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(trimelamol, 1), we have synthesized analogues in which the methyl groups have been replaced by the electron-withdrawing substituents 2,2,2-trifluoroethyl (5), propargyl (13), and cyanomethyl (15) via the respective tris(alkylamino)triazines 3, 12, and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.     

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.     

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.     

Bacterial and Ureaplasma colonization of the airway: radiologic findings in infants with bronchopulmonary dysplasia

OBJECTIVE: We designed this retrospective study to compare radiologic findings in premature infants with bronchopulmonary dysplasia (BPD) in whom gram-positive cocci (GPC), gram-negative bacilli (GNB), or Ureaplasma urealyticum were colonized. Another objective was to correlate the radiologic findings of these patients with the clinical severity of BPD. STUDY DESIGN: We correlated serial tracheal aspirates with radiographic findings from 183 infants whose birth weight was < or = 1250 gm. BPD severity was assessed by oxygen dependency at 36 weeks of postconceptional age (36 w PCA) and at the time of discharge. Two radiologists independently scored films taken at birth and 1, 7, 14, 21, 28, and 35 days of life. RESULTS: Of the study population, 55% were male and 35% were black; 80% received surfactant and 69% received dexamethasone; 91% survived. GPC isolates from throat cultures were mainly Staphylococcus [corrected] epidermidis and Streptococcus haemolyticus. A superimposed GNB colonization was present in 37% of these infants. Most common isolates were Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli. Sepsis caused by GPC developed in 16% of all patients; 7% had sepsis caused by GNB. Infants infected with GNB remained receiving oxygen at 36 w PCA and at the time of discharge twice as often as those noninfected. RADIOLOGIC FINDINGS: Hyperinflation, interstitial changes, and generalized or localized emphysema were prominent features throughout. Mean radiologic scores increased over time in a pattern similar among GPC, GNB, and U. urealyticum infected and noninfected infants. High radiologic scores were not predictive at any time of infants who needed supplemental oxygen at 28 days and at 36 w PCA. Infants infected with U. urealyticum were neither clinically nor radiologically different than noncolonized neonates. CONCLUSION: GPC, GNB, and U. urealyticum airway colonization is not associated with particular radiographic changes at any time. GNB-infected infants had the most severe BPD course, and yet they were radiologically indistinguishable from the other patients. U. urealyticum colonization does not result in more clinically severe BPD or demonstrate a unique radiologic course.     

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)     

Expertise and category-based induction.

The authors examined inductive reasoning among experts in a domain. Three types of tree experts (landscapers, taxonomists, and parks maintenance personnel) completed 3 reasoning tasks. In Experiment 1, participants inferred which of 2 novel diseases would affect "more other kinds of trees" and provided justifications for their choices. In Experiment 2, the authors used modified instructions and asked which disease would be more likely to affect "all trees." In Experiment 3, the conclusion category was eliminated altogether, and participants were asked to generate a list of other affected trees. Among these populations, typicality and diversity effects were weak to nonexistent. Instead, experts' reasoning was influenced by "local" coverage (extension of the property to members of the same folk family) and causal-ecological factors. The authors concluded that domain knowledge leads to the use of a variety of reasoning strategies not captured by current models of category-based induction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

In situ sampling uncovers the dynamics of particle genesis and growth in an aerosol tube reactor

Making metal and ceramic powders using aerosol synthesis from vapour precursors, either in a flame or hot-wall tube reactor, is the basis for producing many thousands of tons of powder on an annual basis. To properly study this system, we have designed and built a model reactor with sampling points at evenly spaced axial positions. This allows us to take snapshots of the aerosol population at many points within the reactor. Nucleation followed by a surface reaction produces a solid phase extremely rapidly, within 0.01 s under typical conditions. This is followed by a transient state where nucleation, surface reaction and coagulation all interact to produce a strongly bimodal size distribution. After nucleation is extinguished, the size distribution approaches the self-preserving limit as predicted for a coagulation-dominated process. The final structure is determined by the dominant sintering mechanism, which can be estimated from theory. The knowledge of this mechanism offers the possibility of selecting reactor conditions to produce powders with optimized properties.