Variation of the hopping exponent in disordered silicon MOSFETs

We observe a complex change in the hopping exponent value from 1/2 to 1/3 as a function of disorder strength and electron density in a sodium-doped silicon MOSFET. The disorder was varied by applying a gate voltage and thermally drifting the ions to different positions in the oxide. The same gate was then used at low temperature to modify the carrier concentration. Magnetoconductivity measurements are compatible with a change in transport mechanisms when either the disorder or the electron density is modified suggesting a possible transition from a Mott insulator to an Anderson insulator in these systems.Comment: 6 pages, 5 figure

α-Adrenergic inhibition of proliferation in HepG2 cells stably transfected with the α1B-adrenergic receptor through a p42MAP kinase/p21Cip1/WAF1-dependent pathway

AbstractActivation of α1B adrenergic receptors (α1BAR) promotes DNA synthesis in primary cultures of hepatocytes, yet expression of α1BAR in hepatocytes rapidly declines during proliferative events. HepG2 human hepatoma cells, which do not express α1BAR, were stably transfected with a rat α1BAR cDNA (TFG2 cells), in order to study the effects of maintained α1BAR expression on hepatoma cell proliferation. TFG2 cells had a decreased rate of growth compared to mock transfected HepG2 cells as revealed by a decrease in [3H]thymidine incorporation into DNA. Stimulation of α1BAR with phenylephrine caused a further large reduction in TFG2 cell growth, whereas no effect on growth was observed in mock transfected cells. Reduced cell growth correlated with increased percentages of cells found in G0/G1 and G2/M phases of the cell cycle. In TFG2 cells, phenylephrine increased p42MAP kinase activity by 1.5- to 2.0-fold for up to 24 h and increased expression of the cyclin dependent kinase inhibitor protein p21Cip1/WAF1. Treatment of TFG2 cells with the specific MEK1 inhibitor PD98059, or infection with a −/− MEK1 recombinant adenovirus permitted phenylephrine to increase rather than decrease [3H]thymidine incorporation. In addition, inhibition of MAP kinase signaling by PD98059 or MEK1 −/− blunted the ability of phenylephrine to increase p21Cip1/WAF1 expression. In agreement with a role for increased p21Cip1/WAF1 expression in causing growth arrest, infection of TFG2 cells with a recombinant adenovirus to express antisense p21Cip1/WAF1 mRNA blocked the ability of phenylephrine to increase p21Cip1/WAF1 expression and to inhibit DNA synthesis. Antisense p21Cip1/WAF1 permitted phenylephrine to stimulate DNA synthesis in TFG2 cells, and abrogated growth arrest. These results suggest that transformed hepatocytes may turn off the expression of α1BARs in order to prevent the activation of a growth inhibitory pathway. Activation of this inhibitory pathway via α1BAR appears to be p42MAP kinase and p21Cip1/WAF1 dependent

Benefit-Cost Analysis in Environmental, Health, and Safety Regulation: A Statement of Principles

Benefit-cost analysis can play a very important role in legislative and regulatory policy debates on improving the environment, health, and safety. It can help illustrate the tradeoffs that are inherent in public policymaking as well as make those tradeoffs more transparent. It can also help agencies set regulatory priorities. Benefit-cost analysis should be used to help decisionmakers reach a decision. Contrary to the views of some, benefit-cost analysis is neither necessary nor sufficient for designing sensible public policy. If properly done, it can be very helpful to agencies in the decisionmaking process. Decisionmakers should not be precluded from considering the economic benefits and costs of different policies in the development of regulations. Laws that prohibit costs or other factors from being considered in administrative decisionmaking are inimical to good public policy. Currently, several of the most important regulatory statutes have been interpreted to imply such prohibitions. Benefit-cost analysis should be required for all major regulatory decisions, but agency heads should not be bound by a strict benefit-cost test. Instead, they should be required to consider available benefit-cost analyses and to justify the reasons for their decision in the event that the expected costs of a regulation far exceed the expected benefits. Agencies should be encouraged to use economic analysis to help set regulatory priorities. Economic analyses prepared in support of particularly important decisions should be subjected to peer review both inside and outside government. Benefits and costs of proposed major regulations should be quantified wherever possible. Best estimates should be presented along with a description of the uncertainties. Not all benefits or costs can be easily quantified, much less translated into dollar terms. Nevertheless, even qualitative descriptions of the pros and cons associated with a contemplated action can be helpful. Care should be taken to ensure that quantitative factors do not dominate important qualitative factors in decisionmaking. The Office of Management and Budget, or some other coordinating agency, should establish guidelines that agencies should follow in conducting benefit-cost analyses. Those guidelines should specify default values for the discount rate and certain types of benefits and costs, such as the value of a small reduction in mortality risk. In addition, agencies should present their results using a standard format, which summarizes the key results and highlights major uncertainties.

Study protocol: imaging brain development in the Childhood to Adolescence Transition Study (iCATS)

BackgroundPuberty is a critical developmental phase in physical, reproductive and socio-emotional maturation that is associated with the period of peak onset for psychopathology. Puberty also drives significant changes in brain development and function. Research to date has focused on gonadarche, driven by the hypothalamic-pituitary-gonadal axis, and yet increasing evidence suggests that the earlier pubertal stage of adrenarche, driven by the hypothalamic-pituitary-adrenal axis, may play a critical role in both brain development and increased risk for disorder. We have established a unique cohort of children who differ in their exposure to adrenarcheal hormones. This presents a unique opportunity to examine the influence of adrenarcheal timing on brain structural and functional development, and subsequent health outcomes. The primary objective of the study is to explore the hypothesis that patterns of structural and functional brain development will mediate the relationship between adrenarcheal timing and indices of affect, self-regulation, and mental health symptoms collected across time (and therefore years of development).Methods/DesignChildren were recruited based upon earlier or later timing of adrenarche, from a larger cohort, with 128 children (68 female; M age 9.51 years) and one of their parents taking part. Children completed brain MRI structural and functional sequences, provided saliva samples for adrenarcheal hormones and immune biomarkers, hair for long-term cortisol levels, and completed questionnaires, anthropometric measures and an IQ test. Parents completed questionnaires reporting on child behaviour, development, health, traumatic events, and parental report of family environment and parenting style.DiscussionThis study, by examining the neurobiological and behavioural consequences of relatively early and late exposure to adrenarche, has the potential to significantly impact our understanding of pubertal risk processes.<br /

Creating New β-Globin-Expressing Lentiviral Vectors by High-Resolution Mapping of Locus Control Region Enhancer Sequences.

Hematopoietic stem cell gene therapy is a promising approach for treating disorders of the hematopoietic system. Identifying combinations of cis-regulatory elements that do not impede packaging or transduction efficiency when included in lentiviral vectors has proven challenging. In this study, we deploy LV-MPRA (lentiviral vector-based, massively parallel reporter assay), an approach that simultaneously analyzes thousands of synthetic DNA fragments in parallel to identify sequence-intrinsic and lineage-specific enhancer function at near-base-pair resolution. We demonstrate the power of LV-MPRA in elucidating the boundaries of previously unknown intrinsic enhancer sequences of the human β-globin locus control region. Our approach facilitated the rapid assembly of novel therapeutic βAS3-globin lentiviral vectors harboring strong lineage-specific recombinant control elements capable of correcting a mouse model of sickle cell disease. LV-MPRA can be used to map any genomic locus for enhancer activity and facilitates the rapid development of therapeutic vectors for treating disorders of the hematopoietic system or other specific tissues and cell types

Evaluation of mesofauna communities as soil quality indicators in a national-level monitoring programme

Mesofauna underpin many ecosystem functions in soils. However, mesofauna communities are often overlooked when discussing these functions on large scales. They have been proposed as bioindicators of soil quality and ecosystem health. This study aimed to evaluate differences amongst mesofauna communities, particularly Acari and Collembola, across multiple habitat and soil types, as well as organic matter levels, and their relationships with soil characteristics, on a national-scale. Soil cores were collected from 685 locations as part of a nationwide soil monitoring programme of Wales. Plant community composition, soil type, as well as physical and chemical variables, including pH, total C and N, were measured at these locations. Mesofauna were extracted from soil cores and identified using a Tullgren funnel technique. Acari were sorted to Order; Collembola were sorted according to Super-family. Abundances of mesofauna were consistently lowest in arable sites and highest in lowland woodlands, except for Mesostigmata. Differences between similar habitat types (e.g. Fertile and Infertile grasslands) were not detected using the national-level dataset and differences in mesofauna communities amongst soil types were unclear. Relationships between mesofauna groups and soil organic matter class, however, were much more informative. Oribatid abundances were lowest in mineral soils and correlated with all soil properties except moisture content. Collembola and Mesostigmata abundances were likely negatively influenced by increased moisture levels in upland peat habitats where their abundances were lowest. These groups also had low abundances in heathlands and this was reflected in low diversity values. Together, these findings show that this national-level soil survey can effectively identify differences in mesofauna community structure and correlations with soil properties. Identification of mesofauna at high taxonomic levels in national-level soil monitoring is encouraged to better understand the ecological context of changes in soil properties