Miracle-dz/UniFAR-FTUs huggingface dataset:
The phosphorylation of ARPP19 by Greatwall renders the auto-amplification of MPF independently of PKA in Xenopus oocytes

Summary Entry into mitosis or meiosis relies on the coordinated action of kinases and phosphatases that ultimately leads to the activation of Cyclin-B–Cdk1, also known as MPF for M-phase promoting factor. Vertebrate oocytes are blocked in prophase of the first meiotic division, an arrest that is tightly controlled by high PKA activity. Re-entry into meiosis depends on activation of Cdk1, which obeys a two-step mechanism: a catalytic amount of Cdk1 is generated in a PKA and protein-synthesis-dependent manner; then a regulatory network known as the MPF auto-amplification loop is initiated. This second step is independent of PKA and protein synthesis. However, none of the molecular components of the auto-amplification loop identified so far act independently of PKA. Therefore, the protein rendering this process independent of PKA in oocytes remains unknown. Using a physiologically intact cell system, the Xenopus oocyte, we show that the phosphorylation of ARPP19 at S67 by the Greatwall kinase promotes its binding to the PP2A-B55&dgr; phosphatase, thus inhibiting its activity. This process is controlled by Cdk1 and has an essential role within the Cdk1 auto-amplification loop for entry into the first meiotic division. Moreover, once phosphorylated by Greatwall, ARPP19 escapes the negative regulation exerted by PKA. It also promotes activation of MPF independently of protein synthesis, provided that a small amount of Mos is present. Taken together, these findings reveal that PP2A-B55&dgr;, Greatwall and ARPP19 are not only required for entry into meiotic divisions, but are also pivotal effectors within the Cdk1 auto-regulatory loop responsible for its independence with respect to the PKA-negative control.
A Duration-Dependent Account of Coarticulation for Hyper- and Hypoarticulation

Abstract Previous studies investigating anticipatory coarticulation in emphatically stressed CV sequences and during fast speaking rates reported that three factors contributed to the overall extent of the documented coarticulation. These factors were: (1) vowel identity, (2) vowel space expansion (emphasis) or reduction (fast rate), and a hypothesized (3) ‘deeper’ and ‘shallower’ stop closure contact in emphatic and faster speech, respectively. The objective of the current research was to conceptually and quantitatively unify these two studies. This was accomplished by showing that the opposite changes to frequency onsets of F2 transitions due to emphatic and rapid speech systematically vary as a function of the durational changes in the stop closure interval. Specifically, the decrease in coarticulation in emphatic speech is characterized by increases in F2 onsets and longer stop closures (relative to a normal baseline); the increase in coarticulation due to rapid speech shows concomitant decreases in F2 onsets coinciding with shorter stop closure intervals. Vocal tract area function simulations corresponding to emphatic and reduced speech implicitly support ‘deeper’ and ‘shallower’ closure contacts as a third factor contributing to the overall extent of anticipatory CV coarticulation.
Cystatin C-Creatinine Based Glomerular Filtration Rate Equation in Obese Chronic Kidney Disease Patients: Impact of Deindexation and Gender

Background: Cystatin C is considered an alternative to creatinine to estimate glomerular filtration rate (GFR). However, studies have reported that increased adiposity is associated with a higher level of circulating cystatin C questioning the performance of estimation of GFR using cystatin C in obese subjects. Methods: We prospectively included 166 obese stages 1-5 chronic kidney disease (CKD) patients between 2013 and 2015. GFR was measured with a reference method without (measured GFR [mGFR]) and with adjustment to body surface area (mGFRr) and estimated (eGFR) or de-indexed eGFR using the Chronic Kidney Disease and Epidemiology (CKD-EPI) equation using creatinine (CKD-EPIcreat), cystatin (CKD-EPIcyst) and the combination of cystatin and creatinine (CKD-EPIcyst-creat). Results: The biases between mGFR and de-indexed CKD-EPIcyst-creat were significantly lower than de-indexed CKD-EPIcreat (p = 0.001). Accuracies were significantly better with de-indexed CKD-EPIcyst-creat compared to CKD-EPIcreat and CKD-EPIcyst, respectively (p = 0.04 and 0.03). Bland and Altman plot showed a great dispersion of all formulae when patients had a GFR >60 ml/min. Interestingly, there is a gender difference; biases, precisions and accuracies of de-indexed CKD-EPIcyst-creat were significantly lower in obese women. These results may be related to a difference in the change of body composition during obesity in men versus women and in fact only waist circumference (WC) was positively and significantly correlated with cystatin C (p < 0.0001) whereas body mass index (BMI; p = 0.3) was not; bias for CKD-EPIcyst-creat was related with WC. Conclusion: Cystatin C-creatinine-based GFR equations outperform creatinine-based formula in obese CKD patients especially those with BMI ≥35 and in obese women.
Rectus and oblique muscles of eyeball: a morphometric study of Indian population

During the strengthening and weakening procedures of intraocular muscles, distance of insertion from the sclerocorneal junction is an important determinant in the identification of muscles. During repositioning of the aponeurosis of the muscles, it is desired that the width should not change in order to avoid diversion of forces. Available anatomic studies on insertions of extraocular muscles are few, date back to early twentieth century and have been conducted on mostly white population. The present study is an attempt to document the insertions of recti and oblique muscles in Indian population. Forty eyeballs were removed from orbit. Insertion of recti and obliqui were cleaned and eyeballs were perfused with normal saline to regain the volume (hence shape and size) before recording observations. Insertion of recti and obliqui muscles were observed under various study parameters. The distance of insertion of recti from the limbus were found to be 7.3 mm, 8.06 mm, 8.71 mm, and 8.74 mm for medial, inferior, lateral, and superior rectus, respectively. The superior oblique was aponeurotic and found to be more variable in mode of insertion as compared to inferior oblique which had a fleshy and relatively constant insertion. The observations on insertion of recti and obliqui as obtained in present study differ from earlier studies to the tune of 1-1.5 mm. This may be attributed to adoption of method of reperfusion of eyeball before recording observations thus maintaining size close to in vivo. The observations are expected to be closer to actual.
Inverse optimal stabilization of cooperative control in networked multi-agent systems

For constructing a decentralized optimal control strategy for networked multi-agent systems that can accomplish consensus in a leaderless structure, we employ the inverse optimal control approach which circumvents the task of solving a HJB equation by introducing a cooperative control Lyapunov function. The decentralized controller we obtain is more flexible than the controller u = Lx in fixed network, because it not only has the advantages to handle systems of high relative degree, but it can also improve the performance of networked multi-agent systems by adjusting a positive definite and symmetrical matrix. On the other hand, the decentralized controller is optimal with respect to a meaningful cost functional which is useful to quantify and improve the performance of networked multi-agent systems. Finally, examples are presented to illustrate both the design process and performance of cooperative controls.
ADAM12‐S Stimulates Bone Growth in Transgenic Mice by Modulating Chondrocyte Proliferation and Maturation

ADAM12‐S transgenic mice exhibit a pronounced increase in the length of bones, such as femur, tibia, and vertebrae. The effect of ADAM12‐S on longitudinal bone growth involves the modulation of chondrocyte proliferation and maturation, likely through proteolytic activities and altered cell–extracellular matrix interactions in the growth plate.
Genetic Background and Expression of the New qepA4 Gene Variant Recovered in Clinical TEM-1- and CMY-2-Producing Escherichia coli

A new QepA4 variant was detected in an O86:H28 ST156-fimH38 Escherichia coli, showing a multidrug-resistance phenotype. PAβN inhibition of qepA4-harboring transconjugant resulted in increase of nalidixic acid accumulation. The qepA4 and catA1 genes were clustered in a 26.0-kp contig matching an IncF-type plasmid, and containing a Tn21-type transposon with multiple mobile genetic elements. This QepA variant is worrisome because these determinants might facilitate the selection of higher-level resistance mutants, playing a role in the development of resistance, and/or confer higher-level resistance to fluoroquinolones in association with chromosomal mutations.
Antecedents, moderators and dimensions of country‐of‐origin evaluations

Purpose – The purpose of this paper is to provide an in‐depth examination of country‐of‐origin (COO) perceptions of consumers in a multinational setting. It shows how explanatory factors like demographics, familiarity with a country's products, purchase behaviour and psychological variables jointly work to explain consumers' COO perceptions.Design/methodology/approach – This is a quantitative study using a drop‐off and pick‐up survey among three samples of consumers in Canada, Morocco and Taiwan. The final sample size was comprised of 506 male consumers. The data were analyzed using factor analysis to group countries of origin and analyses of variance to relate COO perceptions to the explanatory variables.Findings – The familiarity with products made in a country was the strongest predictor of country perceptions, followed by nationality and the manufacturing process and product complexity dimensions of country evaluation. Canadians had the highest propensity to distinguish between countries of origin on .
The role of phenotypic plasticity in driving genetic evolution

Models of population divergence and speciation are often based on the assumption that differences between populations are due to genetic factors, and that phenotypic change is due to natural selection. It is equally plausible that some of the differences among populations are due to phenotypic plasticity. We use the metaphor of the adaptive landscape to review the role of phenotypic plasticity in driving genetic evolution. Moderate levels of phenotypic plasticity are optimal in permitting population survival in a new environment and in bringing populations into the realm of attraction of an adaptive peak. High levels of plasticity may increase the probability of population persistence but reduce the likelihood of genetic change, because the plastic response itself places the population close to a peak. Moderate levels of plasticity arise whenever multiple traits, some of which are plastic and others not, form a composite trait involved in the adaptive response. For example, altered behaviours may drive selection on morphology and physiology. Because there is likely to be a considerable element of chance in which behaviours become established, behavioural change followed by morphological and physiological evolution may be a potent force in driving evolution in novel directions. We assess the role of phenotypic plasticity in stimulating evolution by considering two examples from birds: (i) the evolution of red and yellow plumage coloration due to carotenoid consumption; and (ii) the evolution of foraging behaviours on islands. Phenotypic plasticity is widespread in nature and may speed up, slow down, or have little effect on evolutionary change. Moderate levels of plasticity may often facilitate genetic evolution but careful analyses of individual cases are needed to ascertain whether plasticity has been essential or merely incidental to population differentiation.
Association between a SLC23A2 gene variation, plasma vitamin C levels, and risk of glaucoma in a Mediterranean population

Purpose Several dietary factors have been associated with glaucoma. Among them, dietary antioxidant intake (i.e., vitamin C and vitamin A) in association with glaucoma has been analyzed, but with mixed results. Genetic factors may play a role in modulating the effect of dietary antioxidant intake on glaucoma; however, nutrigenetic studies in this field are scarce. Our aim was to study the association between selected polymorphisms in key proteins related to vitamin C and vitamin A concentrations and primary open-angle glaucoma (POAG). Methods We performed a case-control study matched for age, sex, and bodyweight. We recruited 300 subjects (150 POAG cases and 150 controls) from a Mediterranean population and determined the plasma concentrations of vitamin C and vitamin A for each subject. We selected the following single-nucleotide polymorphisms (SNPs) in genes related to vitamin A and vitamin C concentrations: rs176990 and rs190910 in the retinol-binding protein 1 (RBP1) gene; and rs10063949 and rs1279683 in the Na+-dependent L-ascorbic acid transporters 1 and 2, respectively (encoded by the SLC23A1 and SLC23A2 genes). Results We found a statistically significant association between the rs1279386 (A>G) SNP in SLC23A2 and POAG risk. In the crude analysis, homozygous subjects for the G allele (GG subjects) had higher risk of POAG than other genotypes (OR: 1.67; 95% CI: 1.03–2.71). This association remained statistically significant (p=0.010) after multivariate adjustment for potential confounders. We also found that POAG patients had lower plasma vitamin C concentrations than control subjects (9.9±1.7 µg/ml versus 11.7±1.8 µg/ml, p<0.001). Moreover, we consistently detected a significant association between the rs1279386 SNP in SLC23A2 and plasma vitamin C concentrations: GG subjects had significantly lower plasma vitamin C concentrations than the other genotypes (9.0±1.4 µg/ml versus 10.5±1.6 µg/ml, p<0.001 in POAG cases and 10.9±1.6 µg/ml versus 12.1±1.8 µg/ml, p<0.001 in controls). The rs10063949 SNP in SLC23A1 was not associated with either plasma vitamin C concentrations or POAG risk. Similarly, SNPs in RBP1 were not associated with vitamin A concentrations or POAG risk. Conclusions The rs1279683 SNP in SLC23A2 was significantly associated with lower plasma concentrations of vitamin C and with higher risk of POAG in GG subjects.
Treatment of near-electrode regions in a simple model of blasted electric arc

The paper deals with near-electrode regions of electric arc burning in argon in an arc heater. The arc behavior is described by a mathematical model using the gas transport and thermodynamic properties and real experimental data. The near-electrode regions obey different rules than the intensively blasted arc column alone, but the integral measured data include both of them. For modelling the arc, the near-electrode regions have been previously neglected or described using the data taken from other authors who investigated just the near-electrode phenomena. Now, the influence of near-electrodes regions is tried to be excluded by procedures based just on the measured data. The obtained results are shown in comparison with the data given by other authors.
Modelling tropical landscapes for ecological management: what can we learn from preliminary Savanna.au simulations?

Landscape scale modelling incorporates complex spatial and temporal processes (e.g. soil hydrology, runoff and sediment loss) operating at finer spatial resolutions than the model. It is important that these processes are accurately incorporated into larger scale models either intrinsically or extrinsically. Such hydrological factors ultimately determine plant production important for land use practices such as cattle grazing which occupies vast areas of northern Australia.
Solving the Problem of Unattributed Political Violence

High rates of missing perpetrator information in political violence data pose a serious challenge for studies into militant group behavior and the microdynamics of conflict more generally. In this article we introduce multiple imputation (MI) as the best available method for minimizing the impact of missing perpetrator information on quantitative analyses of political violence, a method that can easily be incorporated into most quantitative research designs. MI will produce unbiased attributions when the reasons for missingness are known and can be controlled for using observed variables, rendering responsibility for unclaimed attacks, “missing at random” (MAR) – which we show is a reasonable assumption in the case of political violence based on current theory of militant group claiming. We lay out the logics and steps of MI, identify variables and data sources, and demonstrate that MI produced better results in the case of the Pakistani Taliban’s response to drone strikes.
Characterization of Structural Features Controlling the Receptiveness of Empty Class II MHC Molecules

MHC class II molecules (MHC II) play a pivotal role in the cell-surface presentation of antigens for surveillance by T cells. Antigen loading takes place inside the cell in endosomal compartments and loss of the peptide ligand rapidly leads to the formation of a non-receptive state of the MHC molecule. Non-receptiveness hinders the efficient loading of new antigens onto the empty MHC II. However, the mechanisms driving the formation of the peptide inaccessible state are not well understood. Here, a combined approach of experimental site-directed mutagenesis and computational modeling is used to reveal structural features underlying “non-receptiveness. ” Molecular dynamics simulations of the human MHC II HLA-DR1 suggest a straightening of the α-helix of the β1 domain during the transition from the open to the non-receptive state. The movement is mostly confined to a hinge region conserved in all known MHC molecules. This shift causes a narrowing of the two helices flanking the binding site and results in a closure, which is further stabilized by the formation of a critical hydrogen bond between residues αQ9 and βN82. Mutagenesis experiments confirmed that replacement of either one of the two residues by alanine renders the protein highly susceptible. Notably, loading enhancement was also observed when the mutated MHC II molecules were expressed on the surface of fibroblast cells. Altogether, structural features underlying the non-receptive state of empty HLA-DR1 identified by theoretical means and experiments revealed highly conserved residues critically involved in the receptiveness of MHC II. The atomic details of rearrangements of the peptide-binding groove upon peptide loss provide insight into structure and dynamics of empty MHC II molecules and may foster rational approaches to interfere with non-receptiveness. Manipulation of peptide loading efficiency for improved peptide vaccination strategies could be one of the applications profiting from the structural knowledge provided by this study.
Relative energy balance, CKD, and risk of cardiovascular and all-cause mortality.

BACKGROUND Mortality risk for people with chronic kidney disease is substantially greater than that for the general population, increasing to a 7-fold greater risk for those on dialysis therapy. Higher body mass index, generally due to higher energy intake, appears protective for people on dialysis therapy, but the relationship between energy intake and survival in those with reduced kidney function is unknown. STUDY DESIGN Prospective cohort study with a median follow-up of 14.5 (IQR, 11.2-15.2) years. SETTING & PARTICIPANTS Blue Mountains Area, west of Sydney, Australia. Participants in the general community enrolled in the Blue Mountains Eye Study (n = 2,664) who underwent a detailed interview, food frequency questionnaire, and physical examination including body weight, height, blood pressure, and laboratory tests. PREDICTORS Relative energy intake, food components (carbohydrates, total sugars, fat, protein, and water), and estimated glomerular filtration rate (eGFR). Relative energy intake was dichotomized at 100%, and eGFR, at 60 mL/min/1.73 m(2). OUTCOMES All-cause and cardiovascular mortality. MEASUREMENTS All-cause and cardiovascular mortality using unadjusted and adjusted Cox proportional regression models. RESULTS 949 people died during follow-up, 318 of cardiovascular events. In people with eGFR<60 mL/min/1.73 m(2) (n = 852), there was an increased risk of all-cause mortality (HR, 1.48; P = 0.03), but no increased risk of cardiovascular mortality (HR, 1.59; P = 0.1) among those with higher relative energy intake compared with those with lower relative energy intake. Increasing intake of carbohydrates (HR per 100g/d, 1.50; P = 0.04) and total sugars (HR per 100g/d, 1.62; P = 0.03) was associated significantly with increased risk of cardiovascular mortality. LIMITATIONS Under-reporting of energy intake, baseline laboratory and food intake values only, white population. CONCLUSIONS Increasing relative energy intake was associated with increased all-cause mortality in patients with eGFR<60 mL/min/1.73 m(2). This effect may be mediated by increasing total sugars intake on subsequent cardiovascular events.
Modelling with stakeholders e Next generation

This paper updates and builds on ‘ Modelling with Stakeholders ’ Voinov and Bousquet, 2010 which demonstrated the importance of, and demand for, stakeholder participation in resource and environmental modelling. This position paper returns to the concepts of that publication and reviews the progress made since 2010. A new development is the wide introduction and acceptance of social media and web applications, which dramatically changes the context and scale of stakeholder interactions and participation. Technology advances make it easier to incorporate information in interactive formats via visualization and games to augment participatory experiences. Citizens as stakeholders are increasingly demanding to be engaged in planning decisions that affect them and their communities, at scales from local to global. How people interact with and access models and data is rapidly evolving. In turn, this requires changes in how models are built, packaged, and disseminated: citizens are less in awe of experts and external authorities, and they are increasingly aware of their own capabilities to provide inputs to planning processes, including models. The continued acceleration of environmental degradation and natural resource depletion accompanies these societal changes, even as there is a growing acceptance of the need to transition to alternative, possibly very different, life styles. Substantive transitions cannot occur without signi ﬁ cant changes in human behaviour and perceptions. The important and diverse roles that models can play in guiding human behaviour, and in disseminating and increasing societal knowledge, are a feature of stakeholder processes today.