Miracle-dz/UniFAR-FTUs huggingface dataset:
Incidence of BRAF p.Val600Glu and p.Val600Lys mutations in a consecutive series of 183 metastatic melanoma patients from a high incidence region

Aim: Approximately 40–60% of melanomas from Caucasian populations carry activating mutations in the BRAF oncogene, with the most common being the p.Val600Glu (V600E) hotspot mutation in exon 15. The aim of the present study was to investigate the frequency of the less common p.Val600Lys (V600K) mutation in metastatic melanoma from a high incidence region. Method: Dideoxy sequencing and fluorescent single strand conformation analysis were used to screen for mutations in exon 15 of BRAF in 183 cases of metastatic melanoma. Results: The overall incidence of BRAF mutation (89/183, 49%) was very similar to other large studies of Caucasian populations. However, the frequency of the p.Val600Lys mutation was higher than in most other studies and comprised almost one-third of all BRAF mutations in our cohort (27/89, 30%). Conclusion: BRAF p.Val600Lys mutations were present at a relatively high frequency in this cohort of metastatic melanoma patients (27/183, 15%). Assays used to screen for BRAF mutations in the clinic should be robust enough to detect the p.Val600Lys mutation, as this may have therapeutic implications.
Networks, Knowledge, and Niches: Competition in the Worldwide Semiconductor Industry, 1984-1991

The authors develop a conceptions of an organization-specific niche in a technological network. This niche is defined by two properties: crowding and status. The authors hypothesize that crowding suppresses and organization's life chances and that status enhances life chances, especially for those organizations in uncrowded niches. They operationalize this conception of the niche using patents and patent citations, and they find support for these hypotheses in an examination of technological competition in the worldwide semiconductor industry. In the conclusion, they compare these findings to earlier research and highlight some of the particular advantages of this conception of the niche.
Naming acronyms: The influence of reading context in skilled reading and surface dyslexia

Background: Within dual-route models of reading, words with regular spelling to sound correspondences can be read successfully using lexical or nonlexical reading processes. Research has indicated that which of these pathways is used is influenced by the other items that form the presentation context. Aims: We extend these findings using acronym stimuli as targets, presenting them in contexts designed to cue reading through grapheme–phoneme conversion or letter naming. Methods & Procedures: In Experiment 1, undergraduate participants (n = 30) read aloud stimuli presented onscreen. Response times and accuracy for target acronyms ambiguous in their print to pronunciation conversion (e.g., HIV versus NASA) were compared between two contexts. In one condition, the majority of items were unambiguous acronyms (e.g., BBC). In the second condition, the nontarget items were regular words (e.g., CAT). Experiment 2 administered the same reading task to a single case of semantic dementia. Outcomes & Results: A significant interaction between presentation context and acronym pronunciation was observed, such that responses were faster and more accurate to items that were pronounced in the same way as the majority of other stimuli in the list. Similar, though more dramatic, context effects were observed in a case of semantic dementia. Conclusions: We argue that context effects are pervasive in reading research and that presentation context should be considered when interpreting future findings, particularly in cases of aphasia and dyslexia.
An Investigation of Traditionality as a Moderator of Reward Allocation

The authors hypothesized that group members' perceptions of group cohesion would affect their tendency to allocate equally to other members in their group and to make egocentric self-allocations. They also posited that individuals' adherence to Chinese traditional values (or traditionality) would moderate these relationships. Two hundred sixty Hong Kong undergraduate students were assigned to groups of five to eight members to complete two in-class projects. The students evaluated peer contributions to the projects and allocated contribution points to themselves and other members in the group. The contribution points formed part of the final grade assigned to the students. The authors found that traditionality moderates the relationship between perceptions of cohesion and deviations from equality when making allocations to their peers. Results are discussed in terms of their implications for the study of reward allocations in groups and for the concept of traditionality in Chinese contexts.
Can Imitation in Pigeons be Explained by Local Enhancement Together with Trial-and-Error Learning?

Zentall Sutton and Sherburne (1996) reported that pigeons observing a conspecific demonstrator either step on or peck at a treadle to obtain food subsequently showed a significant tendency to manipulate the treadle as had their demonstrator Zentall et al suggested this finding showed observer pigeons had learned by imitation to peck at or step on the treadle However, the same result might have been obtained if pigeons had learned to step on the treadle by trial and error, and pigeons exposed to a treadle-pecking demonstrator had come to peck at the treadle as a result of nonimitative social-learning processes such as local enhancement or contagion Here we report the results for two control groups showing that pigeons do not learn to step on or peck at a treadle for food reward unless they observe a relevant demonstrator These results considerably strengthen the original conclusion Future research using the two action method to demonstrate imitative learning should include similar controls
Silver(I), Mercury(II), Cadmium(II), and Zinc(II) Target Exposed Enzymic Iron-Sulfur Clusters when They Toxify Escherichia coli

ABSTRACT The toxicity of soft metals is of broad interest to microbiologists, both because such metals influence the community structures in natural environments and because several metals are used as antimicrobial agents. Their potency roughly parallels their thiophilicity, suggesting that their primary biological targets are likely to be enzymes that contain key sulfhydryl moieties. A recent study determined that copper poisons Escherichia coli in part by attacking the exposed [4Fe-4S] clusters of dehydratases. The present investigation sought to test whether other soft metals also target these enzymes. In vitro experiments revealed that low-micromolar concentrations of Ag(I) and Hg(II) directly inactivated purified fumarase A, a member of the dehydratase family. The enzyme was also poisoned by higher levels of Cd(II) and Zn(II), but it was unaffected by even millimolar concentrations of Mn(II), Co(II), Ni(II), and Pb(II). Electron paramagnetic resonance analysis and measurements of released iron confirmed that damage was associated with destruction of the [4Fe-4S] cluster, and indeed, the reconstruction of the cluster fully restored activity. Growth studies were then performed to test whether dehydratase damage might underlie toxicity in vivo. Barely toxic doses of Ag(I), Hg(II), Cd(II), and Zn(II) inactivated all tested members of the [4Fe-4S] dehydratase family. Again, activity was recovered when the clusters were rebuilt. The metals did not diminish the activities of other sampled enzymes, including NADH dehydrogenase I, an iron-sulfur protein whose clusters are shielded by polypeptide. Thus, the data indicate that dehydratases are damaged by the concentrations of metals that initiate bacteriostasis.
Assessment of the periodontal health and community periodontal index in the Army of Serbia.

BACKGROUND/AIM Promotion of oral health in military population is not only a significant component of general health, but also of the military readiness and represents the strategic orientation of each country. The basic task of military dentistry is to provide oral health of military personnel and to enable their operational readiness at the optimal level. The aim of the study was to assess the periodontal condition in Serbian military population using the community periodontal index of treatment needs (CPITN), and the influence of general life habits and local risk factors on periodontal health. METHODS This prospective cross-sectional pilot study was conducted on 101 examinees at the mean age of 38.94 ± 11.63 years who had dental check-ups at the Dental Clinic of the Military Medical Academy in Belgrade. All the categories of military personnel aged 20-64 years were divided into five groups. The frequency distribution of general and local factors on periodontal health, oral hygiene index, and the assessment of the mean number of sextants by CPITN compared to age were examined. RESULTS The examinees at the age of 51-60 years had the best oral hygiene index (0.95 ± 0.65), whereas the oldest population had the worst (1.63 ± 0.42). Only one person (5.6%) at the age group of 51-60 years had a completely healthy periodontium. Observed in relation to the age groups, the mean values of sextants increased linearly, but in general population, the most frequent CPITN categories were in sextant with the periodontal pockets 4-5 mm (score 3). CONCLUSIONS Compared to the results from other countries shown by the World Health Organization, the periodontal condition in our examinees is below the average. The appropriate preventive program preparation and its implementation are needed, including primarily the appropriate training on oral hygiene, as well as education based on periodontal disease prevention and treatment.
WORKPLACE BULLYING AND SLEEP QUALITY: THE MEDIATING ROLE OF WORRY AND NEED FOR RECOVERY

Several studies have documented the link between exposure to bullying at work and several health problems. However, little is known about the mechanisms underpinning the relationship between bullying and its associated consequences. The aim of this study has been to test a model of mediation whereby need for recovery and worry as indicators of cognitive activation were assumed to influence the relationship between workplace bullying and sleep quality. The sample consisted of 4068 Belgium employees from approximately 30 organisations. The hypotheses were tested following a confirmatory approach involving structural equation modelling. Since the size of the sample is large, two different randomly selected samples of the dataset have been used to test the stability of the theoretical model. A full mediation model, in which need for recovery and worry mediated the relationship between workplace bullying and lack of sleep quality, yielded the best fit to the data in both samples. The results of this study underline the relevance of cognitive activation in understanding sleep disturbances.
Combinational Therapy Enhances the Effects of Anti-IGF-1R mAb Figitumumab to Target Small Cell Lung Cancer

Background Small cell lung cancer (SCLC) is a recalcitrant malignancy with distinct biologic properties. Antibody targeting therapy has been actively investigated as a new drug modality. Methods We tested the expression of IGF-1R and calculated the survival in 61 SCLC patients. We also evaluated the anti-tumor effects of anti-IGF-1R monoclonal antibody Figitumumab (CP) on SCLC, and tried two drug combinations to improve CP therapy. Results Our clinical data suggested that high IGF-1R expression was correlated with low SCLC patient survival. We then demonstrated the effect of CP was likely through IGF-1R blockage and down-regulation without IGF-1R auto-phosphorylation and PI3K/AKT activation. However, we observed elevated MEK/ERK activation upon CP treatment in SCLC cells, and this MEK/ERK activation was enhanced by ß-arrestin1 knockdown while attenuated by ß-arrestin2 knockdown. We found both MEK/ERK inhibitor and metformin could enhance CP treatment in SCLC cells. We further illustrated the additive effect of metformin was likely through promoting further IGF-1R down-regulation. Conclusion Our results highlighted the potential of anti-IGF-1R therapy and the adjuvant therapy strategy with either MEK/ERK inhibitor or metformin to target SCLC, warranting further studies.
Youth Development in After-School Leisure Activities

Leisure activities that occur outside of the school hours may facilitate positive youth development.The experiences of youth in three categories of activities (basketball and football, other sports, and nonsports) are examined in this study. Based on prior research, it is hypothesized that students participating in basketball and football will experience more negative outcomes (i.e., problem behaviors, fewer positive peer influences, and lower academic achievement). Furthermore, specific experiences in these leisure activities are explored as potential mediators of the effects of participation. Results indicate that basketball and football participation is related to more negative experiences and outcomes, but these differences reflect selection of more at-risk youths into these activities. Implications of the findings are discussed.
Moral Discrepancy and Political Discourse: Accountability and the Allocation of Blame in a Political News Interview

During the course of this article we intend to explore some issues surrounding government policy and actions and the moral organisation of political discourse surrounding the recent enquiry into the BSE crisis and the publication of the Phillips Report in the UK. More specifically, we wish to develop the concept of moral discrepancy and it's use in politically accountable settings, in this case the political interview. The paper, through the use of membership categorisation analysis, explores issues surrounding the social organisation of interview settings, the discursive management of policy decisions and ‘bureaucratic mistakes’ and the allocation of blame in situated media/political formats. The paper then relates these issues to notions of democracy-in-action, public ethics and the respecification of structure and agency as a members phenomenon.
Unconditional positive regard reconsidered

Unconditional positive regard is re-examined in the light of theory and practice in an attempt to understand how it operates. The communication of unconditional positive regard is a major curative factor in any approach to therapy; congruence and empathy merely provide the context in which it is credible. It is possible to demonstrate acceptance in a manner apparently conflicting with the client's frame of reference and for it still to effect positive change. The limiting factor in the effectiveness of counselling and psychotherapy is the extent to which the therapist is able perceptibly to extend unconditional positive regard to the client.
Women and sport leadership: perceptions of Malawi women educated in sport business leadership.

Traditional beliefs, cultural expectations and attitudes regarding the position of women in society still exist in the sub-Saharan African patrimonial society. Gender inequality in Africa’s regional and national sport organisations and governance structures is a reality and empirical work on women in sport leadership is lacking. This qualitative investigation is embedded in social constructivism as conceptual framework, which attempted to explore the perceived effect of a sport leadership education program in Malawi. The effect of leadership education is contextually perceived and although the challenge to integrate African leadership and traditional western leadership models is recognised, it was not the aim of this study. The study aimed to understand the leadership experiences of females in a Malawi sport context and sought to reveal if sport leadership development initiatives like this are expected to be merely opportunities to transfer knowledge or if it could affect the self-worth and “voice” of female sport leaders in Malawi. Findings suggest that completing the sport leadership education programme positively affected not only individual self-worth but also the collective voice of female sport leaders. It is proposed that similar courses are expanded and introduced to other sub-Saharan African countries and to research the perceived effect. Key words : Sport leadership education; Gender inequality; Sub-Saharan Africa.
Poor durability of lamivudine effectiveness despite stringent cessation criteria: A prospective clinical study in hepatitis B e antigen‐negative chronic hepatitis B patients

Background and Aims: Lamivudine, a nucleoside analog, is commonly used for treatment of chronic hepatitis B (CHB) but its durability of effectiveness after withdrawal is still uncertain. This study was designed to assess the durability of lamivudine treatment with stringent cessation criteria in hepatitis B e antigen (HBeAg)‐negative patients and to explore potential predictive factors.
Tissue‐Selective Effects of Injected Deoxycholate

BACKGROUND Recent studies suggest that the principal active ingredient in phosphatidylcholine‐containing injectable fat‐reduction formulations is actually deoxycholate (DC). This bile acid acts as a detergent to rapidly disrupt cell membranes. Thus, it is not obvious why DC would preferentially target fat. OBJECTIVE To investigate possible mechanisms for the selectivity of DC for fat tissue using in vivo and in vitro models. METHODS AND MATERIALS Histology, drug distribution studies, and cell viability assays were used to examine possible mechanisms contributing to DC selectivity. RESULTS In vitro, DC caused the lysis of all cell types tested within the tested concentration range. DC injected into fat tissue caused adipocyte death, whereas other cell types appeared less affected. Physiological concentrations of albumin or protein‐rich tissues decrease the ability of DC to lyse cells. Furthermore, DC relocated to the gastrointestinal tract in animals within hours of injection. This suggests that similar mechanisms may be present in humans. CONCLUSION We report observations that provide a possible explanation for the in vivo preferential fat targeting by DC. Fat tissue, being deficient in cell‐associated proteins and interstitial albumin, may be unable to sufficiently neutralize the detergent activity of DC, possibly making fat uniquely sensitive to DC. This study was funded by a grant from Kythera. Drs. Bentow and Knopp are consultants for Kythera, and Nadir Mahmood and Nathaniel David are employees of Kythera.
The Effects of a Technology Delivered Self-Monitoring System and Video Self Modeling on the Disruptive Behavior of Adolescents with Autism

Many students with autism demonstrate a variety of school based challenges, including complex and disruptive behaviors. Given these challenges, and the increases in prevalence widely reported for this population, teachers are in need of effective and efficient interventions to ameliorate the many difficulties faced by students with autism. Self-monitoring and video-based modeling are interventions with empirical support for individuals with ASD to decrease behaviors that are incompatible with successful outcomes. However, there is limited evidence regarding their utility at decreasing these challenging behaviors, when delivered via a mobile technology device. This study evaluated the functional relationship between I-Connect, a technology-delivered self-monitoring application on a smartphone, and decreases in the level of disruptive behavior for three students with ASD in the school setting utilizing a multiple-baseline design with an across participants. It also evaluated the combined effects of a video-self monitoring intervention delivered via the same device on the disruptive behavior of four adolescents with autism in school settings. Results and implications for practice and future research are discussed. iv
The role of the local environment of engineered Tyr to Trp substitutions for probing the denaturation mechanism of FIS

Factor for inversion stimulation (FIS), a 98‐residue homodimeric protein, does not contain tryptophan (Trp) residues but has four tyrosine (Tyr) residues located at positions 38, 51, 69, and 95. The equilibrium denaturation of a P61A mutant of FIS appears to occur via a three‐state (N2 ⇆ I2 ⇆ 2U) process involving a dimeric intermediate (I2). Although it was suggested that this intermediate had a denatured C‐terminus, direct evidence was lacking. Therefore, three FIS double mutants, P61A/Y38W, P61A/Y69W, and P61A/Y95W were made, and their denaturation was monitored by circular dichroism and Trp fluorescence. Surprisingly, the P61A/Y38W mutant best monitored the N2 ⇆ I2 transition, even though Trp38 is buried within the dimer removed from the C‐terminus. In addition, although Trp69 is located on the protein surface, the P61A/Y69W FIS mutant exhibited clearly biphasic denaturation curves. In contrast, P61A/Y95W FIS was the least effective in decoupling the two transitions, exhibiting a monophasic fluorescence transition with modest concentration‐dependence. When considering the local environment of the Trp residues and the effect of each mutation on protein stability, these results not only confirm that P61A FIS denatures via a dimeric intermediate involving a disrupted C‐terminus but also suggest the occurrence of conformational changes near Tyr38. Thus, the P61A mutation appears to compromise the denaturation cooperativity of FIS by failing to propagate stability to those regions involved mostly in intramolecular interactions. Furthermore, our results highlight the challenge of anticipating the optimal location to engineer a Trp residue for investigating the denaturation mechanism of even small proteins.
Non-parametric context-based object classification in images

Segmentation and classification of objects in images is one of the most important and yet one of the most complex problems in computer vision. Many different things contribute to the complexity of this problem, but amongst those that are most significant are variations in object appearance due to various perspectives, changes in scene illumination and typically a large number of partially occluded objects in a scene. Humans have the ability to successfully deal with these complications and to recognize objects in scenes without seemingly much effort. However, to aid their recognition process, humans use different sources of information such as previous experiences, context of objects placed in a scene and rules learned in the past that suggest how the physical world should appear and behave. Computer vision is trying to replicate the same strategies used by human vision and apply them to computer systems with the aim of improving typical tasks of detection, localization and classification of image objects. In this work we propose a new model for natural image object classification using contextual information at the level of image segments. Context modeling is largely independent of appearance-based classification and proposed model enables simple upgrade of existing systems with information from global and/or local context. Context modeling is based on non-parametric use of appearance-based classification results which is a novel approach compared to previous systems that model context on a limited number of rules expressed with a fixed set of parameters. Model implementation resulted in a system that, in our simulations, showed stable improvement of the appearance-based object classification. DOI: http://dx.doi. org/10.5755/j01.itc. 46.1. 13610