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Molecular dynamics simulations of nanometric cutting of single crystal copper sheets using a diamond tool

Nanometric cutting of a single crystal copper workpiece of different crystallographic orientations by a stiff cylindrical cubic diamond tool has been investigated by MD simulations using the freeware LAMMPS. The chip evolves during the cutting process and forms depending on crystal orientation, cutting velocity and tool geometry. It was found that no significant difference in the cutting force mag

Direct role of FLT3 in regulation of early lymphoid progenitors

Given that FLT3 expression is highly restricted on lymphoid progenitors, it is possible that the established role of FLT3 in the regulation of B and T lymphopoiesis reflects its high expression and role in regulation of lymphoid-primed multipotent progenitors (LMPPs) or common lymphoid progenitors (CLPs). We generated a Flt3 conditional knock-out (Flt3fl/fl) mouse model to address the direct role

Circulating lipids and breast cancer prognosis in the Malmö diet and cancer study

Purpose: Examine the association between circulating lipids and breast cancer outcomes in patients enrolled in the Malmö Diet and Cancer Study (MDCS). Patients and methods: Circulating lipid levels were measured in blood sampled upon enrollment in the female MDCS cohort (N = 17,035). We identified all MDCS participants with incident invasive breast cancer diagnosed between 1991 and 2014. Follow-up

Preserved function of afferent parvalbumin-positive perisomatic inhibitory synapses of dentate granule cells in rapidly kindled mice

Parvalbumin- (PV-) containing basket cells constitute perisomatic GABAergic inhibitory interneurons innervating principal cells at perisomatic area, a strategic location that allows them to efficiently control the output and synchronize oscillatory activity at gamma frequency (30–90 Hz) oscillations. This oscillatory activity can convert into higher frequency epileptiform activity, and therefore c

The calcium channel subunit gamma-4 is regulated by MafA and necessary for pancreatic beta-cell specification

Voltage-gated Ca2+ (CaV) channels trigger glucose-induced insulin secretion in pancreatic beta-cell and their dysfunction increases diabetes risk. These heteromeric complexes include the main subunit alpha1, and the accessory ones, including subunit gamma that remains unexplored. Here, we demonstrate that CaV gamma subunit 4 (CaVγ4) is downregulated in islets from human donors with diabetes, diabe

Physical activity and survival following breast cancer

INTRODUCTION:Physical activity (PA) leads to improved survival in women following the diagnosis of breast cancer, but it is less clear whether PA has equally positive effects regardless of age at diagnosis. The purpose of our study was to evaluate the association between post-diagnosis PA and survival in women aged below or over 55 years at diagnosis.METHODS:From a prospective population-based coh

Direct reprogramming of fibroblasts into antigen-presenting dendritic cells

Ectopic expression of transcription factors has been used to reprogram differentiated somatic cells toward pluripotency or to directly reprogram them to other somatic cell lineages. This concept has been explored in the context of regenerative medicine. Here, we set out to generate dendritic cells (DCs) capable of presenting antigens from mouse and human fibroblasts. By screening combinations of 1

A low-frequency inactivating AKT2 variant enriched in the finnish population is associated with fasting insulin levels and type 2 diabetes risk

To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding var

Ultra-high field magnetic resonance imaging parameter mapping in the posterior horn of ex vivo human menisci

Objective: To investigate the relationship between meniscus magnetic resonance (MR) relaxation parameters and meniscus degradation through quantitative imaging of ex vivo posterior horns of menisci from subjects with and without knee osteoarthritis (OA). Design: We sampled medial and lateral menisci from ten medial compartment knee OA patients (mean age 63 years) undergoing total knee replacement

Spatially resolved structural and chemical properties of the white layer in machined Inconel 718 super alloy

Inconel 718 is one type of nickel-based alloy used for a large range of applications, including gas turbines and aeroengines components. Although mechanical and thermodynamic properties of this material have been deeply studied in the past years, a method able to investigate local properties of the thin white layer formed on the alloy surface after machining remains challenging. Here, a 90 nm X-ra

Expression of Stress-Induced Genes in Bronchoalveolar Lavage Cells and Lung Fibroblasts from Healthy and COPD Subjects

Chronic obstructive pulmonary disease (COPD) is commonly caused from smoking cigarettes that induce biological stress responses. Previously we found disorganized endoplasmic reticulum (ER) in fibroblasts from COPD with different responses to chemical stressors compared to healthy subjects. Here, we aimed to investigate differences in stress-related gene expressions within lung cells from COPD and

Associations of modifiable and non-modifiable risk factors with cognitive functions – a prospective, population-based, 17 years follow-up study of 3,229 individuals

Background: Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype. Methods: Participa

Molecular patterns of resistance to immune checkpoint blockade in melanoma

Immune checkpoint blockade (ICB) has improved outcome for patients with metastatic melanoma but not all benefit from treatment. Several immune- and tumor intrinsic features are associated with clinical response at baseline. However, we need to further understand the molecular changes occurring during development of ICB resistance. Here, we collect biopsies from a cohort of 44 patients with melanom

A temporal developmental map separates human NK cells from noncytotoxic ILCs through clonal and single-cell analysis

Natural killer (NK) cells represent the cytotoxic member within the innate lymphoid cell (ILC) family that are important against viral infections and cancer. Although the NK cell emergence from hematopoietic stem and progenitor cells through multiple intermediate stages and the underlying regulatory gene network has been extensively studied in mice, this process is not well characterized in humans

Exploring the Functional Landscape of the p53 Regulatory Domain : The Stabilizing Role of Post-Translational Modifications

This study focuses on the intrinsically disordered regulatory domain of p53 and the impact of post-translational modifications. Through fully atomistic explicit water molecular dynamics simulations, we show the wealth of information and detailed understanding that can be obtained by varying the number of phosphorylated amino acids and implementing a restriction in the conformational entropy of the

A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer

Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.536 T > C; Ile163Thr-substitution in PSA) is associated with reduced prostate cancer risk, however, the functional relevance is unknown. Here, we identify that the SNP variant-induced change in PSA biochemical activity mediates

The climate, the fuel and the land use: long-term regional variability of biomass burning in boreal forests

The influence of different drivers on changes in North American and European boreal forests biomass burning (BB) during the Holocene was investigated based on the following hypotheses: land use was important only in the southernmost regions, while elsewhere climate was the main driver modulated by changes in fuel type. BB was reconstructed by means of 88 sedimentary charcoal records divided into s