Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphorylation of HMG‐I by Protein Kinase C Attenuates Its Binding Affinity to the Promoter Regions of Protein Kinase C γ and Neurogranin/RC3 Genes

Abstract: A 20‐kDa DNA‐binding protein that binds the AT‐rich sequences within the promoters of the brain‐specific protein kinase C (PKC) γ and neurogranin/RC3 genes has been characterized as chromosomal nonhistone high‐mobility‐group protein (HMG)‐I. This protein is a substrate of PKC α, β, γ, and δ but is poorly phosphorylated by PKC ε and ζ. Two major (Ser44 and Ser64) and four minor phosphorylation sites have been identified. The extents of phosphorylation of Ser44 and Ser64 were 1:1, whereas those of the four minor sites all together were <30% of the major one. These PKC phosphorylation sites are distinct from those phosphorylated by cdc2 kinase, which phosphorylates Thr53 and Thr78. Phosphorylation of HMG‐I by PKC resulted in a reduction of DNA‐binding affinity by 28‐fold as compared with 12‐fold caused by the phosphorylation with cdc2 kinase. HMG‐I could be additively phosphorylated by cdc2 kinase and PKC, and the resulting doubly phosphorylated protein exhibited a > 100‐fold reduction in binding affinity. The two cdc2 kinase phosphorylation sites of HMG‐I are adjacent to the N terminus of two of the three predicted DNA‐binding domains. In comparison, one of the major PKC phosphorylation sites, Ser64, is adjacent to the C terminus of the second DNA‐binding domain, whereas Ser44 is located within the spanning region between the first and second DNA‐binding domains. The current results suggest that phosphorylation of the mammalian HMG‐I by PKC alone or in combination with cdc2 kinase provides an effective mechanism for the regulation of HMG‐I function.
Estimation of segregation and linkage parameters in simulated data. II. Simultaneous estimation with one linked marker.

This study examined the method of simultaneous estimation of recombination frequency and parameters for a qualitative trait locus and compared the results with those of standard methods of linkage analysis. With both approaches we were able to detect linkage of an incompletely penetrant qualitative trait to highly polymorphic markers with recombination frequencies in the range of . 00-. 05. Our results suggest that detecting linkage at larger recombination frequencies may require larger data sets or large high-density families. When applied to all families without regard to informativeness of the family structure for linkage, analyses of simulated data could detect no advantage of simultaneous estimation over more traditional and much less time-consuming methods, either in detecting linkage, estimating frequency, refining estimates of parameters for the qualitative trait locus, or avoiding false evidence for linkage. However, the method of sampling affected results.
Di-μ-acetato-bis(dimethylformamide)pentakis(μ-N,2-dioxidobenzene-1-carboximidato)tetrakis(1-ethylimidazole)pentamanganese(III)manganese(II)–diethyl ether–dimethylforamide–methanol–water (1/1/1/1/0.12)

The title compound [Mn6(C7H4NO3)5(CH3CO2)2(C5H8N2)4(C3H7NO)2]·(C2H5)2O·C3H7NO·CH3OH·0.12H2O, abbreviated as MnII(OAc)2[15-MCMnIII(N)shi-5](EtIm)4(DMF)2·diethyl ether·DMF·MeOH·0.12H2O (where −OAc is acetate, MC is metallacrown, shi3− is salicylhydroximate, EtIM is n-ethylimidazole, DMF is N,N-dimethylformamide, and MeOH is methanol) contains five MnIII ions as members of the metallacrown ring and an MnII ion bound in the central cavity. The central MnII ion is seven-coordinate with a distorted face-capped trigonal–prismatic geometry. The five MnIII ions of the metallacrown ring are six-coordinate with distorted octahedral geometries. The configuration of the MnIII ions about the metallacrown ring follow a ΔΛΔPP pattern, with P representing planar. The four 1-ethylimidazole ligands are bound to four different MnIII ions. A diethyl ether solvent molecule was found to be disordered over two mutually exclusive sites with an occupancy ratio of 0.568 (7):0.432 (7). A methanol solvent molecule was found to be disordered over two mutually exclusive sites by being hydrogen bonded either to a dimethylformamide solvent molecule (major occupancy component) or to an O atom of the main molecule (minor occupancy component). The occupancy ratio refined to 0.678 (11):0.322 (11). Associated with the minor component is a partially occupied water molecule [total occupancy 0.124 (15)].
Studies of renal injury III: lipid-induced nephropathy in type II diabetes.

UNLABELLED Studies of renal injury III: Lipid-induced nephropathy in type II diabetes. BACKGROUND Nephrotoxicity from elevated circulating lipids occurs in experimental and clinical situations. We tested the hypothesis that lipid-induced nephropathy causes advanced renal failure in rats with type II diabetes and dyslipidemia. METHODS First generation (F1) hybrid rats derived from the spontaneous hypertensive heart failure rat (SHHF/Gmi-fa) and the LA/NIH-corpulent rat (LA/N-fa) were studied for 41 weeks while being on specific diets. Group 1 (14 rats) ingested 11.5% protein, 47.9% fat, and 40.6% carbohydrate. Group 2 (8 rats) ingested 26.9% protein, 16.7% animal fat, and 56.4% carbohydrate, and group 3 (20 rats) ingested 20.2% protein, 40.4% soy and coconut oil, and 39.4% carbohydrate. RESULTS Hyperglycemia was more severe in rat groups 1 and 2 than in group 3. In contrast, circulating cholesterol and hydroperoxide levels were highest in group 3, intermediate in group 2, and lowest in group 1. Group 3 had severe renal failure secondary to glomerulosclerosis and tubulointerstitial disease, with striking deposition of the lipid peroxidation stress biomarker 4-hydroxynonenal in glomeruli and renal microvessels. Moreover, in group 3, increased arterial wall thickness also connoted vascular injury. In contrast, the glycoxidation stress biomarkers pentosidine and carboxymethyl-lysine were preferentially localized to renal tubules of hyperglycemic rats in groups 1 and 2 and did not segregate with the most severe renal injury. Glomerular and interstitial fibrosis was accompanied by proportional increases in renal transforming growth factor-beta1 levels, which were threefold higher in the hypercholesterolemic rats of group 3 than in the hyperglycemic rats of group 1. CONCLUSIONS Acquisition of non-nodular glomerular sclerosis and tubulointerstitial disease is dependent on lipoxidation stress in rats with type II diabetes. On the other hand, in the absence of hypercholesterolemia, prolonged glycoxidation stress does not appear to be uniquely nephrotoxic.
Quantitative analysis of the effect of Acanthamoeba profilin on actin filament nucleation and elongation.

The current view of the mechanism of action of Acanthamoeba profilin is that it binds to actin monomers, forming a complex that cannot polymerize [Tobacman, L. S. , & Korn, E. D. (1982) J. Biol. Chem. 257, 4166-4170; Tseng, P., & Pollard, T. D. (1982) J. Cell Biol. 94, 213-218; Tobacman, L. S. , Brenner, S. L. , & Korn, E. D. (1983) J. Biol. Chem. 258, 8806-8812]. This simple model fails to predict two new experimental observations made with Acanthamoeba actin in 50 mM KC1, 1 mM MgCl2, and 1 mM EGTA. First, Acanthamoeba profilin inhibits elongation of actin filaments far more at the pointed end than at the barbed end. According, to the simple model, the Kd for the profilin-actin complex is less than 5 microM on the basis of observations at the pointed end and greater than 50 microM for the barbed end. Second, profilin inhibits nucleation more strongly than elongation. According to the simple model, the Kd for the profilin-actin complex is 60-140 microM on the basis of two assays of elongation but 2-10 microM on the basis of polymerization kinetics that reflect nucleation. These new findings can be explained by a new and more complex model for the mechanism of action that is related to a proposal of Tilney and co-workers [Tilney, L. G. , Bonder, E. M. , Coluccio, L. M. , & Mooseker, M. S. (1983) J. Cell Biol. 97, 113-124]. In this model, profilin can bind both to actin monomers with a Kd of about 5 microM and to the barbed end of actin filaments with a Kd of about 50-100 microM. An actin monomer bound to profilin cannot participate in nucleation or add to the pointed end of an actin filament. It can add to the barbed end of a filament. When profilin is bound to the barbed end of a filament, actin monomers cannot bind to that end, but the terminal actin protomer can dissociate at the usual rate. This model includes two different Kd's--one for profilin bound to actin monomers and one for profilin bound to an actin molecule at the barbed end of a filament. The affinity for the end of the filament is lower by a factor of 10 than the affinity for the monomer, presumably due to the difference in the conformation of the two forms of actin or to steric constraints at the end of the filament.
SDN/NFV-based scalable mobile service integration for gradual network evolution

The coexistence of heterogeneous networks is becoming increasingly more common with the evolution towards 5G, increasing the complexity and cost of deploying and managing these networks. Network operators consequently need to find efficient ways of flexibly constructing and operating networks within a heterogeneous network environment in order to reduce operational expenditure (OPEX) and capital expenditure (CAPEX). One possible way to meet this requirement is the accommodation of previous legacy network services in the newly-deployed network while gradually reducing the reliance on physical legacy networks. Software-defined transitional network (SDTN) architecture is a strong candidate to achieve this. In the SDTN, the software-defined networking and the networkf function virtualization (SDN/NFV) plays a key role in integrating legacy network services into the newly-deploying network. This paper proposes an SDTN architecture and presents an example of its deployment in a mobile network evolution scenario in which 3G mobile services are integrated into a 4G network. The unified mobility management, in which 3G mobile services are integrated into a 4G access networks based on SDN/NFV is described. The network nodes for legacy mobility management services are virtualized at the control plane and accommodated into the SDTN architecture. As a result, the mobility management is interoperable between the virtualized legacy network service functions and the underlying 4G network. In order to support various heterogeneous services integration into the 4G mobile network, scalable edge switches are proposed for protocol mapping between incoming heterogeneous service traffic and 4G data. The proposed SDTN approach can be applied to the future deployment of 5G networks by accommodating various pre-existing legacy services in newly-deploying networks.
Systematic mapping of fragile X granules in the mouse brain reveals a potential role for presynaptic FMRP in sensorimotor functions

Loss of Fragile X mental retardation protein (FMRP) leads to Fragile X syndrome (FXS), the most common form of inherited intellectual disability and autism. Although the functions of FMRP and its homologs FXR1P and FXR2P are well studied in the somatodendritic domain, recent evidence suggests that this family of RNA binding proteins also plays a role in the axonal and presynaptic compartments. Fragile X granules (FXGs) are morphologically and genetically defined structures containing Fragile X proteins that are expressed axonally and presynaptically in a subset of circuits. To further understand the role of presynaptic Fragile X proteins in the brain, we systematically mapped the FXG distribution in the mouse central nervous system. This analysis revealed both the circuits and the neuronal types that express FXGs. FXGs are enriched in circuits that mediate sensory processing and motor planning—functions that are particularly perturbed in FXS patients. Analysis of FXG expression in the hippocampus suggests that CA3 pyramidal neurons use presynaptic Fragile X proteins to modulate recurrent but not feedforward processing. Neuron‐specific FMRP mutants revealed a requirement for neuronal FMRP in the regulation of FXGs. Finally, conditional FMRP ablation demonstrated that FXGs are expressed in axons of thalamic relay nuclei that innervate cortex, but not in axons of thalamic reticular nuclei, striatal nuclei, or cortical neurons that innervate thalamus. Together, these findings support the proposal that dysregulation of axonal and presynaptic Fragile X proteins contribute to the neurological symptoms of FXS. J. Comp. Neurol. 520:3687–3706, 2012. © 2012 Wiley Periodicals, Inc.
Drug Metabolites as Cytochrome P450 Inhibitors: A Retrospective Analysis and Proposed Algorithm for Evaluation of the Pharmacokinetic Interaction Potential of Metabolites in Drug Discovery and Development

Understanding drug-drug interactions (DDIs) is a key component of clinical practice ensuring patient safety and efficacy of medicines. The role of drug metabolites in DDIs is a developing area of science, and has been recently highlighted in a draft regulatory guidance. The guidance states that metabolites representing ≥25% of the parent drug’s area under the plasma concentration/time curve and/or >10% of exposure of total drug-related material should trigger in vitro characterization of metabolites for cytochrome P450 inhibition and propensity for DDIs. The relationship between in vitro cytochrome P450 inhibitory potency, systemic exposure, and DDI potential of drug metabolites was examined using the Pfizer development database to identify compounds with pre-existing in vivo biotransformation data, where circulating metabolites were identified in humans. The database yielded 33 structurally diverse compounds with collectively 115 distinct circulating metabolites. Of these, 52% (60/115) achieved exposures >25% of parent drug levels as judged from mass balance/metabolite identification studies. It was noted that 14 metabolite standards for 12 parent drugs had been synthesized, monitored in clinical studies, and examined for cytochrome P450 inhibition. For the 14 metabolite/parent drug pairs, no clinically relevant DDIs were expected to occur against the major human cytochrome P450 isoforms. A review of the literature for parent/metabolite DDI information was also conducted to examine trends using a larger data set. Leveraging the analysis of both internal and literature-based data sets, an algorithm was devised for use in drug discovery/early development to assess cytochrome P450 inhibitory potential of drug metabolites and the propensity to cause a clinically relevant DDI.
Essays in economics of education and training

This thesis collects four studies on the economics of education and training. The first study examines the impact on school attendance of the provision of free school uniforms to children in poor urban areas in Ecuador. Consistent with a sunk-cost effect, it finds that free school uniforms increase absenteeism from school. The second study analyzes the effects of training vouchers for low-skilled workers on their training participation, types of training, earnings and labor market mobility. Vouchers lead to more training but come with a high deadweight loss. Vouchers also seem to shift participation from more specific to more general forms of training. The third study uses data from four waves of PISA to inquire the factors that explain the substantial decline between 2003 and 2012 in math scores of 15 years-old students in the Netherlands. The key finding is that despite substantial changes in the characteristics of students and schools, most of the decline should be attributed to changes in the coefficients from a regression of math scores on characteristics. The last study reports the results from an evaluation of a pilot program in which context learning for the teaching of mathematics is replaced by a new curriculum that emphasizes concepts and mathematical thinking. It turns out that girls tend to shy away from (advanced) math when the new curriculum is offered, but that girls do not perform worse relative to boys when exposed to the new curriculum.
Empty Seats or Empty Threats? Examining the Effects of the 1994-1995 and 2004-2005 Lockouts on Attendance and Revenue in the National Hockey League

Labor-related work stoppages in professional sports have the potential to alienate fans—but whether they generate sustained reductions in demand remains an open question. Existing evidence generally indicates work stoppages may negatively impact attendance but only for a short period of time. Focusing on the 1994, 2004, and 2012 lockouts in the National Hockey League, this article finds evidence consistent with sustained decreases in attendance following the 1994-1995 lockout and revenue following the 2004-2005 and 2012-2013 lockouts. Back-of-the-envelope estimates suggest work stoppages may still be optimal even if there is a sustained negative impact on fan demand.
Controlling Spatially Invariant Systems using Finite Arrays of Actuators and Sensors

Distributed parameter systems, where the underlying dynamics are spatially invariant, are common in a range of applications including the control of flows and smart structures or the cross-directional control of web processes. Bamieh et al. [1] have shown that controllers for these processes are also spatially invariant, leading to controller structures that are particularly simple to implement. However, these controllers use measurements that are continuous in space and generate control inputs that are are also spatially continuous. In practice, most applications use arrays of discrete, but identical actuators and sensors and this paper uses results from sampling theory to show that the controller can be implemented using these discrete arrays without loss of performance, provided that conditions on the separation between actuators and sensors are satisfied in order to avoid aliasing. It is shown that in many practical systems. Under these circumstances, it is better to incorporate the effect of aliasing by including the cross-coupling between aliased spatial frequencies in the system model.
Trending: The Promises and the Challenges of Big Social Data

Today the term " big data " is often used in popular media, business, computer science and computer industry. For instance, in June 2008 Wired magazine opened its special section on " The Petabyte Age " by stating: " Our ability to capture, warehouse, and understand massive amounts of data is changing science, medicine, business, and technology. As our collection of facts and figures grows, so will the opportunity to find answers to fundamental questions " (" The Petabyte Age "). In February 2010, Economist started its special report " Data, data everywhere " with the phrase " the industrial revolution of data " (coined by computer scientist Joe Hellerstein) and then went to note that " The effect is being felt everywhere, from business to science, from government to the arts " (" Data, data everywhere "). Discussions in popular media usually do not define " big data " in qualitative terms. However, in computer industry the term has a more precise meaning: " Big Data is a term applied to data sets whose size is beyond the ability of commonly used software tools to capture, manage, and process the data within a tolerable elapsed time. Big data sizes are a constantly moving target currently ranging from a few dozen terabytes to many petabytes of data in a single data set " (" Big data "). Since its formation in 2008, NEH Office of Digital Humanities has been systematically creating grant opportunities to help humanists work with large data sets. The following statement from 2011 grant competition organized by NEH together with a number of other research agencies in USA, Canada, UK, and Netherlands provides an excellent description of what is at stake: " The idea behind the Digging into Data Challenge is to address how "big data" changes the research landscape for the humanities and social sciences. Now that we have massive databases of materials used by scholars in the humanities and social sciences-ranging from digitized books, newspapers, and music to transactional data like web searches, sensor data or cell phone records-what new, computationally-based research methods might we apply? As the world becomes increasingly digital, new techniques will be needed to search, analyze, and understand these everyday materials. " (" Digging into Data Challenge "). The projects funded by 2009 Digging Into Data Challenge and earlier NEH 2008 Humanities High Performance Computing grant program begin to map the …
Validation of an optical surface plasmon resonance biosensor assay for screening (fluoro)quinolones in egg, fish and poultry

A surface plasmon resonance biosensor immunoassay has been developed for multi-residue determination of 13 (fluoro)quinolone antibiotics in poultry meat, eggs and fish. The following performance characteristics were determined according to the guidelines laid down for screening assay validation in European Decision 2002/657/EC: detection capability, specificity/selectivity, decision limit, repeatability, ruggedness and stability. The detection capability estimated for norfloxacin, the reference fluoroquinolone, was below 0.5, 1 and 1.5 ng g−1 for poultry meat, egg and fish, respectively. The screening assay proved specific and showed satisfactory sensitivity below the MRL levels even though flumequine and oxolinic acid had lower cross-reactivities. A wide range of non-MRL substances were also detected at concentrations below 10 ng g−1. Repeatability was good with both intra- and inter-assay coefficients of variation <6%; ruggedness was also demonstrated.
c-Jun Terminal Kinase-2 Gene Deleted Mice Overexpress Hemeoxygenase-1 and Are Protected From Hepatic Ischemia Reperfusion Injury

Background. Targeted deletion of c-jun amino terminal kinase-2 (jnk-2) upregulates the activator protein-1 transcription factor system. We hypothesized that this would lead to induction of hemeoxygenase-1 (HO-1) and confer protection from hepatic ischemia reperfusion injury. Methods. Wild-type and jnk-2 −/− animals were subjected to hepatic ischemia reperfusion insults in two models: a total hepatic ischemia model involving timed Pringle maneuver, and a partial hepatic ischemia model involving selective occlusion of the portal pedicle supplying the left hepatic lobe. Optimal durations of injury were calibrated for each model. After 24 hr, animals were killed, and blood and tissues were collected for alanine aminotransferase, histologic injury scoring, and other analyses. Before total or partial hepatic ischemia reperfusion insults, some animals were subject to HO-1 inhibition with chromium mesoporphyrin IX or Kupffer cell depletion with liposomal clodronate. Bone marrow-derived monocytes were grown from hemopoietic progenitors taken from wild-type and jnk-2 −/− mice before stimulation with lipopolysaccharide and measurement of tumour necrosis factor-&agr; production. Results. Jnk-2 −/− animals were protected from hepatic ischemia reperfusion injury. HO-1 expression and activity was elevated in jnk-2 −/− animals (2.2-fold; P=0.006). Most HO-1 was expressed in Kupffer cells. Inhibition of HO-1 in jnk-2 −/− animals led to the loss of protection from ischemia. Depletion of Kupffer cells using liposomal clodronate led to loss of hepatic HO-1 expression and much more severe injury in wild-type and jnk-2 −/− animals. In vitro studies of cultured macrophages demonstrated reduced tumour necrosis factor-&agr; secretion after lipopolysacharride stimulus, an effect lost after HO-1 inhibition.