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Aside from its economic value, davidite and its synthetic analogs may have potential applications in materials science. The unique properties of the crichtonite group minerals, including davidite-(La), make them attractive candidates for high-level waste (HLW) immobilization. We studied the thermal evolution of the metamict davidite-(La) from the Radium Hill, Australia. The investigation of the temperature-induced crystallization process was conducted, and the thermal expansion coefficients (TEC) for the recrystallized davidite (RD) were determined for the first time. Our results demonstrate that RD has relatively low TEC indicating its thermophysical stability. The following TECs of davidite- (La) for the temperature range 25–1200 °C were obtained: α ¯ a = α ¯ b = 9.96 (3) × 10–6 ºC−1; α ¯ c = 10.79 (4) × 10–6 ºC−1. The character of the thermal expansion is in agreement with the structure characterized by layers stacked along the c axis. The volume TEC αV = 24.81 (47)—36.80 (48) × 10–6 ºC−1. Davidite-(La) exhibits an almost isotropic thermal expansion and shows one of the most superior thermal performances in comparison to the other mineral-like phases utilized for the immobilization of HLW. [ABSTRACT FROM AUTHOR]

Breast cancer represents a collection of pathologies with different molecular subtypes, histopathology, risk factors, clinical behavior, and responses to treatment. "Basal-like" breast cancers predominantly lack the receptors for estrogen and progesterone (ER/PR), lack amplification of human epidermal growth factor receptor 2 (HER2) but account for 10–15% of all breast cancers, are largely insensitive to targeted treatment and represent a disproportionate number of metastatic cases and deaths. Analysis of interleukin (IL)-3 and the IL-3 receptor subunits (IL-3RA + CSF2RB) reveals elevated expression in predominantly the basal-like group. Further analysis suggests that IL-3 itself, but not the IL-3 receptor subunits, associates with poor patient outcome. Histology on patient-derived xenografts supports the notion that breast cancer cells are a significant source of IL-3 that may promote disease progression. Taken together, these observations suggest that IL-3 may be a useful marker in solid tumors, particularly triple negative breast cancer, and warrants further investigation into its contribution to disease pathogenesis. [ABSTRACT FROM AUTHOR]

Manufacturing industry faces increasing complexity in the performance of assembly tasks due to escalating demand for complex products with a greater number of variations. Operators require robust assistance systems to enhance productivity, efficiency, and safety. However, existing support services often fall short when operators encounter unstructured open questions and incomplete sentences due to primarily relying on procedural digital work instructions. This draws attention to the need for practical application of natural language processing (NLP) techniques. This study addresses these challenges by introducing a domain-specific dataset tailored to assembly tasks, capturing unique language patterns and linguistic characteristics. We explore strategies to process declarative and imperative sentences, including incomplete ones, effectively. Thorough evaluation of three pre-trained NLP libraries—NLTK, SPACY, and Stanford—is performed to assess their effectiveness in handling assembly-related concepts and ability to address the domain's distinctive challenges. Our findings demonstrate the efficient performance of these open-source NLP libraries in accurately handling assembly-related concepts. By providing valuable insights, our research contributes to developing intelligent operator assistance systems, bridging the gap between NLP techniques and the assembly domain within manufacturing industry. [ABSTRACT FROM AUTHOR]

The metamict fergusonite-(Y) with the formula (Y0.70Ln0.20Ca0.13U0.02Th0.02)∑1.07(Nb0.72Ta0.17W0.06Ti0.04)∑1(O3.97(OH)0.11F0.08Cl0.03) · 2.12H2O from the Blyumovskaya Pit, Ilmeny Mountains (Russia) was studied by the means of high-temperature X-ray diffraction, thermal analysis, Raman spectroscopy and microprobe analysis. Thermal expansion was studied for both tetragonal (α-fergusonite) and monoclinic (β-fergusonite) polymorphs. The expansion of β-fergusonite is anisotropic and strongly negative along the α33. In contrast, α-fergusonite exhibits a relatively isotropic thermal expansion upon heating. The volume CTE (αV) for β-fergusonite varies in the range 22.87(94)–75.4(2.5) × 10–6 ºC−1, whereas α-fergusonite has αV = 32.33(57)–31.66(49) × 10-6 ºC−1 in the temperature range 850–1200 °C. After heating to 1100 °C, the mineral develops a porous texture, and the radioactivity is reduced by 37%, which can be attributed to the partial volatilization of some radionuclides. In situ experiments revealed the complete sequence of the thermal evolution of the metamict fergusonite-(Y) for the first time. [ABSTRACT FROM AUTHOR]

One of the main challenges in the industry is having trained and efficient operators in manufacturing lines. Smart adaptive guidance systems are developed that offer assistance to the operator during assembly. Depending on the operator's level of execution, the system should be able to serve a different guidance response. This paper investigates the assessment and classification of the operator's functional state using observed task execution times. Five different classifiers are studied for operator functional state classification on task execution time series. The experiments are based on an industry case and the ground truth is provided by an expert rule-based system. Three classification scenarios are defined that segment the problem on the level of the task, the individual, or the team. Furthermore, the investigation includes the evaluation of four distinct window-size configurations. The examination of how these scenarios and window-sizes influence the studied dataset across diverse classifiers reveals that achieving enhanced accuracy necessitates a larger input dimension. In this context, Convolutional Neural Networks predominantly exhibit superior performance compared to alternative classifiers. Careful attention needs to be paid to performance over classes and skills, but results confirm the validity of the approach for data-driven operator functional state classification. [ABSTRACT FROM AUTHOR]

The design of high‐density non‐volatile memories is a long‐standing dream, limited by conventional storage "0" or "1" bits. An alternative paradigm exists in which regions within candidate materials can be magnetized to intermediate values between the saturation limits. In principle, this paves the way to multivalued bits, vastly increasing storage density. Single‐molecule magnets, are good examples offering transitions between intramolecular quantum levels, but require ultra‐low temperatures and limited relaxation time between magnetization states. It is showed here that the quasi 2D‐Ising compound BaFe2(PO4)2 overcomes these limitations. The combination of giant magneto‐crystalline anisotropy, strong ferromagnetic exchange, and strong intrinsic pinning creates remarkably narrow magnetic domain walls, collectively freezing under Tf ≈15 K. This results in a transition from a soft to a super‐hard magnet (coercive force > 14 T). Any magnetization can then be printed and robustly protected from external fields with an energy barrier >9T at 2 K. [ABSTRACT FROM AUTHOR]

The use of smartphone tracking is seen as the way forward in data collection for travel behavior studies. It overcomes some of the weaknesses of the classical approach (which uses paper trip diaries) in terms of accuracy and user annoyance. This article evaluates if these benefits hold in the practical application of smartphone tracking and compares the findings of a travel behavior survey using smartphone tracking to the findings of a previous paper survey. We compare three phases of the travel behavior study. In the recruitment phase, we expect smartphone tracking to make people more willing to participate in surveys, given the innovative nature and reduced burden to participants. However, we found the recruitment of participants equally challenging as for classical methods. In the data collection phase, however, we observe that participants entering the smartphone tracking survey are much more likely to complete the data collection period than when using paper trip diaries. Because of the limited burden, the risk of drop-out from the survey is significantly lower, making the actual data collection more efficient, even for longer survey periods. Finally, in the data analysis phase, the travel behavior indicators derived from smartphone tracking data result in higher average trip rates, shorter average trip lengths and a higher share of active modes (bike, walking) than the results from the paper survey. Although this is explained by more complete and more consistent trip registration, this finding is problematic for comparability between surveys based on different methods, both for longitudinal monitoring (comparability over consequent surveys) and for benchmarking (comparability over geographical areas). Therefore, it is crucial to clearly report the applied data collection methods when describing or comparing travel indicators. In surveys, a combined approach of both written trip diaries and smartphone tracking is advised, where each method can complement the shortcomings of the other. [ABSTRACT FROM AUTHOR]

Numerous studies expose the potential of brannerite to become a good matrix, concentrating fission products and actinides. Minerals can complement the data collected from the synthetic materials and offer an advantage of a long-time exposure to radiation. Natural metamict brannerite from Akchatau, Kazakhstan, and its annealed sample were studied by EPMA, Raman spectroscopy, TGA, DSC, XRD and HTXRD. The radioactivity of pristine and annealed samples of brannerite was measured. Brannerite from Akchatau is characterized by the absence of significant amounts of REE and yttrium. The studied brannerite regains its structure at a temperature ~650 °C, revealed by the HTXRD and DSC. HTXRD was also performed on the annealed recrystallized brannerite. The thermal expansion for brannerite has been determined for the first time. The brannerite structure expands anisotropically with temperature increase. All the thermal expansion coefficients are positive except for αβ. The decreasing beta parameter indicates a "shear structural deformation". The angle between the 1st axis of the tensor and the crystallographic a axis decreases with the increase of the temperature. The structure expands mostly in the α11 direction, approaching the bisector of the β angle. Brannerite has a low CTE at room temperature—αv = 16 × 10−6 °C−1, which increases up to 39.4 × 10−6 °C−1 at 1100 °C. In general, the thermal stability of brannerite is comparable to that of the other perspective oxide radioactive waste-immobilizing matrices (e.g., Ln2Zr2O7, CePO4, CaTiO3, CaZrTi2O7). The calculated thermal expansion of brannerite and the understanding of its underlying crystal chemical mechanisms may contribute to the behavior prediction of the material (both metamict and crystalline) at high temperatures. [ABSTRACT FROM AUTHOR]

Background and objective: Chronic obstructive pulmonary disease (COPD) is a devastating disease commonly caused by cigarette smoke (CS) exposure that drives tissue injury by persistently recruiting myeloid cells into the lungs. A significant portion of COPD patients also present with overlapping asthma pathology including eosinophilic inflammation. The βc cytokine family includes granulocyte monocyte‐colony‐stimulating factor, IL‐5 and IL‐3 that signal through their common receptor subunit βc to promote the expansion and survival of multiple myeloid cells including monocytes/macrophages, neutrophils and eosinophils. Methods: We have used our unique human βc receptor transgenic (hβcTg) mouse strain that expresses human βc instead of mouse βc and βIL3 in an acute CS exposure model. Lung tissue injury was assessed by histology and measurement of albumin and lactate dehydrogenase levels in the bronchoalveolar lavage (BAL) fluid. Transgenic mice were treated with an antibody (CSL311) that inhibits human βc signalling. Results: hβcTg mice responded to acute CS exposure by expanding blood myeloid cell numbers and recruiting monocyte‐derived macrophages (cluster of differentiation 11b+ [CD11b+] interstitial and exudative macrophages [IM and ExM]), neutrophils and eosinophils into the lungs. This inflammatory response was associated with lung tissue injury and oedema. Importantly, CSL311 treatment in CS‐exposed mice markedly reduced myeloid cell numbers in the blood and BAL compartment. Furthermore, CSL311 significantly reduced lung CD11b+ IM and ExM, neutrophils and eosinophils, and this decline was associated with a significant reduction in matrix metalloproteinase‐12 (MMP‐12) and IL‐17A expression, tissue injury and oedema. Conclusion: This study identifies CSL311 as a therapeutic antibody that potently inhibits immunopathology and lung injury caused by acute CS exposure. Myeloid cells, including macrophages, neutrophils and eosinophils, are important cellular drivers of inflammation and injury. In this study, we blocked granulocyte monocyte‐colony stimulating factor, IL‐5 and IL‐3 signalling with an anti‐βc receptor antibody (CSL311), which greatly reduced lung inflammation and injury in a pre‐clinical model of acute cigarette smoke exposure. [ABSTRACT FROM AUTHOR]

The polar magnetic chalcogenide phase Ba5Fe2ZnIn4S15 was synthesized and its structure was solved by single crystal XRD. It is the first member with a 3d magnetic metal (Fe3+) in the Pb5ZnGa6S15-type structure family of wide bandgap materials with non-linear optical properties. The three-dimensional framework possesses a low dimensional magnetic character through the presence of weakly interacting zig-zag chains made of corner-sharing FeS4 tetrahedra forming chain 1, [FeS2]−∞. The latter chains are separated by InS4 tetrahedra providing weak magnetic super-super exchanges between them. The framework is also constituted by chain 2, [In3Zn1S9]7−∞ (chain of T2-supertetrahedra) extended similarly to chain 1 along the direction c and connected through InS4 tetrahedra. Symmetry analysis shows that the intrinsic polarization observed in this class of materials is mostly due to the anionic framework. Preliminary magnetic measurements and density functional theory calculations suggest dominating antiferromagnetic interactions with strong super-exchange coupling within the Fe-chains. [ABSTRACT FROM AUTHOR]

Calreticulin (CALR) is recurrently mutated in myelofibrosis via a frameshift that removes an endoplasmic reticulum retention signal, creating a neoepitope potentially targetable by immunotherapeutic approaches. We developed a specific rat monoclonal IgG2α antibody, 4D7, directed against the common sequence encoded by both insertion and deletion mutations. 4D7 selectively bound to cells co‐expressing mutant CALR and thrombopoietin receptor (TpoR) and blocked JAK‐STAT signalling, TPO‐independent proliferation and megakaryocyte differentiation of mutant CALR myelofibrosis progenitors by disrupting the binding of CALR dimers to TpoR. Importantly, 4D7 inhibited proliferation of patient samples with both insertion and deletion CALR mutations but not JAK2 V617F and prolonged survival in xenografted bone marrow models of mutant CALR‐dependent myeloproliferation. Together, our data demonstrate a novel therapeutic approach to target a problematic disease driven by a recurrent somatic mutation that would normally be considered undruggable. Synopsis: CALR is recurrently mutated in myelofibrosis, creating a surface‐exposed neoepitope that activates the thrombopoietin receptor. A monoclonal antibody (4D7) with mutation‐specific efficacy in CALR mutant progenitors disrupts the receptor‐CALR complex and inhibits proliferation. 4D7 specifically blocks mutant CALR‐dependent proliferation and TPO‐independent megakaryocyte differentiation.Neoepitope targeting is a feasible and attractive strategy to overcome ruxolitinib‐persistence.Neoepitope targeting disrupts CALR oligomerisation with MPL and subsequent signal transduction.4D7 inhibits proliferation of patient samples with CALR mutations and prolongs survival in xenograft models. [ABSTRACT FROM AUTHOR]

Herein we report the original Ba10Fe7.75Zn5.25S18Si3O12 oxysulfide which crystallizes in a new structural type. Contrary to the usual oxychalcogenides, it crystallizes with a non-centrosymmetric 3D spatial network structure built from large magnetic clusters consisting of twelve (Fe2+/3+/Zn)S3O tetrahedra decorating a central Fe2+S6 octahedron and exhibiting a spin glass state. [ABSTRACT FROM AUTHOR]

Successful treatment of acute myeloid leukemia (AML) with chimeric antigen receptor (CAR) T cells is hampered by toxicity on normal hematopoietic progenitor cells and low CAR T cell persistence. Here, we develop third-generation anti-CD123 CAR T cells with a humanized CSL362-based ScFv and a CD28-OX40-CD3ζ intracellular signaling domain. This CAR demonstrates anti-AML activity without affecting the healthy hematopoietic system, or causing epithelial tissue damage in a xenograft model. CD123 expression on leukemia cells increases upon 5′-Azacitidine (AZA) treatment. AZA treatment of leukemia-bearing mice causes an increase in CTLA-4negative anti-CD123 CAR T cell numbers following infusion. Functionally, the CTLA-4negative anti-CD123 CAR T cells exhibit superior cytotoxicity against AML cells, accompanied by higher TNFα production and enhanced downstream phosphorylation of key T cell activation molecules. Our findings indicate that AZA increases the immunogenicity of AML cells, enhancing recognition and elimination of malignant cells by highly efficient CTLA-4negative anti-CD123 CAR T cells. The success of CAR-T cells for treating acute myeloid leukaemia (AML) is hampered by toxicity to normal cells and low CAR-T cell persistence. Here, the authors show that the demethylating compound 5′-Azacitdine increases anti-CD123 CAR-T cell cytotoxicity against AML. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: The efficacy of short‐term oral corticosteroids in chronic rhinosinusitis without nasal polyps (CRSsNP) is unknown. The aim of this controlled study was to assess the immediate and long‐term outcomes from a short course of a commonly used oral corticosteroid, prednisolone, in well‐defined CRSsNP patients. Study Design: Prospective, observational controlled study. Methods: A prospective‐controlled study of CRSsNP patients treated with prednisolone at 0.5 mg/kg tapered over 10 days and non‐prednisolone treated CRSsNP patients (controls) and follow‐up at 2, 6, and 12 months. Baseline and follow‐up SinoNasal Outcome Test (SNOT)‐22, nasal endoscopy (Lund‐Kennedy), and sinus CT scan scores (Lund‐Mackay) were compared. Results: At 2 months, there was a significant improvement in the SNOT‐22, nasal endoscopy, and sinus CT scan scores in the prednisolone group (P <.0001) compared with controls (p = ns, Mann–Whitney U test). 52.5% of prednisolone‐treated CRSsNP patients had improved symptoms and did not require sinus surgery at 12 months compared with 14.3% of controls (P <.001). Side‐effects were reported in 8.9% of prednisolone‐treated patients. Patients who benefited from prednisolone had a median symptom duration of 7.25 (99% confidence, upper limit of 11) months compared with 18 months in those requiring surgery. Conclusions: Short‐term oral prednisolone significantly improved all three clinical measures of disease in CRSsNP patients and avoided surgical intervention in 52.5% patients in the first 12 months. Patients with symptoms for less than 11 months were most likely to benefit. The side‐effects of oral steroids require careful consideration and further studies are needed to ascertain appropriate dosage and treatment duration. Level of Evidence: 3 Laryngoscope, 131:E2618–E2626, 2021 [ABSTRACT FROM AUTHOR]

Drug repurposing is promoted as a cost- and time-effective mechanism for providing new medicines. Often, however, there is insufficient consideration by academic researchers of the processes required to ensure that a repurposed drug can be used for a new indication. This may explain the inability of drug repurposing to fulfill its promise. Important aspects, often overlooked, include financial and intellectual property considerations, the clinical and regulatory path, and clinical equipoise, which provides ethical justification for randomized controlled trials. The goal of drug repurposing is to obtain a new regulator-approved label for an existing drug, and so, the trajectory for drug repurposing and traditional drug development is similar. Here, we discuss factors critical for a successful repurposed medicine to help academic investigators better identify drug repurposing opportunities. [ABSTRACT FROM AUTHOR]

The fourth industrial revolution has forced most companies to technologically evolve, applying new digital tools, so that their workers can have the necessary skills to face changing work environments. This article presents a scoping review of the literature on virtual reality-based training systems. The methodology consisted of four steps, which pose research questions, document search, paper selection, and data extraction. From a total of 350 peer-reviewed database articles, such as SpringerLink, IEEEXplore, MDPI, Scopus, and ACM, 44 were eventually chosen, mostly using the virtual reality haptic glasses and controls from Oculus Rift and HTC VIVE. It was concluded that, among the advantages of using this digital tool in the industry, is the commitment, speed, measurability, preservation of the integrity of the workers, customization, and cost reduction. Even though several research gaps were found, virtual reality is presented as a present and future alternative for the efficient training of human resources in the industrial field. [ABSTRACT FROM AUTHOR]

Anti- c mAb CSL311 inhibits human nasal polyp pathophysiology in a humanized mouse xenograft model We found that treatment with CSL311 for 1 week resulted in an immediate reduction in NP volume measured externally, which was not observed with positive control prednisolone treatment. CSL311 mAb treatment reduces (A) volume of nasal polyp measured externally every week, (B) granulocytes and plasma B-cell populations, (C) mast cell numbers, (D) mucous gland numbers and mucus production and (E) fibroblast numbers in xenografted nasal polyps compared with isotype control mAb treatment. To understand how CSL311 treatment inhibited NP growth, we examined the immune cell profiles in the xenografted NPs collected at the end of the 5-week engraftment. [Extracted from the article]

The new phase Co2ScSbO6 and Ni2−xCoxScSbO6 solid solutions adopt the polar Ni3TeO6-type structure and order magnetically below 60 K. A series of long-period lock-in [0 0 1/3n] spin structures with n = 5, 6, 8 and 10 is discovered, coexisting with a ferrimagnetic [0 0 0] phase at high Co-contents. The presence of electrical polarisation and spontaneous magnetisations offers possibilities for multiferroic properties. [ABSTRACT FROM AUTHOR]

Although counselors in 44 states are mandatory reporters of child maltreatment, they may lack an understanding of their legally designated role. This article presents the results of a systematic review of child maltreatment reporting laws in all 50 states and the District of Columbia. The authors apply relevant legislation to real‐life contexts for counselors. [ABSTRACT FROM AUTHOR]

Most infections with Mycobacterium tuberculosis (Mtb) manifest as a clinically asymptomatic, contained state, known as latent tuberculosis infection, that affects approximately one-quarter of the global population1. Although fewer than one in ten individuals eventually progress to active disease2, tuberculosis is a leading cause of death from infectious disease worldwide3. Despite intense efforts, immune factors that influence the infection outcomes remain poorly defined. Here we used integrated analyses of multiple cohorts to identify stage-specific host responses to Mtb infection. First, using high-dimensional mass cytometry analyses and functional assays of a cohort of South African adolescents, we show that latent tuberculosis is associated with enhanced cytotoxic responses, which are mostly mediated by CD16 (also known as FcγRIIIa) and natural killer cells, and continuous inflammation coupled with immune deviations in both T and B cell compartments. Next, using cell-type deconvolution of transcriptomic data from several cohorts of different ages, genetic backgrounds, geographical locations and infection stages, we show that although deviations in peripheral B and T cell compartments generally start at latency, they are heterogeneous across cohorts. However, an increase in the abundance of circulating natural killer cells in tuberculosis latency, with a corresponding decrease during active disease and a return to baseline levels upon clinical cure are features that are common to all cohorts. Furthermore, by analysing three longitudinal cohorts, we find that changes in peripheral levels of natural killer cells can inform disease progression and treatment responses, and inversely correlate with the inflammatory state of the lungs of patients with active tuberculosis. Together, our findings offer crucial insights into the underlying pathophysiology of tuberculosis latency, and identify factors that may influence infection outcomes. Integrated analyses of multiple cohorts are used to obtain a better understanding of the immune state of latent infection with Mycobacterium tuberculosis, and factors that mediate and/or predict transitions from latent infection to active disease. [ABSTRACT FROM AUTHOR]

The interleukin-3 (IL-3) receptor is a cell-surface heterodimer that links the haemopoietic, vascular and immune systems and is overexpressed in acute and chronic myeloid leukaemia progenitor cells. It belongs to the type I cytokine receptor family in which the α-subunits consist of two fibronectin III-like domains that bind cytokine, and a third, evolutionarily unrelated and topologically conserved, N-terminal domain (NTD) with unknown function. Here we show by crystallography that, while the NTD of IL3Rα is highly mobile in the presence of IL-3, it becomes surprisingly rigid in the presence of IL-3 K116W. Mutagenesis, biochemical and functional studies show that the NTD of IL3Rα regulates IL-3 binding and signalling and reveal an unexpected role in preventing spontaneous receptor dimerisation. Our work identifies a dual role for the NTD in this cytokine receptor family, protecting against inappropriate signalling and dynamically regulating cytokine receptor binding and function. [ABSTRACT FROM AUTHOR]

Common goals of sustainable mobility approaches are to reduce the need for travel, to facilitate modal shifts, to decrease trip distances and to improve energy efficiency in the transportation systems. Among these issues, modal shift plays an important role for the adoption of vehicles with fewer or zero emissions. Nowadays, the electric bike (e-bike) is becoming a valid alternative to cars in urban areas. However, to promote modal shift, a better understanding of the mobility behaviour of e-bike users is required. In this paper, we investigate the mobility habits of e-bikers using GPS data collected in Belgium from 2014 to 2015. By analysing more than 10,000 trips, we provide insights about e-bike trip features such as: distance, duration and speed. In addition, we offer a deep look into which routes are preferred by bike owners in terms of their physical characteristics and how weather influences e-bike usage. Results show that trips with higher travel distances are performed during working days and are correlated with higher average speeds. Usage patterns extracted from our data set also indicate that e-bikes are preferred for commuting (home-work) and business (work related) trips rather than for recreational trips. [ABSTRACT FROM AUTHOR]

Human travel behaviour has been addressed in many transport studies, where travel survey methods have been widely used to collect self-reported insights of daily mobility patterns. However, since the introduction of Global Navigation Satellite Systems (GNSS) and more recently smartphones with built-in GNSS, researchers have adopted these ubiquitous devices as tools for collecting mobility behaviour data. Although most studies recognize the applicability of this technology, it still has limitations. These are rarely addressed in a quantifiedmanner. Often the quality of the collected data tends to be overestimated and these errors propagate into the aggregated results providing incomplete knowledge of the levels of confidence of the results and conclusions. In this study, we focus on the completeness aspects of data quality using GNSS data from four campaigns in the Flanders region of Belgium. The empirical results are based on mobility behaviour data collected through smartphones and include more than 450 participants over a period of twenty-nine months. Our findings show which transport mode is affected the most and how land use affects the quality of the collected data. In addition, we provide insights into the time to first fix that can be used for a better estimation of travel patterns. [ABSTRACT FROM AUTHOR]

Desmogleins (DSG) are a family of cadherin adhesion proteins that were first identified in desmosomes and provide cardiomyocytes and epithelial cells with the junctional stability to tolerate mechanical stress. However, one member of this family, DSG2, is emerging as a protein with additional biological functions on a broader range of cells. Here we reveal that DSG2 is expressed by non-desmosome-forming human endothelial progenitor cells as well as their mature counterparts [endothelial cells (ECs)] in human tissue from healthy individuals and cancer patients. Analysis of normal blood and bone marrow showed that DSG2 is also expressed by CD34CD45 hematopoietic progenitor cells. An inability to detect other desmosomal components, i.e., DSG1, DSG3 and desmocollin (DSC)2/3, on these cells supports a solitary role for DSG2 outside of desmosomes. Functionally, we show that CD34CD45DSG2 progenitor cells are multi-potent and pro-angiogenic in vitro. Using a 'knockout-first' approach, we generated a Dsg2 loss-of-function strain of mice ( Dsg2 ) and observed that, in response to reduced levels of Dsg2: (i) CD31 ECs in the pancreas are hypertrophic and exhibit altered morphology, (ii) bone marrow-derived endothelial colony formation is impaired, (iii) ex vivo vascular sprouting from aortic rings is reduced, and (iv) vessel formation in vitro and in vivo is attenuated. Finally, knockdown of DSG2 in a human bone marrow EC line reveals a reduction in an in vitro angiogenesis assay as well as relocalisation of actin and VE-cadherin away from the cell junctions, reduced cell-cell adhesion and increased invasive properties by these cells. In summary, we have identified DSG2 expression in distinct progenitor cell subpopulations and show that, independent from its classical function as a component of desmosomes, this cadherin also plays a critical role in the vasculature. [ABSTRACT FROM AUTHOR]

Purpose: To describe the prevalence of epiphora and associated factors after uncomplicated phacoemulsification.Methods: Prospective and descriptive design. A group of 125 patients was asked about tearing one to two weeks after cataract surgery. A comprehensive examination was performed on the patients who answered affirmatively. All patients were re-interviewed by phone after three months and those who complained of epiphora were explored again.Results: Two weeks after surgery, prevalence of epiphora was 10.4%, but only 3.2% appeared after surgery. In patients with preoperative epiphora, the most frequently associated factors were ocular surface alterations (89%) and unctual and canalicular stenosis (56%). In patients with "new onset" epiphora (4 patients), these factors were: blepharitis (2/4), low tear break-up time (2/4), high tear meniscus (2/4), partial nasolacrimal duct obstruction (2/4), and unctual stenosis (1/4). Three months after surgery, the prevalence of epiphora was 13%, but only 7% appeared after surgery (6 patients). Of those 6 patients, 4 were re-examined: nasolacrimal duct obstruction (2/4), ocular surface problems (3/4), and unctual stenosis (1/4).Conclusions: Presence of epiphora two weeks after phacoemulsification was infrequent, despite being present in a high proportion of patients before surgery. There was not a noticeable increase in epiphora at three months. The most frequently related factors were mixed disorders of the ocular surface and lacrimal system, without an important incidence of unctual and canalicular stenosis. We consider that our perception about complaints from patients after phacoemulsification may be biased due to those who had previously suffered from epiphora. [ABSTRACT FROM AUTHOR]

In non-clinical studies, the proteasome inhibitor ixazomib inhibits cell growth in a broad panel of solid tumor cell lines in vitro. In contrast, antitumor activity in xenograft tumors is model-dependent, with some solid tumors showing no response to ixazomib. In this study we examined factors responsible for ixazomib sensitivity or resistance using mouse xenograft models. A survey of 14 non-small cell lung cancer (NSCLC) and 6 colon xenografts showed a striking relationship between ixazomib activity and KRAS genotype; tumors with wild-type (WT) KRAS were more sensitive to ixazomib than tumors harboring KRAS activating mutations. To confirm the association between KRAS genotype and ixazomib sensitivity, we used SW48 isogenic colon cancer cell lines. Either KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cells to generate cells that stably express activated KRAS. SW48 KRAS WT tumors, but neither SW48-KRAS-G13D tumors nor SW48-KRAS-G12V tumors, were sensitive to ixazomib in vivo. Since activated KRAS is known to be associated with metabolic reprogramming, we compared metabolite profiling of SW48-WT and SW48-KRAS-G13D tumors treated with or without ixazomib. Prior to treatment there were significant metabolic differences between SW48 WT and SW48-KRAS-G13D tumors, reflecting higher oxidative stress and glucose utilization in the KRAS-G13D tumors. Ixazomib treatment resulted in significant metabolic regulation, and some of these changes were specific to KRAS WT tumors. Depletion of free amino acid pools and activation of GCN2-eIF2α-pathways were observed both in tumor types. However, changes in lipid beta oxidation were observed in only the KRAS WT tumors. The non-clinical data presented here show a correlation between KRAS genotype and ixazomib sensitivity in NSCLC and colon xenografts and provide new evidence of regulation of key metabolic pathways by proteasome inhibition. [ABSTRACT FROM AUTHOR]

The article discusses the availability of pharmacological interventions for the treatment of Parkinson's disease (PD). It states that pharmacological dopamine replacement considered to be main therapy for treating PD which is caused mainly by progressive loss of dopaminergic neurons in the substantia nigra par compacta (SNpc) owing to one of the axon guidance molecule known as repulsive guidance molecule a (RGMa). It mentions therapies are formulated to tackle all possibilities including RGMa.

Sr2FeMoO6 has been extensively studied for application in spintronic devices. Through the topochemical de-intercalation of oxygen anions with metal hydride reduction, we demonstrate that the high temperature cubic phase is stabilized, at room temperature, whilst leaving the magnetic ordering intact. Synchrotron X-ray and neutron powder diffraction were used to characterize the structure and stoichiometry of the reduced oxide. [ABSTRACT FROM AUTHOR]

Powder neutron diffraction and magnetic susceptibility measurements at 10–300 K have been used to determine the crystal and magnetic structures of brownmillerite type Ca2Cr2O5, which was obtained by reduction of the high pressure phase CaCrO3 through hard–soft chemistry. The ambient temperature crystal structure of Ca2Cr2O5 is refined in space group I2mb and the unusual tetrahedral coordination of Cr3+ results in local structural distortions. Cr3+ spins order antiferromagnetically below 220 K and a substantial observed canting of moments shows that Heisenberg exchange is weak or frustrated and competes with antisymmetric Dzialoshinskii–Moriya interactions. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) blasts express high levels of interlekin-3 (IL-3) receptor-α (CD123). CSL360 is a recombinant, chimeric immunoglobulin G1 (IgG1), anti-CD123 monoclonal antibody (MoAb) that neutralizes IL-3 and demonstrates anti-leukemic activity in vitro. This phase 1 study assessed safety, pharmacokinetics and bioactivity of weekly intravenous CSL360 for 12 weeks in 40 patients with advanced AML across five dose levels (0.1-10.0 mg/kg). Other than mild infusion reactions, CSL360 was well tolerated. The maximal tolerated dose was not reached. The half-life was 4.9 days, and the area under the curve (AUC) and maximum concentration (Cmax) increased proportionally with dose. Doses ≥ 3.0 mg/kg resulted in complete saturation and down-regulation of CD123 and abolition of ex vivo proliferative responsiveness to IL-3, indicating adequate blockade of IL-3 signaling. Two patients responded, with one remaining in complete remission after 17 doses. CSL360 bound CD123 specifically, but did not induce anti-leukemic activity in most patients. While safe, MoAb blockade of CD123 function is insufficient as a therapeutic strategy. [ABSTRACT FROM AUTHOR]

New CaCrO3−δ superstructure phases (δ = 0.33, 0.4, and 0.5) have been discovered through ‘soft’ low temperature reduction of the perovskite CaCrO3 made at ‘hard’ high pressure–temperature conditions. Their structures form a related series based on stacking of octahedral and tetrahedral chromium oxide layers. [ABSTRACT FROM AUTHOR]