Miracle-dz/UniFAR-FTUs huggingface dataset:
Stimulated PI3K-AKT Signaling Mediated through Ligand or Radiation-Induced EGFR Depends Indirectly, but not Directly, on Constitutive K-Ras Activity

Previous results showed an inducible radiation sensitivity selectively observable for K-RAS–mutated cell lines as a function of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor blockade of phosphatidylinositol 3-kinase (PI3K)-AKT signaling. Therefore, the role of K-Ras activity for a direct (i.e., through activation of PI3K by K-Ras) or an indirect stimulation of PI3K-AKT signaling (through K-Ras activity–dependent EGFR ligand production) was investigated by means of small interfering RNA and inhibitor approaches as well as ELISA measurements of EGFR ligand production. K-RASmt tumor cells presented a constitutively activated extracellular signal–regulated kinase-1/2 signaling, resulting in enhanced production and secretion of the EGFR ligand amphiregulin (AREG). Medium supernatants conditioned by K-RASmt tumor cells equally efficiently stimulated EGFR signaling into the PI3K-AKT and mitogen-activated protein kinase pathways. Knocking down K-Ras expression by specific small interfering RNA markedly affected autocrine production of AREG, but not PI3K-AKT signaling, after treatment of K-RAS–mutated or wild-type cells with EGFR ligands or exposure to ionizing radiation. These results indicate that PI3K-mediated activation of AKT in K-RASmt human tumor cells as a function of EGFR ligand or radiation stimulus is independent of a direct function of K-Ras enzyme activity but depends on a K-Ras–mediated enhanced production of EGFR ligands (i.e., most likely AREG) through up-regulated extracellular signal–regulated kinase-1/2 signaling. The data provide new differential insight into the importance of K-RAS mutation in the context of PI3K-AKT–mediated radioresistance of EGFR-overexpressing or EGFR-mutated tumors. (Mol Cancer Res 2007;5(8):863–72)
Optimal Selective Maintenance Strategy for Multi-State Systems Under Imperfect Maintenance

Many systems are required to perform a series of missions with finite breaks between any two consecutive missions. In such a case, one of the most widely used maintenance policies is a selective maintenance in which a subset of feasible maintenance actions is chosen to be performed with the aim at achieving the subsequent mission success under limited maintenance resources. Traditional selective maintenance optimization reported in the literature only focuses on binary state systems. Most systems in industrial applications, however, have more than two states in the deterioration process. In this work, a selective maintenance policy for multi-state systems (MSS) consisting of binary state elements is investigated. Taking the imperfect maintenance quality into consideration, the Kijima model is reviewed, and a cost-maintenance quality relationship which considers the age reduction factor as a function in terms of maintenance cost is established. Moreover, with the assistance of the universal generating function (UGF) method, the probability of the repaired MSS successfully completing the subsequent mission is formulated. In place of enumerative methods, a genetic algorithm (GA) is employed to solve the complicated optimization problem where both multi-state systems, and imperfect maintenance models are taken into account. The effectiveness of the proposed method is demonstrated via a case study of a power station coal transportation system. Finally, a comparative analysis between the strategies with and without considering imperfect maintenance is conducted, and it is concluded that incorporating imperfect maintenance quality into selective maintenance achieves better outcomes.
Demyelinating plaques in relapsing-remitting and secondary-progressive multiple sclerosis: assessment with diffusion MR imaging.

BACKGROUND AND PURPOSE Conventional MR imaging does not provide specific information that can be reliably associated with the pathologic substrate and clinical status of patients with multiple sclerosis (MS). Our goals were 1) to determine whether the orientationally averaged water diffusion coefficient () can be used to distinguish between plaques of different severity in these patients and 2) to assess possible correlations between values and disease duration, Expanded Disability Status Scale (EDSS) score, and signal intensity on T1-weighted MR images. METHODS Twenty patients (10 with relapsing-remitting MS and 10 with secondary-progressive MS) and 11 healthy volunteers underwent a combined conventional and diffusion-weighted MR study of the brain. , a parameter that is proportional to the trace of the diffusion tensor, was computed by averaging the apparent diffusion coefficients measured in the x, y, and z directions. measurements were obtained for selected areas of white matter plaques. Differences in among the three groups were tested using analysis of variance. RESULTS was significantly higher (1.445 +/- 0.129 x 10(-3) mm2/s) in secondary-progressive lesions than in relapsing-remitting lesions (0.951 +/- 0.08), and both values were higher than in normal white matter (0.732 +/- 0.02). There was a significant negative correlation between and the degree of hypointensity on T1-weighted images, and a positive correlation between and both EDSS score and disease duration. CONCLUSION Our findings suggest that is useful for distinguishing MS lesions of different severities, which are associated with different degrees of clinical disability.
Interactions between Neighborhood Social Environment and Walkability to Explain Belgian Older Adults’ Physical Activity and Sedentary Time

This study examined associations between neighborhood social factors and physical activity (PA) and sedentary behavior (SB) in older adults. Furthermore, possible moderating effects of neighborhood walkability were explored. Data from 431 community-dwelling Belgian older adults (≥65 years) were analyzed. Neighborhood social factors included measures of neighboring, social trust and cohesion and social diversity. Neighborhood walkability was measured objectively. Outcome measures were self-reported weekly minutes of domain-specific walking and TV viewing, and accelerometer-assessed weekly minutes of moderate-to-vigorous physical activity (MVPA) and overall SB. A higher frequency of talking to neighbors was associated with higher levels of self-reported walking for transport and for recreation. Moderation analyses showed that only in highly-walkable neighborhoods, higher social diversity of the neighborhood environment was associated with more transport walking; and talking to neighbors and social interactions among neighbors were negatively associated with overall SB and television viewing, respectively. Findings suggest that a combination of a favorable neighborhood social and physical environment are important to promote older adults’ PA and limit SB.
Lamina-specific cell adhesion on living slices of hippocampus.

Laminar distribution of fiber systems is a characteristic feature of hippocampal organization. Ingrowing afferents, e.g. the fibers from the entorhinal cortex, terminate in specific layers, which implies the existence of laminar recognition cues. To identify cues that are involved in the laminar segregation of fiber systems in the hippocampus, we used an in vitro assay to study the adhesion of dissociated entorhinal cells on living hippocampal slices. Here we demonstrate that dissociated entorhinal cells adhere to living hippocampal slices with a lamina-specific distribution that reflects the innervation pattern of the entorhino-hippocampal projection. In contrast, laminae which are not invaded by entorhinal fibers are a poor substrate for cell adhesion. Lamina-specific cell adhesion does not require the neural cell adhesion molecule or the extracellular matrix glycoprotein reelin, as revealed in studies with mutants. However, the pattern of adhesive cues in the reeler mouse hippocampus mimics characteristic alterations of the entorhinal projection in this mutant, suggesting a role of layer-specific adhesive cues in the pathfinding of entorhinal fibers. Lamina-specific cell adhesion is independent of divalent cations, is abolished after cryofixation or paraformaldehyde fixation and is recognized across species. By using a novel membrane adhesion assay, we show that lamina-specific cell adhesion can be mimicked by membrane-coated fluorescent microspheres. Recognition of the adhesive properties of different hippocampal laminae by growing axons, as either a growth permissive or a non-permissive substrate, may provide a developmental mechanism underlying the segregation of lamina-specific fiber projections.
Children's Experiences of Maternal Incarceration-Specific Risks: Predictions to Psychological Maladaptation

Children of incarcerated mothers are at increased risk for social and emotional difficulties, yet few studies have investigated potential mechanisms of risk within this population. This research simultaneously examined the association of children's experience of incarceration-specific risk factors (e.g., witness mother's arrest) and environmental risks (e.g., low educational attainment) to children's psychological maladaptation using a multi-informant design and a latent variable analytic approach. Participants were 117 currently incarcerated mothers (64.1% African American), their 151 children (53.6% boys, M age = 9.8 years, range = 6–12 years, 61.7% African American), and the 118 caregivers (74.8% female, 61.9% grandparents, 62.2% African American) of the children. Mothers, children, and caregivers each provided accounts of children's experiences related to maternal incarceration and children's internalizing and externalizing behavior problems. Mothers and caregivers each supplied information about 10 environmental risk factors. Findings from structural equation modeling indicate that children's incarceration-specific risk experiences predict internalizing and externalizing behavior problems whereas the influence of environmental risks was negligible. Follow-up analyses examining the contribution of specific risks indicate that significant predictors differ by reporter and separate into effects of family incarceration history and direct experiences of maternal incarceration. Incarceration-specific experiences place children at higher risk for maladjustment than exposure to general environmental risk factors. These findings indicate the need to critically examine children's exposure to experiences related to maternal incarceration and family incarceration history to help to clarify the multifaceted stressor of maternal incarceration.
An inter-biome comparison of stream network nitrate dynamics

A simulation model of stream network NO3 dynamics was developed to scale up measurements of stream-reach NO3 uptake in seven catchments. The model explained NO3 dynamics well in two of seven catchments, revealing inter-biome differences in drivers of in-stream NO3 dynamics. Where the model performed poorly, additional drivers included: spatial distribution of NO3 sources; hydrologic delivery pathways of NO3; surface water-groundwater exchange; downstream changes in geomorphology/flow; and variation in uptake. Where the model performed well, uptake was a stronger driver and the network removed a higher proportion of NO3 inputs in Kansas than in North Carolina. In both catchments, small streams removed a substantial proportion of total inputs and were efficient NO3 removers, whereas large streams removed more NO3 mass individually. This research highlights the importance of understanding the influence of hydrology, geomorphology and biology on in-stream NO3 dynamics in order to explain, predict and understand NO3 uptake across biomes.
An adaptive distributed power scheduling algorithm for renewable Microgrid cooperation

Microgrids (MGs) bring considerable advantages in improving reliability, reducing cost, and integrating renewable energy to the future electricity system. However, proper coordination among MGs with renewable resources is necessary for improving the penetration of renewables. In this paper, we propose an adaptive distributed energy scheduling scheme, known as DOPS, for MG cooperation in order to reduce the time-averaged operation cost and improve the utilization of renewable energy (RE) resources. In order to fully utilize the generated RE, a time-averaged RE utilization constraint is proposed and virtual queue technology is utilized to deal with the constraint. Because it is impossible to get the precise information of the future RE generation and load, we make use of Lyapunov optimisation to design the online algorithm for DOPS. Besides, we prove that DOPS can achieve a near-to-optimal performance in terms of the system cost. Furthermore, a trade-off between operation cost and battery size is derived. In the end, our simulation results show that DOPS can help reduce the operation cost and improve the utilization of RE dramatically.
ERCC1-XPF Endonuclease Facilitates DNA Double-Strand Break Repair

ABSTRACT ERCC1-XPF endonuclease is required for nucleotide excision repair (NER) of helix-distorting DNA lesions. However, mutations in ERCC1 or XPF in humans or mice cause a more severe phenotype than absence of NER, prompting a search for novel repair activities of the nuclease. In Saccharomyces cerevisiae, orthologs of ERCC1-XPF (Rad10-Rad1) participate in the repair of double-strand breaks (DSBs). Rad10-Rad1 contributes to two error-prone DSB repair pathways: microhomology-mediated end joining (a Ku86-independent mechanism) and single-strand annealing. To determine if ERCC1-XPF participates in DSB repair in mammals, mutant cells and mice were screened for sensitivity to gamma irradiation. ERCC1-XPF-deficient fibroblasts were hypersensitive to gamma irradiation, and γH2AX foci, a marker of DSBs, persisted in irradiated mutant cells, consistent with a defect in DSB repair. Mutant mice were also hypersensitive to irradiation, establishing an essential role for ERCC1-XPF in protecting against DSBs in vivo. Mice defective in both ERCC1-XPF and Ku86 were not viable. However, Ercc1−/−Ku86−/− fibroblasts were hypersensitive to gamma irradiation compared to single mutants and accumulated significantly greater chromosomal aberrations. Finally, in vitro repair of DSBs with 3′ overhangs led to large deletions in the absence of ERCC1-XPF. These data support the conclusion that, as in yeast, ERCC1-XPF facilitates DSB repair via an end-joining mechanism that is Ku86 independent.
Pharmacokinetics of pars plana intravitreal injections versus microcannula suprachoroidal injections of bevacizumab in a porcine model.

PURPOSE To compare the pharmacokinetics and tissue response between intravitreal and microcannulation injections into the suprachoroidal space using bevacizumab. METHODS Sixty-two pigs were studied. Either a pars plana intravitreal bevacizumab or a viscoelastic-enhanced microcannula suprachoroidal injection was performed with either 1.25 mg (group 1) or 3 mg (group 2). In group 1, six animals were euthanatized at 0.5, 7, 30, 60, 90, and 120 days after injection (n = 36). In group 2, six animals were euthanatized at 0.5, 7, 14, and 32 days (n = 24). Eyes were enucleated, dissected, and snap-frozen, or they were fixed for histology. Analysis of drug tissue levels was performed at two separate laboratories using masked specimens. RESULTS Both laboratories were confirmatory. Intravitreal bevacizumab pharmacokinetics demonstrated a gradual decline in tissue levels over 30 to 60 days in both groups 1 and 2. In addition, suprachoroidal bevacizumab tissue levels declined rapidly and were not measurable at or beyond 7 days. Vitreitis and granulomatous vasculitis were noted in 7 of 30 intravitreal injection eyes. Immunohistology suggested a distinctive drug distribution. CONCLUSIONS Direct intravitreal injection of bevacizumab has a more sustained pharmacologic profile than does a similar dose delivered to the suprachoroidal space. Intravitreal injections distributed more to the inner retina, whereas suprachoroidal delivery occurred primarily at the choroid, retinal pigment epithelium, and photoreceptor outer segments. Sustained release formulation of larger biological molecules should be considered to optimize suprachoroidal delivery. Inflammation from injections is granulomatous, seen only with intravitreal injections, and may result from either an altered immune response or a dose-related effect.
Subviral Dense Bodies of Human Cytomegalovirus Stimulate Maturation and Activation of Monocyte-Derived Immature Dendritic Cells

ABSTRACT Dendritic cells play a central role in the immune control of human cytomegalovirus (HCMV) infection. This work aimed at investigating the impact of noninfectious, subviral dense bodies of HCMV on the maturation and activation of dendritic cells (DC). Treatment of immature DC with dense bodies led to the maturation of these cells and significantly increased their capacity for cytokine release and antigen presentation. Dense body-activated DC may thereby contribute to the development of antiviral immunity.
Acute Myeloid Leukemia in the Setting of Low Dose Weekly Methotrexate Therapy for Rheumatoid Arthritis

Methotrexate is in widespread use as second-line therapy for rheumatoid arthritis. Treatment with methotrexate in this and other settings has not been associated with the development of therapy-related leukemias. Four patients with rheumatoid arthritis are reported who developed acute myeloid leukemia (AML) while receiving low dose weekly methotrexate therapy in the absence of previous or concomitant treatment with known leukemogenic agents. AML in these four patients was of different morphologic subtypes and was associated with heterogeneous cytogenetic abnormalities, cell surface marker expression and multidrug resistance protein expression. None of the recognized features of therapy-related leukemia were present in these four nor in five previously-reported patients. It is likely that the occurrence of AML in patients with rheumatoid arthritis in the setting of methotrexate therapy represents the coincidence of these two diseases, and does not reflect a causal relationship.
Yield Components, Yield and Residual Fertility Status of the Soil after Rice as Influenced by Integrated Nitrogen Management

Rice is one of the most important food grains produced and consumed all over the world. Global rice demand is expected to rise from 439 million tonnes in 2010 to 496 million tonnes in 2020 and further increase to 553 million tonnes in 2035 (FAO, 2013). This shows an overall increase of 26 per cent in the next 25 years, thus global rice yields must raise much faster. Among the rice growing countries, India has the largest area (44 million hectares) and it is the second largest producer (131 million tonnes) of rice next to China (197 million tonnes). The rice productivity in India is 2.98 t ha -1 , while the world average is 4.25 t ha -1 (IRRI, 2011). To meet the food requirement of the growing population, the rice production has to be enhanced with good management practices. Nitrogen (N) application is essential to realize the yield potential of high yielding varieties of rice.
Colonization of the Human Gut by E. coli and Colorectal Cancer Risk

Purpose: The intestinal microbiota is potentially involved in the development of colorectal carcinoma via various mechanisms. Escherichia coli are commensal bacteria of the human gut microbiota, but some pathogenic strains have acquired the ability to induce chronic inflammation and/or produce toxins, such as cyclomodulin, which could participate in the carcinogenesis process. Here, we analyzed the E. coli population associated with mucosa of patients with colon cancer in relation to clinicopathologic characteristics. We assessed carcinogenic properties of a colon cancer–associated E. coli strain in multiple intestinal neoplasia (Min) mice. Experimental design: Mucosa-associated or internalized E. coli were quantified and characterized from tumors and mucosa of patients with colon cancer and the healthy mucosa of diverticulosis controls. Min mice were inoculated with a colon cancer–associated E. coli strain (11G5). The number of colonic polyps was evaluated at 7 weeks after infection. Results: An increased level of mucosa-associated and internalized E. coli was observed in the tumors compared with normal tissue. A relationship between poor prognostic factors for colon cancer (tumor–node–metastasis stage) and colonization of mucosa by E. coli was observed. Pathogenic cyclomodulin-positive E. coli strains were more prevalent on mucosa of patients with stages III/IV than those with stage I colon cancer. Proliferative index and E. coli colonization level of the mucosa distant from the tumor significantly correlated. Min mice infected with the E. coli strain 11G5 displayed a marked increase in the number of visible colonic polyps compared with controls. Conclusion: These findings support that pathogenic E. coli could be a cofactor in pathogenesis of colorectal cancer. Clin Cancer Res; 20(4); 859–67. ©2013 AACR.
Prosodic transfer in L2 speech: evidence from phrasal prominence and rhythm

The current study examines focus and Nuclear Pitch Accent in the second language (L2) speech of Spanish speakers of English. We begin with a discussion of the distinct algorithms said to account for Nuclear Stress (NS) at work in Spanish and English. We then match the theoretical claims with experimental data on the placement of Nuclear Accent for various focus constructions from native speakers of English, followed by a contrasting set of data from L2 speakers. However, the L2 speakers are not a homogenous group, and indeed the production behavior across proficiency groups gives rise to the hypothesis that the acquisition of nuclear pitch accent is hierarchical in nature: learners acquire anaphoric deaccenting before nuclear stress. We conclude with a discussion of further data that supports the notion that phrasal prosodic patterns might be related to some fundamental rhythmic difference between the two languages. 1. Cross-linguistic differences in NS This paper intends to contribute to our understanding of certain aspects of prosodic transfer in SLA, an area that has only recently begun to be a focus of serious research (cf. Goad W Tremblay 2007). More specifically, we look at native Spanish speakers as they progress towards native-like production of Nuclear Stress (NS) in English (their L2), and how this progression toward prosodic representation might be informed by underlying rhythmic/metrical patterns at work in each language. Based on evidence from second language (L2) speech, we argue that the computation of nuclear pitch accent in English arises from the complex interplay of several distinct algorithms. At the heart of this computation is the Nuclear Stress Rule. Due to the pervasive phenomenon of “transfer” of the grammatical properties of the first language (L1) into L2 speech, the latter can constitute a window into the mental representation of the two systems in contact. 1.1. Nuclear Stress: Algorithms at work In Spanish (or more generally in the Romance languages), main phrasal prominence (or NS) aligns with the last word of the Intonational Phrase (IntP) in wide-focus contexts