Modeling and Optimization of Grade Changes for Multistage Polyethylene Reactors

Grade changes in polyethylene reactors, i.e., changes of operating conditions, are performed on a regular basis to adapt to market demands. In this paper, a dynamic optimization procedure is presented built upon the Modelica language extended with Optimica constructs for formulation of optimization problems. A Modelica library for the Borstar R multistage polyethylene reactors at Borealis AB, consisting of two slurry and one gas phase reactor, has been constructed. Using JModelica.org, a framework to translate dynamic optimization problems to NLP problems, optimal grade transitions between grades currently used at Borealis AB, can be calculated. Optimal inflows and grade key variables are shown

Artificial intelligence could alert for focal skeleton/bone marrow uptake in Hodgkin’s lymphoma patients staged with FDG-PET/CT

To develop an artificial intelligence (AI)-based method for the detection of focal skeleton/bone marrow uptake (BMU) in patients with Hodgkin’s lymphoma (HL) undergoing staging with FDG-PET/CT. The results of the AI in a separate test group were compared to the interpretations of independent physicians. The skeleton and bone marrow were segmented using a convolutional neural network. The training of AI was based on 153 un-treated patients. Bone uptake significantly higher than the mean BMU was marked as abnormal, and an index, based on the total squared abnormal uptake, was computed to identify the focal uptake. Patients with an index above a predefined threshold were interpreted as having focal uptake. As the test group, 48 un-treated patients who had undergone a staging FDG-PET/CT between 2017–2018 with biopsy-proven HL were retrospectively included. Ten physicians classified the 48 cases regarding focal skeleton/BMU. The majority of the physicians agreed with the AI in 39/48 cases (81%) regarding focal skeleton/bone marrow involvement. Inter-observer agreement between the physicians was moderate, Kappa 0.51 (range 0.25–0.80). An AI-based method can be developed to highlight suspicious focal skeleton/BMU in HL patients staged with FDG-PET/CT. Inter-observer agreement regarding focal BMU is moderate among nuclear medicine physicians

Physical Activity, Genetic Susceptibility, and the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes

Purpose: Physical activity (PA) has been linked to a reduced risk of type 2 diabetes by reducing weight and improving insulin sensitivity. We investigated whether PA is associated with a lower incidence of latent autoimmune diabetes in adults (LADA) and whether the association is modified by genotypes of human leukocyte antigen (HLA), transcription factor 7-like 2 ( TCF7L2)-rs7903146, or the fat mass and obesity-associated gene, FTO-rs9939609. Methods: We combined data from a Swedish case-control study and a Norwegian prospective study including 621 incident cases of LADA and 3596 cases of type 2 diabetes. We estimated adjusted pooled relative risks (RRs) and 95% CI of diabetes in relation to high (>= 30 minutes of moderate activity 3 times/ week) self-reported leisure time PA, compared to sedentariness. Results: High PA was associated with a reduced risk of LADA (RR 0.61; CI, 0.43-0.86), which was attenuated after adjustment for body mass index (BMI) (RR 0.90; CI, 0.63-1.29). The reduced risk applied only to noncarriers of HLA-DQB1 and -DRB1 (RR 0.49; CI, 0.33-0.72), TCF7L2 (RR 0.62; CI, 0.45-0.87), and FTO (RR 0.51; CI, 0.32-0.79) risk genotypes. Adjustment for BMI attenuated but did not eliminate these associations. For type 2 diabetes, there was an inverse association with PA (RR 0.49; CI, 0.42-0.56), irrespective of genotype. Main Conclusions: Our findings indicate that high PA is associated with a reduced risk of LADA in individuals without genetic susceptibility.Peer reviewe

Infections With the Tick-Borne Bacterium "Candidatus Neoehrlichia mikurensis” Mimic Noninfectious Conditions in Patients With B Cell Malignancies or Autoimmune Diseases

We present a comprehensive study of a new infectious disease in immune compromised patients, neoehrlichiosis. The clinical picture of the disease can be misleading because the symptoms may be misinterpreted to be a worsening of the underlying diseas

Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides

The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments to reach their cytosolic and nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds to increase functional delivery. So far, development of these compounds has been hindered by a lack of high-resolution methods that can correlate SSO trafficking with SSO activity. Here we present in-depth characterization of two novel endosomolytic compounds by using a combination of microscopic and functional assays with high spatiotemporal resolution. This system allows the visualization of SSO trafficking, evaluation of endosomal membrane rupture, and quantitates SSO functional activity on a protein level in the presence of endosomolytic compounds. We confirm that the leakage of SSO into the cytosol occurs in parallel with the physical engorgement of LAMP1-positive late endosomes and lysosomes. We conclude that the new compounds interfere with SSO trafficking to the LAMP1-positive endosomal compartments while inducing endosomal membrane rupture and concurrent ON escape into the cytosol. The efficacy of these compounds advocates their use as novel, potent, and quick-acting transfection reagents for antisense ONs

Selective and Irreversible Inhibitors of Mosquito Acetylcholinesterases for Controlling Malaria and Other Mosquito-Borne Diseases

New insecticides are urgently needed because resistance to current insecticides allows resurgence of disease-transmitting mosquitoes while concerns for human toxicity from current compounds are growing. We previously reported the finding of a free cysteine (Cys) residue at the entrance of the active site of acetylcholinesterase (AChE) in some insects but not in mammals, birds, and fish. These insects have two AChE genes (AP and AO), and only AP-AChE carries the Cys residue. Most of these insects are disease vectors such as the African malaria mosquito (Anopheles gambiae sensu stricto) or crop pests such as aphids. Recently we reported a Cys-targeting small molecule that irreversibly inhibited all AChE activity extracted from aphids while an identical exposure caused no effect on the human AChE. Full inhibition of AChE in aphids indicates that AP-AChE contributes most of the enzymatic activity and suggests that the Cys residue might serve as a target for developing better aphicides. It is therefore worth investigating whether the Cys-targeting strategy is applicable to mosquitocides. Herein, we report that, under conditions that spare the human AChE, a methanethiosulfonate-containing molecule at 6 µM irreversibly inhibited 95% of the AChE activity extracted from An. gambiae s. str. and >80% of the activity from the yellow fever mosquito (Aedes aegypti L.) or the northern house mosquito (Culex pipiens L.) that is a vector of St. Louis encephalitis. This type of inhibition is fast (∼30 min) and due to conjugation of the inhibitor to the active-site Cys of mosquito AP-AChE, according to our observed reactivation of the methanethiosulfonate-inhibited AChE by 2-mercaptoethanol. We also note that our sulfhydryl agents partially and irreversibly inhibited the human AChE after prolonged exposure (>4 hr). This slow inhibition is due to partial enzyme denaturation by the inhibitor and/or micelles of the inhibitor, according to our studies using atomic force microscopy, circular dichroism spectroscopy, X-ray crystallography, time-resolved fluorescence spectroscopy, and liquid chromatography triple quadrupole mass spectrometry. These results support our view that the mosquito-specific Cys is a viable target for developing new mosquitocides to control disease vectors and to alleviate resistance problems with reduced toxicity toward non-target species

On cellular immunology in chronic idiopathic thrombocytopenic purpura (ITP)

Chronic idiopathic thrombocytopenic purpura (ITP) is an acquired autoimmune disease characterized by a low platelet count and mucocutaneous bleedings. Chronic ITP is considered to be mediated by autoantibodies leading to premature destruction of platelets in the reticuloendothelial system. Previous findings indicate that T-helper (Th)-cells are activated by antigen-presenting cells and by subsequent secretion of different Th cytokines initiate the autoantibody production. However, the results are inconsistent. Also, a platelet specific antibody can only be detected in about 60 % of ITP patients. Furthermore, it is well known that cytotoxic T-cells play a key role in immune responses toward virus-infected and malignant cells, through their potent ability to induce apoptotic death in these cells. Even though the potential role of cellular immune response in chronic ITP is being elucidated, a cell-mediated cytotoxic component in the pathogenesis of chronic ITP has not been investigated.The aims of the present study were to investigate the T-cell immune response in chronic ITP by analysing: (i) the Th-cell cytokine profiles in serum/plasma and mononuclear cell cultures, (ii) gene expression profiles of T-cells and (iii) the hypothesis of T-cell mediated cytotoxicity towards platelets. Patients with chronic ITP were divided into different groups based on their platelet count (plc), active disease (plc <50 x 109/L), stable disease (plc 50-150 x 109/L) and in remission (plc >150 x 109/L. Patients with ITP in remission had significantly higher plasma levels of TGF-b1, a Th3 cytokine, compared to patients with active disease and controls. Further, we also found that peripheral mononuclear cells from chronic ITP patients with active disease had a significantly lower production of TGF-b1 compared to patients with stable disease, patients in remission and controls. In a DNA microarray screen several cytotoxic genes, together with genes involved in a Th1 cell response, showed increased expression in both patients with active disease and in remission compared to controls. Also, several members of the killer inhibitory receptor (KIR) family were upregulated in patients in remission compared to both patients with active disease and controls. In addition, analysis by flow cytometry showed a higher percentage of T-cells expressing KIRs in ITP patients in remission. An in vitro assay measuring the destruction of radiolabelled autologous platelets by T-cells showed positive platelet lysis in six of eight ITP patients with active disease, while no platelet lysis was detected in ITP patients in remission. Conclusions: Chronic ITP patients with active disease had low plasma levels and reduced mononuclear cell production of TGF-b1. This could indicate that ITP in active stage is associated with a down-regulated Th3 response, and remission might be induced by up-regulation of the Th3 response and a TGF-b1 mediated immune suppression. Also, our data strongly suggest that cell-mediated cytotoxicity contributes to the destruction of platelets in ITP and that this is inhibited by the up-regulation of KIRs in T-cells, resulting in remission. These findings may open possibilities for novel therapeutic strategies for management of patients with chronic ITP

Core values and brand promises – A mixed quantitative and qualitative study of core values, brand promises.

Title: Core values and brand promises – A mixed quantitative and qualitative study of core values, brand promises and their interdependence among 104 Fortune 500 companies. Date of the seminar: May 31, 2011 Course: BUSM08 Degree Project in International Marketing and Brand Management Authors: Per Andersson and Ola Johansson Supervisor: Associate Professor Mats Urde, PhD; Docent Keywords: Core values, brand promise, the brand core Purpose: The purpose of this master thesis is to investigate the nature of core values and brand promises as entities, their interdependence and its managerial implications. Methodology: A mixed quantitative and qualitative research strategy was applied throughout the different stages of the study. To obtain valuable empirical data, a cross-sectional content analysis of web pages was conducted. Strictly formulated coding manuals have secured a high degree of reliability, validity and replicability of the research process. Theoretical perspective: The thesis takes its theoretical base in brand management literature and existing theories within the field of core values, brand promise and the brand core. Empirical data: A content analysis of 104 companies from Fortune’s list of the 500 largest corporations in the world provided unique primary data regarding the core values and brand promises from these companies. Companies were chosen from different industries and geographical areas in order to identify differences between these variables. Conclusions: Our findings show that: • A major part of the examined companies are using core values of a generic character. • The average number of core values used per company is 5,1. • A typical core value of generic character tend to have the grammatical form of a noun or a noun adjective alloy that either describes a way of working or something you deserve. • Brand promises tend to be of either descriptive or discursive character depending on the linguistic connection between the statements and the core business of the company. • The core values used by the major part of the investigated companies are of a generic character. It is however to be mentioned that the combination of core values together with a brand promises tends to make the brand core more unique