Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of the Penta-EF-hand Protein ALG-2 as a Ca2+-dependent Interactor of Mucolipin-1*

Loss of function mutations in mucolipin-1 (MCOLN1) have been linked to mucolipidosis type IV (MLIV), a recessive lysosomal storage disease characterized by severe neurological and ophthalmological abnormalities. MCOLN1 is an ion channel that regulates membrane transport along the endolysosomal pathway. It has been suggested that MCOLN1 participates in several Ca2+-dependent processes, including fusion of lysosomes with the plasma membrane, fusion of late endosomes and autophagosomes with lysosomes, and lysosomal biogenesis. Here, we searched for proteins that interact with MCOLN1 in a Ca2+-dependent manner. We found that the penta-EF-hand protein ALG-2 binds to the NH-terminal cytosolic tail of MCOLN1. The interaction is direct, strictly dependent on Ca2+, and mediated by a patch of charged and hydrophobic residues located between MCOLN1 residues 37 and 49. We further show that MCOLN1 and ALG-2 co-localize to enlarged endosomes induced by overexpression of an ATPase-defective dominant-negative form of Vps4B (Vps4BE235Q). In agreement with the proposed role of MCOLN1 in the regulation of fusion/fission events, we found that overexpression of MCOLN1 caused accumulation of enlarged, aberrant endosomes that contain both early and late endosome markers. Interestingly, aggregation of abnormal endosomes was greatly reduced when the ALG-2-binding domain in MCOLN1 was mutated, suggesting that ALG-2 regulates MCOLN1 function. Overall, our data provide new insight into the molecular mechanisms that regulate MCOLN1 activity. We propose that ALG-2 acts as a Ca2+ sensor that modulates the function of MCOLN1 along the late endosomal-lysosomal pathway.
The gendered power relations of action learning: a critical analysis of women’s reflections on a leadership development programme

Revealing power relations in HRD research and practice is an important concern for critical HRD scholars, however little attention has been paid to gendered power relations in the HRD practice of action learning. This paper responds to this gap through a critical analysis of a phenomenological study of six women’s reflections of action learning as part of a leadership development programme. Adopting feminist post-structuralist ideas, the paper draws on the study to interrogate gendered power relations in action learning. Key findings include women’s perceptions of gendered power relations in action learning affirm dominant understandings of leaders as male, not attending to gender impedes women’s leadership development in action learning and action learning principles of trust and comradeship can serve simultaneously to avoid difference and to reinforce a dominant set culture that constructs difference. The paper concludes with proposals of how action learning might take gender into account in the leadership development of women.
Summary of contributions to GAW Group 12: Multivariate Methods

Here we summarize the contributions to Group 12 of Genetic Analysis Workshop (GAW) 14, held in Noordwijkerhout, The Netherlands. The theme of this group, multivariate methods, covered a broad range of statistical applications. Most of the contributors considered Problem 1 of the GAW. However, one paper considered the bivariate analysis of two binary phenotypes generated by the simulated data in Problem 2. Some contributors focused on statistical issues involved in considering multiple variables, and others on extensions to the variance‐components methodology for analysis of quantitative traits. Applications to the Collaborative Study on the Genetics of Alcoholism data identified a single‐nucleotide polymorphism (SNP) on chromosome 4 associated with the ttth1–ttth4 phenotypes, and replicated previous findings of linkage on chromosome 4 for alcohol consumption, using microsatellite and SNP data. Genet. Epidemiol. 29(Suppl. 1): S91–S95, 2005. © 2005 Wiley‐Liss, Inc.
The Importance of Attention Diversity and How to Measure It

Studies of political attention often focus on attention to a single issue, such as front-page coverage of the economy. However, examining attention without accounting for the agenda as a whole can lead to faulty assumptions. One solution is to consider the diversity of attention; that is, how narrowly or widely attention is distributed across items (e.g., issues on an agenda or, at a lower level, frames in an issue debate). Attention diversity is an important variable in its own right, offering insight into how agendas vary in their accessibility to policy problems. Yet despite the importance of attention diversity, we lack a standard for how best to measure it. This paper focuses on the four most commonly used measures: the inverse Herfindahl Index, Shannon’s H, and their normalized versions. We discuss the purposes of these measures and compare them through simulations and using three real-world datasets. We conclude that both Shannon’s H and its normalized form are better measures, minimizing the danger of spurious findings that could result from the less sensitive Herfindahl measures. The choice between the Shannon’s H measures should be made based on whether variance in the total number of possible items (e.g., issues) is meaningful.
A generalized framework for network component analysis

The authors recently introduced a framework, named network component analysis (NCA), for the reconstruction of the dynamics of transcriptional regulators' activities from gene expression assays. The original formulation had certain shortcomings that limited NCA's application to a wide class of network dynamics reconstruction problems, either because of limitations in the sample size or because of the stringent requirements imposed by the set of identifiability conditions. In addition, the performance characteristics of the method for various levels of data noise or in the presence of model inaccuracies were never investigated. In this article, the following aspects of NCA have been addressed, resulting in a set of extensions to the original framework: 1) The sufficient conditions on the a priori connectivity information (required for successful reconstructions via NCA) are made less stringent, allowing easier verification of whether a network topology is identifiable, as well as extending the class of identifiable systems. Such a result is accomplished by introducing a set of identifiability requirements that can be directly tested on the regulatory architecture, rather than on specific instances of the system matrix. 2) The two-stage least square iterative procedure used in NCA is proven to identify stationary points of the likelihood function, under Gaussian noise assumption, thus reinforcing the statistical foundations of the method. 3) A framework for the simultaneous reconstruction of multiple regulatory subnetworks is introduced, thus overcoming one of the critical limitations of the original formulation of the decomposition, for example, occurring for poorly sampled data (typical of microarray experiments). A set of Monte Carlo simulations we conducted with synthetic data suggests that the approach is indeed capable of accurately reconstructing regulatory signals when these are the input of large-scale networks that satisfy the suggested identifiability criteria, even under fairly noisy conditions. The sensitivity of the reconstructed signals to inaccuracies in the hypothesized network topology is also investigated. We demonstrate the feasibility of our approach for the simultaneous reconstruction of multiple regulatory subnetworks from the same data set with a successful application of the technique to gene expression measurements of the bacterium Escherichia coli.
Analysis of Sentinel-1 marine applications potential

Ship detectability modelling has been carried out for Sentinel-1, including development of a ship detectability tool that applies to Sentinel-1, RADARSAT-1, RADARSAT-2, and Envisat ASAR image data. Capabilities and limitations of the tool's predictions are discussed. Also considered is Sentinel-1's expected capability for other maritime applications, including iceberg detection, wind retrieval, oil spill detection, sea ice surveillance, and ship wake detection. In general, the Interferometric Wide Swath mode with its high spatial resolution and 250 km swath will be a useful mode for surveillance of the littoral zone.
Building the Pamirs: The view from the underside: Geology

The Pamir mountains are an outstanding example of extreme crustal shortening during continental collision that may have been accommodated by formation of a thick crust—much thicker than is currently thought—and/or by continental subduction. We pre- sent new petrologic data and radiometric ages from xenoliths in Miocene volcanic rocks in the southeastern Pamir mountains that suggest that Gondwanan igneous and sedimentary assemblages were underthrust northward, buried to . 50-80 km during the ear- ly stage of the India-Asia collision, and then heated and partly melted during subsequent thermal relaxation before finally being blasted to the surface. These xenoliths, the deepest crustal samples recovered from under any active collisional belt, provide direct evidence for early Cenozoic thickening of the Pamirs and lower- crustal melting during collision; the xenoliths also suggest that the present mountain range was a steady-state elevated plateau for most of the Cenozoic.
Purification, Characterization, and Potential of Saline Waste Water Remediation of a Polyextremophilic α-Amylase from an Obligate Halophilic Aspergillus gracilis

An obligate halophilic Aspergillus gracilis which was isolated from a hypersaline man-made saltern from Thailand was screened for its potential of producing extracellular α-amylase in the previous studies. In this study the α-amylase was extracted and purified by the help of column chromatography using Sephadex G-100 column. Presence of amylase was verified by SDS-PAGE analysis, showing a single band of approximately 35 kDa. The specific activity of the enzyme was found to be 131.02 U/mg. The Lineweaver-Burk plot showed the V max and K m values of 8.36 U/mg and 6.33 mg/mL, respectively. The enzyme was found to have the best activity at 5 pH, 60°C, and 30% of NaCl concentration, showing its polyextremophilic nature. The use of various additives did not show much variation in the activity of enzyme, showing its resilience against inhibitors. The enzyme, when tested for its use for synthetic waste water remediation by comparing its activity with commercial amylase in different salt concentrations showed that the α-amylase from A. gracilis was having better performance at increasing salt concentrations than the commercial one. This shows its potential to be applied in saline waste water and other low water activity effluents for bioremediation.
Stage-Specific Histone Modification Profiles Reveal Global Transitions in the Xenopus Embryonic Epigenome

Vertebrate embryos are derived from a transitory pool of pluripotent cells. By the process of embryonic induction, these precursor cells are assigned to specific fates and differentiation programs. Histone post-translational modifications are thought to play a key role in the establishment and maintenance of stable gene expression patterns underlying these processes. While on gene level histone modifications are known to change during differentiation, very little is known about the quantitative fluctuations in bulk histone modifications during development. To investigate this issue we analysed histones isolated from four different developmental stages of Xenopus laevis by mass spectrometry. In toto, we quantified 59 modification states on core histones H3 and H4 from blastula to tadpole stages. During this developmental period, we observed in general an increase in the unmodified states, and a shift from histone modifications associated with transcriptional activity to transcriptionally repressive histone marks. We also compared these naturally occurring patterns with the histone modifications of murine ES cells, detecting large differences in the methylation patterns of histone H3 lysines 27 and 36 between pluripotent ES cells and pluripotent cells from Xenopus blastulae. By combining all detected modification transitions we could cluster their patterns according to their embryonic origin, defining specific histone modification profiles (HMPs) for each developmental stage. To our knowledge, this data set represents the first compendium of covalent histone modifications and their quantitative flux during normogenesis in a vertebrate model organism. The HMPs indicate a stepwise maturation of the embryonic epigenome, which may be causal to the progressing restriction of cellular potency during development.
Romanian Preschool Teachers’ Understanding of Emotional and Behavioral Difficulties: Implications for Designing Teacher Trainings

Researchers have emphasized the role of the teacher–child relationship on children’s adjustment. Children lacking such positive relationships are placed at increased risk for emotional and behavioral difficulties (EBD). We propose a qualitative approach to exploring Romanian teachers’ knowledge and strategies related to preschoolers who are at risk. Seven focus groups were conducted and were subjected to thematic analysis. Four main themes were identified: teachers’ understanding of EBD, teachers’ beliefs about parental behaviors as risk factors for EBD, teachers’ role in preventing children’s EBD, and teachers’ strategies for managing EBD-related behaviors in the classroom. Teachers mainly used behavioral descriptions when referring to EBD, and differentiated between transient and clinically relevant problems. Although teachers showed awareness about their role in preventing EBD, there was insufficient procedural knowledge about strategies used to deal with such problems in the classroom. The results suggest that teachers need more training and support from mental health professionals to prevent EBD, and to ensure children’s well-being.
Comparison of symptoms of pediatric bipolar disorder in the manic phase and attention deficit and hyperactivity disorder

OZET: Pediatrik bipolar bozukluk manik donem belirtilerinin dikkat eksikligi ve hiperaktivite bozuklugu belirtileri ile karsilastirilmasi Amac: Eriskin bipolar bozuklugu cogunlukla epizodik seyir gostermektedir. Ancak pediatrik bipolar bozuklukta karma epizodlar ve hizli dongu eriskin bipolar bozukluga gore daha sik gorulen durumlardir ve beraberinde Dikkat Eksikligi ve Hiperaktivite Bozuklugu (DEHB) tanisi siklikla bulunmaktadir. Bu calismanin amaci pediatrik bipolar bozukluk tanisi almis bir grup hastada bu bozuklugun klinik karakteristik ozelliklerini belirlemek ve bu ozellikle- ri DEHB tanisi olan hastalar ile karsilastirmaktir. Yontem: Orneklem DSM-IV tani kritelerine gore pedi- atrik bipolar bozukluk manik donem ve DEHB tanilari konulmus olan 19'ar cocuk veya ergen hastadan olus- maktadir. Hastaligin baslama yasi, belirtiler ve es tanilar analiz edilmistir. Daha sonra iki grup Child Mania Rating Scale ile belirlenmis olan hastalik belirtileri bakimindan karsilastirilmistir. Bulgular: Irritabl duygudurum (%94), hizli duygudurum dalgalanmalari (%89), sanrilar (%94), isitsel (%63) ve gorsel hallusinasyonlar (%43) bipolar bozuklugu olan hastalarda istatistiksel olarak anlamli olarak daha sik saptanmistir. Hareketlilik, dikkat eksikligi ve irritabilite oranlari bakimindan her iki grup arasinda anlamli fark bulunmamistir. Sonuc: Bipolar bozuklugu olan cocuk ve ergenlerde hizli dongu, irritabl duygudurum ve psikotik belirtiler sik ola- rak gorulmektedir ancak irritabilite bipolar bozukluk icin spesifik bir semptom degildir.
Lower Corticosteroid Skin Blanching Response Is Associated with Severe COPD

Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation caused by ongoing inflammatory and remodeling processes of the airways and lung tissue. Inflammation can be targeted by corticosteroids. However, airway inflammation is generally less responsive to steroids in COPD than in asthma. The underlying mechanisms are yet unclear. This study aimed to assess whether skin corticosteroid insensitivity is associated with COPD and COPD severity using the corticosteroid skin blanching test. Methods COPD patients GOLD stage I–IV (n = 27, 24, 22, and 16 respectively) and healthy never-smokers and smokers (n = 28 and 56 respectively) were included. Corticosteroid sensitivity was assessed by the corticosteroid skin blanching test. Budesonide was applied in 8 logarithmically increasing concentrations (0–100 μg/ml) on subject's forearm. Assessment of blanching was performed after 7 hours using a 7-point scale (normal skin to intense blanching). All subjects performed spirometry and body plethysmography. Results Both GOLD III and GOLD IV COPD patients showed significantly lower skin blanching responses than healthy never-smokers and smokers, GOLD I, and GOLD II patients. Their area under the dose-response curve values of the skin blanching response were 586 and 243 vs. 1560, 1154, 1380, and 1309 respectively, p<0.05. Lower FEV1 levels and higher RV/TLC ratios were significantly associated with lower skin blanching responses (p = 0.001 and p = 0.004 respectively). GOLD stage I, II, III and IV patients had similar age and packyears. Conclusions In this study, severe and very severe COPD patients had lower skin corticosteroid sensitivity than mild and moderate COPD patients and non-COPD controls with comparable age and packyears. Our findings together suggest that the reduced skin blanching response fits with a subgroup of COPD patients that has an early-onset COPD phenotype.
Assoziationsnormen für 68 deutsche Homonyme

Zusammenfassung. Im Anschlus an eine einfuhrende Ubersicht zu experimentalpsychologischen Untersuchungen unter Verwendung von Homonymwortern werden die Ergebnisse einer Normierungsstudie von 68 deutschen Homonymen an einer Normalpopulation von 100 gesunden Probanden dargestellt. Berichtet werden Frequenz und Polaritat der Homonyme sowie U-Werte (Index der Ambiguitat). 49 Homonyme wiesen eine eindeutige semantische Praferenz fur ein Bedeutungsfeld auf, 7 Homonyme waren balanciert und bei 12 Homonymen entfielen auf die inferioren Wortbedeutungen jeweils weniger als 5 % der Nennungen. Studien 2a und 2b replizieren fruhere Befunde zur Resolution semantischer Ambiguitat. Fur diskordante Triplett-Bedingungen liesen sich bei langerem Interstimulusintervall zwischen Homonym und Zielreiz Hemmeffekte nachweisen, wahrend eine (insignifikante) Reaktionserleichterung bei kurzerem Intervall gefunden wurden. Die Ergebnisse von Studie 2 bestatigen kontext-sensitive Modelle der Homonymverarbeitung, wonach es im Anschlus a.
The legacy of Nazism: Historical analogies and support for the far right

This paper examined whether perceiving a historical analogy between former Nazi collaborator parties and contemporary far-right parties is negatively associated with support for the current far right. It was predicted that this relationship would be mediated by perceived immorality of far-right anti-Muslim standpoints. A survey study (Study 1) demonstrated that perceiving this historical analogy is negatively related to both electoral support for the far right and opposition to Muslim expressive rights. An experiment (Study 2) showed that drawing this historical analogy reduces both electoral support for the far right and opposition to Muslim expressive rights through perceived immorality of far-right anti-Muslim standpoints. The implications of historical analogies for people's attitudes toward present-day social and political issues are discussed.
Sketch-Based Modeling with the BlobTree ( sketches 0292 )

Sketch-based modeling provides an intuitive and expressive interface for 3D model creation. With the Teddy [Igarashi et al. 1999] system, complex free-form 3D models could be quickly produced using a gesture interface. However, the topological modeling operations implemented in Teddy were limited by the underlying shape representation (triangle meshes). Related systems based on variational implicit surfaces [Araújo and Jorge. 2003] produce smoother results but cannot support complex models.
A qualitative study of the UK academic role: positive features, negative aspects and associated stressors in a mainly teaching-focused university

Abstract The literature demonstrates that stress in the working life of academics has increased over recent years. However, qualitative research on how academics cope with this is very scarce. Using online interviewing with thematic analysis, this paper examines how 31 academics in a post-92 predominantly teaching-focused UK university cope with the stressors of work. An innovation was to ask about both positive and negative experiences at work unlike most stress research which focuses only on negatives. Six themes emerged from the data; administrative loads, coping with stress at work, task preferences, the academic role, and positive and negative feelings around research/scholarship and thoughts around leaving academia. Increases in student numbers, being able to spend less time with students, heavy workloads, increasing administration, poor management, funding cuts and government initiatives threatening the future of education, obtaining research funding, and increasing insecurity of academic posts were all stressors. Positives identified included satisfaction gained from teaching students, support from colleagues, relative autonomy at work and the ability to manage their time more effectively were perceived as factors that can moderate some of the negative consequences of work stress. Overall, academics reported being happy at work because of the satisfaction gained from teaching and research.
Relative age effect in lower categories of international basketball

To be able to value the relative age effect in the male and female World Championships played between 2005 and 2010 in the U17 categories (athletes 17 years or younger), U19 (athletes 19 or younger) and U21 (athletes 21 years or younger) a sample of 954 players has been selected. The variables registered were their dates of birth, the category of the competition, gender, height and official statistics of each player obtained from the International Basketball Federation (FIBA). A clear relative age effect was found (in both male and female categories) fading with age, being higher in the U17 category, slightly less but also significant in the U19, and no significant effect found in U21. This effect persists when the different specific positions were analysed in the male categories, being clearer in the positions that require more physical strength. In female categories the results do not back the existence of the relative age effect. Also, differences were found in height in the male category with regard to the players’ year-quarter of birth, but its interpretation is not consistent with the relative age effect. In the female category no differences were found in height. Finally, the performance difference of the players in the male and female categories hardly varies with regard to the year-quarter of birth.
Psychological Study of Human Judgment: Implications for Investment Decision-Making

"You are-face it-a bunch of emotions, prejudices, and twitches, and this is all very well as long as you know it. Successful speculators do not necessarily have a complete portrait of themselves, warts and all, in their own minds, but they do have the ability to stop abruptly when their own intuition and what is happening Out There are suddenly out of kilter. "If you don't know who you are, this is an expensive place to find out. "