Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR) for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy

Geometric modelling of kink banding in laminated structures

An analytical model founded on geometric and potential energy principles for kink band deformation in laminated composite struts is presented. It is adapted from an earlier successful study for confined layered structures which was formulated to model kink band formation in the folding of geological layers. The principal aim is to explore the underlying mechanisms governing the kinking response of flat, laminated components comprising unidirectional composite laminae. A pilot parametric study suggests that the key features of the mechanical response are captured well and that quantitative comparisons with experiments presented in the literature are highly encouraging

Recategorization of Video Game Genres

While the categories that are typically used to discriminate games have been useful in the past, more recently game mechanics have become utilized by a wider range of games, leading to earlier definitions becoming a less valuable categorization tool. This paper attempts to provide various ways games could be classified by focusing on the types of emotions they evoke, the skills they require or their relations with personality or cognitive variables. A description of those categories and the challenge in using them to define games is outlined as well as five alternate methods that may help make distinctions between games clearer

Sigma1 Targeting to Suppress Aberrant Androgen Receptor Signaling in Prostate Cancer.

Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that treatment with a small-molecule Sigma1 inhibitor prevented 5α- dihydrotestosterone-mediated nuclear translocation of AR and induced proteasomal degradation of AR and ARV, suppressing the transcriptional activity and protein levels of both full-length and splice-variant AR. Consistent with these data, RNAi knockdown of Sigma1 resulted in decreased AR levels and transcriptional activity. Furthermore, Sigma1 physically associated with ARV7 and A

Warming Increases Pollen Lipid Concentration in an Invasive Thistle, with Minor Effects on the Associated Floral-Visitor Community

Climate warming is likely to change the ways in which plants interact with their insect mutualists, for example through changes in phytochemistry. In particular, this may have implications for the ways in which we manage noxious weeds, which may spread more quickly if they experience stronger mutualistic interactions. We grew the invasive nodding thistle, Carduus nutans, in two experimental treatments in the field: either passively warmed with open top chambers or at ambient temperatures. We collected pollen from thistles in each treatment and analysed the total protein, lipid, and carbohydrate content. We observed no difference in the pollen protein or carbohydrate content, but the total lipid content of the pollen was significantly higher in warmed plants. We conducted a total of 12.75 h of observations of putatively mutualistic, flower-visiting insects. In addition, we spent 4.17 h collecting bees that visited thistle inflorescences in the treatments, allowing us to identify them to species. We found a significant increase in the abundance of flower-visiting insects in the observations, but not bee abundance in collections. In addition, there was no treatment effect on the number of flower-visiting morphotypes in the observations, or bee species richness in the collections. However, a nonparametric test did identify a significant effect of warming on the composition of flower-visiting morphotypes in observations and bee species in collections. Overall, the warming treatment significantly increased lipid content of the pollen, but had relatively weak effects on insect visitation patterns. However, these effects may be amplified at larger spatial and temporal scales or higher temperatures

Predicting Dynamics of Aggregate Loafing Behavior in Glaucous-winged Gulls (Larus glaucescens) at a Washington Colony

Seabirds move throughout the day in changing, patchy environments as they engage in various behaviors. We studied the diurnal abundance dynamics of Glaucous-winged Gulls (Larus glaucescens) in a habitat patch dedicated to loafing in the Strait of Juan de Fuca, Washington. We constructed three differential equation models as alternative hypotheses and then used model selection techniques to choose the one that most accurately described the system. We validated the model on an independent data set, made a priori model predictions, and conducted a field test of the predictions. Clear dynamic patterns emerged in the abundance of loafing gulls, even though individuals moved in and out of the loafing area more or less continuously throughout the day. Temporal patterns in aggregate loafing behavior are predicted by three environmental factors: day of the year, height of the tide, and solar elevation. This result is important for several reasons: (1) it reduces the aggregate behavior of complicated vertebrates to a simple mathematical equation, (2) it gives an example of a field system in which animal abundances are determined largely by low dimensional exogenous forces, and (3) it provides an example of accurate quantitative prediction of animal numbers in the field. From the point of view of conservation biology and resource management, the result is important because of the pervasive need to explain and predict numbers of organisms in time and space

Effects of Spinal Fusion for Idiopathic Scoliosis on Lower Body Kinematics During Gait

Objectives The purpose of this study was to compare gait among patients with scoliosis undergoing posterior spinal fusion and instrumentation (PSFI) to typically developing subjects and determine if the location of the lowest instrumented vertebra impacted results. Summary of Background Data PSFI is the standard of care for correcting spine deformities, allowing the preservation of body equilibrium while maintaining as many mobile spinal segments as possible. The effect of surgery on joint motion distal to the spine must also be considered. Very few studies have addressed the effect of PSFI on activities such as walking and even fewer address how surgical choice of the lowest instrumented vertebra (LIV) influences possible motion reduction. Methods Individuals with scoliosis undergoing PSFI (n = 38) completed gait analysis preoperatively and at postoperative years 1 and 2 along with a control group (n = 24). Comparisons were made with the control group at each time point and between patients fused at L2 and above (L2+) versus L3 and below (L3–). Results The kinematic results of the AIS group showed some differences when compared to the Control Group, most notably decreased range of motion (ROM) in pelvic tilt and trunk lateral bending. When comparing the LIV groups, only minor differences were observed, and the results showed decreased coronal trunk and pelvis ROM at the one-year visit and decreased hip rotation ROM at the two-year visit in the L3– group. Conclusions Patients with AIS showed decreased ROM preoperatively with further decreases postoperatively. These changes remained relatively consistent following the two-year visit, indicating that most kinematic changes occurred in the first year following surgery. Limited functional differences between the two LIV groups may be due to the lack of full ROM used during normal gait, and future work could address tasks that use greater ROM

Deindividuation in Anonymous Social Media: Does Anonymous Social Media Lead to an Increase in Non-Normative Behavior?

This research presents several aspects of anonymous social media postings using an anonymous social media application (i.e., Yik Yak) that is GPS-linked to college campuses. Anonymous social media been widely criticized for postings containing threats/harassment, vulgarity and suicidal intentions. However, little research has empirically examined the content of anonymous social media postings, and whether they contain a large quantity of negative social content. To best understand this phenomenon an analysis of the content of anonymous social media posts was conducted in accordance with Deindividuation Theory (Reicher, Spears, & Postmes, 1995). Deindividuation Theory predicts group behavior is congruent with group norms. Therefore, if a group norm is antisocial in nature, then so too will be group behavior. In other words, individuals relinquish their individual identity to a group identity, while they are a part of that group. Since the application used in this study is limited to a radial distance around specific college campuses, we predicted the anonymous social media users would identify as students, and behave closer to the norms expected of a student. Our results confirm that while deindividuation did occur among the college students, it did not exceed what is considered normal behavior for the social identity of a student

The Development and Validation of a Universal Enjoyment Measure: The Enjoy Scale

For decades, the concept of enjoyment has been used to measure the psychological benefits of activities and has been shown to determine future behavior toward activities and objects of interest. However, there has been little consensus on the definition and dimensionality of enjoyment. This study introduced a new measure of enjoyment with scale development and validation reported. CFA and EFA findings from 1466 participants across 739 different activities were reported. The instrument developed measured enjoyment across activities, with demonstrated content validity, internal consistency, discriminant and convergent validity. The final 25-item version of the ENJOY scale is composed of 5 factors: pleasure, relatedness, competence, challenge/improvement, and engagement. Discussion of the ENJOY Scale places it within the conceptual framework of Self-Determination Theory

Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12.

Innate lymphoid cells (ILCs) are tissue-resident sentinels that are essential for early host protection from pathogens at initial sites of infection. However, whether pathogen-derived antigens directly modulate the responses of tissue-resident ILCs has remained unclear. In the present study, it was found that liver-resident type 1 ILCs (ILC1s) expanded locally and persisted after the resolution of infection with mouse cytomegalovirus (MCMV). ILC1s acquired stable transcriptional, epigenetic and phenotypic changes a month after the resolution of MCMV infection, and showed an enhanced protective effector response to secondary challenge with MCMV consistent with a memory lymphocyte response. Memory ILC1 responses were dependent on the MCMV-encoded glycoprotein m12, and were independent of bystander activation by proinflammatory cytokines after heterologous infection. Thus, liver ILC1s acquire adaptive features in an MCMV-specific manner