Effect of sialic acid loss on dendritic cell maturation

Sialic acids are key structural determinants and contribute to the functionality of a number of immune cell receptors. Previously, we demonstrated that differentiation of human dendritic cells (DCs) is accompanied by an increased expression of sialylated cell surface structures, putatively through the activity of the ST3Gal.I and ST6Gal.I sialyltransferases. Furthermore, DC endocytosis was reduced upon removal of the cell surface sialic acid residues by neuraminidase. In the present work, we evaluate the contribution of the sialic acid modifications in DC maturation. We demonstrate that neuraminidase-treated human DCs have increased expression of major histocompatibility complex (MHC) and costimulatory molecules, increased gene expression of specific cytokines and induce a higher proliferative response of T lymphocytes. Together, the data suggest that clearance of cell surface sialic acids contributes to the development of a T helper type 1 proinflammatory response. This postulate is supported by mouse models, where elevated MHC class II and increased maturation of specific DC subsets were observed in DCs harvested from ST3Gal.I(-/-) and ST6Gal.I(-/-) mice. Moreover, important qualitative differences, particularly in the extent of reduced endocytosis and in the peripheral distribution of DC subsets, existed between the ST3Gal.I(-/-) and ST6Gal.I(-/-) strains. Together, the data strongly suggest not only a role of cell surface sialic acid modifications in maturation and functionality of DCs, but also that the sialic acid linkages created by different sialyltransferases are functionally distinct. Consequently, with particular relevance to DC-based therapies, cell surface sialylation, mediated by individual sialyltransferases, can influence the immunogenicity of DCs upon antigen loading.

Home Banking

The object of this dissertation is focused on the study of the home banking service and how the allocation of losses due to computer fraud is processed in the scope of this service. When considering the questions raised by the allocation of losses associated with fraudulent operations, it is important to consider, mainly, the behaviour of the user of the home banking service. In our opinion, courts have been too demanding towards the user when judging his action in the use of this service. In this study, we have concluded that, when the user “falls” into a computer fraud scheme, he should not be liable for gross negligent behaviour, even if, due to the fraud, the user revealed all his access codes to a hacker on a page similar to that of his bank. In general, such facts will not be sufficient to qualify the user’s action as grossly negligent. Therefore, the user, under the terms of the Payment Services’ System, must bear the loss up to a maximum of €150, and the bank will face the remainder of the losses. However, if the user, victim of a fraudulent technique, ignored the safety warnings issued by the bank, one must consider, given the specific case, that he contributed to gross negligence in unauthorised payment transactions. Thus, the user must bear all the losses up to the moment when he notifies the bank about the unauthorised transactions. It is the bank’s responsibility to, given the specific case, adduce evidence of the client’s contribution to the identified losses.

Help-seeking for 'memory loss' by older adults in India : patient, caregiver and health providers' perspectives

ABSTRACT: Background. In India, prevalence rates of dementia and prodromal amnestic Mild Cognitive Impairment (MCI) are 3.1% and 4.3% respectively. Most Indians refer to the full spectrum of cognitive disorders simply as ‘memory loss.’ Barring prevention or cure, these conditions will rise rapidly with population aging. Evidence-based policies and practices can improve the lives of affected individuals and their caregivers, but will require timely and sustained uptake. Objectives. Framed by social cognitive theories of health behavior, this study explores the knowledge, attitudes and practices concerning cognitive impairment and related service use by older adults who screen positive for MCI, their primary caregivers, and health providers. Methods. I used the Montreal Cognitive Assessment to screen for cognitive impairment in memory camps in Mumbai. To achieve sampling diversity, I used maximum variation sampling. Ten adults aged 60+ who had no significant functional impairment but screened positive for MCI and their caregivers participated in separate focus groups. Four other such dyads and six doctors/ traditional healers completed in-depth interviews. Data were translated from Hindi or Marathi to English and analyzed in Atlas.ti using Framework Analysis. Findings. Knowledge and awareness of cognitive impairment and available resources were very low. Physicians attributed the condition to disease-induced pathology while lay persons blamed brain malfunction due to normal aging. Main attitudes were that this condition is not a disease, is not serious and/or is not treatable, and that it evokes stigma toward and among impaired persons, their families and providers. Low knowledge and poor attitudes impeded help-seeking. Conclusions. Cognitive disorders of aging will take a heavy toll on private lives and public resources in developing countries. Early detection, accurate diagnosis, systematic monitoring and quality care are needed to compress the period of morbidity and promote quality of life. Key stakeholders provide essential insights into how scientific and indigenous knowledge and sociocultural attitudes affect use and provision of resources.

The role of dispersion into assets allocation

Dispersion of returns has gained a lot of attention as a measure to distinguish good and bad investment opportunities time. In the following dissertation, the cross-sectional returns volatility is analyzed over a fifteen year period across the S&P100 Index composition. The main inference drawn from the data sample is that the canonical measure of dispersion is highly macro-risk driven and therefore more biased towards returns volatility rather than its correlation component.