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De novo activating mutations drive clonal evolution and enhance clonal fitness in KMT2A-rearranged leukemia

Activating signaling mutations are common in acute leukemia with KMT2A (previously MLL) rearrangements (KMT2A-R). These mutations are often subclonal and their biological impact remains unclear. Using a retroviral acute myeloid mouse leukemia model, we demonstrate that FLT3 ITD, FLT3 N676K, and NRAS G12D accelerate KMT2A-MLLT3 leukemia onset. Further, also subclonal FLT3 N676K mutations accelerate

A bi-objective formulation for robust defense strategies in multi-commodity networks

Characterizing system performance under disruption is a growing area of research, particularly for describing a system's resilience to disruptive events. Within the framework of system resilience, this study approaches the minimization of a multiple-commodity system's vulnerability to multiple disruptions. The vulnerability of a system is defined by the degree to which commodities can no longer fl

Influence of blue maize flour on gluten-free pasta quality and antioxidant retention characteristics

Due to its bioactive compounds, blue maize flour is a valuable ingredient for developing gluten-free products. The incorporation of alternative flours into gluten-free pasta is a challenge as it usually results in products that, despite their enhanced nutraceutical features, show reduced quality characteristics. Composite pasta was prepared with variable (25, 50 and 75%) contents of flours from wh

Power-aware cloud brownout : Response time and power consumption control

Cloud computing infrastructures are powering most of the web hosting services that we use at all times. A recent failure in the Amazon cloud infrastructure made many of the website that we use on a hourly basis unavailable1. This illustrates the importance of cloud applications being able to absorb peaks in workload, and at the same time to tune their power requirements to the power and energy cap

Microsaccade detection using pupil and corneal reflection signals

In contemporary research, microsaccade detection is typically performed using the calibrated gaze-velocity signal acquired from a video-based eye tracker. To generate this signal, the pupil and corneal reflection (CR) signals are subtracted from each other and a differentiation filter is applied, both of which may prevent small microsaccades from being detected due to signal distortion and noise a

Pharmacokinetic modelling and validation of the half-life extension needed to reduce the burden of infusions compared with standard factor VIII

Introduction: Currently, no universally accepted definition of extended half-life (EHL) recombinant FVIII (rFVIII) exists. Identifying the minimum half-life extension ratio required for a reduction in dosing frequency compared with standard rFVIII could enable a more practical approach to decisions around prophylaxis with EHL rFVIII. Aim: To identify the half-life extension ratio required to decre

Identification and use of personalized genomic markers for monitoring circulating tumor DNA

Digital PCR techniques are ideally suited for accurately quantifying trace amounts of target DNA sequences, such as tumor-derived mutant DNA that is present in the blood circulation of patients with cancer. Here, we describe an approach marrying low-coverage whole-genome sequencing of tumor tissues, to enumerate chromosomal rearrangement breakpoints, together with droplet digital PCR (ddPCR)-based

Alterations in Serum MicroRNA Profile during Hemodialysis-Potential Biological Implications

Background/Aims: Hemodialysis implies significant alterations in the profile of serum components. microRNAs (miRNAs) are present in the human serum and are considered to target distant tissues where they can regulate gene expression, thus affecting homeostasis. Whether hemodialysis alters the profile of miRNAs in the serum is not known. Methods: miRNA profiling in serum samples collected before an

Behind the fertility–education nexus : what triggered the French development process?

The education–fertility relationship is a central element of the models explaining the transition to sustained economic growth. But many determinants of this relationship have not yet received more systematic attention. In this paper, we apply a three-stages least-squares estimator on French county-level data, including newly collected data, to better understand the causal effects running from edu

Muscle electrical activity changes over time during stair ascending until exhaustion

BACKGROUND AND AIM Non-stop stair ascending at maximum speed is required to reach a safe refuge level from deep underground structures, such as subways and in high-rise buildings in an emergency evacuation situation. Endurance of stair climbing and identifying the time of the onset of leg’s local muscle fatigue (LMF) are interests in evacuation research. The objective of this laboratory study was

Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site

Many pathogenic bacteria utilise sialic acids as an energy source or use them as an external coating to evade immune detection. As such, bacteria that colonise sialylated environments deploy specific transporters to mediate import of scavenged sialic acids. Here, we report a substrate-bound 1.95 Å resolution structure and subsequent characterisation of SiaT, a sialic acid transporter from Proteus

Increased Gun Violence Among Young Males in Sweden : a Descriptive National Survey and International Comparison

This population-based time-trend study examines gun violence rates among males in Sweden during the years 1996 to 2015 and compares the rate in Sweden to other Western European countries. Data were collected from six registries and are presented descriptively per 100,000 inhabitants. The risks among males in Sweden increased considerably in both lethal and non-lethal gun victimization and perpetra

Regulation of unfolded protein response in hematopoietic stem cells

Hematopoietic stem cells (HSCs) play a central role in hematopoietic regeneration, which has been demonstrated by thorough studies. In contrast, the cell cycle status and metabolic condition of HSCs define these cells as dormant. Recent studies have also revealed that protein metabolism is quite unique, as dormant HSCs have a lower protein synthesis rate and folding capacity. Under proliferative c

Cykelns plats i den kommunala planeringen : En fråga om status och hierarki

Rapporten är en analys av Malmö, Mölndals, Norrköpings och Örebros arbete med cykelplanering och bygger på en genomgång av plandokument från 2000 fram till 2015. Utifrån en nyckelordsökning har kommunernas arbete med att öka attraktiviteten för cykel som ett naturligt och självklart transportslag i stadsmiljö granskats utifrån ett normkritiskt perspektiv på transporter där bilen utgör det självkla

Induction of S100A9 homodimer formation in vivo

We show here that increased S100A8 and S100A9 protein expression is induced in spleen of animals with active inflammation or with inoculated tumors. In tumor bearing animals an increased expression was also detected in the lung. To further analyze the induced proteins, we performed chemical cross-linking followed by Western blotting. We observed in protein extracts from spleen that both S100A8/S10

Autoinhibitory regulation of S100A8/S100A9 alarmin activity locally restricts sterile inflammation

Autoimmune diseases, such as psoriasis and arthritis, show a patchy distribution of inflammation despite systemic dysregulation of adaptive immunity. Thus, additional tissue-derived signals, such as danger-associated molecular patterns (DAMPs), are indispensable for manifestation of local inflammation. S100A8/S100A9 complexes are the most abundant DAMPs in many autoimmune diseases. However, regula

Molecular lineage diversity in the nearly-cosmopolitan Hiatella (Mollusca, Bivalvia) : assessing inter-oceanic relationships on multiple timescales.

Hiatella is one of the most widespread marine bivalve genera, occurring in diverse habitats from the temperate to polar latitudes in both hemispheres, and in fossil strata since almost 150 Myr ago. Despite variation in some biological and morphological traits, characters to resolve the current systematic structure consistently across the range of the genus are not known: all samples are often refe