ANALYSIS OF WELDED POLYPROPYLENE STRUCTURES: COMBINATION OF EXPERIMENTS AND SIMULATIONS

The effect of joining by extrusion welding on the tensional stiffness and strength of a Polypropylene copolymer was analysed. Short-term and creep tests with laboratory specimens were conducted. Welded joint sub-components were simulated with the finite element method and the results were validated by experiments

Exercise Training and Functional Connectivity Changes in Mild Cognitive Empairment and Healthy Elders

Background: Effective interventions are needed to improve brain function in mild cognitive impairment (MCI), an early stage of Alzheimer’s disease (AD). The posterior cingulate cortex (PCC)/precuneus is a hub of the default mode network (DMN) and is preferentially vulnerable to disruption of functional connectivity in MCI and AD. Objective: We investigated whether 12 weeks of aerobic exercise could enhance functional connectivity of the PCC/precuneus in MCI and healthy elders. Methods: Sixteen MCI and 16 healthy elders (age range = 60–88) engaged in a supervised 12-week walking exercise intervention. Functional MRI was acquired at rest; the PCC/precuneus was used as a seed for correlated brain activity maps. Results: A linear mixed effects model revealed a significant interaction in the right parietal lobe: the MCI group showed increased connectivity while the healthy elders showed decreased connectivity. In addition, both groups showed increased connectivity with the left postcentral gyrus. Comparing pre to post intervention changes within each group, the MCI group showed increased connectivity in 10 regions spanning frontal, parietal, temporal and insular lobes, and the cerebellum. Healthy elders did not demonstrate any significant connectivity changes. Conclusion: The observed results show increased functional connectivity of the PCC/precuneus in individuals with MCI after 12 weeks of moderate intensity walking exercise training. The protective effects of exercise training on cognition may be realized through the enhancement of neural recruitment mechanisms, which may possibly increase cognitive reserve. Whether these effects of exercise training may delay further cognitive decline in patients diagnosed with MCI remains to be demonstrated

Improved Cardiorespiratory Fitness Is Associated with Increased Cortical Thickness in Mild Cognitive Impairment

Cortical atrophy is a biomarker of Alzheimer’s disease (AD) that correlates with clinical symptoms. This study examined changes in cortical thickness from before to after an exercise intervention in mild cognitive impairment (MCI) and healthy elders. Thirty physically inactive older adults (14 MCI, 16 healthy controls) underwent MRI before and after participating in a 12-week moderate intensity walking intervention. Participants were between the ages of 61 and 88. Change in cardiorespiratory fitness was assessed using residualized scores of the peak rate of oxygen consumption (V̇O2peak) from pre- to post-intervention. Structural magnetic resonance images were processed using FreeSurfer v5.1.0. V̇O2peak increased an average of 8.49%, which was comparable between MCI and healthy elders. Overall, cortical thickness was stable except for a significant decrease in the right fusiform gyrus in both groups. However, improvement in cardiorespiratory fitness due to the intervention (V̇O2peak) was positively correlated with cortical thickness change in the bilateral insula, precentral gyri, precuneus, posterior cingulate, and inferior and superior frontal cortices. Moreover, MCI participants exhibited stronger positive correlations compared to healthy elders in the left insula and superior temporal gyrus. A 12-week moderate intensity walking intervention led to significantly improved fitness in both MCI and healthy elders. Improved V̇O2peak was associated with widespread increased cortical thickness, which was similar between MCI and healthy elders. Thus, regular exercise may be an especially beneficial intervention to counteract cortical atrophy in all risk groups, and may provide protection against future cognitive decline in both healthy elders and MCI

Stress map of the Mediterranean and Central Europe 2016

The Stress Map of the Mediterranean and Central Europe 2016 displays 5011 A-C quality stress data records of the upper 40 km of the Earth’s crust from the WSM database release 2016 (Heidbach et al, 2016, http://doi.org/10.5880/WSM.2016.001). Focal mechanism solutions determined as being potentially unreliable (labelled as Possible Plate Boundary Events in the database) are not displayed. Further detailed information on the WSM quality ranking scheme, guidelines for the various stress indicators, and software for stress map generation and the stress pattern analysis is available at www.world-stress-map.org

Direct cooling of the catheter tip increases safety for CMR-guided electrophysiological procedures

<p>Abstract</p> <p>Background</p> <p>One of the safety concerns when performing electrophysiological (EP) procedures under magnetic resonance (MR) guidance is the risk of passive tissue heating due to the EP catheter being exposed to the radiofrequency (RF) field of the RF transmitting body coil. Ablation procedures that use catheters with irrigated tips are well established therapeutic options for the treatment of cardiac arrhythmias and when used in a modified mode might offer an additional system for suppressing passive catheter heating.</p> <p>Methods</p> <p>A two-step approach was chosen. Firstly, tests on passive catheter heating were performed in a 1.5 T Avanto system (Siemens Healthcare Sector, Erlangen, Germany) using a ASTM Phantom in order to determine a possible maximum temperature rise. Secondly, a phantom was designed for simulation of the interface between blood and the vascular wall. The MR-RF induced temperature rise was simulated by catheter tip heating via a standard ablation generator. Power levels from 1 to 6 W were selected. Ablation duration was 120 s with no tip irrigation during the first 60 s and irrigation at rates from 2 ml/min to 35 ml/min for the remaining 60 s (Biotronik Qiona Pump, Berlin, Germany). The temperature was measured with fluoroscopic sensors (Luxtron, Santa Barbara, CA, USA) at a distance of 0 mm, 2 mm, 4 mm, and 6 mm from the catheter tip.</p> <p>Results</p> <p>A maximum temperature rise of 22.4°C at the catheter tip was documented in the MR scanner. This temperature rise is equivalent to the heating effect of an ablator's power output of 6 W at a contact force of the weight of 90 g (0.883 N). The catheter tip irrigation was able to limit the temperature rise to less than 2°C for the majority of examined power levels, and for all examined power levels the residual temperature rise was less than 8°C.</p> <p>Conclusion</p> <p>Up to a maximum of 22.4°C, the temperature rise at the tissue surface can be entirely suppressed by using the catheter's own irrigation system. The irrigated tip system can be used to increase MR safety of EP catheters by suppressing the effects of unwanted passive catheter heating due to RF exposure from the MR scanner.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The temporary habitat : a home between retreat and participation

Abweichender Titel nach Übersetzung der Verfasserin/des VerfassersDie Heimat ist ein Sehnsuchtsort, das Wohnen ein Grundbedürfnis des Menschen. Jeder braucht einen Ort, an dem man sich, unabhängig von der Dauer des Bleibens, geborgen und sicher fühlen kann. Dieses Wohlfühlen bringen wir in Verbindung mit dem Schutz unserer Wohnung. Um ein Gefühl der Heimat und Vertrautheit zu erzeugen, braucht es Orte, mit denen man sich identifizieren kann und an denen man mit anderen in Kontakt treten kann. Die Gemeinschaft sowie das sich Verändernde stehen dabei im Fokus dieser Arbeit. Die Städte werden heute mit immer mehr Menschen geteilt und trotzdem distanziert sich das Gemeinsame des Menschen immer weiter voneinander, denn eine Vielzahl an Menschen impliziert nicht zwangsläufig auch ein Miteinander. Obgleich urbane Räume aus allen Nähten zu platzen scheinen, vereinsamt der einzelne Mensch inmitten der menschlichen Gesellschaft. Im Kontext der Individualisierung, der Veränderung der Familienstrukturen wie Wohnverhältnisse, der flexibilisierten Arbeitswelt und der zunehmenden Mobilität entstehen neue Anforderungen an das Wohnen. Diese Veränderungen der Gesellschaft ziehen einen Wandel der Raumstruktur mit sich. So muss die Architektur zukünftig in der Lage sein, Wohnraum zu schaffen, der den Anforderungen des Individuums gerecht wird, als auch der Gemeinschaft, dem Miteinander, Folge leistet. Das Leben wird mobiler, unstetiger und lässt sich nicht mehr so leicht in starre Typologien zwängen. Das Temporäre als das Unvorhersehbare soll im Zuge dieser Arbeit nicht nur als ein Kompromiss akzeptiert werden, sondern zur Basis und zum Bestandteil des planerischen Denkens werden. In Zeiten der nahezu grenzenlos gewordenen menschlichen Mobilität, müssen bewegungslose und unveränderliche Strukturen hinterfragt werden. Es bedarf Gebäude, welche mehr als Summe ihrer Funktionen sind; Gebäude, welche sich auf neu entstehende Bedürfnisse anpassen können und mit den Bewohner*innen wachsen oder schrumpfen. Das Verhältnis zwischen dem Innen und dem Außen, dem Privaten und dem Kollektiven, dem Individuum und der Gemeinschaft – zwischen Rückzug und Öffnung – wird im letzten Teil der Arbeit ausformuliert. Eine Reduzierung des privaten Raums als Zufluchtsort für das Individuum und eine Maximierung der kollektiven Räume, um dem Miteinander der Menschen wieder mehr Platz zu schaffen. Räume, die jeweils ihr eigenes Verhältnis zur Individualität und Kollektivität erhalten, aber immer mit den anderen Raumfragmenten verstanden werden müssen und unentwegt in einer Abhängigkeit zueinander stehen. Es entsteht ein Vorschlag für eine wiederholbare Struktur, die ausgehend vom Raum der individuellen Existenz an verschiedenen Orten in verschiedenen Konfigurationen immer wieder neu umgesetzt werden kann.Home is a place of longing; habitation is a basic human need. Everyone needs a place where they can feel safe and secure, regardless of how long they spend there. We associate this feeling of well-being with the protection of our home. To create a feeling of home and familiarity, we need places with which we can identify and where we can connect to others. The community as well as ongoing change is the focus of this work.Today, cities are shared with more and more people. Yet what people have in common is distancing themselves more and more from each other, because a multitude of people does not necessarily imply togetherness. Although urban spaces seem to be bursting at the seams, the individual human being becomes lonely in the middle of society. In the context of individualization, changes in family structures such as living conditions, an increasingly flexible world of work, and increasing mobility, new demands are being placed on living space. These changes in society necessitate a change in spatial structure. In the future, architecture must be able to create a living space that meets the requirements of the individual as well as those of the community. Life is increasingly mobile, more unsteady, and can no longer be so easily squeezed into rigid typologies. In the course of this paper, the temporary as the unpredictable is not only to be accepted as a compromise but is to become the basis and part of planning thinking. In times of almost limitless human mobility, motionless and unchangeable structures must be questioned. There is a need for buildings that are more than the sum of their functions; buildings that can adapt to newly emerging needs and grow or shrink with the residents.The relationship between the inside and the outside, the private and the collective, the individual and the community – between retreat and opening – is formulated in the last part of this paper. A reduction of the private space as a refuge for the individual and a maximization of the collective spaces to create more space for a renewed togetherness of people. Each space maintains its own relationship to individuality and collectivity but must always be understood in conjunction with the other spatial fragments and are constantly interdependent. The result is a proposal for a repeatable structure, which can be realized over and over in different configurations, starting from the space of individual existence in different places.43