Carbon Chain Length Modulates MDA-MB-231 Breast Cancer Cell Killing Mechanisms by Mitochondrially Targeted Aryl−Urea Fatty Acids

Targeting the tumor cell mitochondrion could produce novel anticancer agents. We designed an aryl−urea fatty acid ( 1 g ; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that disrupted the mitochondrion and decreased MDA-MB-231 breast cancer cell viability. To optimize the aryl−ureas the present study evaluated mitochondrial targeting by 1 g analogues containing alkyl chains between 10–17 carbons. Using the dye JC-1, the C12−C17 analogues efficiently disrupted the mitochondrial membrane potential (IC₅₀s 3.5±1.2 to 7.6±1.1 μM) and impaired ATP production; shorter analogues were less active. 7-Aminoactinomycin D/annexin V staining and flow cytometry showed that these agents activated the killing mechanisms of necrosis and apoptosis to varying extents (7-aminoactinomycin D/annexin V staining ratios 4.3–6.0). Indeed, 1 g and its C17 analogue preferentially activated necrosis and apoptosis, respectively (ratios 2.1 and 16). Taken together, alkyl chain length is a determinant of mitochondrial targeting by aryl−ureas and can be varied to develop analogues that activate apoptosis or necrosis in a regulated fashion.     

Impact-induced delayed detonation in an energetic material debris bubble formed at an air gap

A planar model of a rocket motor has been developed that allows reaction in a central bore perforated by a projectile to be viewed with high-speed photography. Earlier work with this model showed that a “bubble” of propellant debris forms in the air gap between energetic material layers (bore region) as a result of projectile penetration of one of the layers. Ignition of the bubble occurs upon impact with the second layer, followed by a reaction ranging from mild burning to delayed delonation, depending on the width of the air gap, properties of the energetic material, and degree of confinement. The present paper presents the results of experimental and hydrocode studies to characterize the latter (delayed detonation) reaction. Results show that reaction initiates in the frontal portion of the bubble wall through mechanical (impact) shock. It then propagates backward through the bubble wall towards the first layer which then detonates. Detonation of the second layer occurs sympathetically. The reaction is bounded by a lower velocity limit and confined within a range of air gaps that increases with impact velocity. The upper-air-gap limit roughly coincides with the maximum expansion distance for the bubble before breakup, while the lower limit represents the minimum (threshold) damage level for detonation.     

Human Milk Antibodies against S1 and S2 Subunits from SARS-CoV-2, HCoV-OC43, and HCoV-229E in Mothers with a Confirmed COVID-19 PCR,Viral SYMPTOMS,and Unexposed Mothers

Background: Preexisting immunity to SARS-CoV-2 could be related to cross-reactive antibodies to common human-coronaviruses (HCoVs). This study aimed to evaluate whether human milk antibodies against to S1 and S2 subunits SARS-CoV-2 are cross-reactive to S1 and S2 subunits HCoV-OC43 and HCoV-229E in mothers with a confirmed COVID-19 PCR test, in mothers with previous viral symptoms during COVID-19 pandemic, and in unexposed mothers; Methods: The levels of secretory IgA (SIgA)/IgA, secretory IgM (SIgM)/IgM, and IgG specific to S1 and S2 SARS-CoV-2, and reactive to S1 + S2 HCoV-OC43, and HCoV-229E were measured in milk from 7 mothers with a confirmed COVID-19 PCR test, 20 mothers with viral symptoms, and unexposed mothers (6 Ctl1-2018 and 16 Ctl2-2018) using ELISA; Results: The S2 SARS-CoV-2 IgG levels were higher in the COVID-19 PCR (p = 0.014) and viral symptom (p = 0.040) groups than in the Ctl1-2018 group. We detected a higher number of positive correlations between the antigens and secretory antibodies in the COVID-19 PCR group than in the viral symptom and Ctl-2018 groups. S1 + S2 HCoV-OC43-reactive IgG was higher in the COVID-19 group than in the control group (p = 0.002) but did not differ for the other antibodies; Conclusions: Mothers with a confirmed COVID-19 PCR and mothers with previous viral symptoms had preexisting human milk antibodies against S2 subunit SARS-CoV-2. Human milk IgG were more specific to S2 subunit SARS-CoV-2 than other antibodies, whereas SIgA and SIgM were polyreactive and cross-reactive to S1 or S2 subunit SARS-CoV-2.     

Activation of Ni/A12O3 catalysts through modification of the Al2O3 support

The effect of alumina pretreatment on the performance of alumina supported nickel catalysts was demonstrated in gas phase hydrogenation of toluene to methylcyclohexane. The state of the alumina was changed from pure to pure phase through various heat treatments in air. The catalysts were prepared from vapor phase by saturating the accessible binding sites on the pretreated alumina with the nickel precursor. The highest number of active sites for hydrogenation was observed for catalysts prepared on alumina having an incomplete phase transition and a / alumina phase ratio between 0.5 and 10. Results from temperature programmed desorption (TPD) studies revealed that a maximum in weakly chemisorbed hydrogen as well as in total amount of desorbed hydrogen was found for the same catalysts. By hydrogen chemisorption studies the total hydrogen uptake was found to correlate with the observed hydrogenation maximum. It is suggested that both the chemical and physical properties of the alumina influence the activity. An optimal metal-support interaction and structural defects on the alumina due to the phase transition can explain the observed maximum in the number of active sites and in hydrogen uptake.     

Cathodic arc deposition technology

Cathodic arc deposition is a unique technology. An arc spot on a cathode generates a plasma consisting of cathode material with a high degree of ionization. The high concentration of ions allows control of film morphology, high adhesion, efficient reactive deposition of compounds and uniform deposition over a variety of shapes. The composition of the alloys is generally retained from source to substrate. Deposition rates cover a wide range from nanometers per minute to tens of micrometers per minute. Many aspects of the technology warrant further study and its applications are only just beginning.     

Point or pointless – quality of ground data

A method for measuring continuously the inherent optical properties of water together with the salinity and the temperature values was developed and tested at the Division of Geophysics, University of Helsinki. The flow‐through system operates from a moving boat and has been used to collect parameters for optical modelling, coastal zone and inland water studies and to track the path of the fresh water spreading into sea areas. The system was also used in Lake Vänern, Sweden, to calculate the radiance reflectance, R _r, and total back‐scattering efficiency, b _{b eff}, along a transect. An example from the Gulf of Finland is presented, which shows how the spectral behaviour of light changes when moving away from a fresh water source. Data collected from the River Kymijoki estuary showed that the details in a rapidly changing environment were strongly smoothed in a Moderate Resolution Imaging Spectroradiometer (MODIS) data image. The correlation for continuously measured scattering values and MODIS channel 1 data varied between 0.70 and 0.85, n?=?126. Flow‐through measurement datasets can be used to obtain representative sites for vertical profiles or calibration measurements.     

Politics,public servants,and profits: Institutional complexity and temporary hybridization in a public infrastructure alliance project

Public infrastructure projects must comply with the divergent and even conflicting demands of multiple institutional logics causing institutional complexity. Despite the increasing interest in different forms of complexities in projects, we lack empirical illustrations and rigorous theorizing of mechanisms for responding to institutional complexity. This paper demonstrates how public buyers of a tunnel construction project formed a hybrid organization of a multi-party project alliance to respond to institutional complexity. We delineate a process of temporary hybridization through which the competing logics of a bureaucratic state, corporate market, and multiple professions were combined within the temporary project alliance organization. Such temporary hybridization not only focused on selective coupling with external demands but also mitigated internal tensions. Our findings emphasize a blended organizational structure, jointly formed governance and incentive systems, and the facilitation of social interaction to build a temporary yet sustainable hybrid organization capable of combining conflicting institutional logics.     

Value creation dynamics in a project alliance

Project alliance requires all parties to work together in good faith, share project risks, and make unanimous decisions for the betterment of the project. A key feature of successful implementation of a project alliance is a focus on value creation and value for money. This paper proposes a qualitative system dynamics model to specify and explain dynamics of value creation processes in the context of project alliance. By synthesizing the existing literature and reports on project alliancing, this paper identifies four processes that have a strong influence on the value created in the project alliance context: work progression, rework, redesign and innovation, and rescheduling. In addition, we show how these value creation processes are interrelated and evolve over time. The effectiveness of these processes is influenced by the capability and motivation of the project alliance partners to discover works that do not fully utilize the available resources, and make quick decisions to capture these benefits.     

Categorization of ambient media projects on their business models, innovativeness, and characteristics—evaluation of Nokia Ubimedia MindTrek Award Projects of 2010

Ambient Media describe media environments, where the medium is embedded within the natural environment. They follow the anytime, anywhere, and anyhow principle for media access. The Nokia Ubimedia MindTreks Awards have been established a few years ago to explore the potential of ambient media. In this article we analyze the total project portfolio submitted to the 4th Nokia Ubimedia MindTrek Awards in 2010 according to their business value, innovativeness, and use of ambient media. The aim of this article is to gain insights into the general characteristics of ambient media, their properties, and business functions. The article rounds up in providing a substantial framework and guidelines for ambient media developers in their product designs.     

Toward Xeno-Free Differentiation of Human Induced Pluripotent Stem Cell-Derived Small Intestinal Epithelial Cells

The small intestinal epithelium has an important role in nutrition, but also in drug absorption and metabolism. There are a few two-dimensional (2D) patient-derived induced pluripotent stem cell (iPSC)-based intestinal models enabling easy evaluation of transcellular transport. It is known that animal-derived components induce variation in the experimental outcomes. Therefore, we aimed to refine the differentiation protocol by using animal-free components. More specifically, we compared maturation of 2D-cultured iPCSs toward small intestinal epithelial cells when cultured either with or without serum, and either on Geltrex or on animal-free, recombinant laminin-based substrata. Differentiation status was characterized by qPCR, immunofluorescence imaging, and functionality assays. Our data suggest that differentiation toward definitive endoderm is more efficient without serum. Both collagen- and recombinant laminin-based coating supported differentiation of definitive endoderm, posterior definitive endoderm, and small intestinal epithelial cells from iPS-cells equally well. Small intestinal epithelial cells differentiated on recombinant laminin exhibited slightly more enterocyte specific cellular functionality than cells differentiated on Geltrex. Our data suggest that functional small intestinal epithelial cells can be generated from iPSCs in serum-free method on xeno-free substrata. This method is easily converted to an entirely xeno-free method.