Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphoinositide-3-Kinase Inhibition Enhances Radiosensitization of Cervical Cancer In Vivo

Background: Phosphoinositide-3-kinase (PI3K)/Akt pathway is downregulated in several human cancers, and PI3K inhibition can sensitize these cancer cells to radiation. However, no research on cervical cancer in vivo has been reported. The present study further investigated whether PI3K inhibition could sensitize cervical cancer to radiation in vivo. Methods: HeLa cells with sustained PI3K activity and Akt phosphorylation were injected subcutaneously into BALB/C nude mice to establish tumor cell xenograft, which were randomly assigned to control, PI3K inhibitor LY294002 alone, radiation alone, or combined LY294002 and radiation group. Akt phosphorylation was detected by Western blotting to evaluate the blocking efficiency on PI3K activity. The radiosensitization of PI3K inhibition was measured by clonogenic assays, apoptosis analysis, and tumor regrowth assays. Results: The combination of LY294002 and radiation resulted in significant and synergistic suppression of cervical cancer cells in a dose-dependent manner in clonogenic assays (P < 0.05), higher ratio of apoptosis cells, and more remarkable reduction of Akt phosphorylation. Tumor regrowth delay curve showed the lowest increase of tumor volume in the combined group (37 days in average) (P = 0.003). Besides, LY294002 (100 mg/kg) alone decreased cell survival and produced xenograft regrowth delay. Conclusions: Phosphoinositide-3-kinase inhibition by LY294002 can synergistically enhance radiation efficacy via dephosphorylation of Akt in cervical cancer, and PI3K inhibition alone can also suppress tumor regrowth. This may provide novel therapeutic opportunities to enhance the effect of radiotherapy against cervical cancer.
On the Use and Abuse of Economics Journal Rankings

There are several aspects of journal‐level citations that, taken together, provide considerably more information than mean citations per article. This information is likely to be more useful, in terms of helping someone form more accurate expectations of the quality of a given article published in a journal, than the information provided by mean citations per article only. I provide data that both illustrate this point and offer a range of information about the citations to papers published in 248 economics journals during the period 2001–5.
Lease and service for product life‐cycle management: an accounting perspective

Purpose - Previous research in lease finance and evaluation has given little consideration to environmental factors. The purpose of this paper is to add to the literature by analysing how leasing provides a more attractive option than selling and extended producer responsibility (EPR) in helping to close product life-cycle loops, extend the useful life of products, and increase environmental benefits. Design/methodology/approach - This paper revisits the accounting concepts of asset depreciation, residual value and cost of leasing and proposes methods to incorporate these concepts into the “closed loop” lease and service mode for product life-cycle management. Findings - For business, the “closed loop” lease and service mode changes asset values through the extension of the asset's useful life and in particular, the increase of the residual value of the product (i.e. recoverable value to the producer/lessor). Such changes reduce the cost of leasing to the advantage of both lessor and lessee. However, the argument about a “win-win” monetary and environmental outcome being associated with leasing presents several challenges for current accounting standards in terms of recognition of lease and lease revenue, recognition of intangible assets and internalisation of environmental costs and impacts associated with the leasing process. Originality/value - To date, accounting and finance literature seems to focus exclusively on the economic aspects of leasing strategies. This paper uses a different lens to make a call for a rethink about leasing with environmental considerations. It is expected that the findings and suggestions in this study will facilitate the adoption and diffusion of the “closed loop” lease and service mode in the business world for the benefit of the environment in the future.
Low-dose lipopolysaccharide (LPS) pretreatment of mouse macrophages modulates LPS-dependent interleukin-6 production in vitro

Lipopolysaccharide (LPS) can induce mouse macrophages to produce a number of cytokines and other inflammatory mediators. Our laboratory previously reported that LPS-dependent macrophage-derived tumor necrosis factor alpha (TNF-alpha) production could be significantly potentiated by pretreatment with LPS at substimulatory LPS priming doses. The observed potentiation was shown to be coincident with a down-regulation of LPS-dependent nitric oxide (NO) production (X. Zhang and D. C. Morrison, J. Exp. Med. 177: 511-516, 1993). In order to determine whether these LPS reprogramming effects in mouse macrophages were selective for these two macrophage-derived mediators, we have examined the effects of LPS pretreatment on LPS-dependent interleukin 6 (IL-6) production. Thioglycolate-elicited mouse peritoneal macrophages were pretreated with various subthreshold stimulatory concentrations of LPS for 6 h, washed three times, and then stimulated with an effective stimulatory concentration of smooth LPS for 18 h. In confirmation of earlier studies, pretreatment of mouse macrophages with substimulatory doses of LPS inhibited the subsequent LPS-dependent NO production. This down-regulation was accompanied by a coordinate up-regulation of LPS-dependent IL-6 production, similar to what was shown earlier for TNF-alpha production. These priming effects with the substimulatory dose of smooth LPS are shown to be independent of doses of LPS used for subsequent activation and are not restricted to specific LPS stimulation. Moreover, the enhancement of the IL-6 response by LPS pretreatment is still observed in the presence of neutralizing antibody to TNF-alpha. These findings, therefore, provide further support for the conclusion that LPS-dependent macrophage reprogramming is likely to involve common regulatory pathways that control the secretion of both IL-6 and TNF-alpha.
The relevance of therapeutic drug monitoring in plasma and erythrocytes in anti-cancer drug treatment

Abstract Therapeutic drug monitoring generally focuses on the plasma compartment only. Differentiation between the total plasma concentration and the free fraction (plasma water) has been described for a number of limited drugs. Besides the plasma compartment, blood has also a cellular fraction which has by far the largest theoretical surface and volume for drug transport. It is with anti-cancer drugs that major progress has been made in the study of partition between the largest cellular blood compartment, i.e., erythrocytes, and the plasma compartment. The aim of the present review is to detail the progress made in predicting what a drug does in the body, i.e., pharmacodynamics including toxicity and plasma and/or red blood cell concentration monitoring. Furthermore, techniques generally used in anti-cancer drug monitoring are highlighted. Data for complex Bayesian statistical approaches and population kinetics studies are beyond the scope of this review, since this is generally limited to the plasma compartment only.
Lipopolysaccharide‐Induced In Vivo Activation of Follicular Dendritic Cells is Tumor Necrosis Factor Receptor‐1 Independent

It is well recognized that tumor necrosis factor receptor‐1 (TNFR1) signaling pathway (with lymphotoxin‐β receptor) is of critical importance for the development, activation, and clustering of follicular dendritic cells (FDCs) within the lymphoid follicles. However, further information on the molecular control of these processes is very sparse. Here, we show that intravenous application of lipopolysaccharide induces the clear and prominent morphological signs of FDC development and activation in vivo, which is independent of TNFR1 pathway. Anat Rec, 2012. © 2011 Wiley Periodicals, Inc.
Psychosocial aspects of pediatric living donor liver transplantation

While the medical aspects of living donor liver transplantation (LDLT) have been investigated to a comparatively large degree, only in recent years have psychosocial aspects like donors' quality of life and attitude towards living donation been dealt with. In the course of a retrospective study, we examined 36 pediatric living liver donors at an average of 4.5 ± 2.8 years postoperatively. The donation's impact on the family was considered “very high,” “high,” or “average” by 48% of the donors. The physical impact of the donation was regarded as being higher than the emotional impact. Subjective full recovery was achieved at an average of 4.5 months postoperatively. All patients stated that they would donate again. Donors' quality of life, as assessed with the 36‐Item Short‐Form Quality of Life Questionnaire (SF‐36), was significantly higher than the German normative sample. Anxiety and depression, assessed with the Hospital Anxiety and Depression Scale–German version, were significantly lower compared to healthy controls. However, 14 patients (39%) described persistent, mostly physical, symptoms more than 1 yr postoperatively. In conclusion, the study's findings may enable clinicians to achieve a better understanding of living donors' situations, both pre‐ and postoperatively, and may help to assess the psychosocial risk of LDLT. Knowledge of possible ongoing problems may facilitate intervention at an early stage and should be included among the information given to potential living liver donors. Prospective studies using more specific instruments with an emphasis on the long‐term psychosocial outcome of LDLT are needed for future research. Liver Transpl, 2006. © 2006 AASLD.
A novel sensor kinase–response regulator hybrid regulates type III secretion and is required for virulence in Pseudomonas aeruginosa

The type III secretion system (TTSS) of Pseudomonas aeruginosa is induced by contact with eukaryotic cells and by growth in low‐calcium media. We have identified a protein, RtsM, that is necessary for expression of the TTSS genes in P. aeruginosa. RtsM possesses both histidine kinase and response regulator domains common to two‐component signalling proteins, as well as a large predicted periplasmic domain and seven transmembrane domains. Deletion of rtsM resulted in a defect in production and secretion of the type III effectors. Northern blot analysis revealed that mRNAs encoding the effectors ExoT and ExoU are absent in the ΔrtsM strain under TTSS‐inducing conditions. Using transcriptional fusions, we demonstrated that RtsM is required for transcription of the operons encoding the TTSS effectors and apparatus in response to calcium limitation or to host cell contact. The operon encoding the TTSS regulator ExsA does not respond to calcium limitation, but the basal transcription rate of this operon was lower in ΔrtsM than in the wild‐type parent, PA103. The defect in TTSS effector production and secretion of ΔrtsM could be complemented by overexpressing ExsA or Vfr, two transcriptional activators involved in TTSS regulation. ΔrtsM was markedly less virulent than PA103 in a murine model of acute pneumonia, demonstrating that RtsM is required in vivo. We propose that RtsM is a sensor protein at the start of a signalling cascade that induces expression of the TTSS in response to environmental signals.
The Macroeconomic Effects of Foreign Direct Investment

外人直接投資(foreign direct investment, FDI)被視為經濟成長的引擎之一, 主要原因是FDI會帶給接受國新的技術以及外溢效果, 進而促使其經濟成長加速。 但文獻上對FDI帶給總體經濟環境的影響, 看法並不一致。 因此, 本論文將對以下三個議題進行討論, 第一, FDI是否真的會使經濟成長加速; 第二,FDI是否會讓所得不均度下降; 第三, 雙邊FDI在景氣共移中所扮演的角色為何? 第二章主要探討FDI是否對經濟成長存在不對稱的門檻效果, 本章利用Caner and Hansen (2004)所提出的門檻回歸方法並運用期初GDP、人力資本與貿易開放程度為門檻變數,係以1975年至2000年的62個國家為研究對象。 在未考慮門檻效果時, FDI對於經濟成長的效果是不一致的,但納入門檻迴歸時, 實證結果證實期初GDP和人力資本的程度對FDI與經濟成長具有重要的解釋能力。 若FDI的接受國擁有較佳的期初GDP與人力資本, FDI對於經濟成長是正向顯著的影響。 第三章欲重新驗證金融中介機構在FDI對經濟成長的角色, 本章首先建立一個簡單的理論模型說明金融中介與FDI的外溢效果之間的關聯。 在實證分析上, 我們利用工具變數法來處理有可能的內生性問題, 但我們也發現在這個議題上存在弱工具變數的問題, 此問題會讓原先的估計結果產生偏誤。 因此, 本章運用較可信賴的聯合檢定, 如: Anderson and Rubin (1949), Kleibergen (2002)與Moreira (2003)再次檢驗金融中介的角色。 我們也考慮四種在有弱工具變數問題時較佳表現的估計方法進行分析, 如: limited information maximum likelihood (LIML)、Fuller (1977)及Hausman et al. (2008)所提出的兩種heteroskedasticity-robust估計方法(HLIML和HFUL)。 本章與Hermes and Lensink (2003)和Alfaro et al. (2004)不同之處, 我們發現擁有較佳的金融發展國家並不會讓FDI產生外溢效果, 使得經濟快速成長。 在第四章, 運用1980年至2005年56個國家分析在不同基礎建設的水準之下, FDI與所得不均度之間的關係。 本章利用Hansen (2000)所提出的門檻迴歸方法發現, 在基礎建設略差的國家,FDI的引進會讓接受國的所得不均度惡化; 相反地, 擁有較佳的基礎建設時, FDI對所得不均的影響不大。 此外,本章發現國際貿易會使得所得分配更加平均, 此外, 實證結果也支持Kuzents (1955)年所提出的Kuzents inverted-U hypothesis。 第五章利用77個國家組合分析FDI、貿易、產業相似度與景氣共移性的關係, 在過往文獻探討中大部份都忽略FDI的重要性。 本章採用Baltagi (1981)提出的error component three stage least square (EC3SLS)進行實證探討,我們發現FDI關係越緊密的國家會讓提高兩國的景氣共移性, 而貿易及產業相似度對景氣的影響則不顯著,這代表FDI是解釋景氣相關性重要的變數之一。 此外, 本章發現FDI是屬於水平性質, 因為FDI與貿易存在替代關係,FDI取代貿易在景氣共移中的角色, 這也是FDI的重要性提升的原因之一;實證結果亦顯示兩國產業差異性越大, 越會透過貿易來獲取各自所需的商品。
Jacobs Journal of Pharmacology and Pharmacovigilance Cyp 3 A 5 * 3 is Not a Pharmacogenetic Marker for Cyclosporine Treatment Response in Psoriasis

Psoriasis is a chronic skin disease that affects 2-3% of the population worldwide, causing significant morbidity and high financial burden. Cyclosporine is considered to be first-line systemic therapy for moderate to severe psoriasis. However, patients exhibit heterogeneity in their response to therapy, which could be due to genetic factors. Recently, we have shown that the use of a genetic marker in ABCB1, the gene that encodes for P-glycoprotein which is responsible for the influx-efflux of active drug (cyclosporine) into target cells alone or synergistically with the drug-metabolizing enzyme CYP3A4, can predict the response of a 7% of the patients in treatment with cyclosporine. With the scope of increasing this prediction efficiency, in this report we have studied two well-known functional polymorphisms in CYP3A4 and CYP3A5 genes, which contribute around 40-90% of the metabolism of cyclosporine. While the frequencies of these polymorphisms agree with the ones reported in the literature, our results showed no statistically significant association between the polymorphisms rs2740574 and rs776746 and the response of psoriatic patients to treatment with cyclosporine. Thereby we suggest that these two polymorphisms should be further analysed in larger groups prior to their exclusion for use as pharmacogenetic markers for psoriasis-cyclosporine, under a standard dose of treatment, in the Greek/causacian population.
Rosiglitazone, a PPARγ agonist, ameliorates palmitate‐induced insulin resistance and apoptosis in skeletal muscle cells

Palmitate induces insulin resistance and apoptosis in insulin target tissues. Rosiglitazone (RSG), a peroxisome proliferator‐activated receptor γ (PPARγ) agonist, can activate both pro‐apoptotic and anti‐apoptotic pathways in different cells; however, its effect on palmitate‐induced apoptosis in skeletal muscle cells remains to be elucidated. After differentiation of C2C12 cells, myotubes were treated with palmitate, RSG and GW9662 (PPARγ antagonist). MTT and terminal deoxynucleotide transferase dUTP nick end labelling (TUNEL) assays and caspase‐3 activity were used to investigate the apoptosis. To study the underlying mechanism, glucose uptake, gene expression and protein levels were evaluated. A total of 0.75 mM palmitate reduced cell viability by 43% and increased TUNEL‐positive cells and caspase‐3 activity by 15‐fold and 6.6‐fold, respectively. RSG (10 μM) could markedly decrease the level of TUNEL‐positive cells and caspase‐3 activity in palmitate‐treated cells. The protective effect of RSG on apoptosis was abrogated by GW9662. To investigate the molecular mechanism of this effect, gene expression and protein level of protein tyrosine phosphatase 1B (PTP1B) were evaluated. Palmitate and RSG individually increased the expression and protein level of PTP1B, whereas combined treatment (palmitate and RSG) were able to further increase the expression of PTP1B in C2C12 cells. We also evaluated the effect of RSG on palmitate‐induced insulin resistance in muscle cells. RSG could significantly improve glucose uptake by 0.4‐fold in myotubes treated with palmitate. Moreover, RSG could restore the phosphorylation of Akt in palmitate‐treated cells. These data suggest that RSG protects skeletal muscle cells against palmitate‐induced apoptosis and this effect appears to be mediated via the PPARγ‐dependent and PTP1B‐independent mechanisms. Copyright © 2014 John Wiley & Sons, Ltd.
PrP genotype frequencies in German breeding sheep and the potential to breed for resistance to scrapie

Genetic susceptibility to scrapie is associated with polymorphisms in three different codons of the ovine prion protein (PrP) gene (136, 154, 171). Studies of PrP genotypes linked to scrapie have revealed the resistance of homozygous PrPARR/PrPARR animals and the high risk of PrPvRQ/PrPvRQ and PrPvRQ/PrPARQ animals in scrapie-affected flocks. The selection of PrPAR/PrPAR genotypes may therefore provide a strategy for controlling clinical scrapie. The genotypes of 1361 German breeding sheep from 15 different breeds in northern Germany were determined. Apart from the wildtype allele PrPARQ, at least four mutually exclusive allelic variants were found. The greatest variability within the PrP gene was encountered in texel sheep, in which 14 PrP genotypes were found. In the important meat breeds, Suffolk, German whiteheaded mutton and German blackheaded mutton, the PrPARR allele was predominant, and in these breeds the breeding of scrapie-resistant pedigree flocks within four generations seems to be a feasible option. In the texel sheep, the German merino, the German milk and the German land sheep breeds, the frequency of the PrPARR allele was much lower, and in several breeds no homozygous rams were available for breeding purposes. In these breeds the breeding strategy would depend on the number of heterozygous rams available, but resistant pedigree flocks could be achieved within nine generations.
Multiphase level set algorithm for coupled segmentation of multiple regions. Application to MRI segmentation

Classic geometric active contour algorithms have the limitation of segmenting the image into only two regions: background and object of interest. A new multiphase level set algorithm for the segmentation of two or more regions of interest is proposed. This algorithm avoids by construction the presence of overlapped and void regions and no additional coupling terms are required. In addition, the number of iterations needed to reach convergence is small. The algorithm has been tested against a state-of-the-art multiphase method on both simulated and real Magnetic Resonance Imaging (MRI) volumes with favorable results.
Decision-Making and Problem-Solving Practices of Superintendents Confronted by District Dilemmas.

The purpose of this study was to determine the decision-making and problem-solving approaches most frequently used by school superintendents in two mid-western states when confronted with district dilemmas. The research replicated a study conducted by Polka, Litchka, Caizi, Denig and Mete (2011) in five Mid-Atlantic states. The survey used in both studies was based on the work of Tarter and Hoy (1998). Results between the two regions were compared and significant differences were found in how superintendents manage dilemmas and their preferences for making decisions. In addition, significant differences were found between male and female superintendents in the mid-western states.
An Economic Analysis of a Change in an Excise Tax

The authors present an example of the effect a change in the excise tax can have on retail gasoline prices. The findings provide support for standard economic theory, as well as provide a vehicle for illustrating some of the subtleties of the analysis, including the implicit assumptions regarding the implications for the buying and selling prices of middlemen.
Cervical Epithelial Brightness by Optical Coherence Tomography Can Determine Histological Grades of Cervical Neoplasia

Objective The study aimed to determine if the difference in cervical epithelium brightness, as measured by optical coherence tomography (OCT), has potential as a distinguishing characteristic of normal, low-grade, high-grade (cervical intraepithelial neoplasia 2+), and cancer histological findings. Materials and Methods Information from 476 women was available for analysis. Demographic information was collected through in-person interview. All participants were human papillomavirus positive and/or had abnormal cytological finding and underwent colposcopy or unaided visual inspection and examination by OCT by quadrant. All women had a minimum of 4 OCT-matched cervical biopsies and endocervical curettage. Two sample t tests were used to measure differences in OCT image brightness by histological grades. Results Mean OCT image brightness differed significantly between each preinvasive histological grade and invasive cancer (p < .01 for all comparisons). Brightness as measured by OCT was also able to differentiate between squamous metaplasia and cervical intraepithelial neoplasia 3/cancer; p values were . 004 and . 003, respectively. Conclusions Epithelial brightness is an important component of cervical epithelium diagnosis by OCT, and we plan to add it to our diagnostic mathematical algorithm in all future versions of OCT software.
Schwann cell lines derived from malignant peripheral nerve sheath tumors respond abnormally to platelet‐derived growth factor‐BB

Neurofibromatosis type 1 (NF1) is a genetic disease caused by the loss of neurofibromin, which can lead to formation of highly invasive malignant peripheral nerve sheath tumors (MPNST). We characterized platelet‐derived growth factor‐β (PDGF‐β) receptor expression levels and signal transduction pathways in NF1 MPNST cell lines and compared them with the expression of PDGF‐β receptors in normal human Schwann cells (nhSC). As examined by Western blotting, PDGF‐β receptor expression levels were similar in nhSC and NF1 MPNST cell lines. MAPK and Akt also were phosphorylated in both cell types to a similar degree in response to PDGF B chains (PDGF‐BB). However, increased intracellular calcium (Ca2+) levels in response to PDGF‐BB were observed only in the NF1 MPNST cell lines; nhSC did not show any increase in intracellular calcium when stimulated with PDGF‐BB. The calcium response in NF1 MPNST cell lines was blocked with thapsigargin, suggesting that the PDGF‐BB‐stimulated increases in intracellular calcium originated in the internal compartment of the cell rather than reflecting influx of calcium from the extracellular compartment. Calmodulin kinase II (CAMKII) is phosphorylated in response to PDGF‐BB in the NF1 MPNST cell lines, whereas no phosphorylation of CAMKII was observed in nhSCs. The decreased growth of NF1 MPNST cell lines after treatment with a CAMKII inhibitor is consistent with the view that aberrant activation of the calcium‐signaling pathway by PDGF‐BB contributes to the formation of MPNST in NF1 patients. © 2004 Wiley‐Liss, Inc.
Assessing SRI fund performance research: Best practices in empirical analysis

We review the socially responsible investment (SRI) mutual fund performance literature to provide best practices in SRI performance attribution analysis. Based on meta-ethnography and content analysis, five themes in this literature require specific attention: data quality, social responsibility verification, survivorship bias, benchmarking, and sensitivity and robustness checks. For each of these themes, we develop best practices. Specifically, for sound SRI fund performance analysis, it is important that research pays attention to dividend yields and fees, incorporates independent and third party social responsibility verification, corrects for survivorship bias and tests multiple benchmarks, as well as analyzing the impact of fund composition, management influences and SRI strategies through sensitivity and robustness analysis. These best practices aim to enhance the robustness of SRI financial performance analysis. Copyright (C) 2011 John Wiley & Sons, Ltd and ERP Environment.