Miracle-dz/UniFAR-FTUs huggingface dataset:
Heme Oxygenase-1 Induction by Carbon Monoxide Releasing Molecule-3 Suppresses Interleukin-1β-Mediated Neuroinflammation

Neurodegenerative disorders and brain damage are initiated by excessive production of reactive oxygen species (ROS), which leads to tissue injury, cellular death and inflammation. In cellular anti-oxidant systems, heme oxygenase-1 (HO-1) is an oxidative-sensor protein induced by ROS generation or carbon monoxide (CO) release. CO releasing molecules (CORMs), including CORM-3, exert anti-oxidant and anti-inflammatory effects. However, the molecular mechanisms of CORM-3-induced HO-1 expression and protection against interleukin (IL)-1β-induced inflammatory responses have not been fully elucidated in rat brain astrocytes (RBA-1). To study the regulation of CORM-3-induced HO-1 expression, signaling pathways, promoter activity, mRNA and protein expression were assessed following treatment with pharmacological inhibitors and gene-specific siRNA knockdown. We found that CORM-3 mediated HO-1 induction via transcritional and translational processes. Furthermore, CORM-3-induced HO-1 expression was mediated by phosphorylation of several protein kinases, such as c-Src, Pyk2, protein kinase Cα (PKCα) and p42/p44 mitogen-activated protein kinase (MAPK), which were inhibited by respective pharmacological inhibitors or by gene-specific knockdown with siRNA transfections. Next, we found that CORM-3 sequentially activated the c-Src/Pyk2/PKCα/p42/p44 MAPK pathway, thereby up-regulating mRNA for the activator protein (AP)-1 components c-Jun and c-Fos; these effects were attenuated by an AP-1 inhibitor (Tanshinone IIA; TSIIA) and other relevant inhibitors. Moreover, CORM-3-induced upregulation of HO-1 attenuated the IL-1β-induced cell migration and matrix metallopeptidase-9 mRNA expression in RBA-1 cells. These effects were reversed by an matrix metalloproteinase (MMP)2/9 inhibitor or by transfection with HO-1 siRNA.
Macrophage depletion alters the blood–nerve barrier without affecting Schwann cell function after neural injury

Previous work has shown that, during the early phases of chronic nerve compression (CNC) injury, axonal pathology is absent while Schwann cells undergo a dramatic process of cellular turnover with marked proliferation. It is known that macrophages may release Schwann cell mitogens, so we sought to explore the role of macrophages in CNC injury by selectively depleting the population of hematogenously derived macrophages in nerves undergoing CNC injury by injecting clodronate liposomes at days 1, 3, and 6 postinjury and evaluating both the integrity of the blood–nerve barrier (BNB) and Schwann cell function. Integrity of the BNB was evaluated by intravenously injecting Evans blue albumin (EBA), and Schwann cell number was determined via stereologic techniques. The BNB was clearly altered by 2 weeks postinjury and continued to disintegrate at later time points. Macrophage depletion attenuated this response at all observed time points. Quantification of Schwann cell nuclei in CNC nerves showed no differences between compressed sections of macrophage‐depleted and nondepleted animals. Although macrophages are largely responsible for the increased vascular permeability associated with CNC injury, it is likely that the Schwann cell response to CNC injury is not influenced by macrophage‐derived mitogenic signals but rather must be mediated via alternative mechanisms. © 2007 Wiley‐Liss, Inc.
Extrahepatic metastasectomy for hepatocellular carcinoma: Predictors of long‐term survival

Wewould like to sincerely thankDrs. Xiang et al. for their interest in our paper, and the editors for the opportunity to respond. Our study was intended to document current practice. It is a descriptive analysis attempting to find the most predictive factors for survival, not to make definitive statements about mechanisms of causality. The conclusions of our primary analysis: “Long-term survival may be achieved in highly selected HCC patients following extrahepatic metastasectomy (EM). The presence of greater than two extrahepatic lesions correlates independently with poor survival” is a valid, evidence based conclusion derived fromthemostpredictivemodel developed fromourdata. Points raised in the letter that we wish to respond to more specifically follow.
Repeated and Multiple New Vertebral Compression Fractures After Percutaneous Transpedicular Vertebroplasty

Study Design. A retrospective study to detect patients with new-onset compression fractures following vertebroplasty. Objective. To investigate the characteristics and associated risk factors of new-onset vertebral compression fractures after vertebroplasty. Summary of Background Data. Percutaneous vertebroplasty is a well-established technique for treating osteoporotic compression fractures. Short-term results are promising, but longer-term studies have suggested a possible accelerated failure rate in the adjacent vertebral body. Methods. We retrospectively reviewed patients with osteoporotic compression fractures from January 2000 to June 2006. The patients received percutaneous vertebroplasty with bone cement augmentation. Long-term follow-up radiographically identified the occurrence of vertebral fracture (minimum follow-up 24 months) after an initial vertebral fracture. Results. In 852 patients (1131 vertebrae), 58.8% to 63.8% of new compression fractures after vertebroplasty were adjacent compression fractures. Adjacent fractures occurred much sooner than nonadjacent fractures; (71.9 ± 71.8 days vs. 286.8 ± 232.8 days, P < 0.001). In patients who experienced vertebral compression fractures 2 or more times, older age, lower baseline bone mineral density (BMD), and more pre-existing vertebral compression fractures were demonstrated in this study (P < 0.005). The gender and amount of cemented polymethyl methacrylate were not statistically different between Groups A (1 vertebral compression fracture) and B (vertebral compression fracture ≥2 times). Conclusion. New-onset vertebral compression fractures occurred repeatedly within a few years after vertebroplasty. New-onset adjacent-level fractures occurred sooner and were more predominate than nonadjacent level fractures. The results of this study suggest that older patient age, lower baseline BMD, and more pre-existing vertebral fractures were found to be risk factors for multiple vertebral compression fractures.
Valuation of Flexible Transmission Investment Options Under Uncertainty

Significant uncertainty surrounds the future development of electricity systems, primarily in terms of size, location and type of new renewable generation to be connected. In this paper we assess the potential for flexible network technologies, such as phase-shifting transformers, and non-network solutions, such as energy storage and demand-side management, to constitute valuable interim measures within a long-term planning strategy. The benefit of such flexible assets lies not only in the transmission services provided but also in the way they can facilitate and de-risk subsequent decisions by deferring commitment to capital-intensive projects until more information on generation development becomes available. A novel stochastic formulation for transmission expansion planning is presented that includes consideration of investment in these flexible solutions. The proposed framework is demonstrated with a case study on the IEEE-RTS where flexible technologies are shown to constitute valuable investment options when facing uncertainties in future renewable generation development.
Learning New Letter-like Writing Patterns Explicitly and Implicitly in Children and Adults

ABSTRACT A handwriting task was used to test the assumption that explicit learning is dependent on age and working memory, while implicit learning is not. The effect of age was examined by testing both, typically developing children (5–12 years old, n = 81) and adults (n = 27) in a counterbalanced within-subjects design. Participants were asked to repeatedly write letter-like patterns on a digitizer with a non-inking pen. Reproduction of the pattern was better after explicit learning compared to implicit learning. Age had positive effects on both explicit and implicit learning; working memory did not affect learning in either conditions. These results show that it may be more effective to learn writing new letter-like patterns explicitly and that an explicit teaching method is preferred in mainstream primary education.
Synergy between Apc min and an activated ras mutation is sufficient to induce colon carcinomas

Colon carcinomas appear to arise from the cumulative effect of mutations to several genes (APC, DCC, p53, ras, hMLH1, and hMSH2). By using novel colonic epithelial cell lines derived from the Immorto mouse, named the YAMC (young adult mouse colon) cell line, and an Immorto-Min mouse hybrid, named the IMCE (Immorto-Min colonic epithelial) cell line, carrying the Apc min mutation, we investigated the effect of an activated v-Ha-ras gene on tumor progression. The YAMC and IMCE cell lines are normal colonic epithelial cell lines which are conditionally immortalized by virtue of expression of a temperature-sensitive simian virus 40 (SV40) large T antigen. Under conditions which permit expression of a functional SV40 large T antigen (33 degrees C plus gamma interferon), neither the YAMC nor the IMCE cell line grows in soft agar or is tumorigenic in nude mice. In vitro, when the SV40 large T antigen is inactivated (39 degrees C without gamma interferon), the cells stop proliferating and die. By infecting the YAMC and IMCE cell lines with a replication-defective psi2-v-Ha-ras virus, we derived cell lines which overexpress the v-Ha-ras gene (YAMC-Ras and IMCE-Ras). In contrast to the parental cell lines, under conditions in which the SV40 large T antigen is inactive, both the YAMC-Ras and IMCE-Ras cell lines continue to proliferate. Initally YAMC-Ras cells do not form tumors; however, tumors are visible after 90 days of incubation. IMCE-Ras cells form colonies in soft agar under both permissive and nonpermissive culture conditions. Furthermore, IMCE-Ras cells form tumors in nude mice within 3 weeks. The phenotype of the IMCE-Ras cell line thus clearly demonstrates that a defective Apc allele and an activated ras gene are sufficient to transform normal colonic epithelial cells and render them tumorigenic.
Ammonia induces the mitochondrial permeability transition in primary cultures of rat astrocytes

Ammonia is a toxin that has been strongly implicated in the pathogenesis of hepatic encephalopathy (HE), and the astrocyte appears to be the principal target of ammonia toxicity. The specific neurochemical mechanisms underlying HE, however, remain elusive. One of the suggested mechanisms for ammonia toxicity is impaired cellular bioenergetics. Because there is evidence that the mitochondrial permeability transition (MPT) is associated with mitochondrial dysfunction, we determined whether the MPT might be involved in the bioenergetic alterations related to ammonia toxicity. Accordingly, we examined the mitochondrial membrane potential (Δψm) in cultured astrocytes and neurons using laser‐scanning confocal microscopy after loading the cells with the voltage‐sensitive dye JC‐1. We found that ammonia induced a dissipation of the Δψm in a time‐ and concentration‐dependent manner. These findings were supported by flow cytometry using the voltage‐sensitive dye tetramethylrhodamine ethyl ester (TMRE). Cyclosporin A, a specific inhibitor of the MPT, completely blocked the ammonia‐induced dissipation of the Δψm. We also found an increase in the mitochondrial permeability to 2‐deoxyglucose in astrocytes that had been exposed to 5 mM NH4Cl, further supporting the concept that ammonia induces the MPT in these cells. Pretreatment with methionine sulfoximine, an inhibitor of glutamine synthetase, blocked the ammonia‐induced collapse of Δψm, suggesting a role of glutamine in this process. Over a 24‐hr period, ammonia had no effect on the Δψm in cultured neurons. Collectively, our data indicate that ammonia induces the MPT in cultured astrocytes, which may be a factor in the mitochondrial dysfunction associated with HE and other hyperammonemic states. © 2001 Wiley‐Liss, Inc.
Emerging Market Sovereign Credit Spreads: In-Sample and Out-of-Sample Predictability

This paper investigates the quarter-ahead predictability of Brazil, Mexico, Philippines and Turkey credit spreads for short and long maturity bonds during two separate periods preceding and following the Lehman Brothers' default. A model based on the current country-specific credit spread curve predicts no better than the random walk and slope regression benchmarks. Extensions with the global yield curve factors and short-term interest rate volatility notably outperform the benchmark models post-Lehman. Our findings suggest that uncertainty indicators, both global and domestic, contain information about future credit spreads and that bond prices did better align with fundamentals post-crisis.
Selective engagement of G protein coupled receptor kinases (GRKs) encodes distinct functions of biased ligands

CCL19 and CCL21 are endogenous agonists for the seven-transmembrane receptor CCR7. They are equally active in promoting G protein stimulation and chemotaxis. Yet, we find that they result in striking differences in activation of the G protein-coupled receptor kinase (GRK)/ß-arrestin system. CCL19 leads to robust CCR7 phosphorylation and β-arrestin2 recruitment catalyzed by both GRK3 and GRK6 whereas CCL21 activates GRK6 alone. This differential GRK activation leads to distinct functional consequences. Although each ligand leads to β-arrestin2 recruitment, only CCL19 leads to redistribution of β-arrestin2-GFP into endocytic vesicles and classical receptor desensitization. In contrast, these agonists are both capable of signaling through GRK6 and β-arrestin2 to ERK kinases. Thus, this mechanism for “ligand bias” whereby endogenous agonists activate different GRK isoforms leads to functionally distinct pools of β-arrestin.
Polymeric nanoparticles for targeted delivery of therapeutic vaccines to dendritic cells

Dendritic cells (DCs) are the sentries of the immune system. They detect pathogens entering the body and activate immune responses against them through multiple nanoscopic molecular interactions. Pathogen-mimicking nanoparticles capable of such interactions were fabricated by incorporating monophosphoryl lipid A in a biodegradable polymer, poly(D,L-lactic-co-glycolic acid) (PLGA). The uptake of PLGA nanoparticles by human and mouse DCs was conclusively demonstrated by confocal laser scanning microscopy. Delivery of antigens in PLGA nanoparticles was shown to be more efficient than their delivery in soluble form for activation of T cell responses against a variety of antigens including a MUCI peptide (BLP25) cancer vaccine. A PLGA nanoparticulate formulation of BLP25 induced potent T cell responses and anticancer effects in a mouse lung cancer model. These results indicate that PLGA nanoparticles mimicking certain features of pathogens are efficient delivery systems for targeting therapeutic vaccines to DCs and activation of potent T cell responses.
Environmental Protection and Tourism with Urban Unemployment

This study investigates the combined effects of tourism promotion and environmental protection, via a pollution tax, in labor-surplus developing economies. While tourism is expected to provide employment and improve national welfare, the tax is expected to have the opposite effect. This paper is the first of its kind to examine the interaction between tourism and environmental protection by considering production as well as consumption externalities. The results show that, under certain conditions, tourism promotion expands the tourism sector, increases unemployment, and improves welfare. Conversely, under certain conditions, an increase in the pollution tax contracts the sector, decreases unemployment, and reduces welfare. JEL Classifications: F16, O13, O18
Social Movements and Social Capital: A Network Perspective on Movement Outcomes

This article presents an approach to the study of the consequences of social movements that focuses on their capacity to produce "social capital. " By social capital I mean ties that are based on mutual trust and mutual recognition among the actors involved in the relationship, although they do not necessarily imply the presence of collective identity. The influence of social movements may be regarded as dependent on their structural position, i.e., on the solidity of the linkages within the movement sector as well as—more crucially—of the bonds among movement actors, the social milieu in which they operate, and cultural and political elites. Therefore, the impact of a given movement or movement sector will be assessed in the light of changes in its components' relative centrality in various social networks. The broader the range of social capital ties emerging from a period of sustained mobilization, the greater the impact.
Fundamental Drivers of the Cost and Price of Operating Reserves

Operating reserves impose a cost on the electric power system by forcing system operators to keep partially loaded spinning generators available for responding to system contingencies variable demand. In many regions of the United States, thermal power plants provide a large fraction of the operating reserve requirement. Alternative sources of operating reserves, such as demand response and energy storage, may provide more efficient sources of these reserves. However, to estimate the potential value of these services, the cost of reserve services under various grid conditions must first be established. This analysis used a commercial grid simulation tool to evaluate the cost and price of several operating reserve services, including spinning contingency reserves and upward regulation reserves. These reserve products were evaluated in a utility system in the western United States, considering different system flexibilities, renewable energy penetration, and other sensitivities. The analysis demonstrates that the price of operating reserves depend highly on many assumptions regarding the operational flexibility of the generation fleet, including ramp rates and the fraction of fleet available to provide reserves.
Real‐Time Strain Rate Imaging: Validation of Peak Compression and Expansion Rates by a Tissue‐Mimicking Phantom

Strain rate imaging is a new modality in echocardiography intended for analysis of left ventricular function. This modality extends ultrasonographic techniques for analysis of tissue velocities by providing information about rates of local myocardial compression and expansion. Cyclic cardiac deformation is a complex process. Precision and accuracy of real‐time strain rate (rtSR) measurements have not been studied under controlled laboratory conditions. Using a cyclically compressed tissue‐mimicking gelatin phantom, we compared rtSR values to corresponding strain rate values calculated off line from local tissue velocities measured by Doppler echocardiography. We tested a clinically relevant range of strain rates (0.5 − 3.5 sec−1) and different angles of insonation. Initial tests showed high precision (r ≥ 0.973, P < 0.001), but the assessment of accuracy (bias ≤ 0.559 sec−1) suggested a trend toward systematic underestimation of the reference values. We suspected a confounding influence of a clutter filter and repeated the tests with the filter inactive. The resulting accuracy improved tenfold (bias ≤ 0.045 sec−1), and the systematic underestimation was no longer present. We conclude that the rtSR is precise and accurate for a range of the tested values.
Current Status of Surgery for Pancreatic Cancer

Background: In Japan the annual incidence of pancreatic cancer has increased over the last decade, but no advancement has been made in the long-term prognosis after resection. The significant differences in the surgical procedures between Western countries and Japan have been discussed. Therefore, an adequate comparison and analysis of the data from Japan, Europe and the USA is required. This review evaluates many important published reports from Japan which influence surgical procedure. Methods: Several important highlights and controversies regarding the concept of surgical treatment and surgical procedure are discussed comparing the results in Japan with those in Western countries. Results: No significant difference in diagnostic strategy using various imaging methods was observed between Japan and Europe. The stage classification for pancreatic cancer by the Japanese Pancreatic Society (JPS) seems to be superior to others, because the results on long-term prognosis after pancreatectomy of cases with pancreatic head cancer, diagnosed as tubular adenocarcinoma, has been arranged logically. Pancreatectomy with extended radical dissection is recommended in Japan, but several clinical studies from Europe and the USA suggest that this is ineffective. The basic concepts of this controversy have recently come closer altogether. Scientific clinical trials for instance on the necessity of adjuvant treatment, etc., are now on-going. Conclusion: The characteristics on diagnosis and treatment of pancreatic cancer in Japan are described. The JPS registration system for pancreatic cancer can provide much more information, i.e. dependency on diagnostic methods, highly frequent sites of lymph node and of distant metastases, the prognosis of small pancreatic cancers, etc. The indication for any surgical treatments should be limited to cases with the possibility of cancer free margins.
Infections in Craniofacial Surgery: A Combined Report of 567 Procedures from Two Centers

&NA; This retrospective review of infectious complications was undertaken at two craniofacial centers (Dallas and Philadelphia). Fourteen infections were identified over a 6.5‐year period in 567 intracranial procedures primarily for craniosynostosis. There were no infections in infants under 13 months of age and no cases of meningitis. The overall infection rate was 2.5 percent, and 85 percent of infections occurred in secondary reoperative cases. Tracheostomies were not identified as a risk factor for infection. No difference was found in infection rates between patients with shaved and unshaved scalps. Candida and Pseudomonas were the two most common organisms identified, and 28 percent of our infections involved yeast. The average time to diagnose infection was 11.5 days (excluding three patients who averaged 5 months). Thirteen of the fourteen infections were treated surgically with placement of a subgaleal irrigation/drainage system. Initial bony debridement was kept to a minimum. Based on our findings, recommendations are made to further lower infection rates, particularly those caused by opportunistic organisms. (Plast. Reconstr. Surg. 100: 862, 1997.)
An Evaluation of Volatility Forecasting Techniques

The existing literature contains conflicting evidence regarding the relative quality of stock market volatility forecasts. This paper employs daily Indian data to examine the relative ability of various models to forecast monthly stock market volatility. The forecasting models which were selected range from naive model to relatively complex GARCH model. While it is difficult to claim superiority of any one model under all measures used to assess the accuracy of the forecast, the overall results clearly identify two competing models i.e., the RWM and GARCH (1, 1).