First-in-man evaluation of 124I-PGN650: A PET tracer for detecting phosphatidylserine as a biomarker of the solid tumor microenvironment

Purpose: PGN650 is a F(ab′) 2 antibody fragment that targets phosphatidylserine (PS), a marker normally absent that becomes exposed on tumor cells and tumor vasculature in response to oxidative stress and increases in response to therapy. PGN650 was labeled with 124 I to create a positron emission tomography (PET) agent as an in vivo biomarker for tumor microenvironment and response to therapy. In this phase 0 study, we evaluated the pharmacokinetics, safety, radiation dosimetry, and tumor targeting of this tracer in a cohort of patients with cancer. Methods: Eleven patients with known solid tumors received approximately 140 MBq (3.8 mCi) 124 I-PGN650 intravenously and underwent positron emission tomography–computed tomography (PET/CT) approximately 1 hour, 3 hours, and either 24 hours or 48 hours later to establish tracer kinetics for the purpose of calculating radiation dosimetry (from integration of the organ time-activity curves and OLINDA/EXM using the adult male and female models). Results: Known tumor foci demonstrated mildly increased uptake, with the highest activity at the latest imaging time. There were no unexpected adverse events. The liver was the organ receiving the highest radiation dose (0.77 mGy/MBq); the effective dose was 0.41 mSv/MBq. Conclusion: Although 124 I-PGN650 is safe for human PET imaging, the tumor targeting with this agent in patients was less than previously observed in animal studies

Expansion of human mesenchymal stem cells in a fixed-bed bioreactor system based on non-porous glass carrier – Part A: Inoculation, cultivation, and cell harvest procedures

Human mesenchymal stem cells (hMSC) are a promising cell source for several applications of regenerative medicine. The used cells are either autologous or allogenic, whereas the latter enables, especially by using of stem cell lines, a production of cell therapeutic or tissue engineered implants in stock. Therefore, the usually small initial cell number has to be increased. For that purpose bioreactors are demanded, which offer the controlled expansion of the hMSC under GMP-conform conditions. In this study, divided in part A and B, a fixed bed bioreactor system based on non-porous borosilicate glass spheres for the expansion of hMSC, demonstrated with the model cell line hMSC-TERT, is introduced. The system offers a comfortable automation of the inoculation, cultivation, and harvesting procedures. Furthermore the bioreactor owns a simple design which benefits the manufacturing as disposable. Part A is focused on the inoculation, cultivation, and harvesting procedures. Cultivations were performed in lab scales up to a bed volume of 300 cm3. It could be shown that the fixed bed system, based on 2-mm borosilicate glass spheres, as well as the inoculation, cultivation, and harvesting procedures are suitable for the expansion of hMSC with high yield and vitality

Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer

Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer and infectious disease therapeutics

Ein livländisches Herz : Katharina I von Russland : geschichtlicher Roman

http://www.ester.ee/record=b4374851*es

Integrated pest management in historical collections of the 21st century

Many museum collections are at risk for pest infestation, but historical collections in particular are susceptible to these degradations due to the prevalence of materials that attract pests. In the past, collections have been treated with chemical methods, but more recently, a new methodological approach, called Integrated Pest Management, or IPM, has emerged in caring for collections. In this thesis, Integrated Pest Management, defined as an integrative method of pest control, is examined in museums caring for historical collections. A survey of museums in North America that care for historical collections was conducted, resulting in a response rate of roughly 20%. After a discussion, a set of conclusions and recommendations is offered. It is concluded that museums with historical collections have largely integrated IPM into their efforts and that IPM is a significant advance in collections stewardship over traditional methods

Effect of abiotic factors on the diversity and abundance of aquatic macroinvertebrates in the East and West Branches of the Maple River, Michigan, USA

General EcologyStreams are home to a wide variety of aquatic organisms including fish and benthic macroinvertebrates. Variance in diversity and abundance of macroinvertebrates in stream ecosystems is influenced by water chemistry and substrate availability. Different substrates provide macroinvertebrates with varying habitats, protection, and resources. Four distinct sites on the East and West branches of the Maple River around Pellston, MI were sampled and studied to examine the combined effects of abiotic factors on macroinvertebrate diversity and abundance. At each site, three substrates (cobble, gravel, and sand) were studied. Rocky riverbed substrates (i.e. gravel and cobble) contained greater numbers and more diverse macro invertebrate families than sandy substrates. Stable isotope analysis of the water from each site showed a correlation between the abundance of individuals and groundwater concentration but did not show a correlation between diversity of families and groundwater concentration.https://deepblue.lib.umich.edu/bitstream/2027.42/140071/1/Freimark_Jameson_Jubera_Schneider-2017.PDFDescription of Freimark_Jameson_Jubera_Schneider-2017.PDF : Freimark, C., E. Jameson, K. Jubera, and B. Schneider_201

Integrated pest management in historical collections of the 21st century

Many museum collections are at risk for pest infestation, but historical collections\ud in particular are susceptible to these degradations due to the prevalence of materials that\ud attract pests. In the past, collections have been treated with chemical methods, but more\ud recently, a new methodological approach, called Integrated Pest Management, or IPM,\ud has emerged in caring for collections. In this thesis, Integrated Pest Management, defined as an integrative method of pest control, is examined in museums caring for historical collections. A survey of museums in North America that care for historical collections was conducted, resulting in a response rate of roughly 20%. After a discussion, a set of conclusions and recommendations is offered. It is concluded that museums with historical collections have largely integrated IPM into their efforts and that IPM is a significant advance in collections stewardship over traditional methods

Reverse remodeling and the mechanism of mitral regurgitation improvement in patients with dilated cardiomyopathy

Background: Functional mitral regurgitation (MR) is a common finding in dilated cardiomyopathy. Left ventricular (LV) reverse remodeling with LV size reduction and improvement in LV function is a well recognized phenomenon. We aimed to evaluate the impact of LV remodeling on the mechanism leading to functional MR. Methods: Among 188 patients with non-ischemic dilated cardiomyopathy, 10 patients significantly improved their LV function, reduced LV size and MR severity during follow-up (RRMR). A comparison was made between their baseline and follow-up echocardiographic examinations and to a matched-control group of patients who did not improve (no RRMR). LV and left atrium (LA) dimensions and volumes, LV mass (LVM), LV ejection fraction (LVEF) (Simpsons), sphericity index (SI), mitral valve tenting area (TA) coaptation distance (CD), effective regurgitant orifice (ERO), and regurgitant volume were calculated. Multivariable analysis was performed in order to evaluate which echocardiographic parameters related to MR improvement in reverse remodeling. Results: LV and LA dimensions and volumes, LVM, SI, TA, CD, ERO and right ventricle, in the RRMR group significantly decreased at follow-up (p < 0.04 for all). When compared to no RRMR, despite a similar ERO (0.2 ± 0.05 vs. 0.2 ± 0.08, p = 0.13) and a larger regurgitant volume (38 ± 9 vs. 29 ± 8 mL, p = 0.05) and despite similar clinical characteristics and medical treatment we found significantly higher LVEF, smaller LV dimensions and volumes, smaller LVM and SI in the RRMR group (p < 0.05 for all). On multivariable analysis the SI was the sole predictor of RRMR (p = 0.04, OR = 0.76, CI 0.58–0.99). Conclusions: Reverse remodeling characterized by improvement in LV function, reduction in LV size and an associated reduction in MR severity is related to LV SI at baseline.

Seagrass ecosystems reduce disease risk and economic loss in marine farming production.

Seaweed farming comprises over half of global coastal and marine aquaculture production by mass; however, the future of the industry is increasingly threatened by disease outbreaks. Nature-based solutions provided by enhancing functions of coinciding species or ecosystems offer an opportunity to increase yields by reducing disease outbreaks while conserving biodiversity. Seagrass ecosystems can reduce the abundance of marine bacterial pathogens, although it remains unknown whether this service can extend to reducing disease risk in a marine resource. Using a meta-analysis of articles published over the past 40 y, we find that 17 known diseases of seaweeds are attributed to bacteria that have been previously shown to be lower when associated with seagrass ecosystems. Next, we surveyed over 8,000 individual seaweeds among farms in Indonesia and found that disease risk is reduced by 75% when seaweeds are co-cultivated directly within seagrass ecosystems, compared to when seagrass ecosystems were removed. Finally, we estimate that farming seaweed with seagrass ecosystems could increase annual revenue by $292,470 -$1,015,990 USD per km2 from yield loss due to disease reduction and that ~20.7 million km2 in 107 countries and 34 territories have suitable environmental conditions for farming seaweeds with seagrass ecosystems. These results highlight the global utility for nature-based solutions as an ecologically and economically sustainable management strategy