Modeling Momentum-Diffusion in the Solar Wind

Energetic particles accelerated by large solar flares and coronal mass ejections (CMEs) are a threat to astronauts, global positioning systems (GPS), radio communications, and power grids. It is therefore vital that scientists be able to predict how such particles move and gain energy within the interplanetary medium in order to forewarn society impending hazards so that mitigating actions can be taken. In this work, I take a step towards this goal, using the Energetic Particle Radiation Environment Module (EPREM) code, which is used by UNH\u27s radiation-dosage predictions website, I model interstellar-pickup ions (PUIs). I add to the model by including a momentum-diffusion term which contributes to the change in the distribution as it evolves in time. Here, I investigate how the given model of momentum diffusion affects the energetic PUI population ($v\u3eu_{sw}$). This analysis focuses on the power-law spectra of the suprathermal tail of the PUI distribution. When the velocity dependence of the diffusion coefficient is normalized to the local solar-wind velocity, I have found little to no change in the spectra of the suprathermal ion tails when momentum-diffusion is included; however, when the velocity dependence of the diffusion coefficient is not normalized, hardening of the spectra of the suprathermal ion tail is observed. It is possible that the effect of momentum-diffusion and particle acceleration in CIRs is the source of the energetic seed particle population, which makes up the available particles to be accelerated by a shock. In order to understand these potentially dangerous seed particles, we hope to use new observations from Parker Solar Probe to determine the acceleration processes, such as momentum-diffusion, that yield the observed spectra

Modeling Momentum-Diffusion in the Solar Wind

The Sun is both a resource and a danger. We must be able to predict or have forewarning of large solar flares and coronal mass ejections (CMEs) and their potential threats to astronauts, GPS, radio communications, and power grids. I have used the Energetic Particle Radiation Environment Module (EPREM) code, which is used by PREDICCS, UNH\u27s radiation dosage predictions website, to model interstellar-pickup ions (PUIs). I add to the model by including a momentum-diffusion term which contributes to the change in the distribution as it evolves in time. Here, I investigate how the given model of momentum-diffusion affects the energetic PUI population (with velocity greater than the solar wind velocity). This analysis focuses on the power-law spectra of the suprathermal tail of the PUI distribution. When the velocity dependence of the diffusion coefficient is normalized to the local solar wind velocity, I have found little to no change in the spectra of the suprathermal ion tails when momentum-diffusion is included. When the velocity dependence of the diffusion coefficient is not normalized, hardening of the spectra of the suprathermal ion tail is observed. It is possible that the affect of momentum-diffusion and particle acceleration in CIR\u27s are the source of the energetic seed particle population, which makes up the available particles to be accelerated by a shock. In order to understand these potentially dangerous seed particles, we hope to use new observations from Parker Solar Probe to determine the acceleration processes, such as momentum-diffusion, that yield the observed spectra

The Effector Domain of MARCKS Is a Nuclear Localization Signal that Regulates Cellular PIP2 Levels and Nuclear PIP2 Localization

Translocation to the nucleus of diacylglycerol kinase (DGK)– ζ is dependent on a sequence homologous to the effector domain of Myristoylated Alanine Rich C-Kinase Substrate (MARCKS). These data would suggest that MARCKS could also localize to the nucleus. A single report demonstrated immunofluorescence staining of MARCKS in the nucleus; however, further experimental evidence confirming the specific domain responsible for this localization has not been reported. Here, we report that MARCKS is present in the nucleus in GBM cell lines. We then over-expressed wild-type MARCKS (WT) and MARCKS with the effector domain deleted (ΔED), both tagged with V5-epitope in a GBM cell line with low endogenous MARCKS expression (U87). We found that MARCKS-WT localized to the nucleus, while the MARCKS construct without the effector domain remained in the cytoplasm. We also found that over-expression of MARCKS-WT resulted in a significant increase in total cellular phosphatidyl-inositol (4,5) bisphosphate (PIP2) levels, consistent with prior evidence that MARCKS can regulate PIP2 levels. We also found increased staining for PIP2 in the nucleus with MARCKS-WT over-expression compared to MARCKS ΔED by immunofluorescence. Interestingly, we observed MARCKS and PIP2 co-localization in the nucleus. Lastly, we found changes in gene expression when MARCKS was not present in the nucleus (MARCKS ΔED). These data indicate that the MARCKS effector domain can function as a nuclear localization signal and that this sequence is critical for the ability of MARCKS to regulate PIP2 levels, nuclear localization, and gene expression. These data suggests a novel role for MARCKS in regulating nuclear functions such as gene expression

Evaluation of hydrological models on small mountainous catchments: impact of the meteorological forcings

Hydrological modelling of small mountainous catchments is particularly challenging because of the high spatio-temporal resolution required for the meteorological forcings. In situ measurements of precipitation are typically scarce in these remote areas, particularly at high elevations. Precipitation reanalyses propose different alternative forcings for the simulation of streamflow using hydrological models. In this paper, we evaluate the performances of two hydrological models representing some of the key processes for small mountainous catchments (&lt; 300 km2), using different meteorological products with a fine spatial and temporal resolution. The evaluation is performed on 55 small catchments of the northern French Alps. While the simulated streamflows are adequately reproduced for most of the configurations, these evaluations emphasize the added value of radar measurements, in particular for the reproduction of flood events. However, these better performances are only obtained because the hydrological models correct the underestimations of accumulated amounts (e.g. annual) from the radar data in high-elevation areas.</p

Reconstructing 15&thinsp;000 years of southern France temperatures from coupled pollen and molecular (branched glycerol dialkyl glycerol tetraether) markers (Canroute, Massif Central)

Climatic changes in southern Europe during the Holocene are characterized by a strong spatial and temporal heterogeneity whose patterns are still poorly understood, notably the presence or not of a Holocene thermal maximum (HTM; 10 000–6000 cal BP). The climatic patterns also differ according to the proxies used (e.g. pollen, chironomid) and the latitude of the record. Here, a multi-proxy approach combining pollen and lipid biomarkers (branched glycerol dialkyl glycerol tetraethers, brGDGTs) is applied to the Canroute sedimentological sequence (Massif Central, France) to reconstruct the climatic variation over the last 15 000 years in southern Europe. This area is poorly documented in terms of vegetation and climate change. To provide reliable climate reconstructions, we have (1) performed a multi-method approach applied to pollen (modern analogue technique, MAT; weighted averaging partial least squares regression, WA-PLS; boosted regression trees, BRT; and random forest, RF) and molecular biomarkers brGDGTs (five calibrations) and (2) investigated the role of modern databases and calibrations in climate reconstructions. Three different databases were tested for pollen data: one global database based on a Eurasian pollen database and two regional databases corresponding to Mediterranean–Temperate Europe and Temperate Europe–Scandinavian databases respectively. Five global calibrations were tested for lipid biomarkers including four for soil and one for peat. Results show that the use of different modern databases highlights the importance of considering environmental and ecological constraints when using transfer functions on pollen sequences. Pollen- and brGDGT-inferred climate trends are consistent, notably for the Late Glacial and the Early and Late Holocene. However, the reconstructions notably differ concerning the presence of a Holocene thermal maximum with the MAT pollen-based method, but no difference is apparent with the BRT pollen method nor brGDGT. The temperature reconstructions estimated from the two independent pollen and lipid proxies are then compared to regional climate signals (chironomids, pollen, molecular biomarkers) to better understand global regional climatic patterns in southern Europe. Altogether, our results from the Canroute sequence and those already available in southern Europe reveal that for the Late Glacial and Early Holocene, the regional climate trends are consistent between sites and proxies, supporting the reliability of their reconstructions despite some discrepancies. During the Holocene, the temperature signal of Canroute does not indicate the clear presence of a pronounced HTM, but rather stable temperatures.</p

Autoimmune inflammatory disorders, systemic corticosteroids and pneumocystis pneumonia: A strategy for prevention

BACKGROUND: Pneumocystis pneumonia (PCP) is an increasing problem amongst patients on immunosuppression with autoimmune inflammatory disorders (AID). The disease presents acutely and its diagnosis requires bronchoalveolar lavage in most cases. Despite treatment with intravenous antibiotics, PCP carries a worse prognosis in AID patients than HIV positive patients. The overall incidence of PCP in patients with AID remains low, although patients with Wegener's granulomatosis are at particular risk. DISCUSSION: In adults with AID, the risk of PCP is related to treatment with systemic steroid, ill-defined individual variation in steroid sensitivity and CD4+ lymphocyte count. Rather than opting for PCP prophylaxis on the basis of disease or treatment with cyclophosphamide, we argue the case for carrying out CD4+ lymphocyte counts on selected patients as a means of identifying individuals who are most likely to benefit from PCP prophylaxis. SUMMARY: Corticosteroids, lymphopenia and a low CD4+ count in particular, have been identified as risk factors for the development of PCP in adults with AID. Trimethoprim-sulfamethoxazole (co-trimoxazole) is an effective prophylactic agent, but indications for its use remain ill-defined. Further prospective trials are required to validate our proposed prevention strategy

3D genomics across the tree of life reveals condensin II as a determinant of architecture type

We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional(3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedlyduring eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with theabsence of condensin II subunits. Moreover, condensin II depletion converts the architecture of thehuman genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state,centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physicalmodel in which lengthwise compaction of chromosomes by condensin II during mitosis determineschromosome-scale genome architecture, with effects that are retained during the subsequent interphase.This mechanism likely has been conserved since the last common ancestor of all eukaryotes.C.H. is supported by the Boehringer Ingelheim Fonds; C.H., Á.S.C., and B.D.R. are supported by an ERC CoG (772471, “CohesinLooping”); A.M.O.E. and B.D.R. are supported by the Dutch Research Council (NWO-Echo); and J.A.R. and R.H.M. are supported by the Dutch Cancer Society (KWF). T.v.S. and B.v.S. are supported by NIH Common Fund “4D Nucleome” Program grant U54DK107965. H.T. and E.d.W. are supported by an ERC StG (637597, “HAP-PHEN”). J.A.R., T.v.S., H.T., R.H.M., B.v.S., and E.d.W. are part of the Oncode Institute, which is partly financed by the Dutch Cancer Society. Work at the Center for Theoretical Biological Physics is sponsored by the NSF (grants PHY-2019745 and CHE-1614101) and by the Welch Foundation (grant C-1792). V.G.C. is funded by FAPESP (São Paulo State Research Foundation and Higher Education Personnel) grants 2016/13998-8 and 2017/09662-7. J.N.O. is a CPRIT Scholar in Cancer Research. E.L.A. was supported by an NSF Physics Frontiers Center Award (PHY-2019745), the Welch Foundation (Q-1866), a USDA Agriculture and Food Research Initiative grant (2017-05741), the Behavioral Plasticity Research Institute (NSF DBI-2021795), and an NIH Encyclopedia of DNA Elements Mapping Center Award (UM1HG009375). Hi-C data for the 24 species were created by the DNA Zoo Consortium (www.dnazoo.org). DNA Zoo is supported by Illumina, Inc.; IBM; and the Pawsey Supercomputing Center. P.K. is supported by the University of Western Australia. L.L.M. was supported by NIH (1R01NS114491) and NSF awards (1557923, 1548121, and 1645219) and the Human Frontiers Science Program (RGP0060/2017). The draft A. californica project was supported by NHGRI. J.L.G.-S. received funding from the ERC (grant agreement no. 740041), the Spanish Ministerio de Economía y Competitividad (grant no. BFU2016-74961-P), and the institutional grant Unidad de Excelencia María de Maeztu (MDM-2016-0687). R.D.K. is supported by NIH grant RO1DK121366. V.H. is supported by NIH grant NIH1P41HD071837. K.M. is supported by a MEXT grant (20H05936). M.C.W. is supported by the NIH grants R01AG045183, R01AT009050, R01AG062257, and DP1DK113644 and by the Welch Foundation. E.F. was supported by NHGR

The structure and function of Alzheimer's gamma secretase enzyme complex

The production and accumulation of the beta amyloid protein (Aβ) is a key event in the cascade of oxidative and inflammatory processes that characterizes Alzheimer’s disease (AD). A multi-subunit enzyme complex, referred to as gamma (γ) secretase, plays a pivotal role in the generation of Aβ from its parent molecule, the amyloid precursor protein (APP). Four core components (presenilin, nicastrin, aph-1, and pen-2) interact in a high-molecular-weight complex to perform intramembrane proteolysis on a number of membrane-bound proteins, including APP and Notch. Inhibitors and modulators of this enzyme have been assessed for their therapeutic benefit in AD. However, although these agents reduce Aβ levels, the majority have been shown to have severe side effects in pre-clinical animal studies, most likely due to the enzymes role in processing other proteins involved in normal cellular function. Current research is directed at understanding this enzyme and, in particular, at elucidating the roles that each of the core proteins plays in its function. In addition, a number of interacting proteins that are not components of γ-secretase also appear to play important roles in modulating enzyme activity. This review will discuss the structural and functional complexity of the γ-secretase enzyme and the effects of inhibiting its activity

On the visual detection of non-natural records in streamflow time series: challenges and impacts

Large datasets of long-term streamflow measurements are widely used to infer and model hydrological processes. However, streamflow measurements may suffer from what users can consider anomalies, i.e. non-natural records that may be erroneous streamflow values or anthropogenic influences that can lead to misinterpretation of actual hydrological processes. Since identifying anomalies is time consuming for humans, no study has investigated their proportion, temporal distribution, and influence on hydrological indicators over large datasets. This study summarizes the results of a large visual inspection campaign of 674 streamflow time series in France made by 43 evaluators, who were asked to identify anomalies falling under five categories, namely, linear interpolation, drops, noise, point anomalies, and other. We examined the evaluators' individual behaviour in terms of severity and agreement with other evaluators, as well as the temporal distributions of the anomalies and their influence on commonly used hydrological indicators. We found that inter-evaluator agreement was surprisingly low, with an average of 12 % of overlapping periods reported as anomalies. These anomalies were mostly identified as linear interpolation and noise, and they were more frequently reported during the low-flow periods in summer. The impact of cleaning data from the identified anomaly values was higher on low-flow indicators than on high-flow indicators, with change rates lower than 5 % most of the time. We conclude that the identification of anomalies in streamflow time series is highly dependent on the aims and skills of each evaluator, which raises questions about the best practices to adopt for data cleaning.</p