311 research outputs found

    The future of work : the impact of artificial intelligence on the well­being of white­collar employees

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    Given the upward trend in automation, as seen on a mechanical level in manufacturing plants, it is predicted that the next phase will involve artificial intelligence working in conjunction with human employees within the office environment. This research will explore how these predicted future scenarios of human white­collar employees working alongside artificial intelligence agents impacts their well­being. This research follows an experimental approach where participants are exposed to two different scenarios manipulating the independent variable: working with and without an artificial intelligence team member and measures participants’ well­being. The study’s findings indicate that there is no significant difference between the two groups. Implementing artificial intelligence as a new co­worker does not affect the employee’s well­being significantly different than a new human co­worker. Furthermore, attitudes towards AI do not mediate the relationship between type of co­worker and the participants’ well­being.Dada a tendĂȘncia ascendente na automatização, tal como se vĂȘ a nĂ­vel mecĂąnico nas fĂĄbricas, prevĂȘ ­ se que a prĂłxima fase envolverĂĄ inteligĂȘncia artificial trabalhando em conjunto com empregados humanos dentro do ambiente do escritĂłrio. Esta investigação irĂĄ explorar como estes cenĂĄrios futuros previstos de empregados de colarinho branco humanos que trabalham em conjunto com agentes de inteligĂȘncia artificial tĂȘm impacto no seu bem­estar. Esta investigação segue uma abordagem experimental em que os participantes sĂŁo expostos a dois cenĂĄrios diferentes manipulando a variĂĄvel independente: trabalhar com e sem um membro da equipa de inteligĂȘncia artificial e medir o bem­estar dos participantes. Os resultados do estudo indicam que nĂŁo hĂĄ diferença significativa entre os dois grupos. A implementação da inteligĂȘncia artificial como um novo colega de trabalho nĂŁo afecta o bem­estar do empregado significativamente diferente de um novo colega de trabalho humano. AlĂ©m disso, as atitudes em relação Ă  IA nĂŁo medeiam a relação entre o tipo de colega de trabalho e o bem­estar dos participantes

    Monoclonal anti-envelope antibody AP33 protects humanized mice against a patient-derived hepatitis C virus challenge

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    End-stage liver disease caused by hepatitis C virus (HCV) infection is a major indication for liver transplantation. However, immediately after transplantation the liver graft of viremic patients universally becomes infected by circulating virus, resulting in accelerated liver disease progression. Currently available direct-acting antiviral therapies have reduced efficacy in patients with end-stage liver disease and prophylactic strategies to prevent HCV recurrence are still highly needed. In this study we compared the ability of two broadly reactive monoclonal antibodies (mAbs), designated 3/11 and AP33, recognizing a distinct but overlapping epitope in the viral E2 glycoprotein to protect humanized mice from a patient-derived HCV challenge. Their neutralizing activity was assessed using the HCVpp and HCVcc systems expressing multiple patient-derived envelopes and a human-liver chimeric mouse model. HCV RNA was readily detected in all control mice challenged with a patient-derived HCV genotype 1b isolate, while three out of four AP33-treated mice were completely protected. In contrast, only one out of four 3/11-treated mice remained HCV RNA negative throughout the observation period, while the other three had a viral load that was indistinguishable from that in the control group. The increased in vivo efficacy of AP33 was in line with its higher affinity and neutralizing capacity observed in vitro. Conclusion: Although mAbs AP33 and 3/11 target the same region in E2, only mAb AP33 can efficiently protect from challenge with a heterologous HCV population in vivo. Since mAb AP33 efficiently neutralizes viral variants that escaped the humoral immune response and re-infected the liver graft of transplant patients, it may be a valuable candidate to prevent HCV recurrence. In addition our data is valuable for the design of a prophylactic vaccine

    Ɓamanie praw czƂowieka w ChiƄskiej Republice Ludowej oraz wybranych krajach ƛwiata z punktu widzenia Amnesty International

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    Celem niniejszej pracy dyplomowej jest przedstawienie problemu Ƃamania praw czƂowieka na ƛwiecie. Analiza zostaƂa przeprowadzona gƂównie w oparciu o raporty Amnesty International. SzczegĂłlna uwaga zostaƂa poƛwięcona kwestii naruszeƄ praw czƂowieka w ChiƄskiej Republice Ludowej. Praca zostaƂa podzielona na 4 rozdziaƂy. W rozdziale pierwszym zawarto podstawowe pojęcia z zakresu praw czƂowieka. RozdziaƂ 2 jest w caƂoƛci poƛwięcony charakterystyce międzynarodowej organizacji pozarządowej Amnesty International zajmującej się zapobieganiem naruszeniom praw czƂowieka. W rozdziale 3 dokonano analizy przypadkĂłw Ƃamania praw czƂowieka w ChiƄskiej Republice Ludowej. RozdziaƂ 4 zawiera przypadki naruszeƄ praw czƂowieka w wybranych paƄstwach ƛwiata. Analiza pokazaƂa, ĆŒe prawa czƂowieka nadal są Ƃamane na caƂym ƛwiecie. Większoƛć paƄstwa ƛwiata, a szczegĂłlnie Chiny, nie przestrzegają krajowego i międzynarodowego prawa z zakresu ochrony praw czƂowieka.The aim of the thesis I submitted was to describe the human rights violations around the world. The analysis is based on Amnesty International’s reports. The thesis focuses mainly on violations of human rights in the People’s Republic of China. The thesis is divided into 4 chapters. The first chapter explains the basic concept of human rights. The second chapter focuses on international non-governmental organization Amnesty International that is a pioneer for the promotion and protection of human rights. The third chapter includes analysis of human rights abuse in China. The last chapter describes human rights violations in selected countries. The analysis showed that human rights are still violated around the world. Most countries, especially China, don’t obey national and international human rights law

    Wymagająca MiƂoƛć : przesƂanie Jana PawƂa II do mƂodych

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    The term 'message' and the word 'Love' belong to the so-called key words used in the dissertation, determining its nature and significance. The methodological term 'message' has got various dictionary meanings. In case of John Paul II's teachings, this term should be most simply and broadly understood as the most important content the Pope passes to young people, hoping they will understand it and apply in their lives. The main message emerging from the John Paul II's texts intended for young people is about God who is Love and it is because of the logic of love that He demands specific acts from them. That is why the dissertation title contains the term demanding Love. Demanding Love is either the initial thesis and one of the most significant conclusions drawn from the study. The message of John Paul II can be summarised in the quoted expression. Demanding Love has got deep theological roots (compare: 1 John 4.16). At the same time, it reaches further: God loves us unconditionally and because of His Love, taking care of men, He makes certain demands. The structure of the dissertation was based on the classical triad - the paper was divided into three chapters. When directing his message to young people, the Pope draws their attention to the components of demanding Love. These are: Gift (Chapter 1) and Task (Chapters 2 and 3), which serve Love. The main study issue formulated in the dissertation is: why demanding Love may be deemed the core of Pope's message for young people? The main issue is composed of the following detailed problems: how does demanding Love fulfil itself as the Gift? (Chapter 1) and as the Task? (Chapters 2 and 3). The study was performed with the use of analysis and synthesis. The sources are as follows: Parati semper - Letter for young people (31.03.1985), and selected addresses and speeches of the Pope from 1978–2005 intended for the youth, telling about the issues of their concern and interpreted in a dogmatic aspect. The aim of the dissertation was to reveal the essence and value of the Pope's message for young people all over the world. The message for which the hermeneutic key is demanding Love. The First Chapter presents God who loves people and shows His love towards people in various ways. Both types of God's gifts and ways of demanding Love manifestations were presented: (He 'creates', 'educates', 'sends Son', 'teaches', 'forgives', 'dies and rises from the dead', 'revives', 'gives talents', 'enables to act'). While referring to God's revelation, the Pope explains to young people that Love means God-Father, His visualisation, the real and visible image of Whom is Jesus Christ and the revealed Third Person of the Holy Trinity means, according to the Pope, the fire of this Love. The title of the First Chapter contains the second element after the word 'Gift', i.e. 'Divine and Human Dimension'. The divine dimension refers directly to the Speaker, who is the Gift, i.e. God Himself. The term 'human dimension' indicates the addressees of the Gift of Love, i.e. all men (including young people). Simultaneously, the combination of words 'divine and human' reminds of the divine and human nature of Jesus Christ. The Second Chapter emphasises the man's response to the Gift of Love, expressed by fulfilled Tasks, constituting demands in personal terms ('To Love Oneself', 'To Love Fellow Men', 'To Love Love'). Since the main principle of the dissertation is demanding Love, the radicalism of demands is translated into the reality of interpersonal relationships. The Pope convinces young people that human love, which should obtain strength from God-Love, begins - in the scope of demands - from loving oneself (discovering one's vocation, shaping consciousness and confronting the suffering), then it turns to loving fellow men (using the vision of mercy, preserving premarital chastity, aiming at holiness), and then - having obtained the first two stages - it focuses on loving Love Itself (having the Word of God, sacraments, prayers and contemplation available). Love as the Task means not only real obligation in personal terms. That is why the Third Chapter presents the man's reply to the Gift of Love, expressed through the fulfilment of Tasks, constituting demands in social terms. The Pope presents them as the necessity to cultivate the heritage (of faith, freedom and culture), then: to build the civilisation of love (fighting for man's dignity, protecting life, promoting peace) and as the obligation to take up new evangelization (listening to and accepting the Gospel, preaching the Word, giving testimony of life). The message of demanding Love, commenced on the day of pontificate, which did not end with the Pope's death, is not actually restricted to young people only, but may affect all church communities, as well as (in specific areas) all people who search for God or atheists

    Wymagająca miƂoƛć. Wybrane aspekty teologii BoĆŒego ojcostwa w przesƂaniu Jana PawƂa II do mƂodzieĆŒy

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    John Paul II calls God Demanding Love and he puts this truth in the centre of his message for the young people. He does so since he experiences, in his own life, the very presence and actions of God the Father, who loves and demands. The Pope builds the science about Love basing on the Bible. In the light of selected texts from the Old Testament, he directly binds Love with Commandments. Demanding Love becomes a synonym of the Decalogue. In line with the message from the New Testament, he emphasizes that the commandment of love is the continuation and supplementation of the God’s Law and that its only rightness is God’s Love. The article devotes much attention to the Pope’s perception of Jesus. There are good reasons. John Paul II calls Jesus the Nature of God’s Love and keeps underlining that the Son of God points to God the Father with His whole existence and each and every action, thus refl ecting His Love. In order to explain the specifi city of God’s Love, the Pope reaches for biblical images, referring to the scene when Jesus talks with the young man, to the Parable about the merciful father and recalls young John resting on the Master’s chest. In his teaching about God’s love, John Paul II emphasizes the very nature of God’s Love, always preceding human love, Its ability of continuous forgiveness and intensifi cation of Love as the answer for men’s sins. Demanding Love constitutes a hermeneutic key of the Pope’s whole message for the young people. It is the most essential truth the Pope intended to pass to them. It is the key that explains the unexplainable, solving the irresoluble, opening what has remained closed before many young men

    Immobilization by surface conjugation of cyclic peptides for effective mimicry of the HCV-envelope E2 protein as a strategy toward synthetic vaccines

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    Mimicry of the binding interface of antibody-antigen interactions using peptide-based modulators (i.e. epitope mimics) has promising applications for vaccine design. These epitope mimics can be synthesized in a streamlined and straightforward fashion, thereby allowing for high-throughput analysis. The design of epitope mimics is highly influenced by their spatial configuration and structural conformation. It is widely assumed that for proper mimicry sufficient conformational constraints have to be implemented. This paper describes the synthesis of bromide derivatives functional-ized with a flexible TEG linker equipped with a thiol-moiety that could be used to support cyclic or linear peptides. The cyclic and linear epitope mimics were covalently conjugated via the free thiol-moiety on maleimide-activated plate sur-faces. The resulting covalent, uniform, and oriented coated surface of cyclic or linear epitope mimics were subjected to an ELISA to investigate the effect of peptide cyclization with respect to mimicry of an antigen-antibody interaction of the HCV E2 glycoprotein. To our knowledge, the benefit of cyclized peptides over linear peptides has been clearly demon-strated here for the first time. Cyclic epitope mimics, and not the linear epitope mimics, demonstrated specificity towards their monoclonal antibodies HC84.1 and V3.2, respectively. The described strategy for the construction of epitope mimics shows potential for high-throughput screening of key-binding residues by simply changing the amino-acid sequences within synthetic peptides. In this way, leucine-438 has been identified as a key-binding residue for binding monoclonal antibody V3.2

    Peptide Inhibition of Herpes Simplex Virus Type 1 DNA Polymerase

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    Seven proteins encoded by herpes simplex virus have been shown to be essential for the replication of virus DNA and for virus growth. This study is concerned with two of these proteins: Pol and UL42. Pol is the catalytic subunit of DNA polymerase and is encoded by gene UL30; UL42 is an accessory protein which serves to increase polymerase processivity and is encoded by gene UL42. Together these two proteins form the polymerase holoenzyme, and evidence suggests that the interaction between them is an essential one and hence a potential target for antiviral drugs. To identify regions of the UL42 protein of herpes simplex virus type 1 which may affect viral DNA polymerase activity, a series of 96 overlapping pentadecapeptides spanning the entire 488 amino acid residues of the UL42 protein were synthesised and tested for their ability to inhibit polymerase activity on a primed single-stranded M13 DNA template. Two assays were used: (i) formation of full length double-stranded M13 molecules; (ii) rate of incorporation of deoxyribonucleoside triphosphates. Both of the assays were optimised to ensure that any inhibition by the peptides would be detected. Peptides from five non-contiguous regions of the UL42 protein were found to inhibit polymerase activity in both the presence and absence of the UL42 protein. The most active peptides from each region correspond to amino acid residues 23 to38 (peptide 6), 64 to 78 (peptide 14), 89 to 102 (peptide 19), 229 to 243 (peptide 47), and 279 to 293 (peptide 57). By two different methods (DNA mobility shift and DNA precipitation), peptides 14, 19, 47 and 57 were found to bind DNA; they most probably inhibit enzyme activity by this mechanism. Peptide 6 did not bind DNA and must act by some mechanism other than competing for DNA. The inhibitory peptides were also tested for activity against mammalian polymerase alpha and the Klenow fragment of Escherichia coli polymerase. Although some limited specificity was demonstrated (up to 10-fold for peptide 6), all the peptides showed significant activity against both polymerase alpha and E. coli polymerase. UL42 peptides other than those which inhibited polymerase were also found to bind DNA. Twenty-six peptides were shown to have DNA-binding properties by gel mobility shift assay. Twenty-two of these were positively charged, suggesting that non-specific electrostatic interactions were largely responsible for the observed binding. There is evidence that the carboxy-terminus of Pol is required for the formation of a functional complex with UL42. Two peptides spanning the carboxy-terminal 42 amino acid residues of Pol were tested for their ability to inhibit the processivity of the Pol-UL42 holoenzyme. They had no detectable effect

    Glycan shifting on hepatitis C virus (HCV) E2 glycoprotein is a mechanism for escape from broadly neutralizing antibodies

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    Hepatitis C virus (HCV) infection is a major cause of liver disease and hepatocellular carcinoma. Glycan shielding has been proposed to be a mechanism by which HCV masks broadly neutralizing epitopes on its viral glycoproteins. However, the role of altered glycosylation in HCV resistance to broadly neutralizing antibodies is not fully understood. Here, we have generated potent HCV neutralizing antibodies hu5B3.v3 and MRCT10.v362 that, similar to the previously described AP33 and HCV1, bind to a highly conserved linear epitope on E2. We utilize a combination of in vitro resistance selections using the cell culture infectious HCV and structural analyses to identify mechanisms of HCV resistance to hu5B3.v3 and MRCT10.v362. Ultra deep sequencing from in vitro HCV resistance selection studies identified resistance mutations at asparagine N417 (N417S, N417T and N417G) as early as 5 days post treatment. Comparison of the glycosylation status of soluble versions of the E2 glycoprotein containing the respective resistance mutations revealed a glycosylation shift from N417 to N415 in the N417S and N417T E2 proteins. The N417G E2 variant was glycosylated neither at residue 415 nor at residue 417 and remained sensitive to MRCT10.v362. Structural analyses of the E2 epitope bound to hu5B3.v3 Fab and MRCT10.v362 Fab using X-ray crystallography confirmed that residue N415 is buried within the antibody–peptide interface. Thus, in addition to previously described mutations at N415 that abrogate the ÎČ-hairpin structure of this E2 linear epitope, we identify a second escape mechanism, termed glycan shifting, that decreases the efficacy of broadly neutralizing HCV antibodies

    Comprehensive linker-scanning mutagenesis of the hepatitis C virus E1 and E2 envelope glycoproteins reveals new structure–function relationships

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    Despite extensive research, many details about the structure and functions of hepatitis C virus (HCV) glycoproteins E1 and E2 are not fully understood, and their crystal structure remains to be determined. We applied linker-scanning mutagenesis to generate a panel of 34 mutants, each containing an insertion of 5 aa at a random position within the E1E2 sequence. The mutated glycoproteins were analysed by using a range of assays to identify regions critical for maintaining protein conformation, E1E2 complex assembly, CD81 receptor binding, membrane fusion and infectivity. The results, while supporting previously published data, provide several interesting new findings. Firstly, insertion at amino acid 587 or 596 reduced E1E2 heterodimerization without affecting reactivity with some conformation-sensitive mAbs or with CD81, thus implicating these residues in glycoprotein assembly. Secondly, insertions within a conserved region of E2, between amino acid residues 611 and 631, severely disrupted protein conformation and abrogated binding of all conformation-sensitive antibodies, suggesting that the structural integrity of this region is critical for the correct folding of E2. Thirdly, an insertion at Leu-682 specifically affected membrane fusion, providing direct evidence that the membrane-proximal ‘stem’ of E2 is involved in the fusion mechanism. Overall, our results show that the HCV glycoproteins generally do not tolerate insertions and that there are a very limited number of sites that can be changed without dramatic loss of function. Nevertheless, we identified two E2 insertion mutants, at amino acid residues 408 and 577, that were infectious in the murine leukemia virus-based HCV pseudoparticle system
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