178 research outputs found
Resonant instabilities mediated by drag and electrostatic interactions in laboratory and astrophysical dusty plasmas
Dusty plasmas are known to support a diverse range of instabilities,
including both generalizations of standard plasma instabilities and ones caused
by effects specific to dusty systems. It has been recently demonstrated that a
novel broad class of streaming instabilities, termed resonant drag
instabilities (RDIs), can be attributed to a particular resonance phenomenon
caused by defective eigenvalues of the linearized dust/fluid system. In this
work, it is demonstrated that this resonance phenomenon is not unique to RDIs
and can be used as a framework to understand a wider range of instabilities,
termed resonant instabilities. Particular attention is given to the filamentary
ionization instability seen in laboratory dusty plasmas and to the two-stream
instability. It is shown that, due to the commonalities in underlying physics
between the dust-ion-acoustic two-stream instability and the acoustic RDI,
these instabilities should be relevant in strongly overlapping regimes in
astrophysical dusty plasmas. It is proposed that a similar overlap in the
experimental accessibility of these modes (and of the filamentary instability)
allows for the possibility of experimental investigation of complex and
astrophysically relevant instability dynamics.Comment: 18 pages, 15 figure
EUV Debris Mitigation using Magnetic Nulls
Next generation EUV sources for photolithography use light produced by
laser-produced plasmas (LPP) from ablated tin droplets. A major challenge for
extending the lifetime of these devices is mitigating damage caused by
deposition of tin debris on the sensitive collection mirror. Especially
difficult to stop are high energy (up to 10 keV) highly charged tin ions
created in the plasma. Existing solutions include the use of stopping gas,
electric fields, and magnetic fields. One common configuration consists of a
magnetic field perpendicular to the EUV emission direction, but such a system
can result in ion populations that are trapped rather than removed. We
investigate a previously unconsidered mitigation geometry consisting of a
magnetic null by performing full-orbit integration of the ion trajectories in
an EUV system with realistic dimensions, and optimize the coil locations for
the null configuration. The magnetic null prevents a fraction of ions from
hitting the mirror comparable to that of the perpendicular field, but does not
trap any ions due to the chaotic nature of ion trajectories that pass close to
the null. This technology can potentially improve LPP-based EUV
photolithography system efficiency and lifetime, and may allow for a different,
more efficient formulation of buffer gas
Differential Effects of Bariatric Surgery and Caloric Restriction on Hepatic One-Carbon and Fatty Acid Metabolism
Weight loss interventions, including dietary changes, pharmacotherapy, or bariatric surgery, prevent many of the adverse consequences of obesity, and may also confer intervention-specific benefits beyond those seen with decreased weight alone. We compared the molecular effects of different interventions on liver metabolism to understand the mechanisms underlying these benefits. Male rats on a high-fat, high-sucrose diet underwent sleeve gastrectomy (SG) or intermittent fasting with caloric restriction (IF-CR), achieving equivalent weight loss. The interventions were compared t
Genetic analysis of four consanguineous multiplex families with inflammatory bowel disease
Background: Family studies support a genetic predisposition to inflammatory bowel diseases (IBD), but known genetic variants only partially explain the disease heritability. Families with multiple affected individuals potentially harbour rare and high-impact causal variants. Long regions of homozygosity due to recent inbreeding may increase the risk of individuals bearing homozygous loss-of-function variants. This study aimed to identify rare and homozygous genetic variants contributing to IBD. Methods: Four families with known consanguinity and multiple cases of IBD were recruited. In a family-specific analysis, we utilised homozygosity mapping complemented by whole-exome sequencing. Results: We detected a single region of homozygosity shared by Crohn's disease cases from a family of Druze ancestry, spanning 2.6 Mb containing the NOD2 gene. Whole-exome sequencing did not identify any potentially damaging variants within the region, suggesting that non-coding variation may be involved. In addition, affected individuals in the families harboured several rare and potentially damaging homozygous variants in genes with a role in autophagy and innate immunity including LRRK1, WHAMM, DENND3, and C5. Conclusion: This study examined the potential contribution of rare, high-impact homozygous variants in consanguineous families with IBD. While the analysis was not designed to achieve statistical significance, our findings highlight genes or loci that warrant further research. Non-coding variants affecting NOD2 may be of importance in Druze patients with Crohn's disease
POTs: Protective Optimization Technologies
Algorithmic fairness aims to address the economic, moral, social, and
political impact that digital systems have on populations through solutions
that can be applied by service providers. Fairness frameworks do so, in part,
by mapping these problems to a narrow definition and assuming the service
providers can be trusted to deploy countermeasures. Not surprisingly, these
decisions limit fairness frameworks' ability to capture a variety of harms
caused by systems.
We characterize fairness limitations using concepts from requirements
engineering and from social sciences. We show that the focus on algorithms'
inputs and outputs misses harms that arise from systems interacting with the
world; that the focus on bias and discrimination omits broader harms on
populations and their environments; and that relying on service providers
excludes scenarios where they are not cooperative or intentionally adversarial.
We propose Protective Optimization Technologies (POTs). POTs provide means
for affected parties to address the negative impacts of systems in the
environment, expanding avenues for political contestation. POTs intervene from
outside the system, do not require service providers to cooperate, and can
serve to correct, shift, or expose harms that systems impose on populations and
their environments. We illustrate the potential and limitations of POTs in two
case studies: countering road congestion caused by traffic-beating
applications, and recalibrating credit scoring for loan applicants.Comment: Appears in Conference on Fairness, Accountability, and Transparency
(FAT* 2020). Bogdan Kulynych and Rebekah Overdorf contributed equally to this
work. Version v1/v2 by Seda G\"urses, Rebekah Overdorf, and Ero Balsa was
presented at HotPETS 2018 and at PiMLAI 201
Modular Medical Imaging Agents Based on Azide-Alkyne Huisgen Cycloadditions:Synthesis and Pre-Clinical Evaluation of(18)F-Labeled PSMA-Tracers for Prostate Cancer Imaging
Since the seminal contribution of Rolf Huisgen to develop the [3+2] cycloaddition of 1,3-dipolar compounds, its azide–alkyne variant has established itself as the key step in numerous organic syntheses and bioorthogonal processes in materials science and chemical biology. In the present study, the copper(I)-catalyzed azide–alkyne cycloaddition was applied for the development of a modular molecular platform for medical imaging of the prostate-specific membrane antigen (PSMA), using positron emission tomography. This process is shown from molecular design, through synthesis automation and in vitro studies, all the way to pre-clinical in vivo evaluation of fluorine-18- labeled PSMA-targeting ‘F-PSMA-MIC’ radiotracers (t1/2=109.7 min). Pre-clinical data indicate that the modular PSMA-scaffold has similar binding affinity and imaging properties to the clinically used [68Ga]PSMA-11. Furthermore, we demonstrated that targeting the arene-binding in PSMA, facilitated through the [3+2]cycloaddition, can improve binding affinity, which was rationalized by molecular modeling. The here presented PSMA-binding scaffold potentially facilitates easy coupling to other medical imaging moieties, enabling future developments of new modular imaging agents
α-Synuclein Expression Selectively Affects Tumorigenesis in Mice Modeling Parkinson's Disease
Alpha Synuclein (α-Syn) is a protein implicated in mechanisms of neuronal degeneration in Parkinson's disease (PD). α-Syn is primarily a neuronal protein, however, its expression is found in various tumors including ovarian, colorectal and melanoma tumors. It has been hypothesized that neurodegeneration may share common mechanisms with oncogenesis. We tested whether α-Syn expression affects tumorigenesis of three types of tumors. Specifically, B16 melanoma, E0771 mammary gland adenocarcinoma and D122 Lewis lung carcinoma. For this aim, we utilized transgenic mice expression the human A53T α-Syn form. We found that the in vivo growth of B16 and E0771 but not D122 was enhanced in the A53T α-Syn mice. The effect on tumorigenesis was not detected in age-matched APP/PS1 mice, modeling Alzheimer's disease (AD), suggesting a specific effect for α-Syn- dependent neurodegeneration. Importantly, transgenic α-Syn expression was detected within the three tumor types. We further show uptake of exogenously added, purified α-Syn, by the cultured tumor cells. In accord, with the affected tumorigenesis in the young A53T α-Syn mice, over- expression of α-Syn in cultured B16 and E0771 cells enhanced proliferation, however, had no effect on the proliferation of D122 cells. Based on these results, we suggest that certain forms of α-Syn may selectively accelerate cellular mechanisms leading to cancer
Rare coding variant analysis in a large cohort of Ashkenazi Jewish families with inflammatory bowel disease
Rare variants are thought to contribute to the genetics of inflammatory bowel disease (IBD), which is more common amongst the Ashkenazi Jewish (AJ) population. A family-based approach using exome sequencing of AJ individuals with IBD was employed with a view to identify novel rare genetic variants for this disease. Exome sequencing was performed on 960 Jewish individuals including 513 from 199 multiplex families with up to eight cases. Rare, damaging variants in loci prioritized by linkage analysis and those shared by multiple affected individuals within the same family were identified. Independent evidence of association of each variant with disease was assessed. A number of candidate variants were identified, including in genes involved in the immune system. The ability to achieve statistical significance in independent case/control replication data was limited by power and was only achieved for variants in the well-established Crohn's disease gene, NOD2. This work demonstrates the challenges of identifying disease-associated rare damaging variants from exome data, even amongst a favorable cohort of familial cases from a genetic isolate. Further research of the prioritized rare candidate variants is required to confirm their association with the disease
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