Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro and in Vivo Dimerization of Human Endonuclease III Stimulates Its Activity*

Human endonuclease III (hNTH1), a DNA glycosylase with associated abasic lyase activity, repairs various mutagenic and toxic-oxidized DNA lesions, including thymine glycol. We demonstrate for the first time that the full-length hNTH1 positively cooperates in product formation as a function of enzyme concentration. The protein concentrations that caused cooperativity in turnover also exhibited dimerization, independent of DNA binding. Earlier we had found that the hNTH1 consists of two domains: a well conserved catalytic domain, and an inhibitory N-terminal tail. The N-terminal truncated proteins neither undergo dimerization, nor do they show cooperativity in turnover, indicating that the homodimerization of hNTH1 is specific and requires the N-terminal tail. Further kinetic analysis at transition states reveals that this homodimerization stimulates an 11-fold increase in the rate of release of the final product, an AP-site with a 3′-nick, and that it does not affect other intermediate reaction rates, including those of DNA N-glycosylase or AP lyase activities that are modulated by previously reported interacting proteins, YB-1, APE1, and XPG. Thus, the site of modulating action of the dimer on the hNTH1 reaction steps is unique. Moreover, the high intranuclear (2.3 μm) and cytosolic (0.65 μm) concentrations of hNTH1 determined here support the possibility of in vivo dimerization; indeed, in vivo protein cross-linking showed the presence of the dimer in the nucleus of HeLa cells. Therefore, it is likely that the dimerization of hNTH1 involving the N-terminal tail masks the inhibitory effect of this tail and plays a critical role in its catalytic turnover in the cell.
14-3-3 Acts as an Intramolecular Bridge to Regulate cdc25B Localization and Activity*

One of the major regulators of mitosis in somatic cells is cdc25B. cdc25B is tightly regulated at multiple levels. The final activation step involves the regulated binding of 14-3-3 proteins. Previous studies have demonstrated that Ser-323 is a primary 14-3-3 binding site in cdc25B, which influences its activity and cellular localization. 14-3-3 binding to this site appeared to interact with the N-terminal domain of cdc25B to regulate its activity. The presence of consensus 14-3-3 binding sites in the N-terminal domain suggested that the interaction is through direct binding of the 14-3-3 dimer to sites in the N-terminal domain. We have identified Ser-151 and Ser-230 in the N-terminal domain as functional 14-3-3 binding sites utilized by cdc25B in vivo. These low affinity sites cooperate to bind the 14-3-3 dimer bound to the high affinity Ser-323 site, thus forming an intramolecular bridge that constrains cdc25B structure to prevent access of the catalytic site. Loss of 14-3-3 binding to either N-terminal site relaxes cdc25B structure sufficiently to permit access to the catalytic site, and the nuclear export sequence located in the N-terminal domain. Mutation of the Ser-323 site was functionally equivalent to the mutation of all three sites, resulting in the complete loss of 14-3-3 binding, increased access of the catalytic site, and access to nuclear localization sequence.
CARACTERÍSTICAS FÍSICO-QUÍMICAS DE LA LECHE CRUDA EN LAS ZONAS DE AROA Y YARACAL, VENEZUELA Physico-chemical Characteristics of Raw Milk from the Aroa and Yaracal Regions, Venezuela

Durante un periodo de ocho meses, se analizaron 2.535 muestras de leche con o sin almacenamiento en frio, provenientes de vacas en ordeno en 40 fincas de las zonas de Aroa y Yaracal, de los estados Yaracuy y Falcon, Venezuela, determinandose: acidez, crioscopia, cloruros, tiempo de reduccion de azul de metileno, densidad, grasa, solidos totales, solidos no grasos y volumen de produccion. Se obtuvieron promedios, se realizaron analisis de varianza, comparacion de medias y se calcularon correlaciones. Para el analisis de varianza se establecieron grupos de asociaciones: zona-tipo-mes, zona-tipo, zona y mes. De las variables estudiadas se encontraron valores fuera de los establecidos por las normas COVENIN, en crioscopia en la zona de Aroa, leche caliente, mes de abril y leche fria, meses de enero y junio; y en la zona de Yaracal, leche fria en todos los meses estudiados y leche caliente en los meses de marzo, abril, mayo y julio. Los solidos totales resultaron menores a los valores establecidos por las normas COVENIN en la zona de Aroa, leche fria, mes de mayo y leche caliente para los meses de febrero, marzo, abril y mayo ; para la zona de Yaracal tanto para leche fria y leche caliente durante todos los meses estudiados excepto leche caliente, mes de enero. Al aplicar analisis de varianza, se consiguieron diferencias altamente significativas para todas las asociaciones, excepto acidez y crioscopia por zona. Los valores mas altos de acidez se obtuvieron en la zona de Yaracal, leche caliente y durante el mes de agosto. En ambas zonas estudiadas, los valores promedios mas altos en crioscopia se consiguieron en leche fria y los mas bajos en leche caliente en la zona de Aroa. Las correlaciones obtenidas fueron altamente significativas.
Pharmacology of orally administered Δ9‐tetrahydrocannabinol

A systematic study of the oral administration of 35 mg. of Δ9‐tetrahydrocannabinol (Δ9‐THC) in 5 different vehicles indicates that the speed and degree of absorption are greatly influenced by the vehicle. When the same vehicle was used, absorption of the drug varied significantly among individuals. The psychologic effects were characterized by a marihuana‐like “high” qualified by experienced sub;ects to be more intense than that associated with smoked marihuana or hashish. Predominant physiologic effects were congestion of the conjunctiva, tachycardia, and moderate increases in blood pressure. Hypotention with bradycardia occurred when the blood pressure control was challenged by a change in posture or blood volume. The biologic half‐life of the drug appears to be less than 48 hours. Thin‐layer chromatographic analysis indicates that the metabolites in the plasma are the 11‐OH‐Δ9‐THC, an unknown compound, the 8,11‐di‐OH‐Δ9‐THC, and a group of more polar substances located at the origin. Δ9‐THC and its metabolites are excreted extensively in the urine and feces. The maior urinary metabolites are the 8,1l‐di‐OH‐Δ9‐THC and polar substances where cannabinoid acids predominate. Appreciable amounts of Δ9‐THC are found in feces.
Empirical Analysis of the Effects of Supplier Selection and Integration on Customer Satisfaction and Business Performance

There has been an increased focus on supplier selection and integration in the field of international operation management in recent years, which are the core of supply strategies. Based on the database of International Manufacturing Strategy Survey (IMSS) 2003, an empirical study is carried out to examine whether different supplier selection criteria and integration mechanisms can improve customer satisfaction (CS) and business performance (BP). The data analysis shows that supplier selection based on performance and collaboration have direct or indirect positive effects on CS and BP; the effect of supplier selection based on unit price on CS and BP is not statistically significant; information sharing and system coupling, as the major mechanisms of supplier integration, have positive effect on CS and BP significantly. The findings of this research have theoretical and practical implications for enterprises to choose and adjust supply selection criteria and supply integration practice
Involvement of Pre- and Postsynaptic Mechanisms in Posttetanic Potentiation at Aplysia Synapses

Posttetanic potentiation (PTP) is a common form of short-term synaptic plasticity that is generally thought to be entirely presynaptic. Consistent with that idea, PTP of evoked excitatory postsynaptic potentials at Aplysia sensory-motor neuron synapses in cell culture was reduced by presynaptic injection of a slow calcium chelator and was accompanied by an increase in the frequency but not the amplitude of spontaneous excitatory postsynaptic potentials. However, PTP was also reduced by postsynaptic injection of a rapid calcium chelator or postsynaptic hyperpolarization. Thus, PTP at these synapses is likely to involve a postsynaptic induction mechanism in addition to the known presynaptic mechanisms.
Pseudomonas maltophilia endocarditis after replacement of the mitral valve: a case study.

fection [2, 3] and was responsible for three cases of bacteremia after replacement of aortic valves [4]. The source of infection in these cases was a contaminated proprietary disinfectant. The organism causing the infection in the case reported here is not easily recognized as a Pseudomonas because it is oxidase-negative. It is identified by its use of "maltose, DL-lactate, and D-glucose, its failure to use nitrate as a nitrogen source, and its requirement for methionine as a factor in growth [5]. It has been reported as the cause of pneumonia [6], acute mastoiditis [7], and one case of endocarditis after open heart surgery [8]. The patient described by Yeh et al. [8] had P. maltophilia cultured from the pump at the time of surgery and subsequently developed endocardi-
Concordance between patients and informants on the personality disorder examination.

OBJECTIVE Difficulties in the assessment of personality disorders and the burgeoning interest in axis II have led to increased use of informants when studying these conditions. The present study sought to evaluate the correspondence between patients and their informants on symptoms of personality disorders. METHOD A total of 105 outpatients and knowledgeable informants were independently interviewed by using the Personality Disorder Examination, a widely used instrument for the full range of personality disorders. RESULTS Diagnostic concordance between interviews was low (median kappa = -0.01), while correlations between dimensional scores were somewhat higher (median kappa = 0.36). Overall, patient interviews showed more pathology than interviews with informants. However, many of the symptoms obtained from informants were not reported by patients. CONCLUSIONS These data suggest that patient-informant concordance for axis II disorders is poor for diagnoses but somewhat better for dimensional scores. There was no evidence that low agreement can be explained by patients attempting to present themselves in a favorable light. Further work is necessary to elucidate the reasons for discordance and determine which data source provides the most valid information.
Quantitative defects management in iterative development with BiDefect

Iterative development methodology has been widely adopted in recent years since it is flexible and capable of dealing with requirement volatility. However, how to quantitatively manage iterative projects, and in particular, how to quantitatively manage defects across multiple iterations, remains a challenging issue. In this article, we identify three main challenges of quantitative defects management in iterative development in a leading Chinese telecommunications company (named ZZNode). The three challenges are: identifying appropriate ‘control points’ in each iteration, selecting appropriate measures and corresponding measurement methods, and determining the ‘sweet spot’ amount of effort for performing testing and defect-fixing activities. We propose a process performance Baselines based iteration Defects management (BiDefect) method to address the three challenges. We also report an industrial experience where several iterative development projects of ZZNode successfully applied the BiDefect method in initial estimating, analyzing, re-estimating, and controlling number of defects and defect detecting-fixing effort. In addition, we provide the evaluation of using BiDefect method, and discuss the benefits and lessons learned from BiDefect and its application. Copyright © 2009 John Wiley & Sons, Ltd.
GIS-Based Borderlands Modeling and Understanding: A Perspective

Borderland regions are special areas and deserve more attention in global sustainable development. Reliable geo-information and effective analysis tools are requested to support borderlands studies through the integrated utilization of geospatial analysis, web service, as well as the other domain-specific expertise. This paper has reviewed the state-of-the-art of geospatial information sciences, (GIS)-based borderlands modeling, and understanding. From the perspective of GIS, integrated data modeling, comprehensive analysis, and collaborative information service are identified as the three major challenges in this filed. A research agenda is further proposed with four topics, i.e., classification and representation of borderland information, derivation of neighborhood information, development of synergetic analysis, and design and development of a geo-portal for borderlands studies. This interdisciplinary study requires a closer and in-depth collaboration of geopolitics, international relation, geography and geo-spatial information sciences.
User-Driven Economic Data Analysis Framework

Since Big data analysis needs specific algorithms and computation resources, general user should get analysis results unilaterally from information provider who has related infrastructures. In this paper, we show user-driven economic data analysis framework. Using the proposed framework and mobile App, user can select and transmit the kind of data and analysis parameters. The server of information provider which has economic Big data and mathematical algorithms performs analysis process according to transmitted parameters by user and sends back the analysis results.
Hand-grip strength predicts incident disability in non-disabled older men.

OBJECTIVES To verify if hand-grip performance in older men is a predictor of disability. DESIGN Population-based prospective study. SETTING A sample from the Italian rural cohorts of the FINE study (Finland, Italy, Netherlands Elderly), representative of the general population of elderly men surveyed in 1991 and 1995. PARTICIPANTS 140 men aged 71-91 years who reported no disability in performing activities of daily living (ADLs), instrumental activity of daily living (IADLs) and mobility activities at baseline examination and provided information on their functional status at follow-up 4 years later. MEASUREMENTS Disability was defined as needing help in performing ADLs, IADLs and mobility. Hand-grip strength was evaluated at baseline by a mechanical dynamometer. RESULTS After adjusting for potential confounding variables, a lower concentration of high-density lipoprotein cholesterol was the only factor predicting disability in men aged 76 years or younger and only reduced hand-grip strength predicted incident disability in men 77 years or older. CONCLUSION Poor hand strength as measured by hand-grip is a predictor of disability in older people. The hand-grip test is an easy and inexpensive screening tool to identify elderly people at risk of disability.
p60v‐src causes tyrosine phosphorylation and inactivation of the N‐cadherin‐catenin cell adhesion system.

Transformation of chick embryonic fibroblasts with Rous sarcoma virus strongly suppresses N‐cadherin‐mediated cell‐cell adhesion, without inhibiting its expression. This suppression is correlated with tyrosine phosphorylation of N‐cadherin and catenins, the cadherin‐associated proteins, which are known to regulate cadherin function. Experiments with non‐myristylation and temperature‐sensitive mutants of RSV and with herbimycin A, a potent inhibitor of tyrosine kinases, suggest that both the suppression of cell adhesion and tyrosine phosphorylation of catenins are highly transformation‐specific.
A miniaturized lumped element directional coupler with parasitics compensation

This paper presents a miniaturized coupled line directional coupler carefully designed in a lumped element configuration. Due to the fact that all the parasitics (i.e. ohmic losses, inductances and capacitances) were taken into consideration at different stages of the design process, this resulted in a measured response which is in very close agreement with the simulated one. The measurements showed an input return loss and isolation of 22.43 dB and 15.76 dB respectively at 1 GHz with a 10-dB fractional bandwidth of almost 10.85%. The measured coupling and thru coefficients are 3.48 dB and 4.01 dB respectively at the same operating frequency. These values agreed quite well with the ones from the electromagnetic simulations. The reduction in the measured thru coefficient is mainly due to the added losses of solders and co-axial connectors. A phase error of about 2.4° with respect to the expected 90° phase difference was noticed.
A phage display combined with DNA affinity magnetic system can be applied to a screening of DNA binding proteins, such as transcription factors

Here we introduce a new approach for the screening of DNA binding proteins, using a phage library based on a phage display technique. In principal, a complementary DNA (cDNA) library based on the recombinant bacteriophage T7 expressing target proteins on its capsid (phage display) is constructed. These phage particles are hybridized with a biotinylated target DNA fragment which is immobilized on the surface of streptavidin paramagnetic particle (SA-PMP). The phage particles are released from the target DNA fragment by a nuclease treatment and the recovered phages are used to the next round of hybridization. These processes are repeated three times to amplify the target phages in the population. This simple method is faster, and more systemic than other current methods ( e.g. yeast one hybrid system). As a proof of this principle, we tried to isolate transcription factors which specifically bind to the promoter region of the Arabidopsis thaliana AtGST11 gene. Two obtained candidates, RING zinc finger protein and AtHB6, showed DNA binding activity to the AtGST11 promoter region. We could validate that our new application of phage display is a superior method for isolation of DNA binding proteins with a broad range of potential applications.
Similar Predictions of Etravirine Sensitivity Regardless of Genotypic Testing Method Used: Comparison of Available Scoring Systems

Background The aims of this study were to compare various genotypic scoring systems commonly used to predict virological outcome to etravirine, and examine their concordance with etravirine phenotypic susceptibility. Methods Six etravirine genotypic scoring systems were assessed: Tibotec 2010 (based on 20 mutations; TBT 20), Monogram, Stanford HIVdb, ANRS, Rega (based on 37, 30, 27 and 49 mutations, respectively) and virco®TYPE HIV-1 (predicted fold change based on genotype). Samples from treatment-experienced patients who participated in the DUET trials and with both genotypic and phenotypic data (n=403) were assessed using each scoring system. Results were retrospectively correlated with virological response in DUET. κ coefficients were calculated to estimate the degree of correlation between the different scoring systems. Results Correlation between the five scoring systems and the TBT 20 system was approximately 90%. Virological response by etravirine susceptibility was comparable regardless of which scoring system was utilized, with 70-74% of DUET patients determined as susceptible to etravirine by the different scoring systems achieving plasma viral load <50 HIV-1 RNA copies/ml. In samples classed as phenotypically susceptible to etravirine (fold change in 50% effective concentration ≤3), correlations with genotypic score were consistently high across scoring systems (≥70%). Conclusions In general, the etravirine genotypic scoring systems produced similar results, and genotype-phenotype concordance was high. As such, phenotypic interpretations, and in their absence all genotypic scoring systems investigated, may be used to reliably predict the activity of etravirine.
Observational Learning in Octopus vulgaris

Untrained Octopus vulgaris (observers) were allowed to watch conditioned Octopus(demonstrators) perform the task of selecting one of two objects that were presented simultaneously and differed only in color. After being placed in isolation, the observers, in a similar test, consistently selected the same object as did the demonstrators. This learning by observation occurred irrespective of the object chosen by the demonstrators as the positive choice and was more rapid than the learning that occurred during the conditioning of animals. The task was performed correctly without significant errors and further conditioning for 5 days. These results show that observational learning can occur in invertebrates.
The role of the nuclear matrix in the organization and function of DNA.

CONTENTS PERSPECTIVES AND OVERVIEW . •. ••. •. •. •. •. •. • •• • •. • •. •• 457 THE NUCLEAR MATRIX ORGANIZES DNA INTO LOOP-DOMAINS 462 DNA LOOP-DOMAINS AND A MODEL FOR CHROMOSOME STRUCTURE 463 DNA TOPOISOMERASES ASSOCIATED WITH THE NUCLEAR MATRIX 466
Quantitative regulation of alternative splicing in evolution and development

Alternative splicing (AS) is a widespread mechanism with an important role in increasing transcriptome and proteome diversity by generating multiple different products from the same gene. Evolutionary studies of AS have focused primarily on the conservation of alternatively spliced sequences or of the AS pattern of those sequences itself. Less is known about the evolution of the regulation of AS, but several studies, working from different perspectives, have recently made significant progress. Here, we categorize the different levels of AS evolution, and summarize the studies on evolution of AS regulation, which point to a high level of evolutionary conservation of the regulation of AS events conserved between related species. This suggests that the quantitative regulation of AS is an intrinsic part of AS function. We discuss the potential role of changes in developmental regulation of AS as an additional layer in complex gene regulatory networks and in the emergence of genetic novelties.
[Chemical constituents of Ligularia dictyoneura].

AIM To study the chemical constituents of Ligularia dictyoneura. METHODS Various chromatographic techniques were used to separate and purify the compounds. Their spectral data (MS, IR, NMR) were measured for structure elucidation. RESULTS Four sesquiterpenes were isolated from Ligularia dictyoneura and their structures were identified as ligudicin A (1), ligudicin C (2), ligudicin D (3) and isopetasin (4). CONCLUSION Compound 1 is a new compound, compound 2 is a new natural product, and compounds 3 and 4 are obtained from Ligularia dictyoneura for the first time.
Nanosurface design of dental implants for improved cell growth and function

A strategy was proposed for the topological design of dental implants based on an in vitro survey of optimized nanodot structures. An in vitro survey was performed using nanodot arrays with dot diameters ranging from 10 to 200 nm. MG63 osteoblasts were seeded on nanodot arrays and cultured for 3 days. Cell number, percentage undergoing apoptotic-like cell death, cell adhesion and cytoskeletal organization were evaluated. Nanodots with a diameter of approximately 50 nm enhanced cell number by 44%, minimized apoptotic-like cell death to 2.7%, promoted a 30% increase in microfilament bundles and maximized cell adhesion with a 73% increase in focal adhesions. An enhancement of about 50% in mineralization was observed, determined by von Kossa staining and by Alizarin Red S staining. Therefore, we provide a complete range of nanosurfaces for growing osteoblasts to discriminate their nanoscale environment. Nanodot arrays present an opportunity to positively and negatively modulate cell behavior and maturation. Our results suggest a topological approach which is beneficial for the design of dental implants.