Miracle-dz/UniFAR-FTUs huggingface dataset:
Interdomain signalling in the blue-light sensing and GTP-binding protein YtvA: A mutagenesis study uncovering the importance of specific protein sites

YtvA from Bacillus subtilis is a blue-light responsive, flavin-binding photoreceptor, built of a light-sensing LOV domain (aa 25–126) and an NTP (nucleoside triphosphate)-binding STAS domain (aa 147–261). The STAS domain is supposed to be the effector part of the protein or a secondary switch. Both domains are connected by a linker polypeptide. The active form of YtvA is generated upon light excitation, causing the formation of a covalent bond between a cysteine residue (Cys62) in the LOV domain and the position 4a of the flavin chromophore. This photoadduct formation within the LOV domain results in a conformational change of the NTP-binding cavity, evidencing intra-protein signal transmission. We have previously shown that Glu105, localized on the beta-scaffold of the LOV-core, is involved in this process. Here, we extend this work by the identification of further residues that upon mutation supress or strongly impair signal transmission by interfering with the communication between the two domains. These comprise L106 and D109 on the LOV domain; K130 and K134 on the linker region; D193, L194 and G196 within the DLSG GTP-binding motif (switch region) and N201 on the STAS domain. Furthermore in the mutated S195A and D193A proteins, GTP affinity is diminished. Other mutations investigated have little or no effect on signal transmission and GTP-binding affinity: R63K that was found to accelerate the thermal recovery of the parent state ca. ten-fold; K128A, Q129A and Y132A within the linker region, and S183A and S212A on the STAS domain. The results show a key role of the LOV domain beta-scaffold and of positively charged residues within the linker for intra-protein signal transmission. Furthermore they evidence the conformational switch function of a structurally conserved strand-loop-helix region (bearing the DLSG GTP-binding motif and N201) within the STAS domain that constitutes a novel GTP-binding fold.
IMPACT OF ENVIRONMENTAL UNCERTAINTY ON SUPPLY CHAIN INTEGRATION

Today’s ever-changing business environment is often described to be highly competitive, dynamic and complex. Customers are demanding more variability, better quality, higher reliability and faster delivery. Organizations are being faced with more uncertainties from its task environment than before. In order to respond to the uncertainties, organizations are internalizing fewer resources and capabilities, while increasing their integration with partners in the supply chain. Drawing on the resource-dependence theory, this study aims to examine the impact of environmental uncertainty on supply chain integration initiatives. Environmental uncertainty is considered in terms of three types, namely, supply uncertainty, demand or customer uncertainty, and technology uncertainty, based on its sources. Supply chain integration is comprised of internal integration, customer integration, and supplier integration. Based on the empirical study with 108 Japanese manufacturing firms, this study makes significant contributions to the knowledge base and provides theoretical and practical implications.
Essays on Mutual Funds and Fund Managers

This dissertation comprises of three chapters on mutual funds. The first chapter establishes the role of managers in the deceptive practice of window dressing. Employing comprehensive career history of U.S. mutual fund managers, I find strong jointly significant manager fixed effects, which are robust after addressing endogenous matching concerns. I use the connected sample instead of the classical movers sample to substantially enlarge the sample size and reduce the selection bias that long exists in the stream of literature. The estimated manager fixed effects are significant in making out-of-sample predictions. Further I establish that mutual fund interlocks through common managers are important channels that spread window dressing. The second chapter studies the investment strategies of mutual funds regarding their use of credit default swaps (CDS). Matches between mutual funds CDS positions and their underlying portfolio in the holdings facilitate a new approach in identifying CDS strategies that complements the macro level analyses in the existing literature. I find risk reducing incentives are dominated by speculative incentives, especially those to increase credit exposure via naked short CDS contracts. Experienced fund managers tend to take on more credit risk, while female managers are more likely to hedge comparing with their male peers. The third chapter employs the collapse of Lehman Brothers and the resulting sudden closures of CDS positions as a natural experiment to examine the risk and performance implications of mutual funds CDS investments. Funds on average load up on a significant amount of tail risk by trading CDS. While CDS users benefit when market conditions are favorable, they suffer during periods of clustered defaults. Funds forced to resolve their Lehman CDS contracts exhibit persistent inferior performance in the post-crisis period comparing
Local Excision of T2 and T3 Rectal Cancers After Downstaging Chemoradiation

ObjectiveTo evaluate the safety and efficacy of local excision in patients with T2 and T3 distal rectal cancers that have been downstaged by preoperative chemoradiation. Summary Background DataT2 and T3 cancers treated by local excision alone are associated with unacceptably high recurrence rates. The authors hypothesized that preoperative chemoradiation might downstage both T2 and T3 lesions and significantly expand the indications for local excision. MethodsLocal excision was performed after preoperative chemoradiation on patients with a complete clinical response or on patients who were either ineligible for or refused to undergo abdominoperineal resection. Local excision was approached transanally by removing full-thickness rectal wall and the underlying mesorectum. ResultsFrom 1994 to 2000, 95 patients with rectal cancers underwent preoperative chemoradiation and surgical resection for curative intent. Of these, 26 patients (28%), 19 men and 7 women, with a mean age of 63 years (range 44–90), underwent local excision. Pretreatment endoscopic ultrasound classifications included 5 T2N0, 13 T3N0, 7 T3N1, and 1 not done. Pathologic partial and complete responses were achieved in 9 of 26 (35%) and 17 of 26 (65%) patients, respectively. Two of nine partial responders underwent immediate abdominoperineal resection. The mean follow-up was 24 months (median 19, range 6–77). The only recurrence was in a patient who refused to undergo abdominoperineal resection after a partial response. There was one postoperative death from a stroke. This treatment was associated with a low rate of complications. ConclusionLocal excision appears to be an effective alternative treatment to radical surgical resection for a highly select subset of patients with T2 and T3 adenocarcinomas of the distal rectum who show a complete pathologic response to preoperative chemoradiation.
Assessment and manifestation of central sensitisation across different chronic pain conditions

Different neuroplastic processes can occur along the nociceptive pathways and may be important in the transition from acute to chronic pain and for diagnosis and development of optimal management strategies. The neuroplastic processes may result in gain (sensitisation) or loss (desensitisation) of function in relation to the incoming nociceptive signals. Such processes play important roles in chronic pain, and although the clinical manifestations differ across condition processes, they share some common mechanistic features. The fundamental understanding and quantitative assessment of particularly some of the central sensitisation mechanisms can be translated from preclinical studies into the clinic. The clinical perspectives are implementation of such novel information into diagnostics, mechanistic phenotyping, prevention, personalised treatment, and drug development. The aims of this paper are to introduce and discuss (1) some common fundamental central pain mechanisms, (2) how they may translate into the clinical signs and symptoms across different chronic pain conditions, (3) how to evaluate gain and loss of function using quantitative pain assessment tools, and (4) the implications for optimising prevention and management of pain. The chronic pain conditions selected for the paper are neuropathic pain in general, musculoskeletal pain (chronic low back pain and osteoarthritic pain in particular), and visceral pain (irritable bowel syndrome in particular). The translational mechanisms addressed are local and widespread sensitisation, central summation, and descending pain modulation.
Physical activity and the risk of proximal colon and distal colon cancers : A meta-analysis

Terry Boyle , Tessa Keegel, Fiona Bull, Jane Heyworth, Lin Fritschi 1. Western Australian Institute for Medical Research, The University of Western Australia, Australia. 2. School of Population Health, The University of Western Australia, Australia. 3. Monash Centre for Occupational and Environmental Health, Monash University, Australia. 4. McCaughey Centre, School of Population Health, The University of Melbourne, Australia.
Pathogenesis of Pulmonary Vasculitis

Vasculitis is inflammation of blood vessels and can affect any type of vessel in any organ. Pulmonary vasculitis usually is a component of a systemic small vessel vasculitis. Three major forms of small vessel vasculitis that often affect the lungs are Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. These forms of vasculitis are strongly associated with antineutrophil cytoplasmic autoantibodies (ANCA) directed against enzymes contained in the primary granules of neutrophils and peroxidase-positive lysosomes of monocytes. This review discusses the evidence for a pathogenic role of ANCA. In vitro, ANCAs can activate cytokine-primed neutrophils and monocytes resulting in oxygen radical formation and release of lysosomal enzymes. In vivo, antimyeloperoxidase ANCA has been shown to induce crescentic glomerulonephritis and systemic vasculitis. Overall, the available data suggest that ANCA are indeed a pathogenic factor in the development of small-vessel vasculitis. Antiglomerular basement membrane (anti-GBM) disease also causes pulmonary vasculitis through immune attack on alveolar capillaries and glomerulonephritis through antibody mediated injury to glomerular capillaries. Thus, there is evidence that antibodies are important pathogenic factors in both ANCA disease and anti-GBM disease, however, there are also indications that T cells may play important pathogenic roles in both categories of disease as well.
High‐resolution crystal structure of apolipoprotein(a) kringle IV type 7: Insights into ligand binding

Apolipoprotein(a) [apo(a)] consists of a series of tandemly repeated modules known as kringles that are commonly found in many proteins involved in the fibrinolytic and coagulation cascades, such as plasminogen and thrombin, respectively. Specifically, apo(a) contains multiple tandem repeats of domains similar to plasminogen kringle IV (designated as KIV1 to KIV10) followed by sequences similar to the kringle V and protease domains of plasminogen. The KIV domains of apo(a) differ with respect to their ability to bind lysine or lysine analogs. KIV10 represents the high‐affinity lysine‐binding site (LBS) of apo(a); a weak LBS is predicted in each of KIV5–KIV8 and has been directly demonstrated in KIV7. The present study describes the first crystal structure of apo(a) KIV7, refined to a resolution of 1.45 Å, representing the highest resolution for a kringle structure determined to date. A critical substitution of Tyr‐62 in KIV7 for the corresponding Phe‐62 residue in KIV10, in conjunction with the presence of Arg‐35 in KIV7, results in the formation of a unique network of hydrogen bonds and electrostatic interactions between key LBS residues (Arg‐35, Tyr‐62, Asp‐54) and a peripheral tyrosine residue (Tyr‐40). These interactions restrain the flexibility of key LBS residues (Arg‐35, Asp‐54) and, in turn, reduce their adaptability in accommodating lysine and its analogs. Steric hindrance involving Tyr‐62, as well as the elimination of critical ligand‐stabilizing interactions within the LBS are also consequences of this interaction network. Thus, these subtle yet critical structural features are responsible for the weak lysine‐binding affinity exhibited by KIV7 relative to that of KIV10.
Using the Implicit Association Test to Assess Risk Propensity Self–Concept: Analysis of Its Predictive Validity on A Risk–Taking Behaviour in A Natural Setting

The present work analyses the predictive validity of measures provided by several available self–report and indirect measurement instruments to assess risk propensity (RP) and proposes a measurement instrument using the Implicit Association Test: the IAT of Risk Propensity Self–Concept (IAT–RPSC), an adaptation of the prior IAT–RP of Dislich et al. Study 1 analysed the relationship between IAT–RPSC scores and several RP self–report measures. Participants’ risk–taking behaviour in a natural setting was also assessed, analyzing the predictive validity of the IAT–RPSC scores on risk–taking behaviour compared with the self–report measures. Study 2 analysed the predictive validity of the IAT–RPSC scores in comparison with other indirect measures. Results of these studies showed that the IAT–RPSC scores exhibited good reliability and were positively correlated to several self–report and indirect measures, providing evidence for convergent validity. Most importantly, the IAT–RPSC scores predicted risk–taking behaviour in a natural setting with real consequences above and beyond all other self–report and indirect measures analysed. Copyright © 2013 European Association of Personality Psychology
Pengaruh Akuntabilitas dan Transparansi Pengelolaan Zakat terhadap Minat Muzakki Membayar Zakat

Zakat merupakan salah satu rukun islam yang terdiri dari syahadat, salat, zakat, puasa, dan haji bagi yang mampu. Zakat dapat dijadikan bukti nyata kepedulian umat islam terhadap golongan miskin dan tidak mampu. Dalam memudahkan pembayaran dan penyaluran dana zakat pemerintah membentuk Organisasi Pengelola Zakat (OPZ) yang terdiri atas Lembaga Amil Zakat (LAZ) dan Badan Amil Zakat Nasional (BAZNAS) Hasil dari pengujian hipotesis di dalam penelitian secara parsial ditunjukkan nilai t hitung untuk variabel akuntabilitas sebesar 2,914 dan untuk variabel transparansi sebesar 2,382. Sedangkan hasil uji f atau secara simultan variabel akuntabilitas dan transparai ditunjukkan dengan nilai f hitung sebesar 12.532. Jadi hasil dari uji t dan uji f membuktikan baik secara parsial dan simultan variabel akuntabilitas dan transparansi berpengaruh positif dan signifikan terhadap minat muzakki membayar zakat pada BAZNAS Kota Makassar.
First detection of the field star overdensity in the Perseus arm

Aims. The main goal of this study is to detect the stellar overdensity associated with the Perseus arm in the anticenter direction. Methods. We used the physical parameters derived from Stromgren photometric data to compute the surface density distribution as a function of galactocentric distance for different samples of intermediate young stars. The radial distribution of the interstellar absorption has also been derived. Results. We detected the Perseus arm stellar overdensity at 1.6 ± 0.2 kpc from the Sun with a significance of 4–5σ and a surface density amplitude of around 10%, slightly depending on the sample used. Values for the radial scale length of the Galactic disk have been simultaneously fitted obtaining values in the range [2.9,3.5] kpc for the population of the B4–A1 stars. Moreover, the interstellar visual absorption distribution is congruent with a dust layer in front of the Perseus arm. Conclusions. This is the first time that the presence of the Perseus arm stellar overdensity has been detected through individual star counts, and its location matches a variation in the dust distribution. The offset between the dust lane and the overdensity indicates that the Perseus arm is placed inside the co-rotation radius of the Milky Way spiral pattern.
Radiocarbon Dating Using Electrostatic Accelerators: Negative Ions Provide the Key

Mass spectrometric methods have long been suggested as ways of measuring 14C/12C ratios for carbon dating. One problem has been to distinguish between 14N and 14C. With negative ions and a tandem electrostatic accelerator, the 14N background is virtually absent and fewer than three 14C atoms in 1016 atoms of 12C have been easily measured.
The impacts of quality management practices on innovation

Researchers have explored the relationship between quality management (QM) and innovation in a variety of ways. A review of the literature, however, shows a few research gaps in the existing studies. There is a relative dearth of empirical studies on the interrelationships among QM practices and how they affect innovation. Moreover, there is no consistency among previous studies on the contribution of QM to innovation. While some studies have found that QM practices are positively related to innovation, others have concluded that there is no evidence of such a link. Further, the empirical studies are limited to assessing only a few types of innovation and fail to test the interaction effects of contextual variables. The purpose of this study is three-fold: to investigate the impact of QM practices on five different types of innovation, to explore the relationships between behavioural and mechanistic QM practices, and to test the interaction effects of contextual variables. Using structural equation modeling (SEM), the proposed framework and hypotheses based on a sample of 223 ISO 9001 certified companies in Canada were empirically tested. The results indicate that QM practices have either a direct or indirect effect on innovation. Behavioural QM practices, such as management leadership and training, are significantly related to mechanistic QM practices, such as process management and product design. On the other hand, there is no interaction effect of moderating variables in the relationship between QM and innovation. This research contributes to the literature in three ways: it enables academics and practitioners to understand how and why QM practices foster innovation, it provides empirical evidence about the ways behavioural QM practices are related to mechanistic QM practices, and it enhances the understanding of the contextual effects of moderating variables.
Stiffness of knee extensors in Duchenne Muscular Dystrophy

The series elastic component (SEC) of Hill's muscle model is sensitive to a modification in muscle functional demand. In this study, SEC stiffness was quantified from quick‐released movements in knee extensors of Duchenne muscular dystrophy (DMD) boys to look for possible modifications with the stage of disease. A SEC stiffness index (SI) was defined and was found significantly lower for controls than for DMD. Moreover, a linear relationship was established between mean SI and knee extensors involvement. This suggests a role for this parameter, together with other functional tests, for following patients with DMD. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1772–1774, 1998
Modélisation de la réplications des Prions : Implication de la dépendance en taille des agrégats de PrP et de l'hétérogénéité des populations cellulaires.

Les maladies a Prions sont des maladies neurodegeneratives fatales, touchant l'homme et l'animal. Meme si le risque de transmission de la maladie de la vache folle a l'homme semble maitrise, il persiste actuellement un risque de sante publique lie a la transmission iatrogene de cette forme, notamment par transfusion sanguine. Pour controler cette transmission, il est donc essentiel de mieux comprendre les mecanismes moleculaires et cellulaires de replication et de dissemination des Prions. Ces mecanismes de replication se produisent a des echelles de temps et de taille difficilement accessibles experimentalement, et ont ainsi fait l'objet de nombreuses modelisations theoriques utiles pour aider a la comprehension des mecanismes. L'objectif de cette these est de completer ces modeles mathematiques, afin d'etudier plus specifiquement les consequences dynamiques sur la replication des Prions, des proprietes de replication taille-dependante d'une part, et de l'heterogeneite des cellules impliquees dans la replication d'autre part. Dans un premier temps, nous avons generalise un modele de polymerisation nucleee pour prendre en compte un taux d'elongation des fibrilles dependant de leur taille. Nous avons principalement deduit de cette etude que la distribution en taille des agregats semble une donnee experimentale tres informative sur les mecanismes elementaires de replication, au contraire du profil cinetique d'accumulation de la PrPres peu sensibles aux proprietes de replication taille-dependantes. Dans un second temps, apres une caracterisation experimentale de l'heterogeneite cellulaire de replication, nous avons integre le mecanisme de replication intracellulaire a un modele multicellulaire par automate cellulaire continu stochastique. De maniere appliquee, cette etude nous a permis d'identifier des etapes du processus de culture cellulaire critiques pour l'etablissement d'une infection chronique, et nous a permis de proposer plusieurs protocoles pour augmenter la sensibilite des cultures cellulaires aux infections a Prions.
The potential impact of genetic counseling for mental illness

Mental disorders are relatively highly heritable, yet complex with important interactions between genetic risk and environmental factors in determining illness expression. Due to the high prevalence of these complex disorders, steady increase in knowledge about genetic contributions, and increasing public awareness, this area may come to represent a significant proportion of all genetic counseling. The potential impact of genetic counseling in mental illness is broad. As well as the conventional expectations, genetic counseling may have the positive outcomes of reducing the guilt, shame, and stigma associated with mental illness, even within families. However, like many interventions in medicine, genetic counseling for mental disorders could potentially have unintended consequences resulting in increased stigma, guilt, and shame. The potential impacts of genetic education and providing recurrence risks on stigma are reviewed, as well as the role of education about the environment as a way of modifying family members' guilt. The review allows a preliminary formulation of a series of suggestions for genetic counseling in mental illness.
The TTT Curves of the Heterogeneous and Homogeneous Crystallization of Lithium Disilicate – A Stochastic Approach to Crystal Nucleation

The present study explores the temperature and time dependence of heterogeneous crystal nucleation in a lithium disilicate glass using the stochastic approach. In particular a single lithium disilicate sample was repeatedly (284 runs) undercooled to 1173 K in a PtRh-crucible and the crystallization onset time during an isothermal hold was detected in each run. The statistical distribution of the times elapsed before crystallization is described by a first order reaction with a heterogeneous crystal nucleation rate of (9.19 ± 0.04) × 10-4 s-1 while individually shaped crystallization exotherms of each run were recorded which indicate growth of a single or only few crystals during crystallization of the entire volume. The data were used together with results of previous stochastic experiments and those of double-stage heat treatments to calculate the crystallization time of a fraction of 10-4 percent for all temperatures between glass transition and melting. The derived TTT diagram shows a double nose of crystallization in the volume at large undercoolings (0.53–0.61 Tm) and crystallization at the surface at small undercoolings (0.62–0.92 Tm) initiated by homogeneous and heterogeneous crystal nucleation, respectively. The critical cooling rate at the heterogeneous nose is approximately 73 K s-1.