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Optimization of Iron Enriched Extruded Snacks for Anemic People Using Response Surface Methodology (RSM)

Despite advances in precision medicine, the clinical prospects for patients with ovarian and uterine cancers have not substantially improved. Here, we analyzed genome-scale CRISPR-Cas9 loss-of-function screens across 851 human cancer cell lines and found that frequent overexpression of SLC34A2-encoding a phosphate importer-is correlated with sensitivity to loss of the phosphate exporter XPR1, both in vitro and in vivo. In patient-derived tumor samples, we observed frequent PAX8-dependent overexpression of SLC34A2, XPR1 copy number amplifications and XPR1 messenger RNA overexpression. Mechanistically, in SLC34A2-high cancer cell lines, genetic or pharmacologic inhibition of XPR1-dependent phosphate efflux leads to the toxic accumulation of intracellular phosphate. Finally, we show that XPR1 requires the novel partner protein KIDINS220 for proper cellular localization and activity, and that disruption of this protein complex results in acidic "vacuolar" structures preceding cell death. These data point to the XPR1-KIDINS220 complex and phosphate dysregulation as a therapeutic vulnerability in ovarian cancer.

Campus recreation facilities are a critical resource to encourage physical activity at universities. COVID-19 closures in 2020 led to the shutdown of many campuses, which included campus recreation facilities. Little is known about how the closures impacted the physical activity levels of students, faculty, and staff who relied on campus recreation for physical activity opportunities. Therefore, the purpose of this study was to determine if individuals who were users of campus recreation prior to campus closure continued to be physically active when campus closed. The survey was completed by 282 previous users (students, faculty, and staff) of campus recreation. Results indicated that 85.8% of participants were meeting physical activity recommendations following campus closure. To support physical activity off campus, survey respondents suggested online exercise classes via social media and allowing equipment rentals. Future efforts should continue identifying ways campus recreation can support physical activity both on and off campus.

Fluvial aggradation and incision are often linked to Quaternary climate cycles, but it usually remains unclear whether variations in runoff or sediment supply or both drive channel response to climate variability. Here we quantify sediment supply with paleo-denudation rates and provide geochronological constraints on aggradation and incision from the Sfakia and Elafonisi alluvial-fan sequences in Crete, Greece. We report seven optically stimulated luminescence and ten radiocarbon ages, eight Be-10 and eight Cl-36 denudation rates from modern channel and terrace sediments. For five samples, Be-10 and Cl-36 were measured on the same sample by measuring Be-10 on chert and Cl-36 on calcite. Results indicate relatively steady denudation rates throughout the past 80 kyr, but the aggradation and incision history indicates a link with climate shifts. At the Elafonisi fan, we identify four periods of aggradation coinciding with Marine Isotope Stages (MIS) 2, 4, 5a/b, and likely 6, and three periods of incision coinciding with MIS 1, 3, and likely 5e. At the Sfakia fan, rapid aggradation occurred during MIS 2 and 4, followed by incision during MIS 1. Nearby climate and vegetation records show that MIS 2, 4, and 6 stadials were characterized by cold and dry climates with sparse vegetation, whereas forest cover and more humid conditions prevailed during MIS 1, 3, and 5. Our data thus suggest that past changes in climate had little effect on landscape-wide denudation rates but exerted a strong control on the aggradation-incision behaviour of alluvial channels on Crete. During glacial stages, we attribute aggradation to hillslope sediment release promoted by reduced vegetation cover and decreased runoff; conversely, incision occurred during relatively warm and wet stages due to increased runoff. In this landscape, past hydroclimate variations outcompeted changes in sediment supply as the primary driver of alluvial deposition and incision., Earth Surface Processes and Landforms, 48 (2), ISSN:0197-9337, ISSN:1096-9837

When addressing diversity, equity, and inclusion, researchers and organizations often focus on group differences in outcomes of interest. However, groups do not always interpret surveys in the same way, causing measurement nonequivalence. Measurement nonequivalence makes it difficult, if not impossible, to compare group differences presenting a problem for how conclusions are drawn. To better understand group differences in survey responding, the current study assessed measurement invariance across five diversity-related measures using the methods outlined by Nye and colleagues (Nye et al., 2019; Somaraju et al., 2022). Data were collected across three organizations (N = 732) from different industries (i.e., healthcare, construction, information technology). Results indicate that for all five measures, there was significant measurement nonequivalence across organizations such that all but the referent item were found to be nonequivalent. We also examined measurement invariance across race and gender where all measures in all organizations were nonequivalent. Interestingly, these effects were not similar across organizations. The construction company had strong gender effects across measures (dMAC = -.64 to -.13), but weak racial effects (dMAC = -.08 to .34). In contrast, the healthcare company had relatively stronger racial effects (dMAC = -.62 to -.35) than gender (dMAC = -.43 to -.01). The information technology company had low effects for both race (dMAC = -.29 to .04) and gender (dMAC = -.20 to .09). Given these results, there are several implications for both research and practice. Researchers should not assume that samples collected across multiple organizations are equivalent and the use of hierarchically nest models may be necessary to account for group differences. Further, greater attention is needed in measurement development to ensure their validity across groups. For practitioners, we recommend utilizing open-ended survey items to better capture group differences due to the prevalence of high measurement nonequivalence in closed-items.

Background Biallelic mutations in the GBA1 gene encoding glucocerebrosidase cause Gaucher's disease, whereas heterozygous carriers are at risk for Parkinson's disease (PD). Glucosylsphingosine is a clinically meaningful biomarker of Gaucher's disease but could not be assayed previously in heterozygous GBA1 carriers. Objective The aim of this study was to assess plasma glucosylsphingosine levels in GBA1 N370S carriers with and without PD. Methods Glucosylsphingosine, glucosylceramide, and four other lipids were quantified in plasma from N370S heterozygotes with (n = 20) or without (n = 20) PD, healthy controls (n = 20), idiopathic PD (n = 20), and four N370S homozygotes (positive controls; Gaucher's/PD) using quantitative ultra-performance liquid chromatography tandem mass spectrometry. Results Plasma glucosylsphingosine was significantly higher in N370S heterozygotes compared with noncarriers, independent of disease status. As expected, Gaucher's/PD cases showed increases in both glucocerebrosidase substrates, glucosylsphingosine and glucosylceramide. Conclusions Plasma glucosylsphingosine accumulation in N370S heterozygotes shown in this study opens up its future assessment as a clinically meaningful biomarker of GBA1-PD. © 2021 International Parkinson and Movement Disorder Society.

The article presents the current state of the use of cobalt in various industries and its possible elimination in the field of welding. In this area, it is used in the form of cobalt alloys which are affected by various mechanical and chemical influences. These alloys are produced by the secondary metallurgical area. The primary area is the chemical industry which reserves all the use of cobalt for the production of Li-ion batteries for electric vehicles at an increasing price. The primary area is the chemical industry which reserves all the use of cobalt for the production of Li-ion batteries for electric vehicles at an increasing price. As it becomes unprofitable for other areas, its savings must be sought. From the point of view of welding technology, the solution could be the use of unconventional and hybrid methods that do not require filler material for the connection of elements. Based on these aspects, the methods of a laser beam, electron beam, and combination of a laser beam with TIG method were selected. Verification of the suitability of the use of the mentioned methods was performed on the abrasion-resistant alloy Stellite 6B. The quality of the joints was evaluated by destructive methods such as microstructure, macrostructure, microhardness, and EDS. After evaluating the results of all samples, the hybrid method in the combination of a laser beam and TIG method seems to be the best.

The article describes problems of hard depositional brazing of wolfram-carbide grains in various matrixes. Especially iron and nickel base matrix on base material from constructional carbon steel. The experimental part was brazed by oxyacetylene flame (method 912 according to EN ISO 4063). The major goals of the experiment were to describe the technological procedure of hard depositional brazing of this specific part. Consequently, were proved wolfram-carbide deposit on two test coupons. These test coupons were metallographically and qualitatively evaluated. The advantage of wolfram-carbide depositional brazing is a service life of deposit, that could be multiple higher, than standard weld deposit with carbon, chromium and vanadium filler material. The advantage is also costly because this kind of braze is cheaper than hard surfacing filler material. This specific application of the wolfram-carbide layer is one of the hardest coatings that could be by flame brazing technology performed. Usage of this application is for example in the mining, woodcutting industry, where it is necessary to improve abrasion and resistance, service life, and guaranteed durability or hardness for cutting tools.

Spaceborne impact ionization mass spectrometers, such as the Cosmic Dust Analyzer on board the past Cassini spacecraft or the SUrface Dust Analyzer being built for NASA's upcoming Europa Clipper mission, are of crucial importance for the exploration of icy moons in the Solar System, such as Saturn's moon Enceladus or Jupiter's moon Europa. For the interpretation of data produced by these instruments, analogue experiments on Earth are essential. To date, thousands of laboratory mass spectra have been recorded with an analogue experiment for impact ionization mass spectrometers. Simulation of mass spectra of ice grains in space is achieved by a Laser Induced Liquid Beam Ion Desorption (LILBID) approach. The desorbed cations or anions are analyzed in a time‐of‐flight mass spectrometer. The amount of unstructured raw data is increasingly challenging to sort, process, interpret and compare with data from space. Thus far this has been achieved manually for individual mass spectra because no database containing the recorded reference spectra was available. Here we describe the development of a comprehensive, extendable database containing cation and anion mass spectra from the laboratory LILBID facility. The database is based on a Relational Database Management System with a web server interface and enables filtering of the laboratory data using a wide range of parameters. The mass spectra can be compared not only with data from past and future space missions but also mass spectral data generated by other, terrestrial, techniques. The validated and approved subset of the database is available for general public (https://lilbid-db.planet.fu-berlin.de)., Plain Language Summary: Thousands of laboratory mass spectra, each with an individual set of experimental parameters, have been recorded so far using a facility situated at Freie Universität Berlin, Germany. The mass spectra help analyze and interpret data returned from spacecraft in the vicinity of icy moons in the Solar System. The unstructured laboratory data is increasingly challenging to sort and compare to the data from space. We developed an extendable database containing the laboratory data. The database is available for general public and allows filtering the stored data for a wide range of experimental parameters and, in turn, significantly improves analysis of data not only from past space missions but also future missions in particular., Key Points: We describe the development of a comprehensive spectral database containing laboratory analogue data for spaceborne mass spectrometers. The database is based on a Relational Database Management System with a web interface and accessible for community use. Filtering the laboratory data using a wide range of experimental parameters allows a straightforward analysis of returned flight data., EC, Horizon 2020 Framework Programme (H2020) http://dx.doi.org/10.13039/100010661, Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659, https://doi.org/10.5281/zenodo.6863855, https://sbnarchive.psi.edu/pds3/cassini/cda/COCDA_0007.tar.gz

Deep learning can accurately represent sub‐grid‐scale convective processes in climate models, learning from high resolution simulations. However, deep learning methods usually lack interpretability due to large internal dimensionality, resulting in reduced trustworthiness in these methods. Here, we use Variational Encoder Decoder structures (VED), a non‐linear dimensionality reduction technique, to learn and understand convective processes in an aquaplanet superparameterized climate model simulation, where deep convective processes are simulated explicitly. We show that similar to previous deep learning studies based on feed‐forward neural nets, the VED is capable of learning and accurately reproducing convective processes. In contrast to past work, we show this can be achieved by compressing the original information into only five latent nodes. As a result, the VED can be used to understand convective processes and delineate modes of convection through the exploration of its latent dimensions. A close investigation of the latent space enables the identification of different convective regimes: (a) stable conditions are clearly distinguished from deep convection with low outgoing longwave radiation and strong precipitation; (b) high optically thin cirrus‐like clouds are separated from low optically thick cumulus clouds; and (c) shallow convective processes are associated with large‐scale moisture content and surface diabatic heating. Our results demonstrate that VEDs can accurately represent convective processes in climate models, while enabling interpretability and better understanding of sub‐grid‐scale physical processes, paving the way to increasingly interpretable machine learning parameterizations with promising generative properties., Plain Language Summary: Deep neural nets are hard to interpret due to their hundred thousand or million trainable parameters without further postprocessing. We demonstrate in this paper the usefulness of a network type that is designed to drastically reduce this high dimensional information in a lower‐dimensional space to enhance the interpretability of predictions compared to regular deep neural nets. Our approach is, on the one hand, able to reproduce small‐scale cloud related processes in the atmosphere learned from a physical model that simulates these processes skillfully. On the other hand, our network allows us to identify key features of different cloud types in the lower‐dimensional space. Additionally, the lower‐order manifold separates tropical samples from polar ones with a remarkable skill. Overall, our approach has the potential to boost our understanding of various complex processes in Earth System science., Key Points: A Variational Encoder Decoder (VED) can predict sub‐grid‐scale thermodynamics from the coarse‐scale climate state. The VED's latent space can distinguish convective regimes, including shallow/deep/no convection. The VED's latent space reveals the main sources of convective predictability at different latitudes., EC ERC HORIZON EUROPE European Research Council http://dx.doi.org/10.13039/100019180, Columbia sub‐award 1, Advanced Research Projects Agency - Energy http://dx.doi.org/10.13039/100006133, Deutsches Klimarechenzentrum http://dx.doi.org/10.13039/100018730, National Science Foundation Science and Technology Center Learning the Earth with Artificial intelligence and Physics

The article describes a replacement and benefits between manual gas metal arc welding (GMAW) with solid wire and semi-automatic flux-cored arc welding (FCAW) with metal flux-cored wire for a specific application of a welded steel compensator used for connecting piping systems to form larger units. For the replacement of the technologies and improvement of the welding efficiency and productivity a specific type of carbon steel mounting insert, DN300 PN16, was selected. Since these pressure parts are subject to the directive 2014/68/EU, both the welding processes have to meet the same welding quality requirements. In particular, they are the welding procedure qualification report (WPQR) and the welder’s or welding operator’s qualification in accordance with valid European standards. Based on this requirement, a sample was selected so that it would cover the widest possible range of carbon steel mounting inserts produced. This article describes the whole experiment including the selection of the right equipment and filler material, finding the ideal welding parameters, and the subsequent qualification of the welding procedure and the operator with emphasis on the largest possible increase in the welding speed and productivity for these specific weldments.

Winter roads are highly vulnerable to a warming climate, since a sufficient number of cold days are required for the ground and bodies of water to freeze to the required depth to create a strong foundation for the safe passage of traffic. A framework to review and assess the climate risk and vulnerability of winter roads in Canada has been developed, as well as the structure of a Winter Roads Module for Crown-Indigenous Relations and Northern Affairs Canada’s Climate Risk Index. Both are intended to evolve over time as more data and information becomes available, and both are based on published scientific methods, field data from winter road operations, as well as stakeholder observation, experience and concerns. A number of case studies have been completed using available data to validate and refine the framework and the Winter Roads Module.