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Investigating agency: methodological and empirical challenges

The promise of connecting agency and structure in studies of regional development is to disentangle causal effects and to better understand to what extent and how individuals, groups of individuals, and organisations can shape regional trajectories. This is not without challenges because agency and structure are deep theoretical constructs, which are not easily translated into empirical research.

Distinct mechanisms of resistance to fulvestrant treatment dictate level of ER independence and selective response to CDK inhibitors in metastatic breast cancer

BACKGROUND: Resistance to endocrine treatment in metastatic breast cancer is a major clinical challenge. Clinical tools to predict both drug resistance and possible treatment combination approaches to overcome it are lacking. This unmet need is mainly due to the heterogeneity underlying both the mechanisms involved in resistance development and breast cancer itself.METHODS: To study the complexity

Identification of Extracellular Matrix Proteins Secreted by Human Dermal Fibroblasts Cultured in 3D Electrospun Scaffolds

The appreciation that cell interactions in tissues is dependent on their three dimensional (3D) distribution has stimulated the development of 3D cell culture models. We constructed an artificial 3D tumour by culturing human breast cancer JIMT-1 cells and human dermal fibroblasts (HDFs) in a 3D network of electrospun polycaprolactone fibres. Here, we investigate ECM components produced by the cell

Human epidermal growth factor receptor-3 expression is regulated at transcriptional level in breast cancer settings by junctional adhesion molecule-a via a pathway involving beta-catenin and foxa1

The success of breast cancer therapies targeting the human epidermal growth factor receptor-2 (HER2) is limited by the development of drug resistance by mechanisms including upregulation of HER3. Having reported that HER2 expression and resistance to HER2-targeted therapies can be regulated by Junctional Adhesion Molecule-A (JAM-A), this study investigated if JAM-A regulates HER3 expression. Expre

A Static-99R Validation Study on Individuals With Mental Disorders : 5 to 20 Years of Fixed Follow-Up After Sexual Offenses

‘The Static-99R is one of the most commonly used risk assessment instruments for individuals convicted of sexual offenses. It has been validated for use on many populations, but few studies specifically target and describe individuals with mental disorders. Additionally, research on the discriminative properties (how well the instrument separates recidivists from non-recidivists) of the instrument

A novel mouse monoclonal antibody c42 against c-terminal peptide of alpha-1-antitrypsin

The C-terminal-fragments of alpha1-antitrypsin (AAT) have been identified and their diverse biological roles have been reported in vitro and in vivo. These findings prompted us to develop a monoclonal antibody that specifically recognizes C-36 peptide (corresponding to residues 359–394) resulting from the protease-associated cleavage of AAT. The C-36-targeting mouse mono-clonal Immunoglobulin M (I

Driven quadrature and spin squeezing in a cavity-coupled ensemble of two-level states

The generated magnitude of quadrature squeezing in a cavity-coupled ensemble, which is continuously driven using a coherent off-axis field, is theoretically explored. Using a truncated set of equations of motion derived from a Dicke Hamiltonian, steady-state quadrature squeezing of the cavity field is numerically calculated to approach a limit of -3dB, while frequency-modulated quadrature squeezin

A Local Barycentric Version of the Bak–Sneppen Model

We study the behaviour of an interacting particle system, related to the Bak–Sneppen model and Jante’s law process defined in Kennerberg and Volkov (Adv Appl Probab 50:414–439, 2018). Let N≥ 3 vertices be placed on a circle, such that each vertex has exactly two neighbours. To each vertex assign a real number, called fitness (we use this term, as it is quite standard for Bak–Sneppen models). Now f

Runaway stars masquerading as star formation in galactic outskirts

In the outskirts of nearby spiral galaxies, star formation is observed in extremely low gas surface densities. Star formation in these regions, where the interstellar medium is dominated by diffuse atomic hydrogen, is difficult to explain with classic star formation theories. In this letter, we introduce runaway stars as an explanation for this observation. Runaway stars, produced by collisional d

Generation of the human pluripotent stem-cell-derived astrocyte model with forebrain identity

Astrocytes form functionally and morphologically distinct populations of cells with brain-region-specific properties. Human pluripotent stem cells (hPSCs) offer possibilities to generate astroglia for studies investigating mechanisms governing the emergence of astrocytic diversity. We established a method to generate human astrocytes from hPSCs with forebrain patterning and final specification wit

BCAT1 decreases the sensitivity of cancer cells to cisplatin by regulating mTOR-mediated autophagy via branched-chain amino acid metabolism

Cisplatin is one of the most effective chemotherapy drugs and is widely used in the treatment of cancer, including hepatocellular carcinoma (HCC) and cervical cancer, but its therapeutic benefit is limited by the development of resistance. Our previous studies demonstrated that BCAT1 promoted cell proliferation and decreased cisplatin sensitivity in HCC cells. However, the exact role and mechanism

Modelling of energy-dependent spectral resolution for SPECT Monte Carlo simulations using SIMIND

Monte Carlo (MC) modelling techniques have been used extensively in Nuclear Medicine (NM). The theoretical energy resolution relationship (∝1/E−−√), does not accurately predict the gamma camera detector response across all energies. This study aimed to validate the accuracy of an energy resolution model for the SIMIND MC simulation code emulating the Siemens Symbia T16 dual-head gamma camera.Me

The genetics of sudden infant death syndrome—towards a gene reference resource

Sudden infant death syndrome (SIDS) is the unexpected death of an infant under one year of age that remains unexplained after a thorough investigation. Despite SIDS remaining a diagnosis of exclusion with an unexplained etiology, it is widely accepted that SIDS can be caused by environmental and/or biological factors, with multiple underlying candidate genes. However, the lack of biomarkers raises

HiggsSignals-2 : probing new physics with precision Higgs measurements in the LHC 13 TeV era

The program HiggsSignals confronts the predictions of models with arbitrary Higgs sectors with the available Higgs signal rate and mass measurements, resulting in a likelihood estimate. A new version of the program, HiggsSignals-2, is presented that contains various improvements in its functionality and applicability. In particular, the new features comprise improvements in the theoretical input f

C-Reactive Protein Levels in Systemic Lupus Erythematosus Are Modulated by the Interferon Gene Signature and CRP Gene Polymorphism rs1205

Objectives: Patients with systemic lupus erythematosus (SLE) often display modest elevations of C-reactive protein (CRP) despite raised disease activity and increased interleukin (IL-) 6. We asked to what extent IL-6 levels, the CRP polymorphism rs1205, and the type I interferon (IFN) gene signature affects the basal CRP levels in patients with SLE during a quiescent phase of the disease. Methods:

New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases

The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of p