Nanopore-Based Analysis of Chemically Modified DNA and Nucleic Acid Drug Targets

Nucleic acids are central figures in many of life’s key molecular processes, e.g., enzymatic activity, epigenetics/gene regulation, viral replication, aging, cancer, and other diseases. Over the past two decades, nanopores have emerged as a new tool for studying the properties of nucleic acids at the single-molecule level. In this review, we summarize the use of nanopores as sensors of nucleic acid structure, particularly for studying chemically modified and damaged DNA, and for probing the interactions of small-molecule drugs with nucleic acid targets.     

Alternative Australian climate change plans: The public’s views

Climate change has come to the forefront of Australian politics and there is now an active on-going policy debate about how to best reach a commonly agreed long term goal. This paper looks at five major dimensions of this debate and constructs policy options based on them. A discrete choice experiment approach was used with a representative sample from a major internet panel provider. Survey respondents made choices between pairs of policy options with different characteristics. They favored policies starting in 2010 rather than 2012, and spending 20% of revenue raised on energy-related R&D. They were almost evenly split on whether the plan should initially exempt the transport sector and two competing approaches that redistribute revenue from the plan, and, they opposed plans giving special treatment to energy-intensive sectors of the economy. A number of other policy relevant questions related to understanding Australian views and knowledge related to climate change also were asked.     

Possible dihydroepiandrosterone-induced mania

BACKGROUND: Dehydroepiandrosterone (DHEA) is among the most abundant steroids in the human body and appears to have diverse biochemical activities. This multifunctional hormone has long been a compound of interest to research psychiatrists. Its recent promotion and availability as an over-the-counter supplement to the general public has led to widespread use. Little is known about potential adverse effects of DHEA when consumed on an acute or chronic basis. We report a case of mania in an older man acutely admitted to our psychiatric facility with no previous personal or family history of bipolar disorder that appeared to be related to recent DHEA use. The patient had initiated DHEA use 6 months prior to admission and was taking 200-300 mg/day at the time of presentation. METHODS: He was treated with valproic acid 500 mg twice daily. RESULTS: The patient showed sufficient improvement to be discharged following a 7-day inpatient hospitalization. CONCLUSIONS: A wide range of medications have been associated with the induction of hypomania and mania, and we have provided a brief discussion of the potential for DHEA to trigger manic symptoms.     

Measurements of the thermal diffusivity of linear-medium-density-polyethylene/aluminium composites using a transient comparative method

Metal-powder/polymer composites are an interesting class of material because their physical properties may, within limits, be selected to match a particular application. It is therefore important to be able to measure and model the physical properties of these composites. The effective diffusivity of linear-medium-density-polyethylene/aluminium composites was measured for a range of volume fractions using a simple, transient comparative method. Effective thermal conductivity data were calculated from the effective thermal diffusivity data. The effective thermal conductivity data were modelled well by the EMT equation.     

Modelling Thermal Conductivity in Heterogeneous Media with the Finite Element Method

Three-dimensional finite element simulations were developed to predict the effective thermal conductivity of theoretical composite materials having complex structures. The models simulated a steady-state thermal conductivity measurement device performing measurements on theoretical materials with varying structures. The structure of a composite was considered to be composed of some simplified basic models. When the geometry, orientation type and number of dispersion are specified, the computer randomly generated the position and orientation for each dispersion and created the geometrical model and finite element mesh. The effective thermal conductivity of the theoretical composite was calculated using this method and compared to the values obtained by simple effective thermal conductivity models methods. The influence of some factors such as the volume fraction and the ratio of the thermal conductivities of the heterogeneities and the surrounding material on the effective thermal conductivity is discussed.     

MRT letter: Auto‐fluorescence by human alveolar macrophages after in vitro exposure to air pollution particles

Macrophages from smokers demonstrate an increased auto‐fluorescence. Similarly, auto‐fluorescence follows in vitro exposure of macrophages to cigarette smoke condensate (i.e., the particulate fraction of cigarette smoke). The composition of particles in cigarette smoke can be comparable to air pollution particles. We tested the postulate that macrophages exposed to air pollution particles could demonstrate auto‐fluorescence. Healthy nonsmoking and healthy smoking volunteers (both 18–40 years of age) underwent fiberoptic bronchoscopy with bronchoalveolar lavage and alveolar macrophages isolated. Macrophages were incubated at 37°C in 5% CO₂ with either PBS or 100 μg/mL particle for both 1 and 24 h. Particles included a residual oil fly ash, Mt. St. Helens volcanic ash, and ambient air particles collected from St. Louis, Missouri and Salt Lake City, Utah. At the end of incubation, 50 μL of the cell suspension was cytocentrifuged and examined at modes for viewing fluorescein isothiocyanate (FITC) and rhodamine fluorescence. Both emission source air pollution particles demonstrated FITC and rhodamine auto‐fluorescence at 1 and 24 h, but the signal following incubation of the macrophages with oil fly ash appeared greater. Similarly, the ambient particles were associated with auto‐fluorescence by the alveolar macrophages and this appeared to be dose‐dependent. We conclude that exposure of macrophages to air pollution particles can be associated with auto‐fluorescence in the FITC and rhodamine modes. Microsc. Res. Tech., 2010. © 2009 Wiley‐Liss, Inc.     

Abrupt weaning reduces postweaning growth and is associated with alterations in gastrointestinal markers of development in dairy calves fed an elevated plane of nutrition during the preweaning period

The benefits of feeding elevated quantities of milk to dairy calves have been well established. However, there is a reluctance to adopt this method of feeding in commercial dairy production because of concerns around growth, health, and ruminal development during weaning. The objective of this study was to characterize the effect of an abrupt (0 d step-down) or gradual (12 d step-down) feeding scheme when calves are fed an elevated plane of nutrition (offered 1.35 kg of milk replacer/d). For this experiment, a total of 54 calves were randomly assigned to an abrupt or a gradual weaning protocol before weaning at 48 d of life. Calves were housed and sampled in individual pens for the duration of the experiment, and milk, starter, and straw intake were measured on a daily basis. Body weight was measured every 6 d, whereas blood, rumen fluid, and fecal samples were collected on d 36 (pre-step-down), 48 (preweaning), and 54 (postweaning) of the experiment. Although the growth rates of the step-down calves were lower from d 37 to weaning (0.62 ± 0.04 vs. 1.01 ± 0.04 kg/d), the postweaning average daily gain was greater compared with the group that was abruptly weaned (0.83 ± 0.06 vs. 0.22 ± 0.06 kg/d). Total ruminal volatile fatty acid was greater in the step-down group on the day of weaning (d 48; 59.80 ± 2.25 vs. 45.01 ± 2.25 mmol), whereas the fecal starch percentage was lower during postweaning compared with the abruptly weaned calves (d 54; 3.31 ± 0.76 vs. 6.34 ± 0.76%). Analysis of the digestive tract of bull calves on d 55 revealed minimal differences between gross anatomy measurements of gut compartments as well as no morphological differences in rumen papillae development, yet the total mass of rumen when full of contents was larger in the step-down calves (7.83 ± 0.78 vs. 6.02 ± 0.78 kg). Under the conditions of this study, the results showcase the benefits of a step-down feeding strategy from an overall energy balance standpoint, due to increased adaptation of the gastrointestinal tract preweaning.     

High-throughput screening of ionic conductivity in polymer membranes

Combinatorial and high-throughput techniques have been successfully used for efficient and rapid property screening in multiple fields. The use of these techniques can be an advantageous new approach to assay ionic conductivity and accelerate the development of novel materials in research areas such as fuel cells. A high-throughput ionic conductivity (HTC) apparatus is described and applied to screening candidate polymer electrolyte membranes for fuel cell applications. The device uses a miniature four-point probe for rapid, automated point-to-point AC electrochemical impedance measurements in both liquid and humid air environments. The conductivity of Nafion^® 112 HTC validation standards was within 1.8% of the manufacturer's specification. HTC screening of 40 novel Kynar^® poly(vinylidene fluoride) (PVDF)/acrylic polyelectrolyte (PE) membranes focused on varying the Kynar^® type (5×) and PE composition (8×) using reduced sample sizes. Two factors were found to be significant in determining the proton conducting capacity: (1) Kynar^® PVDF series: membranes containing a particular Kynar^® PVDF type exhibited statistically identical mean conductivity as other membranes containing different Kynar^® PVDF types that belong to the same series or family. (2) Maximum effective amount of polyelectrolyte: increments in polyelectrolyte content from 55 wt% to 60 wt% showed no statistically significant effect in increasing conductivity. In fact, some membranes experienced a reduction in conductivity.