An Enantioselective Synthesis of the ABD Tricycle for (-)-Phomactin A Featuring Rawal's Asymmetric Diels-Alder Cycloaddition.

An enantioselective synthesis of the ABD-ring of (-)-phomactin A is described here. The sequence features Rawal's asymmetric Diels-Alder cycloaddition. The overall length is significantly reduced from our previous attempt.

Association and decontamination of Bacillus spores in a simulated drinking water system.

The objective of this work was to elucidate the disinfectant susceptibility of Bacillus anthracis Sterne (BA) and a commercial preparation of Bacillus thuringiensis (BT) spores associated with a simulated drinking water system. Biofilms composed of indigenous water system bacteria were accumulated on copper and polyvinyl chloride (PVC) pipe material surfaces in a low-flow pipe loop and uniformly mixed tank reactor (CDC biofilm reactor). Application of a distributed shear during spore contact resulted in approximately a 1.

Physical demand levels in individuals completing a sports performance-based work conditioning/hardening program after lumbar fusion.

Background Context: Pain and disability after lumbar fusion surgery contributes to the over $20 billion dollars spent in health-care costs and estimated $28 billion in lost wages annually. With the goal of returning to work, an intensive program designed to build functional strength may be used. Previous interventions for this subgroup report the outcome measure of return to work (RTW), but do not account for the physical demand of the job to which they are returning.

Recoil-ion momentum distributions for two-photon double ionization of He and Ne by 44 eV free-electron laser radiation.

Recoil-ion momentum distributions for two-photon double ionization of He and Ne (variant Planck's over omega=44 eV) have been recorded with a reaction microscope at FLASH (the free-electron laser at Hamburg) at an intensity of approximately 1 x 10(14) W/cm2 exploring the dynamics of the two fundamental two-photon-two-electron reaction pathways, namely, sequential and direct (or nonsequential) absorption of the photons. We find strong differences in the recoil-ion momentum patterns for the two mechanisms pointing to the significantly different two-electron emission dynamics and thus provide serious constraints for theoretical models.

Identification of ALK as a major familial neuroblastoma predisposition gene.

Neuroblastoma is a childhood cancer that can be inherited, but the genetic aetiology is largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase (ALK) gene explain most hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at chromosome bands 2p23-24 using a whole-genome scan in neuroblastoma pedigrees.

Trophic transfer of nanoparticles in a simplified invertebrate food web.

The unique chemical and physical properties of engineered nanomaterials that make them attractive for numerous applications also contribute to their unexpected behaviour in the environment and biological systems. The potential environmental risks, including their impact on aquatic organisms, have been a central argument for regulating the growth of the nanotechnology sector. Here we show in a simplified food web that carboxylated and biotinylated quantum dots can be transferred to higher trophic organisms (rotifers) through dietary uptake of ciliated protozoans.

Substance use among early adolescent girls: risk and protective factors.

Disquieting rates of alcohol and drug use among adolescent girls call for original research on gender-specific risk and protective factors for substance use. Particularly salient are data on theory-driven factors that can inform prevention programming. Surveying 781 adolescent girls and their mothers, we found relationships between girls' use of alcohol, prescription drugs, and inhalants and girls' after-school destinations, body images, depression, best friend's substance use, maternal drinking behavior, mother-daughter interactions, and family norms surrounding substance use.

Increasing the number of attacks increases the conversion rate in laparoscopic diverticulitis surgery.

Background: This study aimed to determine whether the number of diverticulitis or complicated diverticulitis episodes affects the conversion rate or postoperative complication rate in elective laparoscopic sigmoid colectomy.

Methods: In this study, 216 charts were reviewed for baseline characteristics, diverticulitis history, and intra- and postoperative complications. Analysis was performed with the Student's t-test, the chi-square test, and Fisher's exact tests.

A functional screen identifies miR-34a as a candidate neuroblastoma tumor suppressor gene.

MicroRNAs are small noncoding RNAs that have critical roles in regulating a number of cellular functions through transcriptional silencing. They have been implicated as oncogenes and tumor suppressor genes (oncomirs) in several human neoplasms. We used an integrated genomics and functional screening strategy to identify potential oncomirs in the pediatric neoplasm neuroblastoma.

Ultrafast probing of core hole localization in N2.

Although valence electrons are clearly delocalized in molecular bonding frameworks, chemists and physicists have long debated the question of whether the core vacancy created in a homonuclear diatomic molecule by absorption of a single x-ray photon is localized on one atom or delocalized over both. We have been able to clarify this question with an experiment that uses Auger electron angular emission patterns from molecular nitrogen after inner-shell ionization as an ultrafast probe of hole localization. The experiment, along with the accompanying theory, shows that observation of symmetry breaking (localization) or preservation (delocalization) depends on how the quantum entangled Bell state created by Auger decay is detected by the measurement.

Chemical Synthesis of the GHIJKLMNO Ring System of Maitotoxin.

As the largest secondary metabolite to be discovered as of yet, the polyether marine neurotoxin maitotoxin constitutes a major structural and synthetic challenge. After its originally proposed structure ( 1) had been questioned on the basis of biosynthetic considerations, we provided computational and experimental support for structure 1. In an effort to provide stronger experimental evidence of the molecular architecture of maitotoxin, its GHIJKLMNO ring system 3 was synthesized.

Chromosome 6p22 locus associated with clinically aggressive neuroblastoma.

Background: Neuroblastoma is a malignant condition of the developing sympathetic nervous system that most commonly affects young children and is often lethal. Its cause is not known.

Methods: We performed a genomewide association study by first genotyping blood DNA samples from 1032 patients with neuroblastoma and 2043 control subjects of European descent using the Illumina HumanHap550 BeadChip.

Effects of environmental enrichment on sensitivity to mu, kappa, and mixed-action opioids in female rats.

Several studies report that environmental enrichment enhances sensitivity to opioid receptor agonists in male rats. Very few studies have examined the effects of enrichment in female rats, and thus it is not clear whether females are similarly sensitive to these effects. Consequently, the purpose of the present study was to examine the effects of environmental enrichment on sensitivity to representative mu, kappa, and mixed-action opioids in female rats.

Lifting a familiar object: visual size analysis, not memory for object weight, scales lift force.

The brain can accurately predict the forces needed to efficiently manipulate familiar objects in relation to mechanical properties such as weight. These predictions involve memory or some type of central representation, but visual analysis of size also yields accurate predictions of the needed fingertip forces. This raises the issue of which process (weight memory or visual size analysis) is used during everyday life when handling familiar objects.

The inactive 44-kDa processed form of membrane type 1 matrix metalloproteinase (MT1-MMP) enhances proteolytic activity via regulation of endocytosis of active MT1-MMP.

Membrane type 1 (MT1) matrix metalloproteinase (MMP-14) is a membrane-tethered MMP considered to be a major mediator of pericellular proteolysis. MT1-MMP is regulated by a complex array of mechanisms, including processing and endocytosis that determine the pool of active proteases on the plasma membrane. Autocatalytic processing of active MT1-MMP generates an inactive membrane-tethered 44-kDa product (44-MT1) lacking the catalytic domain.

Process monitoring the inactivation of ricin and model proteins by disinfectants using fluorescence and biological activity.

It is important to develop rapid and reliable processes to monitor the decontamination of toxins released to the environment. The inactivation of the protein toxin ricin by the disinfectants bleach (sodium hypochlorite) and monochloramine was measured by the effect on mammalian cell cytotoxicity. The effect of the disinfectants on the native fluorescence (due mainly to tryptophan and to a lesser extent tyrosine) of ricin was also measured in parallel.

Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine.

Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques.

Geographical and climatic limits of needle types of one- and two-needled pinyon pines.

AIM: The geographical extent and climatic tolerances of one- and two-needled pinyon pines (Pinus subsect. Cembroides) are the focus of questions in taxonomy, palaeoclimatology and modelling of future distributions. The identification of these pines, traditionally classified by one- versus two-needled fascicles, is complicated by populations with both one- and two-needled fascicles on the same tree, and the description of two more recently described one-needled varieties: the fallax-type and californiarum-type.

Cross-clade protective immune responses to influenza viruses with H5N1 HA and NA elicited by an influenza virus-like particle.

Background: Vaccination is a cost-effective counter-measure to the threat of seasonal or pandemic outbreaks of influenza. To address the need for improved influenza vaccines and alternatives to egg-based manufacturing, we have engineered an influenza virus-like particle (VLP) as a new generation of non-egg or non-mammalian cell culture-based candidate vaccine.

Methodology/principal Findings: We generated from a baculovirus expression system using insect cells, a non-infectious recombinant VLP vaccine from both influenza A H5N1 clade 1 and clade 2 isolates with pandemic potential.

Bacillus anthracis spore suspensions: determination of stability and comparison of enumeration techniques.

Aim: To determine the stability and variability in concentration of spore suspensions of Bacillus anthracis (BA) spore suspensions by comparing different methods of enumeration and to detect changes, if any, under different storage conditions.

Methods And Results: Plate and microscope counts were compared to measuring the genomic equivalents based on DNA content BA spore suspensions. We developed chemical methods to extract spore DNA and extra-spore (ES) DNA.

Monoclonal antibody selection for interleukin-4 quantification using suspension arrays and forward-phase protein microarrays.

A recombinant mouse interleukin-4 (IL-4) and three different purified rat antimouse IL-4 monoclonal antibodies (Mab) with different clonalities were employed as a model system. This system was used to examine monoclonal antibody effectiveness using both conventional and high-throughput measurement techniques to select antibodies for attaining the most sensitive detection of the recombinant IL-4 through the "sandwich-type" immunoassays. Surface plasmon resonance (SPR) measurements and two high-throughput methods, suspension arrays (also called multiplexed bead arrays) and forward-phase protein microarrays, predicted the same capture (BVD4-1D11) and detection (BVD6-24G2) antibody pair for the most sensitive detection of the recombinant cytokine.

Animal-assisted therapy in patients hospitalized with heart failure.

Background: Animal-assisted therapy improves physiological and psychosocial variables in healthy and hypertensive patients.

Objectives: To determine whether a 12-minute hospital visit with a therapy dog improves hemodynamic measures, lowers neurohormone levels, and decreases state anxiety in patients with advanced heart failure.

Methods: A 3-group randomized repeated-measures experimental design was used in 76 adults.