Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase II study of docetaxel alternating with cisplatin in chemotherapy-naïve patients with advanced non-small cell lung cancer

The objective of this study was to evaluate a regimen of full doses of docetaxel and cisplatin, using an alternating schedule, as first-line therapy for patients with inoperable non-small cell lung cancer (NSCLC). The standard concomitant schedule does not allow full doses of both drugs to be administered. We wanted to see if there was an advantage to be gained by administering full doses of both docetaxel and cisplatin, using a different schedule. Docetaxel 100 mg/m2 was given once every 6 weeks from week 1 and cisplatin (120 mg/m2 for two doses and 100 mg/m2 thereafter) once every 6 weeks from week 4, for six cycles (three docetaxel and three cisplatin). Thirty-six of the 44 patients enrolled were evaluable for efficacy. Forty-eight percent of the patients had good (KPS 90-100%) performance status. A median of five cycles was administered, for which no dose reductions were necessary. There were 13 of 36 partial responses (36%; 95% CI 21-54%) and 15 of 36 patients achieved stable disease (42%). The median duration of response was 10.5 months, the median time to progression was 4.5 months and the median survival was 9 months. The 1 and 2 year survival rates were 39 and 16%, respectively. The most frequent grade 3-4 toxicities were nausea (23% of patients), vomiting (18%) and neutropenia (77%). Infections were also common, but not severe. The alternating schedule produced response, toxicity and survival figures that compared favorable with those using the concomitant schedule. This study could serve as a model for future studies of non-cisplatin-containing regimens, in which full doses of docetaxel could alternate with full doses of other new agents active against NSCLC.
[The effect of virginiamycin on rumen fermentation in vitro after adaptation of donors to the inoculum].

Virginiamycin is an antibiotic active against grampositive bacteria in the alimentary tract, which is also suitable for supplementation of diets of growing and finishing ruminants. The aim of this work was to specify the effect of virginiamycin on some parameters of rumen fermentation in vitro with inoculi taken from wethers adapted or non-adapted to the virginiamycin intake. Incubations were performed anaerobically at 39 degrees C in serum bottles closed with Bunsen valves. Virginiamycin was added at 0 or 10 mg/l to the rumen fluid diluted with McDougall buffer. Virginiamycin significantly decreased production and utilization of lactic acid, production of methane and decomposition of casein when rumen fluid was taken from non-adapted wethers. Most of its effects disappeared when rumen fluid was sampled from wethers adapted to the virginiamycin intake (100 mg per head daily for 2 months). Adaptation of wethers to virginiamycin was further confirmed by analyses of the rumen fluid which was used for inoculation of in vitro cultures. Molar percentages of acetate, propionate, butyrate and valerate were the same before and after the adaptation. Therefore it can be concluded that the effects of virginiamycin on rumen parameters are not stable and its addition to ruminant diets cannot be recommended, with exception of the milk nutrition period. In the last experiment the stability of virginiamycin in the rumen fluid of adapted wethers was investigated. (ABSTRACT TRUNCATED AT 250 WORDS)
Effect of long‐ and short‐term treatments with pravastatin on diabetes mellitus and pancreatic fibrosis in the Otsuka–Long–Evans–Tokushima Fatty rat

Background and purpose: The effects of statins on diabetes mellitus (DM) are controversial, and their effects on pancreatic fibrosis are poorly defined. We investigated the effect of long‐ and short‐term treatments with pravastatin on the development of DM and pancreatic fibrosis in DM‐prone Otsuka–Long–Evans–Tokushima Fatty (OLETF) rats.
Doppler analysis and placental nitric oxide synthase expression during fetal growth restriction

Objective. To assess placental nitric oxide (NO) metabolism related to changes in the uteroplacental circulation during fetal growth restriction (FGR). Methods. The resistance index (RI) from the uterine arteries and pulsatility index (PI) from the umbilical artery were determined by Doppler analysis in 15 patients with FGR and 12 healthy controls, before elective cesarean section. Inducible (iNOS) and endothelial (eNOS) NO synthase expression were measured in placental samples. Immunohistochemistry was performed for iNOS location in the placenta. Results. During FGR, we observed a significant elevation of iNOS when compared with controls. Conversely, eNOS did not differ between the two groups. A negative correlation with eNOS (r = −0.85) and a positive correlation with iNOS (r = 0.91) was found correlating to umbilical PI. The iNOS proteins were reduced in syncytiotrophoblast cells and increased in endothelium in the FGR group compared to the controls. Conclusions. During FGR, placental iNOS expression is significantly increased; this increase possibly represents an adaptive physiological mechanism for overcoming a fetoplacental circulation deficiency.
First principles calculation of current-voltage characteristics of defected zigzag graphene nanoribons

Interesting phenomena in the electronic transport of ultra-narrow zigzag graphene nanoribbons (ZGNRs) has been demonstrated in previous works. It has been reported that although the two classes of ZGNRs, with odd and even number of transversal layers, have similar electronic structures, but they show very different I-V characteristics. In this work, we present the results of our calculations based on a combination of density functional theory and non-equilibrium Green's function for the defected ZGNRs. The favored sites for carbon vacancies are determined according to the defect formation energies. It has been shown that the peculiar difference between the I-V characteristics of two ZGNRs classes has been removed in the presence of defects.
The human papillomavirus type 16 E2 transcription factor binds with low cooperativity to two flanking sites and represses the E6 promoter through displacement of Sp1 and TFIID

The E6 promoters of all genital human papillomaviruses have a characteristic alignment of transcription factor binding sites. Activation of the basic transcription complex at the TATA box depends upon a sequence-aberrant Sp1 site. Repression of E6 promoters is achieved by two binding sites for the viral E2 protein positioned between the Sp1 site and the TATA box. We have purified the human papillomavirus type 16 E2 protein after expression in Escherichia coli and studied its binding and repression properties with oligonucleotides representing the homologous promoter sequences. A Kd value of 3 x 10(-10) M indicated binding properties expected for a native protein. We found low cooperativity in the binding of two E2 dimers to flanking sites, both when these sites were separated by 3 nucleotides, as in the natural promoter, and when they were further apart. E2 protein, bound close to the distal Sp1 site, displaced the Sp1 factor even when the aberrant sequence was replaced by a typical Sp1 core recognition site. The high affinity of E2 protein for its binding site even led to Sp1 displacement at concentrations of E2 protein nearly 2 orders of magnitude lower than those of Sp1. Functional analyses of mutated E6 promoter sequences showed repression by this distal E2 binding site in the complete absence of binding to the proximal E2 binding site. From our findings and observations published by others, we conclude that each of the E2 binding sites in the E6 promoter of genital human papillomaviruses plays a separate role by displacing the transcription factors Sp1 and TFIID.
Programmed Heterogeneity: Epigenetic Mechanisms in Bacteria

Contrary to the traditional view that bacterial populations are clonal, single-cell analysis reveals that phenotypic heterogeneity is common in bacteria. Formation of distinct bacterial lineages appears to be frequent during adaptation to harsh environments, including the colonization of animals by bacterial pathogens. Formation of bacterial subpopulations is often controlled by epigenetic mechanisms that generate inheritable phenotypic diversity without altering the DNA sequence. Such mechanisms are diverse, ranging from relatively simple feedback loops to complex self-perpetuating DNA methylation patterns.
Genome-wide DNA methylome alterations in acute coronary syndrome

Acute coronary syndrome (ACS) is a common disease with high mortality and morbidity rates. The methylation status of blood DNA may serve as a potential early diagnosis and prevention biomarker for numerous diseases. The present study was designed to explore novel genome-wide aberrant DNA methylation patterns associated with ACS. The Infinium HumanMethylation450 assay was used to examine genome-wide DNA methylation profiles in 3 pairs of ACS and control group samples. Epigenome-wide DNA methylation, genomic distribution, Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The results were confirmed using methylation-specific polymerase chain reaction (MSP) and Sequenom MassARRAY analyses in ACS, stable coronary artery disease (SCAD) and control samples. A total of 11,342 differentially methylated (DM) 5′-C-phosphate-G-3′ (CpG) sites were identified, including 8,865 hypomethylated and 2,477 hypermethylated CpG sites in the ACS group compared with the control samples. They varied in frequency across genomic compartments, but were particularly notable in gene bodies and shores. The results of GO term and KEGG pathway enrichment analyses revealed that the methylated genes were associated with certain biological processes and pathways. Despite the considerable variability in methylation data, the candidate selected possessed significant methylation alteration in mothers against decapentaplegic homolog 3 (SMAD3) transcription start site 155 (Chr1:67356838-Chr1:67356942). MSP analysis from 81 ACS samples, 74 SCAD samples and 53 healthy samples, and Sequenom MassARRAY analysis, confirmed that differential CpG methylation of SMAD3 was significantly corrected with the reference results of the HumanMethylation450 array. The data identified an ACS-specific DNA methylation profile with a large number of novel DM CpG sites, some of which may serve as candidate markers for the early diagnosis of ACS.
Crystal structure of type I ryanodine receptor amino-terminal β-trefoil domain reveals a disease-associated mutation “hot spot” loop

Muscle contraction and relaxation is regulated by transient elevations of myoplasmic Ca2+. Ca2+ is released from stores in the lumen of the sarco(endo)plasmic reticulum (SER) to initiate formation of the Ca2+ transient by activation of a class of Ca2+ release channels referred to as ryanodine receptors (RyRs) and is pumped back into the SER lumen by Ca2+-ATPases (SERCAs) to terminate the Ca2+ transient. Mutations in the type 1 ryanodine receptor gene, RYR1, are associated with 2 skeletal muscle disorders, malignant hyperthermia (MH), and central core disease (CCD). The evaluation of proposed mechanisms by which RyR1 mutations cause MH and CCD is hindered by the lack of high-resolution structural information. Here, we report the crystal structure of the N-terminal 210 residues of RyR1 (RyRNTD) at 2.5 Å. The RyRNTD structure is similar to that of the suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor (IP3Rsup), but lacks most of the long helix-turn-helix segment of the “arm” domain in IP3Rsup. The N-terminal β-trefoil fold, found in both RyR and IP3R, is likely to play a critical role in regulatory mechanisms in this channel family. A disease-associated mutation “hot spot” loop was identified between strands 8 and 9 in a highly basic region of RyR1. Biophysical studies showed that 3 MH-associated mutations (C36R, R164C, and R178C) do not adversely affect the global stability or fold of RyRNTD, supporting previously described mechanisms whereby mutations perturb protein–protein interactions.
Audio based soccer game summarization

This papers presents a simple and near real-time performance system for detecting highlighted events of soccer game retransmissions and generating their video summaries. The proposed detection algorithm is based on two acoustic features of the audio track: the block energy and the acoustic repetition index. To the authors' knowledge, the acoustic repetition index has not been used previously in similar applications. This index represents the correlation between a narrow acoustic section and the seconds just after and before it, in order to detect sections of audio where repetitions occur. The system has been validated on a corpus with EUFA EURO competition games, achieving good scores in goal recall.
Exercise tolerance, body composition and blood lipids in obese African-American women following short-term training.

BACKGROUND The purpose of this investigation was to examine the exercise tolerance, body composition and blood lipids in African-American women, possessing greater than or equal to 30% body fat, following six weeks of endurance training. METHODS Oxygen consumption (VO2), central hemodynamics, blood lipids, body weight, body fat, and the body mass index of seven subjects (21.0 +/- 0.8 yrs) were studied. Heart rate (HR), blood pressure (BP), exercise duration, rating of perceived exertion (RPE), blood lactate (bLA) and VO2 were obtained in response to a maximal exercise tolerance test on a motorized treadmill. Subjects trained three times per week for 50 minutes per session (30 minutes at 70% maximal oxygen consumption (VO2max). RESULTS Dependent "t"-tests revealed significant (p < 0.05) increases in VO2max, 27%; exercise duration, 31%; as well as peak HR, systolic blood pressure (SBP), and bLA. Values for submaximal HR, SBP, RPE during the post-training test were lower. In addition, body weight, body fat and the body mass index decreased 2.2%, 1.3% and 3.4% respectively. There were no changes in blood lipids. CONCLUSIONS These findings suggest short-term training at 70% VO2max provides the necessary stimulus for obese women to improve exercise tolerance and body composition. However, the training stimulus is insufficient to alter lipid profiles.
Effects of Coffee Management on Deforestation Rates and Forest Integrity

Knowledge about how forest margins are utilized can be crucial for a general understanding of changes in forest cover, forest structure, and biodiversity across landscapes. We studied forest‐agriculture transitions in southwestern Ethiopia and hypothesized that the presence of coffee (Coffea arabica)decreases deforestation rates because of coffee's importance to local economies and its widespread occurrence in forests and forest margins. Using satellite images and elevation data, we compared changes in forest cover over 37 years (1973–2010) across elevations in 2 forest‐agriculture mosaic landscapes (1100 km2 around Bonga and 3000 km2 in Goma‐Gera). In the field in the Bonga area, we determined coffee cover and forest structure in 40 forest margins that differed in time since deforestation. Both the absolute and relative deforestation rates were lower at coffee‐growing elevations compared with at higher elevations (−10/20% vs. −40/50% comparing relative rates at 1800 m asl and 2300–2500 m asl, respectively). Within the coffee‐growing elevation, the proportion of sites with high coffee cover (>20%) was significantly higher in stable margins (42% of sites that had been in the same location for the entire period) than in recently changed margins (0% of sites where expansion of annual crops had changed the margin). Disturbance level and forest structure did not differ between sites with 30% or 3% coffee. However, a growing body of literature on gradients of coffee management in Ethiopia reports coffee's negative effects on abundances of forest‐specialist species. Even if the presence of coffee slows down the conversion of forest to annual‐crop agriculture, there is a risk that an intensification of coffee management will still threaten forest biodiversity, including the genetic diversity of wild coffee. Conservation policy for Ethiopian forests thus needs to develop strategies that acknowledge that forests without coffee production may have higher deforestation risks than forests with coffee production and that forests with coffee production often have lower biodiversity value.
The Dynamical Balance of the Brain at Rest

The authors review evidence that spontaneous, that is, not stimulus or task driven, activity in the brain at the level of large-scale neural systems is not noise, but orderly and organized in a series of functional networks that maintain, at all times, a high level of coherence. These networks of spontaneous activity correlation or resting state networks (RSN) are closely related to the underlying anatomical connectivity, but their topography is also gated by the history of prior task activation. Network coherence does not depend on covert cognitive activity, but its strength and integrity relates to behavioral performance. Some RSN are functionally organized as dynamically competing systems both at rest and during tasks. Computational studies show that one of such dynamics, the anticorrelation between networks, depends on noise-driven transitions between different multistable cluster synchronization states. These multistable states emerge because of transmission delays between regions that are modeled as coupled oscillators systems. Large-scale systems dynamics are useful for keeping different functional subnetworks in a state of heightened competition, which can be stabilized and fired by even small modulations of either sensory or internal signals.
Antenna optimization using an evolutionary programming algorithm with a hybrid mutation operator

Conventional implementation of evolutionary programming (EP) for continuous parameter optimization uses Gaussian mutations. However, an implementation of EP with Cauchy mutation operator has empirically been shown to outperform EP using the Gaussian mutations for optimizations of multi-modal functions with many local optima. The faster convergence of EP with Cauchy mutation has been explained in terms of the fatter tails of the Cauchy probability density function, which results in a higher probability of escaping from a local optimum. In this work we present an implementation of EP consisting of a hybrid linear combination of the Cauchy and Gaussian mutations for antenna optimization problems in order to exploit the desirable properties of these two operators. The implementation follows a procedure similar to the one described by Chellapilla (see IEEE Trans. on Evolutionary Computation, September 1998) for function optimization and uses a self-adaptive scheme for updating the standard deviation and the scale parameter of Gaussian and Cauchy distributions, respectively, during the evolution. As an example the optimization of a six-element Yagi-Uda array of dipoles using the hybrid method is presented.
RNA codewords and protein synthesis, 8. Nucleotide sequences of synonym codons for arginine, valine, cysteine, and alanine.

Materials and Methods. -Components of reactions: The preparation of E. coli W3100 ribo-somes,9 sRNA,10 components of reaction mixtures, and assay for ribosomal-bound sRNA1 have been described. Each sRNA preparation was acylated with one H3- or C'4-amino acid and 19 C"2-amino acids. The properties of the radioactive AA-sRNA preparations not described pre-viously5' are shown in Table The purity of the Thr-, Cys-, and Ser-sRNA preparations was checked by deacylating the sRNA in ammonium formate (0.1 M, pH 10) for 1 hr at 37°, fol-TABLE Materials and Methods. -P32-labeled nucleohistone: We have used P32-labeled histone-RNA complex for the major part of this work. For each preparation ca. 5 kg of pea seeds (var. Alaska)
Thromboembolic disease in systemic vasculitis is associated with enhanced microparticle‐mediated thrombin generation

*Department of Paediatric Rheumatology, Institute of Child Health, London; and Infectious Diseases and Microbiology Unit, Institute of ChildHealth, London, UKTo cite this article: Eleftheriou D, Hong Y, Klein NJ, Brogan PA. Thromboembolic disease in systemic vasculitis is associated with enhancedmicroparticle-mediated thrombin generation. J Thromb Haemost 2011; 9: 1864–7.
Treatment of acute and chronic synovitis by non‐surgical means

Summary. This paper reviews personal experience in the treatment of recurrent haemarthrosis and chronic synovitis by non‐surgical means. Experience with synoviorthesis with rifampicine and radioactive colloids is analyzed, and a multiple chromosomal study to demonstrate safety of radioactive injections is described. The results obtained are so very satisfactory as to recommend non‐aggressive synoviorthesis as the treatment of choice to prevent recurrence of bleeding. Long experience in the treatment of chronic arthropathy with intrarticular corticosteroids and hyaluronic acid has shown very promising results.
Dilation and reduced distensibility of carotid artery in patients with abdominal aortic aneurysms.

BACKGROUND Although patients with abdominal aortic aneurysms (AAA) frequently have coexisting systemic atherosclerosis, the dilatative manifestation of AAA is the opposite of the occlusion characteristic of atherosclerotic disease. It has been suggested that this dilatative disease is caused by an alteration in connective tissue metabolism in systemic arterial wall. Such a condition might alter systemic arterial diameter and wall behavior. We investigated arterial characteristics in AAA patients, including morphologic changes and wall mechanics in the carotid artery. METHODS AND RESULTS Atherosclerotic intimal changes such as intima-media thickness (IMT), plaque formation, diameter, and wall elasticity of the carotid artery were determined ultrasonographically in patients with AAA (n = 102) and compared with age-matched patients with the atherosclerotic diseases arteriosclerosis obliterans (ASO, n = 115) and coronary artery disease (CAD, n = 123) and with age-matched healthy control patients (CTL, n = 45). Intimal disease in AAA was significantly milder than in ASO, at the same level as CAD, and more severe than in CTL. Although end-diastolic luminal diameters (mm) in AAA (7.05 +/- 1.08), ASO (6.74 +/- 0.18), and CAD (6.66 +/- 0.83) were significantly higher than in CTL (5.97 +/- 0.93), they were also excessively increased compared with the equivalent diameters seen in ASO (P <.01) and CAD (P <.01). Luminal distensibility (x 10(-6) cm(2). dyne(-1)) in AAA (0.83 +/- 0.48) was excessively decreased compared not only with CTL (1.70 +/- 1.11, P <.01) but also with ASO (1.12 +/- 0.47, P <.01) and CAD (1.18 +/- 0.59, P <. 01). These relations remained true when adjusted for blood pressure and luminal diameter. Intra-AAA group analysis showed that distensibility in ruptured cases (n = 14) was significantly lower than in nonruptured cases (n = 88) (0.58 +/- 0.24 vs 0.88 +/- 0.50, P <.05). CONCLUSIONS Excessive arterial dilation and reduced distensibility without severe intimal disease were found in the carotid arteries of patients with AAA. This suggests that these patients may be subject to systemic arterial alterations, including structural and functional abnormalities.