% screened all patientswho had received a blood transfusion before 1992. For HCV-infected patients, 47% of the physicians always advised against breastfeeding, 70% recommended condom use with a long-term steady partner, and 64% advised against alcohol consumption. Respondents who considered themselves to be primary care providers were no more likely to screen or provide appropriate counseling messages than were other providers. Conclusions: Most obstetrician—gynecologists are routinely collecting information that can be used to assess HCV infection risk, but HCV screening practices and counseling that are provided for those with HCV infection are not always consistent with current Centers for Disease Control and Prevention and ACOG recommendations