High-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), is the most common and deadliest type of ovarian cancer. HGSC appears to arise from the ovary, fallopian tube, or ...peritoneum. As most HGSC cases present with widespread peritoneal metastases, it is often not clear where HGSC truly originates. Traditionally, the ovarian surface epithelium (OSE) was long believed to be the origin of HGSC. Since the late 1990s, the fallopian tube epithelium has emerged as a potential primary origin of HGSC. Particularly, serous tubal intraepithelial carcinoma (STIC), a noninvasive tumor lesion formed preferentially in the distal fallopian tube epithelium, was proposed as a precursor for HGSC. It was hypothesized that STIC lesions would progress, over time, to malignant and metastatic HGSC, arising from the fallopian tube or after implanting on the ovary or peritoneum. Many clinical studies and several mouse models support the fallopian tube STIC origin of HGSC. Current evidence indicates that STIC may serve as a precursor for HGSC in high-risk women carrying germline
or
mutations. Yet not all STIC lesions appear to progress to clinical HGSCs, nor would all HGSCs arise from STIC lesions, even in high-risk women. Moreover, the clinical importance of STIC remains less clear in women in the general population, in which 85⁻90% of all HGSCs arise. Recently, increasing attention has been brought to the possibility that many potential precursor or premalignant lesions, though composed of microscopically-and genetically-cancerous cells, do not advance to malignant tumors or lethal malignancies. Hence, rigorous causal evidence would be crucial to establish that STIC is a bona fide premalignant lesion for metastatic HGSC. While not all STICs may transform into malignant tumors, these lesions are clearly associated with increased risk for HGSC. Identification of the molecular characteristics of STICs that predict their malignant potential and clinical behavior would bolster the clinical importance of STIC. Also, as STIC lesions alone cannot account for all HGSCs, other potential cellular origins of HGSC need to be investigated. The fallopian tube stroma in mice, for instance, has been shown to be capable of giving rise to metastatic HGSC, which faithfully recapitulates the clinical behavior and molecular aspect of human HGSC. Elucidating the precise cell(s) of origin of HGSC will be critical for improving the early detection and prevention of ovarian cancer, ultimately reducing ovarian cancer mortality.
Fifty-seven bacterial isolates were obtained from a previous study; these were
collected out of twenty-seven soil-contaminated samples in Iraq. Rumaila oil field,
Bai-Hassan oil field, and East ...Baghdad oil field are located in Iraq. The results of
bacterial degradation of hydrocarbons components showed that 44% of P. aeruginosa as well as 50% of S. marcescens possessed the ability to degrade anthracene, as well 60% of P. aeruginosa and 50% of each S. marcescens, B. cepacia,
and A. radioersistens with 100% of K. pneumoniae possessed the degradation
ability of phenathrene. Finally, the results illustrated that 55.56%, 83.3%, and 50%
of P. aeruginosa, S. marcescens, and B. cepacia, respectively, in addition to 100%
of each A. radioersistens and K. pneumoniae had the degradation ability of
naphthalene. Optimization results showed that pH 7 and temperature 35ºwith
peptone as a nitrogen source were the best degradation parameters. Finally, the
results showed significant activity of OSE II in the bacterial degradation of
naphthalene without any effects on phenathrene and anthracene.
Keywords: OSE II, hydrocarbons, bacterial degradation, anthracene, phenanthrene, and naphthalene
Our understanding of the molecular determinants of cancer is still inadequate because of cancer heterogeneity. Here, using epithelial ovarian cancer (EOC) as a model system, we analyzed a minute ...amount of patient-derived epithelial cells from either healthy or cancerous tissues by single-shot mass-spectrometry-based phosphoproteomics. Using a multi-disciplinary approach, we demonstrated that primary cells recapitulate tissue complexity and represent a valuable source of differentially expressed proteins and phosphorylation sites that discriminate cancer from healthy cells. Furthermore, we uncovered kinase signatures associated with EOC. In particular, CDK7 targets were characterized in both EOC primary cells and ovarian cancer cell lines. We showed that CDK7 controls cell proliferation and that pharmacological inhibition of CDK7 selectively represses EOC cell proliferation. Our approach defines the molecular landscape of EOC, paving the way for efficient therapeutic approaches for patients. Finally, we highlight the potential of phosphoproteomics to identify clinically relevant and druggable pathways in cancer.
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•We analyze ex-vivo-cultured primary cells using phosphoproteomics•We investigate epithelial ovarian cancer (EOC) and healthy tissue•We uncover expression of cancer-specific proteins and kinase signatures•The kinase CDK7 phosphorylates POLR2A and regulates EOC cell proliferation
Francavilla et al. use mass-spectrometry-based phosphoproteomics as a powerful tool to reveal cancer signatures. They analyze changes in the proteome and phosphoproteome of primary cells derived from epithelial ovarian cancer (EOC) compared to healthy tissues and reveal a role for the kinase CDK7 in EOC cell proliferation.
Operational status evaluation (OSE) is essential for the health management of smart electricity meters (SEM). This article develops a machine learning-enabled OSE method for SEM. Specifically, the ...Gaussian process regression (GPR) is developed for modeling analysis, where an optimized automatic relevance determination (OARD) kernel is first used. Though the conventional ARD kernel structure can capture the potential mapping relationship between running time, temperature, humidity, and measurement error (ME), it cannot extract the influence degree of different stresses on the ME. To address this problem, an OARD kernel structure is proposed to identify the contribution of each part in ARD structure to the target data. Furthermore, the quartiles line instead of 95% confidence interval is exploited to enhance the performance of GPR for long-term prediction. Combining the two above improvements, a novel OSE model is established for the future-oriented long-term operation of the SEM. It is the first-known data-driven application that utilizes the GPR with OARD kernel to perform OSE for SEM. Actual SEM datasets collected from both dry and hot region are used for model validation and prediction. The results demonstrate that the proposed GPR model with OARD Matern52 kernel outperforms other conventional kernel approaches in the aspect of interpretability. More importantly, the operational status of the SEM in future can be assessed via the proposed OSE framework.
The essay's primary purpose is to bring to the attention of readers interested in the history of the Jewish people that the dramatic 20th century is not only the victims of the Holocaust–and not only ...the heroism of the military on the battlefields. It is active resistance to barbarism–the rescue of defenseless people through daily civilian activities, nevertheless associated with a constant risk to life. This paper examines non-political and non-religious secular Jewish welfare society within Jewish political and national movements. This essay considers five historical periods of the activity of OSE. These periods are: 1912–1922; 1922–1933; 1933–1945; 1945–1950; 1950–present time. This chronological classification is somewhat imperfect; however, each period reflects the dynamic of functional changes in the initial tasks of the society to review the goals of the organization to satisfy the urgent needs of the European Jewish community in a debatable circumstance of the 20th–21st centuries.
Cannabis plant has long been execrated by law in different nations due to the psychoactive properties of only a few cannabinoids. Recent scientific advances coupled with growing public awareness of ...cannabinoids as a medical commodity drove legislation change and brought about a historic transition where the demand rose over ten-fold in less than five years. On the other hand, the technology required for cannabis processing and the extraction of the most valuable chemical compounds from the cannabis flower remains the bottleneck of processing technology. This paper sheds light on the downstream processing steps and principles involved in producing cannabinoids from Cannabis sativa L. (Hemp) biomass. By categorizing the extraction technology into seed and trichome, we examined and critiqued different pretreatment methods and technological options available for large-scale extraction in both categories. Solvent extraction methods being the main focus, the critical decision-making parameters in each stage, and the applicable current technologies in the field, were discussed. We further examined the factors affecting the cannabinoid transformation that changes the medical functionality of the final cannabinoid products. Based on the current trends, the extraction technologies are continuously being revised and enhanced, yet they still fail to keep up with market demands.
High-dimensional imaging features extracted from diagnostic imaging, called radiomics, are increasingly reported for diagnosis, prognosis, and response to therapy. Establishing the sensitivity of ...radiomic features to variation in scan protocols is necessary because acquisition and reconstruction parameters can vary widely across and within institutions. Our objective was to assess the reproducibility of radiomic features derived from computed tomography (CT) images by varying tube current (mA), noise index, and reconstruction adaptive statistical iterative reconstruction (ASiR), parameters increasingly varied by institutions seeking to reduce radiation dose in their patients. We extracted radiomic features from CT images of a uniform water phantom, anthropomorphic phantom, and a human scan. Scans were acquired from the phantoms with six tube currents (50, 100, 200, 300, 400, and 500 mA) and five noise index levels (12, 14, 16, 18, and 20), respectively. Scans of the phantoms and patient were reconstructed from 0% ASiR (i.e., filtered back projection) to 100% ASiR in increments of 10%. Two hundred and forty-eight well-known radiomic features were extracted from all scans. The concordance correlation coefficient was used to assess agreement of features. Our analysis suggests that image acquisition parameters (tube current, noise index) as well as the reconstruction technique strongly influence radiomic feature reproducibility and demonstrate a subset of reproducible features potentially usable in clinical practice.
•We extended the OSE (optimum sequence estimation) method to the group-coupling case.•We resolved multiplets by using GC of OSE.•We compared with GC and SC results of the mode 4S2 in the pair ...4S2-0S10.•We resolved modes 4S1, 0S8, 2S7, 6S1, 4S3, 7S1, 5S3, 5S4, 6S2, 3S8-6S3 by GC of OSE.
The splitting and coupling observations for the normal modes may reveal details about large-scale structure of the 3D Earth. In the frequency domain, especially for frequency >1.5mHz, the mode-coupling should be taken into account as the modes become denser and closer. There are many S-S type clusters below 3mHz which need to be resolved, such as 0S7-2S3, 1S5-2S4, 4S1-0S8-3S3, 0S9-1S0, 1S7-2S6 and other similar clusters. This paper explores whether the obtained splitting singlets of normal modes in high frequency band have higher SNRs and precision under the condition of considering coupling effects into the optimum sequence estimate (OSE). On the basis of the OSE method, we started experiments by extending the equations for vertical and transverse components to the group-coupling scheme that the splitting coefficient matrix B is not only determined by a target multiplet alone but also includes several cross-coupling multiplets. Then the results of self-coupling and group-coupling of the singlets are compared to determine whether the across-multiplet coupling plays an important role in the stripping of the modes. The results showed that the singlets of higher modes could be observed more clearly and resolved more completely by considering group-coupled modes for the narrow-band frequency. After comparing observations with predictions of the PREM−tidal model, the differences may provide valuable information about the deep Earth and further constraints on the 3D structure of the Earth.
Lily is one of the most important cut flowers in the world, with a rich floral fragrance. To further explore the fragrance emission mechanisms of lily cultivars, headspace solid-phase ...microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and organic solvent extraction-gas chromatography-mass spectrometry (OSE-GC-MS) were used to unveil the volatile organic compounds (VOCs) and endogenous extracts of seven lily cultivars. Furthermore, real-time quantitative PCR (qRT-PCR) was used to determine the expression levels of two key genes (
and
) related to the biosynthesis of monoterpenoids and methyl benzoate. The results show that forty-five VOCs were detected in the petals of seven lily cultivars, and the main compounds were monoterpenoids and phenylpropanoids/benzenoids. Dichloromethane was the best solvent for extracting the endogenous extracts of
'Viviana' petals and eighteen endogenous extracts were detected using dichloromethane to extract the petals of seven lily cultivars. Each compound's emission ratio (natural logarithm of the ratio of VOC content to endogenous extract content) was calculated, and linear regression analyses between emission ratios and boiling points were conducted. Significant linear negative correlations existed between the emission ratios and boiling points of compounds, and the regression equations' coefficients of determination (
) were all greater than 0.7.
was expressed highly in 'Viviana', 'Pink News', and 'Palazzo', and
was expressed highly in 'Pink News' and 'Palazzo'. Correlation analyses between the gene expression levels and the monoterpenoids and methyl benzoate contents found that the
expression levels have strong positive correlations with monoterpenoids content, while no correlations were found between the expression levels of
and the contents of methyl benzoate. This study lays the foundation for research on the release patterns of VOCs in the flowers of
, and the breeding of lilies for their floral fragrance.
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