Triple functionalisation of single-walled carbon nanotubes with doxorubicin, a monoclonal antibody, and a fluorescent marker for targeted cancer therapy

Single-walled carbon nanotubes (SWCNTs) have been identified as a transporter for anti-cancer drugs, as they are capable of penetrating mammalian cell membranes and allow for a high drug loading due to their nanoscale dimensions and high aspect ratio. In addition, they can assist the targeting of therapeutic agents to the desired site of action by conjugation to antibodies or ligands of cancer cell surface receptors, which increases the effectiveness of the treatment and reduces side effects. In this work, we present a method for the triple functionalisation of oxidised SWCNTs with the anti-cancer drug doxorubicin, a monoclonal antibody, and a fluorescent marker at non-competing binding sites. The proposed methodology allows for the targeted delivery of the anti-cancer drug to cancer cells and the visualisation of the cellular uptake of SWCNTs by confocal microscopy. We show that the complex is efficiently taken up by cancer cells with subsequent intracellular release of doxorubicin, which then translocates to the nucleus while the nanotubes remain in the cytoplasm.     

A new technique to derive particle size distributions and aerosol number concentrations directly from thermophoretic data

The manufacture of many high value-added powders takes place by the decomposition of gaseous precursors in aerosol tube reactors. Historically, process improvements were achieved by making changes on the outside of the reactor and observing what comes out at the end of the pipe. The development of increasingly accurate aerosol dynamics models based on engineering first principles has been limited because models were typically validated on integral properties of ex situ product, instead of particle properties measured at multiple positions inside the reactor. In this study, a model reactor was equipped to capture samples thermophoretically from 15 internal positions. Additional in-line measurements were achieved with a multi-stage inertial impactor and by traditional analysis of ex situ product. Calculations were performed to verify that thermophoresis was the dominant mechanism of particle capture. The thermophoretic samples were analyzed by electron beam microscopy and image analysis to develop particle size distributions at each of the internal positions inside the reactor. An approximation of Talbot's Equation for thermophoretic velocity allowed experimental measurements to be combined with thermophoretic sample data to give predictions of particle number concentration corresponding to the precise sampling locations. The combinations of particle size distributions and number concentrations provide powerful insights on particle nucleation and growth dynamics.     

Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines

CONTEXT: Many groups have developed guidelines to shorten hospital length of stay in pneumonia in order to decrease costs, but the length of time until a patient hospitalized with pneumonia becomes clinically stable has not been established. OBJECTIVE: To describe the time to resolution of abnormalities in vital signs, ability to eat, and mental status in patients with community-acquired pneumonia and assess clinical outcomes after achieving stability. DESIGN: Prospective, multicenter, observational cohort study. SETTING: Three university and 1 community teaching hospital in Boston, Mass, Pittsburgh, Pa, and Halifax, Nova Scotia. PATIENTS: Six hundred eighty-six adults hospitalized with community-acquired pneumonia. MAIN OUTCOME MEASURES: Time to resolution of vital signs, ability to eat, mental status, hospital length of stay, and admission to an intensive care, coronary care, or telemetry unit. RESULTS: The median time to stability was 2 days for heart rate (< or =100 beats/min) and systolic blood pressure (> or =90 mm Hg), and 3 days for respiratory rate (< or =24 breaths/min), oxygen saturation (> or =90%), and temperature (< or =37.2 degrees C [99 degrees F]). The median time to overall clinical stability was 3 days for the most lenient definition of stability and 7 days for the most conservative definition. Patients with more severe cases of pneumonia at presentation took longer to reach stability. Once stability was achieved, clinical deterioration requiring intensive care, coronary care, or telemetry monitoring occurred in 1% of cases or fewer. Between 65% to 86% of patients stayed in the hospital more than 1 day after reaching stability, and fewer than 29% to 46% were converted to oral antibiotics within 1 day of stability, depending on the definition of stability. CONCLUSIONS: Our estimates of time to stability in pneumonia and explicit criteria for defining stability can provide an evidence-based estimate of optimal length of stay, and outline a clinically sensible approach to improving the efficiency of inpatient management.     

Synthesis and cytotoxicity of potential tumor-inhibitory analogues of trimelamol (2,4,6-tris[(hydroxymethyl)methylamino]-1,3,5-triazine) having electron-withdrawing groups in place of methyl

In exploring the structural features which determine the antitumor activity of 2,4,6-tris-[(hydroxymethyl)methylamino]-1,3,5-triazine (trimelamol, 1), we have synthesized analogues in which the methyl groups have been replaced by the electron-withdrawing substituents 2,2,2-trifluoroethyl (5), propargyl (13), and cyanomethyl (15) via the respective tris(alkylamino)triazines 3, 12, and 14. Three mono[(hydroxymethyl)amino]triazines (4, 7, and 10) were also prepared. All the new tris(hydroxymethyl) derivatives showed cytotoxicities toward a variety of experimental rodent and human ovarian tumor cell lines similar to those shown by 1, the cyanomethyl analogue (15) having the most favorable profile. Mono(hydroxymethyl) derivatives (4 and 7) were ca. one-third as toxic. The new tris(hydroxymethyl) analogues were more stable to aqueous hydrolysis than was 1. Half-life (pH 7.5) values were, for 1, 120 min, for 5, 690 min, for 13, 450 min, and for 15, 275 min, but at pH 2.0, 15 (t1/2 350 min) was the most stable. This cyanomethyl analogue was also the most water-soluble, being comparable to 1 whereas 5 and 13 were poorly soluble.     

Experimental component analysis of a behavioral HIV–AIDS prevention intervention for inner-city women.

A component analysis of a behavioral HIV risk reduction intervention was conducted among 87 women recruited from an inner-city community. Women were randomly assigned to an intervention consisting of (a) sexual communication skills training, (b) self-management skills training, (c) a combination of sexual communication and self-management skills, or (d) HIV education and risk sensitization. Results showed that all 4 intervention conditions increased AIDS knowledge and intentions to reduce risk behaviors. Communication skills training resulted in higher rates of risk reduction conversations and risk refusals. However, the combined skills training condition showed the lowest rates of unprotected sexual intercourse at the 3-month follow-up. This study is the first to experimentally control HIV risk reduction elements in an analysis of a skills-based HIV prevention intervention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Assessing the risk of climate change for buildings: A comparison between multi-year and probabilistic reference year simulations

Given a changing climate, there is a need to provide data for future years so that practicing engineers can investigate the impact of climate change on particular designs and examine any risk the client might be exposed to. In addition, such files are of use to building scientists in developing generic solutions to problems such as elevated internal temperatures and poor thermal comfort. With the release of the UK Climate Projections (UKCP09) [1], and the publication of a methodology for the creation of probabilistic future reference years using the UKCP09 weather generator [2], it is possible to model future building performance. However, the collapse of the distribution of possibilities inherent in the UKCP09 method into a single reference year or a small number of reference years, potentially means the loss of most of the information about the potential range of the response of the building and of the risk occupants might be subject to. In this paper we model for the first time the internal conditions and energy use of a building with all 3000 example years produced by the UKCP09 weather generator in an attempt to study the full range of response and risk. The resultant histograms and cumulative distribution functions are then used to examine whether single reference years can be used to answer questions about response and risk under a changing climate, or whether a more probabilistic approach is unavoidable.     

Corrosion potential oscillation of stainless steel in concentrated sulphuric acid: I. Electrochemical aspects

The spontaneous oscillation of corrosion potential between the active and passive states of UNS S30403 stainless steel has been studied in 93.5 wt.% sulphuric acid at 60 °C. Detailed electrochemical analysis of the kinetics of the oscillating potential has suggested the presence of a nickel salt which is stable over a limited potential range. The nickel salt is subject to dissolution at potentials more positive than −0.25 V (MSE), while at lower potentials—less than −0.35 V (MSE)—a stable salt film is formed. A critical coverage of the salt on the surface is the prerequisite for the mixed potential to be shifted into the passive range by an increase in the exchange current density for the sulphuric acid cathodic reaction. However, when the coverage exceeds a critical value, such as can be produced by a potentiostatic hold, the salt effectively blocks the formation of a passive film.