Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Posterolateral Lumbar Fusion Rates of Grafton Putty and OP-1 Putty in an Athymic Rat Model

Study Design. Posterolateral lumbar spine fusions in athymic rats. Objectives. To compare spine fusion rates of two different osteoinductive products. Summary of Background Data. Many osteoinductive bone graft alternatives are available. Grafton (a demineralized bone matrix [DBM]) and Osteogenic Protein-1 (OP-1, an individual recombinant bone morphogenetic protein) are two such alternatives. The relative efficacy of products from these two classes has not been previously studied. The athymic rat spine fusion model has been validated and demonstrated useful to minimize inflammatory responses to xenogeneic or differentially expressed proteins such as those presented by DBMs of human etiology. Methods. Single-level intertransverse process fusions were performed in 60 athymic nude rats with 2 cc/kg of Grafton or OP-1 Putty. Half of each study group was killed at 3 weeks and half at 6 weeks. Fusion masses were assessed by radiography, manual palpation, and histology. Results. At 3 weeks, manual palpation revealed a 13% fusion rate with Grafton and a 100% fusion rate with OP-1 (P = 0.0001). At 6 weeks, manual palpation revealed a 39% fusion rate of with Grafton and a 100% fusion rate with OP-1 (P = 0.0007). Similar fusion rates were found by histology at 3 and 6 weeks. Of note, one or two adjacent levels were fused in all of the OP-1 animals and none of the Grafton animals. Conclusions. Significant differences between the ability of Grafton and OP-1 to induce bone formation in an athymic rat posterolateral lumbar spine fusion model were found.
Laboratory Case Identification of Arsenic in Ronpibul Village, Thailand (2000–2002)

Abstract Ronpibul village dwellers in the southern part of Thailand have been exposed to arsenic in the water and the environment over three generations. Over the past decades, clean water supplies, utilization and consumption have been introduced to the area. The villagers still use and select rainwater to other forms of potable water. In 2000, the epidemiological survey by Siripitayakunkit (Siripitayakunkit, U. Survey of Chronic Arsenic Poisoning in Ronpiboon, Nakhon Si Thammarat, Thailand, 2000. Proc. 6th International Conference on the Biochemistry of Trace Elements, Guelph, Canada) showed prevalence rate at 24.7%, by using the skin lesion as selection criteria. In 2000–2002, attempt to initiate the local arsenic patient center, we investigated the population at risk in three villages. The laboratory analyses cover urine arsenic level, urine sugar screening and skin lesion classified by dermatologist. The result showed the prevalence of 5.99% of melanosis and 8.67% of hyperkeratosis, 3.84% of urine sugar>100 mg/dL and 6.33% urine arsenic>50 µg/g creatinine. There were low to negligible correlation between arsenic urine with urine sugar (r 2 = 0.241) and arsenic urine with skin lesion (r 2 = 0.058).
The labyrinth of interactions of Epstein–Barr virus‐encoded small RNAs

Epstein–Barr Virus (EBV) is an oncogenic herpesvirus implicated in the pathogenesis of a number of human malignancies. However, the mechanism by which EBV leads to malignant transformation is not clear. A number of viral latent gene products, including non‐protein coding small RNAs, are believed to be involved. Epstein–Barr virus‐encoded RNA 1 (EBER1) and EBER2 are two such RNA molecules that are abundantly expressed (up to 107 copies) in all EBV‐infected cells, but their function remains poorly understood. These polymerase III transcripts have extensive secondary structure and exist as ribonucleoproteins. An accumulating body of evidence suggests that EBERs play an important role, directly or indirectly, in EBV‐induced oncogenesis. Here, we summarize the current understanding of the complex interactions of EBERs with various cellular factors and the potential pathways by which these small RNAs are able to influence EBV‐infected cells to proliferate and to induce tumorigenesis. The exosome pathway is probably involved in the cellular excretion of EBERs and facilitating some of their biological effects. Copyright © 2013 John Wiley & Sons, Ltd.
Microblogging, Online Expression, and Political Efficacy Among Young Chinese Citizens: The Moderating Role of Information and Entertainment Needs in the Use of Weibo

In 2011, China's Internet population reached over half a billion users and the popular Twitter-like social networking service, Weibo, has been adopted by half of the users since its launch in August 2009. Given the potential of the Internet to facilitate a civic culture in the authoritarian state, the use of Weibo and its effects on citizens' political attitudes and behaviors are of important concern. A survey of 499 Weibo users found that intensity of use was related to increased willingness to express opinions about government and politics, the perception that one has the ability to participate in politics, and feelings that the government is not responsive to the demands of citizens. Moreover, the above relationships were moderated by the motivations of Weibo use, such that information motives strengthened the relationships while entertainment motives weakened the relationships.
Human plasma concentrations of cytochrome P450 probes extrapolated from pharmacokinetics in cynomolgus monkeys using physiologically based pharmacokinetic modeling

Abstract 1. Cynomolgus monkeys are widely used in preclinical studies as non-human primate species. Pharmacokinetics of human cytochrome P450 probes determined in cynomolgus monkeys after single oral or intravenous administrations were extrapolated to give human plasma concentrations. 2. Plasma concentrations of slowly eliminated caffeine and R-/S-warfarin and rapidly eliminated omeprazole and midazolam previously observed in cynomolgus monkeys were scaled to human oral biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Results of the simplified human PBPK models were consistent with reported experimental PK data in humans or with values simulated by a fully constructed population-based simulator (Simcyp). 3. Oral administrations of metoprolol and dextromethorphan (human P450 2D probes) in monkeys reportedly yielded plasma concentrations similar to their quantitative detection limits. Consequently, ratios of in vitro hepatic intrinsic clearances of metoprolol and dextromethorphan determined in monkeys and humans were used with simplified PBPK models to extrapolate intravenous PK in monkeys to oral PK in humans. 4. These results suggest that cynomolgus monkeys, despite their rapid clearance of some human P450 substrates, could be a suitable model for humans, especially when used in conjunction with simple PBPK models.
Great Places to Work®: Resilience in Times of Crisis

We study the resilience of the “100 Best Companies to Work for in America” in times of financial crises by analyzing their long-term financial performance. Apart from implementing methods that tackle the statistical problems of stock returns, we use a conditional model to measure financial performance in periods of market growth (bull markets) and market downturn (bear markets). Our results sustain the proposition that best companies to work for are resilient in times of crisis since neither their financial performance nor their systematic risk are affected during bear markets: top companies continue to outperform the market during periods of crises, and the performance of lower-ranked great workplaces does not deteriorate. Moreover, we find that previous studies were overestimating performance, and only great workplaces on the top half of the rankings exhibit positive excessive returns. We conclude that, in general, this award has an impact on these firms’ reputations that allows investors to acknowledge the value of outstanding employee relations and correctly incorporate it into stock prices. They fail to do so for the top ranking companies, however, reinforcing the notion that outstanding people management entails intrinsic benefits with financial value that are difficult to discern due to its intangible nature.
Low Serum Levels of Tricyclic Antidepressants in Amitriptyline- and Doxepin-Treated Inpatients with Depressive Syndromes are Associated with Nonresponse

Nonresponse to tricyclic antidepressant (TCA) treatment is observed in about one-third of depressed patients. The cause(s) for nonresponse - apart from disease-specific effects - might be the failure to build up sufficiently high serum TCA levels due to noncompliance, substance abuse, rapid metabolism, or low dose. We carried out a retrospective analysis relating antidepressant serum levels to patient data obtained in the naturalistic setting of the Psychiatric Hospital of the Bonn University during the introductory phase of drug-monitoring. Case reports of 110 depressed inpatients who were treated with amitriptyline or doxepin were analyzed with respect to the following: medication and comedication, daily dose, type and duration of treatment, serum TCA concentrations (analyzed by the fluorescence polarization immunoassay), age, sex, body weight, abuse of nicotine or alcohol intake, serum transaminases (ALT, alanine aminotransferase, and AST, aspartate amino transferase), gamma-glutamyltranspeptidase (gamma-GT) and creatinine, compliance, and response. The salient findings were: 1. Serum TCA concentrations increased linearly with the daily amitriptyline dose but not with that of doxepin. 2. Interindividually, there was an eight to ten-fold difference in serum TCA concentrations at steady-state with 150 mg/day of either drug; longitudinally, we observed intraindividually a coefficient of variation of 8% and 12% for amitriptyline and doxepin respectively. 3. With amitriptyline (150 mg/day), the correlation between age and serum TCA concentrations was low (r = 0.33, p < 0.055) and no correlation was found after the administration of doxepin (150 mg/day), nor was there any correlation between age and dose-adjusted serum TCA concentrations after the administration of either drug. 4. Nonresponders had significantly lower serum levels than responders. These results suggest that patients should not qualify as nonresponders unless it can be demonstrated (and it is clinically applicable) that the steady-state serum TCA levels are stable within the upper limit of the recommended therapeutic range and serum level.
Price Competitive Alliance Projects: Identification of Success Factors for Public Clients

The need to identify the critical factors in the successful development and management of the price competitive alliance model has become a priority for public sector clients, as there is an increasing need to obtain better value for money (VfM) for its infrastructure projects. Yet, there has been limited research undertaken about the nature and use of price competitive alliances. This research determines the success factors (SFs) for price competitive alliances during their relationship development phases as this form of alliance contract is being used extensively by public sector clients to procure critical infrastructure projects in Western Australia (WA). A review of the literature of partnering and alliance contracting is used to develop a conceptual model of potential SFs. Interviews with 21 practitioners who participated in alliances on behalf of a WA public sector client were conducted to determine their perceived SF for price competitive alliances throughout the relationship development process. Contrary to the literature, each of the SFs identified was required in each stage of the relationship development process. In particular, the development of a leadership enriched culture (where people view the project as an extension of themselves and feel good about what they personally achieve through cooperation) was deemed necessary for the successful implementation of a price competitive alliance. Moreover it was revealed that the establishment of trust for the client began to arise at the point when a realistic target outturn cost that was able to deliver VfM, as well as an innovative sustainable outcome could be attained. Price competitive alliance models are considered to be an appropriate procurement method, albeit during the current economic climate an alternative to public private partnerships, for delivering large complex infrastructure projects.
Hydroxyurea accelerates the loss of epidermal growth factor receptor genes amplified as double-minute chromosomes in human glioblastoma multiforme.

OBJECTIVE We sought to determine whether hydroxyurea could accelerate the loss of amplified epidermal growth factor receptor (EGFR) genes from glioblastoma multiforme (GBM). There is good reason to think that elimination of amplified EGFR genes from GBMs will negatively impact tumor growth. Hydroxyurea has previously been shown to induce the loss of amplified genes from extrachromosomal double minutes (dmin) but not from chromosomal homogeneously staining regions. METHODS Pulsed-field gel electrophoresis and Southern blot hybridization were used to demonstrate EGFR genes amplified as dmin. Giemsa-stained metaphase spreads were prepared in an attempt to visualize dmin. A GBM cell line containing amplified EGFR genes was treated continuously in vitro with 0 to 150 mumol/L hydroxyurea, and slot blot analysis was used to show the loss of amplified EGFR genes. RESULTS Amplified EGFR genes were found on dmin in 4 of 11 (36%) fresh human GBM biopsy specimens. None of the GBMs contained EGFR genes amplified as homogeneously staining regions. Amplified dmin were not microscopically visible when stained with Giemsa because of their small size. Slot blot analysis showed that these low doses of hydroxyurea accelerated the loss of amplified EGFR genes in a dose- and time-dependent fashion. Pulsed-field gel electrophoresis and Southern blot analysis confirmed that EGFR gene loss was accompanied by amplified dmin loss in a dose-dependent fashion. CONCLUSION These studies suggest the potential use of low-dose hydroxyurea in the treatment of GBMs.
Dissection of brefeldin A-sensitive and -insensitive steps in apicoplast protein targeting

The apicoplast is a relict plastid found in many apicomplexans, including the pathogens Toxoplasma gondii and Plasmodium falciparum. Nucleus-encoded apicoplast proteins enter the ER, and after cleavage of the signal sequence, are routed to the apicoplast by virtue of a transit peptide, which is subsequently removed. To assess the mechanisms of localization we examined stable transfectants of T. gondii for the localization and processing of various GFP fusion proteins. GFP fusions bearing apicoplast targeting sequences targeted efficiently to the plastid, with no retention in the ER, even when an ER retention/retrieval sequence was added. Incubation with brefeldin A, which blocks ER-to-Golgi trafficking by inhibiting a GTP exchange factor required for retrograde trafficking, blocked the processing of the protein. Surprisingly, it did not affect the immunofluorescence pattern. To avoid the potentially misleading presence of pre-existing GFP fusion protein in the apicoplast, we used a ligand-regulated aggregation system to arrest the GFP fusion protein in the ER prior to trafficking. Upon addition of ligand to promote disaggregation, the fusion protein targeted to the plastid, even in the presence of brefeldin A. Ligand release at 15°C, which blocks trafficking of Golgirouted proteins, also allowed significant localization to the plastid. Our data indicate that apicoplast proteins can localize to the region of the plastid when Golgi trafficking is inhibited, but suggest that some steps in import or maturation of the proteins may require a brefeldin A-sensitive GTP exchange factor.
Epidermal growth factor (EGF/URO) induces expression of regulatory peptides in damaged human gastrointestinal tissues

The pS2 gene encodes for a small cysteine‐rich protein, and was originally found by differential screening of a cDNA library from the human breast carcinoma cell line, MCF‐7. The presence of pS2 is closely correlated with oestrogen dependence in breast carcinomas. While the function of pS2 is unknown, pS2 protein has been shown to be homologous with the gastrointestinal peptide hormone pancreatic spasmolytic polypeptide (PSP) and its human counterpart hSP, in which a 5‐cysteine domain is tandemly repeated. The 5′ flanking region of the pS2 gene contains an enhancer region responsive to oestrogens and to epidermal growth factor (EGF/URO). We now report that pS2 and hSP expression occurs in a wide range of endodermally‐derived tissues, including the duodenum, the pancreas, and in a recently defined cell lineage associated with chronic gastrointestinal ulceration. In each case, this expression was associated with secretion of immunoreactive EGF/URO. We further show that the co‐expression of pS2 and hSP in gastric surface epithelial cells is also associated with the secretion of EGF/URO in the subjacent mucous neck cells. Our results indicate that local EGF/URO secretion induces pS2 and hSP in adjacent cells, and that these molecules are then available to participate in pathophysiological responses. The finding of similar patterns of EGF/URO, hSP and pS2 expression in association with chronic damage suggests that this is a fundamental response in the healing of these tissues.
Sofosbuvir and Ribavirin Liver Pharmacokinetics in Patients Infected with Hepatitis C Virus

ABSTRACT Sofosbuvir and ribavirin exert their anti-hepatitis C virus (anti-HCV) activity following metabolic activation in the liver. However, intrahepatic concentrations of the pharmacologically active nucleotide metabolites in humans are poorly characterized due to the inaccessibility of tissue and technical challenges with measuring nucleotide levels. A clinical study assessing the efficacy of sofosbuvir and ribavirin administered prior to liver transplantation to prevent HCV recurrence provided a unique opportunity to quantify nucleotide concentrations in human liver. We analyzed nucleotides using high-performance liquid chromatography coupled to tandem mass spectrometry in liver tissue from 30 HCV-infected patients with hepatocellular carcinoma who were administered sofosbuvir (400 mg/day) and ribavirin (1,000 to 1,200 mg/day) for 3 to 52 weeks prior to liver transplantation. Median total hepatic metabolite concentrations (the sum of nucleoside and mono-, di-, and triphosphates) were 77.1 μM for sofosbuvir and 361 μM for ribavirin in patients on therapy at the time of transplantation. Ribavirin and sofosbuvir efficiently loaded the liver, with total hepatic metabolite concentrations exceeding maximal levels in plasma by approximately 30-fold. Ribavirin metabolite levels suggest that its monophosphate is in great excess of its inhibition constant for IMP dehydrogenase and that its triphosphate is approaching the binding constant for incorporation by the HCV NS5B RNA-dependent RNA polymerase. In accordance with the potent antiviral activity of sofosbuvir, these results demonstrate that the liver triphosphate levels achieved following sofosbuvir administration greatly exceed the inhibition constant for HCV NS5B. In conclusion, this study expands the quantitative understanding of the pharmacology of sofosbuvir and ribavirin by establishing efficient hepatic delivery in the clinic. (This study has been registered at ClinicalTrials.gov under identifier NCT01559844.)
A Novel Approach to the Appraisal of Technological Risk: A Multicriteria Mapping Study of a Genetically Modified Crop

The recent controversy over genetically modified (GM) foods amply demonstrates the general difficulties encountered in the social appraisal of technological risk. Existing procedures for regulatory appraisal neglect many possible forms of impact and routinely exclude important cultural and social dimensions of risk. A narrow, expert, ‘science-based’ approach is now widely acknowledged to be insufficient. There is a need for new approaches that are more broadly based, transparent, pluralistic and ready to acknowledge uncertainty as well as being practically feasible and robust. The authors investigate the potential for a novel ‘multicriteria mapping’ (MCM) method as one such possible tool. Drawing on a variety of perspectives in the current UK debate, a range of agricultural strategies for the production of oilseed rape, including both GM and non-GM options were explored in this MCM pilot exercise. The results demonstrate the general feasibility and positive potential of this type of approach, with specific findings providing modest insights for policymaking in this difficult area.
Farm Size, Land Reallocation, and Labour Migration in Rural China

This paper explores the factors that determine a farm household migration decision, particularly the influence of the current land tenure system in China. Land endowment per labour is used to measure farm size. Reallocation times and expectation of future land reallocation are used to measure the land reallocation situation. Data used in this study are from a farm household survey conducted in 2009 in 17 villages in Northeast Henan province. By using a Heckman two-stage model, the empirical findings show that there are some differences in terms of the magnitude and direction of determinants significantly affecting the decision to migrate and its duration. China's land tenure arrangements are based on egalitarian land distribution and frequent reallocation stimulates rather than deters migration in the case of land rental market imperfections. However, it is the main reason for the unique temporary and individual migration patterns. With the development of land rental markets, the importance of land transferability becomes prominent. Policies aimed at improving land security and promoting land transfer will also benefit rural labour emigration. Other factors that also have significant influence on labour migration are household size, number of household dependents, household assets and whether a household has a land-use contract. Copyright © 2013 John Wiley & Sons, Ltd.
Cross-Cultural Differences in Social Identity Formation through Travel Blogging

ABSTRACT Blogs are an Internet application that continues to grow in popularity. Many blogs contain travel-related postings and, thus, are of importance for researchers and practitioners in the tourism field. Differences in blog use have been found across different cultures. This study seeks to test whether social identity theory can explain some of the differences in extent and type of blog use. A sample of 120 travel blogs written by Korean and U.S. bloggers about three different destinations (Paris, Hawaii, and Tokyo) was analyzed. The results show significant differences that fit the assumptions derived from social identity theory.