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.     

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.     

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.     

Mannans as stabilizers of oil-in-water beverage emulsions

The stabilizing effect of spruce galactoglucomannan (GGM) on a model beverage emulsion system was studied and compared to that of guar gum and locust bean gum galactomannans, konjac glucomannan, and corn arabinoxylan. In addition, guar gum was enzymatically modified in order to examine the effect of the degree of polymerization and the degree of substitution of galactomannans on emulsion stability. Use of GGM increased the turbidity of emulsions both immediately after preparation and after storage of up to 14 days at room temperature. GGM emulsions had higher turbidity than the emulsions containing other mannans. The initial turbidity increased with increasing GGM content, but after 14 days storage at room temperature, the turbidity was the highest for GGM/oil ratio of 0.10:1 when ethanol-precipitated GGM was used. Increasing the storage temperature to +45 °C led to rapid emulsion breakdown, but a decrease in storage temperature increased emulsion stability after 14 days. Confocal microscopy showed that the average particle size in the bottom part of GGM emulsions stored for 14 days was smaller than 1 μm. A low degree of polymerization and a high degree of substitution of the modified galactomannans were associated with a decrease in emulsion turbidity.     

Biological effects of casein-derived tripeptide powders are not affected by fermentation process

Milk casein-derived biologically active tripeptides isoleucine–proline–proline and valine–proline–proline have shown antihypertensive effects both in animal and clinical studies. Contradictory findings from clinical intervention studies may be related to different manufacturing processes. The present study aimed to compare cardiovascular effects of two different tripeptide powders in spontaneously hypertensive rat (SHR). Rats received tripeptide powders produced either by Lactobacillus helveticus fermentation (A) or Lb. helveticus plus proline specific endoprotease (B) in drinking fluid for 8 weeks. Systolic blood pressure was recorded weekly. At the end, blood and tissue samples were collected and arterial responses studied. Blood pressure was 13.6 and 14.2 mmHg lower in the groups A and B, respectively, versus the water group (P < 0.01). Vascular responses of aorta and mesenteric artery did not differ between the groups. Both tripeptide products increased urinary cGMP (P < 0.001) and decreased albumin (P < 0.05). The fermentation process did not influence the cardiovascular effects of the tripeptide powders.     

On the realization of periodic functions

In this article, canonical and spectrally minimal infinite-dimensional state space realizations for periodic functions are considered. It is shown that the periodic functions having ℓ₁ Fourier coefficients are precisely those realizable by a Riesz spectral system (RSS) in which the system operator generates a periodic strongly continuous semigroup and the observation operator is bounded. This realization can easily be converted to a canonical and spectrally minimal form. It is shown how the use of RSS and Cesáro sums of Fourier series allows the construction of a state space realization for a given periodic function merely integrable over its period. Simple finite-dimensional approximations with error bounds are derived for the RSS realization. Regular well-posed linear systems (WPLS) are used to construct a Fuhrmann-type realization for a given periodic function integrable over its period. It is shown that the RSS realizations and WPLS realizations are precisely equally good at coping with the possible ill behavior of a given bounded periodic function integrable over its period, but the WPLS realization is not always spectrally minimal or canonical.     

Bovine muscle glycogen concentration in relation to finishing diet, slaughter and ultimate pH

The aim of this study was to investigate the effects of a high-energy diet provided for a rather short time prior to transportation to slaughter on muscle glycogen concentration on farm, after transportation and after refrigeration of the carcasses. The experiment involved 60 Ayrshire bulls which were fed either a low energy diet of 100% grass silage or a compound feed based diet providing 10.8 and 12.9 MJ of metabolizable energy per kg of dry matter, respectively. Identical setup of 30 bulls was carried out in spring and in summer. Three muscle samples were obtained from the longissimus dorsi and gluteus medius muscles: a biopsy prior to initiation of experimental feeding (B1); another biopsy after 14 days on diet (B2); a post mortem sample at 48 h after slaughter (3) (also M. semimembranosus). Initial resting muscle glycogen concentration affected the responsiveness of glycogen to diet. The more glycogen there was initially the less glycogen increased (r=-0.678, p<0.0001). However, compared to the low energy diet the high energy diet seemed to protect cattle from potentially glycogen-depleting stressors such as high temperatures and transportation. The cattle on high energy lost 7±4.0 (se) mmol/kg and 23±3.9 mmol/kg during transportation in spring (cool weather) and in summer (hot weather), respectively, whereas the cattle on low energy diet lost 16±3.8 mmol/kg in spring and 33±4.1 mmol/kg in summer. The overall protective effect of high energy diet corresponded to 0.65 pH units. The effects of diet were reflected all the way to ultimate pH values [5.69±0.03 (high energy); 5.93±0.03 (low energy)] (p<0.0001) and residual glycogen concentrations (p<0.0001). It seems indeed that providing a diet high in energy for a couple of weeks prior to transportation to slaughter is one of the many appropriate measures to take in the fight against bovine dark-cutting.