76 research outputs found
Transmission line design for a power distribution system at 20 kHz for aircraft
A low inductance, low characteristic impedance transmission line was designed for a 20 kHz power distribution system. Several different conductor configurations were considered: strip lines, interdigitated metal ribbons, and standard insulated wires in multiwire configurations (circular and rectangular cylindrical arrangements). The final design was a rectangular arrangement of multiple wires of the same gauge with alternating polarities from wire to wire. This offered the lowest inductance per unit length (on the order of several nanohenries/meter) and the lowest characteristic impedance (on the order of one Ohm). Standard multipin connectors with gold-plated elements were recommended with this transmission line, the junction boxes to be internally connected with flat metal ribbons for low inductance, and the line to be constructed in sections of suitable length. Computer programs for the calculation of inductance of multiwire lines and of capacitances of strip lines were developed
Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan
INTRODUCTION: Although breast carcinoma (BC) is the most common malignancy affecting Jordanian females and the affected population in Jordan is younger than that in the West, no information is available on its biological characteristics. Our aims in this study are to evaluate the expression of estrogen receptor (ER) and progesterone receptor (PR) and Her-2/neu overexpression in BC in Jordan, and to compare the expression of these with other prognostic parameters for BC such as histological type, histological grade, tumor size, patients' age, and number of lymph node metastases. METHOD: This is a retrospective study conducted in the Department of Pathology at Jordan University of Science and Technology. A confirmed 91 cases of BC diagnosed in the period 1995 to 1998 were reviewed and graded. We used immunohistochemistry to evaluate the expression of ER, PR, and Her-2. Immunohistochemical findings were correlated with age, tumor size, grade and axillary lymph node status. RESULTS: Her-2 was overexpressed in 24% of the cases. The mean age of Her-2 positive cases was 42 years as opposed to 53 years among Her-2 negative cases (p = 0.0001). Her-2 expression was inversely related to ER and PR expression. Her-2 positive tumors tended to be larger than Her-2 negative tumors with 35% overexpression among T3 tumors as opposed to 22% among T2 tumors (p = 0.13). Her-2 positive cases tended to have higher rates of axillary metastases, but this did not reach statistical significance. ER and PR positive cases were seen in older patients with smaller tumor sizes. CONCLUSION: Her-2 overexpression was seen in 24% of BC affecting Jordanian females. Her-2 overexpression was associated with young age at presentation, larger tumor size, and was inversely related to ER and PR expression. One-fifth of the carcinomas were Her-2 positive and ER negative. This group appears to represent an aggressive form of BC presenting at a young age with large primary tumors and a high rate of four or more axillary lymph node metastases
Use of mitogenic cascade blockers for treatment of C-Raf induced lung adenoma in vivo: CI-1040 strongly reduces growth and improves lung structure
BACKGROUND: Signaling networks promoting cell growth and proliferation are frequently deregulated in cancer. Tumors often are highly dependent on such signaling pathways and may become hypersensitive to downregulation of key components within these signaling cascades. The classical mitogenic cascade transmits stimuli from growth factor receptors via Ras, Raf, MEK and ERK to the cell nucleus and provides attractive molecular targets for cancer treatment. For example, Ras and Raf kinase inhibitors are already in a number of ongoing phase II and phase III clinical trials. In this study the effect of the Raf kinase inhibitor BAY 43-9006 and of the MEK inhibitor CI-1040 (PD184352) on a Raf dependent lung tumor mouse model was analyzed in detail. METHODS: We have generated a lung cancer mouse model by targeting constitutively active C-Raf kinase to the lung. These mice develop adenomas within 4 months of life. At this time-point they received daily intraperitoneal injections of either 100 mg/kg BAY 43-9006 or CI-1040 for additional 21 days. Thereafter, lungs were isolated and the following parameters were analyzed using histology and immunohistochemistry: overall lung structure, frequency of adenoma foci, proliferation rate, ERK activity, caspase-3 activation, and lung differentiation. RESULTS: Both inhibitors were equally effective in vitro using a sensitive Raf/MEK/ERK ELISA. In vivo, the systemic administration of the MEK inhibitor CI-1040 reduced adenoma formation to a third and significantly restored lung structure. The proliferation rate of lung cells of mice treated with CL-1040 was decreased without any obvious effects on differentiation of pneumocytes. In contrast, the Raf inhibitor BAY 43-9006 did not influence adenoma formation in vivo. CONCLUSION: The MEK inhibitor CI-1040 may be used for the treatment of Ras and/or Raf-dependent human malignancies
Development of Grb2 SH2 Domain Signaling Antagonists: A Potential New Class of Antiproliferative Agents
Aberrant signaling through protein-tyrosine kinase (PTK)-dependent pathways is associated with several proliferative diseases. Accordingly, PTK inhibitors are being developed as new approaches for the treatment of certain cancers. Growth factor receptor bound protein 2 (Grb2) is an important downstream mediator of PTK signaling that serves obligatory roles in many pathogenic processes. One of the primary functions of Grb2 is to bind to specific phosphotyrosyl (pTyr)-containing sequences through its Src homology 2 (SH2) domain. Agents that bind to the Grb2 SH2 domain and prevent its normal function could disrupt associated PTK signaling and serve as alternatives to kinase-directed inhibitors. Starting from the X-ray crystal structure of a lead peptide bound to the Grb2 SH2 domain, this review will summarize important contributions to these efforts. The presentation will be thematically arranged according to the region of peptide modified, proceeding from the N-terminus to the C-terminus, with a special section devoted to aspects of conformational constraint
Ethical Awareness, Ethical Judgment and Whistleblowing: A Moderated Mediation Analysis
This study aims to examine the ethical decision-making (EDM) model proposed by Schwartz (J Bus Ethics, doi:10.1007/s10551-015-2886-8,2016), where we consider the factors of non-rationality and aspects that affect ethical judgments of auditors to make the decision to blow the whistle. In this paper, we argue that the intention of whistleblowing depends on ethical awareness (EAW) and ethical judgment (EJW) as well as there is a mediation–moderation due to emotion (EMT) and perceived moral intensity (PMI) of auditors. Data were collected using an online surveywith 162 external auditors who worked on audit firms in Indonesia as well as 173 internal auditors working in the manufacturing and financial services. The result of multigroup analysis shows that emotion (EMT) can mediate the relationship between EAW and EJW. The nature of this relationship is more complex and then tested by adding moderating variables using consistent partial least squares approach. We found that EMT and PMI can improve the relationship between ethical judgments and whistleblowing intentions. These findings indicate that internal auditors are more likely to blow the whistle than external auditors; and reporting wrongdoing internally and anonymously are the preferred way of professional accountants to blow the whistle in Indonesia
How Does Moral Intensity Impact the Moral Judgments and Whistleblowing Intentions of Professional Accountants?
Moral intensity is the degree of feeling we have about the consequences of moral choices, similar, for example, to those perceived for crimes, from petty larceny to murder. Moral intensity is thought to increase moral sensitivity and judgment. Because the accounting professions require members to respond to accounting fraud with more sensitivity and intensity, we examine this response in 220 professional accountants (mostly Certified Public Accountants) under a controlled experiment using two different cases. We examine the first three parts of the Rest (1986) model including ethical evaluation, judgment, and intention to act. We measure moral intensity in the accountant’s perception of overall harm and societal pressure. As in prior research, we find that the degree of moral intensity may be contextual. We find that the ethical evaluations may become affected by perceived overall harm, and whistleblowing intentions by perceived societal pressure. However, in both cases, the professional’s judgments are most affected by moral intensity. Consistent with prior research, whistleblowing intentions may involve many other mitigating variables, such as audit reporting or non-audit reporting limited by codes of conduct. These findings relate to the increasing attention paid by the SEC to finding accounting fraud.
This manuscript makes three important contributions to the existing literature. First, there are few studies in this area and Jones (1991) identifies that moral intensity is issue contingent; therefore, replication studies using different scenarios are needed. Second, Bailey, Scott, and Thoma (2010) have suggested that accounting ethics research has focused too narrowly on Component II of Rest’s Four-Component Model. None of the previous studies looked at all three steps in Rest’s Model; therefore, our manuscript provides an important contribution over the other previous studies. Third, our sample uses professionals and not students as surrogates for professionals
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