The Rb-E2F axis is an important pathway involved in cell-cycle control that is deregulated in a number of cancers. E2f transcription factors have distinct roles in the control of cell proliferation, ...cell survival and differentiation in a variety of tissues. We have previously shown that E2fs are important downstream targets of a CSF-1 signaling cascade involved in myeloid development. In cancer, tumor-associated macrophages (TAMs) are recruited to the tumor stroma in response to cytokines secreted by tumor cells, and are believed to facilitate tumor cell invasion and metastasis. Using the MMTV-Polyoma Middle T antigen (PyMT) mouse model of human ductal carcinoma, we show that the specific ablation of E2f3 in TAMs, but not in tumor epithelial cells, attenuates lung metastasis without affecting primary tumor growth. Histological analysis and gene expression profiling suggest that E2f3 does not impact the proliferation or survival of TAMs, but rather controls a novel gene expression signature associated with cytoskeleton rearrangements, cell migration and adhesion. This E2f3 TAM gene expression signature was sufficient to predict cancer recurrence and overall survival of estrogen receptor (ER)-positive breast cancer patients. Interestingly, we find that E2f3b but not E2f3a levels are elevated in TAMs from PyMT mammary glands relative to controls, suggesting a differential role for these isoforms in metastasis. In summary, these findings identify E2f3 as a key transcription factor in TAMs, which influences the tumor microenvironment and tumor cell metastasis.
The impressed current cathodic protection (ICCP) scheme is a more reliable and efficient method of corrosion prevention mechanism than the sacrificial method. Currently, the grid connected ...transformer rectifier units supported with a battery banks are used for the ICCP-based corrosion protection system in the desalination plant. This conventional method is entirely grid-dependent, more expensive, and suffers during prolonged grid failure. The present trend of industrialization is the application of multi-renewable energy sources based on a nanogrid to power the station’s auxiliary power supply. This paper introduces a concept of distributed energy resources (DERs) operated integrated nanogrid (ING) system to provide a stable power supply solution to the ICCP scheme. A 100-million-litter per day capacity-based seawater desalination plant (SWDP) in India has been chosen as the test station. The conceptual hardware design and operational logic details for smooth integration of the integrated nanogrid module into the ICCP scheme of the Desalination plant is proposed. This research aims to investigate the behaviour of DERs during on-grid, off-grid and switching over from one mode of operation to another and vice-versa by using the accelerated Gauss–Seidel method in ETAP software (version 16.0.0). The simulation results confirm that the ING suffers from a high-frequency change rate during islanded operation, and in some cases, a complete blackout occurs. A PLC-based Smart Versatile ING Controller has been suggested to overcome the blackout issue. Finally, it has been proven that the stability of an industrial power system can be improved further by introducing the ING module into it.
The aim of the current study was to test the hypothesis that maternal lipid metabolism was modulated during normal pregnancy and that these modulations are altered in gestational diabetes mellitus ...(GDM). We tested this hypothesis using an established mouse model of diet-induced obesity with pregnancy-associated loss of glucose tolerance and a novel lipid analysis tool, Lipid Traffic Analysis, that uses the temporal distribution of lipids to identify differences in the control of lipid metabolism through a time course. Our results suggest that the start of pregnancy is associated with several changes in lipid metabolism, including fewer variables associated with de novo lipogenesis and fewer PUFA-containing lipids in the circulation. Several of the changes in lipid metabolism in healthy pregnancies were less apparent or occurred later in dams who developed GDM. Some changes in maternal lipid metabolism in the obese-GDM group were so late as to only occur as the control dams' systems began to switch back towards the non-pregnant state. These results demonstrate that lipid metabolism is modulated in healthy pregnancy and the timing of these changes is altered in GDM pregnancies. These findings raise important questions about how lipid metabolism contributes to changes in metabolism during healthy pregnancies. Furthermore, as alterations in the lipidome are present before the loss of glucose tolerance, they could contribute to the development of GDM mechanistically.
Collaborations between ecosystem ecologists and engineers have led to impressive progress in developing complex models of biogeochemical fluxes in response to global climate change. Ecology and ...engineering iteratively inform and transform each other in these efforts. Nested data streams from local sources, adjacent networks, and remote sensing sources together magnify the capacity of ecosystem ecologists to observe systems in near real-time and address questions at temporal and spatial scales that were previously unobtainable. We describe our research experiences working in a Costa Rican rainforest ecosystem with the challenges presented by constant high humidity, 4300 mm of annual rainfall, flooding, small invertebrates entering the tiniest openings, stinging insects, and venomous snakes. Over the past two decades, we faced multiple challenges and learned from our mistakes to develop a broad program of ecosystem research at multiple levels of integration. This program involved integrated networks of diverse sensors on a series of canopy towers linked to multiple belowground soil sensor arrays that could transport sensor data streams from the forest directly to an off-site location via a fiber optic cable. In our commentary, we highlight three components of our work: (1) the eddy flux measurements using canopy towers; (2) the soil sensor arrays for measuring the spatial and temporal patterns of CO2 and O2 fluxes at the soil–atmosphere interface; and (3) focused investigations of the ecosystem impact of leaf-cutter ants as “ecosystem engineers” on carbon fluxes.
In this paper, we focus on the problem of speckle removal by means of anisotropic diffusion and, specifically, on the importance of the correct estimation of the statistics involved. First, we derive ...an anisotropic diffusion filter that does not depend on a linear approximation of the speckle model assumed, which is the case of a previously reported filter, namely, SRAD. Then, we focus on the problem of estimation of the coefficient of variation of both signal and noise and of noise itself. Our experiments indicate that neighborhoods used for parameter estimation do not need to coincide with those used in the diffusion equations. Then, we show that, as long as the estimates are good enough, the filter proposed here and the SRAD perform fairly closely, a fact that emphasizes the importance of the correct estimation of the coefficients of variation
Changes in the maternal nutritional environment during fetal development can influence offspring's metabolic risk in later life. Animal models have demonstrated that offspring of diet-induced obese ...dams develop metabolic complications, including nonalcoholic fatty liver disease. In this study we investigated the mechanisms in young offspring that lead to the development of nonalcoholic fatty liver disease (NAFLD). Female offspring of C57BL/6J dams fed either a control or obesogenic diet were studied at 8 wk of age. We investigated the roles of oxidative stress and lipid metabolism in contributing to fatty liver in offspring. There were no differences in body weight or adiposity at 8 wk of age; however, offspring of obese dams were hyperinsulinemic. Oxidative damage markers were significantly increased in their livers, with reduced levels of the antioxidant enzyme glutathione peroxidase-1. Mitochondrial complex I and II activities were elevated, while levels of mitochondrial cytochrome c were significantly reduced and glutamate dehydrogenase was significantly increased, suggesting mitochondrial dysfunction. Offspring of obese dams also had significantly greater hepatic lipid content, associated with increased levels of PPARγ and reduced triglyceride lipase. Liver glycogen and protein content were concomitantly reduced in offspring of obese dams. In conclusion, offspring of diet-induced obese dams have disrupted liver metabolism and develop NAFLD prior to any differences in body weight or body composition. Oxidative stress may play a mechanistic role in the progression of fatty liver in these offspring.
Abstract
STUDY QUESTION
In lesbian couples, is shared motherhood IVF (SMI) associated with an increase in perinatal complications compared with artificial insemination with donor sperm (AID)?
SUMMARY ...ANSWER
Singleton pregnancies in SMI and AID had very similar outcomes, except for a non-significant increase in the rate of preeclampsia/hypertension (PE/HT) in SMI (recipient’s age-adjusted odds ratio (OR) = 1.9, 95% CI = 0.7–5.2; P = 0.19), but twin SMI pregnancies had a much higher frequency of PE/HT than AID twins (recipient’s age-adjusted OR = 21.7, 95% CI = 2.8–289.4; P = 0.01).
WHAT IS KNOWN ALREADY
Oocyte donation (OD) pregnancies are associated with an increase in perinatal complications, in particular, preterm delivery and low birth weight, and PE/HT. However, it is unclear to what extent these complications are due to OD process or to the conditions why OD was performed, such as advanced age and underlying health conditions. Unfortunately, the literature concerning perinatal outcomes in SMI is scarce.
STUDY DESIGN, SIZE, DURATION
Retrospective study involving 660 SMI cycles (299 pregnancies) and 4349 AID cycles (949 pregnancies) assisted over a 10-year period.
PARTICIPANTS/MATERIALS, SETTING, METHODS
All cycles fulfilling the inclusion criteria performed in lesbian couples seeking fertility treatment in 17 Spanish clinics of the same group. Pregnancy rates of SMI and AID cycles were compared. Perinatal outcomes were compared: gestational length, newborn weight, preterm and low birth rates, PE/HT rates, cesarean section rates, perinatal mortality, and newborn malformations.
MAIN RESULTS AND THE ROLE OF CHANCE
Pregnancy rates were higher in SMI than in AID (45.3% versus 21.8%, P < 0.001). There was a non-significant trend to higher multiple rate in AID (4.7% versus 8.5%, P = 0.08). In single pregnancies, there were no differences between SMI and AID in gestational age (278 days (268–285) versus 279 (272–284), P = 0.24), preterm rate (8.3% versus 7.3%, P = 0.80), preterm <28 weeks (0.6% versus 0.4%, P = 1.00), newborn weight (3195 g (2915–3620) versus 3270 g (2980–3600), P = 0.296), low birth rate (6.4% versus 6.4%, P = 1.00), extremely low birth weight (0.6% versus 0.5%, P = 1.00), and the distribution of newborns by weight groups. Cesarean section rate, newborn malformation rate, and perinatal mortality were also similar in SMI and AID. Additionally, there was non-significant trend in hypertensive disorders to an increase in PE/HT among SMI (recipient’s age-adjusted OR = 1.9, 95% CI = 0.7–5.2). Overall, perinatal data are consistent with what is reported in the general population. In twin pregnancies, the aforementioned perinatal parameters were also very similar in SMI and AID. However, SMI twin pregnancies had a very high risk of PE/HT when compared with AID (recipient’s age-adjusted OR = 21.7, 95% CI = 2.8–289.4, P = 0.01).
LIMITATIONS, REASONS FOR CAUTION
Our data regarding the pregnancy course were obtained from information registered in the delivery report as well as from what was reported by the patients themselves, so a certain degree of inaccuracy cannot be ruled out. Additionally, in some parameters, there was up to 10% of data missing. However, since the methodology of reporting was the same in SMI and AID groups, one should not expect a differential reporting bias. It cannot be ruled out that the risk of PE/HT in simple gestations would be significant in a larger study. Additionally, in the SMI group allocation to the transfer of 2 embryos was not randomized so some bias is possible.
WIDER IMPLICATIONS OF THE FINDINGS
SMI, if single embryo transfer is performed, seems to be is a safe procedure. Double embryo transfer should not be performed in SMI. Our data suggest that the majority of complications in OD could be related more with recipient status than with OD itself, since with SMI (performed in women without fertility problems) the perinatal complications were much lower than usually described in OD.
STUDY FUNDING/COMPETING INTEREST(S)
No external funding was received. The authors declare that they have no conflict of interest.
TRIAL REGISTRATION NUMBER
N/A.
Summary
What is known and objectives
The safety of continued ustekinumab (UST) therapy during pregnancy remains unclear in patients with Crohn's disease (CD). There are no meta‐analysis reports of ...exposure to UST during pregnancy. The objective was to describe a case of a pregnant patient with CD who was successfully treated with UST maintenance therapy throughout the pregnancy and delivered a baby boy without any congenital malformations, neurological abnormalities or birth defects.
Case summary
A 37‐year‐old patient with CD treated with UST became pregnant. She had been receiving UST for 8 months at the time. After discussion with the patient and the obstetric team, the UST therapy was continued. The result of treatment was an uneventful pregnancy with delivery, at term, of a healthy boy and the maintenance of clinical, biological and endoscopic remission of CD during and after pregnancy.
What is new and conclusion
To our knowledge, this is the first reported use of continued UST therapy for CD throughout a pregnancy. The result of treatment was an uncomplicated pregnancy with the mother giving birth to a healthy boy at term and the maintenance of clinical biological and endoscopic remission of CD during and after pregnancy.
A new grouping genetic algorithm for clustering problems Agustı´n-Blas, L.E.; Salcedo-Sanz, S.; Jiménez-Fernández, S. ...
Expert systems with applications,
August 2012, 2012-08-00, 20120801, Volume:
39, Issue:
10
Journal Article
Peer reviewed
► A hybrid grouping-encoding algorithm for clustering problems is presented. ► Details on the encoding, operators and parallelization are given. ► Results in synthetic and real clustering problems ...are provided.
In this paper we present a novel grouping genetic algorithm for clustering problems. Though there have been different approaches that have analyzed the performance of several genetic and evolutionary algorithms in clustering, the grouping-based approach has not been, to our knowledge, tested in this problem yet. In this paper we fully describe the grouping genetic algorithm for clustering, starting with the proposed encoding, different modifications of crossover and mutation operators, and also the description of a local search and an island model included in the algorithm, to improve the algorithm’s performance in the problem. We test the proposed grouping genetic algorithm in several experiments in synthetic and real data from public repositories, and compare its results with that of classical clustering approaches, such as K-means and DBSCAN algorithms, obtaining excellent results that confirm the goodness of the proposed grouping-based methodology.
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