Miracle-dz/UniFAR-FTUs huggingface dataset:
Fentanyl buccal soluble film (FBSF) for breakthrough pain in patients with cancer: a randomized, double-blind, placebo-controlled study

Background: Fentanyl buccal soluble film (FBSF) has been developed as a treatment of breakthrough pain in opioid-tolerant patients with cancer. The objective of this study was to evaluate the efficacy of FBSF at doses of 200–1200 μg in the management of breakthrough pain in patients with cancer receiving ongoing opioid therapy. Patients and methods: This was a multicenter, randomized, double-blind, placebo-controlled, multiple-crossover study that included opioid-tolerant adult patients with chronic cancer pain who experienced one to four daily episodes of breakthrough pain. The primary efficacy assessment was the sum of pain intensity differences at 30 min (SPID30) postdose. Results: The intent-to-treat population consisted of 80 patients with ≥1 post-baseline efficacy assessment. The least-squares mean (LSM ± SEM) of the SPID30 was significantly greater for FBSF-treated episodes of breakthrough pain than for placebo-treated episodes (47.9 ± 3.9 versus 38.1 ± 4.3; P = 0.004). There was statistical separation from placebo starting at 15 min up through 60 min (last time point assessed). There were no unexpected adverse events (AEs) or clinically significant safety findings. Conclusions: FBSF is an effective option for control of breakthrough pain in patients receiving ongoing opioid therapy. In this study, FBSF was well tolerated in the oral cavity, with no reports of treatment-related oral AEs.
On GPU pass-through performance for cloud gaming: Experiments and analysis

Cloud Gaming renders interactive gaming applications remotely in the cloud and streams the scenes back to the local console over the Internet. Virtualization plays a key role in modern cloud computing platforms, allowing multiple users and applications to share a physical machine while maintaining isolation and performance guarantees. Yet the Graphical Processing Unit (GPU), which advanced game engines heavily rely upon, is known to be difficult to virtualize. Recent advances have enabled virtual machines to directly access physical GPUs and exploit their hardware's acceleration. This paper presents a experimental study on the performance of real world gaming applications as well as ray-tracing applications with GPUs. Despite the fact that the VMs are accelerated with dedicated physical GPUs, we find that the gaming applications perform poorly when virtualized, as compared to non-virtualized bare-metal base-line. For example, experiments with the Unigine gaming benchmark run at 85 FPS on our bare-metal hardware, however, when the same benchmark is run within a Xen or KVM based virtual machine the performance drops to less than 51 FPS. In contrast, ray-tracing application fares much better. Our detailed performance analysis using hardware profiling on KVM further reveals the memory bottleneck in the pass through access, particularly for real-time gaming applications.
Control of mobile platforms using a virtual vehicle approach

Two model independent solutions to the problem of controlling wheel-based mobile platforms are proposed. These two algorithms are based on a so called virtual vehicle approach, where the motion of the reference point on the desired trajectory is governed by a differential equation containing error feedback. This, combined with the fact that the proven stable control algorithms are basically proportional regulators with arbitrary positive gains, make the solutions robust with respect to errors and disturbances, as demonstrated by the experimental results.
A novel class of clathrin-coated vesicles budding from endosomes

Clathrin-coated vesicles transport selective integral membrane proteins from the plasma membrane to endosomes and from the TGN to endosomes. Recycling of proteins from endosomes to the plasma membrane occurs via unidentified vesicles. To study this pathway, we used a novel technique that allows for the immunoelectron microscopic examination of transferrin receptor-containing endosomes in nonsectioned cells. Endosomes were identified as separate discontinuous tubular-vesicular entities. Each endosome was decorated, mainly on the tubules, with many clathrin-coated buds. Endosome-associated clathrin-coated buds were discerned from plasma membrane-derived clathrin-coated vesicles by three criteria: size (60 nm and 100 nm, respectively), continuity with endosomes, and the lack of labeling for alpha-adaptin. They were also distinguished from TGN-derived clathrin-coated vesicles by their location at the periphery of the cell, size, and the lack of labeling for gamma-adaptin. In the presence of brefeldin A, a large continuous endosomal network was formed. Transferrin receptor recycling as well as the formation of clathrin-coated pits at endosomes was inhibited in the presence of brefeldin A. Together with the localization of transferrin receptors at endosome-associated buds, this indicates that a novel class of clathrin-coated vesicles serves an exit pathway from endosomes. The target organelles for endosome-derived clathrin-coated vesicles remain, however, to be identified.
Association rules for rat spatial learning: The importance of the hippocampus for binding item identity with item location

Three cohorts of rats with extensive hippocampal lesions received multiple tests to examine the relationships between particular forms of associative learning and an influential account of hippocampal function (the cognitive map hypothesis). Hippocampal lesions spared both the ability to discriminate two different digging media and to discriminate two different room locations in a go/no‐go task when each location was approached from a single direction. Hippocampal lesions had, however, differential effects on a more complex task (biconditional discrimination) where the correct response was signaled by the presence or absence of specific cues. For all biconditional tasks, digging in one medium (A) was rewarded in the presence of cue C, while digging in medium B was rewarded in the presences of cue D. Such biconditional tasks are “configural” as no individual cue or element predicts the solution (AC+, AD−, BD+, and BC−). When proximal context cues signaled the correct digging choice, biconditional learning was seemingly unaffected by hippocampal lesions. Severe deficits occurred, however, when the correct digging choice was signaled by distal room cues. Also, impaired was the ability to discriminate two locations when each location was approached from two directions. A task demand that predicted those tasks impaired by hippocampal damage was the need to combine specific cues with their relative spatial positions (“structural learning”). This ability makes it possible to distinguish the same cues set in different spatial arrays. Thus, the hippocampus appears necessary for configural discriminations involving structure, discriminations that potentially underlie the creation of cognitive maps. © 2013 The Authors. Hippocampus Published by Wiley Periodicals, Inc.
Rural and urban disparities in quality of life and health-related behaviors among chronically ill patients.

INTRODUCTION The purpose of this study was to describe rural and urban disparities in quality of life and health-related behaviors among chronically ill patients. Additionally, effects of health status and health-related behaviors on healthcare utilization were investigated. METHODS The study included 1239 chronically ill patients from primary care centers in rural areas (eligible patients; response rate: 62.0%). The analyzed group was compared with the urban group, homogeneous in respect of gender and age (n=1886). Quality of life (QoL) was measured using the World Health Organization Quality of Life Instrument Short Form (WHOQoL-Bref). The authors also used the Health Behavior Inventory (HBI). RESULTS Only the results in Domain 4 (Environmental) were higher among patients from rural areas (13.6 vs 13.4, p=0.015) within the WHOQoL-Bref. Differences between rural and urban areas in the contributors to lower QoL referred to such variables as gender, height, body mass, BMI and level of healthcare utilization. Results of HBI were higher in patients from urban areas (85.0 vs 83.1, p<0.001). The differences in factors potentially contributing to lower levels of health behavior concerned gender, age, height, body mass, BMI, having a partner, number of chronic diseases and level of healthcare utilization. The authors observed among the rural patients fewer visits of district nurses (12.1 vs 15.3, p=0.003). Odds ratio (OR) for QoL in the case of place of residence (rural vs urban) was OR=1.341 (95% CI: 1.067-1.687). CONCLUSIONS Higher quality of life may reduce the level of healthcare utilization among residents of rural and urban areas. Educational programs, promoting health behaviors, should be primarily addressed to rural patients, men, younger individuals, patients with a lower number of chronic diseases, and those using healthcare services less often.
Investing in low-carbon transitions: energy finance as an adaptive market

The amount of capital required to transition energy systems to low-carbon futures is very large, yet analysis of energy systems change has been curiously quiet on the role of capital markets in financing energy transitions. This is surprising given the huge role finance and investment must play in facilitating transformative change. We argue this has been due to a lack of suitable theory to supplant neoclassical notions of capital markets and innovation finance. This research draws on the notion from Planetary economics: Energy, climate change and the three domains of sustainable development, by Grubb and colleagues, that planetary economics is defined by three ‘domains’, which describe behavioural, neoclassical, and evolutionary aspects of energy and climate policy analysis. We identify first- and second-domain theories of finance that are well established, but argue that third-domain approaches, relating to evolutionary systems change, have lacked a compatible theory of capital markets. Based on an analysis of electricity market reform and renewable energy finance in the UK, the ‘adaptive market hypothesis' is presented as a suitable framework with which to analyse energy systems finance. Armed with an understanding of financial markets as adaptive, scholars and policy makers can ask new questions about the role of capital markets in energy systems transitions. Policy relevance This article explores the role of financial markets in capitalising low-carbon energy systems and long-term change. The authors demonstrate that much energy and climate policy assumes financial markets are efficient, meaning they will reliably capitalise low-carbon transitions if a rational return is created by subsidy regimes or other market mechanisms. The authors show that the market for renewable energy finance does not conform to the efficient markets hypothesis, and is more in line with an ‘adaptive’ markets understanding. Climate and energy policy makers that design policy, strategy, and regulation on the assumption of efficient financial markets will not pay attention to structural and behavioural constraints on investment; they risk falling short of the investment levels needed for long-term systems change. In short, by thinking of financial markets as adaptive, the range of policy responses to enable low-carbon investment can be much broader.
The porcine SRY promoter is transactivated within a male genital ridge environment

Summary: In mammals the SRY gene functions as a dominant genetic switch for testis determination (Gubbay et al.: Nature 346:1128–1135, 1990; Koopman et al.: Nature 351:117–121, 1991; Sinclair et al.: Nature 346:240–244, 1990). To study SRY transcriptional regulation within an evolutionary context, we have generated transgenic mice that express green fluorescent protein (GFP) under the control of 4.5 kb of pig SRY 5′ flanking sequences (pSRYp‐GFP). Autofluorescence was observed in the genital ridges of e11.5 male embryos (18–21 tail somites), and by e12.5 (27 tail somites) autofluorescence was observed within the testes cords. The expression of the transgene did not display the abrupt termination characteristic of endogenous mouse SRY, but rather showed a gradual reduction in expression characteristic of human, pig and sheep SRY. Surprisingly, no autofluorescence was observed in normal XX genital ridges, although more sensitive RT‐PCR analysis detected transgene transcription. When the transgene was bred into a constitutively male line of mice (Odsex; Bishop et al.: Nat Genet 26:490–494, 2000), autofluorescence was visible in genital ridges of XX animals, in the genetic absence of Sry protein. Via RT‐PCR analysis, purified autofluorescent cells from e12.5 gonadal ridges expressed mouse SRY but not Oct4 transcripts, whereas autofluorescent cells from e14.5 gonadal ridges expressed MIS but not Oct4 transcripts, in each case consistent with a pre‐Sertoli cell phenotype. In vitro expression studies performed in CV‐1 cells demonstrated that pig SOX9 cDNA transactivated the pig SRY promoter but that pig SRY cDNA did not. When a SOX9 potential binding site identified at −205 of the pig SRY 5′ flanking sequences was mutated, the SOX9 transactivation effect was reduced by 70%. This site is conserved in the 5′ flanking sequences of bovine and human SRY genes but not in the mouse gene. Gel retardation assays using this binding site showed specific binding to SOX9‐enriched nuclear extracts that was competed by excess unlabelled binding site but not by mutated binding site. We suggest that pig SRY gene is responsive to a testicular environment and propose a model of feedback amplification of pig SRY transcription by SOX9. genesis 33:170–180, 2002. © 2002 Wiley‐Liss, Inc.
PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients.

BACKGROUND It has been reported that KRAS mutations (and to a lesser extent KRAS mutations with the BRAF V600E mutation) negatively affect response to anti-epidermal growth factor receptor (EGFR) mAbs in metastatic colorectal cancer (mCRC) patients, while the biological impact of the EGFR pathway represented by PI3K/PTEN/AKT on anti-EGFR treatment is still not clear. PATIENTS AND METHODS We analysed formalin-fixed samples from a cohort of 32 mCRC patients treated with cetuximab by means of EGFR immunohistochemistry, EGFR and PTEN FISH analysis, and KRAS, BRAF, PI3KCA, and PTEN genomic sequencing. RESULTS Ten (31%) of 32 patients showed a partial response to cetuximab and 22 (69%) did not [nonresponder (NR)]. EGFR immunophenotype and FISH-based gene status did not predict an anti-EGFR mAb response, whereas KRAS mutations (24%) and PI3K pathway activation, by means of PI3KCA mutations (13%) or PTEN mutation (10%)/loss (13%), were significantly restricted to, respectively, 41% and 37% of NRs. CONCLUSION These findings suggested that KRAS mutations and PI3KCA/PTEN deregulation significantly correlate with resistance to cetuximab. In line with this, patients carrying KRAS mutations or with activated PI3K profiles can benefit from targeted treatments only by switching off molecules belonging to the downstream signalling of activated EGFR, such as mammalian target of rapamycin.
Developing and Proposing the Ethno-Cultural Gerontological Nursing Model

By 2050, for the first time in U.S. history, almost half of elders will be from ethnic minority groups. To meet the needs of this rapidly diversifying population, nurses need to be able to marry transcultural nursing knowledge with gerontological nursing knowledge. The purpose of this article is to propose a new theoretical model for explaining health outcomes and health responses for older individuals in unique ethno-cultural groups and to discuss implications and applications of the model to transcultural gerontological nursing practice and research. The discussion will include (1) an overview of currently available theoretical knowledge in the area, (2) a description of the theory development process, (3) presentation of the proposed ethno-cultural gerontological nursing theoretical model, and (4) discussion of how this model can enhance nursing’s contributions to reducing health disparities. This model is presented not as a finished product but as a basis for future discussion and refinement.
IS THERE A BLACK HOLE IN NGC 4382?

We present Hubble Space Telescope (HST) Space Telescope Imaging Spectrograph observations of the galaxy NGC 4382 (M85) and axisymmetric models of the galaxy to determine mass-to-light ratio (ϒV) and central black hole mass (MBH). We find ϒV = 3.74 ± 0.1 M☉/L☉ and MBH = 1.3+5.2 − 1.2 × 107 M☉ at an assumed distance of 17.9 Mpc, consistent with no black hole. The upper limit, MBH < 9.6 × 107 M☉(2σ) or MBH < 1.4 × 108(3σ), is consistent with the current M–σ relation, which predicts MBH = 8.8 × 107 M☉ at σe = 182 km s−1, but low for the current M – L relation, which predicts MBH = 7.8 × 108 M☉ at LV = 8.9 × 1010 L☉, V. HST images show the nucleus to be double, suggesting the presence of a nuclear eccentric stellar disk, analogous to the Tremaine disk in M31. This conclusion is supported by the HST velocity dispersion profile. Despite the presence of this non-axisymmetric feature and evidence of a recent merger, we conclude that the reliability of our black hole mass determination is not hindered. The inferred low black hole mass may explain the lack of nuclear activity.
Functional Growth in Tissue-Engineered Living, Vascular Grafts: Follow-Up at 100 Weeks in a Large Animal Model

Background— Living autologous vascular grafts with the capacity for regeneration and growth may overcome the limitations of contemporary artificial prostheses. Particularly in congenital cardiovascular surgery, there is an unmet medical need for growing replacement materials. Here we investigate growth capacity of tissue-engineered living pulmonary arteries in a growing lamb model. Methods and Results— Vascular grafts fabricated from biodegradable scaffolds (ID 18±l mm) were sequentially seeded with vascular cells. The seeded constructs were grown in vitro for 21days using biomimetic conditions. Thereafter, these tissue-engineered vascular grafts (TEVGs) were surgically implanted as main pulmonary artery replacements in 14 lambs using cardiopulmonary bypass and followed up for ≤100 weeks. The animals more than doubled their body weight during the 2-year period. The TEVG showed good functional performance demonstrated by regular echocardiography at 20, 50, 80, and 100 weeks and computed tomography–angiography. In particular, there was no evidence of thrombus, calcification, stenosis, suture dehiscence, or aneurysm. There was a significant increase in diameter by 30% and length by 45%. Histology showed tissue formation reminiscent of native artery. Biochemical analysis revealed cellularity and proteoglycans and increased collagen contents in all of the groups, analogous to those of native vessels. The mechanical profiles of the TEVG showed stronger but less elastic tissue properties than native pulmonary arteries. Conclusions— This study provides evidence of growth in living, functional pulmonary arteries engineered from vascular cells in a full growth animal model.
Efficient resonant frequency doubling of a cw Nd:YAG laser in bulk periodically poled KTiOPO(4).

A cw Nd:YAG laser was quasi-phase-matched frequency doubled by a bulk periodically poled flux-grown KTiOPO(4) crystal in an external resonant cavity. The conversion efficiency and the second-harmonic power with a pump of 225 mW were 55% and 123.5 mW, respectively. The loss of the 1-cm-long crystal, which operated near room temperature, was 1.3% and was dominated by scatter from the cleaved facets of the crystal. No damage, photorefractive or other, was observed at intensites of 370Wmm(-2) , but beam size had to be optimized to eliminate thermal-induced instabilities in the doubling cavity.
Optimization of photonic crystal laser cavity for DWDM applications

In this paper, we modelize an optical source that can be used for Dense Wavelength Division Multiplexing optical access networks. Thus, we adopt a Photonic crystal (Phc) structure which provides larger capacity and faster services. Our purpose is to generate wavelengths according to the ITU-T (Telecommunication Standardization Sector of the International Telecommunications Union). Moreover, our structure provides several Quality of Services by improving transmission efficiency and reducing services cost. We vary the lattice constant a, the radius r and the ratio r/a to find a range of values that suits with the ITU-T grid, then we extract the most effective values providing the smallest bandwidth and the highest quality factor.
Alfalfa Growth and Development

All aspects of alfalfa management require a thorough understanding of the growth and development of the crop. Basic knowledge of the botanical features of alfalfa, its growth patterns, and its developmental stages are keys to better management of a healthy, productive stand. Plant growth affects yield components, while plant morphology impacts many management decisions, including scheduling of herbicide treatments and harvest. This chapter describes the processes of alfalfa growth and defines precise stages of development.
Metacognitive confidence: A neuroscience approach

Abstract Metacognition refers to thinking about our own thinking and implies a distinction between primary and secondary cognition. This article reviews how neuroscience has dealt with this distinction between first and second-order cognition, with special focus on meta-cognitive confidence. Meta-cognitive confidence is important because it affects whether people use their primary cognitions in guiding judgments and behaviors. The research described in this review is organized around the type of primary thoughts for which people have confidence, including judgments about memory, choices, and evaluative judgments. Along with other areas, prefrontal cortex and parietal regions have been consistently associated with judgments of meta-cognitive confidence in these three domains. Although metacognitive confidence might be associated with particular brain activity in most of the studies reviewed, confidence often seems to be confounded with other potentially important dimensions, such as effort and ease. Given that people tend to be less certain in tasks that are more difficult, more research is needed to examine the brain activity specifically linked to confidence.
Serological markers predict inflammatory bowel disease years before the diagnosis

Objective Anti-neutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae mannan antibodies (ASCAs) have been detected in the serum of patients with ulcerative colitis (UC) and Crohn's disease (CD) and their unaffected family members. The aim of this study was to establish the value of serological markers as predictors of UC and CD. Design Individuals who developed CD or UC were identified from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. At recruitment, none of the participants had a diagnosis of CD or UC. For each incident case, two controls were randomly selected matched for centre, date of birth, sex, date of recruitment and time of follow-up. Serum of cases and controls obtained at recruitment were analysed for ASCA IgG, ASCA IgA, perinuclear anti-neutrophil cytoplasmic antibody (pANCA), antibodies against Escherichia coli outer membrane porin C (OmpC) and flagellin CBir1. Conditional logistic regression was used to determine risk of CD and UC. Receiver operating characteristic curves were constructed to test accuracy. Results A total of 77 individuals were diagnosed with CD and 167 with UC after a mean follow-up of 4.5 (SD 3.2) and 4.4 (SD 3.1) years following blood collection, respectively. Combinations of pANCA, ASCA, anti-CBir1 and anti-OmpC were most accurate in predicting incident CD and UC (area under curve 0.679 and 0.657, respectively). The predictive value of the combination of markers increased when time to diagnosis of CD or UC decreased. Conclusion A panel of serological markers is able to predict development of CD and UC in individuals from a low-risk population.