1,304 research outputs found
Assets at risk:menstrual cycle variation in the envisioned formidability of a potential sexual assailant reveals a component of threat assessment
Abstract Situations of potential agonistic conflict demand rapid and effective deci-sion-making. The process of threat assessment includes assessments of relative fighting capacity, assessments of the likelihood of attack, and assessments of the extent to which one′s assets are at risk. The dimensions of physical size and strength appear to serve as key parameters in a cognitive representation summarizing multiple constituents of threat assessment. Here, we examine the thesis that this same representation summa-rizes asset risk. The fitness costs of sexual assault are in part a function of conception risk, as pregnancy due to assault compromises female choice and imperils existing and subsequent male investment. Prior research indicates that women′s attitudes and behaviors vary systematically across the menstrual cycle in a manner that would have reduced the likelihood of sexual assault during periods of greatest fertility in ancestral women. If the envisioned size and strength of a potential antagonist is used to represent asset risk, and if the threat that sexual assault poses to a woman′s reproductive assets is in part a product of her fertility, then the conceptualized size and strength of a potential sexual assailant should be a function of conception risk. We find support for thi
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The SMAC mimetic LCL-161 selectively targets JAK2V617F mutant cells.
Background:Evasion from programmed cell death is a hallmark of cancer and can be achieved in cancer cells by overexpression of inhibitor of apoptosis proteins (IAPs). Second mitochondria-derived activator of caspases (SMAC) directly bind to IAPs and promote apoptosis; thus, SMAC mimetics have been investigated in a variety of cancer types. particularly in diseases with high inflammation and NFĸB activation. Given that elevated TNFα levels and NFĸB activation is a characteristic feature of myeloproliferative neoplasms (MPN), we investigated the effect of the SMAC mimetic LCL-161 on MPN cell survival in vitro and disease development in vivo. Methods:To investigate the effect of the SMAC mimetic LCL-161 in vitro, we utilized murine and human cell lines to perform cell viability assays as well as primary bone marrow from mice or humans with JAK2V617F-driven MPN to interrogate myeloid colony formation. To elucidate the effect of the SMAC mimetic LCL-161 in vivo, we treated a JAK2V617F-driven mouse model of MPN with LCL-161 then assessed blood counts, splenomegaly, and myelofibrosis. Results:We found that JAK2V617F-mutated cells are hypersensitive to the SMAC mimetic LCL-161 in the absence of exogenous TNFα. JAK2 kinase activity and NFĸB activation is required for JAK2V617F-mediated sensitivity to LCL-161, as JAK or NFĸB inhibitors diminished the differential sensitivity of JAK2V617F mutant cells to IAP inhibition. Finally, LCL-161 reduces splenomegaly and may reduce fibrosis in a mouse model of JAK2V617F-driven MPN. Conclusion:LCL-161 may be therapeutically useful in MPN, in particular when exogenous TNFα signaling is blocked. NFĸB activation is a characteristic feature of JAK2V617F mutant cells and this sensitizes them to SMAC mimetic induced killing even in the absence of TNFα. However, when exogenous TNFα is added, NFĸB is activated in both mutant and wild-type cells, abolishing the differential sensitivity. Moreover, JAK kinase activity is required for the differential sensitivity of JAK2V617F mutant cells, suggesting that the addition of JAK2 inhibitors to SMAC mimetics would detract from the ability of SMAC mimetics to selectively target JAK2V617F mutant cells. Instead, combination therapy with other agents that reduce inflammatory cytokines but preserve JAK2 signaling in mutant cells may be a more beneficial combination therapy in MPN
The spiraling and spillover of misconduct: Perceived workplace bullying, subclinical psychopathy, and businesspersons’ recognition of an ethical issue
Workplace bullying can potentially spiral into numerous counterproductive behaviors and negative organizational outcomes. Therefore, the purpose of this study was to determine the degree to which increased perceptions of workplace bullying were associated with stronger expressions of (subclinical) psychopathic traits and weakened ethical decision making. Data were collected from national and regional samples of selling and business professions using a self-report questionnaire that contained relevant measures and an ethics scenario, and structural equation modeling was employed to investigate the proposed relationships. Findings indicated that perceived workplace bullying operated through psychopathy to influence the recognition of an ethical issue (or full mediation). The implications of these findings are discussed, along with the study’s limitations and suggestions for future research
Why we should not build autonomous robotic weapons
We discuss robotic weapons, their advantages and disadvantages, and their effect on the way humans wage war. We consider the factors favoring the development of lethal robotic weapons that can operate autonomously. We discuss the attempt to mitigate the dangers inherent in such weapons by means of an ethical controller implemented in software. We conclude that this is impossible to achieve and therefore that autonomous lethal robotic weapons should not be developed.Workshop: III Ethicomp latinoaméricaRed de Universidades con Carreras en Informática (RedUNCI
Testing the affiliation hypothesis of homoerotic motivation in humans:the effects of progesterone and priming
The frequency of homoerotic behavior among individuals who do not identify as having an exclusively homosexual sexual orientation suggests that such behavior potentially has adaptive value. Here, we define homoerotic behavior as intimate erotic contact between members of the same sex and affiliation as the motivation to make and maintain social bonds. Among both male and female nonhuman primates, affiliation is one of the main drivers of homoerotic behavior. Correspondingly, in humans, both across cultures and across historical periods, homoerotic behavior appears to play a role in promoting social bonds. However, to date, the affiliation explanation of human homoerotic behavior has not been adequately tested experimentally. We developed a measure of homoerotic motivation with a sample of 244 men and women. Next, we found that, in women (n = 92), homoerotic motivation was positively associated with progesterone, a hormone that has been shown to promote affiliative bonding. Lastly, we explored the effects of affiliative contexts on homoerotic motivation in men (n = 59), finding that men in an affiliative priming condition were more likely to endorse engaging in homoerotic behavior compared to those primed with neutral or sexual concepts, and this effect was more pronounced in men with high progesterone. These findings constitute the first experimental support for the affiliation account of the evolution of homoerotic motivation in humans
Behavior studies related to pesticides: Agricultural chemicals and Iowa agricultural-chemical dealers
The agricultural sector of the United States economy has long been recognized for its productive capacity and relative efficiency. This has resulted in abundant, high-quality, and relatively low-cost food and fiber. Many factors have made contributions to this phenomenon: adequate natural resources, research and resulting technology, the ready availability of this technology to farmers, available capital and labor, and the entrepreneurial ability of the American farmer to combine these resources efficiently.
One type of research and technology that has made a major contribution to the productive capacity and efficiency is that which relates to agricultural chemicals — pesticides for the control of insects, weeds, and diseases. The positive contribution of agricultural chemicals is generally accepted and can be validated. However, there is an expressed concern regarding the possible consequences of improper use of agricultural chemicals that might result in danger to the user, crops, livestock, aquatic and wildlife, and to the ultimate consumer of food products. In its extreme form this concern is expressed in terms of strict control or the abolition of the use of agricultural chemicals. Other proposals call for much stricter control over the clearance, sale, and use of chemicals
Establishment of performance-based seismic design factors for precast concrete floor diaphragms
This paper presents an analytical study used to establish design factors for a new seismic design methodology for precast concrete floor diaphragms. The design factors include diaphragm force amplification factors Ψ and diaphragm shear overstrength factors Ωv
Accuracy of Ultrasonography-Guided Fine-Needle Aspiration in Detecting Persistent Nodal Disease After Chemoradiotherapy
IMPORTANCE: Few patients with persistent adenopathy following chemoradiotherapy (CRT) for head and neck squamous cell carcinoma harbor viable disease. Improved selectivity for surgical salvage is needed to prevent unnecessary salvage neck dissection.
OBJECTIVE: To determine whether ultrasonography-guided fine-needle aspiration (FNA) can be used to identify viable cancer cells in the lymph nodes of patients with persistent radiographic adenopathy following CRT.
DESIGN, SETTING, AND PARTICIPANTS: A pilot study included patients undergoing preoperative ultrasonography-guided FNA of lymph nodes considered suspicious on radiography prior to planned neck dissection at a quaternary care facility from February 28, 2011, to March 18, 2013. Data analysis was performed from April 28 to December 24, 2013. Patients treated for head and neck squamous cell carcinoma with CRT who were determined to have persistent neck disease on a 6-week posttreatment computed tomographic scan of the neck and scheduled for salvage neck dissection were considered candidates for this pilot study. All patients enrolled in the study underwent ultrasonography-guided FNA of the suspicious lymph nodes within 2 weeks of the planned neck dissection. The cytopathologist reading the samples was blinded to the patient's identity.
EXPOSURES: Fine-needle aspiration with a 23- to 25-gauge needle following CRT.
MAIN OUTCOMES AND MEASURES: The accuracy of ultrasonography-guided FNA cytologic results was compared with the standard of surgical pathologic examination of neck dissection specimens.
RESULTS: Fourteen patients (11 [79%] men; mean [SD] age, 57.8 [11.2] years) were enrolled in this pilot study; data were collected on 17 lymph nodes. Among these 14 patients with incomplete radiographic clinical response, 17 lymph node aspirations were performed. Ultrasonography-guided FNA identified squamous cell carcinoma in the aspirates of 4 (80%) of the 5 nodes with squamous cell carcinoma identified on pathologic testing and confirmed the absence of disease in the remaining 12 (71%) lymph nodes. The statistical analysis of these results revealed a sensitivity of 80%; specificity, 100%; positive predictive value, 100%; and negative predictive value, 92.3%. The diagnostic accuracy of ultrasonography-guided FNA at detecting residual persistent cancer was 88%.
CONCLUSIONS AND RELEVANCE: This pilot study suggests that ultrasonography-guided FNA may be a feasible ancillary diagnostic imaging tool to imaging to assess patients with radiographic persistent disease prior to consideration of salvage neck dissection
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