Miracle-dz/UniFAR-FTUs huggingface dataset:
ADynamic De-Escalating Dosing Strategy to Determine the Optimal Biological Dose forAntiangiogenic Drugs 55 Commentary on Dowlati et al . , p . 7938

The concept and application of antiangiogenic therapy for the treatment of cancer has been on a long roller coaster ride. After years of promising, and sometimes exciting, preclinical studies, the first antiangiogenic drug clinical trials began in the early 1990s with the fumagillin analogue, TNP-470, eventually followed by phase III trials evaluating such diverse agents as SU5416, a small-molecule vascular endothelial growth factor receptor-2 antagonist, matrix metalloproteinase inhibitors, and bevacizumab (Avastin), the humanized anti–vascular endothelial growth factor monoclonal antibody (1). The first such trials yielded negative results, and the inevitable feeling of disappointment (2). The mood changed dramatically in May 2003 with the announcement of positive results in a randomized phase III trial of bevacizumab and irinotecan, fluorouracil, and leucovorin chemotherapy for the first-line treatment of metastatic colorectal cancer—the results of which were published in 2004 (3). Bevacizumab was approved for this indication by the U.S. Food and Drug Administration in February 2004, and more recently in many other countries. The drug has been on a tear since then with a string of positive results involving randomized phase III clinical trials in secondline colorectal cancer, first-line metastatic breast cancer, and late stage nonsquamous non–small cell lung cancer, as a firstline therapy. All these final results (or interim trial results in the case of breast cancer) were presented recently at the 2005 American Society for Clinical Oncology meeting (4). There were also encouraging results presented involving single-agent (but multitargeted) small-molecule receptor tyrosine kinase inhibitors, notably Sutent (SU11248) and Sorafenib (BAY 439006) in renal cell carcinoma (4). The results highlight several important questions. Why does a tumor-starving drug, such as bevacizumab, which presumably suppresses blood flow within a tumor and increases hypoxia, enhance rather than diminish the efficacy of chemotherapy? Could the modest survival benefits detected in the aforementioned trials using such combination treatments be improved by selecting different doses of a drug such as bevacizumab? Furthermore, related to the latter question, how does one go about determining the best dose of an antiangiogenic drug?
A fully integrated low phase noise VCO for IEEE 802.11a WLAN transceivers in 0.18μm CMOS

A fully integrated voltage-controlled oscillator (VCO) for IEEE 802.11a WLAN transceivers is proposed and implemented in 0.18 μm CMOS technology with 1.8 V supply voltage. The VCO core adopts the topology of complementary cross-coupled differential inductance-capacitance (LC) tank. The VCO operates from 4.56 to 4.77 GHz with the varactor control voltage (Vtune) changing from 0.3 to 1.5 V and has a gain (Kv) of 175 MHz/V. A phase noise of -122.3 dBc/Hz at 1 MHz offset frequency is demonstrated for an oscillation frequency of 4.56 GHz. The average power consumption of this VCO is 30.24 mW.
Long-term efficacy of modified-release recombinant human thyrotropin augmented radioiodine therapy for benign multinodular goiter: results from a multicenter, international, randomized, placebo-controlled, dose-selection study.

BACKGROUND Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine ((131)I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with (131)I therapy. METHODS In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2 ± 9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0 mL; range 31.9-242.2 mL) were randomized to receive placebo (n=32), 0.01 mg MRrhTSH (n=30), or 0.03 mg MRrhTSH (n=33) 24 hours before a calculated (131)I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by computed tomography scan) at baseline, six months, and 36 months. Thyroid function and quality of life (QoL) was evaluated at three-month and yearly intervals respectively. RESULTS At six months, TV reduction was enhanced in the 0.03 mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01 mg MRrhTSH group. At 36 months, the mean percent TV reduction from baseline was 44 ± 12.7% (SD) in the placebo group, 41 ± 21.0% in the 0.01 mg MRrhTSH group, and 53 ± 18.6% in the 0.03 mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03 mg MRrhTSH group, the subset of patients with basal (131)I uptake <20% had a 24% greater TV reduction at 36 months than the corresponding subset of patients in the placebo group (p=0.01). At 36 months, the largest relative increase in SCAT was observed in the 0.03 mg MRrhTSH group (13.4 ± 23.2%), but this was not statistically different from the increases observed in the placebo or the 0.01 mg MRrhTSH group (p=0.15). Goiter-related symptoms were reduced and QoL improved, without any enhanced benefit from using MRrhTSH. At three years, the prevalence of permanent hypothyroidism was 13%, 33%, and 45% in the placebo, 0.01 mg, and 0.03 mg MRrhTSH groups respectively. The overall safety profile of the study was favorable. CONCLUSIONS When used as adjuvant to (131)I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤ 0.03 mg, indicating that the lower threshold for efficacy is around this level.
Automated building energy performance simulation : a review of approaches and outline research opportunities

This paper offers a review of approaches to the automated creation of input data for building energy simulation. Such data may be obtained by translation of available data from architectural and HVAC models. However, a full energy performance model also requires missing data to be completed. Two criteria for the assessment of the reviewed methods were their level of automation and the completeness of the obtained models.
Spartinoxide, a New Enantiomer of A82775C with Inhibitory Activity toward HLE from the Marine-derived Fungus Phaeosphaeria spartinae

The fungus Phaeosphaeria spartinae is an endophyte of the marine alga Ceramium sp. Investigation of this marine-derived fungus led to the isolation of spartinoxide (1), which is the enantiomer of the known compound A82775C (2). Additionally, the known metabolites 4-hydroxy-3-prenyl-benzoic acid (4) and anofinic acid (5) were obtained. The structures of all compounds were established from extensive spectroscopic investigations. Compounds 1, 4 and 5 were assayed against the enzymes human leukocyte elastase (HLE), trypsin, acetylcholinesterase and cholesterolesterase. Compounds 1 and 4 showed potent inhibition of HLE with IC50 values of 1.71 ± 0.30 μg/mL (6.5 μM) and 1.67 ± 0.32 μg/mL (8.1 μM), respectively.
Proposal of an analytical solution for the load imbalance problem in parallel systems

In this paper, a parallel dynamic load balancing algorithm; which offers a good trade-off between the balancing degree and communication costs; is proposed. The proposed algorithm is analyzed, investigated, and implemented. Also, a new mathematical solution for that algorithm is presented. The analytical solution is tested on standard task graphs (STG) as common test-bed benchmarks. All the different parameters concerned with processors, memory, interconnection networks, and task programs are also presented. The new proposed algorithm is compared and evaluated with a traditional dynamic load balancing one. Experimental results are presented by considering a set of criteria for evaluating the overall performance. Simulation and analytical results proved that the proposed algorithm outperforms the chosen one.
Staphylococcal Enterotoxins A and B Enhance Rhinovirus Replication in A549 Cells

Background Staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB) have been reported to be important in the pathogenesis of chronic rhinosinusitis (CRS). To elucidate the pathophysiological responses in the nasal mucosae of CRS patients associated with rhinovirus (RV) infection, we investigated the effects of SEA and SEB on RV infection in A549 cells. Methods Changes in expression of intercellular adhesion molecule (ICAM) 1 were assessed by flow cytometry, and effects on cytokine secretion were measured by ELISA. The changes of ICAM-1, IL-1beta, IL-6, and IL-8 mRNA were assayed by real-time polymerase chain reaction. The effect of RV replication in the cells was assessed by viral culture, followed by determination of viral titer. Results RV infection increased ICAM-1 expression and cytokine secretion, but the SEs did not further increase the RV-induced expression of ICAM-1, IL-1beta, IL-6, and IL-8 mRNA and protein. The SEs, however, induced dose-dependent increases in viral titer. Conclusion SEA and SEB enhanced rhinoviral replication in airway epithelial cells, indicating that airway epithelial cells with CRS are more favorable environments for RV infection.
Does Service Affect Citizenship?

The idea of citizen service has been given increasing attention as a remedy for problems of civic disengagement. This study reviews 37 empirical studies about the relationship between service and citizenship. A formal model of change is used to guide the review. Six types of citizenship outcomes are discussed: citizenship-related cognitive understanding, citizenship attitudes, citizenship skills, institutional change, philanthropic and civic behaviors, and political behavior. Based on the review, several conclusions are drawn about what is known about the service-citizenship relationship.
Cost-effectiveness of exercise therapy after corticosteroid injection for moderate to severe shoulder pain due to subacromial impingement syndrome: a trial-based analysis.

OBJECTIVE To perform a cost-effectiveness analysis of subacromial corticosteroid injection combined with exercise compared with exercise alone in patients with moderate to severe shoulder pain from subacromial impingement syndrome. METHODS A within-trial cost-effectiveness analysis with 232 patients randomized to physiotherapy-led injection combined with exercise (n = 115) or exercise alone (n = 117). The analysis was from a health care perspective with 24-week follow-up. Resource use information was collected from all patients on interventions, medication, primary and secondary care contacts, private health care use and over-the-counter purchases. The measure of outcome was quality-adjusted life years (QALYs), calculated from EQ-5D responses at baseline and three further time points. An incremental cost-effectiveness analysis was conducted. RESULTS Mean per patient NHS costs (£255 vs £297) and overall health care costs (£261 vs £318) were lower in the injection plus exercise arm, but this difference was not statistically significant. Total QALYs gained were very similar in the two trial arms (0.3514 vs 0.3494 QALYs), although slightly higher in the injection plus exercise arm, indicating that injection plus exercise may be the dominant treatment option. At a willingness to pay of £20,000 per additional QALY gained, there was a 61% probability that injection plus exercise was the most cost-effective option. CONCLUSION Injection plus exercise delivered by therapists may be a cost-effective use of resources compared with exercise alone and lead to lower health care costs and less time off work. TRIAL REGISTRATION International Standard Randomised Controlled Trial Number Register, http://www.controlled-trials.com/isrctn/, ISRCT 25817033.
Visual Design of coherent Technology-Enhanced Learning Systems: a few lessons learned from CPM language

Visual instructional design languages currently provide notations for representing the intermediate and final results of a knowledge engineering process. As some languages particularly focus on the formal representation of a learning design that can be transformed into machine interpretable code (i.e., IML-LD players), others have been developed to support the creativity of designers while exploring their problem-spaces and solutions. This chapter introduces CPM (Computer Problem-based Metamodel), a visual language for the instructional design of Problem-Based Learning (PBL) situations. On the one hand, CPM sketches of a PBL situation can improve communication within multidisciplinary ID teams; on the other hand, CPM blueprints can describe the functional components that a Technology-Enhanced Learning (TEL) system should offer to support such a PBL situation. We first present the aims and the fundamentals of CPM language. Then, we analyze CPM usability using a set of CPM diagrams produced in a case study in a 'real-world' setting.
A 200-Second Quasi-Periodicity After the Tidal Disruption of a Star by a Dormant Black Hole

Oscillating Black Hole The massive black holes that reside in the centers of galaxies can occasionally capture and tidally disrupt stars that wander too close. One such tidal disruption event was detected last year by the Swift satellite. Follow-up x-ray observations analyzed by Reis et al. (p. 949, published online 2 August; see the Perspective by McKinney) show quasi-periodic oscillations that suggest that an accretion disk formed around the black hole shortly after the tidal disruption event. This type of oscillation is commonly seen in the x-ray light from the much lighter black holes that result from the gravitational collapse of stars, but has been seen only once in a massive black hole residing in the center of a galaxy. Oscillations in x-ray emission from a galaxy’s central black hole imply that a disc formed after the hole captured a star. Supermassive black holes (SMBHs; mass is greater than or approximately 105 times that of the Sun) are known to exist at the center of most galaxies with sufficient stellar mass. In the local universe, it is possible to infer their properties from the surrounding stars or gas. However, at high redshifts we require active, continuous accretion to infer the presence of the SMBHs, which often comes in the form of long-term accretion in active galactic nuclei. SMBHs can also capture and tidally disrupt stars orbiting nearby, resulting in bright flares from otherwise quiescent black holes. Here, we report on a ~200-second x-ray quasi-periodicity around a previously dormant SMBH located in the center of a galaxy at redshift z = 0.3534. This result may open the possibility of probing general relativity beyond our local universe.
Optimization for a superscalar out-of-order machine

Compiler optimization plays a key role in unlocking the performance of the PA-8000, an innovative dynamically-scheduled machine which is the first implementation of the 64-bit PA 2.0 member of the HP PA-RISC architecture family. This wide superscalar, long out-of-order machine provides significant execution bandwidth and automatically hides latency at runtime; however despite its ample hardware resources, many of the optimizing transformations which proved effective for the PA-8000 served to augment its ability to exploit the available bandwidth and to hide latency. Further machine-specific factors influenced all levels of optimization to a degree without precedent in the set of previous PA-RISC processors. While legacy codes benefit from the PA-8000's sophisticated hardware, recompilation of old binaries can be vital to realizing the full potential of the PA-8000, given the impact of new compilers in achieving peak performance for this machine.
Biocompatibility of wire electrodes improved by MPC polymer coating

We investigated the use of poly (2-methacryloyl-oxyethyl phosphorylcholine-co-n-butyl methacrylate) (MPC polymer) coating to suppress the adsorption of protein by a wire surface. Reduced adsorption would slow the encapsulation of wires implanted in a living body. Coated and uncoated gold, silver, and tungsten wires were implanted into rat brain. The silver and tungsten coated wires had a significantly lower immunoreactive astrocyte count compared to the reference wires. These results demonstrate that coating wires with MPC polymer can reduce encapsulation. The use of such wires for implanting microelectrodes would facilitate long-term neural recording because it would slow the growth of encapsulation tissue, which causes electrodes to separate from the brain tissue.
Globalisation, Regionalism and Labour Interests in the New International Political Economy

This article has two main objectives. First, it provides a critical appraisal of the theoretical accounts of globalisation/regionalisation provided by the left structuralist or ‘hyperglobalist’ approach and the new constitutionalist version of the neo-Gramscian approach. It is argued that both approaches have been essentially negative in their evaluation of the role and position of organised labour in the changing IPE. Such pessimism is particularly marked (perhaps not surprisingly) in the left structuralist approach, but nevertheless (and more surprisingly) still pervades the new constitutionalism. I argue that in both cases pessimism is to a significant degree misplaced and I seek to show the various points at which, in my view, each approach has gone wrong. Generally speaking, however, I would suggest that the problems highlighted have rather less to do with the general theoretical perspectives deployed (for both left structuralism and neo-Gramscian analysis have a great deal to offer the study of IPE) than with the specific treatments of these approaches critiqued here. Briefly stated, these treatments suffer from a common failure to conceptualise changing world orders in terms of the dialectic of structure and agency. Second, the article focuses on a more empirical analysis of (mainly British) labour movement agency within the context of European integration since the mid 1980s, concentrating particularly, although not exclusively, on trade union responses to and understandings of economic and monetary union (EMU). This is designed partly as a corrective to the new constitutionalists’ emphasis on elite agency. I argue that the evidence indicates a significant galvanisation of labour agency at the European Union (EU) level. This needs to be understood partly in terms of a (negative/defensive) response to economic globalisation but also as a positive engagement with the globalisation/regionalism, structure/agency dialectic which reveals broader and more positive trade union purposes and objectives grounded in what Robert Cox has called ‘critical theory’ and directed at forms of social transformation.4 This engagement has, in turn, been partly facilitated by the EU’s own determination of the structure/agency dialectic evident in the changing and politically contested (as opposed to elite-determined) governance structures of the EU. I argue that the starting theoretical assumptions of European labour movement agency are positive in their assertion of feasible alternatives to neoliberal economic governance at the EU level. This corresponds to the more optimistic version of neo-Gramscianism that has informed the work of Alain Lipietz
Effectiveness of Anti-TNFα for Crohn Disease: Research in a Pediatric Learning Health System

OBJECTIVES: ImproveCareNow (ICN) is the largest pediatric learning health system in the nation and started as a quality improvement collaborative. To test the feasibility and validity of using ICN data for clinical research, we evaluated the effectiveness of anti-tumor necrosis factor-α (anti-TNFα) agents in the management of pediatric Crohn disease (CD). METHODS: Data were collected in 35 pediatric gastroenterology practices (April 2007 to March 2012) and analyzed as a sequence of nonrandomized trials. Patients who had moderate to severe CD were classified as initiators or non-initiators of anti-TNFα therapy. Among 4130 patients who had pediatric CD, 603 were new users and 1211 were receiving anti-TNFα therapy on entry into ICN. RESULTS: During a 26-week follow-up period, rate ratios obtained from Cox proportional hazards models, adjusting for patient and disease characteristics and concurrent medications, were 1.53 (95% confidence interval [CI], 1.20–1.96) for clinical remission and 1.74 (95% CI, 1.33–2.29) for corticosteroid-free remission. The rate ratio for corticosteroid-free remission was comparable to the estimate produced by the adult SONIC study, which was a randomized controlled trial on the efficacy of anti-TNFα therapy. The number needed to treat was 5.2 (95% CI, 3.4–11.1) for clinical remission and 5.0 (95% CI, 3.4–10.0) for corticosteroid-free remission. CONCLUSIONS: In routine pediatric gastroenterology practice settings, anti-TNFα therapy was effective at achieving clinical and corticosteroid-free remission for patients who had Crohn disease. Using data from the ICN learning health system for the purpose of observational research is feasible and produces valuable new knowledge.
Cross-Border Regionalization, the INTERREG III a Initiative, and Local Cooperation at the Finnish-Swedish Border

Whereas most studies to date have viewed cross-border regionalization and cooperation from ‘top-down’ regional and institutional perspectives, and within the context of urban regions, I am concerned with the implementation of cross-border initiatives in the rural Finnish–Swedish border area. The focus is firstly on the implementation of cross-border projects in the European Union's INTERREG III A North programme (2000–06), and secondly on grassroots cooperation and local actors' experiences of cross-border initiatives. The findings indicate that cooperation is not a straightforward process of ‘ignoring’ state borders and creating new regional spaces across borders. The INTERREG programme documents emphasize the development of a functional, harmonious cross-border region. When the examination is moved to the local level and everyday institutional practices are considered, cooperation and the implementation of initiatives appear in a rather different light. Practices of cooperation are intertwined with different governmental and nongovernmental structures across multiple scales, but it is the state border which determines the norms and spatial organization of this cooperation and cross-border networks are still sparse compared with their national counterparts. What this paper suggests is that we should include the national as a significant scalar dimension more profoundly in our analysis of cross-border regionalization and cooperation.
Salt resistance and synergistic effect with vancomycin of alpha-helical antimicrobial peptide P18.

P18 (KWKLFKKIPKFLHLAKKF-NH(2)) is an alpha-helical antimicrobial peptide designed from a cecropin A-magainin 2 hybrid. In this study, P18 was found to show strong antimicrobial activity against several antibiotic-resistant bacterial and fungal strains. Both the salt resistance on antimicrobial activity and the synergistic effect with clinically used antibiotic agents are critical factors in developing effective peptide antibiotic drugs. For this reason, we investigated the salt resistance of P18 to antagonism by NaCl, CaCl(2), and MgCl(2) on antimicrobial activity and the synergistic effect of P18 with vancomycin against vancomycin-resistant Enterococcus faecium (VREF). Compared to magainin 2, P18 showed strong resistance on antimicrobial activity against bacterial strains and C. albicans under high NaCl concentrations of 100-200 mM. In addition, P18 displayed much greater salt resistance on antibacterial activity against Gram-negative bacteria at the physiological or elevated concentrations of CaCl(2) and MgCl(2) than magainin 2. Furthermore, the combination study revealed that P18 has a relatively effective synergistic effect with vancomycin against VREF. Thus, these results support that P18 may prove to be a salt-resistant antibiotic peptide potentially useful in the treatment of cystic fibrosis patients as well as a valuable adjuvant for antimicrobial chemotherapy.