Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of membrane-bound mucins in human nasal mucosa: different patterns for MUC4 and MUC16.

OBJECTIVE To acquire basic information concerning the function of the membrane-bound mucin MUC16 in nasal mucosa compared with the best-characterized membrane-bound mucin, MUC4. DESIGN In vitro study using semiquantatitive reverse transcription-polymerase chain reaction analysis and immunoassay. SETTING Yeungnam University College of Medicine. SUBJECTS We examined the nasal polyps obtained during endoscopic sinus surgery in 10 patients, the normal ethmoid sinus mucosa obtained from 10 patients, and human nasal polyp epithelial (HNPE) cells. MAIN OUTCOME MEASURES Gene expression of MUC4 and MUC16 in nasal polyps and normal nasal mucosa. In addition, we evaluated the effect of 4 physiologically relevant agents, including retinoic acid, interleukin 1beta, phorbol 12-myristate 13-acetate (PMA), and dexamethasone, on the expression of MUC4 and MUC16 in HNPE cells at the gene and protein levels. RESULTS In nasal polyps, MUC4 was upregulated compared with normal nasal mucosa (P = .009), whereas MUC16 expression did not differ between nasal polyps and normal nasal mucosa. Retinoic acid and interleukin 1beta increased MUC4 expression at the gene and protein level in HNPE cells, whereas MUC16 expression was not affected. Unlike retinoic acid and interleukin 1beta, PMA and dexamethasone increased MUC16 expression, whereas they had no significant effect on MUC4 expression. CONCLUSIONS Expression of MUC4 and MUC16 are regulated differently in nasal mucosa. Dexamethasone and PMA are potent mediators for the expression of MUC16 in nasal polyps.
Herceptin® Alone or in Combination with Chemotherapy in the Treatment of HER2-Positive Metastatic Breast Cancer: Pivotal Trials

Large pivotal phase II and III clinical trials investigated the therapeutic efficacy and safety of the humanized anti-HER2 monoclonal antibody, Herceptin®, alone and in combination with standard chemotherapy, respectively, in HER2-positive metastatic breast cancer. Eligible patients were HER2 2+ and 3+ overexpressors, as determined by immunohistochemistry (IHC). Herceptin was well tolerated in both trials. Single-agent second/third-line Herceptin produced durable tumor responses. First-line Herceptin in combination with chemotherapy, in particular paclitaxel, significantly improved time to disease progression, duration of response and time to treatment failure. Combination therapy also provided a significant 25% improvement in overall survival. These clinical benefits have led to the approval of Herceptin for clinical use in the USA and elsewhere. Greater efficacy was noted in IHC 3+ patients compared with the overall population in both trials. Retrospective fluorescent in situ hybridization (FISH) testing of patient-tumor HER2 status revealed similar clinical outcomes in IHC 3+ and FISH-positive patients, consistent with the reported high concordance between IHC and FISH. Responses in the single-agent Herceptin trial were seen exclusively in FISH-positive patients. Approximately a quarter of HER2 2+ patients test FISH positive and may therefore benefit from therapy. Numerous studies are underway or planned to evaluate other Herceptin combinations and regimens in the metastatic and adjuvant settings.
ComC is required for the processing and translocation of ComGC, a pilin‐like competence protein of Bacillus subtilis

ComGC is a cell surface‐localized protein required for DNA binding during transformation in Bacillus subtilis. It resembles type IV prepilins in its N‐terminal domain, particularly in the amino acid sequence surrounding the processing cleavage sites of these proteins. ComC is another protein required for DNA binding, which resembles the processing proteases that cleave type IV prepilins. We show here that ComGC is processed in competent cells and that this processing requires ComC. We also demonstrate that the PilD protein of Neisseria gonorrhoeae, a ComC homologue, can process ComGC in Escherichia coli, and that the ComC protein itself is the only B. subtilis protein needed to accomplish cleavage of ComGC in the latter organism. Based on NaOH‐solubility studies, we have shown that in the absence of ComC, but in the presence of all other competence proteins, B. subtilis is incapable of correctly translocating ComGC to the outer face of the cell membrane. Finally, we show that ComGC can be cross‐linked to yield a form with higher molecular mass, possibly a dimer, and present evidence suggesting that formation of the higher mass complex takes place in the membrane, prior to translocation. Formation of this complex does not require ComC or any of the comG products, other than ComGC itself.
Biologic Characteristics and Osteogenic Differentiation of Maxillary Primordium Mesenchymal Cells

ObjectiveThe aim of this study was to investigate the biologic characteristics and osteogenic differentiation of mouse maxillary primordium mesenchymal cells (MPMCs) in vitro. MethodsThe MPMCs were obtained from the E13.5 mouse embryos and cultured in vitro. The biologic characteristics were studied based on general observation and 5-Bromo-2-deoxyUridine (BrdU) label. The MPMCs from the first passage were cultured in the osteogenic medium for 1 week. Then, the immunofluorescence staining, alkaline phosphatase staining, Alizarin red S staining, and quantity polymerase chain reaction were used to evaluate the osteogenic capability of MPMCs. ResultsThe E13.5 MPMCs were successfully adherent cultured and passaged in vitro. These cells expressed Dlx2 and SMAD7, two genes that play important roles in the development of maxillary primordium. The percentage of 5-Bromo-2-deoxyUridine-labeled MPMCs was 32.1%. Osteogenic induction could promote the expression of Runx2, osteocalcin, and osteopontin, 3 osteogenic markers, in MPMCs. In addition, osteogenic induction could stimulate the secretion of alkaline phosphatase and promote the deposition of calcium nodules in MPMCs. ConclusionsThe MPMCs could be cultured in vitro and could differentiate into osteoblast in vitro through osteogenic induction. It offered an alternative cell source to regenerate craniofacial bone and offered a useful cell model to study the craniofacial bone development.
Preoperative and perioperative chemotherapy with 5-fluorouracil as continuous infusion in operable breast cancer expressing a high proliferation fraction: cytotoxic treatment during the surgical phase.

BACKGROUND Experimental data on perioperative chemotherapy (PeCT) indicate that its initiation might be most useful if administered as close as possible to the time of first 'disturbance of the tumour'. Regimens including 5-fluorouracil (5-FU) as continuous infusion are commonly used in the preoperative setting, especially for large tumours and locally advanced disease. We therefore evaluated the role of PeCT with 5-FU as continuous infusion after preoperative chemotherapy (PreCT), covering the surgical phase and acute wound healing period, in patients with breast cancer too large to attempt breast-conserving surgery upon diagnosis. PATIENTS AND METHODS Breast cancer patients, clinical stages T2-T3, N0-N2, M0, and Ki-67 labelling index >/= 20%, were treated every 3 weeks with a maximum of six courses of vinorelbine 20 mg total dose intravenously (i.v.) on days 1 and 3, cisplatin 60 mg/ m(2) i.v. on day 1 and 5-FU 200 mg/m(2)/day as a continuous infusion (ViFuP regimen). Patients who achieved a clinical and radiological objective remission with PreCT were also treated with perioperative 5-FU that was continued until 30 min before, and restarted immediately after surgery, prolonging infusion until 15 days after surgery. RESULTS Following preoperative treatment, 39 of 49 evaluable patients [80%; 95% confidence interval (CI) 70% to 90%] had an objective response. Pathological complete remission (pCR) was achieved in 14 (29%) patients. No relevant clinical or haematological toxicity due to PeCT was observed. In 36 patients submitted to PeCT the rate of pCR was 33% (95% CI 18% to 48%). The highest response of the primary tumour to PreCT and PeCT was observed in women with tumours not expressing estrogen and progesterone receptors (pCR 46%; 95% CI 19% to 73%). CONCLUSIONS Preoperative therapy can be protracted into the surgical (and wound healing) period without significant additional short-term toxicity. Proper selection of patients according to biological features might improve the therapeutic yield of preoperative therapies.
Human F1F0 ATP Synthase, Mitochondrial Ultrastructure and OXPHOS Impairment: A (Super-)Complex Matter?

Mitochondrial morphogenesis is a key process of cell physiology. It is essential for the proper function of this double membrane-delimited organelle, as it ensures the packing of the inner membrane in a very ordered pattern called cristae. In yeast, the mitochondrial ATP synthase is able to form dimers that can assemble into oligomers. Two subunits (e and g) are involved in this supramolecular organization. Deletion of the genes encoding these subunits has no effect on the ATP synthase monomer assembly or activity and only affects its dimerization and oligomerization. Concomitantly, the absence of subunits e and g and thus, of ATP synthase supercomplexes, promotes the modification of mitochondrial ultrastructure suggesting that ATP synthase oligomerization is involved in cristae morphogenesis. We report here that in mammalian cells in culture, the shRNA-mediated down-regulation of subunits e and g affects the stability of ATP synthase and results in a 50% decrease of the available functional enzyme. Comparable to what was shown in yeast, when subunits e and g expression are repressed, ATP synthase dimers and oligomers are less abundant when assayed by native electrophoresis. Unexpectedly, mammalian ATP synthase dimerization/oligomerization impairment has functional consequences on the respiratory chain leading to a decrease in OXPHOS activity. Finally these structural and functional alterations of the ATP synthase have a strong impact on the organelle itself leading to the fission of the mitochondrial network and the disorganization of mitochondrial ultrastructure. Unlike what was shown in yeast, the impairment of the ATP synthase oligomerization process drastically affects mitochondrial ATP production. Thus we propose that mutations or deletions of genes encoding subunits e and g may have physiopathological implications.
According to need?: needs assessment and decision-making in the humanitarian sector

Adele Harmer is a Research Officer with HPG. Andre Griekspoor (Emergencies and Humanitarian Action Department, WHO) is an adviser on health issues (Southern Africa study and main report). Fiona Watson (NutritionWorks) is an independent consultant on food security (Southern Africa study and main report). Mark Bradbury is an independent consultant. He was team leader for the field study on Southern Sudan and Somalia. Stephanie Maxwell is an independent consultant on food security (Sudan/Somalia study). Abigail Montani is an independent consultant on internal displacement (Sudan/Somalia study). Dineke Venekamp is an independent consultant on health issues (Sudan/Somalia study). Chris Johnson is an independent consultant (Afghanistan study). Moira Reddick is an independent consultant (study on rapid-onset disasters). Jeremy Shoham (NutritionWorks) is an independent consultant on food security (main report). Acknowledgements Much assistance was given to the study by a range of individuals and organisations in addition to those named above. The ODI team would like to thank in particular the members of the advisory group for the study and others who gave particular help: Allessandro Colombo and colleagues in the Emergencies and Humanitarian Action Department of Others who gave their time and assistance are listed in the separate reports of the case studies. Many thanks also to colleagues in the Humanitarian Policy Group at ODI, in particular Joanna Macrae, for invaluable help in drafting and editing the various materials. The views expressed in the study reports were informed by discussion with the individuals named above, but do not necessarily reflect the views of those individuals or of their organisations. The study was funded by contributions from the UK Department for International Development (DFID), the European Community Humanitarian Office (ECHO), and the Australian government (AusAID). 1 Preface 3 Executive summary 5 Chapter 1 Introduction and background 9 1.1 Overview 9 1.2 Background 10 1.3 Study background and methodology 11 1.4 Structure 11 Chapter 2 Conceptual issues 13 2.1 Concepts, definitions and frameworks of analysis 13 2.1.1 Defining the humanitarian agenda 13 2.1.2 What is the aim of humanitarian action? 13 2.1.3 Defining 'humanitarian crisis' 14 2.1.4 Defining 'humanitarian need' 16 2.1. 5 Other bases for analysis: risk, vulnerability, capacity 17 2.2 Analytical frameworks and conceptual models 20 2.3 Relief, development and the institutional divide 20 2.4 Rights and needs 22 2.5 Conclusions 23 Chapter 3 The practice of needs assessment 25 3.1 The nature and purpose of assessment 25 3.1.1 Formal and non-formal assessment 25 …
Application of DC choppers in HVDC grids

This paper investigates the use and need for DC choppers in VSC HVDC grids. Sudden increases in the DC link voltage, caused by AC grid side voltage drops, can lead to potential damage of the DC equipment. Therefore, DC choppers are currently used in point-to-point links to keep the voltage within safe margins. Given that the HVDC grid topology is expected to change from point-to-point connected offshore wind farms to multi-terminal HVDC structures in the future, the potential of DC choppers in HVDC grids, is investigated. Simulations on a multi-terminal HVDC model are presented to show the performance of the system equipped with a DC chopper. The system influence of over-voltage protection using DC choppers in different grid topologies is examined. Investigations include the combination of DC choppers with DC voltage droop control. Concluding from simulations, DC choppers are a feasible measure to reach proper fault ride-through (FRT). However, the requirements for DC choppers in HVDC grids are comparatively low compared to point-to-point connections through the use of droop control.
Populism and the changing media landscape: understanding the rise of the Five Star Movement in Italy

The thesis develops an understanding of the relationship between populism and the changes in the media landscape brought about by the advent of web 2.0. Its aim is to explain the rapid emergence of the Beppe Grillo’s Five Star Movement in Italy. A contextual analysis of the structures of opportunities reveals that the key to understand the ‘success’ of 5SM lays in the fact that the political actor fully exploited the affordances of the Web 2.0, making them resonate with the ‘thin’ ideology of populism. The advent of web 2.0 can then benefit political actors employing a populist ideology in three ways; enhancing the declining trust and separation between people and the political establishment, providing a seemingly more direct form of communication with the electorate and providing a new way of constructing the ‘people’ of populism through the networks.
Association of the bradykinin receptors genes variants with hypertension: a case–control study and meta-analysis

Abstract Background: The present study was to investigate the role of bradykinin receptors genes polymorphisms on hypertension risk in Northern Han Chinese population. We also carried out a meta-analysis on Chinese to derive a more full assessment of this association. Methods and results: A total of 976 subjects from Northern Han Chinese and 7 studies with 1599 cases and 1425 controls were included in this case–control study and in the current meta-analysis, respectively. For the case–control study, we identified the genotypes of −58T/C and 1098A/G polymorphism in BDKRB2 and BDKRB1 genes, respectively, by TaqMan PCR method. Overall, we found significant association between the −58T/C polymorphism and the increased risk of hypertension in the allele comparison (p = 0.01, OR = 1.386, 95%CI [1.138–1.688]). Subgroup analysis by gender suggested that this obvious association could still be found in males, but not in females. For the 1098A/G polymorphism, no significant association was revealed in overall and subgroup analysis. For the meta-analysis involving the −58T/C polymorphism, a significant association between this polymorphism and hypertension was observed in the whole group. In Chinese Han subgroup, we found significant association with hypertension in allele comparison(C vs. T: p = 0.03, OR = 1.28, 95%CI 1.03–1.59, pheterogeneity = 0.05). Conclusions: Our case–control study indicated that −58T/C might be significantly associated with the increased risk of hypertension in Northern Han Chinese population, which was partially confirmed by our meta-analysis.
Monitoring and CEO Contractual Incentive Pay

This paper finds that a CEO who is better monitored tends to have smaller wealth&#8208;performance sensitivity (WPS). The results are consistent with the optimal contracting view and are robust to different measures of WPS. The findings suggest caution in drawing conclusions when researchers use WPS as an observable outcome of monitoring to test the effectiveness of monitoring. The association of monitoring and WPS is not necessarily positive, as assumed by prior corporate governance research.
The detection of the epstein‐barr virus (ebv) nuclear antigen (ebna) by anti‐complement immunofluorescence. Immunoglobulin class of antibodies and role of complement

The Epstein‐Barr virus (EBV)‐associated nuclear antigen (EBNA) was detected by anti‐complement immunofluorescence (ACIF) in Raji lymphoblastoid cell line, and the mechanism of the reaction explored, using Ig fractions of anti‐EBNA sera and purified components of complement. Following fractionation of serum from 13 donors, anti‐EBNA antibodies were always found to be associated with IgG, but were also detectable in the IgM fraction of four sera. Sequential addition of functionally pure complement components in the ACIF reaction showed that the classical sequence of complement activation is involved. Anti‐EBNA antibody reactions in Raji cell nuclei can also be detected by anti‐Ig immunofluorescence with a low level of sensitivity. The same pattern of granular fluorescence was observed when C3 (β1A/β1C), or C4 or IgG anti‐EBNA antibodies were revealed with the corresponding fluorescein‐conjugated reagents. Blocking of the ACIF reaction was achieved with Fab'2 anti‐EBNA antibody fragments, which therefore provided an appropriate specificity control for the detection of EBNA.
Adaptive content adjustment of digital power saving for display application

Display application often requires a procedure to control panel brightness and decrease the power consumption for different environmental condition. The most of digital power saving (DPS) techniques are applied to determine the flexibility of content adjustment. By the characteristics of display, global brightness usually presents the intensity of power consumption and DPS technique is requested to adjust image content for power saving. In this paper, we utilize luminance estimation and bilinear mapping process to implement DPS. The variance of local illumination and the flexibility of content adjustment exists an interrelation. From the simulation results, the proposed method can maintain more features than current methods and provide a scalability of power consumption for display application.
RpoS and quorum sensing control expression and polar localization of Vibrio cholerae chemotaxis cluster III proteins in vitro and in vivo

The diarrheal pathogen Vibrio cholerae contains three gene clusters that encode chemotaxis‐related proteins, but only cluster II appears to be required for chemotaxis. Here, we present the first characterization of V. cholerae's ‘cluster III’ chemotaxis system. We found that cluster III proteins assemble into foci at bacterial poles, like those formed by cluster II proteins, but the two systems assemble independently and do not colocalize. Cluster III proteins are expressed in vitro during stationary phase and in conjunction with growth arrest linked to carbon starvation. This expression, as well as expression in vivo in suckling rabbits, is dependent upon RpoS. V. cholerae's CAI‐1 quorum sensing (QS) system is also required for cluster III expression in stationary phase and modulates its expression in vivo, but is not required for cluster III expression in response to carbon starvation. Surprisingly, even though the CAI‐1 and AI‐2 QS systems are thought to feed into the same signaling pathway, the AI‐2 system inhibited cluster III gene expression, revealing that the outputs of the two QS systems are not always the same. The distinctions between genetic determinants of cluster III expression in vitro and in vivo highlight the distinctive nature of the in vivo environment.
Machine learning in cell biology – teaching computers to recognize phenotypes

Summary Recent advances in microscope automation provide new opportunities for high-throughput cell biology, such as image-based screening. High-complex image analysis tasks often make the implementation of static and predefined processing rules a cumbersome effort. Machine-learning methods, instead, seek to use intrinsic data structure, as well as the expert annotations of biologists to infer models that can be used to solve versatile data analysis tasks. Here, we explain how machine-learning methods work and what needs to be considered for their successful application in cell biology. We outline how microscopy images can be converted into a data representation suitable for machine learning, and then introduce various state-of-the-art machine-learning algorithms, highlighting recent applications in image-based screening. Our Commentary aims to provide the biologist with a guide to the application of machine learning to microscopy assays and we therefore include extensive discussion on how to optimize experimental workflow as well as the data analysis pipeline.
A Long-term Prospective Population Pharmacokinetic Study on Imatinib Plasma Concentrations in GIST Patients

Purpose: Imatinib minimal (trough) plasma concentrations after one month of treatment have shown a significant association with clinical benefit in patients with gastrointestinal stromal tumors (GIST). Considering that a retrospective pharmacokinetic analysis has also suggested that imatinib clearance increases over time in patients with soft tissue sarcoma and GIST, the primary aim of this study was to assess systemic exposure to imatinib at multiple time points in a long-term prospective population pharmacokinetic study. As imatinib is mainly metabolized in the liver, our secondary aim was to elucidate the potential effects of the volume of liver metastases on exposure to imatinib. Experimental Design: Full pharmacokinetic blood sampling was conducted in 50 patients with GIST on the first day of imatinib treatment, and after one, six, and 12 months. In addition, on day 14, and monthly during imatinib treatment, trough samples were taken. Pharmacokinetic analysis was conducted using a compartmental model. Volume of liver metastases was assessed by computed tomographic (CT) imaging. Results: After 90 days of treatment, a significant decrease in imatinib systemic exposure of 29.3% compared with baseline was observed (P < 0.01). For every 100 cm3 increase of metastatic volume, a predicted decrease of 3.8% in imatinib clearance was observed. Conclusions: This is the first prospective pharmacokinetic study in patients with GIST, showing a significant decrease of approximately 30% in imatinib exposure after long-term treatment. This means that future "trough level – clinical benefit" analyses should be time point specific. GIST liver involvement, however, has a marginal effect on imatinib clearance. Clin Cancer Res; 18(20); 5780–7. ©2012 AACR.