448 research outputs found

    Heat conduction of (111) Co/Cu superlattices

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    We report the observation of a large negative magnetothermal resistance in (111) Co/Cu superlattices grown by molecular beam epitaxy (MBE) techniques. The observed field dependence is proportional to that of the electrical resistance, in accordance with the Wiedemannā€“Franz law. The Lorentz number deduced from the measurements is (2.7Ā±0.3)Ɨ10āˆ’8ā€‚V2/K2(2.7Ā±0.3)Ɨ10āˆ’8V2/K2. The magnetothermopower also shows a similar correlation with resistivity. These findings reveal that large-angle elastic scattering of conduction electrons, arising from a spin-dependent density of states at the Fermi level, is the dominant process responsible for the observed large magnetotransport effects. In zero field, both electrons and phonons contribute to the thermal conduction of the MBE-grown Co/Cu system, at a ratio of about 1:2 near 300 K becoming nearly equal below 150 K. Ā© 1997 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70031/2/JAPIAU-81-8-4586-1.pd

    Techniques for combinatorial molecular beam epitaxy

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    Basic considerations for implementing combinatorial approach to molecular beam epitaxy (MBE) are discussed, focusing on the key issues relevant to conventional MBE synthesis using solid sources and characterization. The primary objective for implementing combinatorial approach is to make MBE do more, more able to carry out controlled and systematic work in large parameter space, without sacrificing any existing capabilities of conventional MBE. Methods for accomplishing this by integrating current instrumentation technology are described

    Structureā€“Activity Relationship Study Reveals ML240 and ML241 as Potent and Selective Inhibitors of p97 ATPase

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    To discover more potent p97 inhibitors, we carried out a structureā€“activity relationship study of the quinazoline scaffold previously identified from our HTS campaigns. Two improved inhibitors, ML240 and ML241, inhibit p97 ATPase with IC_(50) values of 100 nM. Both compounds inhibited degradation of a p97-dependent but not a p97-independent proteasome substrate in a dual-reporter cell line. They also impaired the endoplasmic-reticulum-associated degradation (ERAD) pathway. Unexpectedly, ML240 potently stimulated accumulation of LC3-II within minutes, inhibited cancer cell growth, and rapidly mobilized the executioner caspases 3 and 7, whereas ML241 did not. The behavior of ML240 suggests that disruption of the protein homeostasis function of p97 leads to more rapid activation of apoptosis than is observed with a proteasome inhibitor. Further characterization revealed that ML240 has broad antiproliferative activity toward the NCI-60 panel of cancer cell lines, but slightly lower activity toward normal cells. ML240 also synergizes with the proteasome inhibitor MG132 to kill multiple colon cancer cell lines. Meanwhile, both probes have low off-target activity toward a panel of protein kinases and central nervous system targets. Our results nominate ML240 as a promising starting point for the development of a novel agent for the chemotherapy of cancer, and provide a rationale for developing pathway-specific p97 inhibitors

    Epitaxial growth of CoxMnySiz (111) thin films in the compositional range around the Heusler alloy Co2MnSi

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    Epitaxial growth and structural properties of CoxMnySiz thin films on Ge (111) substrates, including the Heusler alloy Co2MnSi (111), have been studied using combinatorial molecular beam epitaxy (MBE) techniques. In situ reflection high energy electron diffraction and ex situ x-ray diffraction experiments show that high quality coherent MBE growth with fcc (111) stacking can be achieved over a relatively large composition space that includes Co2MnSi. The highest structural and chemical ordering is observed near the composition of Co0.63Mn0.14Si0.23 rather than that at the Heusler stoichiometry of Co2MnSi. The in-plane crystallographic axis of the fcc film exhibits a 60Ā° rotation with respect to that of the Ge substrate. The rotation appears to be originated at the film-substrate interface, as a result of the symmetry and stacking of the Ge (111) surface reconstruction

    Heat conduction in Ba 1āˆ’x K x BiO 3

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    We have investigated heat conduction of single crystal Ba 1āˆ’x K x BiO 3 in the temperature range of 2ā€“300 K and in a magnetic field of up to 6 Tesla. Temperature dependence of thermal conductivity Īŗ(T) reveals the participation of both electrons and phonons with their relative contributions that depend critically on the potassium doping concentration. Crystals underdoped with potassium (samples with higher T c ) exhibit a strong suppression of Īŗ and a glass-like temperature dependence. In contrast, those with a higher potassium content (lower T c ) show an increase as temperature decreases with a peak near 23 K. Field dependence of Īŗ(H) is also very sensitive to the level of potassium doping. Crystals exhibiting a large phonon contribution show an initial drop in Īŗ(H) at low fields followed by a minimum and then a slow rise to saturation as the field increases. The initial drop is due to the additional phonon scattering by magnetic vortices as the sample enters a mixed state. The high field behavior of Īŗ(H) , arising from a continuous break-up of Cooper pairs, exhibits scaling which suggests the presence of an unconventional superconducting gap structure in this material.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45123/1/10948_2004_Article_BF00722826.pd

    The maize (Zea mays L.) roothairless3 gene encodes a putative GPI-anchored, monocot-specific, COBRA-like protein that significantly affects grain yield

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    The rth3 (roothairless 3) mutant is specifically affected in root hair elongation. We report here the cloning of the rth3 gene via a PCR-based strategy (amplification of insertion mutagenized sites) and demonstrate that it encodes a COBRA-like protein that displays all the structural features of a glycosylphosphatidylinositol anchor. Genes of the COBRA family are involved in various types of cell expansion and cell wall biosynthesis. The rth3 gene belongs to a monocot-specific clade of the COBRA gene family comprising two maize and two rice genes. While the rice (Oryza sativa) gene OsBC1L1 appears to be orthologous to rth3 based on sequence similarity (86% identity at the protein level) and maize/rice synteny, the maize (Zea mays L.) rth3-like gene does not appear to be a functional homolog of rth3based on their distinct expression profiles. Massively parallel signature sequencing analysis detected rth3 expression in all analyzed tissues, but at relatively low levels, with the most abundant expression in primary roots where the root hair phenotype is manifested.In situ hybridization experiments confine rth3 expression to root hair-forming epidermal cells and lateral root primordia. Remarkably, in replicated field trials involving near-isogenic lines, the rth3 mutant conferred significant losses in grain yield

    Semi-structured Interview to Analyse Needs of Family Caregivers for People with Dementia

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    Background: Globally, our population is aging. The prevalence of dementia increases dramatically with advancing age. Caring for a person living with dementia affects different people in different ways. Objectives: In response, this research study was conducted to explore the role, needs and stress of family caregivers (FCGs) for people with dementia as a means of understanding their experience of caring. The study also targeted to identify coping strategies employed by FCGs and explore positive aspects of the caring relationship in relation to their quality of life, information needs, day care and respite care, and emotional support.Methods: To measure individualsā€™ uniqueness and their specificity in their care-giving experience, this study employed qualitative research design, through semi-structure interview (SSI) as research methods to explore the grounded theory on role, needs and stress of caregivers. The needs of caregivers were documented under their continuum of care: seeking understanding, stabilization, preparation, implementation and adaptation. Results: Twenty FCG were recruited through purposeful sampling. Results indicated caregiving to dementia is a very demanding task both mentally and physically. Two main categories were formulated from the data: the impact of caring and the need to support their caregivers' role. The need to develop understanding of the effectiveness of specific health and social care interventions showed as highly important. Conclusion: Individualsā€™ perspectives need to be integrated into future service planning and decision-making processes. Suggested strategies from FCGā€™ perspectives that can potentially alleviating their care stress would be illustrated

    Roothairless5, which functions in maize (Zea mays L.) root hair initiation and elongation encodes a monocot-specific NADPH oxidase

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    Citation: Nestler, J., Liu, S., Wen, T. -., Paschold, A., Marcon, C., Tang, H. M., et al. (2014). Roothairless5, which functions in maize (zea mays L.) root hair initiation and elongation encodes a monocot-specific NADPH oxidase. Retrieved from krex.k-state.edu.Root hairs are instrumental for nutrient uptake in monocot cereals. The maize (Zea mays L.) roothairless5 (rth5) mutant displays defects in root hair initiation and elongation manifested by a reduced density and length of root hairs. Map-based cloning revealed that the rth5 gene encodes a monocot-specific NADPH oxidase. RNA-Seq, in situ hybridization and qRT-PCR experiments demonstrated that the rth5 gene displays preferential expression in root hairs but also accumulates to low levels in other tissues. Immunolocalization detected RTH5 proteins in the epidermis of the elongation and differentiation zone of primary roots. Because superoxide and hydrogen peroxide levels are reduced in the tips of growing rth5 mutant root hairs as compared to wild-type, and ROS is known to be involved in tip growth, we hypothesize that the RTH5 protein is responsible for establishing the high levels of ROS in the tips of growing root hairs required for elongation. Consistent with this hypothesis, a comparative RNA-Seq analysis of 6-day-old rth5 versus wild-type primary roots, revealed significant over-representation of only two gene ontology (GO) classes related to the biological functions (i.e., oxidation/reduction and carbohydrate metabolism) among 893 differentially expressed genes (FDR <5%). Within these two classes the subgroups ā€œresponse to oxidative stressā€ and ā€œcellulose biosynthesisā€ were most prominently represented

    Specific Inhibition of p97/VCP ATPase and Kinetic Analysis Demonstrate Interaction between D1 and D2 ATPase domains

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    The p97 AAA (ATPase associated with diverse cellular activities), also called VCP (valosin-containing protein), is an important therapeutic target for cancer and neurodegenerative diseases. p97 forms a hexamer composed of two AAA domains (D1 and D2) that form two stacked rings, and an N-terminal domain that binds numerous cofactor proteins. The interplay between the three domains in p97 is complex, and a deeper biochemical understanding is needed in order to design selective p97 inhibitors as therapeutic agents. It is clear that the D2 ATPase domain hydrolyzes ATP in vitro, but whether D1 contributes to ATPase activity is controversial. Here, we use Walker A and B mutants to demonstrate that D1 is capable of hydrolyzing ATP, and show for the first time that nucleotide binding in the D2 domain increases the catalytic efficiency (k_(cat)/K_m) of D1 ATP hydrolysis 280-fold, by increasing k_(cat) 7-fold and decreasing K_m about 40-fold. We further show that an ND1 construct lacking D2 but including the linker between D1 and D2 is catalytically active, resolving a conflict in the literature. Applying enzymatic observations to small-molecule inhibitors, we show that four p97 inhibitors (DBeQ, ML240, ML241, and NMS-873) have differential responses to Walker A and B mutations, to disease-causing IBMPFD mutations, and to the presence of the N-domain binding cofactor protein p47. These differential effects provide the first evidence that p97 cofactors and disease mutations can alter p97 inhibitor potency and suggest the possibility of developing context-dependent inhibitors of p97

    Specific Inhibition of p97/VCP ATPase and Kinetic Analysis Demonstrate Interaction between D1 and D2 ATPase domains

    Get PDF
    The p97 AAA (ATPase associated with diverse cellular activities), also called VCP (valosin-containing protein), is an important therapeutic target for cancer and neurodegenerative diseases. p97 forms a hexamer composed of two AAA domains (D1 and D2) that form two stacked rings, and an N-terminal domain that binds numerous cofactor proteins. The interplay between the three domains in p97 is complex, and a deeper biochemical understanding is needed in order to design selective p97 inhibitors as therapeutic agents. It is clear that the D2 ATPase domain hydrolyzes ATP in vitro, but whether D1 contributes to ATPase activity is controversial. Here, we use Walker A and B mutants to demonstrate that D1 is capable of hydrolyzing ATP, and show for the first time that nucleotide binding in the D2 domain increases the catalytic efficiency (kcat/Km) of D1 ATP hydrolysis 280-fold, by increasing kcat 7-fold and decreasing Km about 40-fold. We further show that an ND1 construct lacking D2 but including the linker between D1 and D2 is catalytically active, resolving a conflict in the literature. Applying enzymatic observations to small-molecule inhibitors, we show that four p97 inhibitors (DBeQ, ML240, ML241, and NMS-873) have differential responses to Walker A and B mutations, to disease-causing IBMPFD mutations, and to the presence of the N-domain binding cofactor protein p47. These differential effects provide the first evidence that p97 cofactors and disease mutations can alter p97 inhibitor potency and suggest the possibility of developing context-dependent inhibitors of p97
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