Small Covers over Prisms

In this paper we calculate the number of equivariant diffeomorphism classes of small covers over a prism

Heterogeneous Activity Causes a Nonlinear Increase in the Group Energy Use of Ant Workers Isolated from Queen and Brood

Increasing evidence has shown that the energy use of ant colonies increases sublinearly with colony size so that large colonies consume less per capita energy than small colonies. It has been postulated that social environment (e.g., in the presence of queen and brood) is critical for the sublinear group energetics, and a few studies of ant workers isolated from queens and brood observed linear relationships between group energetics and size. In this paper, we hypothesize that the sublinear energetics arise from the heterogeneity of activity in ant groups, that is, large groups have relatively more inactive members than small groups. We further hypothesize that the energy use of ant worker groups that are allowed to move freely increases more slowly than the group size even if they are isolated from queen and brood. Previous studies only provided indirect evidence for these hypotheses due to technical difficulties. In this study, we applied the automated behavioral monitoring and respirometry simultaneously on isolated worker groups for long time periods, and analyzed the image with the state‐of‐the‐art algorithms. Our results show that when activity was not confined, large groups had lower per capita energy use, a lower percentage of active members, and lower average walking speed than small groups; while locomotion was confined, however, the per capita energy use was a constant regardless of the group size. The quantitative analysis shows a direct link between variation in group energy use and the activity level of ant workers when isolated from queen and brood

An integrated cell line development platform for generation of high yielding CHO stable cell lines expressing a stabilized trimeric pre-fusion RSV F recombinant viral glycoprotein

Accelerating timelines to deliver stable cell lines with high productivity is challenging, especially for biologics portfolios which include complex recombinant vaccine constructs. The VRC’s current integrated approach to shorten CHO cell line development timeline utilizes host cells pre-adapted to production medium, optimization of the expression vectors, improved pre and post-transfection methodology, automated ClonePixTM technology and top clone selection and ranking in micro-scale ambr bioreactor technology. This platform was developed with monoclonal antibodies as model proteins. While this integrated platform enabled generation of high yielding clones expressing monoclonal antibodies, it was initially much less successful with a difficult to express recombinant stabilized trimeric RSV F protein. Initial stable CHO cell lines produced the RSV F protein at very low levels that were not suitable for GMP manufacturing and the protein did not have quality attributes similar to the initial transient expression-based research protein. The RSV F trimer requires enzymatic cleavage of the protein for proper folding and trimer formation. However, the need for stable co-expression of a furin-like molecule in CHO cells was initially unknown. This case study summarizes the successful development of stable CHO cell lines expressing the stabililzed RSV F trimer and a cell line development protocol for difficult to express trimeric viral glycoproteins for clinical manufacturing. Implications for cell line development of next generation trimeric HIV envelope vaccines will be discussed

On the growth of national geoparks in China: distribution, interpretation, and regional comparison

Since the year 2000 China has created 139 National Geoparks; it started under the guidance of the former UNESCO\u27s Division of Earth Science, and has therefore become one of the pioneers in this aspect. Many National Geoparks in China have been described over the past decade, but an understanding of the range of various landform features and their connection with geological and climatic constraints has not previously been published. Based on an increasing awareness of National Geoparks, the aim of this contribution is to provide a comprehensive overview of the National Geoparks of China by reviewing the geological heritage and their intrinsic linkages with geological and climatic controls. A regional comparison of the widespread clastic and karst Geopark landforms indicates that the development of these terrains can only be understood within a synthesis of tectonic constraints, climatic changes and lithological properties, whereas the variety of types, forms, scales and development patterns reflect processes in various climatic settings

Radiologisch-interventionelle Therapie vaskulärer Komplikationen nach Lebertransplantation

In Heidelberg wurde die erste erfolgreiche Lebertransplantation im Juni 1987 durchgeführt. Seit 2001 verzeichnet das Transplantationszentrum einen beachtlichen Anstieg an Lebertransplantationen, von vorher rund 31 auf rund 86 Patienten jährlich. Bis Dezember 2013 sind in Heidelberg über 1554 Lebertransplantationen durchgeführt worden. Die orthotope Lebertransplantation ist eine gängige, kurative Therapiemethode bei verschiedenen akuten und chronischen Lebererkrankungen. Allerdings können im postoperativen Verlauf Komplikationen auftreten, wobei vor allem vaskuläre Komplikationen mit einer hohen Morbidität und Mortalität verbunden sind. Diese werden eingeteilt in arterielle, venöse und portalvenöse Komplikationen. Am häufigsten kommen in diesem Zusammenhang arterielle Komplikationen vor. Zu diesen gehören Gefäßstenosen, die zu Thrombosen führen können, sowie Spasmen, Aneurysmen und Steal-Effekte der beteiligten arteriellen Gefäße. Seltener kommt es zu portalvenösen und venösen Komplikationen, beispielsweise zu Stenosen oder Thrombosen der Pfortader oder zu Stenosen der venösen (Piggy-Back-) Anastomose. Mit der fortschreitenden Entwicklung interventionell-radiologischer Verfahren können diese Komplikationen minimalinvasiv angegangen werden. Über 7% der lebertransplantierten Patienten der Universität Heidelberg wurden im Verlauf mit vaskulären postoperativen Komplikationen vorgestellt und interventionell- radiologisch therapiert. Der Langzeitverlauf wurde dokumentiert. Insgesamt wurden 56 Interventionen, davon 44 arterielle, 8 venöse und vier portalvenöse Interventionen vorgenommen, wobei 52 Interventionen technisch erfolgreich durchgeführt werden konnten. In drei Fällen kam es periinterventionell zu interventionsassoziierten Komplikationen. Zusätzlich traten bei einigen Patienten im weiteren Verlauf interventionsassoziierte Komplikationen, wie Restenosierungen nach PTA in 3 Fällen, sowie Stentdislokation oder Entwicklung einer arterioportalvenösen Fistel in je einem Fall, auf. Alle interventionsassoziierten Komplikationen (insgesamt 14,3%) konnten interventionell therapiert werden. Die Mehrzahl der vaskulären Komplikationen nach Lebertransplantation, die interventionell angegangen wurden, konnten erfolgreich interventionell behandelt werden. Der klinische Erfolg lag bei insgesamt 63,3%. Eine Ausnahme stellt die Lysetherapie der Leberarterie dar, bei der ein klinischer Erfolg nur in einem von acht Fällen erreicht werden konnte. Technische Weiterentwicklungen der zur Verfügung stehenden Materialien, beispielsweise der zunehmende Einsatz von Stentgrafts zur Behandlung von Aneurysmen, dürften in Zukunft weitere Möglichkeiten zur interventionellen Therapie eröffnen und somit die minimalinvasive Versorgung von Patienten nach Lebertransplantation weiter verbessern.The first successful liver transplantation was performed in Heidelberg in June 1987. Since 2001 the transplantation centre has recorded an immense increase in liver transplantations, increasing from about 31 to about 86 patients annually. In Heidelberg over 1554 liver transplantations were performed until December 2013. The orthotopic liver transplantation is a common and curative therapy method for variant acute and chronic liver diseases. But after the surgery complications can occur, in which mainly vascular complications are connected with a high morbidity and mortality. These vascular complications are categorized in arterial, venous or portal venous outflow complications. In this relation mainly arterial complications occur. They consist of vascular stenosis, which can lead to hepatic artery thombosis, hepatic artery aneurysm, spasm and steal-effect of the involved arteries. Venous and portal venous outflow complications, like stenosis oder thrombosis of the portal artery or stenosis of the venous piggy-back-anastomosis, are less common. With the onward development of interventional radiologic procedures these complications can be approached minimally invasive. Over 7% of the liver transplantated patients at the University of Heidelberg have been introduced with vascular complications after surgery and been treated with interventional radiology. The longterm development has been documented. 56 procedures were performed, thereof 44 were to be arterial, 8 venous and 4 portal venous procedures. Of these 56 procedures 52 could be performed technically successful. In three cases interventinal associated complications occured during the procedure. Additionally a few patients witnessed interventional associated complications like restenosis after PTA in three cases or stent dislocation or development of an arterioportalvenous fistula in one case respectively. All interventional associated complications (a total of 14,3%) could be treated interventional. The majority of vascular complications after liver transplantation could be treated successfully with interventional radiology with a clinical success rate of 63,3%. An exception poses thrombolysis of hepatic artery thrombosis, where a clinical success could only be achieved in one out of eight patients. Technical enhancements of the available materials, for example the increasing use of stentgrafts for the therapy of hepatic artery aneurysm, will establish the potentional for interventional therapy and thus improve the minimally invasive provision of patients after liver transplantation

Towards Control-Centric Representations in Reinforcement Learning from Images

Image-based Reinforcement Learning is a practical yet challenging task. A major hurdle lies in extracting control-centric representations while disregarding irrelevant information. While approaches that follow the bisimulation principle exhibit the potential in learning state representations to address this issue, they still grapple with the limited expressive capacity of latent dynamics and the inadaptability to sparse reward environments. To address these limitations, we introduce ReBis, which aims to capture control-centric information by integrating reward-free control information alongside reward-specific knowledge. ReBis utilizes a transformer architecture to implicitly model the dynamics and incorporates block-wise masking to eliminate spatiotemporal redundancy. Moreover, ReBis combines bisimulation-based loss with asymmetric reconstruction loss to prevent feature collapse in environments with sparse rewards. Empirical studies on two large benchmarks, including Atari games and DeepMind Control Suit, demonstrate that ReBis has superior performance compared to existing methods, proving its effectiveness

Development of a stabilized trimer pre-fusion RSV F recombinant viral glycoprotein vaccine

It has been known that the RSV fusion protein F is a target vaccine protein to produce a protective immune response. The VRC has shown (Ngwuta, et.al.) through binding competition assays that the amount of pre-fusion site Ø–specific antibodies correlates with neutralizing (NT) activity, whereas the pre/post-fusion site II mAbs does not correlate with neutralization. Our results indicate that RSV NT activity in human sera is primarily derived from pre-F–specific antibodies, and therefore, inducing or boosting NT activity by vaccination will be facilitated by using pre-F antigens that preserve site Ø. Therefore, the instability of the RSV pre-fusion conformation has limited the potential of this as a vaccine antigen. Therefore, the VRC has designed a structurally stabilized glycoprotein pre-fusion RSV F trimer vaccine antigen and has shown it to be highly immunogenic in preclinical studies. A description of challenges in the development of a high productivity CHO cell line, production process and product quality and antigenic characterization assays for Phase I clinical material will be presented along with comparison of pre-clinical results of research to development material. Please click Additional Files below to see the full abstract