First Study of the

New astronomical observations point to a nucleosynthesis picture that goes beyond what was accepted until recently. The intermediate "i" process was proposed as a plausible scenario to explain some of the unusual abundance patterns observed in metal-poor stars. The most important nuclear physics properties entering i-process calculations are the neutron-capture cross sections and they are almost exclusively not known experimentally. Here we provide the first experimental constraints on the ^{139}Ba(n,γ)^{140}Ba reaction rate, which is the dominant source of uncertainty for the production of lanthanum, a key indicator of i-process conditions. This is an important step towards identifying the exact astrophysical site of stars carrying the i-process signature.

Quantifying potentially infectious sharing patterns among people who inject drugs in Baltimore, USA.

Mixing matrices quantify how people with similar or different characteristics make contact with each other, creating potential for disease transmission. Little empirical data on mixing patterns among persons who inject drugs (PWID) are available to inform models of blood-borne disease such as HIV and hepatitis C virus. Egocentric drug network data provided by PWID in Baltimore, Maryland between 2005 and 2007 were used to characterise drug equipment-sharing patterns according to age, race and gender. Black PWID and PWID who were single (i.e. no stable sexual partner) self-reported larger equipment-sharing networks than their white and non-single counterparts. We also found evidence of assortative mixing according to age, gender and race, though to a slightly lesser degree in the case of gender. Highly assortative mixing according to race and gender highlights the existence of demographically isolated clusters, for whom generalised treatment interventions may have limited benefits unless targeted directly. These findings provide novel insights into mixing patterns of PWID for which little empirical data are available. The age-specific assortativity we observed is also significant in light of its role as a key driver of transmission for other pathogens such as influenza and tuberculosis.

Genetic variation in Pythium myriotylum based on SNP typing and development of a PCR-RFLP detection of isolates recovered from Pythium soft rot ginger.

Pythium myriotylum is responsible for severe losses in both capsicum and ginger crops in Australia under different regimes. Intraspecific genomic variation within the pathogen might explain the differences in aggressiveness and pathogenicity on diverse hosts. In this study, whole genome data of four P. myriotylum isolates recovered from three hosts and one Pythium zingiberis isolate were derived and analysed for sequence diversity based on single nucleotide polymorphisms (SNPs). A higher number of true and unique SNPs occurred in P. myriotylum isolates obtained from ginger with symptoms of Pythium soft rot (PSR) in Australia compared to other P. myriotylum isolates. Overall, SNPs were discovered more in the mitochondrial genome than those in the nuclear genome. Among the SNPs, a single substitution from the cytosine (C) to the thymine (T) in the partially sequenced CoxII gene of 14 representatives of PSR P. myriotylum isolates was within a restriction site of HinP1I enzyme which was used in the PCR-RFLP for detection and identification of the isolates without sequencing. The PCR-RFLP was also sensitive to detect PSR P. myriotylum strains from artificially infected ginger without the need for isolation for pure cultures. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study of intraspecific variants of Pythium myriotylum isolates recovered from different hosts and origins based on single nucleotide polymorphism (SNP) genotyping of multiple genes. The SNPs discovered provide valuable makers for detection and identification of P. myriotylum strains initially isolated from Pythium soft rot (PSR) ginger by using PCR-RFLP of the CoxII locus. The PCR-RFLP was also sensitive to detect P. myriotylum directly from PSR ginger sampled from pot trials without the need of isolation for pure cultures.

Direct Evidence of Octupole Deformation in Neutron-Rich

The neutron-rich nucleus ^{144}Ba (t_{1/2}=11.5 s) is expected to exhibit some of the strongest octupole correlations among nuclei with mass numbers A less than 200. Until now, indirect evidence for such strong correlations has been inferred from observations such as enhanced E1 transitions and interleaving positive- and negative-parity levels in the ground-state band. In this experiment, the octupole strength was measured directly by sub-barrier, multistep Coulomb excitation of a post-accelerated 650-MeV ^{144}Ba beam on a 1.0-mg/cm^{2} ^{208}Pb target. The measured value of the matrix element, ⟨3_{1}^{-}∥M(E3)∥0_{1}^{+}⟩=0.65(+17/-23) eb^{3/2}, corresponds to a reduced B(E3) transition probability of 48(+25/-34) W.u. This result represents an unambiguous determination of the octupole collectivity, is larger than any available theoretical prediction, and is consistent with octupole deformation.

Agreement of anthropometric and body composition measures predicted from 2D smartphone images and body impedance scales with criterion methods.

BACKGROUND/OBJECTIVES: Body composition and anthropometry assessment from two-dimensional smartphone images is possible through advancement of computational hardware and artificial intelligence (AI) techniques. This study established agreement of a novel smartphone assessment, compared with traditional bioelectrical impedance analysis (BIA), and criterion measures. SUBJECTS/METHODS: Body composition of 929 adults was measured using DXA (GE lunar iDXA), a foot-to-foot BIA machine (TANITA BC-313), and predictions from two-dimensional smartphone images. Anthropometry measures were also collected. Body composition and anthropometry estimates were compared via concordance coefficient correlation (CCC), equivalence testing, Bland-Altman analysis, and root mean square error (RMSE). RESULTS: 2D smartphone image predictions for percent body fat (%BF) (males: CCC = 0.90 and RMSE = 2.9, and females: CCC = 0.90 and RMSE = 2.8) reported greater agreement with DXA measures than the BIA measures (males: CCC = 0.66 and RMSE = 5.6, and females: CCC = 0.79 and RMSE = 4.6). All anthropometry 2D smartphone image predictions had a strong agreement with criterion measurements (CCC ≥ 0.84 and RMSE ≤ 3.3). Body composition and anthropometry measures predicted by the 2D smartphone images were clinically equivalent at ±2.5 and ±5.0% thresholds. BIA %BF was not equivalent at either threshold; with only female BIA fat-free mass equivalent at the ±5% threshold. CONCLUSION: Body composition predictions from 2D smartphone application images provide a promising alternative to BIA scales for in-home body composition assessment. Future research should assess the validity of this method for longitudinally tracking body composition and indicating an individual's potential risk of chronic diseases.

Beam particle identification and tagging of incompletely stripped heavy beams with HEIST.

A challenge preventing successful inverse kinematics measurements with heavy nuclei that are not fully stripped is identifying and tagging the beam particles. For this purpose, the HEavy ISotope Tagger (HEIST) has been developed. HEIST utilizes two micro-channel plate timing detectors to measure the time-of-flight, a multi-sampling ion chamber to measure energy loss, and a high-purity germanium detector to identify isomer decays and calibrate the isotope identification system. HEIST has successfully identified 198Pb and other nearby nuclei at energies of about 75 MeV/A. In the experiment discussed, a typical cut containing 89% of all 198Pb80+ in the beam had a purity of 86%. We examine the issues of charge state contamination. The observed charge state populations of these ions are presented and, using an adjusted beam energy, are well described by the charge state model GLOBAL.

Aromatic amino acids in the juxtamembrane domain of severe acute respiratory syndrome coronavirus spike glycoprotein are important for receptor-dependent virus entry and cell-cell fusion.

The severe acute respiratory syndrome coronavirus (SARS-CoV) spike glycoprotein (S) is a class I viral fusion protein that binds to its receptor glycoprotein, human angiotensin converting enzyme 2 (hACE2), and mediates virus entry and cell-cell fusion. The juxtamembrane domain (JMD) of S is an aromatic amino acid-rich region proximal to the transmembrane domain that is highly conserved in all coronaviruses. Alanine substitutions for one or two of the six aromatic residues in the JMD did not alter the surface expression of the SARS-CoV S proteins with a deletion of the C-terminal 19 amino acids (S Delta19) or reduce binding to soluble human ACE2 (hACE2). However, hACE2-dependent entry of trypsin-treated retrovirus pseudotyped viruses expressing JMD mutant S Delta19 proteins was greatly reduced. Single alanine substitutions for aromatic residues reduced entry to 10 to 60% of the wild-type level. The greatest reduction was caused by residues nearest the transmembrane domain. Four double alanine substitutions reduced entry to 5 to 10% of the wild-type level. Rapid hACE2-dependent S-mediated cell-cell fusion was reduced to 60 to 70% of the wild-type level for all single alanine substitutions and the Y1188A/Y1191A protein. S Delta19 proteins with other double alanine substitutions reduced cell-cell fusion further, from 40% to less than 20% of wild-type levels. The aromatic amino acids in the JMD of the SARS-CoV S glycoprotein play critical roles in receptor-dependent virus-cell and cell-cell fusion. Because the JMD is so highly conserved in all coronavirus S proteins, it is a potential target for development of drugs that may inhibit virus entry and/or cell-cell fusion mediated by S proteins of all coronaviruses.

Long-term colonisation with donor bacteriophages following successful faecal microbial transplantation.

BACKGROUND: Faecal microbiota transplantation (FMT) is used in the treatment of recurrent Clostridium difficile infection. Its success is typically attributed to the restoration of a diverse microbiota. Viruses (including bacteriophages) are the most numerically dominant and potentially the most diverse members of the microbiota, but their fate following FMT has not been well studied. RESULTS: We studied viral transfer following FMT from 3 donors to 14 patients. Recipient viromes resembled those of their donors for up to 12 months. Tracking individual bacteriophage colonisation revealed that engraftment of individual bacteriophages was dependent on specific donor-recipient pairings. Specifically, multiple recipients from a single donor displayed highly individualised virus colonisation patterns. CONCLUSIONS: The impact of viruses on long-term microbial dynamics is a factor that should be reviewed when considering FMT as a therapeutic option.

Thoughtflow: Standards and Tools for Provenance Capture and Workflow Definition to Support Model-Informed Drug Discovery and Development.

Pharmacometric analyses are complex and multifactorial. It is essential to check, track, and document the vast amounts of data and metadata that are generated during these analyses (and the relationships between them) in order to comply with regulations, support quality control, auditing, and reporting. It is, however, challenging, tedious, error-prone, and time-consuming, and diverts pharmacometricians from the more useful business of doing science. Automating this process would save time, reduce transcriptional errors, support the retention and transfer of knowledge, encourage good practice, and help ensure that pharmacometric analyses appropriately impact decisions. The ability to document, communicate, and reconstruct a complete pharmacometric analysis using an open standard would have considerable benefits. In this article, the Innovative Medicines Initiative (IMI) Drug Disease Model Resources (DDMoRe) consortium proposes a set of standards to facilitate the capture, storage, and reporting of knowledge (including assumptions and decisions) in the context of model-informed drug discovery and development (MID3), as well as to support reproducibility: "Thoughtflow." A prototype software implementation is provided.

Ornithine decarboxylase overexpression leads to increased epithelial tumor invasiveness.

Ornithine decarboxylase (ODC) overexpression cooperates with genetic lesions such as an activated c-rasHa to enhance epithelial tumorigenesis. To assess the invasiveness of ODC-overexpressing cells, two noninvasive epidermal cell lines, nontumorigenic BK-1 cells, and the papilloma-derived cell line SP-1 were infected with a replication-defective retrovirus that overexpresses ODC, inoculated into deepithelialized rat tracheas, and transplanted into athymic nude mice. After 5 weeks, ODC-overexpressing BK-1 cells remained localized on the luminal surface of the tracheal xenotransplants, whereas the ODC-overexpressing SP-1 cells were extremely invasive, with the whole tracheal wall penetrated. This invasiveness of ODC-overexpressing SP-1 cells was accompanied by elevated proteinase expression, including increased urokinase plasminogen activator activity in ODC-overexpressing cells and elevated stromelysin-1 mRNA expression in the stromal cells of invaded tracheal transplants.

Evidence for a link between translocation and processing during protein import into soybean mitochondria.

The effect of metal chelators on protein import was investigated using isolated soybean mitochondria and soybean precursor proteins. Adding 1,10-phenanthroline, a metal chelator that can cross both mitochondrial membranes abolished import of both the alternative oxidase, and the F(A)d subunit of the ATP synthase, a matrix located protein. Other metal chelators such as EDTA, 1,7-phenanthroline and 4,7-phenanthroline, which cannot cross the mitochondrial membranes, had no effect on import. When processing, a known metal-dependent step inside mitochondria, was inhibited using a mutagenesis approach (changing a -2 arginine to a -2 glycine in the pre-piece of the precursor), so was import. Thus it would appear that in soybean, at least, translocation of proteins across the mitochondrial membrane, as well as processing, relies on a metal dependent step. Taken together, the data suggest the two processes may be directly connected in these mitochondria.

Pharmacometrics Markup Language (PharmML): Opening New Perspectives for Model Exchange in Drug Development.

The lack of a common exchange format for mathematical models in pharmacometrics has been a long-standing problem. Such a format has the potential to increase productivity and analysis quality, simplify the handling of complex workflows, ensure reproducibility of research, and facilitate the reuse of existing model resources. Pharmacometrics Markup Language (PharmML), currently under development by the Drug Disease Model Resources (DDMoRe) consortium, is intended to become an exchange standard in pharmacometrics by providing means to encode models, trial designs, and modeling steps.

Left ventricular function in patients with and without myocardial infarction and one, two or three vessel coronary artery disease.

Ninety-six patients with chest pain were studied to determine the relation between left ventricular function and severity of coronary artery disease in patients with and without a history of myocardial infarction. Coronary arteriography was performed obtaining cineangiograms (60 frames/sec) and large roll film angiograms (2 to 6 frames/sec) for precise definition of the coronary anatomy. The criteria for diagnosis of myocardial infarction were a typical history, a rise and fall in serum glutamic oxaloacetic transaminase levels and evolutionary S-T segment changes associated with Q waves of at least 0.03 second. Left ventricular function was assessed by measurement of left ventricular end-diastolic pressure and volume, and left ventricular ejection fraction, mass and compliance. Fifteen patients had normal findings; 81 were classified according to number of diseased vessels and presence or absence of myocardial infarction. There were no group differences in age or heart rate. Left ventricular end-diastolic pressure was abnormally increased in patients with three vessel disease and myocardial infarction. Left ventricular end-diastolic volume was increased and the ejection fraction was reduced in patients in each vessel disease group with myocardial infarction. Although ejection fraction was reduced in patients with three vessel disease without myocardial infarction, it was further reduced when infarction occurred. Left ventricular mass increased in patients with three vessel disease with or without myocardial infarction. Values for ventricular compliance were reduced in all patients with myocardial infarction and were lower in those with two and three vessel disease and infarction than in those with two and three vessel disease without infarction. These findings suggest that a previous history of myocardial infarction needs to be considered together with anatomic abnormalities of the coronary arteries in assessing cardiac performance in patients with ischemic heart disease, a previous myocardial infarction significantly alters left ventricular performance; the ejection fraction is a more sensitive measurement of left ventricular function than left ventricular end-diastolic pressure or volume.

The uterine lumen of the pregnant guinea-pig contains a large macrophage population.

Cellular constituents of the uterine lumen were investigated. Fourteen pregnant sows of 40 + days' gestation were anaesthetized and naturally occurring peritoneal fluid was collected. A uterine horn was delivered and 0.25 ml Gey's solution injected into the uterine lumen to collect free cells. The fluid was aspirated into a syringe and the cells extracted, counted and prepared for phagocytosis experiments and microscopy. The cells were stained with alpha-naphthyl-acetate-esterase (ANAE) to determine the fraction that was non-specific esterase-positive, a feature of mononuclear phagocytes. Differential cells counts were also made. Both uterine and peritoneal compartments yielded large numbers of cells (greater than 10(6)/ml). Peritoneal fluid cells were 47 +/- 6 per cent (SD) macrophages and 49 +/- 6 per cent eosinophils (the remainder being 'other' cells); 47 +/- 6 per cent also stained positively for ANAE. Uterine cells were 78 +/- 12 per cent macrophages, the remainder being mostly lymphocytes (18 +/- 11 per cent); 85 +/- 13 per cent stained positively with ANAE. Electron microscopy of the uterine cells confirmed that most had morphology consistent with being mononuclear phagocytes. Uterine and peritoneal cells phagocytized carbon particles and yeast cells when incubated at 37 degrees C. The origin and role of this macrophage population is unknown but uterine lumenal macrophages may be present to remove antigen-antibody complexes thus facilitating uptake of maternally derived IgG by the fetal yolk sac.

Reproductive toxicology of disinfection by-products.

The chronic exposure of large segments of the population to disinfected drinking water has necessitated an evaluation of the health effects of the by-products of the chlorination process. This paper reviews the available information concerning the reproductive consequences associated with exposure to disinfection by-products. Four groups of compounds are discussed: the trihalomethanes, in particular chloroform; the chlorinated phenols; chlorinated humic substances; and the haloacetonitriles. In the pregnant female, chloroform and the 2- and 2,4-chlorophenols produced low levels of embryo- and fetotoxicity. Chloroform induced terata when administered by inhalation. The chlorinated humic substances and 2,4,6-trichlorophenol were without significant reproductive effects. The haloacetonitriles showed in utero toxicity, becoming more severe with increasing halogen substitution.

Reproductive effects of alternative disinfectants.

Organohalides formed through the reaction of chlorine and organic compounds in natural and waste waters pose potential health hazards. For this reason, alternative water disinfectants that do not form organohalides are being investigated with great interest. Limited data are available on the health effects, in particular reproductive toxicity effects, of these compounds. In our laboratory, we have examined the reproductive effects of chloramine and chlorine administered by gavage in Long-Evans rats. Animals were treated for a total of 66 to 76 days. Males were treated for 56 days and females for 14 days prior to breeding and throughout the 10-day breeding period. Females were treated throughout gestation and lactation. Following breeding, the males were necropsied and evaluated for sperm parameters and reproductive tract histopathology. Adult females and some pups were necropsied at weaning on postnatal day 21. Other pups were treated postweaning until 28 or 40 days of age. These pups were evaluated for the day of vaginal patency and thyroid hormone levels. No differences were observed between control rats and those rats exposed to up to 5 mg/kg/day chlorine or 10 mg/kg/day chloramine when fertility, viability, litter size, day of eye opening, or day of vaginal patency were evaluated. No alterations in sperm count, sperm direct progressive movement (micron/sec), percent motility, or sperm morphology were observed among adult male rats. In addition, male and female reproductive organ weights were comparable to their respective control groups, and no significant histopathologic changes were observed among chlorine- or chloramine-treated male and female rats.

Informed consent and medical ethics.

Informed consent is based on a shared decision between physician and patient, with the physician understanding the relevant values of the patient and the patient understanding the nature of the disease and intervention, including risks and benefits. Informed consent has developed rapidly since it was introduced in the 1950s, reflecting recent changes in the practice of medicine that respect the increase of patient autonomy. The purpose of the written consent form is to document that a process of informed consent has taken place. It is generally agreed that all surgical as well as research procedures require written consent. For certain nonsurgical procedures, the decision regarding obtaining written consent will consider both the risk involved for the patient and the general community standard. Informed consent serves as an important symbol of a physician-patient relationship that adheres to the valued principles of medical ethics.

Regulating bone formation via controlled scaffold degradation.

It is widely assumed that coupling the degradation rate of polymers used as cell transplantation carriers to the growth rate of the developing tissue will improve its quantity or quality. To test this hypothesis, we developed alginate hydrogels with a range of degradation rates by gamma-irradiating high-molecular-weight alginate to yield polymers of various molecular weights and structures. Decreasing the size of the polymer chains increased the degradation rate in vivo, as measured by implant retrieval rates, masses, and elastic moduli. Rapidly and slowly degrading alginates, covalently modified with RGD-containing peptides to control cell behavior, were then used to investigate the effect of biodegradation rate on bone tissue development in vivo. The more rapidly degrading gels led to dramatic increases in the extent and quality of bone formation. These results indicate that biomaterial degradability is a critical design criterion for achieving optimal tissue regeneration with cell transplantation.

The automated analysis of rat sperm motility following subchronic epichlorohydrin administration: methodologic and statistical considerations.

The automated analysis of sperm motion endpoints is potentially useful in identifying male reproductive toxicants and ultimately in predicting fertility in humans. The present study was designed to evaluate the automated analysis of rat sperm motility characteristics following subchronic administration of epichlorohydrin. This type of validation is a prerequisite for inclusion of sperm motion measurements in the process of reproductive risk assessment. In the present studies videotapes were made of cauda epididymal spermatozoa from Long-Evans rats, both untreated and treated with epichlorohydrin. From analysis of videotapes of control epididymal spermatozoa, the relationship of various sperm motion endpoints and settings of the CellSoft computer-assisted sperm motion analysis system (Cryo Resources, Ltd., New York, NY) is described. Optimal settings of the system for analysis of rat spermatozoa are detailed. Employing data from both control and epichlorohydrin-treated animals, a statistical methodology is described that evaluates: (1) the distributions of CellSoft generated sperm motion endpoints, (2) the correlations between these endpoints, and (3) techniques for detection of dose-related effects.

Correlation of sperm motion parameters with fertility in rats treated subchronically with epichlorohydrin.

We investigated the relationship between fertility and sperm motin endpoints in rats treated subchronically with the male reproductive toxicant, epichlorohydrin (ECH). Male rats were given ECH orally for 23 days at dosages of 0, 6.25, 12.5, or 25 mg/kg/day. They were mated twice (at 19 and 22 days) to estimate fertility by (1) detection of fertilized ova (presence of sperm head and tail or two pronuclei) 18 hours after mating and by (2) counting implants on day 14 of gestation. Both indices showed dose-related reductions (P less than 0.001). Motion parameters of cauda epididymal sperm were assessed using the CellSoft computer-assisted sperm motion analysis (CASA) system after the rats were asphyxiated on day 25. Curvilinear velocity, straight-line velocity, linearity, and amplitude of lateral head displacement were reduced in a dose-related manner. The fertility indices, percent fertilized ova, and percent implantation on day 14 of gestation were correlated significantly (r = 0.68; P = 0.0001). The following motion parameters were also correlated significantly with fertility (P less than 0.0003; r1 = percent fertilized ova and r2 = percent implantation): linearity (r1 = 0.42; r2 = 0.40), amplitude of lateral head displacement (r1 = 0.54; r2 = 0.48), curvilinear velocity (r1 = 0.53; r2 = 0.50), straight-line velocity (r1 = 0.55; r2 = 0.50), and percent motile sperm (r1 = 0.42; r2 = 0.32). These results suggest a relationship between toxicant-induced reductions in sperm motion and fertility.