Products Liability and Evidence of Subsequent Repairs

Cannabis är den mest använda drogen i världen och attityderna gentemot den blir allt mer liberala. Då många syntetiskt framställda cannabinoider ständigt dyker upp på marknaden visar studier på olika resultat angående utbredningen av drogen. Det är personer i de yngre åldrarna som i störst utsträckning använder cannabis. I dagens samhälle ställs det allt mer krav på unga vuxna, inte minst när det gäller att skaffa sig en utbildning. Syftet med denna studie var därför att undersöka om det fanns något samband mellan användningen av cannabis och upplevelser av studiesituationen bland studenter vid Linköpings universitet.Studiens teoretiska utgångspunkt utgjordes av Robert K. Mertons strainteori där fokus låg på huruvida studenterna upplevde sig ha förutsättningar och medel att uppnå sitt mål; att klara av en utbildning. Populationen för studien var alla studenter som var registrerade på ett program. En totalundersökning gjordes av de studenter som våren 2014 studerade på ett program i termin fyra. Det empiriska materialet samlades in via en onlineenkät som besvarades av 1 481 respondenter.Resultatet visade att 36,8 % av respondenterna någon gång hade testat cannabis, männen var signifikant överrepresenterade. De flesta hade testat cannabis första gången då de studerade på gymnasiet. Respondenterna var över lag nöjda med sin studiesituation. Det var inte möjligt att se något samband mellan användningen av cannabis och upplevelser av studiesituationen som helhet

Regulation of non-responsiveness and death in cytotoxic T cells by the agonistic potency of MHC : Peptide ligands

CD8+ T lymphocytes are important for immunological control of infections and tumors. The key interaction required to initiate the process of T cell activation is the engagement of the T cell receptor (TCR) with a major histocompatibility complex (MHC) class I/peptide complex on an antigen presenting cell (APC). Depending on the affinity of the interaction between the TCR and MHC class I molecule, different arrays of signaling pathways can be activated in the T cell. Molecular alterations in the peptide bound to the MHC class I can lead to a lower affinity of the MHCTCRinteraction resulting in incomplete or qualitatively different T-cell responses. Altered peptide ligands (APLs) exhibiting such activity are referred to as partial agonists and often occur naturally through genetic instability, which affects T cell epitopes derived from rapidly mutating viruses or tumor-associated cellular antigens. We studied the molecular basis of partial agonism using MHC class I/peptide tetramer complexes. By using tetramers assembled with a fully agonist peptide or its synthetic variant we could study the relationship between tetramer staining, cytokine production and different pathways of activation induced cell death (AICD). We found that positive tetramer staining correlated with at least two different activation programs in CD8+ T lymphocytes: full scale activation associated with Fas-dependent AICD and an incomplete activation followed by Fasindependent AICD. Further, we used raft-disrupting agents to assess the role of lipid rafts in determining the agonistic potency of different peptide ligands. We showed that overall binding of specific tetramers to CTLs was reduced upon raft disruption, although the half-life of tetramer:TCR complexes formed under these conditions was not affected. These findings suggest that different TCR complexes on the surface of CTLs may have different requirements for cholesterol and CTLs may be heterogeneous in their raft structure. In addition we analyzed programs of negative regulation of CD8+ T lymphocytes and the capacity of APLs to activate and modulate such programs. Upon specific triggering CD8+ T-cells become refractory to a secondary stimulus; a condition referred to Activation induced Non-Responsiveness (AINR). We have shown that TCRtriggering results in a novel degradation pathway of Lck, a kinase which plays a critical role in the initiation of T cell activation. Down-regulation of Lck through degradation correlated with AINR in CTLs. By blocking Lck degradation we could prevent the development of AINR. We further investigated how activation of CTLs with APLs affected Lck expression. The capacity of different peptide variants to induce Lck degradation correlated with their agonistic potency. Inefficient recognition of APLs by specific T lymphocytes is believed to contribute to the failure of the immune system to control certain tumor types and progressive viral diseases. To better understand the regulation of APL, activity by immunologic help, we analyzed the capacity of exogenous IL-2 and IL-15 to influence different aspects of activation triggered in CTLs by either fully or partially agonistic peptide ligands. We showed that signals induced by the lymphokines synergize with weak TCR signaling induced by partially agonistic APL, converting many of these peptides from inhibitory to stimulatory ligands. We also demonstrated that IL-2 and IL-15 suppress induction of a death receptor-independent apoptotic program triggered by partially agonistic APL. In conclusion, we have analyzed the molecular basis of partial agonism in CTL recognition of peptide epitopes and characterized molecular changes associated with death and AINR in specific CTLs. We have shown that structural changes in the sequence of CTL peptide epitopes may decrease the affinity of MHC/TCR interactions and generate APLs, which not only trigger incomplete activation programs but also induce and modulate negative regulation programs in CTLs. This APL induced signaling of suppressive nature appears to be more prominent in the absence of immunological help, suggesting that under conditions of immune deregulation APLs may actively suppress CTL responses against infectious agents or tumors

Regulation and binding properties of S fimbriae cloned from E. coli strains causing urinary tract infection and meningitis

S fimbriae are able to recognize receptor molecules containing sialic acid and are produced by pathogenic E. coli strains causing urinary tract infection and menigitis. In order to characterize the corresponding genetic determinant, termed S fimbrial adhesin ( sfa) gene duster, we have cloned the S-specific genes from a urinary pathogen and from a meningitis isolate. Nine genes are involved in the production of S fimbriae, two of these, sfaB and sfaC code for regulatory proteins being necessary for the expression of S fimbriae. Two promoters, PB and Pc, are located in front of these genes. Transcription of the sfa determinant is influenced by activation of the promotersvia SfaB and SfaC, the action of the H-NS protein and an RNaseE-specific mRNA processing. In addition, a third promoter, P A• located in front of the major subunit gene sfaA, can be activated under special circumstances. Four genes of the sfa determinant code for the subunit-specific proteins, SfaA (16 kda), SfaG (17 kda), SfaS (14 kda) and SfaH (29 kda). It was demonstrated that the protein SfaA is the major subunit protein while SfaS is identical to the sialic-acid-specific adhesin of S fimbriae. The introduction of specific mutations into sfaS revealed that a region of six amino acids of the adhesin which includes two lysine and one arginine residues is involved in the receptor specific interaction of S fimbriae. Additionally, it has been shown that SfaS is necessary for the induction of fimbriation while SfaH plays a role in the stringency of binding of S fimbriae to erythrocytes

Serum levels and removal by haemodialysis and haemodiafiltration of tryptophan-derived uremic toxins in ESKD patients

Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, -0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (-72%, -39%, -43%, respectively), serum tryptophan levels increased, resulting in negative RR (-8%) towards the end of the dialysis session (p < 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis (p < 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses

D i g i t a l i z a t i o n a n d N e w B u y e r B e h a v i o r i s C h a n g i n g B 2 B R e l a t i o n s h i p M a r k e t i n g

Problem definition: The increasingly informed customer will lead to an even greater demand for expertise and knowledge of marketers. Firms need to find new ways to utilize the informed customer as a co-creator of value by more proficiently analyzing behavior, both online and offline. An uncertainty lies in to which extent the operational standards of KIBS firms translate to their marketing and sales efforts, or to what degree they are using potential customers to help shape their value propositions. The research question that has been identified is how the relationships seen in knowledgeintensive B2B marketing are affected by the digitalization of society and the change in buyer behavior that is a result of these societal changes. Purpose: The purpose of this thesis will be to identify the effects of digitalization and changing buyer behavior on relationships seen across marketing and sales of knowledge-intensive services in a B2B context. This will lead to a recommendation for the case company’s future direction of its marketing and sales functions. Methodology: The research approach of this master’s thesis has been a combination of a descriptive and !! ! IV! Digitalization and New Buyer Behavior is Changing B2B Relationship Marketing Tobias Olsson Emil Uhlin an explorative study. The descriptive approach intends to describe the overall areas of the problem formulation, while the explorative approach aims to collect as much information as possible regarding these areas. The goal of research has been to put more weight on the explorative approach. The research is approached as a case study focusing on a company that is both B2B and in a sector that includes many interesting angles of the problem. Case company: The choice of Company X as case company for this thesis was rooted in three overall observations. First off, the area of digital marketing is currently seeing increased urgency in B2B. The sector of IT and business consultancy is also interesting. The companies in this sector often have many different ways of working within the same company. The choice of a B2B company is motivated by the fact that the new wave of digital marketing has seen greater advancements in B2C. B2B is historically stronger in much of the relationship marketing basics, like close network relationships. The digital advancements in B2B deviate from those in B2C, and are probably not as standardized. Lastly, an interesting aspect of Company X is that it offers business units on opposite sides of the spectrum in regards to overall digital advancements. Conclusions: Information really is the common denominator for everything that pertains to the power balance of supplier and customer. The authors believe that the presented framework provides a good intersection of assessing relational strength in B2B, the ability to grade strengths and weaknesses as well as opportunities and threats in digitalization, and lastly the level of current buyer insight. The models are secondary and may be modified, but the choice to observe relationships, digitalization and more in-depth buyer behavior should provide a holistic view for similar studies

Civil Society Elites: A Research Agenda

This editorial introduces the thematic issue on ‘civil society elites,’ a topic that has been neglected in elite research as well as civil society studies. It elaborates on the concept of ‘civil society elites’ and explains why this is an important emerging research field. By highlighting different methodological approaches and key findings in the contributions to the thematic issue, this article aims at formulating an agenda for future research in this field

Cyclic sieving, skew Macdonald polynomials and Schur positivity

When $\lambda$ is a partition, the specialized non-symmetric Macdonald polynomial $E_{\lambda}(x;q;0)$ is symmetric and related to a modified Hall--Littlewood polynomial. We show that whenever all parts of the integer partition $\lambda$ is a multiple of $n$, the underlying set of fillings exhibit the cyclic sieving phenomenon (CSP) under a cyclic shift of the columns. The corresponding CSP polynomial is given by $E_{\lambda}(x;q;0)$. In addition, we prove a refined cyclic sieving phenomenon where the content of the fillings is fixed. This refinement is closely related to an earlier result by B.~Rhoades. We also introduce a skew version of $E_{\lambda}(x;q;0)$. We show that these are symmetric and Schur-positive via a variant of the Robinson--Schenstedt--Knuth correspondence and we also describe crystal raising- and lowering operators for the underlying fillings. Moreover, we show that the skew specialized non-symmetric Macdonald polynomials are in some cases vertical-strip LLT polynomials. As a consequence, we get a combinatorial Schur expansion of a new family of LLT polynomials

Lymphocytes in Placental Tissues: Immune Regulation and Translational Possibilities for Immunotherapy

Immune modulation at the fetomaternal interface is crucial to ensure that the fetal allograft is not rejected. In the present review, the focus is to describe basic functions of lymphocyte populations and how they may contribute to fetomaternal immune regulation, as well as determining what proportions and effector functions of these cells are reported to be present in placental tissues in humans. Also explored is the possibility that unique cell populations at the fetomaternal interface may be targets for adoptive cell therapy. Increasing the understanding of immune modulation during pregnancy can give valuable insight into other established fields such as allogeneic hematopoietic stem cell transplantation and solid organ transplantation. In these settings, lymphocytes are key components that contribute to inflammation and rejection of either patient or donor tissues following transplantation. In contrast, an allogeneic fetus eludes rejection by the maternal immune system