Stanley's despatches to the New York herald, 1871-1872, 1874-1877

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Effect of hydrogen bond cooperativity on the behavior of water

Four scenarios have been proposed for the low--temperature phase behavior of liquid water, each predicting different thermodynamics. The physical mechanism which leads to each is debated. Moreover, it is still unclear which of the scenarios best describes water, as there is no definitive experimental test. Here we address both open issues within the framework of a microscopic cell model by performing a study combining mean field calculations and Monte Carlo simulations. We show that a common physical mechanism underlies each of the four scenarios, and that two key physical quantities determine which of the four scenarios describes water: (i) the strength of the directional component of the hydrogen bond and (ii) the strength of the cooperative component of the hydrogen bond. The four scenarios may be mapped in the space of these two quantities. We argue that our conclusions are model-independent. Using estimates from experimental data for H bond properties the model predicts that the low-temperature phase diagram of water exhibits a liquid--liquid critical point at positive pressure.Comment: 18 pages, 3 figure

Contamination Control Assessment of the World's Largest Space Environment Simulation Chamber

The Space Power Facility s thermal vacuum test chamber is the largest chamber in the world capable of providing an environment for space simulation. To improve performance and meet stringent requirements of a wide customer base, significant modifications were made to the vacuum chamber. These include major changes to the vacuum system and numerous enhancements to the chamber s unique polar crane, with a goal of providing high cleanliness levels. The significance of these changes and modifications are discussed in this paper. In addition, the composition and arrangement of the pumping system and its impact on molecular back-streaming are discussed in detail. Molecular contamination measurements obtained with a TQCM and witness wafers during two recent integrated system tests of the chamber are presented and discussed. Finally, a concluding remarks section is presented

Acceleration of Enterococcus faecalis Biofilm Formation by Aggregation Substance Expression in an Ex Vivo Model of Cardiac Valve Colonization

Infectious endocarditis involves formation of a microbial biofilm in vivo. Enterococcus faecalis Aggregation Substance (Asc10) protein enhances the severity of experimental endocarditis, where it has been implicated in formation of large vegetations and in microbial persistence during infection. In the current study, we developed an ex vivo porcine heart valve adherence model to study the initial interactions between Asc10+ and Asc10− E. faecalis and valve tissue, and to examine formation of E. faecalis biofilms on a relevant tissue surface. Scanning electron microscopy of the infected valve tissue provided evidence for biofilm formation, including growing masses of bacterial cells and the increasing presence of exopolymeric matrix over time; accumulation of adherent biofilm populations on the cardiac valve surfaces during the first 2–4 h of incubation was over 10-fold higher than was observed on abiotic membranes incubated in the same culture medium. Asc10 expression accelerated biofilm formation via aggregation between E. faecalis cells; the results also suggested that in vivo adherence to host tissue and biofilm development by E. faecalis can proceed by Asc10-dependent or Asc10-independent pathways. Mutations in either of two Asc10 subdomains previously implicated in endocarditis virulence reduced levels of adherent bacterial populations in the ex vivo system. Interference with the molecular interactions involved in adherence and initiation of biofilm development in vivo with specific inhibitory compounds could lead to more effective treatment of infectious endocarditis

Missense-depleted regions in population exomes implicate ras superfamily nucleotide-binding protein alteration in patients with brain malformation.

Genomic sequence interpretation can miss clinically relevant missense variants for several reasons. Rare missense variants are numerous in the exome and difficult to prioritise. Affected genes may also not have existing disease association. To improve variant prioritisation, we leverage population exome data to identify intragenic missense-depleted regions (MDRs) genome-wide that may be important in disease. We then use missense depletion analyses to help prioritise undiagnosed disease exome variants. We demonstrate application of this strategy to identify a novel gene association for human brain malformation. We identified de novo missense variants that affect the GDP/GTP-binding site of ARF1 in three unrelated patients. Corresponding functional analysis suggests ARF1 GDP/GTP-activation is affected by the specific missense mutations associated with heterotopia. These findings expand the genetic pathway underpinning neurologic disease that classically includes FLNA. ARF1 along with ARFGEF2 add further evidence implicating ARF/GEFs in the brain. Using functional ontology, top MDR-containing genes were highly enriched for nucleotide-binding function, suggesting these may be candidates for human disease. Routine consideration of MDR in the interpretation of exome data for rare diseases may help identify strong genetic factors for many severe conditions, infertility/reduction in reproductive capability, and embryonic conditions contributing to preterm loss

More than one dynamic crossover in protein hydration water

Studies of liquid water in its supercooled region have led to many insights into the structure and behavior of water. While bulk water freezes at its homogeneous nucleation temperature of approximately 235 K, for protein hydration water, the binding of water molecules to the protein avoids crystallization. Here we study the dynamics of the hydrogen bond (HB) network of a percolating layer of water molecules, comparing measurements of a hydrated globular protein with the results of a coarse-grained model that has been shown to successfully reproduce the properties of hydration water. With dielectric spectroscopy we measure the temperature dependence of the relaxation time of protons charge fluctuations. These fluctuations are associated to the dynamics of the HB network of water molecules adsorbed on the protein surface. With Monte Carlo (MC) simulations and mean--field (MF) calculations we study the dynamics and thermodynamics of the model. In both experimental and model analyses we find two dynamic crossovers: (i) one at about 252 K, and (ii) one at about 181 K. The agreement of the experiments with the model allows us to relate the two crossovers to the presence of two specific heat maxima at ambient pressure. The first is due to fluctuations in the HB formation, and the second, at lower temperature, is due to the cooperative reordering of the HB network

Analysis of opioid and non-opioid end products of pro-dynorphin in the substantia nigra of the rat

The substantia nigra is among the richest pro-dynorphin terminal field regions in the rat brain. We therefore contrasted processing in this area to the known processing in the posterior pituitary. Fractionation of acid extracts of the posterior pituitary by gel filtration followed by analysis by radioimmunoassay indicated that the molar ratio of dynorphin A(1-17) to dynorphin A(1-8) averaged 1:2. The levels of dynorphin A-related end products to [alpha]-neo-endorphin and bridge peptide (a 2K nonopioid end product of pro-dynorphin) were approximately equimolar; however, the levels of dynorphin B-sized material were 50% lower than dynorphin A levels. Similar analysis of acid extracts of the substantia nigra also indicated that the levels of dynorphin A, [alpha]-neo-endorphin, and bridge peptide were approximately equimolar. In this terminal field the levels of dynorphin B-sized material were approximately 60% lower than dynorphin A. A striking feature of the nigral system was that the molar ratio of dynorphin A(1-17) to dynorphin A(1-8) averaged 1:16. Thus, in the nigra, dynorphin A(1-17) is primarily a biosynthetic intermediate rather than as an end product.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25774/1/0000335.pd

IRG and GBP host resistance factors target aberrant, ‘‘Non-self’’ vacuoles characterized by the missing of ‘‘Self’’ IRGM proteins

Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. Targeting of Interferon-inducible GTPases to PVs requires the formation of higher-order protein oligomers, a process negatively regulated by a subclass of IRG proteins called IRGMs. We found that the paralogous IRGM proteins Irgm1 and Irgm3 fail to robustly associate with ‘‘non-self’’ PVs containing either the bacterial pathogen Chlamydia trachomatis or the protozoan pathogen Toxoplasma gondii. Instead, Irgm1 and Irgm3 reside on ‘‘self’’ organelles including lipid droplets (LDs). Whereas IRGM-positive LDs are guarded against the stable association with other IRGs and GBPs, we demonstrate that IRGM-stripped LDs become high affinity binding substrates for IRG and GBP proteins. These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of ‘‘self’’ IRGM proteins from these structures.Fil: Haldar, Arun K.. University Of Duke; Estados UnidosFil: Saka, Hector Alex. University Of Duke; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Piro, Anthony S.. University Of Duke; Estados UnidosFil: Dunn, Joe Dan. University Of Duke; Estados UnidosFil: Henry, Stanley C.. University Of Duke; Estados Unidos. Veteran Affairs Medical Center; Estados UnidosFil: Taylor, Gregory A.. University Of Duke; Estados Unidos. Veteran Affairs Medical Center; Estados UnidosFil: Frickel, Eva M.. National Institute for Medical Research; Reino UnidoFil: Valdivia, Raphael H.. University Of Duke; Estados UnidosFil: Coers, Jörn. University Of Duke; Estados Unido

Neonicotinoid pesticide limits improvement in buzz pollination by bumblebees

Neonicotinoid pesticides have been linked to global declines of beneficial insects such as bumblebees. Exposure to trace levels of these chemicals causes sub-lethal effects, such as reduced learning and foraging efficiency. Complex behaviours may be particularly vulnerable to the neurotoxic effects of neonicotinoids. Such behaviours may include buzz pollination (sonication), in which pollinators, usually bees, use innate and learned behaviours to generate high-frequency vibrations to release pollen from flowers with specialised anther morphologies. This study assesses the effect of field-realistic, chronic exposure to the widely-used neonicotinoid thiamethoxam on the development of sonication buzz characteristics over time, as well as the collection of pollen from buzz-pollinated flowers. We found that the pollen collection of exposed bees improved less with increasing experience than that of unexposed bees, with exposed bees collecting between 47% and 56% less pollen by the end of 10 trials. We also found evidence of two distinct strategies for maximising pollen collection: (1) extensions to the duration of individual buzzes and (2) extensions of the overall time spent buzzing. We find new complexities in buzz pollination, and conclude that the impacts of field-realistic exposure to a neonicotinoid pesticide may seriously compromise this important ecosystem service

Science and Ideology in Economic, Political, and Social Thought

This paper has two sources: One is my own research in three broad areas: business cycles, economic measurement and social choice. In all of these fields I attempted to apply the basic precepts of the scientific method as it is understood in the natural sciences. I found that my effort at using natural science methods in economics was met with little understanding and often considerable hostility. I found economics to be driven less by common sense and empirical evidence, then by various ideologies that exhibited either a political or a methodological bias, or both. This brings me to the second source: Several books have appeared recently that describe in historical terms the ideological forces that have shaped either the direct areas in which I worked, or a broader background. These books taught me that the ideological forces in the social sciences are even stronger than I imagined on the basis of my own experiences. The scientific method is the antipode to ideology. I feel that the scientific work that I have done on specific, long standing and fundamental problems in economics and political science have given me additional insights into the destructive role of ideology beyond the history of thought orientation of the works I will be discussing