Miracle-dz/UniFAR-FTUs huggingface dataset:
Cathepsin K mRNA and Protein Expression in Prostate Cancer Progression

Prostate cancer (CaP) is the most commonly diagnosed malignancy in men and is often associated with bone metastases, which cause much of the morbidity associated with CaP. Lesions associated with CaP generally exhibit increased bone formation and resorption. Increased bone resorption may release factors from the extracellular matrix that contribute to tumor growth. Cathepsin K (cat K) is a cysteine protease that exhibits strong degradative activity against the extracellular matrix and is involved in osteoclast‐mediated bone destruction. In this study, we analyzed the expression of cat K in CaP cell lines and patient samples. Cat K message was detected in CaP cell lines by reverse transcription‐polymerase chain reaction (RT‐PCR) and in primary CaP and metastases by in situ hybridization. Immunohistochemistry revealed variable expression of cat K in primary CaP samples, as well as nonosseous metastases, whereas expression in bone metastases was significantly higher than in primary CaP, and normal prostate tissues were negative. Cat K protein was detected in CaP cell lines by Western blotting after immunoprecipitation. Cat K enzymatic activity was also detected in CaP cell lines by a fluorogenic assay and by an assay for degradation of collagen type I. Increased levels of NTx, a marker of bone matrix degradation mediated primarily by cat K, were also detected in sera of patients with CaP bone metastases. We hypothesize that CaP‐expressed cat K may contribute to the invasive potential of CaP, while increased expression in bone metastases is consistent with a role in matrix degradation.
Enhancement of tumor uptake and therapeutic efficacy of EGFR‐targeted antibody cetuximab and antibody–drug conjugates by cholesterol sequestration

Cetuximab, a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR), has been intensively investigated as a promising cancer treatment strategy. The specific mechanism of cetuximab endocytosis and its influence on cetuximab uptake, biodistribution and efficacy still remain elusive. Recently, statins have been reported to synergize with EGFR‐targeting agents. Our prior work established that nystatin, a cholesterol‐sequestering antifungal drug, facilitates endocytosis via the clathrin‐dependent pathway. This study aimed to investigate whether nystatin regulates the uptake and efficacy of cetuximab and cetuximab‐based antibody–drug conjugates (cetuximab‐ADCs). In vitro and in vivo efficacies of nystatin on the uptake and activity of cetuximab/cetuximab‐ADCs were studied in multiple human carcinoma cell lines and xenograft models, respectively. We identified that cholesterol sequestration by nystatin enhanced cetuximab internalization in EGFR‐positive carcinoma cells by regulating EGFR trafficking/turnover and facilitating a switch from lipid rafts to clathrin‐mediated endocytosis. Combination treatment with cetuximab and nystatin selectively increased cetuximab uptake by tumor tissues, translating into potentiated antitumor efficacy of cetuximab in vivo (A431 and A549 tumors). Nystatin‐enhanced internalization of cetuximab further improved the uptake and potency of cetuximab‐doxorubicin and cetuximab‐methotrexate conjugates in EGFR‐positive cetuximab‐resistant tumors. Combination therapy with nystatin plus either cetuximab or cetuximab‐ADC further prolonged animal survival and significantly suppressed tumor growth, as compared with single‐agent cetuximab or cetuximab‐ADC. In summary, our results identify a novel mechanism whereby cholesterol sequestration enhances the uptake of EGFR‐targeting mAb and ADCs, therefore providing preclinical proof‐of‐concept that combination with nystatin can potentiate the delivery and efficacy of these EGFR‐targeted agents.
Preparation of 125I-labeled human growth hormone of high quality binding properties endowed with long-term stability.

125I-labeled human growth hormone (125I-labeled.hGH) was prepared by using two variants of the chloramine T labelling procedure and purified by polyacrylamide gel electrophoresis (PAGE) of the reaction mixture. Variant A produced a tracer with high specific activity (100 +/- 10 microCi/microgram), high maximal binding capacity to antibodies (93%) and long-term stability (at least 150 days at -20 degrees C). No diiodinated tyrosil residues could be detected in this tracer. Variant B was devised to obtain higher yields of labeled hormone. The electrophoresis of the iodination mixture revealed two radioactive components with Rm values of 0.49 and 0.55 which result from the iodination of hGH variants preexisting in the starting material. Both tracers had similar specific activities (70 +/- 10 microCi/microgram), high maximal binding capacity to antibodies or receptors (80-100%, after 80 days of their obtention) and high stability (at least 100 days at -20 degrees C). It is concluded that the iododerivatives of hGH obtained by either method are adequate to perform radioimmunoassay and receptor studies and have long-term stability.
Fuzzy predictive control based on Takagi-Sugeno model for nonlinear systems

In this paper, a method of designing a nonlinear predictive controller based on a fuzzy model of the system is presented. The Takagi-Sugeno fuzzy model is used as a powerful structure for representing nonlinear dynamic systems. So, the strategy of the fuzzy predictive control based on a fuzzy Takagi-Sugeno model is applied to the control of a chemical reactor. Indeed, the work is consists to develop, in a first step, a fuzzy model from a merger of a number of local models obtained by the principle of linearization around an operating point, or by learning through the gradient algorithm. In a second stage and basis on local models already developed, a fuzzy predictive control is synthesized with different approaches. The principal aim is to apply local generalized predictive control.
pH‐dependent uptake of irinotecan and its active metabolite, SN‐38, by intestinal cells

Irinotecan (CPT‐11) and its active metabolite, 7‐ethyl‐10‐hydroxycamptothecin (SN‐38), are believed to be reabsorbed by intestinal cells and to enter the entero‐hepatic circulation, but there is little information to date. Our objective was to investigate the intestinal transport of CPT‐11 and SN‐38 in correlation with their associated cytotoxicity. Using either isolated hamster intestinal epithelial cells or/and human colon carcinoma HT29 cells, the uptake rates of [14C]CPT‐11 and [14C]SN‐38, both as respective non‐ionic lactone form at acidic pH and anionic carboxylate form at basic pH, were investigated by the rapid vacuum filtration technique. The effect of physiologic intestinal luminal pH (6.2–8.0) on the uptake rate and cytotoxicity of SN‐38 were estimated by the above method and the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide (MTT) assay, respectively. The lactone forms of CPT‐11 and SN‐38 were transported passively, while the respective carboxylate form was absorbed actively. Uptake rates of both lactones were significantly higher than those of their carboxylates. Under physiologic pH, the respective uptake rates of CPT‐11 and SN‐38 were pH sensitive and decreased significantly by around 65%, at pH greater than 6.8. Furthermore, with decreasing pH, a higher uptake rate of SN‐38 into HT29 cells correlates with a greater cytotoxic effect (r = 0.987). CPT‐11 and SN‐38 have absorption characteristics of weakly basic drugs such as short‐chain fatty acids, suggesting that alkalization of the intestinal lumen may be critical to reduce their reabsorption and associated side effects. Int. J. Cancer 83:491–496, 1999. © 1999 Wiley‐Liss, Inc.
The embedded-agency approach to bank regulation: the case of Latin America

This working paper examines how and why four Latin American democracies —Argentina, Brazil, Chile and Mexico— have regulated commercial banks in the past three decades. The objective is to explain variation across countries and time in the regulatory regimes of the commercial bank sector, meaning government’s decisions about the levels of restrictions imposed on both the structure and the risk-management behavior of banks. It finds that traditional approaches to regulation – based on interests, ideology and institutions— are insufficient to elucidate the political economy of banking regulation in Latin America. In offering a new typological —the embeddedagency— approach to regulation, I argue that variation in bank regulatory regimes depends on the nature of the principal-agent (P-A) relationship among regulators and its interaction with what I call “conjunctural” determinants (i.e., systemic banking crises, international pressures and technological advances).
Stability of haemoglobin A1c (HbA1c) measurements from frozen whole blood samples stored for over a decade

Objective Haemoglobin A1c (HbA1c), a measure of long‐term glycaemic control, is at the centre of the clinical management of diabetes mellitus. However, the reproducibility of HbA1c measurements from whole blood samples which have been in long‐term storage is unknown. We undertook this study to assess the reproducibility of HbA1c measurements from whole blood samples that had been in storage at −70°C for over a decade.
Tinjauan Hukum Islam terhadap Musyawarah dalam Penyelesaian Sengketa Ekonomi Syariah

Musyawarah merupakan salah satu bentuk penyelesaian sengketa di luar pengadilan, mencakup segala sesuatu yang diambil dari orang termasuk pendapat. Sebagai langkah awal dalam menyelesaikan sengketa memberikan kemudahan bagi yang berperkara karena bersifat informal, sederhana dan fleksibel.Manfaat musywarah menggunakan biaya yang ringan, sengketa ekonomi syariah diselesaikan tanpa melibatkan pengadilan agama dan kemenangan didapatkan dari kedua belah pihak sehingga tetap terjalin silahturahmi.Musyawarah sangat dianjurkan dalam hukum Islam untuk mengakhiri pertikaian dan mengedepankan musyawarah dalam menyelesaiakan persoalan umat. Deliberation is one of the dispute resolutions out of the court, in terms of people including their opinions. As a first step in resolving the dispute is to put the litigants at ease as it is informal, simple and flexible.The benefits of deliberation are using a low cost, resolved without involving religious courts, and the victory is obtained from both parties with the result that the relationship continues.Deliberation is highly recommended in Islamic law to resolve the dispute and to prior the deliberation in solving the problems of the people.
The p38 mitogen‐activated protein kinase pathway is involved in the regulation of heme oxygenase‐1 by acidic extracellular pH in aortic smooth muscle cells

Extracellular acidosis (EA) regulates Heme Oxygenase‐1 (HO‐1) expression in vascular smooth muscle cells via transcriptional and posttranscriptional mechanisms but the signaling pathways involved are not known. We examined the role of Mitogen‐Activated Protein Kinase (MAPK) pathways in HO‐1 regulation by EA. Primary rat aortic smooth muscle cells were exposed to EA or physiologic pH. Levels of the total and phosphorylated forms of p38, extracellular signal‐regulated protein kinases1/2 (ERK1/2), c‐Jun N‐terminal kinases/stress‐activated protein kinases (JNK1/2), and HO‐1 protein were assessed by Western analysis and HO‐1 mRNA levels were assessed by quantitative PCR. Inhibition of p38 MAPK was achieved with the chemical inhibitor SB203580, or adenoviral infection of a dominant‐negative form of p38α. Phospho p38 MAPK activity was evaluated with an in vitro kinase activity assay. Binding of Activator Protein‐1 (AP‐1), a known target of MAPK pathways, was assessed by Electromobility shift assay (EMSA). EA induced phosphorylation of p38 MAPK in a biphasic manner while total p38 was unchanged. EA did not alter levels of phospho ERK 1/2 and phospho JNK 1/2. There was increased phospho p38 MAPK activity in the setting of EA which preceded the induction of HO‐1. Inhibition of phospho p38 activity with either SB20358 or a dominant negative p38α oligonucleotide abrogated the induction of HO‐1 by EA. Increased specific binding of AP‐1 in the setting of EA was shown by EMSA. Increased phospho p38 activity precedes and likely mediates HO‐1 induction by EA. Increased AP‐1 binding may underlie the transcriptional regulation of HO‐1 by EA. J. Cell. Biochem. 105: 1298–1306, 2008. © 2008 Wiley‐Liss, Inc.
A data-driven prognostics approach for RUL based on principle component and instance learning

The research of Remaining Useful Life (RUL) estimation is one of the most common tasks of Prognostics and Health Management (PHM). This paper presents a data-driven approach for estimating RUL using principle component and instance learning. The approach is especially suitable for situations in which abundant run-to-failure (RtF) data are available. Firstly, the principal component analysis (PCA) is used to find the low-dimensional principal components (PCs) from the statistical features of the measured signals. Then, the health indicators (HI) can be obtained by using weighted Euclid distance (WED), and regressed by the data-driven methods or model-based methods. Finally, the method based on instance learning is employed to estimate the RUL of the machine under operation. The performance of the prognostics approach introduced in this paper is demonstrated by using turbofan engine degradation simulation data set, which is supplied by NASA Ames.
The financial economy of Viet Nam in an age of reform, 1986–2016

Before the Doi Moi reforms in 1986, Viet Nam’s economy was devastated by 30 years of warfare with two major military powers, France and the US, ending in 1975. In the subsequent 10 years, Viet Nam suffered from failing economic experiments, including agricultural cooperatization, “industry-commerce rehabilitation,” price-wage-currency reform, among others, under the centrally planned mechanism (Wood 1989), as well as the international isolation and a US trade embargo when its troops entered Cambodia to overthrow the Khmer Rouge (Riedel and Turley 1999). Its per-capita gross domestic product (GDP) declined to USD 97 in 1989 whereas the ratio of external debt to GDP reached 330%. The economy languished and became one of the poorest in the world (VGP 2016). Things have since changed. With a population of 92 million, its GDP was USD 204 billion in 2015, after 30 years of socio-economic transitions. Doi Moi has enabled the marketization and internationalization of the economy, bringing about the fruits of the market (Dutta 1995; Riedel and Turley 1999), with the financial system facilitating the transformation (Siregar 1997). The banking system then had total assets of USD 307 billion, about 150% of GDP.
Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy

Background Allergen‐specific immunotherapy, subcutaneous immunotherapy (SCIT) or oral, has been used for almost a century to redirect inappropriate immune responses in atopic patients. A new mode of administration through the intact skin [epicutaneous immunotherapy (EPIT)], using an original epicutaneous delivery system, may represent an alternative to these classical methods.
Phenolic content and antioxidant activity of Pereskia grandifolia Haw. (Cactaceae) extracts

The leaves of Pereskia grandifolia Haw. (Cactaceae), commonly known as “Jarum Tujuh Bilah” in Malaysia, have been traditionally used as natural remedy in folk medicine by the locals. In the present study, the antioxidant potential of P. grandifolia crude methanol and its fractionated extracts (hexane, ethyl acetate and water) have been investigated, employing three different established testing systems, such as scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, reducing power assay and β-carotene method. The total phenolic content of the P. grandifolia extracts was also assessed by the Folin-Ciocalteau’s method. The ethyl acetate extract showed significantly the highest total phenolic content, DPPH scavenging ability and antioxidant activity in β-carotene bleaching assay while the hexane extract possessed significantly strongest reducing power. The data obtained in these testing systems clearly establish the antioxidant potency of P. grandifolia. As such, this is the first report on the antioxidant activities of P. grandifolia.
Enhancing the task performance of bank employees: relevance of trust, self-efficacy, and budget participation

This study investigates the extent to which participation in budgeting leverages task performance through trust and self-efficacy. To achieve the goal of this research, we conducted a survey involving the service industry, particularly among banks listed on the Indonesian stock exchange. We distributed questionnaires to bank employees and received 97 completed and usable responses. We performed SmartPLS statistical analysis and determined that the participation in the budgeting process, directly and indirectly, leverage task performance through self-efficacy. The result indicates that self-efficacy mediates between budget participation and task performance. However, trust does not stimulate the relationship between the two processes. This research contributes to the field of management accounting for the service sector and low-level employees.
Emergency Department Management of Patients With Febrile Neutropenia: Guideline Concordant or Overly Aggressive?

OBJECTIVES The Infectious Diseases Society of America and the American Society of Clinical Oncology recommend risk stratification of patients with febrile neutropenia (FN) and discharge with oral antibiotics for low-risk patients. We studied guideline concordance and clinical outcomes of FN management in our emergency department (ED). METHODS Our urban, tertiary care teaching hospital provides all emergency and inpatient services to a large comprehensive cancer center. We performed a structured chart review of all FN patients seen in our ED from January 2010 to December 2014. Using electronic medical records, we identified all visits by patients with fever and an absolute neutrophil count of <1000 cells/mm3 and then included only patients without a clear source of infection. Following national guidelines, we classified patients as low or high risk and assessed guideline concordance in disposition and parenteral versus oral antibiotic therapy by risk category as our main outcome measure. RESULTS Of 173 qualifying visits, we classified 44 (25%) as low risk and 129 (75%) as high risk. Management was guideline concordant in 121 (70%, 95% confidence interval [CI] = 63% to 77%). Management was guideline discordant in 43 (98%, 95% CI = 88% to 100%) of low-risk patients versus 9 (7%, 95% CI = 3% to 13%) of high-risk patients (relative risk [RR] = 14, 95% CI = 7.5 to 26). Of 52 guideline-discordant cases, 36 (83%, 95% CI = 72% to 93%) involved low-risk cases with treatment that was more aggressive than recommended. CONCLUSIONS Guideline concordance was low among low-risk patients, with management tending to be more aggressive than recommended. Unless data emerge that undermine the guidelines, we believe that many of these hospitalizations and parenteral antibiotic regimens can be avoided, decreasing the risks associated with hospitalization, while improving antibiotic stewardship and patient comfort.
A role for the Werner syndrome protein in epigenetic inactivation of the pluripotency factor Oct4

Werner syndrome (WS) is an autosomal recessive disorder, the hallmarks of which are premature aging and early onset of neoplastic diseases ( Orren, 2006 ; Bohr, 2008 ). The gene, whose mutation underlies the WS phenotype, is called WRN. The protein encoded by the WRN gene, WRNp, has DNA helicase activity ( Gray et al., 1997 ; Orren, 2006 ; Bohr, 2008 ; Opresko, 2008 ). Extensive evidence suggests that WRNp plays a role in DNA replication and DNA repair ( Chen et al., 2003 ; Hickson, 2003 ; Orren, 2006 ; Turaga et al., 2007 ; Bohr, 2008 ). However, WRNp function is not yet fully understood. In this study, we show that WRNp is involved in de novo DNA methylation of the promoter of the Oct4 gene, which encodes a crucial stem cell transcription factor. We demonstrate that WRNp localizes to the Oct4 promoter during retinoic acid‐induced differentiation of human pluripotent cells and associates with the de novo methyltransferase Dnmt3b in the chromatin of differentiating pluripotent cells. Depletion of WRNp does not affect demethylation of lysine 4 of the histone H3 at the Oct4 promoter, nor methylation of lysine 9 of H3, but it blocks the recruitment of Dnmt3b to the promoter and results in the reduced methylation of CpG sites within the Oct4 promoter. The lack of DNA methylation was associated with continued, albeit greatly reduced, Oct4 expression in WRN‐deficient, retinoic acid‐treated cells, which resulted in attenuated differentiation. The presented results reveal a novel function of WRNp and demonstrate that WRNp controls a key step in pluripotent stem cell differentiation.
Preferences and Ratings of Partner Traits in Female Survivors of Childhood Abuse With PTSD and Healthy Controls

There is growing empirical evidence for an association between childhood abuse (CA) and intimate partner violence (IPV) in adulthood. We tested whether revictimized survivors of severe to extreme severities of child sexual abuse (CSA) and severe severities of child physical abuse (CPA) differed from nonvictimized healthy controls in their trait preferences in intimate partners and their current mate choice. In a sample of 52 revictimized female patients with posttraumatic stress disorder (PTSD) after CSA/CPA and 52 female healthy controls, the validated Intimate Partner Preferences Questionnaire (IPPQ) was used to assess (a) the desirability of tenderness, dominance, and aggression traits in potential partners, and (b) the presence of these traits in their current intimate partners. Factors potentially associated with partner preference and mate choice, for example, chronicity of traumatic events and lower self-esteem, were explored. Our results showed that, in general, revictimized PTSD patients did not have a preference for dominant or aggressive partners. However, revictimized women displayed a significantly larger discrepancy than did healthy controls between their preferences for tenderness traits and their ratings of the presence of tenderness traits in their current partners. Our results indicated that revictimized patients had lower self-esteem values; however, these values were associated with higher demands for tenderness traits. Furthermore, our results revealed that compared with patients who experienced early-onset childhood abuse (CA), those who experienced later onset CA were more accepting of dominant traits in potential partners. Women who had experienced IPV rated their current partners to be overly dominant. A higher tolerance of dominance traits might increase the risk of IPV in a specific subgroup of abused women (women with a later onset of abuse experiences and experiences of IPV).