An investigation of Prussian Blue analogues by Mossbauer spectroscopy and magnetic susceptibility

The Mossbauer spectra and magnetic susceptibilities have been obtained for a series of Prussian Blue analogues of general formula MjA[MB(CN)6]k[middle dot]mH2O where MA and MB are transition metal ions, j and k vary with the oxidation states of MA and MB and m typically has values from 8 to 14. The compounds were prepared from the hexacyano acids or with large quaternary ammonium counterions and are therefore not contaminated with alkali cations. In each analogue, A or B is iron and the second metal is Mn, Cu, Co, Cr or Ru. In each case it was possible to assign the site (A or B), oxidation state and spin state to each transition metal ion. This group of compounds are all class II mixed valence species from their colours, but do not show evidence of linkage isomerism or redox changes compared to the starting materials. The Mossbauer linewidths are consistent with the Ludi model of Prussian Blue.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24978/1/0000405.pd

Discovery of Novel Cyclic Ethers with Synergistic Antiplasmodial Activity in Combination with Valinomycin

With drug resistance threatening our first line antimalarial treatments, novel chemotherapeutics need to be developed. Ionophores have garnered interest as novel antimalarials due to their theorized ability to target unique systems found in the Plasmodium-infected erythrocyte. In this study, during the bioassay-guided fractionation of the crude extract of Streptomyces strain PR3, a group of cyclodepsipeptides, including valinomycin, and a novel class of cyclic ethers were identified and elucidated. Further study revealed that the ethers were cyclic polypropylene glycol (cPPG) oligomers that had leached into the bacterial culture from an extraction resin. Molecular dynamics analysis suggests that these ethers are able to bind cations such as K+, NH4+ and Na+. Combination studies using the fixed ratio isobologram method revealed that the cPPGs synergistically improved the antiplasmodial activity of valinomycin and reduced its cytotoxicity in vitro. The IC50 of valinomycin against P. falciparum NF54 improved by 4–5-fold when valinomycin was combined with the cPPGs. Precisely, it was improved from 3.75 ± 0.77 ng/mL to 0.90 ± 0.2 ng/mL and 0.75 ± 0.08 ng/mL when dosed in the fixed ratios of 3:2 and 2:3 of valinomycin to cPPGs, respectively. Each fixed ratio combination displayed cytotoxicity (IC50) against the Chinese Hamster Ovary cell line of 57–65 µg/mL, which was lower than that of valinomycin (12.4 µg/mL). These results indicate that combinations with these novel ethers may be useful in repurposing valinomycin into a suitable and effective antimalarial

Impairment of Methotrexate Transport Is Common in Osteosarcoma Tumor Samples

Osteosarcoma does not respond well to conventional dose methotrexate but does respond to high-dose methotrexate. Previous work has indicated that this resistance may be due to impaired transport of methotrexate across the cell membrane. In this study, the PT430 competitive displacement assay was adapted to evaluate methotrexate transport in 69 high-grade osteosarcoma tumor samples. All samples studied were shown to have relatively impaired methotrexate transport by PT430 assay. Ninety-nine percent of the samples had less than 20% PT430 displacement by methotrexate. Eighty-eight percent exhibited displacement by methotrexate at less than 50% of the displacement by trimetrexate. The high frequency of impaired transport suggests the presence of decreased functionality of the reduced folate carrier protein. The overwhelming presence of impaired transport may explain why methotrexate needs to be given in high doses to be effective in osteosarcoma therapy and suggests that reduced folate carrier-independent antifolates should be explored

Duration of adjuvant chemotherapy for stage III colon cancer

BACKGROUND Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures. METHODS We performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12. RESULTS After 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority). CONCLUSIONS Among patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.

Bioaccumulation and histopathological effects of oil on a stony coral

Colonies of the shallow-water Caribbean coral Manicina areolata incorporated petroleum hydrocarbons into their tissues during exposure to water accommodated fractions of No. 2 fuel oil for three months. This contamination was not removed after depuration periods of up to two weeks. Although these corals remained alive, evidence of pathological responses was found which included impaired development of reproductive tissues, degeneration and loss of symbiotic zooxanthellae, and atrophy of mucous secretory cells and muscle bundles.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24242/1/0000505.pd

Application of the Priestley–Taylor Approach in a Two-Source Surface Energy Balance Model

The Priestley–Taylor (PT) approximation for computing evapotranspiration was initially developed for conditions of a horizontally uniform saturated surface sufficiently extended to obviate any significant advection of energy. Nevertheless, the PT approach has been effectively implemented within the framework of a thermal-based two-source model (TSM) of the surface energy balance, yielding reasonable latent heat flux estimates over a range in vegetative cover and climate conditions. In the TSM, however, the PT approach is applied only to the canopy component of the latent heat flux, which may behave more conservatively than the bulk (soil + canopy) system. The objective of this research is to investigate the response of the canopy and bulk PT parameters to varying leaf area index (LAI) and vapor pressure deficit (VPD) in both natural and agricultural vegetated systems, to better understand the utility and limitations of this approximation within the context of the TSM. Micrometeorological flux measurements collected at multiple sites under a wide range of atmospheric conditions were used to implement an optimization scheme, assessing the value of the PT parameter for best performance of the TSM. Overall, the findings suggest that within the context of the TSM, the optimal canopy PT coefficient for agricultural crops appears to have a fairly conservative value of ~1.2 except when under very high vapor pressure deficit (VPD) conditions, when its value increases. For natural vegetation (primarily grasslands), the optimal canopy PT coefficient assumed lower values on average (~0.9) and dropped even further at high values of VPD. This analysis provides some insight as to why the PT approach, initially developed for regional estimates of potential evapotranspiration, can be used successfully in the TSM scheme to yield reliable heat flux estimates over a variety of land cover types

Proposed Revision to the Taxonomy of the Genus Pestivirus; Family Flaviviridae

We propose the creation of seven new species in the genus Pestivirus (family Flaviviridae) in addition to the four existing species, and naming species in a host-independent manner using the format Pestivirus X. Only the virus species names would change; virus isolates would still be referred to by their original names. The original species would be re-designated as Pestivirus A (original designation Bovine viral diarrhea virus 1), Pestivirus B (Bovine viral diarrhea virus 2), Pestivirus C (Classical swine fever virus) and Pestivirus D (Border disease virus). The seven new species (and example isolates) would be Pestivirus E (pronghorn pestivirus), Pestivirus F (Bungowannah virus), Pestivirus G (giraffe pestivirus), Pestivirus H (Hobi-like pestivirus), Pestivirus I (Aydin-like pestivirus), Pestivirus J (rat pestivirus) and Pestivirus K (atypical porcine pestivirus). A bat-derived virus and pestiviruses identified from sheep and goat (Tunisian sheep pestiviruses), which lack complete coding region sequences, may represent two additional species

Pseudo-arthrosis repair of a posterior cruciate ligament avulsion fracture

A pseudo-arthrosis repair of a 4-year-old bony avulsion fracture of the PCL using a minimally invasive technique, screw fixation, and bone grafting is reported. The case presented seems to be rather unique due to the fragment size and the approach for pseudo-arthrosis repair. There was a good functional result following minimally invasive pseudo-arthrosis repair of a posterior cruciate ligament avulsion fracture. There are no previous reports of similar pseudo-arthrosis repairs, and other authors report good results of delayed refixation of PCL avulsion fractures. Therefore, refixation and pseudo-arthrosis repair should be considered as a viable treatment

Engaging with community researchers for exposure science: lessons learned from a pesticide biomonitoring study

A major challenge in biomonitoring studies with members of the general public is ensuring their continued involvement throughout the necessary length of the research. The paper presents evidence on the use of community researchers, recruited from local study areas, as a mechanism for ensuring effective recruitment and retention of farmer and resident participants for a pesticides biomonitoring study. The evidence presented suggests that community researchers' abilities to build and sustain trusting relationships with participants enhanced the rigour of the study as a result of their on-the-ground responsiveness and flexibility resulting in data collection beyond targets expected

Probing the angular and polarization reconstruction of the ARIANNA detector at the South Pole

The sources of ultra-high energy (UHE) cosmic rays, which can have energies up to 10^20 eV, remain a mystery. UHE neutrinos may provide important clues to understanding the nature of cosmic-ray sources. ARIANNA aims to detect UHE neutrinos via radio (Askaryan) emission from particle showers when a neutrino interacts with ice, which is an efficient method for neutrinos with energies between 10^16 eV and 10^20 eV. The ARIANNA radio detectors are located in Antarctic ice just beneath the surface. Neutrino observation requires that radio pulses propagate to the antennas at the surface with minimum distortion by the ice and firn medium. Using the residual hole from the South Pole Ice Core Project, radio pulses were emitted from a transmitter located up to 1.7 km below the snow surface. By measuring these signals with an ARIANNA surface station, the angular and polarization reconstruction abilities are quantified, which are required to measure the direction of the neutrino. After deconvolving the raw signals for the detector response and attenuation from propagation through the ice, the signal pulses show no significant distortion and agree with a reference measurement of the emitter made in an anechoic chamber. Furthermore, the signal pulses reveal no significant birefringence for our tested geometry of mostly vertical ice propagation. The origin of the transmitted radio pulse was measured with an angular resolution of 0.37 degrees indicating that the neutrino direction can be determined with good precision if the polarization of the radio-pulse can be well determined. In the present study we obtained a resolution of the polarization vector of 2.7 degrees. Neither measurement show a significant offset relative to expectation