1,171 research outputs found
Amyloid positron emission tomography candidates may focus more on benefits than risks of results disclosure
IntroductionGiven mounting calls to disclose biomarker test results to research participants, we explored factors underlying decisions by patients with mild cognitive impairment to receive amyloid imaging results.MethodsProspective, qualitative interviews were conducted with 59 participants (30 = mild cognitive impairment patients, 29 = care partners) from the scan arm of a randomized controlled trial on the effects of amyloid PET results disclosure in an Alzheimer Disease Research Center setting.ResultsSixty‐three percent of the participants were female, with an average age of 72.9 years, and most had greater than a high school level of education (80%). Primary motivations included: (1) better understanding one’s mild cognitive impairment etiology and prognosis to plan ahead, and (2) learning one’s brain amyloid status for knowledge’s sake, regardless of whether the information is actionable. Most participants demonstrated an adequate understanding of the scan’s limitations, yet instances of characterizing amyloid PET as a definitive test for Alzheimer’s disease occurred. Mention of potential drawbacks, such as negative psychological outcomes, was minimal, even among care partners.DiscussionFindings demonstrate a risk of disproportionate focus on possible benefits of testing among amyloid scan candidates and suggest a need to clearly emphasize the limitations of amyloid PET when counseling cognitively impaired patients and their families before testing. Future research should examine whether minimizing drawbacks at the pre‐imaging stage has adverse consequences on results disclosure.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152635/1/dad2jdadm201805003.pd
Perturbation of the Hematopoietic System during Embryonic Liver Development Due to Disruption of Polyubiquitin Gene Ubc in Mice
Disruption of the polyubiquitin gene Ubc leads to a defect in fetal liver development, which can be partially rescued by increasing the amount of ubiquitin. However, it is still not known why Ubc is required for fetal liver development and the nature of the defective cell types responsible for embryonic lethality have not been characterized. In this study, we assessed the cause of embryonic lethality with respect to the fetal liver hematopoietic system. We found that Ubc was highly expressed in the embryonic liver, and the proliferation capacity of fetal liver cells was reduced in Ubc−/− embryos. Specifically, Ubc was most highly expressed in hematopoietic cells, and the proliferation capacity of hematopoietic cells was significantly impaired in Ubc−/− embryos. While hematopoietic cell and hematopoietic stem cell (HSC) frequency was maintained in Ubc−/− embryos, the absolute number of these cells was diminished because of reduced total liver cell number in Ubc−/− embryos. Transplantations of fetal liver cells into lethally irradiated recipient mice by non-competitive and competitive reconstitution methods indicated that disruption of Ubc does not significantly impair the intrinsic function of fetal liver HSCs. These findings suggest that disruption of Ubc reduces the absolute number of HSCs in embryonic livers, but has no significant effect on the autonomous function of HSCs. Thus, the lethality of Ubc−/− embryos is not the result of intrinsic HSC failure
The Price of Anarchy in Transportation Networks: Efficiency and Optimality Control
Uncoordinated individuals in human society pursuing their personally optimal
strategies do not always achieve the social optimum, the most beneficial state
to the society as a whole. Instead, strategies form Nash equilibria which are
often socially suboptimal. Society, therefore, has to pay a price of anarchy
for the lack of coordination among its members. Here we assess this price of
anarchy by analyzing the travel times in road networks of several major cities.
Our simulation shows that uncoordinated drivers possibly waste a considerable
amount of their travel time. Counterintuitively,simply blocking certain streets
can partially improve the traffic conditions. We analyze various complex
networks and discuss the possibility of similar paradoxes in physics.Comment: major revisions with multicommodity; Phys. Rev. Lett., accepte
クラリスロマイシンはインフルエンザAウイルスに感染したマウスにおいて、monocyte chemoattractant protein-1とmatrix metalloproteinase-9の発現誘導を抑制し、肺と心臓における病理学的変化を改善する
The influenza A virus (IAV)–cytokine–trypsin/matrix metalloproteinase-9 (MMP-9) cycle is one of the important mechanisms of multiple organ failure in severe influenza. Clarithromycin, a macrolide antibiotic, has immune modulatory and anti-inflammatory effects. We analyzed the effects of clarithromycin on the induction of chemokines, cytokines, MMP-9, trypsin, vascular hyper-permeability and inflammatory aggravation in mice with IAV infection. IAV/Puerto Rico/8/34(H1N1) infection increased the levels of monocyte chemoattractant protein- 1 (MCP-1) and cytokines in serum, and MMP-9 and trypsin in serum and/or the lungs and heart. Clarithromycin significantly suppressed the induction of serum MCP-1 and MMP-9 and vascular hyperpermeability in these organs in the early phase of infection, but did not suppress the induction of trypsin, IL-6 or IFN-γ. Histopathological examination showed that clarithromycin tended to reduce inflammatory cell accumulation in the lungs and heart. These results suggest that clarithromycin suppresses infection-related inflammation and reduces vascular hyperpermeability by suppressing the induction of MCP-1 and MMP-9
Electric Field-Tuned Topological Phase Transition in Ultra-Thin Na3Bi - Towards a Topological Transistor
The electric field induced quantum phase transition from topological to
conventional insulator has been proposed as the basis of a topological field
effect transistor [1-4]. In this scheme an electric field can switch 'on' the
ballistic flow of charge and spin along dissipationless edges of the
two-dimensional (2D) quantum spin Hall insulator [5-9], and when 'off' is a
conventional insulator with no conductive channels. Such as topological
transistor is promising for low-energy logic circuits [4], which would
necessitate electric field-switched materials with conventional and topological
bandgaps much greater than room temperature, significantly greater than
proposed to date [6-8]. Topological Dirac semimetals(TDS) are promising systems
in which to look for topological field-effect switching, as they lie at the
boundary between conventional and topological phases [3,10-16]. Here we use
scanning probe microscopy/spectroscopy (STM/STS) and angle-resolved
photoelectron spectroscopy (ARPES) to show that mono- and bilayer films of TDS
Na3Bi [3,17] are 2D topological insulators with bulk bandgaps >400 meV in the
absence of electric field. Upon application of electric field by doping with
potassium or by close approach of the STM tip, the bandgap can be completely
closed then re-opened with conventional gap greater than 100 meV. The large
bandgaps in both the conventional and quantum spin Hall phases, much greater
than the thermal energy kT = 25 meV at room temperature, suggest that ultrathin
Na3Bi is suitable for room temperature topological transistor operation
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Developing multiscale and integrative nature–people scenarios using the Nature Futures Framework
1. Scientists have repeatedly argued that transformative, multiscale global scenarios are needed as tools in the quest to halt the decline of biodiversity and achieve sustainability goals.
2. As a first step towards achieving this, the researchers who participated in the scenarios and models expert group of the Intergovernmental Science‐Policy Platform on Biodiversity and Ecosystem Services (IPBES) entered into an iterative, participatory process that led to the development of the Nature Futures Framework (NFF).
3. The NFF is a heuristic tool that captures diverse, positive relationships of humans with nature in the form of a triangle. It can be used both as a boundary object for continuously opening up more plural perspectives in the creation of desirable nature scenarios and as an actionable framework for developing consistent nature scenarios across multiple scales.
4. Here we describe the methods employed to develop the NFF and how it fits into a longer term process to create transformative, multiscale scenarios for nature. We argue that the contribution of the NFF is twofold: (a) its ability to hold a plurality of perspectives on what is desirable, which enables the development of joint goals and visions and recognizes the possible convergence and synergies of measures to achieve these visions and (b), its multiscale functionality for elaborating scenarios and models that can inform decision‐making at relevant levels, making it applicable across specific places and perspectives on nature.
5. If humanity is to achieve its goal of a more sustainable and prosperous future rooted in a flourishing nature, it is critical to open up a space for more plural perspectives of human–nature relationships. As the global community sets out to develop new goals for biodiversity, the NFF can be used as a navigation tool helping to make diverse, desirable futures possible
Discovery of Novel Human Breast Cancer MicroRNAs from Deep Sequencing Data by Analysis of Pri-MicroRNA Secondary Structures
MicroRNAs (miRNAs) are key regulators of gene expression and contribute to a
variety of biological processes. Abnormal miRNA expression has been reported in
various diseases including pathophysiology of breast cancer, where they regulate
protumorigenic processes including vascular invasiveness, estrogen receptor
status, chemotherapy resistance, invasion and metastasis. The miRBase sequence
database, a public repository for newly discovered miRNAs, has grown rapidly
with approximately >10,000 entries to date. Despite this rapid growth, many
miRNAs have not yet been validated, and several others are yet to be identified.
A lack of a full complement of miRNAs has imposed limitations on recognizing
their important roles in cancer, including breast cancer. Using deep sequencing
technology, we have identified 189 candidate novel microRNAs in human breast
cancer cell lines with diverse tumorigenic potential. We further show that
analysis of 500-nucleotide pri-microRNA secondary structure constitutes a
reliable method to predict bona fide miRNAs as judged by experimental
validation. Candidate novel breast cancer miRNAs with stem lengths of greater
than 30 bp resulted in the generation of precursor and mature sequences
in vivo. On the other hand, candidates with stem length
less than 30 bp were less efficient in producing mature miRNA. This approach may
be used to predict which candidate novel miRNA would qualify as bona fide miRNAs
from deep sequencing data with approximately 90% accuracy
Developing multiscale and integrative nature–people scenarios using the Nature Futures Framework
1. Scientists have repeatedly argued that transformative, multiscale global scenarios
are needed as tools in the quest to halt the decline of biodiversity and achieve
sustainability goals.
2. As a first step towards achieving this, the researchers who participated in the
scenarios and models expert group of the Intergovernmental Science-Policy
Platform on Biodiversity and Ecosystem Services (IPBES) entered into an iterative,
participatory process that led to the development of the Nature Futures Framework
(NFF).
3. The NFF is a heuristic tool that captures diverse, positive relationships of humans
with nature in the form of a triangle. It can be used both as a boundary object
for continuously opening up more plural perspectives in the creation of desirable
nature scenarios and as an actionable framework for developing consistent nature
scenarios across multiple scales.
4. Here we describe the methods employed to develop the NFF and how it fits into a
longer term process to create transformative, multiscale scenarios for nature. We
argue that the contribution of the NFF is twofold: (a) its ability to hold a plurality
of perspectives on what is desirable, which enables the development of joint goals
and visions and recognizes the possible convergence and synergies of measures to
achieve these visions and (b), its multiscale functionality for elaborating scenarios
and models that can inform decision-making at relevant levels, making it applicable
across specific places and perspectives on nature.
5. If humanity is to achieve its goal of a more sustainable and prosperous future
rooted in a flourishing nature, it is critical to open up a space for more plural per-
spectives of human–nature relationships. As the global community sets out to de-
velop new goals for biodiversity, the NFF can be used as a navigation tool helping
to make diverse, desirable futures possible
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