Miracle-dz/UniFAR-FTUs huggingface dataset:
Activating Transcription Factor 2 Mediates Matrix Metalloproteinase-2 Transcriptional Activation Induced by p 38 in Breast Epithelial Cells

Mounting evidence suggests a role for matrix metalloproteinase (MMP)-2 in the malignant progression of breast cancer cells. We showed previously that H-Ras, but not N-Ras, induced invasion of MCF10A human breast epithelial cells through Rac-MKK3/6-p38 pathway resulted in MMP-2 upregulation. Activation of p38 pathway by MKK6 caused a selective up-regulation of MMP-2. In this study, we aimed to elucidate the transcriptional regulation of MMP-2 by p38 pathway leading to the invasive phenotype of MCF10A cells. By using 5¶ deletion mutant constructs of MMP-2 promoter, we showed that deletion of the region containing activator protein-1 (AP-1) site caused the greatest reduction of MMP-2 promoter activity both in MKK6and H-Ras-activated MCF10A cells, suggesting that the AP-1 binding site is critical for the MMP-2 promoter activation. DNA binding and transcriptional activities of AP-1 were increased by MKK6 or H-Ras as evidenced by electrophoretic mobility shift assay and luciferase assay using an AP-1-driven plasmid. By doing immunoinhibition assay and chromatin immunoprecipitation assay, we revealed the activating transcription factor (ATF) 2 as a transcription factor for MMP-2 gene expression through binding to the functional AP-1 site. Activation of ATF2, which depended on p38 activity, was crucial for MMP-2 promoter activity as well as induction of invasive and migrative phenotypes in MCF10A cells. This is the first report revealing ATF2 as an essential transcription factor linking MKK3/6-p38 signaling pathway to MMP-2 up-regulation, providing evidence for a direct role of ATF2 activation in malignant phenotypic changes of human breast epithelial cells. (Cancer Res 2006; 66(21): 10487-96)
The relational reframe and parents’ problem constructions in attachment-based family therapy

Abstract The authors studied the impact of relational reframes on parents’ problem constructions and the reciprocal impact of parents’ problem constructions on therapists’ use of the relational reframe in five early sessions of attachment-based family therapy for depressed adolescents. Across all five sessions, relational reframes led parents to construct problems in interpersonal terms in at least two of their six subsequent speech turns. There was partial support for the hypothesis that reframes led to shifts in parents’ constructions, from intrapersonal to interpersonal. In good, but not poor alliance sessions, parents’ interpersonal problem constructions led therapists to use relational reframes. Future research should examine not only how interpersonal problem constructions are generated but their quality as well.
Sorption of organic genotoxins to particulate matter in industrial effluents

In an earlier work [White PA et al. (1996): Environ Mol Mutagen 27:116–139] we examined the genotoxicity of dichloromethane extracts from a variety of industrial effluent samples. In this companion work, we used the SOS Chromotest to investigate the sorption of the extracted genotoxins to effluent suspended particulate matter. The affinity of the genotoxins for particulate matter is expressed as a genotoxicity sorption partition coefficient (Kd‐genotox). The results indicate that industries known for their emission of combustion by‐products, such as polycyclic aromatic hydrocarbons, often have high Kd‐genotox values (≥106). These include metal refining and founding industries as well metal surface treatment facilities. In contrast, Kd‐genotox values for pulp and paper mills and sewage treatment facilities are several orders of magnitude lower (≤104). In several cases the calculated Kd‐genotox values are in agreement with the Kow values of genotoxic substances isolated from genotoxic industrial waste samples studied by other researchers. The sorption partition coefficient, in conjunction with the concentration of available particulate matter, was used to determine the percent of organic genotoxins adsorbed to effluent suspended particulate matter. Values range from 2.3% to 99.8%. High values (>70%) were obtained for metal surface treatment and inorganic and organic chemical production facilities. Low values (<30%) were obtained for sewage treatment facilities and pulp and paper mills. The results also demonstrate the effect of variations in the concentration of available particulate matter on the genotoxicity of both aqueous and particulate extracts. The results suggest that the sorptive properties of the particulate matter itself are reduced when the concentration of particulate matter is very high (>1,000 mg per l). The use of sorption partition information in inferring the physical‐chemical nature of the putative genotoxins and the implications of the results for assessing the hazard posed to aquatic biota by industrial genotoxins are discussed. © 1996 Wiley‐Liss, Inc.
Vascular Function and Short-Term Exposure to Fine Particulate Air Pollution

ABSTRACT Exposure to fine particulate air pollution has been implicated as a risk factor for cardiopulmonary disease and mortality. Proposed biological pathways imply that particle-induced pulmonary and systemic inflammation play a role in activating the vascular endothelium and altering vascular function. Potential effects of fine particulate pollution on vascular function are explored using controlled chamber exposure and uncontrolled ambient exposure. Research subjects included four panels with a total of 26 healthy nonsmoking young adults. On two study visits, at least 7 days apart, subjects spent 3 hr in a controlled-exposure chamber exposed to 150–200 μg/m3 of fine particles generated from coal or wood combustion and 3 hr in a clean room, with exposure and nonexposure periods alternated between visits. Baseline, postexposure, and post-clean room reactive hyperemia–peripheral arterial tonometry (RH-PAT) was conducted. A microvascular responsiveness index, defined as the log of the RH-PAT ratio, was calculated. There was no contemporaneous vascular response to the few hours of controlled exposure. Declines in vascular response were associated with elevated ambient exposures for the previous 2 days, especially for female subjects. Cumulative exposure to real-life fine particulate pollution may affect vascular function. More research is needed to determine the roles of age and gender, the effect of pollution sources, the importance of cumulative exposure over a few days versus a few hours, and the lag time between exposure and response. IMPLICATIONS This study found no contemporaneous vascular response in healthy young adults to exposure to a few hours of generated fine particulate matter in a controlled experimental setting. Two-day uncontrolled ambient fine particulate pollution at much lower concentrations was associated with small but significant changes in vascular function, primarily for female subjects only. Clearly, additional research is needed to establish the potential effect of cumulative exposure over a few days versus a few hours and the lag time between exposure and response.
Three-dimensional chemical imaging of embedded nanoparticles using atom probe tomography

Analysis of nanoparticles is often challenging especially when they are embedded in a matrix. Hence, we have used laser-assisted atom probe tomography (APT) to analyze the Au nanoclusters synthesized in situ using ion-beam implantation in a single crystal MgO matrix. APT analysis along with scanning transmission electron microscopy and energy dispersive spectroscopy (STEM-EDX) indicated that the nanoparticles have an average size ∼ 8–12 nm. While it is difficult to analyze the composition of individual nanoparticles using STEM, APT analysis can give three-dimensional compositions of the same. It was shown that the maximum Au concentration in the nanoparticles increases with increasing particle size, with a maximum Au concentration of up to 50%.
Blockholders: A Survey of Theory and Evidence

This paper reviews the theoretical and empirical literature on the role of blockholders (large shareholders) in corporate governance. We start with the underlying property rights of public corporations; we discuss how blockholders are critical in addressing free-rider problems and why, like owners of private property in general, blockholders are likely to be active in firm governance. We then examine what distinguishes a blockholder from an ordinary shareholder and advocate additional definitions from the typical threshold of 5% ownership. We next present new evidence on the frequency and characteristics of blockholders in United States corporations. Then we develop a simple unifying model to present theories of blockholder governance through both voice (direct intervention) and exit (selling one's shares). We survey the empirical evidence on blockholder governance, emphasizing the empirical challenges in identifying causal effects involving blockholders. We highlight the lack of credible instruments for blockholders and argue that exogenous variation should not be a prerequisite for research --- a narrow focus on identification may lead to a focus on identifying narrow questions. We emphasize the value of descriptive research with blockholders and how endogeneity concerns can be addressed with economic logic and by directly testing alternative explanations. We close with suggestions for future research.
Hepatitis C virus E1 envelope glycoprotein interacts with apolipoproteins in facilitating entry into hepatocytes

Our previous studies demonstrated that hepatitis C virus (HCV) envelope glycoproteins 1 and 2 (E1 and E2) display distinct reactivity to different cell‐surface molecules. In this study, we characterized the interaction of E1 and E2 with apolipoproteins in facilitating virus entry. The results suggested a higher neutralization of vesicular stomatitis virus (VSV)/HCV E1‐G pseudotype infectivity by antibodies to apolipoprotein E (ApoE) than apolipoprotein B (ApoB), with VSV/HCV E2‐G pseudotype infectivity remaining largely unaffected. Neutralization of cell‐culture–grown HCV infectivity by antiserum to ApoE and, to a lesser extent, by ApoB further verified their involvement in virus entry. HCV E1, but not E2, displayed binding with ApoE and ApoB by enzyme‐linked immunosorbent assay. Binding of E1 with apolipoproteins were further supported by coimmunoprecipitation from human hepatocytes expressing E1. Rabbit antiserum to a selected E1 ectodomain‐derived peptide displayed ∼50% neutralization of E1‐G pseudotype infectivity. Furthermore, E1 ectodomain‐derived synthetic peptides significantly inhibited the interaction of E1 with both the apolipoproteins. Investigation on the role of low‐density lipoprotein receptor (LDL‐R) as a hepatocyte surface receptor for virus entry suggested a significant reduction in E1‐G pseudotype plaque numbers (∼70%) by inhibiting LDL‐R ligand‐binding activity using human proprotein convertase subtilisin/kexin type 9 and platelet factor‐4, whereas they had a minimal inhibitory effect on the E2‐G pseudotype. Conclusion: Together, the results suggested an association between HCV E1 and apolipoproteins, which may facilitate virus entry through LDL‐R into mammalian cells. (HEPATOLOGY 2011;)
EFFECT OF HUMAN RESOURCE MANAGEMENT PRACTICES ON EMPLOYEE PERFORMANCE IN COMMERCIAL BANKS IN NAIROBI COUNTY, KENYA

The purpose of this study was to examine the effect of Human Resource Management Practices (HRMP) on employee performance in commercial banks in Nairobi County in Kenya. The specific HR practices examined in the study were reward management practices, performance appraisal practices, employee involvement practices and training and development practices. The study employed descriptive study design. A sample of 235 respondents was selected through stratified random sampling technique. Data was collected using questionnaires and analysed using multiple regression analysis. The study findings indicated that the relationship between HRM practices and employee performance is positive although only the relationship between reward management, performance appraisal as well as training and development practices and employee performance were found to be significant while the relationship between employee involvement and employee performance was not significant. Based on the study conclusions, the study recommended that in order to realize improvement in employee performance, commercial banks as well as other companies, should aim to improve reward structure of their employees by developing a reward structure which recognizes outstanding performance by teams and individual employees, developing pay package that competes with other like organizations in the market as well as salary increment and promotions schemes which are linked to employee performance. The study also recommended that commercial banks should design better performance appraisal schemes which distribute timely and relevant information on performance or goal plansto employees. Lastly the study recommended that those commercial banks and other companies aiming to achieve improved employee performance should also consider developing training and development policies and strategies which aim to identify training needs with full participation of employees, which have fairness in addressing staff training and development needs as well as those policies which create an enabling environment for transfer of learning to succeed. Key words: Reward management practices, Performance appraisal practices, Employee involvement practices, Training and development practices, Employee performance
The integument of the ocean sunfish (Mola mola L.) (Plectognathi) with observations on the lesions from two ectoparasites, Capsala martinierei (Trematoda) and Philorthagoriscus serratus (Copepoda).

The constituent layers of the integument of the ocean sunfish are described. An eosinophilic epidermal cell is reported. The method of formation and calcification of the fibrillar plates and tubercles is suggested. Regional variation in the fibrillar-plate formation was observed, and its possible role in the movement of the tail discussed. The tubercle is contrasted with placoid and ganoid scales. The lesions associated with the copepod Philorthagoriscus serratus and the trematode Capsala martinierei are described. P. serratus could, in heavy infections, impare the host. C. martinierei causes only superficial damage. The most important pathological implication of both parasites is that they expose the host to secondary infection.
Increased Cardiac Risk in Concomitant Methadone and Diazepam Treatment: Pharmacodynamic Interactions in Cardiac Ion Channels

Methadone, a synthetic opioid for treatment of chronic pain and withdrawal from opioid dependence, has been linked to QT prolongation, potentially fatal torsades de pointes, and sudden cardiac death. Concomitant use of diazepam or other benzodiazepines in methadone maintenance treatment can increase the risk of sudden death. Therefore, we determined the effects of methadone and diazepam singly and in combination on cardiac action potentials (APs) and on the major ion channels responsible for cardiac repolarization. Using patch clamp recording in human stem cell-derived cardiomyocytes and stably transfected mammalian cells, we found that methadone produced concentration-dependent AP prolongation and ion channel block at low micromolar concentrations: hERG (IC50 = 1.7 μM), hNav1.5 (11.2 μM tonic block; 5.5 μM phasic block), and hCav1.2 (26.7 μM tonic block; 7.7 μM phasic block). Methadone was less potent in hKv4.3/hKChIP2.2 (IC50 = 39.0 μM) and hKvLQT1/hminK (53.3 μM). In contrast, diazepam blocked channels only at much higher concentrations and had no effect on AP duration at 1 μM. However, coadministration of 1-μM diazepam with methadone caused a statistically significant increase in AP duration and a 4-fold attenuation of hNav1.5 block (IC50 values were 44.2 μM and 26.6 μM, respectively, for tonic and phasic block), with no significant effect on methadone-induced block of hERG, hCav1.2, hKv4.3/hKChIP2.2, and hKvLQT1/hminK channels. Thus, although diazepam alone does not prolong the QT interval, the relief of methadone-induced Na+ channel block may leave hERG K+ channel block uncompensated, thereby increasing cardiac risk.
Performance of MMSE turbo equalization using outer LDPC coding for magnetic recording channels

We investigate the performance of minimum meansquare error turbo-equalization for LDPC-coded transmission over intersymbol-interference channels. The EXIT-chart technique is used to study the effect of code rate on the convergence of the turbo-equalization process. The analysis is conducted for partial-response channels of various types and for the magnetic recording channel. Performance results obtained from simulations show good agreement with the EXIT-chart analysis. They indicate that for applications requiring high code rates equalizerbased detection may suffer from a nonnegligible loss in performance as compared with maximum a posteriori detection.
Previously suicidal adolescents: predictors of six-month outcome.

OBJECTIVE To determine the baseline variables, including borderline personality disorder (BPD), associated with the six-month outcome of previously suicidal adolescents (n=263) presenting to an emergency department and treated predominantly as out-patients. METHODS Multivariate logistic regression was used to analyze the associations between baseline variables and suicidality at six-month follow-up. RESULTS BPD, previous suicide attempt(s), drug use and female gender were associated with subsequent suicidality. CONCLUSIONS These findings corroborate previously reported risk factors for recurring suicidality among adolescents and broaden their generalizability to those presenting to an emergency department, many diagnosed with BPD.
Developmental stress, social rank and song complexity in the European starling (Sturnus vulgaris)

Bird song is a sexually selected trait and females have been shown to prefer males that sing more complex songs. However, for repertoire size to be an honest signal of male quality it must be associated with some form of cost. This experiment investigates the effects of food restriction and social status during development on song complexity in the European starling (Sturnus vulgaris). Birds that experienced an unpredictable food supply early in life produced a significantly smaller repertoire of song phrases than those with a constant food supply. Social status during development was also significantly correlated with repertoire size, with dominant birds producing more phrase types. This study therefore provides novel evidence that social as well as nutritional history may be important in shaping the song signal in this species.
Priority Setting for Improvement of Cervical Cancer Prevention in Iran.

BACKGROUND Cervical cancer is the fourth most common cancer among women worldwide. Organized cervical screening and vaccination against human papilloma virus (HPV) have been successful interventions for prevention of invasive cervical cancer (ICC). Because of cultural and religious considerations, ICC has low incidence in Iran and many other Muslim countries. There is no organized cervical screening in these countries. Therefore, ICC is usually diagnosed in advanced stages with poor prognosis in these countries. We performed a priority setting exercise and suggested priorities for prevention of ICC in this setting. METHODS We invited experts and researchers to a workshop and asked them to list important suggestions for ICC prevention in Iran. After merging similar items and removing the duplicates, we asked the experts to rank the list of suggested items. We used a strategy grid and Go-zone analysis to determine final list of priorities for ICC prevention in Iran. RESULTS From 26 final items suggested as priorities for prevention of ICC, the most important priorities were developing national guidelines for cervical screening and quality control protocol for patient follow-up and management of precancerous lesions. In addition, we emphasized considering insurance coverage for cervical screening, public awareness, and research priorities, and establishment of a cervical screening registry. CONCLUSION A comprehensive approach and implementation of organized cervical screening program is necessary for prevention of ICC in Iran and other low incidence Muslim countries. Because of high cost for vaccination and low incidence of cervical cancer, we do not recommend HPV vaccination for the time being in Iran.
- 1-Embedding Object Files in an Existing Operating System : A Practical Approach

This article describes an approach to embed ObjectOriented file structure in an existing operating system. The Object-Oriented file structure (Object File) is a part of an effort to create a fully Object-Oriented Operating System (OOOS). The concepts, design, and implementation are explained. Text and multimedia files are tested. The experiment has shown that tested files can be handled correctly by the standard applications without any unsatisfactory effect from existing environment. With this concept, the application and platform dependency constraints can be avoided. To the users, the files are transparently manipulated.
Multiple doses of sclerostin antibody romosozumab in healthy men and postmenopausal women with low bone mass: A randomized, double‐blind, placebo‐controlled study

Romosozumab (formerly AMG 785/CDP7851) is a monoclonal antibody that blocks sclerostin from inhibiting osteoblast maturation and function. This double‐blind, placebo‐controlled, randomized, ascending multiple‐dose study enrolled 32 postmenopausal women and 16 healthy men with low bone mass. Women received six doses of 1 or 2 mg/kg once every 2 weeks (Q2W) or three doses of 2 or 3 mg/kg once every 4 weeks (Q4W) or placebo; and men received 1 mg/kg Q2W or 3 mg/kg Q4W or placebo. Mean serum romosozumab exposures increased approximately dose‐proportionally. Romosozumab increased serum type 1 aminoterminal propeptide (PINP) by 66–147%, decreased serum C‐telopeptide (sCTX) by 15–50%, and increased lumbar spine bone mineral density by 4–7%. Two subjects developed neutralizing antibodies without discernable effects on pharmacokinetics, pharmacodynamics, or safety. Adverse event rates were balanced between groups without any significant safety findings. These data support continued investigation of sclerostin inhibition in disorders that could benefit from increased bone formation.
NONPARAMETRIC LOGISTIC REGRESSION: REPRODUCING KERNEL HILBERT SPACES AND STRONG CONVEXITY

We study maximum penalized likelihood estimation for lo- gistic regression type problems. The usual diculties encountered when the log-odds ratios may become large in absolute value are circumvented by imposing a priori bounds on the estimator, depending on the sample size (n) and smoothing parameter. We pay for this in the convergence rate of the mean integrated squared error by a factor logn. When the "true" log odds ratios are bounded, these factors logn disappear. The main technical tools employed are reproducing kernel Hilbert spaces and convexity inequalities.