Miracle-dz/UniFAR-FTUs huggingface dataset:
Epoxyeicosatrienoic Acid Pathway in Human Health and Diseases

Abstract: In response to endothelial cell activation, arachidonic acid can be converted by cytochrome P450 (CYP) epoxygenases to epoxyeicosatrienoic acids (EETs), which have potent vasodilator and anti-inflammatory properties. EETs are rapidly degraded in vivo to the less active dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). Since the beginning of the 2000s, the role of EET pathway in human health and its alteration in diseases has been shown by measuring EETs/DHET levels in blood, by evaluating the relationship between CYP/sEH gene polymorphisms, which modify enzyme activity and thus EETs/DHET level, and by assessing the inhibitory effect of the local administration of CYP epoxygenase inhibitor on endothelium-dependent dilatation. By combining these functional and biological approaches, we demonstrated that EETs are the endothelial factors released by CYP epoxygenases involved in the flow-mediated dilatation of conduit arteries in healthy subjects, together with the impairment of EET availability in essential hypertensive patients at this level. The modulation of EET pathway now emerges as a new promising pharmacological target that may improve the clinical management of patients at high cardiovascular risk. In this respect, the restoration of EET availability using a new class of agents, the inhibitors of sEH, gave promising results in various animal models of cardiovascular diseases, reducing blood pressure and target organ damage, and a first product has entered clinical evaluation.
The Value of Multiple Proxies

Direct measurements of climate data such as temperatures are rare before the 20th century. Climate reconstructions for earlier centuries and millenia rely on a range of different climate indicators or proxies. In his Perspective, [Mann][1] explains how these proxies can be used in multiproxy climate reconstructions to obtaina reliable record of climatic variations over the last millenium. [1]: http://www.sciencemag. org/cgi/content/full/297/5586/1481
Growth up to 2 Years in Relationship to Maternal Smoking During Pregnancy

Smoking during pregnancy causes intrauterine growth retardation, but the subsequent growth of these children is not well understood. Two hundred four newborns of mothers who smoked during pregnancy and 204 control neonates were studied. Children were re-examined at 1 and 2 years. Newborns of mothers who smoked 1-9 cigarettes/day had similar anthropometric parameters with the controls. Significant retardation in weight, length, and head circumference was present in the newborns whose mothers smoked >10 cigarettes/day. At follow-up, in children of smoking mothers the retardation of weight improved, head circumference remained stable, and length retardation increased even in children whose mothers smoked <10 cigarettes/day.
Cysteine-rich Protein 61 (CCN1) Domain-specific Stimulation of Matrix Metalloproteinase-1 Expression through αVβ3 Integrin in Human Skin Fibroblasts*

Background: Elevated MMP-1 is a prominent feature of human skin aging. Results: The CCN1 VWC domain interacts with αVβ3 integrin and cooperates with adjacent IGFBP and TSP1 domains to stimulate MMP-1 expression. Conclusion: CCN1 structural domains contribute to human skin aging. Significance: Targeting the CCN1/αVβ3 integrin pathway may provide a therapeutic approach to improve the health of aged human skin. Human skin largely comprises collagenous extracellular matrix. The hallmark of skin aging is fragmentation of collagen fibrils. Matrix metalloproteinases (MMPs) are largely responsible for collagen degradation. MMP-1, principally derived from dermal fibroblasts, is the major protease capable of initiating degradation of native fibrillar collagens. Presently, we report that CCN1, a secreted and extracellular matrix-associated protein, is elevated in aged human skin dermal fibroblasts in vivo and stimulates MMP-1 expression through functional interaction with αVβ3 integrin in human dermal fibroblasts. CCN1 contains four conserved structural domains. Our results indicate that the three N-terminal domains (IGFBP, VWC, and TSP1), but not the C-terminal CT domain, are required for CCN1 to stimulate MMP-1 expression. This stimulation is dependent on interaction between the active structural domains and αVβ3 integrin. The interaction of VWC domain with integrin αVβ3 is necessary and requires functional cooperation with adjacent IGFBP and TSP1 domains to stimulate MMP-1 expression. Finally, induction of MMP-1 expression in dermal fibroblasts by CCN1 N-terminal domains resulted in fragmentation of type I collagen fibrils in a three-dimensional collagen lattice model. These data suggest that domain-specific interactions of CCN1 with αVβ3 integrin contribute to human skin aging by stimulating MMP-1-mediated collagen fibril fragmentation.
Novel Roles of c-Met in the Survival of Renal Cancer Cells through the Regulation of HO-1 and PD-L1 Expression*

Background: Tyrosine kinase receptor c-Met plays critical roles in the growth of RCC. Results: c-Met-mediated Ras activation and HO-1 overexpression promote anti-apoptotic signals, and increase PD-L1 expression, which inhibits immune cell-mediated killing of RCC cells. Conclusion: c-Met-induced HO-1 and PD-L1 expression promotes RCC cell survival. Significance: HO-1 and PD-L1 can serve as novel therapeutic targets for c-Met-induced RCC. The receptor tyrosine kinase c-Met is overexpressed in renal cancer cells and can play major role in the growth and survival of tumor. We investigated how the c-Met-mediated signaling through binding to its ligand hepatocyte growth factor (HGF) can modulate the apoptosis and immune escape mechanism(s) of renal cancer cells by the regulations of novel molecules heme oxygenase-1 (HO-1) and programmed death-1 ligand 1 (PD-L1). We found that HGF/c-Met-mediated signaling activated the Ras/Raf pathway and down-regulated cancer cell apoptosis; and it was associated with the overexpression of cytoprotective HO-1 and anti-apoptotic Bcl-2/Bcl-xL. c-Met-induced HO-1 overexpression was regulated at the transcriptional level. Next, we observed that c-Met induction markedly up-regulated the expression of the negative co-stimulatory molecule PD-L1, and this can be prevented following treatment of the cells with pharmacological inhibitors of c-Met. Interestingly, HGF/c-Met-mediated signaling could not induce PD-L1 at the optimum level when either Ras or HO-1 was knocked down. To study the functional significance of c-Met-induced PD-L1 expression, we performed a co-culture assay using mouse splenocytes (expressing PD-L1 receptor PD-1) and murine renal cancer cells (RENCA, expressing high PD-L1). We observed that the splenocyte-mediated apoptosis of cancer cells during co-culture was markedly increased in the presence of either c-Met inhibitor or PD-L1 neutralizing antibody. Finally, we found that both c-Met and PD-L1 are significantly up-regulated and co-localized in human renal cancer tissues. Together, our study suggests a novel mechanism(s) by which c-Met can promote increased survival of renal cancer cells through the regulation of HO-1 and PD-L1.
Stored energy balance for distributed PV-based active generators in an AC microgrid

In this paper, a decentralized strategy based on fuzzy logic is proposed for balancing the state of charge of the energy storage units for distributed PV-based active generators. The proposed method, weights the action of conventional droop control loops for privileging the charge of the energy storage unit with the smallest state of charge or force a faster discharge of the energy storage system with the biggest state of charge. The units are self-controlled by using local variables, hence, the microgrid can operate without relying on communication systems. The proposed strategy is completely expandable and can be applied to a several number of power generators interconnected in a microgrid. Frequency and voltage bus signaling is used in order to coordinate the control operation mode between units. Simulation results in a low-voltage, three-phase, islanded AC microgrid show the feasibility of the proposed method and its applicability even for several active generators.
Multi-Speaker Localization Using Convolutional Neural Network Trained with Noise

The problem of multi-speaker localization is formulated as a multi-class multi-label classification problem, which is solved using a convolutional neural network (CNN) based source localization method. Utilizing the common assumption of disjoint speaker activities, we propose a novel method to train the CNN using synthesized noise signals. The proposed localization method is evaluated for two speakers and compared to a well-known steered response power method.
MULTIDISCIPLINARY MANAGEMENT OF RECTAL CANCER - A RETROSPECTIVE STUDY -

MULTIDISCIPLINARY MANAGEMENT OF RECTAL CANCER - A R ETROSPECTIVE STUDY - (Abstract): Background: The procedure of low or very low anterior resection of the rectum with total mesorectal excision (TME) it is now widely accepted for tumours of the middle and lower third of the r ectum. It has become the gold standard for the treatment of c ancer of the rectum, except where the tumor is clos e to or is involving the anal sphincter complex. Patients and methods: A retrospective study on 120 patients diagnosed with colorectal cancer and operated on between 2000 and 2004 was carried out. There were 120 anterior resection of the rectum, in 34 cases the total meso rectal excision has been performed and in 11 cases a very low anterior resection was made. All 45 cases where tot al mesorectal excision was made, had undertaken preoperative radiotherapy, surgery being performed after 4 to 6 weeks from the last session of radioth erapy. Results : The overall operative morbidity rate was 16.10% i n direct relation with the distal limit of dissecti on. Postoperative complications that we note: anastomot ic leakages, recto-vaginal fistulas, evisceration, peritonitis, occlusion, urinary dysfunctions. Conclusions : For the total mesorectal excision to be effective a n early diagnosis is necessary, and a tumor which is not local invasi ve, the use of preoperative radiotherapy decreasing the local recurrence.
Two element planar dipole array antenna for wireless LAN

In this paper, two element planar dipole array antenna fed by the parallel line has been proposed for 2.4 GHz band wireless LAN mesh network. In the numerical analysis, the electromagnetic simulator ldquoWIPL-Drdquo based on the method of moment is used. This antenna is numerically and experimentally analyzed. The current distributions of antenna elements are controlled by adjusting the lengths of dipole elements and the distance between them. The directivity of more than 6.69 dBi has been obtained from 2.4 GHz to 2.5 GHz.
A survey of query recommendation techniques for data warehouse exploration

Lots of data are gathered in datawarehouses that are navigated andexplored for analytical purposes. Only recently has the problem of recommending a datawarehouse query to a datawarehouse user attracted attention. In this paper, we propose a simple formal framework for expressing datawarehouse queryrecommendations. We propose to see the problem of recommending a datawarehouse query for exploration purposes as a function computing a set of queriesand associated ratings given a query log, a session, a user profile, a datawarehouse instance, and an expectation function. The rating computed indicates theusefulness of each query for a session. With this viewpoint, we review and categorize the few techniques that, to the best of our knowledge, have been proposedand we illustrate them with a case study.
Genomic instability occurs in colorectal carcinomas but not in adenomas

Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary non‐polyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER+). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4–15 microsatellite markers. Seven (6.5%) of carcinomas were RER+, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma‐carcinoma and carcinoma‐metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas. © 1993 Wiley‐Liss, Inc.
Bone mass and breast cancer risk in older women: differences by stage at diagnosis.

BACKGROUND Older women with low bone mineral density (BMD) have a decreased incidence of breast cancer. It is not known whether this association is confined to early-stage, slow-growing tumors. METHODS We prospectively studied 8905 women who were 65 years of age or older during the period from 1986 through 1988 and had no history of breast cancer. At study entry, we used single-photon absorptiometry to measure each woman's BMD at three skeletal sites: the wrist, forearm, and heel. The women were followed for a mean of 6.5 years for the occurrence of breast cancer. All statistical tests were two-sided. RESULTS During 57 516 person-years of follow-up, 315 women developed primary invasive or in situ breast cancer. Multivariate analyses that adjusted for age, obesity, and other covariates revealed that the risk of breast cancer for women in the highest quartile of BMD for all three skeletal sites was 2.7 (95% confidence interval [CI] = 1.4 to 5.3) times greater than that for women in the lowest quartile at all three skeletal sites. The magnitude of increased risk associated with high BMD differed by the stage of disease at diagnosis and was greater for more advanced tumors (relative risk [RR] for TNM [i.e., tumor-lymph node-metastasis] stage II or higher tumors = 5.6; 95% CI = 1.2 to 27.4) than for early-stage disease (RR for in situ/TNM stage I tumors = 2.2; 95% CI = 1.0 to 4.8). CONCLUSIONS Elderly women with high BMD have an increased risk of breast cancer, especially advanced cancer, compared with women with low BMD. These findings suggest an association between osteoporosis and invasive breast cancer, two of the most prevalent conditions affecting an older woman's health.
As racionalidades para projeto organizacional no contexto da gestão de operações

O desenvolvimento da integracao organizacional e um desafio para os sistemas de operacoes contemporâneos. Tal integracao pode ser obtida a partir da formulacao, desenvolvimento e implantacao de um projeto de natureza organizacional. Fundamentando-se em um modelo organizacional que inter-relaciona as dimensoes processos, espacos e estrutura organizacional, desenvolve-se tanto uma racionalidade de projeto, como tambem uma racionalidade de processo associada ao projeto organizacional. O desenvolvimento das racionalidades tem como objetivo construir a base teorica do projeto organizacional, destacando os principios que orientam a sua concepcao e realizacao. Este artigo apresenta uma contribuicao de natureza teorico-conceitual, atraves do desenvolvimento das racionalidades de projeto e processo e de um framework de referencia para o projeto organizacional.
Validation and calibration of food-frequency questionnaire measurements in the Northern Sweden Health and Disease cohort

Abstract Objectives: To evaluate the reproducibility of, and to compare and calibrate, diet measures by the Northern Sweden 84-item food-frequency questionnaire (FFQ) with measures from 24-hour diet recalls (24-HDR). Design: Randomly selected respondents (n=246) from the EPIC (diet-cancer) and MONICA (diet-cardiovascular disease) study cohort in Northern Sweden were invited to answer the FFQ twice over a one-year interval (FFQ1 and FFQ2), and to complete ten 24-hour recalls (reference method) in the months between. Plasma β-carotene concentrations were determined from a subset of 47 participants. Setting: Vasterbotten and Norrbotten, Northern Sweden. Participants: Ninety-six men and 99 women, who completed the study. Results: The reproducibility of the FFQ was high in terms of both mean energy and nutrient intakes and relative ranking of participants by intake levels (median Pearson correlation of 0.68). Moderately higher food intake frequencies were recorded by FFQ1 compared with 24-hour recalls for dairy products, bread/cereals, vegetables, fruits and potato/rice/pasta, whereas meat, fish, sweet snacks and alcoholic beverage intakes were lower. The median Spearman coefficient of correlation between FFQ1 and the average of ten 24-HDR measurements was 0.50. Daily energy and nutrient intakes were similar for FFQ1 and 24-HDR measurements, except for fibre, vitamin C, β-carotene and retinol (FFQ1<24-HDR) and sucrose and cholesterol (FFQ1>4-HDR). Pearson coefficients of correlation between FFQ1 and 24-HDR corrected for attenuation due to residual day-to-day variation in the 24-HDR measurements ranged from 0.36 to 0.79 (median 0.54). Adjustment for energy had only very moderate effects on the correlation estimates. Calibration coefficients estimated by linear regression of the 24-HDR on the FFQ1 measurements varied between 0.30 and 0.59 for all nutrients except alcohol, which had calibration coefficients close to 1.0. These low calibration coefficients indicate that relative risk estimates corresponding to an absolute difference in dietary intake levels measured by the FFQ will generally be biased towards 1.0. Plasma β-carotene levels had a Pearson coefficient of correlation of 0.47 with the 24-HDR measurements, and of 0.23 with FFQ1 measurements. Conclusions: The Northern Sweden FFQ measurements have good reproducibility and an estimated level of validity similar to that of FFQ measurements in other prospective cohort studies. The results from this study will form the basis for the correction of attenuation and regression dilution biases in relative risk estimates, in future studies relating FFQ measurements to disease outcomes.
Inversion in the lactose region of Escherichia coli K-12

A spontaneous mutant of Escherichia coli K-12, strain SY99, with an inversion in the lactose region was isolated and partially characterized. The inversion was detected due to inverse chromosomal conjugational transfer after introduction of an F42 (F'lac) episome. The termini of the inversion are between proAB and lac on one side and lac and proC on the other. The inverse conjugational transfer in SY99 did not appear to be absolute but was always accompanied by a residual "normal" counterclockwise mobilization. This residual transfer was further shown to be caused by the intrinsic instability of this region (at least in the line W3110). The possible involvement of IS3 elements flanking the lactose operon is discussed.
An actin‐like protein is involved in regulation of mitochondrial and flagellar functions as well as in intramacrophage survival of Leishmania donovani

Actin‐related proteins are ubiquitous actin‐like proteins that show high similarity with actin in terms of their amino acid sequence and three‐dimensional structure. However, in lower eukaryotes, such as trypanosomatids, their functions have not yet been explored. Here, we show that a novel actin‐related protein (ORF LmjF.13.0950) is localized mainly in the Leishmania mitochondrion. We further reveal that depletion of the intracellular levels of this protein leads to an appreciable decrease in the mitochondrial membrane potential as well as in the ATP production, which appears to be accompanied with impairment in the flagellum assembly and motility. Additionally, we report that the mutants so generated fail to survive inside the mouse peritoneal macrophages. These abnormalities are, however, reversed by the episomal gene complementation. Our results, for the first time indicate that apart from their classical roles in the cytoplasm and nucleus, actin‐related proteins may also regulate the mitochondrial function, and in case of Leishmania donovani they may also serve as the essential factor for their survival in the host cells.
Anti‐protein S antibodies following a varicella infection: detection, characterization and influence on thrombin generation

Summary. Postinfectious purpura fulminans is a rare disease. Varicella is one of the precipitating conditions and we recently observed such a case. The 4‐year‐old child was found to have a severe transient protein S deficiency. By enzyme‐linked immunosorbent assay and surface plasmon resonance we first demonstrated that anti‐protein S antibodies were present and also transient. Next we characterized the epitopes against which these antibodies were directed and found that they predominantly recognized the N‐terminal part of protein S. Finally we showed by thrombography a transient dramatic hypercoagulable state as a result of thrombin being unregulated by the dynamic protein C inhibitory system: in vitro thrombin generation, in response to a low concentration of tissue factor, was almost insensitive to activated protein C up to 25 nmol L−1 on day 4 while it was normally sensitive on day 42. For the first time, we demonstrated a temporal relationship between protein S deficiency, antibodies to protein S and hypercoagulability, thus supporting the pathogenic role of these antibodies.
Eosinophils: The unsung heroes in cancer?

ABSTRACT Prolonged low-grade inflammation or smoldering inflammation is a hallmark of a cancer. Eosinophils are components of the immune microenvironment that modulates tumor initiation and progression. Although canonically associated with a detrimental role in allergic disorders, these cells can induce a protective immune response against helminthes, viral and bacterial pathogens. Eosinophils are a source of anti-tumorigenic (e.g., TNF-α, granzyme, cationic proteins, and IL-18) and protumorigenic molecules (e.g., pro-angiogenic factors) depending on the milieu. In several neoplasias (e.g., melanoma, gastric, colorectal, oral and prostate cancer) eosinophils play an anti-tumorigenic role, in others (e.g., Hodgkin's lymphoma, cervical carcinoma) have been linked to poor prognosis, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of eosinophils and their mediators could be cancer-dependent. The microlocalization (e.g., peritumoral vs intratumoral) of eosinophils could be another important aspect in the initiation/progression of solid and hematological tumors. Increasing evidence in experimental models indicates that activation/recruitment of eosinophils could represent a new therapeutic strategy for certain tumors (e.g., melanoma). Many unanswered questions should be addressed before we understand whether eosinophils are an ally, adversary or neutral bystanders in different types of human cancers.
Prognostic Value of Molecular Subtypes in Pancreatic Cancer.

To the Editor:Pancreatic ductal adenocarcinoma is one of the most aggressive human cancers with 338,000 new cases and 331,000 deaths in 2012 worldwide.1 Its incidence is rising.2 The 5-year survival is dismal, inferior to 10%. Complete surgical removal of the tumor followed by adjuvant chemotherapy