Utvärdering av vägkonstruktioner med stabilisering

Swedish transport administration has over the past few years changed its way of purchasing contractors. The new way is totalentreprenad, which gives the contractor the opportunity to develop and renew the construction methods. Stabilization is one of the outcomes of that development. It is an unusual method in Sweden and therefore it is important to learn more about its characteristics. Analyses of bearing capacity and deformation have been made in this thesis along with interviews. Knowledge of possible E-modulus on the stabilized layers has been calculated in the program PVD. Experiences and knowledge have been collected and together with the results from the investigation part, given the conclusion that stabilization evolves rut depth and unevenness slower. Furthermore, the investigations have shown that stabilization has good opportunities in future road projects

A Novel Strategy for Live Detection of Viral Infection in Drosophila melanogaster

We have created a transgenic reporter for virus infection, and used it to study Nora virus infection in Drosophila melanogaster. The transgenic construct, Munin, expresses the yeast transcription factor Gal4, tethered to a transmembrane anchor via a linker that can be cleaved by a viral protease. In infected cells, liberated Gal4 will then transcribe any gene that is linked to a promoter with a UAS motif, the target for Gal4 transcription. For instance, infected cells will glow red in the offspring of a cross between the Munin stock and flies with a UAS-RFP(nls) transgene (expressing a red fluorescent protein). In such flies we show that after natural infection, via the faecal-oral route, 5-15% of the midgut cells are infected, but there is little if any infection elsewhere. By contrast, we can detect infection in many other tissues after injection of virus into the body cavity. The same principle could be applied for other viruses and it could also be used to express or suppress any gene of interest in infected cells

Serology assessment of antibody response to SARS-CoV-2 in patients with COVID-19 by rapid IgM/IgG antibody test

The coronavirus disease 2019 (COVID-19) pandemic has created a global health- and economic crisis. Detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19 by serological methods is important to diagnose a current or resolved infection. In this study, we applied a rapid COVID-19 IgM/IgG antibody test and performed serology assessment of antibody response to SARS-CoV-2. In PCR-confirmed COVID-19 patients (n = 45), the total antibody detection rate is 92% in hospitalized patients and 79% in non-hospitalized patients. The total IgM and IgG detection is 63% in patients with 2 weeks disease duration; and 91% in hospitalized patients with >2 weeks disease duration. We also compared different blood sample types and suggest a higher sensitivity by serum/plasma over whole blood. Test specificity was determined to be 97% on 69 sera/plasma samples collected between 2016-2018. Our study provides a comprehensive validation of the rapid COVID-19 IgM/IgG serology test, and mapped antibody detection patterns in association with disease progress and hospitalization. Our results support that the rapid COVID-19 IgM/IgG test may be applied to assess the COVID-19 status both at the individual and at a population level. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Peer reviewe

High-throughput muscle fiber typing from RNA sequencing data

Background Skeletal muscle fiber type distribution has implications for human health, muscle function, and performance. This knowledge has been gathered using labor-intensive and costly methodology that limited these studies. Here, we present a method based on muscle tissue RNA sequencing data (totRNAseq) to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for a larger number of individuals to be tested. Methods By using single-nuclei RNA sequencing (snRNAseq) data as a reference, cluster expression signatures were produced by averaging gene expression of cluster gene markers and then applying these to totRNAseq data and inferring muscle fiber nuclei type via linear matrix decomposition. This estimate was then compared with fiber type distribution measured by ATPase staining or myosin heavy chain protein isoform distribution of 62 muscle samples in two independent cohorts (n = 39 and 22). Results The correlation between the sequencing-based method and the other two were rATPas = 0.44 [0.13–0.67], [95% CI], and rmyosin = 0.83 [0.61–0.93], with p = 5.70 × 10–3 and 2.00 × 10–6, respectively. The deconvolution inference of fiber type composition was accurate even for very low totRNAseq sequencing depths, i.e., down to an average of ~ 10,000 paired-end reads. Conclusions This new method (https://github.com/OlaHanssonLab/PredictFiberType) consequently allows for measurement of fiber type distribution of a larger number of samples using totRNAseq in a cost and labor-efficient way. It is now feasible to study the association between fiber type distribution and e.g. health outcomes in large well-powered studies.journal articl

Nora Virus Persistent Infections Are Not Affected by the RNAi Machinery

Drosophila melanogaster is widely used to decipher the innate immune system in response to various pathogens. The innate immune response towards persistent virus infections is among the least studied in this model system. We recently discovered a picorna-like virus, the Nora virus which gives rise to persistent and essentially symptom-free infections in Drosophila melanogaster. Here, we have used this virus to study the interaction with its host and with some of the known Drosophila antiviral immune pathways. First, we find a striking variability in the course of the infection, even between flies of the same inbred stock. Some flies are able to clear the Nora virus but not others. This phenomenon seems to be threshold-dependent; flies with a high-titer infection establish stable persistent infections, whereas flies with a lower level of infection are able to clear the virus. Surprisingly, we find that both the clearance of low-level Nora virus infections and the stability of persistent infections are unaffected by mutations in the RNAi pathways. Nora virus infections are also unaffected by mutations in the Toll and Jak-Stat pathways. In these respects, the Nora virus differs from other studied Drosophila RNA viruses

Subliminal influence on generosity

We experimentally subliminally prime subjects prior to charity donation decisions by showing words that have connotations of pro-social values for a very brief time (17ms). Our main fnding is that, compared to a baseline condition, the pro-social prime increases donations by approximately 10-17 percent among subjects with strong pro-social preferences (universalism values). We find a similar effect when interacting the prime with the Big 5 personality characteristic of agreeableness. We furthermore introduce a novel method for testing for priming, "subliminity". This method reveals that some subjects are capable of recognizing prime words, and the overall results are weaker when we control for this capacity

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

Algorithms for Aligning Genetic Sequences to Reference Genomes

The technologies for sequencing genetic materials have improved vastly during the last fifteen years. Sequences can now be determined to affordable costs and therefore are more genetic sequences available than ever before. The bottleneck is no longer to obtain genetic sequences but rather to analyze all the sequence data. A primary step in sequence analysis is to determine a sequence fragment’s position in the genome, a process called aligning. From Computing Science point of view, this is essentially text matching. This is however a much more complex task than searching for strings in ordinary text documents. First, there is large amount of data. An ordinary sequencing experiment could generate more than 100 million sequences. Each sequence should be matched to a reference genome sequence, which is some billions characters in size. Second, the obtained sequences may have differences compared to the reference genome sequence. The algorithms are thus not only searching for exact matches, but for the best approximate matches. In this work I review the algorithms behind modern sequence alignment softwares. I also propose to evaluate to the fast Fourier transform for the task

Ljungan Virus Replication in Cell Culture

Ljungan virus (LV) is a recently identified picornavirus of the genus Parechovirus. LV has been isolated from voles trapped in Sweden and also in the United States. LV infected small rodents may suffer from diabetes type 1 and type 2 like symptoms, myocarditis and encephalitis. LV has been proposed as a human pathogen, with indications of causing diabetes type 1, myocarditis and intrauterine fetal deaths. In this thesis, cell culture adapted LV strains were utilised for development and adaptation of several basic methodological protocols to study the LV biology, e.g. real time PCR, highly specific antibodies and a reverse genetics system. These methods allowed detailed studies of this virus and how it interacts with the host cell. The genomic 5'-end was identified and modelling showed unique secondary structure folding of this region. The LV encodes an aphthovirus-like 2A protein with a DvExNPGP motif. This motif was found to mediate primary cleavage of the LV polyprotein in vitro and is proposed to constitute the carboxy terminus of the structural protein VP1 in LV. Rabbit polyclonal antibodies generated against recombinant structural proteins were used to verify that the LV virion is composed of the structural proteins VP0, VP1 and VP3. Cell culture studies showed that LV replicates to low titer with an absent or delayed cell lysis. LV is proposed to be able to spread by a, for picornaviruses, not previously demonstrated direct cell-to-cell transmission. All results taken together suggest a maintenance strategy of LV including low amounts of the LV genome and persistently infected hosts. Stability studies showed that the LV virion not only maintain activity in acidic and alkaline environments but also exhibit resistance to the commonly used disinfectant Virkon®.The results presented in this thesis show that LV has several unique properties, not previously observed for a picornavirus

HJÄRTATS KÄNSLOR : — om känslor vid hjärtsvikt: En litteraturstudie

Bakgrund: Hjärtsvikt har dålig prognos och drabbar ett stort antal människor i Sverige. De som drabbas upplever många problematiska symtom och medicineringen har många biverkningar som kan vara svåra att leva med. Obehagliga känslor kan förvärra symtom hos personer med hjärtsvikt. Sjuksköteskan bör kunna identifiera känslor och förstå varför dessa uppstår hos personer med hjärtsvikt för att bättre kunna vårda dessa. Syfte: Syftet är att beskriva hur personer som lever med hjärtsvikt beskriver sina känslor. Metod: Elva vårdvetenskapliga artiklar analyserades med inspiration från Evans metod för systematiska litteraturstudier. Nyckelfynd sammanfördes och bildade två huvudteman och nio subteman. Resultat: Resultatet indikerade att de finns många känslor associerade med hjärtsvikt. De delades in i positiva och negativa känslor. Känslor som riktar sig utåt, känslor som framkallas av hot, känslor av skuld, känslor av saknad, känslor inför det okända, känslor kring beroende, känslor kring uppskattning av livet, känslor kring säkerhet och positiva känslor om framtiden framkom som subteman. Slutsats: Denna uppsats berikar bilden av känslorna hos personer med hjärtsvikt. Sjuksköterskor bör använda denna kunskap för att på ett bättre sätt främja hälsa. Det framkom slutligen att det behövs mer forskning kring genus och känslor. Nyckelord: Hjärtsvikt, kvalitativ litteraturstudie, känslor, negativa, positivaBackground: A major number of people in Sweden suffer from heart failure and often succumb to the poor prognosis associated with the disease. Experiences among the affected include the various negative symptoms that heart failure generates as well as side effects from medical treatment. Such side effects may be difficult to deal with. Unpleasant emotions can worsen symptoms in people that have heart failure. Nurses should be able to identify these emotions and understand why they emerge in people that have heart failure as a means to better care for them. Aim: The aim is to describe how people living with heart failure describe their emotions. Method: Eleven scientific nursing articles were analyzed using Evans systematic method for reviewing literature as inspiration. Key findings were brought together and formed two major themes and nine sub-themes. Result: The result indicated numerous emotions associated with heart failure. They were divided into positive and negative emotions. Emotions that are extrovert, emotions caused by threat, emotions of guilt, emotions of loss, emotions facing the unknown, emotions encompassing dependency, emotions encompassing appreciation of life, emotions encompassing security and positive emotions concerning ones future appeared as sub-themes. Conclusion: This body of work provides a better picture of the emotional outcomes associated with heart failure. Nurses should use this knowledge to better promote health. Finally it emerged that more research concerning gender and emotion are needed. Keywords: Emotions, heart failure, negative, positive, qualitative literature revie