Influence of aggregate size and fraction on shrinkage induced micro-cracking of mortar and concrete

In this paper, the influence of aggregate size and volume fraction on shrinkage induced micro-cracking and permeability of concrete and mortar was investigated. Nonlinear finite element analyses of model concrete and mortar specimens were performed. The aggregate diameter was varied between 2 and 16 mm. Furthermore, a range of volume fractions between 0.1 and 0.5 was studied. The nonlinear analyses were based on a 2D lattice approach in which aggregates were simplified as monosized cylindrical inclusions. The analysis results were interpreted by means of crack width and change of permeability. The results show that increasing aggregate diameter (at equal volume fraction) and decreasing volume fraction (at equal aggregate diameter) greatly increases permeability.Comment: 12th International Conference on Fracture (ICF 12

An Interprofessional Curriculum on Antimicrobial Stewardship Improves Knowledge and Attitudes Toward Appropriate Antimicrobial Use and Collaboration.

BackgroundInappropriate antimicrobial use can threaten patient safety and is the focus of collaborative physician and pharmacist antimicrobial stewardship teams. However, antimicrobial stewardship is not comprehensively taught in medical or pharmacy school curricula. Addressing this deficiency can teach an important concept as well as model interprofessional healthcare.MethodsWe created an antimicrobial stewardship curriculum consisting of an online learning module and workshop session that combined medical and pharmacy students, with faculty from both professions. Learners worked through interactive, branched-logic clinical cases relating to appropriate antimicrobial use. We surveyed participants before and after the curriculum using validated questions to assess knowledge and attitudes regarding antimicrobial stewardship and interprofessional collaboration. Results were analyzed using paired χ2 and t tests and mixed-effects logistic regression.ResultsAnalysis was performed with the 745 students (425 medical students, 320 pharmacy students) who completed both pre- and postcurriculum surveys over 3 years. After completing the curriculum, significantly more students perceived that they were able to describe the role of each profession in appropriate antimicrobial use (34% vs 82%, P < .001), communicate in a manner that engaged the interprofessional team (75% vs 94%, P < .001), and describe collaborative approaches to appropriate antimicrobial use (49% vs 92%, P < .001). Student favorability ratings were high for the online learning module (85%) and small group workshop (93%).ConclusionsA curriculum on antimicrobial stewardship consisting of independent learning and an interprofessional workshop significantly increased knowledge and attitudes towards collaborative antimicrobial stewardship among preclinical medical and pharmacy students

A first-in-human study of AMG 208, an oral MET inhibitor, in adult patients with advanced solid tumors.

BackgroundThis first-in-human study evaluated AMG 208, a small-molecule MET inhibitor, in patients with advanced solid tumors.MethodsThree to nine patients were enrolled into one of seven AMG 208 dose cohorts (25, 50, 100, 150, 200, 300, and 400 mg). Patients received AMG 208 orally on days 1 and days 4-28 once daily. The primary objectives were to evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of AMG 208.ResultsFifty-four patients were enrolled. Six dose-limiting toxicities were observed: grade 3 increased aspartate aminotransferase (200 mg), grade 3 thrombocytopenia (200 mg), grade 4 acute myocardial infarction (300 mg), grade 3 prolonged QT (300 mg), and two cases of grade 3 hypertension (400 mg). The MTD was not reached. The most frequent grade ≥3 treatment-related adverse event was anemia (n = 3) followed by hypertension, prolonged QT, and thrombocytopenia (two patients each). AMG 208 exposure increased linearly with dose; mean plasma half-life estimates were 21.4-68.7 hours. One complete response (prostate cancer) and three partial responses (two in prostate cancer, one in kidney cancer) were observed.ConclusionsIn this study, AMG 208 had manageable toxicities and showed evidence of antitumor activity, particularly in prostate cancer

Iron in Ice Cores from Law Dome, East Antarctica: Implications for Past Deposition of Aerosol Iron

Total-dissolvable iron has been measured in sections of three ice cores from Law Dome, East Antarctica, and the results used to calculate atmospheric iron deposition over this region during the late Holocene and to provide a preliminary est. of aerosol iron deposition during the Last Glacial Maximum (LGM). Ice-core sections dating from 56-2730 BP (late Holocene) and ∼18 000 BP (LGM) were decontaminated using trace-metal clean techniques, and total-dissolvable iron was determined in the acidified meltwaters by flow-injection analysis. Our results suggest that the atmospheric iron flux onto the Law Dome region has varied significantly over time-scales ranging from seasonal to glacial-interglacial. The iron concentrations in ice-core sections from the past century suggest (1) a 2-4-fold variation in the atmospheric iron flux over a single annual cycle, with the highest flux occurring during the spring and summer, and (2) a nearly 7-fold variation in the annual maximum atmospheric iron flux over a 14 yr period. The average estimated atmospheric iron flux calculated from our late-Holocene samples is 0.056-0.14 mg m-2 a-1, which agrees well with Holocene flux estimates derived from aluminum measurements in inland Antarctic ice cores and a recent order-of-magnitude estimate of present-day atmospheric iron deposition over the Southern Ocean. The iron concentration of an ice-core section dating from the LGM was more than 50 times higher than in the late-Holocene ice samples. Using a snow-accumulation rate est. of 130 kg m-2 a-1 for this period, we calculate 0.87 mg m-2 a-1 as a preliminary estimate of atmospheric iron deposition during the LGM, which is 6-16 times greater than our average Late-Holocene iron flux. Our data are consistent with the suggestion that there was a significantly greater flux of atmospheric iron onto the Southern Ocean during the LGM than during the Holocene

Inhibiting HIV-1 Entry Discovery of D-Peptide Inhibitors that Target the gp41 Coiled-Coil Pocket

AbstractThe HIV-1 gp41 protein promotes viral entry by mediating the fusion of viral and cellular membranes. A prominent pocket on the surface of a central trimeric coiled coil within gp41 was previously identified as a potential target for drugs that inhibit HIV-1 entry. We designed a peptide, IQN17, which properly presents this pocket. Utilizing IQN17 and mirror-image phage display, we identified cyclic, D-peptide inhibitors of HIV-1 infection that share a sequence motif. A 1.5 Å cocrystal structure of IQN17 in complex with a D-peptide, and NMR studies, show that conserved residues of these inhibitors make intimate contact with the gp41 pocket. Our studies validate the pocket per se as a target for drug development. IQN17 and these D-peptide inhibitors are likely to be useful for development and identification of a new class of orally bioavailable anti-HIV drugs

First-principles calculations of the dispersion of surface phonons of the unreconstructed and reconstructed Pt(110)

We present result of calculations of the surface phonon dispersion curves for Pt(110) using density functional theory in the local density approximation and norm conserving pseudopotentials in a mixed-basis approach. Linear response theory is invoked and both the unreconstructed, and the missing row (1x2) reconstructed surfaces are considered. We find that the reconstruction is not driven by a phonon instability. Most of the observed phonon modes for the (1x2) structure can be understood in terms of simple folding of the (1x1) Brillouin zone onto that for the (1x2) surface. Largest changes in the phonon frequencies on surface reconstruction occur close to the zone boundary in the (001) direction. Detailed comparison of atomic force constants for the (1x1) and the (1x2) surfaces and their bulk counterparts show that the bulk value is attained after three layers. Our calculations reproduce nicely the Kohn anomaly observed along the (110) direction in the bulk. We do not find a corresponding effect on the surface