bluuebunny/crossref_metadata_2025 huggingface dataset:
Influences on place of death in Botswana
Authors: Lazenby Mark , Ma Tony , Moffat Howard J. , Funk Marjorie , Knobf M. Tish , McCorkle Ruth
Published: March 2010

Objective:

There is an emerging body of research aimed at understanding the determinants of place of death, as where people die may influence the quality of their death. However, little is known about place of death for people of Southern Africa. This study describes place of death (home or hospital) and potential influencing factors (cause of death, age, gender, occupation, and district of residence).

Method:

We collected the death records for years 2005 and 2006 for all adult non-traumatic deaths that occurred in Botswana, described them, and looked for associations using bivariate and multivariate analyses.

Results:

The evaluable sample consisted of 18,869 death records. Home deaths accounted for 36% of all deaths, and were predominantly listed with “unknown” cause (82.3%). Causes of death for hospital deaths were HIV/AIDS (49.7%), cardiovascular disease (13.8%), and cancer (6.6%). The mean age at the time of all deaths was 53.2 years (SD = 20.9); with 61 years (SD = 22.5) for home deaths and 48.8 years (SD = 18.6) for hospital deaths (p < .001). Logistic regression analysis revealed the following independent predictors of dying at home: unknown cause of death; female gender; >80 years of age; and residing in a city or rural area (p < .05).

Significance of Results:

A major limitation of this study was documentation of cause of death; the majority of people who died at home were listed with an unknown cause of death. This finding impeded the ability of the study to determine whether cause of death influenced dying at home. Future study is needed to determine whether verbal autopsies would increase death-certificate listings of causes of home deaths. These data would help direct end-of-life care for patients in the home.
On the road again: Patient perspectives on commuting for palliative care
Authors: Pesut Barbara , Robinson Carole A. , Bottorff Joan L. , Fyles Gillian , Broughton Sandra
Published: March 2010

Objective:

The aim of this research project was to gain an understanding of the experiences of rural cancer patients who commute to an urban cancer center for palliative care.

Method:

The study utilized a mixed method design. Fifteen individuals with a palliative designation participated in semi-structured interviews and filled out the Problems and Needs in Palliative Care Questionnaire.

Results:

Qualitative findings included three major themes: cultures of rural life and care, strategies for commuting, and the effects of commuting. Participants valued their rural lifestyles and gained significant support from their communities. Strategies included preparing for the trip with particular attention to pain management, making the most of time, and maintaining significant relationships. Establishing a routine helped to offset the anxiety of commuting. Commuting was costly but the quality of life and supportive relationships obtained through treatment were significant benefits. Questionnaire data suggested that participants were experiencing a number of problems but few indicated they desired more professional attention to those problems.

Significance of Results:

Rural lifestyles are often an important part of overall well-being and commuting for care is both costly and complex. Health care providers should assist individuals to weigh the relative contributions of staying in their rural locale versus commuting for care to their overall quality of life. Palliative-care individuals in this study indicated a number of ongoing problems but were not inclined to seek further assistance from health care providers in addressing those problems. Clinicians should actively inquire about problems and further research is needed to understand why patients are reluctant to seek help.
Childhood trauma, attachment style, and a couple's experience of terminal cancer: Case study
Authors: McLean Linda M. , Hales Sarah
Published: March 2010

Objective:

The primary objective of this article is to elucidate the significance of psychosocial distress and risk in a sub-population of end-stage cancer patients and their spouse caregivers who present with an especially challenging attachment style and histories of childhood trauma. The case study presented highlights the need to both identify and offer an empirically validated couple–based intervention, along with a multi-disciplinary team approach over the trajectory of the illness and at end of life.

Method:

A validated marital protocol (emotionally focused couple therapy [EFT]) is modified for this population and conducted by an EFT-trained psychologist as part of a pilot investigation as to the feasibility and effectiveness of EFT for the terminal cancer population. Measures of marital distress, depression, hopelessness, and attachment security are completed at baseline and subsequent intervals, as reported in another publication. Attachment insecurity and the exquisitely intimate relationship with caregiving and care receiving are underscored, given the couple's traumatic childhood history.

Results:

The couple described herein, followed from diagnosis of metastatic disease to end of life illuminates the potential effectiveness of a modified EFT protocol, and underscores the need to both identify and intervene with a population potentially at significantly high risk for marital distress, suicidality, depression, and hopelessness.

Significance of Results:

The benefits of a multidisciplinary team is evident as the patient's symptoms of physical distress increased toward end of life and she returned to earlier behaviors, namely suicidal ideation and an attempt to alleviate her experience of suffering. The strength of the marital bond, possibly as a result of the intervention, and the efforts of the multidisciplinary team approach, demonstrate potential to mitigate a catastrophic end of life and a complicated spousal bereavement. This case study adds to the current empirical literature in an area that is currently under-studied and under-reported.
Overview of AlGaN/GaN HEMT technology for L- to Ku-band applications
Authors: Piotrowicz Stéphane , Morvan Erwan , Aubry Raphaël , Callet Guillaume , Chartier Eric , Dua Christian , Dufraisse Jérémy , Floriot Didier , Jacquet Jean-Claude , Jardel Olivier , Mancuso Yves , Mallet-Guy Benoit , Oualli Mourad , Ouarch Zineb , Di-Forte Poisson Marie-Antoinette , Sarazin Nicolas , Stanislawiak Michel , Delage Sylvain
Published: March 2010

The present paper presents an overview of the AlGaN/GaN-based circuits realized over the years. Two technological processes with 0.25 and 0.7 μm gate length allowed one to address applications from L- to Ku-bands. Depending on the process development and frequency of the operation, results on hybrid or MMIC technology are presented. GaN technology is evaluated through the realization of high-power amplifiers, robust low-noise amplifiers, or power switches to prepare the next generation of Tx-Rx modules.
Reliability issues of Gallium Nitride High Electron Mobility Transistors
Authors: Meneghesso Gaudenzio , Meneghini Matteo , Tazzoli Augusto , Ronchi Nicolo' , Stocco Antonio , Chini Alessandro , Zanoni Enrico
Published: March 2010

In the present paper we review the most recent degradation modes and mechanisms recently observed in AlGaN/GaN (Aluminum Gallium Nitride/Gallium Nitride). High Electron-Mobility Transistors (HEMTs), as resulting from a detailed accelerated testing campaign, based on reverse bias tests and DC accelerated life tests at various temperatures. Despite the large efforts spent in the last few years, and the progress in mean time to failure values, reliability of GaN HEMTs, and millimeter microwave integrated circuits still represent a relevant issue for the market penetration of these devices. The role of temperature in promoting GaN HEMT failure is controversial, and the accelerating degradation factors are largely unknown. The present paper proposes a methodology for the analysis of failure modes and mechanisms of GaN HEMTs, based on (i) DC and RF stress tests accompanied by an (ii) extensive characterization of traps using deep level transient spectroscopy and pulsed measurements, (iii) detailed analysis of electrical characteristics, and (iv) comparison with two-dimensional device simulations. Results of failure analysis using various microscopy and spectroscopy techniques are presented and failure mechanisms observed at the high electric field values typical of the operation of these devices are reviewed.
Observations of infrared radiative cooling in the thermosphere on daily to multiyear timescales from the TIMED/SABER instrument
Authors: Mlynczak Martin G. , Hunt Linda A. , Thomas Marshall B. , Martin‐Torres F. Javier , Mertens Christopher J. , Russell James M. , Remsberg Ellis E. , López‐Puertas Manuel , Picard Richard , Winick Jeremy , Wintersteiner Peter , Thompson R. Earl , Gordley Larry L.
Published: March 2010

We present observations of the infrared radiative cooling by carbon dioxide (CO2) and nitric oxide (NO) in Earth's thermosphere. These data have been taken over a period of 7 years by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the NASA Thermosphere‐Ionosphere‐Mesosphere Energetics and Dynamics (TIMED) satellite and are the dominant radiative cooling mechanisms for the thermosphere. From the SABER observations we derive vertical profiles of radiative cooling rates (W m−3), radiative fluxes (W m−2), and radiated power (W). In the period from January 2002 through January 2009, we observe a large decrease in the cooling rates, fluxes, and power consistent with the declining phase of solar cycle 23. The power radiated by NO during 2008 when the Sun exhibited few sunspots was nearly one order of magnitude smaller than the peak power observed shortly after the mission began. Substantial short‐term variability in the infrared emissions is also observed throughout the entire mission duration. Radiative cooling rates and radiative fluxes from NO exhibit fundamentally different latitude dependence than do those from CO2, with the NO fluxes and cooling rates being largest at high latitudes and polar regions. The cooling rates are shown to be derived relatively independent of the collisional and radiative processes that drive the departure from local thermodynamic equilibrium (LTE) in the CO2 15 μm and the NO 5.3 μm vibration‐rotation bands. The observed NO and CO2 cooling rates have been compiled into a separate data set and represent a climate data record that is available for use in assessments of radiative cooling in upper atmosphere general circulation models.
Anticipated electrical environment within permanently shadowed lunar craters
Authors: Farrell W. M. , Stubbs T. J. , Halekas J. S. , Killen R. M. , Delory G. T. , Collier M. R. , Vondrak R. R.
Published: March 2010

Shadowed locations near the lunar poles are almost certainly electrically complex regions. At these locations near the terminator, the local solar wind flows nearly tangential to the surface and interacts with large‐scale topographic features such as mountains and deep large craters. In this work, we study the solar wind orographic effects from topographic obstructions along a rough lunar surface. On the leeward side of large obstructions, plasma voids are formed in the solar wind because of the absorption of plasma on the upstream surface of these obstacles. Solar wind plasma expands into such voids, producing an ambipolar potential that diverts ion flow into the void region. A surface potential is established on these leeward surfaces in order to balance the currents from the expansion‐limited electron and ion populations. We find that there are regions near the leeward wall of the craters and leeward mountain faces where solar wind ions cannot access the surface, leaving an electron‐rich plasma previously identified as an “electron cloud.” In this case, some new current is required to complete the closure for current balance at the surface, and we propose herein that lofted negatively charged dust is one possible (nonunique) compensating current source. Given models for both ambipolar and surface plasma processes, we consider the electrical environment around the large topographic features of the south pole (including Shoemaker crater and the highly varied terrain near Nobile crater), as derived from Goldstone radar data. We also apply our model to moving and stationary objects of differing compositions located on the surface and consider the impact of the deflected ion flow on possible hydrogen resources within the craters.
Impact of environmental traders on water markets: An experimental analysis
Authors: Tisdell John G.
Published: March 2010

This paper reports the results of a series of economic experiments in which an environmental agency with a stochastic demand function enters an existing water market to buy or sell water for instream use. Previous experimental studies have examined the use of tenders to reduce water extractions and social suasion to maintain aggregate flow levels and compared imposing minimum flow restrictions with subsidizing downstream water use and the allocation of tradeable minimum flow rights. The important contribution of this paper is that it explores the consequence of having an environmental agency enter an existing water market. In this paper we explore the consequences of (1) formally allocating tradeable water rights to the environmental agency, (2) allocating funding to purchase water as required, and (3) having the trading actions of the environmental agency a matter of public record. The research, while contextualized to water markets in this paper, addresses an important and timely issue that could have implication beyond water markets. In pollution permit markets, for example, there is the question of what the impact on the market would be if a government agency were to begin buying back permits, particularly if this represented a relatively large volume of trades and entered into such purchases on a needs basis.
Venus OH nightglow distribution based on VIRTIS limb observations from Venus Express
Authors: Soret L. , Gérard J.‐C. , Piccioni G. , Drossart P.
Published: March 2010

The full set of VIRTIS‐M limb observations of the OH Venus nightglow has been analyzed to determine its characteristics. Based on 3328 limb profiles, we find that the mean peak intensity along the line of sight of the OH(Δv = 1 sequence) is 0.35−0.21+0.53 MR and is located at 96.4 ± 5 km. The emission is highly variable and no dependence of the airglow layer altitude versus the antisolar angle is observed. The peak brightness appears to decrease away from the antisolar point even if the variability at a given location is very strong. Some correlation between the intensity of the OH and the O2(a1Δ) emissions is also observed, presumably because atomic oxygen is a common precursor to the formation of O2(a1Δ) and O3, whose reaction with H produces excited OH. Comparing our results with predictions from a photochemical model, a constant H flux does not match the simultaneous OH and O2 airglow observations.
Dendritic cells and humoral immunity in humans
Authors: Ueno Hideki , Schmitt Nathalie , Palucka A Karolina , Banchereau Jacques
Published: March 2010

Dendritic cells (DCs) orchestrate the innate and adaptive immune systems to induce tolerance and immunity. DC plasticity and subsets are prominent determinants in the regulation of immune responses. Our recent studies suggest that humoral and cellular immunity is regulated by different myeloid DC subsets with distinct intrinsic properties in humans. Although antibody response is preferentially mediated by CD14+ dermal DCs, cytotoxic T‐cell response is preferentially mediated by Langerhans cells (LCs). Thus, mechanisms whereby DCs induce humoral and cellular immunity seem to be fundamentally distinct. In this review, we will focus on the role of DCs in the development of humoral immunity. We will also discuss the mechanisms whereby DCs induce CD4+ T cells associated with aiding B‐cell response, including T follicular helper (Tfh) cells, and why human LCs lack this ability.
New insights into the role of VIP on the ratio of T‐cell subsets during the development of autoimmune diabetes
Authors: Jimeno Rebeca , Gomariz Rosa P , Gutiérrez‐Cañas Irene , Martínez Carmen , Juarranz Yasmina , Leceta Javier
Published: March 2010

Type I diabetes is an autoimmune T‐cell‐mediated disease associated with overexpression of inflammatory mediators and the disturbance of different T‐cell subsets. Vasoactive intestinal peptide (VIP) is a potent anti‐inflammatory agent with regulatory effects on activated T cells. As the equilibrium between different T‐cell subsets is involved in the final outcome, leading to tolerance or autoimmunity, we studied the evolution of markers for T cells in nonobese diabetic (NOD) mice. The study of different transcription factors, cytokines or cytokine receptors, shows that VIP interferes with functional phase of T helper 17 (Th17) cells and prevents the increase in the proportion of Th1 to Th17 cells. On the other hand, VIP‐treated NOD mice show an increase in the proportion of CD4+CD25+ cells in the spleen. Thus, VIP switches the Tregs/Th17 ratio leading to tolerance in NOD mice. Similarly, VIP reverses the ratio of Th1‐/Th2‐cell subsets associated with autoimmune pathology. All these effects on the ratio of T‐cell subsets and the anti‐inflammatory effect of VIP in decreasing proinflammatory mediators result in a reduction of β‐cell destruction in pancreas. Taken together, these results show that VIP provides significant protection against spontaneous diabetes by modulating T‐cell subsets and counterbalancing tolerance and immunity.
The cytoplasmic domains of TNFα-converting enzyme (TACE/ADAM17) and L-selectin are regulated differently by p38 MAPK and PKC to promote ectodomain shedding
Authors: Killock David J. , Ivetić Aleksandar
Published: March 2010

L-selectin mediates the initial tethering and subsequent rolling of leucocytes along luminal walls of inflamed venules. TACE [TNFα (tumour necrosis factor α)-converting enzyme] is responsible for cleaving the membrane-proximal extracellular domain of L-selectin (also known as shedding), which reduces the efficiency of leucocyte recruitment to sites of inflammation. Many reports have highlighted roles for PKC (protein kinase C) and p38 MAPK (mitogen-activated protein kinase) in promoting L-selectin shedding with little insight into the mechanism involved. By using PMA and the phosphatase inhibitors cantharidin and calyculin A, we could selectively activate PKC or p38 MAPK respectively to promote TACE-dependent shedding of L-selectin. Interestingly, the intracellular mechanisms leading to the shedding event differed dramatically. For example, regulatory elements within the L-selectin cytoplasmic tail, such as ERM (ezrin/radixin/moesin)-binding and serine residues, were important for PKC- but not p38 MAPK-dependent shedding. Also, increased and sustained cell surface levels of TACE, and phosphorylation of its cytoplasmic tail (a hallmark of TACE activation), occurred in lymphocytes and monocytes following p38 MAPK activation. Finally, we showed that TNFα-induced shedding of L-selectin in monocytes was strikingly similar to cantharidin-induced shedding and suggest that this newly characterized mechanism could be physiologically relevant in inflammatory cells.
Novel insights into the assembly and function of human nuclear-encoded cytochromecoxidase subunits 4, 5a, 6a, 7a and 7b
Authors: Fornuskova Daniela , Stiburek Lukas , Wenchich Laszlo , Vinsova Kamila , Hansikova Hana , Zeman Jiri
Published: March 2010

Mammalian CcO (cytochrome c oxidase) is a hetero-oligomeric protein complex composed of 13 structural subunits encoded by both the mitochondrial and nuclear genomes. To study the role of nuclear-encoded CcO subunits in the assembly and function of the human complex, we used stable RNA interference of COX4, COX5A and COX6A1, as well as expression of epitope-tagged Cox6a, Cox7a and Cox7b, in HEK (human embryonic kidney)-293 cells. Knockdown of Cox4, Cox5a and Cox6a resulted in reduced CcO activity, diminished affinity of the residual enzyme for oxygen, decreased holoCcO and CcO dimer levels, increased accumulation of CcO subcomplexes and gave rise to an altered pattern of respiratory supercomplexes. An analysis of the patterns of CcO subcomplexes found in both knockdown and overexpressing cells identified a novel CcO assembly intermediate, identified the entry points of three late-assembled subunits and demonstrated directly the essential character as well as the interdependence of the assembly of Cox4 and Cox5a. The ectopic expression of the heart/muscle-specific isoform of the Cox6 subunit (COX6A2) resulted in restoration of both CcO holoenzyme and activity in COX6A1-knockdown cells. This was in sharp contrast with the unaltered levels of COX6A2 mRNA in these cells, suggesting the existence of a fixed expression programme. The normal amount and function of respiratory complex I in all of our CcO-deficient knockdown cell lines suggest that, unlike non-human CcO-deficient models, even relatively small amounts of CcO can maintain the normal biogenesis of this respiratory complex in cultured human cells.
Myogenic regulatory factors transactivate the Tceal7 gene and modulate muscle differentiation
Authors: Shi Xiaozhong , Garry Daniel J.
Published: March 2010

Recurrent injuries eventually exhaust the capacity of skeletal muscle to fully restore or regenerate its cellular architecture. Therefore a comprehensive understanding of the muscle regeneration programme is needed to provide a platform for new therapies for devastating diseases such as Duchenne muscular dystrophy. To begin to decipher the molecular programme that directs muscle regeneration, we undertook an unbiased strategy using microarray analysis of cardiotoxin-injured skeletal muscle at defined time periods in the adult mouse. Using this strategy, we identified Tceal7 [transcription elongation factor A (SII)-like 7], which was dynamically regulated during muscle regeneration. Our studies revealed that Tceal7 was restricted to the skeletal muscle lineage during embryogenesis. Using transgenic technologies and transcriptional assays, we defined an upstream 0.7 kb fragment of the Tceal7 gene that directed the LacZ reporter to the developing skeletal muscle lineage. Analysis of the Tceal7 promoter revealed evolutionarily conserved E-box motifs within the 0.7 kb upstream fragment that were essential for promoter activity, as mutation of the E-box motifs resulted in the loss of reporter expression in the somites of transgenic embryos. Furthermore, we demonstrated that MRFs (myogenic regulatory factors) were Tceal7 upstream transactivators using transcriptional assays, EMSAs (electrophoretic mobility-shift assays), and ChIP (chromatin immunoprecipitation) assays. Overexpression of Tceal7 in C2C12 myoblasts decreased cellular proliferation and enhanced differentiation. Further studies revealed that p27 expression was up-regulated following Tceal7 overexpression. These studies support the hypothesis that MRFs transactivate Tceal7 gene expression and promote muscle differentiation during muscle development and regeneration.
Novel mechanism for regulation of plasma platelet-activating factor acetylhydrolase expression in mammalian cells
Authors: Gardner Alison A. , Reichert Ethan C. , Alexander Timothy S. , Topham Matthew K. , Stafforini Diana M.
Published: March 2010

The plasma form of PAF-AH [PAF (platelet-activating factor) acetylhydrolase; also known as LpPLA2 (lipopoprotein-associated phospholipase A2), PLA2G7] catalyses the release of sn-2 fatty acyl residues from PAF, oxidatively fragmented phospholipids, and esterified isoprostanes. The plasma levels of this enzyme vary widely among mammalian species, including mice and humans, but the mechanisms that account for these differences are largely unknown. We investigated the basis for these variations using molecular and biochemical approaches. We identified an N-terminal domain that played key roles in the determination of steady-state expression levels. The mouse N-terminal domain robustly enhanced protein expression levels, possibly owing to its ability to adopt a globular conformation that is absent in the human protein. We investigated the mechanism(s) whereby the N-terminal stretch modulated PAF-AH levels and found that differential expression was not due to variations in the efficiency of transcription, translation, or mRNA stability. Studies designed to evaluate the ability of precursor forms of PAF-AH to mature to fully active proteins indicated that the N-terminal end of human and mouse PAF-AH played important and opposite roles in this process. These domains also modulated the levels of expression of an unrelated polypeptide by affecting the stability of precursor forms of the protein. These studies provide insights that contribute to our understanding of the molecular features and mechanisms that contribute to differential expression of plasma PAF-AH in mammals.
A role for Na+/H+ exchangers and intracellular pH in regulating vitamin C-driven electron transport across the plasma membrane
Authors: Lane Darius J.R. , Robinson Stephen R. , Czerwinska Hania , Lawen Alfons
Published: March 2010

Ascorbate (vitamin C) is the major electron donor to a tPMET (transplasma membrane electron transport) system that was originally identified in human erythrocytes. This plasma membrane redox system appears to transfer electrons from intracellular ascorbate to extracellular oxidants (e.g. non-transferrin-bound iron). Although this phenomenon has been observed in nucleated cells, its mechanism and regulation are not well understood. In the present study we have examined both facets of this phenomenon in K562 cells and primary astrocyte cultures. Using ferricyanide as the analytical oxidant we demonstrate that tPMET is enhanced by dehydroascorbate uptake via facilitative glucose transporters, and subsequent accumulation of intracellular ascorbate. Additionally, we demonstrate that this stimulation is not due to ascorbate that is released from the cells, but is dependent only on a restricted intracellular pool of the vitamin. Substrate-saturation kinetics suggest an enzyme-catalysed reaction across the plasma membrane by an as-yet-unidentified reductase that relies on extensive recycling of intracellular ascorbate. Inhibition of ascorbate-stimulated tPMET by the NHE (Na+/H+-exchanger) inhibitors amiloride and 5-(N-ethyl-N-isopropyl)amiloride, which is diminished by bicarbonate, suggests that tPMET activity may be regulated by intracellular pH. In support of this hypothesis, tPMET in astrocytes was significantly inhibited by ammonium chloride-pulse-induced intracellular acidification, whereas it was significantly stimulated by bicarbonate-induced intracellular alkalinization. These results suggest that ascorbate-dependent tPMET is enzyme-catalysed and is modulated by NHE activity and intracellular pH.
What does the commonly used DCF test for oxidative stress really show?
Authors: Karlsson Markus , Kurz Tino , Brunk Ulf T. , Nilsson Sven E. , Frennesson Christina I.
Published: March 2010

H2DCF-DA (dihydrodichlorofluorescein diacetate) is widely used to evaluate ‘cellular oxidative stress’. After passing through the plasma membrane, this lipophilic and non-fluorescent compound is de-esterified to a hydrophilic alcohol [H2DCF (dihydrodichlorofluorescein)] that may be oxidized to fluorescent DCF (2′,7′-dichlorofluorescein) by a process usually considered to involve ROS (reactive oxygen species). It is, however, not always recognized that, being a hydrophilic molecule, H2DCF does not cross membranes, except for the outer fenestrated mitochondrial ones. It is also not generally realized that oxidation of H2DCF is dependent either on Fenton-type reactions or on unspecific enzymatic oxidation by cytochrome c, for neither superoxide, nor H2O2, directly oxidizes H2DCF. Consequently, oxidation of H2DCF requires the presence of either cytochrome c or of both redox-active transition metals and H2O2. Redox-active metals exist mainly within lysosomes, whereas cytochrome c resides bound to the outer side of the inner mitochondrial membrane. Following exposure to H2DCF-DA, weak mitochondrial fluorescence was found in both the oxidation-resistant ARPE-19 cells and the much more sensitive J774 cells. This fluorescence was only marginally enhanced following short exposure to H2O2, showing that by itself it is unable to oxidize H2DCF. Cells that were either exposed to the lysosomotropic detergent MSDH (O-methylserine dodecylamide hydrochloride), exposed to prolonged oxidative stress, or spontaneously apoptotic showed lysosomal permeabilization and strong DCF-induced fluorescence. The results suggest that DCF-dependent fluorescence largely reflects relocation to the cytosol of lysosomal iron and/or mitochondrial cytochrome c.
Label-free detection of protein-ligand interactions in real time using micromachined bulk acoustic resonators
Authors: Zhang Hao , Pang Wei , Marma Mong S. , Lee Chuang-Yuan , Kamal-Bahl Sanat , Kim Eun Sok , McKenna Charles E.
Published: March 2010

In this paper, we present a micromachined film bulk acoustic resonator (FBAR) to detect protein-ligand interactions in real-time. The surface of the FBAR device has a thin layer of gold deposited on it to immobilize thiol-modified biotin. The resonant frequency of the biotin modified FBAR was measured to decrease by 170 ppm when exposed to streptavidin solution with a concentration of 5×10−7 M, corresponding to an added mass of 120 pg on the FBAR surface due to the biotin-streptavidin interaction. Consequently, the biotin modified FBAR can be used to observe in real time the biotin-streptavidin interaction without the use of labeling or molecular tags. The FBAR can be used in a variety of protein-ligand systems, and be designed for testing in array formats to give high throughput screening for drug discovery.
Exciton scattering approach for branched conjugated molecules and complexes. IV. Transition dipoles and optical spectra
Authors: Li Hao , Malinin Sergey V. , Tretiak Sergei , Chernyak Vladimir Y.
Published: March 2010

The electronic excitation energies and transition dipole moments are the essential ingredients to compute an optical spectrum of any molecular system. Here we extend the exciton scattering (ES) approach, originally developed for computing excitation energies in branched conjugated molecules, to the calculation of the transition dipole moments. The ES parameters that characterize contributions of molecular building blocks to the total transition dipole can be extracted from the quantum-chemical calculations of the excited states in simple molecular fragments. Using these extracted parameters, one can then effortlessly calculate the oscillator strengths and optical spectra of various large molecular structures. We illustrate application of this extended ES approach using an example of phenylacetylene-based molecules. Absorption spectra predicted by the ES approach show close agreement with the results of the reference quantum-chemical calculations.
Low thermal conductivity of CsBiNb2O7 epitaxial layers
Authors: Cahill David G. , Melville Alexander , Schlom Darrell G. , Zurbuchen Mark A.
Published: March 2010

The thermal conductivity of an epitaxial layer of CsBiNb2O7 grown by pulsed-laser deposition is measured by time-domain thermoreflectance in the temperature range 100<T<600 K. Characterization by x-ray diffraction and cross-sectional transmission electron microscopy show that the sample has the n=2 structure of the Dion–Jacobson series of phases. The conductivity of this layered oxide is ≈60% of the predicted minimum thermal conductivity in this temperature range; the thermal conductivity at room temperature, 0.4 W m−1 K−1, is comparable to the lowest conductivity ever observed in an oxide crystal.
Reduced saturation magnetization in cobalt antidot thin films prepared by polyethylene oxide-assisted self-assembly of polystyrene nanospheres
Authors: Ho Chi-Chih , Hsieh Tung-Wu , Kung Hsiang-Hsi , Juan Wen-Tau , Lin Keng-Hui , Lee Wei-Li
Published: March 2010

We have developed an approach to prepare large array nanostructured thin films using polyethylene oxide assisted self-assembly of polystyrene nanospheres as a template. By tuning the antidot diameter in the cobalt thin films, we found a crossover behavior in the magnetization reversal process. In addition, the effective moment per cobalt atom turns out to drop with growing antidot diameter which effectively increases the surface to bulk volume fraction. Our results suggest a tendency of reduced saturation magnetization in a ferromagnet/normal metal interface, where the mixing of itinerant electrons with ferromagnetic d electrons can give rise to observable effect.
Room-temperature operation type-II GaSb/GaAs quantum-dot infrared light-emitting diode
Authors: Lin Shih-Yen , Tseng Chi-Che , Lin Wei-Hsun , Mai Shu-Cheng , Wu Shung-Yi , Chen Shu-Han , Chyi Jen-Inn
Published: March 2010

A GaSb/GaAs quantum-dot light-emitting diode (QD LED) with a single GaSb QD layer is investigated in this paper. The room-temperature photoluminescence peak blueshift with increasing excitation power densities suggests a type-II alignment of the GaSb/GaAs heterostructures. Significant electroluminescence (EL) is observed for the device under forward biases, which suggests that pronounced dipole transitions occur at the GaSb/GaAs interfaces. With increasing forward biases, the observed EL peak blueshift confirms that the origin of luminescence is from the type-II GaSb/GaAs QD structures. A model is established to explain the operation mechanisms of the type-II QD LED.
Economics of camel control in central Australia
Authors: Drucker Adam G. , Edwards Glenn P. , Saalfeld William K.
Published: March 2010

A cost-effectiveness analysis based on a bioeconomic model was carried out with regard to specific feral camel control strategies in central Australia.
Two different aerial control strategies were modelled for the period 2009–20. Strategy 1 involved annual removals, whereas strategy 2 involved periodic removals only when a specific feral camel density was reached. The direct benefits to the pastoral industry of feral camel control were also modelled in terms of reduced grazing competition together with infrastructure damage. A single environmental service related to reducing greenhouse gas emissions was further considered.
Although the present costs of control under the two strategies are considerable ($4.10–4.95 million over 12 years at a 5% discount rate), they are far outweighed by the present benefits to the livestock industry from reduced competition ($46.3 million), as well as to society as a whole through reduced greenhouse gas emissions ($32.1 million). Including reduced infrastructure damage, the net present value of control is $75.2 million under strategy 1 and $73.3 million under strategy 2 (over 12 years at a 5% discount rate), suggesting that a control strategy based on annual removals should be preferred over a strategy of periodic removals. Given the large positive net present value of control and the robustness of the overall findings, there would appear to be a strong argument for considering the implementation of a full-scale, long-term feral camel control programme in the near future.
Demography of feral camels in central Australia and its relevance to population control
Authors: Pople A. R. , McLeod S. R.
Published: March 2010

Since their release over 100 years ago, camels have spread across central Australia and increased in number. Increasingly, they are being seen as a pest, with observed impacts from overgrazing and damage to infrastructure such as fences. Irregular aerial surveys since 1983 and an interview-based survey in 1966 suggest that camels have been increasing at close to their maximum rate. A comparison of three models of population growth fitted to these, albeit limited, data suggests that the Northern Territory population has indeed been growing at an annual exponential rate of r = 0.074, or 8% per year, with little evidence of a density-dependent brake. A stage-structured model using life history data from a central Australian camel population suggests that this rate approximates the theoretical maximum. Elasticity analysis indicates that adult survival is by far the biggest influence on rate of increase and that a 9% reduction in survival from 96% is needed to stop the population growing. In contrast, at least 70% of mature females need to be sterilised to have a similar effect. In a benign environment, a population of large mammals such as camels is expected to grow exponentially until close to carrying capacity. This will frustrate control programs, because an ever-increasing number of animals will need to be removed for zero growth the longer that culling or harvesting effort is delayed. A population projection for 2008 suggests ~10 500 animals need to be harvested across the Northern Territory. Current harvests are well short of this. The ability of commercial harvesting to control camel populations in central Australia will depend on the value of animals, access to animals and the presence of alternative species to harvest when camels are at low density.
Estrogen receptor ESR1 controls cell migration by repressing chemokine receptor CXCR4 in the zebrafish posterior lateral line system
Authors: Gamba Laurent , Cubedo Nicolas , Ghysen Alain , Lutfalla Georges , Dambly-Chaudière Christine
Published: March 2010

The primordium that generates the embryonic posterior lateral line of zebrafish migrates from the head to the tip of the tail along a trail of SDF1-producing cells. This migration critically depends on the presence of the SDF1 receptor CXCR4 in the leading region of the primordium and on the presence of a second SDF1 receptor, CXCR7, in the trailing region of the primordium. Here we show that inactivation of the estrogen receptor ESR1 results in ectopic expression ofcxcr4bthroughout the primordium, whereas ESR1 overexpression results in a reciprocal reduction in the domain ofcxcr4bexpression, suggesting that ESR1 acts as a repressor ofcxcr4b. This finding could explain why estrogens significantly decrease the metastatic ability of ESR-positive breast cancer cells. ESR1 inactivation also leads to extinction ofcxcr7bexpression in the trailing cells of the migrating primordium; this effect is indirect, however, and due to the down-regulation ofcxcr7bby ectopic SDF1/CXCR4 signaling in the trailing region. Both ESR1 inactivation and overexpression result in aborted migration, confirming the importance of this receptor in the control of SDF1-dependent migration.
xCT deficiency accelerates chemically induced tumorigenesis
Authors: Nabeyama Ami , Kurita Ai , Asano Kenichi , Miyake Yasunobu , Yasuda Takuwa , Miura Ikuo , Nishitai Gen , Arakawa Satoko , Shimizu Shigeomi , Wakana Shigeharu , Yoshida Hisahiro , Tanaka Masato
Published: March 2010

During the course of inflammation and its resolution, macrophages are exposed to various cytotoxic materials, including reactive oxygen species. Thus, macrophages require a protective machinery against oxidative stress to survive at the inflammatory site. Here, we showed that xCT, a component of transport system xc−, was significantly up-regulated in activated infiltrating cells, including macrophages and neutrophils at the inflammatory site. System xc−mediates the uptake of extracellular L-cystine and is consequently responsible for maintenance of intracellular glutathione levels. We established a loss-of-function mouse mutant line of xCT by N-ethyl-N-nitrosourea mutagenesis. Macrophages from xCTmu/mumice showed cell death in association with the excessive release of high mobility group box chromosomal protein 1 upon stimulation with LPS, suggesting that xCT deficiency causes unremitting inflammation because of the impaired survival of activated macrophages at the inflammatory site. Subcutaneous injection of 3-methylcholanthrene (3-MCA) induced the generation of fibrosarcoma in association with inflammation. When 3-MCA was injected s.c. into mice, xCT mRNA was up-regulated in situ. In xCTmu/mumice, inflammatory cytokines (such as IL-1β and TNFα) were overexpressed, and the generation of 3-MCA-induced fibrosarcoma was accelerated. These results clearly indicate that the defect of the protective system against oxidative stress impaired survival of activated macrophages and subsequently enhanced tumorigenecity.
Imaging extrasynaptic glutamate dynamics in the brain
Authors: Okubo Yohei , Sekiya Hiroshi , Namiki Shigeyuki , Sakamoto Hirokazu , Iinuma Sho , Yamasaki Miwako , Watanabe Masahiko , Hirose Kenzo , Iino Masamitsu
Published: March 2010

Glutamate is the major neurotransmitter in the brain, mediating point-to-point transmission across the synaptic cleft in excitatory synapses. Using a glutamate imaging method with fluorescent indicators, we show that synaptic activity generates extrasynaptic glutamate dynamics in the vicinity of active synapses. These glutamate dynamics had magnitudes and durations sufficient to activate extrasynaptic glutamate receptors in brain slices. We also observed crosstalk between synapses—i.e., summation of glutamate released from neighboring synapses. Furthermore, we successfully observed that sensory input from the extremities induced extrasynaptic glutamate dynamics within the appropriate sensory area of the cerebral cortex in vivo. Thus, the present study clarifies the spatiotemporal features of extrasynaptic glutamate dynamics, and opens up an avenue to directly visualizing synaptic activity in live animals.
HR23B is a biomarker for tumor sensitivity to HDAC inhibitor-based therapy
Authors: Khan Omar , Fotheringham Susan , Wood Victoria , Stimson Lindsay , Zhang Chunlei , Pezzella Francesco , Duvic Madeleine , Kerr David J. , La Thangue Nicholas B.
Published: March 2010

Histone deacetylase (HDAC) inhibitors are emergent cancer drugs. HR23B is a candidate cancer biomarker identified in a genome-wide loss-of-function screen which influences sensitivity to HDAC inhibitors. Because HDAC inhibitors have found clinical utility in cutaneous T-cell lymphoma (CTCL), we evaluated the role of HR23B in CTCL cells. Our results show that HR23B governs the sensitivity of CTCL cells to HDAC inhibitors. Furthermore, proteasome activity is deregulated in HDAC inhibitor-treated CTCL cells through a mechanism dependent upon HR23B, and HDAC inhibitors sensitize CTCL cells to the effects of proteasome inhibitors. The predictive power of HR23B for clinical response to HDAC inhibitors was investigated through an analysis of a unique collection of CTCL biopsies taken from a phase II clinical trial, where there was a frequent coincidence between HR23B expression and clinical response to HDAC inhibitor. Our study supports the personalized medicine approach for treating cancer and the increasing drive to translate laboratory-based findings into clinical utility.
Inducible gene expression from the plastid genome by a synthetic riboswitch
Authors: Verhounig Andreas , Karcher Daniel , Bock Ralph
Published: March 2010

Riboswitches are natural RNA sensors that regulate gene expression in response to ligand binding. Riboswitches have been identified in prokaryotes and eukaryotes but are unknown in organelles (mitochondria and plastids). Here we have tested the possibility to engineer riboswitches for plastids (chloroplasts), a genetic system that largely relies on translational control of gene expression. To this end, we have used bacterial riboswitches and modified them
in silico
to meet the requirements of translational regulation in plastids. These engineered switches were then tested for functionality in vivo by stable transformation of the tobacco chloroplast genome. We report the identification of a synthetic riboswitch that functions as an efficient translational regulator of gene expression in plastids in response to its exogenously applied ligand theophylline. This riboswitch provides a novel tool for plastid genome engineering that facilitates the tightly regulated inducible expression of chloroplast genes and transgenes and thus has wide applications in functional genomics and biotechnology.
Transmission distortion by loss of p21 or p27 cyclin-dependent kinase inhibitors following competitive spermatogonial transplantation
Authors: Kanatsu-Shinohara Mito , Takashima Seiji , Shinohara Takashi
Published: March 2010

Spermatogonial stem cells (SSCs) undergo self-renewal division to support spermatogenesis. Although several positive regulators of SSC self-renewal have been identified, little is known about the mechanisms that negatively regulate SSCs. Here we developed a novel transplantation assay for SSCs and demonstrate that p21 and p27 cyclin-dependent kinase inhibitors play critical roles in SSC self-renewal and differentiation. Overexpression of p21 or p27 abrogated proliferation of cultured SSCs in vitro, and their expression levels were downregulated by exogenous self-renewal signals. In contrast, no apparent defects were found in p21 or p27-deficient SSCs by spermatogonial transplantation. However, competitive spermatogonial transplantation with WT SSCs revealed that the loss of either gene causes distortion of germline transmission: p21-deficiency facilitated mutant offspring production, whereas germline transmission was limited by p27-deficiency. Serial transplantation also showed that the loss of p27, but not p21, decreases secondary colony formation, suggesting that appropriate amounts of p27 are necessary for sustaining SSC self-renewal. Thus, p21 and p27 cyclin-dependent kinase inhibitors play critical roles in germline transmission by regulating the balance between SSC self-renewal and differentiation, and competitive spermatogonial transplantation technique will be useful for analyzing subtle defects in spermatogenesis that are not evident by traditional spermatogonial transplantation.
UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production
Authors: Becklund Bryan R. , Severson Kyle S. , Vang Souriya V. , DeLuca Hector F.
Published: March 2010

Although the exact cause of multiple sclerosis (MS) is unknown, a number of genetic and environmental factors are thought to influence MS susceptibility. One potential environmental factor is sunlight and the subsequent production of vitamin D. A number of studies have correlated decreased exposure to UV radiation (UVR) and low serum 25-hydroxyvitamin D3[25(OH)D3] levels with an increased risk for developing MS. Furthermore, both UVR and the active form of vitamin D, 1α,25-dihydroxyvitamin D3, suppress disease in the experimental autoimmune encephalomyelitis (EAE) animal model of MS. These observations led to the hypothesis that UVR likely suppresses disease through the increased production of vitamin D. However, UVR can suppress the immune system independent of vitamin D. Therefore, it is unclear whether UVR, vitamin D, or both are necessary for the putative decrease in MS susceptibility. We have probed the ability of UVR to suppress disease in the EAE model of MS and assessed the effect of UVR on serum 25(OH)D3and calcium levels. Our results indicate that continuous treatment with UVR dramatically suppresses clinical signs of EAE. Interestingly, disease suppression occurs with only a modest, transient increase in serum 25(OH)D3levels. Further analysis demonstrated that the levels of 25(OH)D3obtained upon UVR treatment were insufficient to suppress EAE independent of UVR treatment. These results suggest that UVR is likely suppressing disease independent of vitamin D production, and that vitamin D supplementation alone may not replace the ability of sunlight to reduce MS susceptibility.