1,155 research outputs found

    Pass a Law, Any Law, Fast! State Legislative Responses to the Kelo Backlash

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    The Supreme Court in Kelo v. City of New London left protection of property against takings for economic development to the states. Since Kelo, thirty-seven states have enacted legislation to update their eminent domain laws. This paper is the first to theoretically and empirically analyze the factors that influence whether, in what manner, and how quickly states change their laws through new legislation. Fourteen of the thirty-seven new laws offer only weak protections against development takings. The legislative response to Kelo was responsive to measures of the backlash but only in the binary decision whether to pass any new law. The decision to enact a meaningful restriction was more a function of relevant political economy measures. States with more economic freedom, greater value of new housing construction, and less racial and income inequality are more likely to have enacted stronger restrictions, and sooner. Of the thirteen states that have not updated, Arkansas, Oklahoma and Mississippi are highly likely to do so in the future. Hawaii, Massachusetts and New York are unlikely to update ever if at all

    Identification of a novel synthetic lethal vulnerability in non-small cell lung cancer by co-targeting TMPRSS4 and DDR1

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    Finding novel targets in non-small cell lung cancer (NSCLC) is highly needed and identification of synthetic lethality between two genes is a new approach to target NSCLC. We previously found that TMPRSS4 promotes NSCLC growth and constitutes a prognostic biomarker. Here, through large-scale analyses across 5 public databases we identified consistent co-expression between TMPRSS4 and DDR1. Similar to TMPRSS4, DDR1 promoter was hypomethylated in NSCLC in 3 independent cohorts and hypomethylation was an independent prognostic factor of disease-free survival. Treatment with 5-azacitidine increased DDR1 levels in cell lines, suggesting an epigenetic regulation. Cells lacking TMPRSS4 were highly sensitive to the cytotoxic effect of the DDR1 inhibitor dasatinib. TMPRSS4/DDR1 double knock-down (KD) cells, but not single KD cells suffered a G0/G1 cell cycle arrest with loss of E2F1 and cyclins A and B, increased p21 levels and a larger number of cells in apoptosis. Moreover, double KD cells were highly sensitized to cisplatin, which caused massive apoptosis (~40%). In vivo studies demonstrated tumor regression in double KD-injected mice. In conclusion, we have identified a novel vulnerability in NSCLC resulting from a synthetic lethal interaction between DDR1 and TMPRSS4

    Structural dynamics during laser induced ultrafast demagnetization

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    The mechanism underlying femtosecond laser pulse induced ultrafast magnetization dynamics remains elusive despite two decades of intense research on this phenomenon. Most experiments focused so far on characterizing magnetization and charge carrier dynamics, while first direct measurements of structural dynamics during ultrafast demagnetization were reported only very recently. We here present our investigation of the infrared laser pulse induced ultrafast demagnetization process in a thin Ni film, which characterizes simultaneously magnetization and structural dynamics. This is achieved by employing femtosecond time resolved X-ray resonant magnetic reflectivity (tr-XRMR) as probe technique. The experimental results reveal unambiguously that the sub-picosecond magnetization quenching is accompanied by strong changes in non-magnetic X-ray reflectivity. These changes vary with reflection angle and changes up to 30%\% have been observed. Modeling the X-ray reflectivity of the investigated thin film, we can reproduce these changes by a variation of the apparent Ni layer thickness of up to 1%\%. Extending these simulations to larger incidence angles we show that tr-XRMR can be employed to discriminate experimentally between currently discussed models describing the ultrafast demagnetization phenomenon

    Oscillatons revisited

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    In this paper, we study some interesting properties of a spherically symmetric oscillating soliton star made of a real time-dependent scalar field which is called an oscillaton. The known final configuration of an oscillaton consists of a stationary stage in which the scalar field and the metric coefficients oscillate in time if the scalar potential is quadratic. The differential equations that arise in the simplest approximation, that of coherent scalar oscillations, are presented for a quadratic scalar potential. This allows us to take a closer look at the interesting properties of these oscillating objects. The leading terms of the solutions considering a quartic and a cosh scalar potentials are worked in the so called stationary limit procedure. This procedure reveals the form in which oscillatons and boson stars may be related and useful information about oscillatons is obtained from the known results of boson stars. Oscillatons could compete with boson stars as interesting astrophysical objects, since they would be predicted by scalar field dark matter models.Comment: 10 pages REVTeX, 10 eps figures. Updated files to match version published in Classical and Quantum Gravit

    Galactic Collapse of Scalar Field Dark Matter

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    We present a scenario for galaxy formation based on the hypothesis of scalar field dark matter. We interpret galaxy formation through the collapse of a scalar field fluctuation. We find that a cosh potential for the self-interaction of the scalar field provides a reasonable scenario for galactic formation, which is in agreement with cosmological observations and phenomenological studies in galaxies.Comment: 4 pages, 3 figue

    Perturbative evolution of particle orbits around Kerr black holes: time domain calculation

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    Treating the Teukolsky perturbation equation numerically as a 2+1 PDE and smearing the singularities in the particle source term by the use of narrow Gaussian distributions, we have been able to reproduce earlier results for equatorial circular orbits that were computed using the frequency domain formalism. A time domain prescription for a more general evolution of nearly geodesic orbits under the effects of radiation reaction is presented. This approach can be useful when tackling the more realistic problem of a stellar-mass black hole moving on a generic orbit around a supermassive black hole under the influence of radiation reaction forces.Comment: 8 pages, 5 figures, problems with references and double-printing fixe

    Diagnostic and prognostic value of B4GALT1 hypermethylation and its clinical significance as a novel circulating cell-free DNA biomarker in colorectal cancer

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    Epigenetic modifications of glyco-genes have been documented in different types of cancer and are tightly linked to proliferation, invasiveness, metastasis, and drug resistance. This study aims to investigate the diagnostic, prognostic, and therapy-response predictive value of the glyco-gene B4GALT1 in colorectal cancer (CRC) patients. A Kaplan-Meier analysis was conducted in 1418 CRC patients (GEO and TCGA datasets) to assess the prognostic and therapy-response predictive values of the aberrant expression and methylation status of B4GALT1. Quantitative methylation-specific PCR (QMSP) and droplet digital quantitative methylation-specific PCR (dd-QMSP) were respectively used to detect hypermethylated B4GALT1 in metastasis and plasma in four cohorts of metastatic CRC cases (mCRC). Both the downregulated expression and promoter hypermethylation of B4GALT1 have a negative prognostic impact on CRC. Interestingly a low expression level of B4GALT1 was significantly associated with poor cetuximab response (progression-free survival (PFS) p = 0.01) particularly in wild-type (WT)-KRAS patients (p = 0.03). B4GALT1 promoter was aberrantly methylated in liver and lung metastases. The detection of hypermethylated B4GALT1 in plasma of mCRC patients showed a highly discriminative receiver operating characteristic (ROC) curve profile (area under curve (AUC) value 0.750; 95% CI: 0.592-0.908, p = 0.008), clearly distinguishing mCRC patients from healthy controls. Based on an optimal cut-off value defined by the ROC analysis, B4GALT1 yield a 100% specificity and a 50% sensitivity. These data support the potential value of B4GALT1 as an additional novel biomarker for the prediction of cetuximab response, and as a specific and sensitive diagnostic circulating biomarker that can be detected in CRC

    The effect of chest compression frequency on the quality of resuscitation by lifeguards. A prospective randomized crossover multicenter simulation trial

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    BACKGROUND: The ability to perform high-quality cardiopulmonary resuscitation is one of the basic skills for lifeguards. The aim of the study was to assess the influence of chest compression frequency on the quality of the parameters of chest compressions performed by lifeguards. METHODS: This prospective observational, randomized, crossover simulation study was performed with 40 lifeguards working in Warsaw, Wroclaw, and Poznan, Poland. The subjects then participated in a target study, in which they were asked to perform 2-min cycles of metronome-guided chest compressions at different rates: 80, 90, 100, 110, 120, 130, 140, and 150 compressions per minute (CPM). RESULTS: The study involved 40 lifeguards. Optimal chest compression score calculated by manikin software was achieved for 110-120 CPM. Chest compression depth achieved 53 (interquartile range [IQR] 52-54) mm, 56 (IQR 54-57) mm, 52.5 (IQR 50-54) mm, 53 (IQR 52-53) mm, 50 (IQR 49-51) mm, 47 (IQR 44-51) mm, 41 (IQR 40-42) mm, 38 (IQR 38-43) mm for 80, 90, 100, 110, 120, 130, 140 and 150 CPM, respectively. The percentage of chest compressions with the correct depth was lower for rates exceeding 120 CPM. CONCLUSIONS: The rate of 100-120 CPM, as recommended by international guidelines, is the optimal chest compression rate for cardiopulmonary resuscitation performed by lifeguards. A rate above 120 CPM was associated with a dramatic decrease in chest compression depth and overall chest compression quality. The role of full chest recoil should be emphasized in basic life support training

    CT Radiomics in Colorectal Cancer: Detection of KRAS Mutation Using Texture Analysis and Machine Learning

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    In this work, by using descriptive techniques, the characteristics of the texture of the CT (computed tomography) image of patients with colorectal cancer were extracted and, subsequently, classified in KRAS+ or KRAS-. This was accomplished by using different classifiers, such as Support Vector Machine (SVM), Grading Boosting Machine (GBM), Neural Networks (NNET), and Random Forest (RF). Texture analysis can provide a quantitative assessment of tumour heterogeneity by analysing both the distribution and relationship between the pixels in the image. The objective of this research is to demonstrate that CT-based Radiomics can predict the presence of mutation in the KRAS gene in colorectal cancer. This is a retrospective study, with 47 patients from the University Hospital, with a confirmatory pathological analysis of KRAS mutation. The highest accuracy and kappa achieved were 83% and 64.7%, respectively, with a sensitivity of 88.9% and a specificity of 75.0%, achieved by the NNET classifier using the texture feature vectors combining wavelet transform and Haralick coefficients. The fact of being able to identify the genetic expression of a tumour without having to perform either a biopsy or a genetic test is a great advantage, because it prevents invasive procedures that involve complications and may present biases in the sample. As well, it leads towards a more personalized and effective treatmentThis work has received financial support from the Xunta de Galicia (Centro singular de investigación de Galicia, accreditation 2020–2023) and the European Union (European Regional Development Fund—ERDF), Project MTM2016-76969-PS

    Pathogenesis and Clinical Relevance of Candida Biofilms in Vulvovaginal Candidiasis

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    The ability of Candida spp. to form biofilms is crucial for its pathogenicity, and thus, it should be considered an important virulence factor in vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). Its ability to generate biofilms is multifactorial and is generally believed to depend on the site of infection, species and strain involved, and the microenvironment in which the infection develops. Therefore, both cell surface proteins, such as Hwp1, Als1, and Als2, and the cell wall-related protein, Sun41, play a critical role in the adhesion and virulence of the biofilm. Immunological and pharmacological approaches have identified the NLRP3 inflammasome as a crucial molecular factor contributing to host immunopathology. In this context, we have earlier shown that Candida albicans associated with hyphae-secreted aspartyl proteinases (specifically SAP4-6) contribute to the immunopathology of the disease. Transcriptome profiling has revealed that non-coding transcripts regulate protein synthesis post-transcriptionally, which is important for the growth of Candida spp. Other studies have employed RNA sequencing to identify differences in the 1,245 Candida genes involved in surface and invasive cellular metabolism regulation. In vitro systems allow the simultaneous processing of a large number of samples, making them an ideal screening technique for estimating various physicochemical parameters, testing the activity of antimicrobial agents, and analyzing genes involved in biofilm formation and regulation (in situ) in specific strains. Murine VVC models are used to study C. albicans infection, especially in trials of novel treatments and to understand the cause(s) for resistance to conventional therapeutics. This review on the clinical relevance of Candida biofilms in VVC focuses on important advances in its genomics, transcriptomics, and proteomics. Moreover, recent experiments on the influence of biofilm formation on VVC or RVVC pathogenesis in laboratory animals have been discussed. A clear elucidation of one of the pathogenesis mechanisms employed by Candida biofilms in vulvovaginal candidiasis and its applications in clinical practice represents the most significant contribution of this manuscript
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