Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of receptor tyrosine kinase signalling in HER-2-positive cells and trastuzumab (Herceptin) resistancein breast cancer

HER-2 gene amplification or overexpression occurs in approximately 25 % of breast cancers, and trastuzumab (Tmab) is a monoclonal antibody currently used to treat patients with HER-2-overexpressing breast cancer. Signalling through alternative receptor tyrosine kinases, such as insulin-like growth factor I receptor (IGF-IR), has been implicated in resistance to Tmab. The main aim of this study was to investigate mechanisms of resistance and in particular the role of IGF-IR in resistance to Tmab. Response to Tmab was analysed in a panel of HER-2-positive breast cancer cell lines; no correlation was found between HER-2, IGF-IR, EGFR expression or phosphorylation and response to Tmab. However, both HER-2 and phospho-HER-2 levels were found to correlate positively with phospho-IGF-IR levels (HER-2, p = 0.16; p-HER-2, p = 0.002). Tmab (T)-resistant cells showed reduced response to Tmab compared to parental cells. T-resistant BT474 have significantly elevated HER-2, phospho-HER-2, EGFR and phospho-EGFR levels compared to parental cells, while T-resistant SKBR3 cells have significantly elevated IGF-IR levels compared to parental cells (p = 0.026). Targeting IGF-IR with anti-IGF-IR siRNA or an IGF-IR tyrosine kinase inhibitor (TKI) (NVP-AEW541) inhibited the growth of both parental and T-resistant SKBR3 and BT474 cells. Combined treatment with Tmab and IGF-IR inhibitors also inhibited significantly more proliferation than single agents in T-resistant BT474 cells, and in parental and T-resistant SKBR3 cells. SKBR3 cells were conditioned in lapatinib (a dual HER-2/EGFR TKI), and the conditioned SKBR3-L cells showed significantly reduced response to lapatinib, and to Tmab, compared to parental SKBR3 cells. Phosphoproteomic analysis revealed alterations in the levels of a number of phosphoproteins in lapatinib resistant cells. HER-2 and IGF-IR expression were measured by immunohistochemistry in tissue microarrays (TMAs) of patient breast tumour samples. Membrane IGF-IR staining correlated inversely with HER-2 expression (p = 0.026). In conclusion, these data suggest that increased signalling through alternative RTKs may play a role in acquired resistance to Tmab. The combination of anti-IGF-IR therapies with Tmab may be clinically beneficial for patients with HER-2-positive breast cancer. We have identified a number of phosphoproteins with potential involvement in trastuzumab and/or lapatinib resistance, and further analysis of these targets may lead to novel therapeutic targets in HER-2-resistant breast cancer.
PREFORMULATION AND BIOLOGICAL EVALUATIONS FOR THE INTRAVAGINAL DELIVERY OF GRIFFITHSIN FOR HIV PREVENTION

HIV/AIDS persists as a global health concern, with the overwhelming majority of infections caused by sexual transmission. The lack of effective prevention modalities for women has prompted research of novel approaches to prevent disease spread. One such approach includes vaginal microbicides. The work presented within this dissertation project contributes significantly to the vaginal microbicide field, focusing on preformulation assessments, stability in the biological environment, and drug targeting of the biopharmaceutical microbicide candidate Griffithsin (GRFT). We hypothesized that GRFT will undergo physical and chemical instabilities that will affect successful formulation and vaginal delivery of this microbicide candidate. We further hypothesized that GRFT will undergo binding interactions within cervicovaginal secretions that will negatively impacting GRFT-gp120 binding and that GRFT will not be able to inhibit HIV binding to the DC-SIGN receptor and transfer to CD4 cells because GRFT will not permeate cervical tissue. Identification of degradation pathways for GRFT was conducted by performing preformulation experiments under selected conditions of temperature, light, shear, ionic strength, and oxidation. Analytical methods included HPLC, CD, UV-spectroscopy, ELISA, and SDS-PAGE. GRFT chemical modifications, including intact mass analyses and peptide sequencing, were evaluated in the presence of hydrogen peroxide and human cervicovaginal secretions. The effects of human cervicovaginal secretions on GRFT-gp120 binding was also assessed with ELISA. Tissue permeability and localization of GRFT was evaluated using excised human ectocervical tissue. Major findings from this dissertation indicate that: (1) GRFT is prone to oxidation, by both hydrogen peroxide exposure and human cervicovaginal secretion exposure; (2) Methionine at position 78 in the amino acid sequence of GRFT is oxidized; (3) GRFT-gp120 binding is inhibited in human cervicovaginal secretions containing normal microflora, but not in secretions with BV; and (4) GRFT does not permeate deep into or through human cervical tissue, but does adheres to the superficial epithelial tissue. Overall, this dissertation has created more knowledge about a drug candidate in the microbicide field and will guide further development of GRFT. Further, the methodologies implemented throughout this dissertation can be used or adapted as part of a strategy to preclinically evaluate other vaginal microbicide candidates.
Carbon emission: motivation to disclose

Reporting carbon emission is one of the crucial steps in to effectively managing carbon footprint and mitigating climate change. Countries around the world has been encouraging their private and government organizations to voluntarily disclose their carbon emissions with the absent of mandatory regulations. Reporting carbon footprint not only alert organizations of their contribution to climate change; but also provide the basis for the country in determining whether they can achieve their carbon emission reduction target and sustainable environment. In many countries, despite its voluntary reporting environment; previous studies have shown that numbers of organizations have produced carbon disclosures. On the other hand, despite the mandatory requirements, some companies (such as in the UK) do not disclose their carbon footprint data and practices. This situations suggests that there are more motivation factor other than regulation that pushing organizations to disclose carbon emission data. Hence, this paper aims to investigate the motivating factors that inspire and impact the organizations’ carbon disclosure behavior in voluntary and mandatory environment. The finding shows that image and reputation appear to be the key motivations of carbon disclosure, regardless of whether the regimen is voluntary or mandatory. In addition to that, no doubt that regulation requirements is one of the important reasons for disclosure in mandatory environment.
Institutional Support and Role in Increasing The Interdependence of Cocoa Farmers in Central Sulawesi Province

Indonesia is the third largest cocoa producer in the world after Ivory Coast and Ghana. Central Sulawesi is a center of Indonesian cocoa commodity, yet has low improvement. This is presumably due to the lack of support of farmer institutions that were formed not based on farmers' needs or the interests of farmers. The objectives of this study were to: (1) analyze the level of institutional support for cocoa farmers in Central Sulawesi Province, and (2) analyze the role and strategy of increasing institutional support for cocoa farmers in Central Sulawesi Province. The study was conducted in four districts in Central Sulawesi Province: Poso, Sigi, Morowali Utara and Donggala Regencies. The research sample was 380 farmers. To describe the research variables used descriptive statistical analysis in the frequency table and Duncan’s Multiple Range Test (DMRT). The results showed that most farmers (70.2%–98.7%) assessed that institutional support in the contexts of marketing, capital, processing, and technical guidance were relatively low so it tended to be less conducive to increasing farmers' independence. The institutional role of those four contexts was also low categoryzed (26.6–43.0) so that it needs serious attention in an effort to increase the weak independence of farmers.
Measuring Customer-Oriented Organizational Citizenship Behavior on the Employees of Railway Transportation Service Provider

This research aimed to describe Customer-Oriented Organizational Citizenship Behavior (CO-OCB) on the employees of the railway transportation service provider in Jakarta, Indonesia. A survey research was conducted by distributing the questionnaires to the employees and conducting a Focus Group Discussion (FGD). The sampling was taken by using a convenience sampling technique. The participants were 161 employees from different job levels. Consisting of managers, supervisors, and staff. Data analysis, the researchers used descriptive statistics analysis and inferential analysis with the Kruskal Wallis test by using Statistical Package for the Social Sciences software for Windows 21.0 and theme analysis. The results show that generally, the respondents have high COOCB. Then, the result of the inferential analysis shows that there are significant differences among CO-OCB. The dominant dimension shown by the employees is organizational compliance, followed by other dimensions such as sportsmanship, helping behavior, self-development, civic virtue, individual initiative, and organizational loyalty. The results also suggest that CO-OCB on the employees is influenced by individual characteristic factors like working attitude, and contextual factors.
Assessing the Consistency of Clinical Diagnosis and Ancillary Tests For Brain Death

Beyin ölümü için klinik tanı ve yardımcı testlerin tutarlılığı Öz Amaç: Beyin ölümü (BÖ), beyin ve beyin sapı işlevlerinin kalıcı yokluğunu ifade eder. Doğrulayıcı testler kullanılarak beyin sapı dışında bile tüm beyin bölgelerinde kan akışı olmadığı gösterilmelidir. BÖ tanısının uyumsuzluğunu klinik ve yardımcı testler (bilgisayarlı tomografik anjiyografi (BTA), manyetik rezonans görüntüleme anjiyografisi (MRIA), transkranial Doppler ultrasonografi (TKD-USG), elektroensefalografi (EEG)) ile değerlendirmeyi amaçladık. Yöntemler: 2012-2018 yılları arasında yoğun bakım ünitemize başvuran hastalar retrospektif olarak değerlendirildi. BÖ için 22 hasta değerlendirildi ve ayrıca 12 tanesinde, BÖ tanısında kesin tanı için yardımcı testler yapıldı. Tüm hastalar için demografik veriler, BÖ’nün nedenleri ve takipleri kaydedildi. Bulgular: On iki hastaya BÖ tanısı kondu. BÖ’ye neden olan nedenler intrakraniyal kanama, kardiyak arrest, intrakraniyal tümörler, pulmoner emboli, anevrizmal kanama, menenjit, subaraknoid kanama idi. Yaş ortalaması 40,86±15,62, ortalama APACHE II skoru 28,23±16,33 idi. Beyin ölümü 10 hastada klinik olarak teşhis edildi ve 12 hasta yardımcı testlerle değerlendirildi. Sonuç: Beyin ölümü klinik kriterlere göre teşhis edilebilir, ancak bir şekilde doğrulayıcı testler gerekli olabilir. BÖ’nün klinik olarak tanısı her zaman BTA ile tutarlı değildir ve tekrarlanması için prosedür gereklidir veya başka ileri teknikler kullanılmalıdır. Anahtar Sözcükler: Beyin ölümü, yardımcı tanı testleri, bilgisayarlı tomografik anjiyografi
Cochlear implantation for infants and children : advances

Preface. Contributors. Acknowledments. Introduction. Historical Perspectives. Biological Safety. The Melbourne Cochlear Implant Clinic Program. Preoperative Medical Evaluation. Preoperative Audiological, Speech, and Language Evaluation. Surgery. Engineering. Speech Processor Programming. Habilitation: Infants and Young Children. Habilitation: Shool-Age Children/Adolescents. Evaluation of Benefit: Infants and Children. Socio-economic and Educational Management Issues. Ethical Issues. Epilogue. Index.
Role of Medical Therapy in Chronic Mitral Regurgitation

Mitral regurgitation is one of the most commonly encountered valvular heart diseases in both the developing and the developed world. From various studies, it is known that chronic mitral regurgitation is associated with progressive left ventricular dysfunction, and eventually death if left untreated. This disease has a long silent period before symptoms manifest. During this latent period, left ventricular function progressively deteriorates and results in poor outcomes for patients even if surgery is performed. A few studies have evaluated the role of medical therapy in patients with chronic mitral regurgitation. This chapter will provide an overview of the use of medical therapy in chronic mitral regurgitation.
The Effect of Public Share Ownership on Tax Evasion: Study on Companies Listed in Indonesia Stock Exchange Between 2008-2011

Increasing the concentration of ownership and control of public companies in Indonesia is more likely to increase the likelihood of earnings management practices through tax avoidance. The high percentage of concentrated ownership has encouraged the government and capital market regulators to more broadly promote regulations related to tax incentives and public ownership in order to encourage more transparent practices. This study aims to analyze the policy of public ownership of tax avoidance conducted by Indonesian public companies, specifically after the regulation of Government Regulation No. 81 of 2007 concerning Reduction of Income Tax Rates for Domestic Corporate Taxpayers in the Form of Public Companies, and Minister of Financial Regulation No. 238 / PMK.03 / 2008 concerning Procedures for Implementing and Supervision of Granting Tariff Reductions for Domestic Corporate Taxpayers in the Form of Public Companies. More specifically, this study aims to analyze the impact of public share ownership on tax avoidance by Indonesian public companies. The samples of 320 observations that conducted (firm-years) during 2008-2011. The software that will be used in data analysis is STATA 12. The results showed that the increase in public ownership have a significant effect in improve the practice of corporate tax avoidance, which it is also evidenced by the significant differences in the corporate tax avoidance practices before than after the enactment of these regulations. The findings show that the greater the proportion of public share ownership would result the decreasing number of ETR or ETRC which can be indicated that the greater the practice of corporate tax avoidance. Furthermore, the ROA variable has a negative and significant effect on corporate tax avoidance practices, meaning that the greater the profitability ratio of a company can cause the reported and paid tax burden to decrease.
The Moderating Effects of Dividend Policy on the Impact of Financial Disclosure Towards Corporate Value: A Study of Listed Jordanian Industrial Firms

This study is primarily designed to examine the moderating effects of dividend policy on the impact of financial statement disclosure towards the corporate value of the Jordanian industrial companies listed in Amman Stock Exchange (ASE). In this study, the unit of analysis consist of 61 industrial firms, which is equivalent to 63% of the total number of Jordanian listed industries in ASE as at 2011. Therefore, secondary data was used, in which the data was collected from the annual financial reports disclosed by the selected industrial firms covering the period of 13 years from 2005 to 2017. Analysis was made through SPSS version 21 and SmartPLS version 3. Accordingly, findings of this study revealed that the total direct effects between the variables were positively significant at p-value 0.05. Moreover, the total contribution of the exogenous variables in the prediction of endogenous variable is 85%. Based on the findings, it is recommended that, Jordanian listed industrial firms should consider a full disclosure of their financial transaction since accountability and transparency attracts potential investors and creditors alike to pick interest in doing business with utmost financial security. It is recommended that the listed industrial firms of Jordanian should be given a maximum consideration to the indicators used in this study since the indicators were perfects to measure the variables under study for a better management decisions. Keywords: Dividend policy, Financial Disclosure, Corporate Value, Management Decisions DOI : 10.7176/RJFA/10-6-13 Publication date :March 31 st 2019
The Impact of Relationship Quality on Adoption Barrier Evaluation - An Explorative Study on B2B Networks for Commercialization

In order to enable an effective and efficient adoption of radical innovations in networks, science-based organizations should be aware of the challenges and resistance they may face within their network relationships, resulting from the interconnected structure of high-tech networks as well as the uncertain nature of their radical innovations. By analyzing how nuances of relationship quality influence the barriers of radical innovation adoption, this study contributes through the provision of a condensed and more focused approach to the fragmented and underresearched topic of B2B adoption barriers. The paper presents an explorative research approach with data gathered from multiple case studies, including published and unpublished articles, personal interviews and internet sources. An influence of relationship quality on adoption barrier evaluation has been confirmed. Further, details on how each barrier is influenced by relationship quality have emerged in the form of five proposals and have been further validated based on evidence from primary and secondary sources.
Critical Thinking Skills in Health Care Professional Students: A Systematic Review

Background and Purpose. The purpose of this systematic review is to determine if critical‐thinking skills in health care professional students change as a result of participating in a health care professional education program, and to assess the quality of the evidence evaluating this change. Method/Model Description and Evaluation. The study design was a systematic review. Six electronic databases were searched. Articles were graded using the Evaluation Guidelines for Rating the Quality of an Intervention Study. Outcomes. Eighteen articles were identified as meeting the inclusion criteria. Ten articles were identified in nursing, 5 in physical therapy and occupational therapy, 2 in pharmacy, and 1 in medicine. The scores on the Evaluation Guidelines for Rating the Quality of an Intervention Study ranged from 17 to 26 out of 48. The intraclass correlation of the 2 raters on the Evaluation Guidelines for Rating the Quality of an Intervention Study was 0.87. Eight studies in nursing, 2 studies in physical therapy, 1 study each in occupational therapy, pharmacy, and medicine showed statistically significant change in criticalthinking skills. Discussion and Conclusion. The evidence measuring the acquisition of criticalthinking skills in the fields of physical therapy, occupational therapy, pharmacy, and medicine is scarce. In nursing, although the majority of the studies support the acquisition of critical‐ thinking skills, none of the studies established appropriate sample size and statistical power analysis, and the cross‐sectional studies did not perform group matching beyond sex and age. In physical therapy, the results are mixed and the studies lack adequate statistical power. In occupational therapy, pharmacy, and medicine, the studies that showed a statistically significant increase in critical‐thinking skills had relatively small sample sizes and weak statistical power. There is a need for additional welldesigned studies looking at the acquisition of critical‐thinking skills in all health care fields.
Strategies to Improve Capacity for Policy Monitoring and Evaluation in the Public Sector

Scholars around the globe have contested the inadequate infrastructure and tools used by public sector agencies to monitor and evaluate public policies and programmes. Some of the urgent issues of concern deal with the inadequate human capacity in public agencies and departments to conduct fair and credible evaluations in the public sector. South Africa is not the only country that has adopted a government wide monitoring and evaluation system, other countries like Ghana, Kenya, Benin and Uganda have also endorsed formal monitoring and evaluation practice in the public sector. This article argues that monitoring and evaluation must not just measure the effectiveness and efficiency of public programmes and processes, but it must create a sustainable process whereby participants and evaluators can learn from the process. Capacity building in monitoring and evaluation must be fairly and continuous conducted to offer credible and valid information and knowledge on M&E by training agencies and institutions like universities. This theoretical paper adopted document analysis strategy to review and evaluate documents used as data source. Lessons learnt from this article contribute towards the existing strategies to enhance monitoring and evaluation.
Experimental Skin Graft In Hairless Descendants Of Mexican Hairless Dogs

In order to enhance the successful rate of skin transplantation, tie-over method and occlusive dressings were investigated using the skin of hairless dogs. Tie-over method had no accelerative effects of the skin grafting of hairless dogs. In contrast, at 2 weeks after grafting, the graft skin has taken well under the moist environment. The hydrocolloid dressing accelerated wound healing in the donor sites. In both the graft and the donor sites, wound contraction and crust formation were not found throughout the study, although the skin of hairless dogs lagged considerably behind that of other haired dogs in wound healing. At 2 weeks after the skin grafting, histologically, the epidermis of the grafts showed thickening and irregular hyperplasia with prominent rete ridges, suggesting a relatively high rate of cell proliferation and/or differentiation. In the dermis, the formation of granulation tissues was found, and neovascularization was obscure. At 4 weeks after skin grating, the epidermis remained thick and hair follicles with well-developed sebaceous glands were observed in some portions. In the donor sites, at 2 weeks after the treatment with hydrocolloid dressing, there was reepithelialization arising from the wound margin. In the dermis, dense granulation tissues containing many fibroblasts and collagen fibers were formed. At 4 weeks after the treatment, the regenerated skin exhibited a remarkable thickening of the epidermis, especially the granular layer, and well-developed rete ridges. These findings revealed that the treatment with the hydrocolloid dressing was a valuable measure in accelerating graft take and wound healing in the donor sites of hairless dogs.