No borders during the post-glacial assembly of European bryophytes.

Climatic fluctuations during the Last Glacial Maximum (LGM) exerted a profound influence on biodiversity patterns, but their impact on bryophytes, the second most diverse group of land plants, has been poorly documented. Approximate Bayesian computations based on coalescent simulations showed that the post-glacial assembly of European bryophytes involves a complex history from multiple sources. The contribution of allochthonous migrants was 95-100% of expanding populations in about half of the 15 investigated species, which is consistent with the globally balanced genetic diversities and extremely low divergence observed among biogeographical regions. Such a substantial contribution of allochthonous migrants in the post-glacial assembly of Europe is unparalleled in other plants and animals. The limited role of northern micro-refugia, which was unexpected based on bryophyte life-history traits, and of southern refugia, is consistent with recent palaeontological evidence that LGM climates in Eurasia were much colder and drier than what palaeoclimatic models predict.

High power single-mode delivery of mid-infrared sources through chalcogenide fiber.

Mechanically robust and low loss single-mode arsenic sulfide fibers are used to deliver high power mid-infrared sources. Anti-reflection coatings were deposited on the fiber facets, enabling 90% transmission through 20 cm length fibers. 10.3 W was transmitted through an anti-reflection coated fiber at 2053 nm, and uncoated fibers sustained 12 MW/cm2 intensities on the facet without failure. A Cr:ZnSe laser transmitted >1 W at 2520 nm, and a Fe:ZnSe laser transmitted 0.5 W at 4102 nm. These results indicate that by improving the anti-reflection coatings and using a high beam quality mid-infrared source, chalcogenide fibers can reliably deliver ≥10 W in a single mode, potentially out to 6.5 µm.

Isospin Symmetry at High Spin Studied via Nucleon Knockout from Isomeric States.

One-neutron knockout reactions have been performed on a beam of radioactive ^{53}Co in a high-spin isomeric state. The analysis is shown to yield a highly selective population of high-spin states in an exotic nucleus with a significant cross section, and hence represents a technique that is applicable to the planned new generation of fragmentation-based radioactive beam facilities. Additionally, the relative cross sections among the excited states can be predicted to a high level of accuracy when reliable shell-model input is available. The work has resulted in a new level scheme, up to the 11^{+} band-termination state, of the proton-rich nucleus ^{52}Co (Z=27, N=25). This has in turn enabled a study of mirror energy differences in the A=52 odd-odd mirror nuclei, interpreted in terms of isospin-nonconserving (INC) forces in nuclei. The analysis demonstrates the importance of using a full set of J-dependent INC terms to explain the experimental observations.

Quadrupole transition strength in the (74)Ni nucleus and core polarization effects in the neutron-rich Ni isotopes.

The reduced transition probability B(E2;0(+)→2(+)) has been measured for the neutron-rich nucleus (74)Ni in an intermediate energy Coulomb excitation experiment performed at the National Superconducting Cyclotron Laboratory at Michigan State University. The obtained B(E2;0(+)→2(+))=642(-226)(+216) e(2) fm(4) value defines a trend which is unexpectedly small if referred to (70)Ni and to a previous indirect determination of the transition strength in (74)Ni. This indicates a reduced polarization of the Z=28 core by the valence neutrons. Calculations in the pfgd model space reproduce well the experimental result indicating that the B(E2) strength predominantly corresponds to neutron excitations. The ratio of the neutron and proton multipole matrix elements supports such an interpretation.

Relationship between land use classification and grass shrimp Palaemonetes spp. population metrics in coastal watersheds.

Estuaries in the southeastern USA have experienced increased loading of contaminants from nonpoint source runoff as well as changes in habitat (e.g., loss of wetlands) due to urbanization. These changes may pose significant risks to estuarine fauna, including crustaceans. Several studies have shown relationships between land use classification and levels of stress in estuarine populations. The grass shrimp of the genus Palaemonetes is one of the dominant species found in estuarine tidal creeks, accounting for more than 50 % of all macropelagic fauna. Grass shrimp populations were sampled monthly for 3 years at six estuarine creeks on Kiawah Island, SC. Creek watersheds were estimated using National Aerial Photograph Program color infrared and low-altitude true color aerial photography combined with in situ differentially corrected global positioning system mapping of engineered features. Land classifications delineated included water, marsh, buildings, roads, and lawns. Pairwise comparisons for grass shrimp densities among sites showed significant differences on an annual and seasonal basis. Significant relationships (p < 0.05) between land class variables and grass shrimp density were identified both annually and seasonally. These findings suggest an influence of land use on Palaemonetes spp. populations.

Mirror energy differences at large isospin studied through direct two-nucleon knockout.

The first spectroscopy of excited states in 52Ni (T(z)=-2) and 51Co (T(z)=-3/2) has been obtained using the highly selective two-neutron knockout reaction. Mirror energy differences between isobaric analogue states in these nuclei and their mirror partners are interpreted in terms of isospin nonconserving effects. A comparison between large-scale shell-model calculations and data provides the most compelling evidence to date that both electromagnetic and an additional isospin nonconserving interactions for J=2 couplings, of unknown origin, are required to obtain good agreement.

Quadrupole collectivity beyond N = 28: intermediate-energy Coulomb excitation of (47,48)Ar.

We report on the first experimental study of quadrupole collectivity in the very neutron-rich nuclei (47,48)Ar using intermediate-energy Coulomb excitation. These nuclei are located along the path from doubly magic Ca to collective S and Si isotopes, a critical region of shell evolution and structural change. The deduced B(E2) transition strengths are confronted with large-scale shell-model calculations in the sdpf shell using the state-of-the-art SDPF-Uand EPQQM effective interactions. The comparison between experiment and theory indicates that a shell-model description of Ar isotopes around N=28 remains a challenge.

Probing configuration mixing in 12Be with Gamow-Teller transition strengths.

We present a novel technique for studying the quenching of shell gaps in exotic isotopes. The method is based on extracting Gamow-Teller (ΔL=0, ΔS=1) transition strengths [B(GT)] to low-lying states from charge-exchange reactions at intermediate beam energies. These Gamow-Teller strengths are very sensitive to configuration mixing between cross-shell orbitals, and this technique thus provides an important complement to other tools currently used to study cross-shell mixing. This work focuses on the N=8 shell gap. We populated the ground and 2.24 MeV 0+ states in 12Be using the 12B(1+) (7Li, 7Be) reaction at 80 MeV/u in inverse kinematics. Using the ground-state B(GT) value from ß-decay measurements (0.184±0.007) as a calibration, the B(GT) for the transition to the second 0+ state was determined to be 0.214±0.051. Comparing the extracted Gamow-Teller strengths with shell-model calculations, it was determined that the wave functions of the first and second 0+ states in 12Be are composed of 25±5% and 60±5% (0s)4(0p)8 configurations, respectively.

Knockout reactions from p-shell nuclei: tests of ab initio structure models.

Absolute cross sections have been determined following single neutron knockout reactions from 10Be and 10C at intermediate energy. Nucleon density distributions and bound-state wave function overlaps obtained from both variational Monte Carlo (VMC) and no core shell model (NCSM) ab initio calculations have been incorporated into the theoretical description of knockout reactions. Comparison to experimental cross sections demonstrates that the VMC approach, with the inclusion of 3-body forces, provides the best overall agreement while the NCSM and conventional shell-model calculations both overpredict the cross sections by 20% to 30% for 10Be and by 40% to 50% for 10C, respectively. This study gains new insight into the importance of 3-body forces and continuum effects in light nuclei and provides a sensitive technique to assess the accuracy of ab initio calculations for describing these effects.

Enhanced quadrupole collectivity at N = 40: the case of neutron-rich Fe isotopes.

The transition rates for the 2(1)+ states in (62,64,66)Fe were studied using the recoil distance Doppler-shift technique applied to projectile Coulomb excitation reactions. The deduced E2 strengths illustrate the enhanced collectivity of the neutron-rich Fe isotopes up to N = 40. The results are interpreted using the generalized concept of valence proton symmetry which describes the evolution of nuclear structure around N = 40 as governed by the number of valence protons with respect to Z ≈ 30. The trend of collectivity suggested by the experimental data is described by state-of-the-art shell-model calculations with a new effective interaction developed for the fpgd valence space.

Lifetime measurement of the 2(1)+ state in 20C.

Establishing how and when large N/Z values require modified or new theoretical tools is a major quest in nuclear physics. Here we report the first measurement of the lifetime of the 2(1)+ state in the near-dripline nucleus 20C. The deduced value of τ(2(1)+)=9.8±2.8(stat)(-1.1)(+0.5)(syst) ps gives a reduced transition probability of B(E2; 2(1)+→0(g.s.)+)=7.5(-1.7)(+3.0)(stat)(-0.4)(+1.0)(syst) e2 fm4 in good agreement with a shell model calculation using isospin-dependent effective charges.

Increased OLED radiative efficiency using a directive optical antenna.

We investigate the improvement in efficiency of organic light emitting diodes/displays (OLEDs) by embedding a typical OLED structure within a metallic patch grating resonator. A patch grating resonator is similar to the more familiar Fabry-Perot resonator, except that one mirror of the resonator is a metallic patch grating with a pitch approximately lambda /2 that reduces lateral propagation of radiative emission. FDTD simulations of the proposed structure indicate a potential 71% increase in emitted power over that of a reference OLED structure, and an additional 5% gain from adding an ITO spacer adjacent to the metallic electrode layer (for a total 76% increase). Implementation of this structure requires little to no modification of the OLED manufacturing process.

Genomic scanning using AFLP to detect loci under selection in the moss Funaria hygrometrica along a climate gradient in the Sierra Nevada Mountains, Spain.

The common cord moss Funaria hygrometrica has a worldwide distribution and thrives in a wide variety of environments. Here, we studied the genetic diversity in F. hygrometrica along an abiotic gradient in the Mediterranean high mountain of Sierra Nevada (Spain) using a genome scan method. Eighty-four samples from 17 locations from 24 to 2700 m were fingerprinted based on their amplified fragment length polymorphism (AFLP) banding pattern. Using PCA and Bayesian inference we found that the genetic diversity was structured in three or four clusters, respectively. Using a genome scan method we identified 13 outlier loci, which showed a signature of positive selection. Partial Mantel tests were performed between the Euclidean distance matrices of geographic and climatic variables, versus the pair-wise genetic distance of the AFLP dataset and AFLP-positive outliers dataset. AFLP-positive outlier data were significantly correlated with the gradient of the climatic variables, suggesting adaptive variation among populations of F. hygrometrica along the Sierra Nevada Mountains. We highlight the additional analyses necessary to identify the nature of these loci, and their biological role in the adaptation process.

Lipopolysaccharide Biosynthesis Genes of Yersinia pseudotuberculosis Promote Resistance to Antimicrobial Chemokines.

Antimicrobial chemokines (AMCs) are a recently described family of host defense peptides that play an important role in protecting a wide variety of organisms from bacterial infection. Very little is known about the bacterial targets of AMCs or factors that influence bacterial susceptibility to AMCs. In an effort to understand how bacterial pathogens resist killing by AMCs, we screened Yersinia pseudotuberculosis transposon mutants for those with increased binding to the AMCs CCL28 and CCL25. Mutants exhibiting increased binding to AMCs were subjected to AMC killing assays, which revealed their increased sensitivity to chemokine-mediated cell death. The majority of the mutants exhibiting increased binding to AMCs contained transposon insertions in genes related to lipopolysaccharide biosynthesis. A particularly strong effect on susceptibility to AMC mediated killing was observed by disruption of the hldD/waaF/waaC operon, necessary for ADP-L-glycero-D-manno-heptose synthesis and a complete lipopolysaccharide core oligosaccharide. Periodate oxidation of surface carbohydrates also enhanced AMC binding, whereas enzymatic removal of surface proteins significantly reduced binding. These results suggest that the structure of Y. pseudotuberculosis LPS greatly affects the antimicrobial activity of AMCs by shielding a protein ligand on the bacterial cell surface.

Dobutamine stress echocardiography early after heart transplantation predicts development of allograft coronary artery disease and outcome.

OBJECTIVES: This study sought to determine the prognostic significance of serial dobutamine stress echocardiography (DSE) in new heart transplant recipients and to examine the relation between persistent wall motion abnormalities and the eventual development of coronary artery disease (CAD) as assessed by angiography. BACKGROUND: Allograft CAD is a major cause of graft failure. However, clinical diagnosis of the early disease remains difficult. The reasons for this include the diffuse nature of the disease and its predilection for the microvasculature, which are not easily detected by coronary angiography. Identifying patients at risk for the development of angiographic CAD early after transplantation may allow such patients to be targeted for aggressive treatment options to prevent subsequent cardiac events and early graft failure. METHODS: Twenty-two new heart transplant recipients were selected to undergo serial DSE at the time of their regularly scheduled endomyocardial biopsy. In addition, patients underwent scheduled annual coronary angiography. DSE was performed in 5-min stages with infusion of intravenous dobutamine at 5, 10, 20, 30 and 40 microg/kg body weight per min. RESULTS: Twenty-two patients had 91 DSE studies and 45 coronary angiograms. The patients were categorized into three groups based on the echocardiographic results. Group 1 (n = 7) had normal serial stress echocardiographic studies. Group 2 (n = 4) had transient inducible wall motion abnormalities. Group 3 (n = 11) developed persistent wall motion abnormalities. During a mean follow-up time of 32 +/- 11 months (range 5 to 50), 8 (73%) of 11 patients in Group 3 developed events. The events included angiographic CAD (n = 7), myocardial infarction (MI) (n = 1) and cardiac death (n = 3). The patient who developed an MI had a normal coronary angiogram. No cardiac event or angiographic disease occurred in either Group 1 or 2 patients. CONCLUSIONS: These results suggest that dobutamine-induced wall motion abnormalities, which are persistent in new heart transplant recipients, are predictive of the development of angiographic CAD, MI or death.

L-735,524: the design of a potent and orally bioavailable HIV protease inhibitor.

A series of HIV protease inhibitors possessing a hydroxylaminepentanamide transition state isostere have been developed. Incorporation of a basic amine into the backbone of the L-685,434 (2) series provided antiviral potency combined with a highly improved pharmacokinetic profile in animal models. Guided by molecular modeling and an X-ray crystal structure of the inhibited enzyme complex, we were able to design L-735,524. This compound is potent and competitively inhibits HIV-1 PR and HIV-2 PR with Ki values of 0.52 and 3.3 nM, respectively. It also stops the spread of the HIV-1IIIb-infected MT4 lymphoid cells at concentrations of 25-50 nM. To date, numerous HIV-PR inhibitors have been reported, but few have been studied in humans because they lack acceptable oral bioavailability. L-735,524 is orally bioavailable in three animals models, using clinically acceptable formulations, and is currently in phase II human clinical trials.

Identification of MK-944a: a second clinical candidate from the hydroxylaminepentanamide isostere series of HIV protease inhibitors.

Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a K(i) value of 0.049 nM. It stops the spread of the HIV(IIIb)-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of alpha(1) acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.

Anorexic effect of K+ channel blockade in mesenteric arterial smooth muscle and intestinal epithelial cells.

Activity of voltage-gated K+ (Kv) channels controls membrane potential (E(m)). Membrane depolarization due to blockade of K+ channels in mesenteric artery smooth muscle cells (MASMC) should increase cytoplasmic free Ca2+ concentration ([Ca2+]cyt) and cause vasoconstriction, which may subsequently reduce the mesenteric blood flow and inhibit the transportation of absorbed nutrients to the liver and adipose tissue. In this study, we characterized and compared the electrophysiological properties and molecular identities of Kv channels and examined the role of Kv channel function in regulating E(m) in MASMC and intestinal epithelial cells (IEC). MASMC and IEC functionally expressed multiple Kv channel alpha- and beta-subunits (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5, Kv2.1, Kv4.3, and Kv9.3, as well as Kvbeta1.1, Kvbeta2.1, and Kvbeta3), but only MASMC expressed voltage-dependent Ca2+ channels. The current density and the activation and inactivation kinetics of whole cell Kv currents were similar in MASMC and IEC. Extracellular application of 4-aminopyridine (4-AP), a Kv-channel blocker, reduced whole cell Kv currents and caused E(m) depolarization in both MASMC and IEC. The 4-AP-induced E(m) depolarization increased [Ca2+]cyt in MASMC and caused mesenteric vasoconstriction. Furthermore, ingestion of 4-AP significantly reduced the weight gain in rats. These results suggest that MASMC and IEC express multiple Kv channel alpha- and beta-subunits. The function of these Kv channels plays an important role in controlling E(m). The membrane depolarization-mediated increase in [Ca2+]cyt in MASMC and mesenteric vasoconstriction may inhibit transportation of absorbed nutrients via mesenteric circulation and limit weight gain.

Pharmacokinetics, immunogenicity, and efficacy of dimeric TNFR binding proteins in healthy and bacteremic baboon.

Immunogenicity, pharmacokinetics, and therapeutic efficacy of three novel dimeric soluble tumor necrosis factor (TNF)-receptor I constructs [TNF-binding protein (bp)] were evaluated in 28 baboons, 12 of which were healthy and 16 were challenged with a lethal Escherichia coli bacteremia. The three constructs differed only in the number of extracellular domains of the TNF receptor I and were dimerized with polyethylene glycol. Although all three constructs had generally similar pharmacokinetics when administered to a naive animal, they differed quantitatively in their immunogenicity. Antibodies were detected more frequently, and titers were significantly higher (P < 0.05) in both healthy and septic baboons that received the 4.0-domain TNF-bp construct, compared with animals receiving the 2.6-domain construct. When the TNF-bp constructs were administered a second time (21 days later), the half-lives of the three constructs were significantly shorter in animals that had an antibody response after the first injection. In contrast, all three TNF-bp constructs were equally effective at improving outcome, blocking a systemic TNF-alpha response, and attenuating the cytokine responses when administered at a dose of 1.0 mg/kg body wt 1 h before a lethal E. coli infusion. The findings suggest that immunogenicity of TNF-bp constructs can be altered by changing the number of functional domains, without affecting their capacity to neutralize TNF-alpha and to abrogate TNF-mediated pathology.

Prevention of bacterial adherence to implant surfaces with a crosslinked albumin coating in vitro.

Titanium surfaces were coated with bovine serum albumin using carbodiimide, a crosslinking agent. The durability of the coated surfaces and the inhibitory effect of the albumin coating on bacterial adherence were tested in vitro for 20 consecutive days at 37 degrees C in phosphate buffered saline, with intermittent agitation. The results showed that only 10% of the coated bovine serum albumin decayed off the surface during the 20-day incubation period. The inhibition rate of the albumin coating on bacterial adherence remained high (greater than 8.5%) throughout the experiment. The results suggested potential use of this crosslinked albumin coating to reduce bacterial adherence and thus the subsequent possibility of prosthetic or implant infection in vivo.