Miracle-dz/UniFAR-FTUs huggingface dataset:
Vorinostat and Sorafenib Synergistically Kill Tumor Cells via FLIP Suppression and CD95 Activation

Purpose and Design: Mechanism(s) by which the multikinase inhibitor sorafenib and the histone deacetylase inhibitor vorinostat interact to kill hepatic, renal, and pancreatic adenocarcinoma cells has been defined. Results: Low doses of sorafenib and vorinostat interacted in vitro in a synergistic fashion to kill hepatic, renal, and pancreatic adenocarcinoma cells in multiple short-term viability (24-96 h) and in long-term colony formation assays. Cell killing was suppressed by inhibition of cathepsin proteases and caspase-8 and, to a lesser extent, by inhibition of caspase-9. Twenty-four hours after exposure, the activities of extracellular signal-regulated kinase 1/2, AKT, and nuclear factor-κB were only modestly modulated by sorafenib and vorinostat treatment. However, 24 h after exposure, sorafenib- and vorinostat-treated cells exhibited markedly diminished expression of c-FLIP-s, full-length BID, BCL-2, BCL-XL, MCL-1, XIAP, increased expression of BIM, and increased activation of BAX, BAK, and BAD. Expression of eIF2α S51A blocked sorafenib- and vorinostat-induced suppression of c-FLIP-s levels and overexpression of c-FLIP-s abolished lethality. Sorafenib and vorinostat treatment increased surface levels of CD95 and CD95 association with caspase-8. Knockdown of CD95 or FADD expression significantly reduced sorafenib/vorinostat-mediated lethality. Conclusions: These data show that combined exposure of epithelial tumor cell types to sorafenib and vorinostat diminishes expression of multiple antiapoptotic proteins and promotes activation of the CD95 extrinsic apoptotic and the lysosomal protease pathways, and that suppression of c-FLIP-s expression represents a critical event in transduction of the proapoptotic signals from CD95 to promote mitochondrial dysfunction and death.
Tracking Wildebeest, Locating Knowledge: Maasai and Conservation Biology Understandings of Wildebeest Behavior in Northern Tanzania

In this paper I argue for building dialogues between scientific and Maasai knowledge articulations, utilizing knowledge of wildebeest as an example. By locating Maasai and scientific knowledges regarding a particular subject (wildebeest) in relation to each other—in discourse and in practice—my intention is to create the space for their active engagement. I strive to (1) expose the situatedness, strengths, and weaknesses of both Maasai knowledge and scientific knowledge, and (2) illustrate the conditions within which collaborative dialogues can be constructed between the situated knowledges or knowledge spaces embodied by Maasai and conservation scientists. In doing so I hope to contribute to a shift in theoretical debates regarding knowledge integration for natural-resource management, away from ‘building bridges’ and towards the building of dialogues.
Need for Cognition Moderates Responses to Framed Smoking-Cessation Messages 1

Smoking-cessation messages usually emphasize the costs of continuing to smoke (lossframed). However, prospect theory suggests that messages that instead emphasize the benefits of quitting smoking (gain-framed) could be more effective than loss-framed messages because smoking cessation is likely viewed as a cancer-prevention behavior with a certain rather than a risky outcome. In this study, smokers at public events read brochures containing brief gainor loss-framed smoking-cessation messages. The influence of framing was moderated by participants’ need for cognition (NFC). Individuals lower in NFC had greater intention to quit after reading a gain-framed message than after reading a lossframed message—a finding consistent with our predictions—whereas framing did not affect the persuasiveness of messages among people higher in NFC.
Arthroscopic Treatment of Osteochondral Lesions of the Tibial Plafond

Background: Osteochondral lesions of the distal tibial plafond (OLTPs) are an uncommon problem. The purpose of this study was to evaluate clinical outcomes following arthroscopic treatment of OLTPs. Methods: Retrospective chart review was performed on all patients treated arthroscopically for OLTPs. Treatment consisted of generalized synovectomy followed by curettage of the lesion and microfracture. If a cartilage cap was intact, antegrade drilling was performed. Cystic defects were treated with curettage of the cyst and filling of any defect with bone graft. Results: A total of 13 patients were included. Nine patients had isolated lesions, while four had lesions of the distal tibial plafond and talar dome. Average followup was 156 (range, 38 to 402 ± 117.9) weeks and average patient age was 32.9 (range, 14 to 50 ± 11.8) years. Eleven of 13 patients were available for followup modified AOFAS score. The average preoperative score was 35.2 (range, 24 to 49 ± 7.1). The average postoperative modified AOFAS score was 50.4 (range, 33 to 56 ± 7.6). There were four patients (30.8%) with a poor outcome. Conclusion: OLTPs can be challenging to treat. Arthroscopic treatment can lead to improved outcomes. However, the higher incidence of poor outcomes in our series may indicate less predictability in the treatment of OLTPs and that outcomes may not be equivalent to previous reported studies on OLTPs or osteochondral lesions of the talus. Level of Evidence: IV, Retrospective Case Series
Solid-Waste Recycling Behavior and Support for Curbside Textile Recycling

This study examines determinants of residents' support for a curbside textile-recycling policy in southern Nevada. Based on the existing solid-waste recycling behavior literature and 817 responses to a mail survey of the residents, a model for support of curbside textile-recycling policy is developed. The model is empirically tested, using univariate analyses such as chi-square tests and student t tests and multivariate analysis using binary logit regression. Results from the univariate analyses indicate that the likelihood of support for a curbside textile-recycling policy is significantly influenced by regular waste-recycling habits, political affiliation, family size, minority status, home ownership, and income. Results from the binary logit regression analysis indicate that (a) current waste-recycling behavior is a good predictor of support for a curbside textile-recycling policy, and (b) the importance of recycling habits is manifested by its impact on the effect of political affiliation on support for a policy.
Nanotechnology Systems of Innovation: Investigation of Scientific Disciplines' Fusion Trend into Nanotech

Nanotechnology, manipulating atoms and molecules at the nanometer level, is an emerging technology, introducing new dimensions to science and technology by the convergence of traditional disciplines. In the early stage of nanotechnology development and diffusion, many expected benefits have not yet been fully accomplished. However, researchers of many countries in the scientific disciplines aggressively got involved in the relevant research as a parallel way to boost nanotech competitiveness through academic research, and corporations direct their R&D activities towards the exploration of nanotech opportunities. Through a combination of quantitative (bibliometric exploration) and qualitative method (primary data analysis), the paper attempts to establish the trend of science disciplines' knowledge fusion into nanotechnology field. In terms of fusing disciplines together, a number of approaches were considered: i) looking for nanoscientific output of journals of general disciplines categorized by ISI (find to what extent were nanotech papers coming from scientific disciplines over time and how it has changed over time? ); ii) to look for a set of nanoscience papers in each disciplinary journals at present, 5 and 10 years ago and their reference citations (classify the citing references into disciplines using ISI journal based classification scheme and what proportions were coming out or linking with each disciplines. This study also identified the concerned factors driving multi-disciplines' fusion into nanotech, that would be a good evidence of fusing previously separate disciplinary activities into nanotech. The research offers useful insights for science & technology policy makers as well as for researchers of traditional science fields in the global community, revealing fusion trend of the emerging nanotechnological systems, existing domain-level competencies and differences between disciplines.
The epidemiology of anxiety disorders: a review

Epidemiological studies show that anxiety disorders are highly prevalent and an important cause of functional impairment; they constitute the most frequent menial disorders in the community. Phobias are the most common with the highest rates for simple phobia and agoraphobia. Panic disorder (PD) and obsessive-compulsive disorder (OCD) are less frequent (2% lifetime prevalence), and there are discordant results for social phobia (SP) (2%-16%) and generalized anxiety disorder (GAD) (3%-30%). These studies underline the importance of an accurate definition of disorders using unambiguous diagnostic and assessment criteria. The boundaries between anxiety disorders are often ill defined and cases may vary widely according to the definition applied. Simple phobia, agoraphobia, and GAD are more common in vmrnen, while there is no gender différence for SP, PD, and OCD, Anxiety disorders are more common in separated, divorced, and widowed subjects; their prevalence is highest in subjects aged 25 to 44 years and lowest in subjects aged >65 years. The age of onset of the different types of anxiety disorders varies widely: phobic disorders begin early in life, whereas PD occurs in young adulthood. Clinical - rather than epidemiological - studies have examined risk factors such as life events, childhood experiences, and familial factors. Anxiety disorders have a chronic and persistent course, and are frequently comorbid with other anxiety disorders, depressive disorders, and substance abuse. Anxiety disorders most frequently precede depressive disorders or substance abuse, Comorbid diagnoses may influence risk factors like functional impairment and quality of life. It remains unclear whether certain anxiety disorders (eg, PD) are risk factors for suicide. The comorbidity of anxiety disorders has important implications for assessment and treatment and the risk factors should be explored. The etiology, natural history, and outcome of these disorders need to be further addressed in epidemiological studies.
Developmental Psychopathology from Family Systems and Family Risk Factors Perspectives: Implications for Family Research, Practice, and Policy

Author(s): Cowan, PA; Pape Cowan, C | Abstract: © 2006 John Wiley a Sons, Inc. All rights reserved. This chapter reviews family systems and developmental psychopathology, noting some aspects of the political /policy/practice context about the role of families in the development of psychopathology. To provide a focused account of family systems theory, it illustrates examples drawn primarily from the United States. After a brief historical look at how these theories have changed over time, the chapter illustrates how family systems and family risk factors approaches can be applied to the understanding of developmental psychopathology. It examines how family processes are implicated in explaining what happens when nonclinical families go through major life transitions, both expected and unexpected. The chapter then shows how formulations from a family systems or family risk factor perspective can provide value-added information, both in predicting the trajectories people follow in their journeys toward or away from diagnosed disorders, and in planning interventions for those at risk or distressed.
Health decline and well-being in old age: the need of coping

Objectives It is often assumed that ageing is accompanied by diverse and constant functional and cognitive decline and it is therefore surprising that the of older persons does not appear to decline in the same way. This study investigates longitudinally whether in older persons changes due to Persistent Deterioration of Functioning (PDF). Methods The data were collected in the context of the Longitudinal Aging Study Amsterdam (LASA). Conditions of PDF are persistent decline in cognitive functioning, physical functioning and increase of chronic diseases. Measurements of included life satisfaction, positive affect and valuation of life. T-tests were used to analyse mean difference scores for and univariate and multivariate regression analyses were performed to examine changes in three outcomes in relation to PDF. Results Cross-sectional analyses showed significant differences and associations between two PDF subgroups and non-PDF for at T3. In longitudinal analyses we found significant decrease in and associations with over time in respondents fulfilling one PDF condition (mild PDF). For respondents fulfilling Two or more PDF conditions (severe PDF) longitudinally no significant associations were found. Conclusion Cognitive aspects of (life satisfaction and valuation of life) and the affective element (positive affect) of appear to be influenced negatively by mild PDF, whereas in persons with more severe PDF does not seem to be diminished. This may be due to the ability to finally accept to the inevitable situation of severe PDF.
Dual Modes of Munc18-1/SNARE Interactions Are Coupled by Functionally Critical Binding to Syntaxin-1 N Terminus

The SM (Sec1/Munc18-like) protein Munc18-1 and the soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins syntaxin-1, SNAP-25, and synaptobrevin/VAMP (vesicle-associated membrane protein) constitute the core fusion machinery for synaptic vesicle exocytosis. Strikingly, Munc18-1 interacts with neuronal SNARE proteins in two distinct modes (i.e., with isolated syntaxin-1 alone in a “closed” conformation and with assembled SNARE complexes containing syntaxin-1 in an “open” conformation). However, it is unclear whether the two modes of Munc18/SNARE interactions are linked. We now show that both Munc18/SNARE interaction modes involve the same low-affinity binding of the extreme syntaxin-1 N terminus to Munc18-1, suggesting that this binding connects the two Munc18/SNARE interaction modes to each other. Using transfected cells as an in vitro assay system, we demonstrate that truncated syntaxins lacking a transmembrane region universally block exocytosis, but only if they contain a free intact N terminus. This block is enhanced by coexpression of either Munc18-1 or SNAP-25, suggesting that truncated syntaxins block exocytosis by forming an untethered inhibitory SNARE complex/Munc18-1 assembly in which the N-terminal syntaxin/Munc18 interaction is essential. Introduction of an N-terminal syntaxin peptide that disrupts this assembly blocks neurotransmitter release in the calyx of Held synapse, whereas a mutant peptide that does not disrupt the SNARE complex/Munc18 assembly has no effect. Viewed together, our data indicate that binding of Munc18 to the syntaxin N terminus unites different modes of Munc18/SNARE interactions and is essential for exocytic membrane fusion.
HUMAN FACTORS FOR THE DESIGN OF FORCE-REFLECTING HAPTIC INTERFACES

This paper discusses the design criteria imposed by the capabilities of the human user on the design of force reflecting controllers for hands and arms. A framework of issues regarding human capabilities is presented that maps directly to mechanical design requirements. The state of knowledge for each capability is briefly summarized along with presentation of new experimental measurements. Finally, the implications of the human factors data to haptic interface design are discussed.
Survey of flea infestation in cats in Spain

Fleas are a common cause of feline skin disorders as well as vectors of zoonotic diseases. This study evaluated the flea species infesting domestic cats in Spain and assessed factors influencing their distribution. Fleas from 217 cats from 57 localities in Spain were identified and associations between abundance, and host‐dependent, host habitat and environmental factors were examined. Variations in infracommunity and component community structure were also explored. Three species were present, of which Ctenocephalides felis (Bouché) (Siphonaptera: Pulicidae) was the most abundant (98.4%), followed by Ctenocephalides canis (Curtis) (1.1%) and Pulex irritans (L.) (Siphonaptera: Pulicidae) (0.5%). Overall abundance and abundances of both C. felis and C. canis were higher on farms than in apartments, but overall flea abundance and abundances of both C. felis and C. canis were lower in rural than urban environments. Overall abundance and C. felis abundance were lower during the warmest months, and mean annual rainfall was positively correlated with overall, C. felis and C. canis abundances. No relationship between the number of species per cat and any host, habitat or physiographical variable was found. Species richness was not correlated with mean annual temperature or rainfall. Flea abundance was mainly associated with host habitat and environmental factors.
Comparison of two approaches of infraclavicular brachial plexus block for orthopaedic surgery below mid-humerus

The brachial plexus in infraclavicular region can be blocked by various approaches. Aim of this study was to compare two approaches (coracoid and clavicular) regarding success rate, discomfort during performance of block, tourniquet tolerance and complications. The study was randomised, prospective and observer blinded. Sixty adult patients of both sexes of ASA status 1 and 2 requiring orthopaedic surgery below mid-humerus were randomly assigned to receive nerve stimulator guided infraclavicular brachial plexus block either by lateral coracoid approach (group L, n = 30) or medial clavicular approach (group M, n = 30) with 25–30 ml of 0.5% bupivacaine. Sensory block in the distribution of five main nerves distal to elbow, motor block (Grade 1–4), discomfort during performance of block and tourniquet pain were recorded by a blinded observer. Clinical success of block was defined as the block sufficient to perform the surgery without any supplementation. All the five nerves distal to elbow were blocked in 77 and 67% patients in groups L and M respectively. Successful block was observed in 87 and 73% patients in groups L and M, respectively (P > 0.05). More patients had moderate to severe discomfort during performance of block due to positioning of limb in group M (14 vs. 8 in groups M and L). Tourniquet was well tolerated in most patients with successful block in both groups. No serious complication was observed. Both the approaches were equivalent regarding success rate, tourniquet tolerance and safety. Coracoid approach seemed better as positioning of operative limb was less painful, coracoids process was easy to locate and the technique was easy to learn and master.
Abnormalities of the TITF-1 Lineage-Specific Oncogene in NSCLC: Implications in Lung Cancer Pathogenesis and Prognosis

Purpose: Emerging evidence suggests that aberrant expression of oncogenes contributes to development of lung malignancy. The thyroid transcription factor 1 (TITF-1) gene functions as a lineage survival gene abnormally expressed in a significant fraction of non–small cell lung cancers (NSCLC), in particular lung adenocarcinomas. Experimental Design: To better characterize TITF-1 abnormality patterns in NSCLC, we studied TITF-1's gene copy number using FISH and quantitative PCR, as well as its protein expression by immunohistochemistry analysis in a tissue microarray comprising surgically resected NSCLC (N = 321) including 204 adenocarcinomas and 117 squamous cell carcinomas (SCC). TITF-1 copy number and protein expression were correlated with patients' clinicopathologic characteristics, and in a subset of adenocarcinomas with EGFR and KRAS mutation status. Results: We found that increased TITF-1 protein expression was prevalent in lung adenocarcinomas only and was significantly associated with female gender (P < 0.001), never-smokers (P = 0.004), presence of EGFR mutations (P = 0.05), and better overall survival (all stages, P = 0.0478; stages I and II, P = 0.002). TITF-1 copy number gain(CNG) was detected by FISH analysis in both adenocarcinomas (18.9%; high CNG, 8.3%) and SCCs (20.1%; high CNG, 3.0%), and correlated significantly with the protein product (P = 0.004) and presence of KRAS mutations (P = 0.008) in lung adenocarcinomas. Moreover, multivariate analysis revealed that TITF-1 copy number gain was an independent predictor of poor survival of NSCLC (P = 0.039). Conclusions: Our integrative study demonstrates that the protein versus genomic patterns of TITF-1 have opposing roles in lung cancer prognosis and may occur preferentially in different subsets of NSCLC patients with distinct oncogene mutations. Clin Cancer Res; 17(8); 2434–43. ©2011 AACR.
Transcription Factor Arabidopsis Activating Factor1 Integrates Carbon Starvation Responses with Trehalose Metabolism1[OPEN]

A transcription factor regulates trehalase expression and induces a carbon starvation transcriptome and metabolome. Plants respond to low carbon supply by massive reprogramming of the transcriptome and metabolome. We show here that the carbon starvation-induced NAC (for NO APICAL MERISTEM/ARABIDOPSIS TRANSCRIPTION ACTIVATION FACTOR/CUP-SHAPED COTYLEDON) transcription factor Arabidopsis (Arabidopsis thaliana) Transcription Activation Factor1 (ATAF1) plays an important role in this physiological process. We identified TREHALASE1, the only trehalase-encoding gene in Arabidopsis, as a direct downstream target of ATAF1. Overexpression of ATAF1 activates TREHALASE1 expression and leads to reduced trehalose-6-phosphate levels and a sugar starvation metabolome. In accordance with changes in expression of starch biosynthesis- and breakdown-related genes, starch levels are generally reduced in ATAF1 overexpressors but elevated in ataf1 knockout plants. At the global transcriptome level, genes affected by ATAF1 are broadly associated with energy and carbon starvation responses. Furthermore, transcriptional responses triggered by ATAF1 largely overlap with expression patterns observed in plants starved for carbon or energy supply. Collectively, our data highlight the existence of a positively acting feedforward loop between ATAF1 expression, which is induced by carbon starvation, and the depletion of cellular carbon/energy pools that is triggered by the transcriptional regulation of downstream gene regulatory networks by ATAF1.