Multivariate modulation of the Zr MOF UiO-66 for defect-controlled multimodal anticancer drug delivery

Metal‐organic frameworks (MOFs) are emerging as leading candidates for nanoscale drug delivery, as a consequence of their high drug capacities, ease of functionality, and the ability to carefully engineer key physical properties. Despite many anticancer treatment regimens consisting of a cocktail of different drugs, examples of delivery of multiple drugs from one MOF are rare, potentially hampered by difficulties in postsynthetic loading of more than one cargo molecule. Herein, we report a new strategy, multivariate modulation, which allows incorporation of up to three drugs in the Zr MOF UiO‐66 by defect‐loading. The drugs are added to one‐pot solvothermal synthesis and are distributed throughout the MOF at defect sites by coordination at the metal clusters. This tight binding comes with retention of crystallinity and porosity, allowing a fourth drug to be postsynthetically loaded into the MOFs to yield nanoparticles loaded with cocktails of drugs that show enhancements in selective anticancer cytotoxicity against MCF‐7 breast cancer cells in vitro. We believe that multivariate modulation is a significant advance in the application of MOFs in biomedicine, and anticipate the protocol will also be adopted in other areas of MOF chemistry, to easily produce defective MOFs with arrays of highly functionalised pores for potential application in gas separations and catalysis

Gadolinium Doped Layered Double Hydroxides for Simultaneous Drug Delivery and Magnetic Resonance Imaging

In this study, gadolinium (Gd) doped MgAl layered double hydroxides (LDHs) were synthesized via a ‘bottom-up’ method and fully characterized by X-ray diffraction, infrared spectroscopy and relaxivity measurements. Two cytotoxic agents were then intercalated via ion-exchange. X-ray diffraction patterns exhibit expanded interlayer spacings as a result of successful drug intercalation. Infrared spectra also showed characteristic peaks of the incorporated methotrexate (MTX) or 5-fluorouracil (5-FU). The LDHs were found to be highly stable under physiological conditions, while in acidic conditions a small proportion of Gd was freed into the immersion medium. Dissolution tests revealed that both 5FU and MTX were rapidly released from the LDH carrier. The longitudinal relaxivity of Gd-LDHs remains largely stable during drug release over 24 h, and was higher in acidic environments. Overall, the drug-loaded Gd-LDH systems prepared in this study could serve as pH-sensitive theranostic platforms for MRI-guided anti-cancer therapy.</p

Workgroup Report: Indoor Chemistry and Health

Chemicals present in indoor air can react with one another, either in the gas phase or on surfaces, altering the concentrations of both reactants and products. Such chemistry is often the major source of free radicals and other short-lived reactive species in indoor environments. To what extent do the products of indoor chemistry affect human health? To address this question, the National Institute for Occupational Safety and Health sponsored a workshop titled “Indoor Chemistry and Health” on 12–15 July 2004 at the University of California–Santa Cruz. Approximately 70 experts from eight countries participated. Objectives included enhancing communications between researchers in indoor chemistry and health professionals, as well as defining a list of priority research needs related to the topic of the workshop. The ultimate challenges in this emerging field are defining exposures to the products of indoor chemistry and developing an understanding of the links between these exposures and various health outcomes. The workshop was a step toward meeting these challenges. This summary presents the issues discussed at the workshop and the priority research needs identified by the attendees

The impact of future sea-level rise on the global tides

Tides are a key component in coastal extreme water levels. Possible changes in the tides caused by mean sea-level rise (SLR) are therefore of importance in the analysis of coastal flooding, as well as many other applications. We investigate the effect of future SLR on the tides globally using a fully global forward tidal model: OTISmpi. Statistical comparisons of the modelled and observed tidal solutions demonstrate the skill of the refined model setup with no reliance on data assimilation. We simulate the response of the four primary tidal constituents to various SLR scenarios. Particular attention is paid to future changes at the largest 136 coastal cities, where changes in water level would have the greatest impact. Spatially uniform SLR scenarios ranging from 0.5 to 10 m with fixed coastlines show that the tidal amplitudes in shelf seas globally respond strongly to SLR with spatially coherent areas of increase and decrease. Changes in the M2 and S2 constituents occur globally in most shelf seas, whereas changes in K1 and O1 are confined to Asian shelves. With higher SLR tidal changes are often not proportional to the SLR imposed and larger portions of mean high water (MHW) changes are above proportional. Changes in MHW exceed ±10% of the SLR at ~10% of coastal cities. SLR scenarios allowing for coastal recession tend increasingly to result in a reduction in tidal range. The fact that the fixed and recession shoreline scenarios result mainly in changes of opposing sign is explained by the effect of the perturbations on the natural period of oscillation of the basin. Our results suggest that coastal management strategies could influence the sign of the tidal amplitude change. The effect of a spatially varying SLR, in this case fingerprints of the initial elastic response to ice mass loss, modestly alters the tidal response with the largest differences at high latitudes

Associations between sole ulcer, white line disease and digital dermatitis and the milk yield of 1824 dairy cows on 30 dairy cow farms in England and Wales from February 2003–November 2004

The milk yields of 1824 cows were used to investigate the effect of lesion-specific causes of lameness, based on farmer treatment and diagnosis of lame cows, on milk yield. A three level hierarchical model of repeated test day yields within cows within herds was used to investigate the impact of lesion-specific causes of lameness (sole ulcer, white line disease, digital dermatitis and other causes) on milk yield before and after treatment compared with unaffected cows. Cattle which developed sole ulcer (SU) and white line disease (WLD) were higher yielding cattle before they were diagnosed. Their milk production fell to below that of the mean of unaffected cows before diagnosis and remained low after diagnosis. In cattle which developed digital dermatitis (DD) there was no significant difference in milk yield before treatment and a slightly raised milk yield immediately after treatment. The estimated milk loss attributable to SU and WLD was approximately 570kg and 370kg respectively. These results highlight that specific types of lameness vary by herds and within herds they are associated with higher yielding cattle. Consequently lesion-specific lameness reduction programmes targeting the cow and farm specific causes of lameness might be more effective than generic recommendations. They also highlight the importance of milk loss when estimating the economic impact of SU and WLD on the farms profitability

Higgs boson mass limits in perturbative unification theories

Motivated in part by recent demonstrations that electroweak unification into a simple group may occur at a low scale, we detail the requirements on the Higgs mass if the unification is to be perturbative. We do this for the Standard Model effective theory, minimal supersymmetry, and next-to-minimal supersymmetry with an additional singlet field. Within the Standard Model framework, we find that perturbative unification with sin2(thetaW)=1/4 occurs at Lambda=3.8 TeV and requires mh<460 GeV, whereas perturbative unification with sin2(thetaW)=3/8 requires mh<200 GeV. In supersymmetry, the presentation of the Higgs mass predictions can be significantly simplified, yet remain meaningful, by using a single supersymmetry breaking parameter Delta_S. We present Higgs mass limits in terms of Delta_S for the minimal supersymmetric model and the next-to-minimal supersymmetric model. We show that in next-to-minimal supersymmetry, the Higgs mass upper limit can be as large as 500 GeV even for moderate supersymmetry masses if the perturbative unification scale is low (e.g., Lambda=10 TeV).Comment: 20 pages, latex, 6 figures, references adde