Modeling of droplet breakup in a microfluidic T--shaped junction with a phase--field model

A phase--field method is applied to the modeling of flow and breakup of droplets in a T--shaped junction in the hydrodynamic regime where capillary and viscous stresses dominate over inertial forces, which is characteristic of microfluidic devices. The transport equations are solved numerically in the three--dimensional geometry, and the dependence of the droplet breakup on the flow rates, surface tension and viscosities of the two components is investigated in detail. The model reproduces quite accurately the phase diagram observed in experiments performed with immiscible fluids. The critical capillary number for droplet breakup depends on the viscosity contrast, with a trend which is analogous to that observed for free isolated droplets in hyperbolic flow

Primary osteoblast-like cells from patients with end-stage kidney disease reflect gene expression, proliferation, and mineralization characteristics ex vivo.

Osteocytes regulate bone turnover and mineralization in chronic kidney disease. As osteocytes are derived from osteoblasts, alterations in osteoblast function may regulate osteoblast maturation, osteocytic transition, bone turnover, and skeletal mineralization. Thus, primary osteoblast-like cells were cultured from bone chips obtained from 24 pediatric ESKD patients. RNA expression in cultured cells was compared with RNA expression in cells from healthy individuals, to RNA expression in the bone core itself, and to parameters of bone histomorphometry. Proliferation and mineralization rates of patient cells were compared with rates in healthy control cells. Associations were observed between bone osteoid accumulation, as assessed by bone histomorphometry, and bone core RNA expression of osterix, matrix gla protein, parathyroid hormone receptor 1, and RANKL. Gene expression of osteoblast markers was increased in cells from ESKD patients and signaling genes including Cyp24A1, Cyp27B1, VDR, and NHERF1 correlated between cells and bone cores. Cells from patients with high turnover renal osteodystrophy proliferated more rapidly and mineralized more slowly than did cells from healthy controls. Thus, primary osteoblasts obtained from patients with ESKD retain changes in gene expression ex vivo that are also observed in bone core specimens. Evaluation of these cells in vitro may provide further insights into the abnormal bone biology that persists, despite current therapies, in patients with ESKD

Use of Denosumab in Children With Osteoclast Bone Dysplasias: Report of Three Cases.

Denosumab has been used successfully to treat disease-associated osteoclast overactivity, including giant cell tumor of bone. Given its mechanism of action, denosumab is a potent potential treatment of other osteoclast bone dysplasias including central giant cell granuloma (CGCG), aneurysmal bone cyst (ABC), and cherubism. Relatively little is known about the safety and efficacy of denosumab in patients with these conditions, especially in children. We report on 3 pediatric patients treated with denosumab over a 3-year period at UCLA Medical Center (Los Angeles and Santa Monica, CA, USA): a 12-year-old with recurrent ABC of the pelvis, a 14-year-old with CGCG of the mandible, and a 12-year-old with cherubism. All were started on a 1-year course of 15 doses 120 mg s.c., given monthly with two loading doses on day 8 and 15. All patients demonstrated rapid and pronounced clinical improvement while on denosumab, including a significant reduction in pain and sclerosis of lytic lesions on radiographs. Within 1 month of initiating therapy, 2 patients experienced hypocalcemia (Common Terminology Criteria for Adverse Events [CTCAE] grade 2) and hypophosphatemia, with 1 patient experiencing symptoms. One patient went on to experience symptomatic rebound hypercalcemia (CTCAE grade 4) 5 months after completing therapy, requiring bisphosphonates and calcitonin. For the second patient, we developed a schedule to wean denosumab involving the progressive lengthening of time between doses from 1 to 4 months in 1-month increments before cessation. We found that denosumab therapy results in significant clinical and radiographic improvement for pediatric patients with nonresectable ABC, CGCG, and cherubism. Problems with serum calcium may be more common in younger patients, with symptomatic and protracted rebound hypercalcemia after cessation of therapy the most significant. We present a potential solution to this problem with progressive spacing of doses. Potential serious adverse events from alterations in calcium homeostasis should be explored in prospective clinical trials. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

Effect of fresh water supply on agriculture in the southwest of the Netherlands.

Soil water deficits for twelve crops during each summer from 1933 to 1980 were calculated for a 15,000 ha region of southwestern Netherlands, and the chloride load of the drainage ditches, due to the seepage of salt water from the sea, was determined. Water requirements for sprinkling irrigation and for flushing the water courses for quality control were computed. The maximum water requirement for sprinkling and flushing was 3.4 mm day-1. The average increase in crop yields due to sprinkling ranged fro

The expression pattern of MUC1 (EMA) is related to tumour characteristics and clinical outcome of invasive ductal breast carcinoma

Aims: To clarify MUC1 patterns in invasive ductal breast carcinoma and to relate them to clinicopathological parameters, coexpression of other biological markers and prognosis. Methods and results: Samples from 243 consecutive patients with primary ductal carcinoma were incorporated into tissue microarrays (TMAs). Slides were stained for MUC1, oestrogen receptor (ER), progesterone receptor (PR), Her2/neu, p53 and cyclin D1. Apical membrane MUC1 expression was associated with smaller tumours (P = 0.001), lower tumour grades (P < 0.001), PR positivity (P = 0.003) and increased overall survival (OS; P = 0.030). Diffuse cytoplasmic MUC1 expression was associated with cyclin D1 positivity (P = 0.009) and increased relapse-free survival (RFS; P = 0.034). Negativity for MUC1 was associated with ER negativity (P = 0.004), PR negativity (P = 0.001) and cyclin D1 negativity (P = 0.009). In stepwise multivariate analysis MUC1 negativity was an independent predictor of both RFS [hazard ratio (HR) 3.5, 95% confidence interval (CI) 1.5, 8.5; P = 0.005] and OS (HR 14.7, 9 5% Cl 4.9, 44. 1; P < 0.001). Conclusions: The expression pattern of MUC1 in invasive ductal breast carcinoma is related to tumour characteristics and clinical outcome. In addition, negative MUC1 expression is an independent risk factor for poor RFS and OS, besides 'classical' prognostic indicators

Intracellular Ca2+ Concentration and Phosphatidylserine Exposure in Healthy Human Erythrocytes in Dependence on in vivo Cell Age

After about 120 days of circulation in the blood stream, erythrocytes are cleared by macrophages in the spleen and the liver. The "eat me" signal of this event is thought to be the translocation of phosphatidylserine from the inner to the outer membrane leaflet due to activation of the scramblase, while the flippase is inactivated. Both processes are triggered by an increased intracellular Ca2+ concentration. Although this is not the only mechanism involved in erythrocyte clearance, in this minireview, we focus on the following questions: Is the intracellular-free Ca2+ concentration and hence phosphatidylserine exposure dependent on the erythrocyte age, i.e. is the Ca2+ concentration, progressively raising during the erythrocyte aging in vivo? Can putative differences in intracellular Ca2+ and exposure of phosphatidylserine to the outer membrane leaflet be measured in age separated cell populations? Literature research revealed less than dozen of such publications with vastly contradicting results for the Ca2+ concentrations but consistency for a lack of change for the phosphatidylserine exposure. Additionally, we performed reanalysis of published data resulting in an ostensive illustration of the situation described above. Relating these results to erythrocyte physiology and biochemistry, we can conclude that the variation of the intracellular free Ca2+ concentration is limited with 10 μM as the upper level of the concentration. Furthermore, we propose the hypothesis that variations in measured Ca2+ concentrations may to a large extent depend on the experimental conditions applied but reflect a putatively changed Ca2+ susceptibility of erythrocytes in dependence of in vivo cell age

Red Blood Cells Actively Contribute to Blood Coagulation and Thrombus Formation

The chapter describes the likely molecular mechanisms leading to the aggregation of human red blood cells (RBCs) under conditions of physiological coagulation when prostaglandin E2 (PGE2) or lysophosphatidic acid (LPA) is released from activated platelets and under pathophysiological conditions, in particular thrombi formation in sickle cell disease when patients are in a vaso-occlusive crisis. In both scenarios cation channels are activated. This leads to an increase of the free intracellular Ca2+ concentration resulting in an activation of the lipid scramblase, which in turn mediates a movement of phosphatidylserine (PS) from the inner to the outer membrane leaflet. In addition, the increased Ca2+ concentration leads to the activation of the Gardos channel. Experiments suggesting this mechanism have been performed with fluorescence microscopy, flow cytometry as well as single-cell force spectroscopy. The Ca2+-triggered RBC aggregation force has been identified to be close to 100 pN, a value large enough to play a significant role during thrombus formation or in pathological situations

Фільтраційні справи радянських громадян, примусово вивезених до Німеччина в роки Великої Вітчизняної війни, як історичне джерело

We ask how incumbent car manufacturers and their political coalitions changed their political strategy with respect to the Californian zero emission vehicle mandate over the period 2000-2013. Building on the Corporate Political Activities literature we conceptualize firms' political strategies and their underlying tactics and actions. Our longitudinal case study builds on a dataset comprising governmental reports, documents, and public hearing transcripts, letters from industry, and complementary interviews with stakeholders. We find that car manufacturers became less defensive over time and more proactive and compliant in their political strategies towards the zero emission vehicle mandate. Car manufacturers' coalitions on the other hand, remain relatively defensive in their political actions as they continue to do the manufacturers' "dirty work". We provide insights in the Corporate Political Activities used to influence policymakers. To deal with industry opposition to policy interventions, our research suggests that policy makers might focus their interaction with industry on individual firms instead of industry associations, craft policies that stimulate competition between firms to break apart their closed industry front, and complement technology-forcing policies with demand-pull initiatives

Alternative reproductive tactics, sperm mobility and oxidative stress in Carollia perspicillata (Seba's short-tailed bat)

In social systems with alternative reproductive tactics, sneakers face a higher level of sperm competition than harem males and hence are predicted to allocate more resources to ejaculates. Antioxidants can protect sperm against oxidative stress, and thus, their allocation to the ejaculate may depend on mating tactic. In this study on the frugivorous bat Carollia perspicillata, we assessed, for harem and sneaker males, four spermmobility traits, blood and ejaculatemarkers of the redox balance and the ejaculate to blood ratios of the redox markers. Under higher sperm competition, sneaker males should allocate proportionally more antioxidant resources to the protection of sperm than harem males. In contrast, harem males should favour pre-copulatory functions, which comprise the protection of blood. We found significantly higher sperm velocity and sperm survival in sneakers. There was no correlation between spermmobility and spermenzymatic antioxidant activity or ejaculate levels of lipid peroxidation (oxidative damage). Ejaculate levels of lipid peroxidation and sperm survival showed a significantly positive correlation, which could be attributed to the role of reactive oxygen species for sperm capacitation. Harem and sneaker males showed similar levels of redox balance markers in ejaculate and blood. However, harem males showed a higher ratio of oxidized over reduced glutathione in blood, which may indicate higher cellular stress due to higher metabolism. Overall, our findings suggest that sneakers of C. perspicillata compensate for a higher level of sperm competition by higher sperm mobility. Significance statement In social systems with alternative reproductive tactics, sneakers face higher level of sperm competition than harem males and hence are predicted to allocate more resources to ejaculates. Antioxidants can protect sperm against oxidative stress, and thus, their allocation to the ejaculate may depend on mating tactic. In this study on the frugivorous bat Carollia perspicillata, we found sperm swimming significantly faster and longer in sneaker males compared to harem males. However, traits other than the investigated antioxidant may favour higher sperm mobility. Measured redox pattern in blood of harem males may indicate higher cellular stress due to higher metabolism. Our results provide support to the current sperm competition models at the intraspecific level, which is still debated for internal fertilizers. This study contributes to better understanding the trade-offs and adaptations resulting from alternative reproductive tactics in mammals