The Effects of Card Playing on Cognition

The present study aimed to examine the potential effects of card playing and socialization on cognition. Participants completed a battery of cognitive tests in order to obtain a baseline of cognitive function. Each participant was randomized to one of three training paradigms: group socialization, group card playing, and individual card playing. The socialization group met once a week for an hour for eight weeks and discussed topics of their choice. The card playing groups played Hearts either in a group or on the computer for one hour a week for eight weeks. After eight weeks of their training, participants completed post-testing which consisted of the same battery of cognitive tests in order to measure changes in cognition from pre- to post-testing. The results revealed that participants who were exposed to socialization during training demonstrated the most significant improvements on the cognitive tests. Groups that only received the card playing intervention demonstrated little change. Greatest improvement was seen for those tests that indexed verbal information processing, such as the Cognitive Linguistic Quick Test language domain, the California Verbal Learning Test, and the Excluded Letter Fluency test

Behandlung des schwergradig persistierenden Asthma bronchiale mit Interferon-α: Charakterisierung der klinischen, pharmakologischen und immunologischen Wirkung im Rahmen einer Pilotstudie

Schwergradig persistierende Asthma bronchiale (Schweregrad IV) ist eine lebensbedrohliche und die Lebensqualität auf Dauer erheblich beeinträchtigende Erkrankung, für die - trotz aller Fortschritte bei der Therapie des Asthma bronchiale in den letzten Jahren - unverändert eine Behandlungslücke besteht. In der vorliegenden Arbeit wird das therapeutische Potenzial von Interferon α bei der Behandlung des schwergradig persistierenden Asthma bronchiale anhand einer patientenbezogenen Studie analysiert. Nach definiertem Therapieschema wurden 8 weibliche Asthmatiker s.c. mit Interferon α über einen Zeitraum von 12 Monaten behandelt. Die Resultate der Studie belegen, dass die Therapie des schwergradig persistierenden Asthma bronchiale mit Interferon α zu einer deutlichen Reduktion der Krankheitssymptome, einer verbesserten Krankheitskontrolle, einer „Stabilisierung“ der Lungenfunktion führt und die Reduktion des Einsatzes systemischer Glukokortikoide und inhalativer β2-Mimetika erlaubt

A Cohort Study Followed for 13 Years

Background There is growing evidence of an association between oral health, specifically dental status, and chronic systemic diseases. However, varying measures of dental status across different populations and low study sample has made comparison of studies and conclusion of findings unclear. Our aim is to examine whether the number of teeth as a measure of dental status is associated with incident chronic diseases in a cohort setting. Methods We conducted a cohort study among 24,313 middle-aged Germans followed up for 13 years. Data on number of teeth as a measure of dental status were obtained through self-reports. Outcomes were clinically–verified incident non–fatal myocardial infarction, stroke, type 2 diabetes mellitus, and cancer. Hazard ratio (HR) and 95% confidence intervals (CI) were obtained from Cox regression models. Results Increasing number of teeth is inversely related to risk of myocardial infarction (HR: 0.97; 95% CI: 0.96, 0.99). The full multivariate model of teeth groups showed a strong linear trend for myocardial infarction, a less strong trend for stroke, and no relation with type 2 diabetes mellitus and cancer in a competing risk model. Participants with 18–23 teeth and those without teeth were at 76% (95%CI: 1.04, 3) and 2.93 times (95%CI: 1.61, 5.18) higher risk of myocardial infarction compared to those with nearly all teeth (28–32 teeth). Conclusions Number of teeth is specifically associated with myocardial infarction and not with other chronic disease indicating that dental status further strengthens the link between oral health and cardiovascular diseases

In situ accurate determination of the zero time delay between two independent ultrashort laser pulses by observing the oscillation of an atomic excited wave packet

We propose a novel method that uses the oscillation of an atomic excited wave packet observed through a pump-probe technique to accurately determine the zero time delay between a pair of ultrashort laser pulses. This physically-based approach provides an easy fix for the intractable problem of synchronizing two different femtosecond laser pulses in a practical experimental environment, especially where an in situ time zero measurement with high accuracy is required.Comment: 12 pages, 3 figures, accepted to Optics Letter

Relatório de Estágio Supervisionado

Relatório Final de Estágio Supervisionado, agregando os resultados das disciplinas de ESI e ESII, apresentado como requisito à obtençao do titulo de licenciado em Letras - Espanhol da Universidade Federal de Santa Catarina (UFSC), realizado no Colégio de Aplicação – UFSC

Extended half-life target module for sustainable UniCAR T-cell treatment of STn-expressing cancers

Background: Adapter chimeric antigen receptor (CAR) approaches have emerged has promising strategies to increase clinical safety of CAR T-cell therapy. In the UniCAR system, the safety switch is controlled via a target module (TM) which is characterized by a small-size and short half-life. The rapid clearance of these TMs from the blood allows a quick steering and self-limiting safety switch of UniCAR T-cells by TM dosing. This is mainly important during onset of therapy when tumor burden and the risk for severe side effects are high. For long-term UniCAR therapy, the continuous infusion of TMs may not be an optimal setting for the patients. Thus, in later stages of treatment, single infusions of TMs with an increased half-life might play an important role in long-term surveillance and eradication of residual tumor cells. Given this, we aimed to develop and characterize a novel TM with extended half-life targeting the tumor-associated carbohydrate sialyl-Tn (STn). Methods: The extended half-life TM is composed of the STn-specific single-chain variable fragment (scFv) and the UniCAR epitope, fused to the hinge region and Fc domain of a human immunoglobulin 4 (IgG4) antibody. Specific binding and functionality of the αSTn-IgG4 TM as well as pharmacokinetic features were assessed using in vitro and in vivo assays and compared to the already established small-sized αSTn TM. Results: The novel αSTn-IgG4 TM efficiently activates and redirects UniCAR T-cells to STn-expressing tumors in a target-specific and TM-dependent manner, thereby promoting the secretion of proinflammatory cytokines and tumor cell lysis in vitro and in experimental mice. Moreover, PET-imaging results demonstrate the specific enrichment of the αSTn-IgG4 TM at the tumor site, while presenting a prolonged serum half-life compared to the short-lived αSTn TM. Conclusion: In a clinical setting, the combination of TMs with different formats and pharmacokinetics may represent a promising strategy for retargeting of UniCAR T-cells in a flexible, individualized and safe manner at particular stages of therapy. Furthermore, as these molecules can be used for in vivo imaging, they pose as attractive candidates for theranostic approaches.publishersversionpublishe

Approach for the monetary evaluation of process innovations in early innovation phases focusing on manufacturing and material costs

In early innovation phases, the monetary evaluation of process innovations is a challenge for companies due to a lack of data. However, an innovation evaluation is essential in an early innovation phase to ensure that process innovations deliver economic value added (EVA) in early innovation phases and to channel technology transfer expenditures in a goal-oriented manner. This paper presents an approach for a semi-quantitative procedure for the monetary evaluation of process innovations in the early innovation phase focusing on manufacturing and material costs. Exemplarily, the approach is applied to process innovations of the Collaborative Research Center 1368 on oxygen-free production. In order to ensure the net present value orientation within the innovation evaluation, the procedure developed is based on a driver tree of the EVA. To link value drivers of the EVA and innovation-driven factors influencing EVA, the EVA driver tree is further systematized with a focus on manufacturing and material costs using a literature-based impact model. Based on the last level of the impact model, a guideline for a semi-structured expert interview is developed. Using this interview guideline, data is collected in the form of innovation-driven influencing factors, which represent the input for the final monetary innovation evaluation. An adapted weighted scoring model is used to draw a semi-quantitative conclusion regarding the EVA achieved by the process innovation. The practical application of the approach developed to process innovations in oxygen-free production has shown that, in the context of three process innovations under consideration, their implementation with the aim of achieving an EVA through reduced manufacturing and material costs at the current innovation status is not effective. However, based on the impact model developed, corresponding levers can be identified to positively influence the EVA and thus also the industrialization of the process innovation. Finally, further necessary steps are identified to evolve the presented approach into a complete method for monetary innovation evaluation in early innovation phases

Single-cell resolution of lineage trajectories in the Arabidopsis stomatal lineage and developing leaf

Dynamic cell identities underlie flexible developmental programs. The stomatal lineage in the Arabidopsis leaf epidermis features asynchronous and indeterminate divisions that can be modulated by environmental cues. The products of the lineage, stomatal guard cells and pavement cells, regulate plant-atmosphere exchanges, and the epidermis as a whole influences overall leaf growth. How flexibility is encoded in development of the stomatal lineage and how cell fates are coordinated in the leaf are open questions. Here, by leveraging single-cell transcriptomics and molecular genetics, we uncovered models of cell differentiation within Arabidopsis leaf tissue. Profiles across leaf tissues identified points of regulatory congruence. In the stomatal lineage, single-cell resolution resolved underlying cell heterogeneity within early stages and provided a fine-grained profile of guard cell differentiation. Through integration of genome-scale datasets and spatiotemporally precise functional manipulations, we also identified an extended role for the transcriptional regulator SPEECHLESS in reinforcing cell fate commitment.Peer reviewe

Cryogel-supported stem cell factory for customized sustained release of bispecific antibodies for cancer immunotherapy

Combining stem cells with biomaterial scaffolds provides a promising strategy for the development of drug delivery systems. Here we propose an innovative immunotherapeutic organoid by housing human mesenchymal stromal cells (MSCs), gene-modified for the secretion of an anti-CD33-anti-CD3 bispecific antibody (bsAb), in a small biocompatible star-shaped poly(ethylene glycol)-heparin cryogel scaffold as a transplantable and low invasive therapeutic machinery for the treatment of acute myeloid leukemia (AML). The macroporous biohybrid cryogel platform displays effectiveness in supporting proliferation and survival of bsAb-releasing-MSCs overtime in vitro and in vivo, avoiding cell loss and ensuring a constant release of sustained and detectable levels of bsAb capable of triggering T-cell-mediated anti-tumor responses and a rapid regression of CD33 + AML blasts. This therapeutic device results as a promising and safe alternative to the continuous administration of short-lived immunoagents and paves the way for effective bsAb-based therapeutic strategies for future tumor treatments

Production and Characterization of Peptide Antibodies to the C-Terminal of Frameshifted Calreticulin Associated with Myeloproliferative Diseases

Myeloproliferative Neoplasms (MPNs) constitute a group of rare blood cancers that are characterized by mutations in bone marrow stem cells leading to the overproduction of erythrocytes, leukocytes, and thrombocytes. Mutations in calreticulin (CRT) genes may initiate MPNs, causing a novel variable polybasic stretch terminating in a common C-terminal sequence in the frameshifted CRT (CRTfs) proteins. Peptide antibodies to the mutated C-terminal are important reagents for research in the molecular mechanisms of MPNs and for the development of new diagnostic assays and therapies. In this study, eight peptide antibodies targeting the C-terminal of CRTfs were produced and characterised by modified enzyme-linked immunosorbent assays using resin-bound peptides. The antibodies reacted to two epitopes: CREACLQGWTE for SSI-HYB 385-01, 385-02, 385-03, 385-04, 385-07, 385-08, and 385-09 and CLQGWT for SSI-HYB 385-06. For the majority of antibodies, the residues Cys1, Trp9, and Glu11 were essential for reactivity. SSI-HYB 385-06, with the highest affinity, recognised recombinant CRTfs produced in yeast and the MARIMO cell line expressing CRTfs when examined in Western immunoblotting. Moreover, SSI-HYB 385-06 occasionally reacted to CRTfs from MPN patients when analysed by flow cytometry. The characterized antibodies may be used to understand the role of CRTfs in the pathogenesis of MPNs and to design and develop new diagnostic assays and therapeutic targets. Keywords: calreticulin; epitope mapping; frameshift mutations; myeloproliferative neoplasms; peptide antibodies