526 research outputs found
On the -th smallest modulus of a covering system with distinct moduli
Covering systems were introduced by Erd\H{o}s in 1950. In the same article
where he introduced them, he asked if the minimum modulus of a covering system
with distinct moduli is bounded. In 2015, Hough answered affirmatively this
long standing question. In 2022, Balister, Bollob\'as, Morris, Sahasrabudhe and
Tiba gave a simpler and more versatile proof of Hough's result. Building upon
their work, we show that there exists some absolute constant such that
the -th smallest modulus of a minimal covering system with distinct moduli
is .Comment: 8 pages, minor corrections and changes. Final version, to appear in
Int. J. Number Theor
Investigation On The Influence Of Remanufacturing On Production Planning And Control â A Systematic Literature Review
Production planning and control (PPC) is one of the focal operational tasks of a company, and it is used to design logistics services in a target-orientated manner so that individual customer requirements can be fulfilled. However, existing PPC framework models are still based on the prevailing linear economic procedure (take - make - dispose). Due to customers' increasing interest in sustainability and growing regulatory pressure, the Circular Economy (CE) meets these changing conditions by closing material cycles, improving resource efficiency and extending product life cycles. However, for a company to guarantee a high logistics performance, the operational PPC must be adapted to this new economic model. To this end, it needs to be investigated whether and how the adaptation of circular strategies influences existing PPC processes.
This paper focuses on the circular strategy of remanufacturing and its influence on different PPC-main tasks. The latter will be examined using a systematic literature review. Finally, the results of this analysis are compared with the Hanoverian Supply Chain Model as a PPC framework model. This comparison shows which PPC tasks are affected and which existing approaches have already been developed. Ultimately, these results provide the basis for developing a framework model for operational PPC regarding the CE
Single copy/knock-in models of ALS SOD1 in C. elegans suggest loss and gain of function have different contributions to cholinergic and glutamatergic neurodegeneration
Mutations in Cu/Zn superoxide dismutase 1 (SOD1) lead to Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease that disproportionately affects glutamatergic and cholinergic motor neurons. Previous work with SOD1 overexpression models supports a role for SOD1 toxic gain of function in ALS pathogenesis. However, the impact of SOD1 loss of function in ALS cannot be directly examined in overexpression models. In addition, overexpression may obscure the contribution of SOD1 loss of function in the degeneration of different neuronal populations. Here, we report the first single-copy, ALS knock-in models in C. elegans generated by transposon- or CRISPR/Cas9- mediated genome editing of the endogenous sod-1 gene. Introduction of ALS patient amino acid changes A4V, H71Y, L84V, G85R or G93A into the C. elegans sod-1 gene yielded single-copy/knock-in ALS SOD1 models. These differ from previously reported overexpression models in multiple assays. In single-copy/knock-in models, we observed differential impact of sod-1 ALS alleles on glutamatergic and cholinergic neurodegeneration. A4V, H71Y, G85R, and G93A animals showed increased SOD1 protein accumulation and oxidative stress induced degeneration, consistent with a toxic gain of function in cholinergic motor neurons. By contrast, H71Y, L84V, and G85R lead to glutamatergic neuron degeneration due to sod-1 loss of function after oxidative stress. However, dopaminergic and serotonergic neuronal populations were spared in single-copy ALS models, suggesting a neuronal-subtype specificity previously not reported in invertebrate ALS SOD1 models. Combined, these results suggest that knock-in models may reproduce the neurotransmitter-type specificity of ALS and that both SOD1 loss and gain of toxic function differentially contribute to ALS pathogenesis in different neuronal populations.Peer reviewe
Myelination of neuronal cell bodies when myelin supply exceeds axonal demand
The correct targeting of myelin is essential for nervous system formation and function. Oligodendrocytes in the CNS myelinate some axons, but not others, and do not myelinate structures including cell bodies and dendrites [1]. Recent studies indicate that extrinsic signals, such as neuronal activity [2, 3] and cell adhesion molecules [4], can bias myelination toward some axons and away from cell bodies and dendrites, indicating that, in vivo, neuronal and axonal cues regulate myelin targeting. In vitro, however, oligodendrocytes have an intrinsic propensity to myelinate [5-7] and can promiscuously wrap inert synthetic structures resembling neuronal processes [8, 9] or cell bodies [4]. A current therapeutic goal for the treatment of demyelinating diseases is to greatly promote oligodendrogenesis [10-13]; thus, it is important to test how accurately extrinsic signals regulate the oligodendrocyte's intrinsic program of myelination in vivo. Here, we test the hypothesis that neurons regulate myelination with sufficient stringency to always ensure correct targeting. Surprisingly, however, we find that myelin targeting in vivo is not very stringent and that mistargeting occurs readily when oligodendrocyte and myelin supply exceed axonal demand. We find that myelin is mistargeted to neuronal cell bodies in zebrafish mutants with fewer axons and independently in drug-treated zebrafish with increased oligodendrogenesis. Additionally, by increasing myelin production of oligodendrocytes in zebrafish and mice, we find that excess myelin is also inappropriately targeted to cell bodies. Our results suggest that balancing oligodendrocyte-intrinsic programs of myelin supply with axonal demand is essential for correct myelin targeting in vivo and highlight potential liabilities of strongly promoting oligodendrogenesis
Behavioral Health in Rural America: Understanding Citizen Perceptions and Willingness to Respond to Community Needs
Amid nationwide efforts to address behavioral health needs, rural communities often face unique challenges and a lack of resources. This study presents a bottom-up approach used by one rural community in the Midwest to respond to their needs regarding mental health and substance use. A survey instrument was developed from interviews with community stakeholders and disseminated in both online and paper formats. The survey sought to understand citizen perspectives regarding quality of life, barriers to treatment, and willingness to engage in efforts to address the communityâs needs. Data from 1,303 respondents (71.5% women, 54.7% income \u3c$42,000) were analyzed using descriptive statistics and chi-square analyses. Results indicate that cost of treatment, shame, and lack of privacy were a barrier for most citizensâ treatment-seeking behavior. In addition, many citizens were willing to engage in strategies to address the communityâs needs, including increased county spending, forming a neighborhood watch, and donating money. Differences associated with gender and income emerged across perceptions and willingness to support efforts. Implications for community efforts are discussed
HLA-E-restricted, Gag-specific CD8+ T cells can suppress HIV-1 infection, offering vaccine opportunities
Human leukocyte antigen-E (HLA-E) normally presents an HLA class Ia signal peptide to the NKG2A/C-CD94 regulatory receptors on natural killer (NK) cells and T cell subsets. Rhesus macaques immunized with a cytomegalovirus-vectored simian immunodeficiency virus (SIV) vaccine generated Mamu-E (HLA-E homolog)-restricted T cell responses that mediated post-challenge SIV replication arrest in >50% of animals. However, HIV-1-specific, HLA-E-restricted T cells have not been observed in HIV-1-infected individuals. Here, HLA-E-restricted, HIV-1-specific CD8
+
T cells were primed in vitro. These T cell clones and allogeneic CD8
+
T cells transduced with their T cell receptors suppressed HIV-1 replication in CD4
+
T cells in vitro. Vaccine induction of efficacious HLA-E-restricted HIV-1-specific T cells should therefore be possible
Fourth Workshop on Sustainable Software for Science: Practice and Experiences (WSSSPE4)
This report records and discusses the Fourth Workshop on Sustainable Software
for Science: Practice and Experiences (WSSSPE4). The report includes a
description of the keynote presentation of the workshop, the mission and vision
statements that were drafted at the workshop and finalized shortly after it, a
set of idea papers, position papers, experience papers, demos, and lightning
talks, and a panel discussion. The main part of the report covers the set of
working groups that formed during the meeting, and for each, discusses the
participants, the objective and goal, and how the objective can be reached,
along with contact information for readers who may want to join the group.
Finally, we present results from a survey of the workshop attendees
The search for freedom in extreme sports: A phenomenological exploration
Participation in extreme sports is continuing to grow, yet there is still little understanding of participant motivations in such sports. The purpose of this paper is to report on one aspect of motivation in extreme sports, the search for freedom. The study utilized a hermeneutic phenomenological methodology. Fifteen international extreme sport participants who participated in sports such as BASE jumping, big wave surfing, extreme mountaineering, extreme skiing, rope free climbing and waterfall kayaking were interviewed about their experience of participating in an extreme sport. Results reveal six elements of freedom: freedom from constraints, freedom as movement, freedom as letting go of the need for control, freedom as the release of fear, freedom as being at one, and finally freedom as choice and responsibility. The findings reveal that motivations in extreme sport do not simply mirror traditional images of risk taking and adrenaline and that motivations in extreme sports also include an exploration of the ways in which humans seek fundamental human values. © 2013 Elsevier Ltd
Community Organizations: Changing the Culture in Which Research Software Is Developed and Sustained
Software is the key crosscutting technology that enables advances in
mathematics, computer science, and domain-specific science and engineering to
achieve robust simulations and analysis for science, engineering, and other
research fields. However, software itself has not traditionally received
focused attention from research communities; rather, software has evolved
organically and inconsistently, with its development largely as by-products of
other initiatives. Moreover, challenges in scientific software are expanding
due to disruptive changes in computer hardware, increasing scale and complexity
of data, and demands for more complex simulations involving multiphysics,
multiscale modeling and outer-loop analysis. In recent years, community members
have established a range of grass-roots organizations and projects to address
these growing technical and social challenges in software productivity,
quality, reproducibility, and sustainability. This article provides an overview
of such groups and discusses opportunities to leverage their synergistic
activities while nurturing work toward emerging software ecosystems
Catching Element Formation In The Act
Gamma-ray astronomy explores the most energetic photons in nature to address
some of the most pressing puzzles in contemporary astrophysics. It encompasses
a wide range of objects and phenomena: stars, supernovae, novae, neutron stars,
stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays
and relativistic-particle acceleration, and the evolution of galaxies. MeV
gamma-rays provide a unique probe of nuclear processes in astronomy, directly
measuring radioactive decay, nuclear de-excitation, and positron annihilation.
The substantial information carried by gamma-ray photons allows us to see
deeper into these objects, the bulk of the power is often emitted at gamma-ray
energies, and radioactivity provides a natural physical clock that adds unique
information. New science will be driven by time-domain population studies at
gamma-ray energies. This science is enabled by next-generation gamma-ray
instruments with one to two orders of magnitude better sensitivity, larger sky
coverage, and faster cadence than all previous gamma-ray instruments. This
transformative capability permits: (a) the accurate identification of the
gamma-ray emitting objects and correlations with observations taken at other
wavelengths and with other messengers; (b) construction of new gamma-ray maps
of the Milky Way and other nearby galaxies where extended regions are
distinguished from point sources; and (c) considerable serendipitous science of
scarce events -- nearby neutron star mergers, for example. Advances in
technology push the performance of new gamma-ray instruments to address a wide
set of astrophysical questions.Comment: 14 pages including 3 figure
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