Heat propagation models for superconducting nanobridges at millikelvin temperatures

Nanoscale superconducting quantum interference devices (nanoSQUIDs) most commonly use Dayem bridges as Josephson elements to reduce the loop size and achieve high spin sensitivity. Except at temperatures close to the critical temperature T c, the electrical characteristics of these bridges exhibit undesirable thermal hysteresis which complicates device operation. This makes proper thermal analysis an essential design consideration for optimising nanoSQUID performance at ultralow temperatures. However the existing theoretical models for this hysteresis were developed for micron-scale devices operating close to liquid helium temperatures, and are not fully applicable to a new generation of much smaller devices operating at significantly lower temperatures. We have therefore developed a new analytic heat model which enables a more accurate prediction of the thermal behaviour in such circumstances. We demonstrate that this model is in good agreement with experimental results measured down to 100 mK and discuss its validity for different nanoSQUID geometries

Influence of relative NK-DC abundance on placentation and its relation to epigenetic programming in the offspring

Normal placentation relies on an efficient maternal adaptation to pregnancy. Within the decidua, natural killer (NK) cells and dendritic cells (DC) have a critical role in modulating angiogenesis and decidualization associated with pregnancy. However, the contribution of these immune cells to the placentation process and subsequently fetal development remains largely elusive. Using two different mouse models, we here show that optimal placentation and fetal development is sensitive to disturbances in NK cell relative abundance at the fetal–maternal interface. Depletion of NK cells during early gestation compromises the placentation process by causing alteration in placental function and structure. Embryos derived from NK-depleted dams suffer from intrauterine growth restriction (IUGR), a phenomenon that continued to be evident in the offspring on post-natal day 4. Further, we demonstrate that IUGR was accompanied by an overall reduction of global DNA methylation levels and epigenetic changes in the methylation of specific hepatic gene promoters. Thus, temporary changes within the NK cell pool during early gestation influence placental development and function, subsequently affecting hepatic gene methylation and fetal metabolism.Fil: Freitag, Nancy. Medicine University of Berlin; AlemaniaFil: Zwier, M. V.. University of Groningen; Países BajosFil: Barrientos, Gabriela Laura. Medicine University of Berlin; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tirado González, Irene. Medicine University of Berlin; AlemaniaFil: Conrad, Melanie L.. Medicine University of Berlin; AlemaniaFil: Rose, Matthias. Medicine University of Berlin; AlemaniaFil: Scherjon, S. A.. University of Groningen; Países BajosFil: Plösch, T.. University of Groningen; Países BajosFil: Blois, Sandra M.. Medicine University of Berlin; Alemani

Uterine NK cells are critical in shaping DC immunogenic functions compatible with pregnancy progression.

Dendritic cell (DC) and natural killer (NK) cell interactions are important for the regulation of innate and adaptive immunity, but their relevance during early pregnancy remains elusive. Using two different strategies to manipulate the frequency of NK cells and DC during gestation, we investigated their relative impact on the decidualization process and on angiogenic responses that characterize murine implantation. Manipulation of the frequency of NK cells, DC or both lead to a defective decidual response characterized by decreased proliferation and differentiation of stromal cells. Whereas no detrimental effects were evident upon expansion of DC, NK cell ablation in such expanded DC mice severely compromised decidual development and led to early pregnancy loss. Pregnancy failure in these mice was associated with an unbalanced production of anti-angiogenic signals and most notably, with increased expression of genes related to inflammation and immunogenic activation of DC. Thus, NK cells appear to play an important role counteracting potential anomalies raised by DC expansion and overactivity in the decidua, becoming critical for normal pregnancy progression

Toxic Site Identification Program in Azerbaijan

The need to protect communities from hazardous waste is an important agenda for any nation. Although pollutant management and policy development are attempted in many developing countries, it is not always successful due to limited funds, project resources, and access to trained experts to conduct toxic site identification projects. For this reason, Pure Earth created the Toxic Site Identification Program (TSIP). The goal of the TSIP program is to provide reliable information and data that identifies location of toxic sites and the level of toxic severity. TSIP is significant because it provides developing countries a database of ranked toxic sites identified as hazardous risk to human health. For example, Azerbaijan is one of the most polluted post-Soviet nations, but has limited resources to address and manage its polluted sites. The Azerbaijani TSIP database is the first reliable data source that identifies hazardous pollutants in the country. Our study is significant because it discusses how the TSIP labels and ranks the level of toxic severity to human health. It is also the first data source in Azerbaijan that identifies which Soviet legacy toxic sites are affecting local communities. Although our study is specific to Azerbaijan, the TSIP method can be applied to nations with similar data limitations and the need for a database that identifies country specific environmental and hazardous locations. The data sampling method and results are mapped and accompanied by tables of the collected pollutant types to identify communities at greatest health-risk to legacy toxic sites

Implementing Ac-225 labelled radiopharmaceuticals:practical considerations and (pre-)clinical perspectives

BackgroundIn the past years, there has been a notable increase in interest regarding targeted alpha therapy using Ac-225, driven by the observed promising clinical anti-tumor effects. As the production and technology has advanced, the availability of Ac-225 is expected to increase in the near future, making the treatment available to patients worldwide.Main bodyAc-225 can be labelled to different biological vectors, whereby the success of developing a radiopharmaceutical depends heavily on the labelling conditions, purity of the radionuclide source, chelator, and type of quenchers used to avoid radiolysis. Multiple (methodological) challenges need to be overcome when working with Ac-225; as alpha-emission detection is time consuming and highly geometry dependent, a gamma co-emission is used, but has to be in equilibrium with the mother-nuclide. Because of the high impact of alpha emitters in vivo it is highly recommended to cross-calibrate the Ac-225 measurements for used quality control (QC) techniques (radio-TLC, HPLC, HP-Ge detector, and gamma counter). More strict health physics regulations apply, as Ac-225 has a high toxicity, thereby limiting practical handling and quantities used for QC analysis.ConclusionThis overview focuses specifically on the practical and methodological challenges when working with Ac-225 labelled radiopharmaceuticals, and underlines the required infrastructure and (detection) methods for the (pre-)clinical application

Measurement of reaction kinetics of [177Lu]Lu-DOTA-TATE using a microfluidic system

Microfluidic synthesis techniques can offer improvement over batch syntheses which are currently used for radiopharmaceutical production. These improvements are, for example, better mixing of reactants, more efficient energy transfer, less radiolysis, faster reaction optimization, and overall improved reaction control. However, scale-up challenges hinder the routine clinical use, so the main advantage is currently the ability to optimize reactions rapidly and with low reactant consumption. Translating those results to clinical systems could be done based on calculations, if kinetic constants and diffusion coefficients were known. This study describes a microfluidic system with which it was possible to determine the kinetic association rate constants for the formation of [177Lu]Lu-DOTA-TATE under conditions currently used for clinical production. The kinetic rate constants showed a temperature dependence that followed the Arrhenius equation, allowing the determination of Arrhenius parameters for a Lu-DOTA conjugate (A = 1.24 ± 0.05 × 1019 M-1 s-1, EA = 109.5 ± 0.1 × 103 J mol-1) for the first time. The required reaction time for the formation of [177Lu]Lu-DOTA-TATE (99% yield) at 80 °C was 44 s in a microfluidic channel (100 μm). Simulations done with COMSOL Multiphysics® indicated that processing clinical amounts (3 mL reaction solution) in less than 12 min is possible in a micro- or milli-fluidic system, if the diameter of the reaction channel is increased to over 500 μm. These results show that a continuous, microfluidic system can become a viable alternative to the conventional, batch-wise radiolabelling technique

Time to better integrate paleoecological research infrastructures with neoecology to improve understanding of biodiversity long-term dynamics and to inform future conservation

Anthropogenic pressures are causing a global decline in biodiversity. Successful attempts at biodiversity conservation requires an understanding of biodiversity patterns as well as the drivers and processes that determine those patterns. To deepen this knowledge, neoecologists have focused on studying present-day or recent historical data, while paleoecologists usually study long-term data through the composition of various biological proxies and environmental indicators. By establishing standard protocols or gathering databases, research infrastructures (RIs) have been instrumental to foster exchange and collaboration among scientists within neoecology (e.g. Global Information Biodiversity Facility or National Ecological Observatory Network) and paleoecology (e.g. Paleobiology Database, Neotoma Paleoecology Database or European Pollen Database). However, these two subdisciplines (and their RIs) have traditionally remained segregated although both provide valuable information that combined can improve our understanding of biodiversity drivers and underlying processes, as well as our predictions of biodiversity responses in the future. For instance, integrative studies between paleo- and neoecology have addressed the global challenge of biodiversity loss by validating climate and ecological models, estimating species fundamental niches, understanding ecological changes and trajectories, or establishing baseline conditions for restoration. Supporting and contributing to research infrastructures from both paleo- and neoecology, as well as their further integration, could boost the amount and improve the quality of such integrative studies. We argue this will enable improved capabilities to anticipate the impacts of global change and biodiversity losses. To boost such integration and illustrate our arguments, we (1) review studies integrating paleo- and neoecology to advance in the light of global changes challenge, (2) describe RIs developed in paleoecology, and (3) discuss opportunities for further integration of RIs from both disciplines (i.e. paleo- and neoecology).publishedVersio

Differential Spatiotemporal Patterns of Galectin Expression are a Hallmark of Endotheliochorial Placentation

Problem: Galectins influence the progress of pregnancy by regulating key processes associated with embryo-maternal cross talk, including angiogenesis and placentation. Galectin family members exert multiple roles in the context of hemochorial and epitheliochorial placentation; however, the galectin prolife in endotheliochorial placenta remains to be investigated. Method of study: Here, we used immunohistochemistry to analyze galectin (gal)-1, gal-3 and gal-9 expression during early and late endotheliochorial placentation in two different species (dogs and cats). Results: We found that during early feline gestation, all three galectin members were more strongly expressed on trophoblast and maternal vessels compared to the decidua. This was accompanied by an overall decrease of gal-1, gal-3 and gal-9 expressions in late feline gestation. In canine early pregnancy, we observed that gal-1 and gal-9 were expressed strongly in cytotrophoblast (CTB) cells compared to gal-3, and no galectin expression was observed in syncytiotrophoblast (STB) cells. Progression of canine gestation was accompanied by increased gal-1 and gal-3 expressions on STB cells, whereas gal-9 expression remained similar in CTB and STB. Conclusion: These data suggest that both the maternal and fetal compartments are characterized by a spatiotemporal regulation of galectin expression during endotheliochorial placentation. This strongly suggests the involvement of the galectin family in important developmental processes during gestation including immunemodulation, trophoblast invasion and angiogenesis. A conserved functional role for galectins during mammalian placental development emerges from these studies.Facultad de Ciencias Veterinaria