Miracle-dz/UniFAR-FTUs huggingface dataset:
The Clinical Effect of the Dual-Targeting Strategy Involving PI3K/AKT/mTOR and RAS/MEK/ERK Pathways in Patients with Advanced Cancer

Purpose: This study evaluated the clinical relevance of the dual-targeting strategy involving PI3K/AKT/mTOR and RAF/MEK/ERK pathways. Experimental Design: We investigated safety, efficacy, and correlations between tumor genetic alterations and clinical benefit in 236 patients with advanced cancers treated with phase I study drugs targeting phosphoinositide 3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathways in our Phase I Clinical Trials Program. Results: Seventy-six (32.2%) patients received a PI3K pathway inhibitor in combination with a MAPK pathway inhibitor (D), whereas 124 (52.5%) and 36 (15.3%), respectively, received an inhibitor of either the PI3K or MAPK pathways (S). The rates of drug-related grade >III adverse events were 18.1% for (S) and 53.9% for (D; P < 0.001); the rates of dose-limiting toxicities were 9.4% for (S) and 18.4% for (D; P = 0.06). The most frequent grade >III adverse events were transaminase elevations, skin rash, and mucositis. In our comprehensive tumor genomic analysis, of 9 patients who harbored coactivation of both pathways (colorectal cancer, n = 7; melanoma, n = 2), all 5 patients treated with (D) had tumor regression ranging from 2% to 64%. Conclusions: These results suggest that dual inhibition of both pathways may potentially exhibit favorable efficacy compared with inhibition of either pathway, at the expense of greater toxicity. Furthermore, this parallel pathway targeting strategy may be especially important in patients with coexisting PI3K pathway genetic alterations and KRAS or BRAF mutations and suggests that molecular profiling and matching patients with combinations of these targeted drugs will need to be investigated in depth. Clin Cancer Res; 18(8); 2316–25. ©2012 AACR.
Genetic Determinants for Gestational Diabetes Mellitus and Related Metabolic Traits in Mexican Women

Epidemiological and physiological similarities among Gestational Diabetes Mellitus (GDM) and Type 2 Diabetes (T2D) suggest that both diseases, share a common genetic background. T2D risk variants have been associated to GDM susceptibility. However, the genetic architecture of GDM is not yet completely understood. We analyzed 176 SNPs for 115 loci previously associated to T2D, GDM and body mass index (BMI), as well as a set of 118 Ancestry Informative Markers (AIMs), in 750 pregnant Mexican women. Association with GDM was found for two of the most frequently replicated T2D loci: a TCF7L2 haplotype (CTTC: rs7901695, rs4506565, rs7903146, rs12243326; P=2.16x10-06; OR=2.95) and a KCNQ1 haplotype (TTT: rs2237892, rs163184, rs2237897; P=1.98x10-05; OR=0.55). In addition, we found two loci associated to glycemic traits: CENTD2 (60’ OGTT glycemia: rs1552224, P=0.03727) and MTNR1B (HOMA B: rs1387153, P=0.05358). Remarkably, a major susceptibility SLC16A11 locus for T2D in Mexicans was not shown to play a role in GDM risk. The fact that two of the main T2D associated loci also contribute to the risk of developing GDM in Mexicans, confirm that both diseases share a common genetic background. However, lack of association with a Native American contribution T2D risk haplotype, SLC16A11, suggests that other genetic mechanisms may be in play for GDM.
Inhibition of NO2, PGE2, TNF-α, and iNOS EXpression by Shorea robusta L.: An Ethnomedicine Used for Anti-Inflammatory and Analgesic Activity

This paper is an attempt to evaluate the anti-inflammatory and analgesic activities and the possible mechanism of action of tender leaf extracts of Shorea robusta, traditionally used in ailments related to inflammation. The acetic-acid-induced writhing and tail flick tests were carried out for analgesic activity, while the anti-inflammatory activity was evaluated in carrageenan-and dextran- induced paw edema and cotton-pellet-induced granuloma model. The acetic-acid-induced vascular permeability, erythrocyte membrane stabilization, release of proinflammatory mediators (nitric oxide and prostaglandin E2), and cytokines (tumor necrosis factor-α, and interleukins-1β and -6) from lipopolysaccharide-stimulated human monocytic cell lines were assessed to understand the mechanism of action. The results revealed that both aqueous and methanol extract (400 mg/kg) caused significant reduction of writhing and tail flick, paw edema, granuloma tissue formation (P < 0.01), vascular permeability, and membrane stabilization. Interestingly, the aqueous extract at 40 μg/mL significantly inhibited the production of NO and release of PGE2, TNF-α, IL-1β, and IL-6. Chemically the extract contains flavonoids and triterpenes and toxicity study showed that the extract is safe. Thus, our study validated the scientific rationale of ethnomedicinal use of S. robusta and unveils its mechanism of action. However, chronic toxicological studies with active constituents are needed before its use.
Tailoring of organic nanofiber growth for a new type of waveguides

It has been shown recently, that organic nanofibers grown from para-hexaphenyl and from α-sexithiophene molecules can be used as a new type of nanoscopic waveguides. Their growth is due to a self-assembly process, thus large quantities of aligned nanofibers can be fabricated simultaneously. Because of the growth mechanism of the nanofibers, their widths and heights are limited to a few 100 nm and a few 10 nm, respectively. In this paper we show how this kind of control has been obtained via modification of the bare muscovite surface before organic molecule deposition. Introducing e.g. a thin layer of Au islands before nanofiber growth results in an up to 15-fold increase in height, whereas the mean width and the optical properties of the fibers remain almost unchanged. Au films of varying thickness lead to tailor-made height profiles along the fiber. Using atomic force microscopy the details of these Au/organic heterostructures are examined and the growth is compared to growth on untreated mica. By scratching the fibers with an AFM tip grating structures have been written into the fibers.
Coordinated Laboratory Studies of Meteorites Supporting Rosetta Mission's Asteroid Flyby Target: 2867

ASTEROID FLYBY TARGET: 2867 STEINS. L.A. McFadden , E. Ammonito, E.A. Cloutis, A. Coradini, M.C. deSanctis,M. Fulchignoni, E. Hadamcik, T. Hiroi , L. Kolokolova, A.C. Levasseur-Regourd ,V. Psarev, J.-B. Renard. U. Maryland (Department of Astronomy, College Park, MD 20742-2421 mcfadden@astro.umd.edu), IFSI-INAF Rome, U. Winnipeg (Department of Geography, Winnipeg, MB, Canada R3B 2E9, 4 University of Paris/Observatoire de Paris-Meudon, UPMC Univ. Paris 06, UMR 7620, 91371 Verrières, France, Brown University, Providence, RI, Kharkiv Astronomical Observatory, Kharkiv, Ukraine.
Reflection / Suppression Coatings For 900 - 1200 A Radiation

We describe the design and performance of multiple-layer, selective-reflection, selective-suppression coatings for the 900 - 1200 Å band. These coatings are designed to optimize both high reflectivity at a desirable wavelength and low reflectivity at an undesirable wavelength. The minimum structure for a selective coating consists of a thin metal or metal oxide layer (50 - 150 Å thickness) over an aluminum substrate protected with a semi-transparent dielectric (100 - 1000 Å. thickness). Predicted coating performance is strongly effected by varying the layer combination and thickness. Selec-tivity may be enhanced or augmented with further dielectric / metal layers. A graphical method of optimizing the coat-ing layer structure is developed. Aluminum, silicon, their oxides, and gold have been investigated as coating layer materials. We have fabricated a very simple coating with a 1026 to 1216 Å reflectivity ratio. greater than 100. Such reflection / suppression coatings may be of great utility to spaceborne EUV spectrographs. Strong background geocoronal emission lines could be rejected by use of properly coated collecting optics. By eliminating a diffraction element to reject background lines, efficiency losses and scattering may be avoided.
Using IR methods for labeling source code artifacts: Is it worthwhile?

Information Retrieval (IR) techniques have been used for various software engineering tasks, including the labeling of software artifacts by extracting “keywords” from them. Such techniques include Vector Space Models, Latent Semantic Indexing, Latent Dirichlet Allocation, as well as customized heuristics extracting words from specific source code elements. This paper investigates how source code artifact labeling performed by IR techniques would overlap (and differ) from labeling performed by humans. This has been done by asking a group of subjects to label 20 classes from two Java software systems, JHotDraw and eXVantage. Results indicate that, in most cases, automatic labeling would be more similar to human-based labeling if using simpler techniques - e.g., using words from class and method names - that better reflect how humans behave. Instead, clustering-based approaches (LSI and LDA) are much more worthwhile to be used on source code artifacts having a high verbosity, as well as for artifacts requiring more effort to be manually labeled.
Synthesis of 1,4-disubstituted 1,2,3-triazole Derivatives Using Click Chemistry and their Src Kinase Activities.

BACKGROUND Tyrosine kinases (TK) are enzymes that catalyze the phosphorylation of tyrosine residues on proteins by the transfer of phosphate moiety of ATP. TK are key regulators of various cell functions, such as cellular growth, proliferation, migration, differentiation, and apoptosis. Src mutations and/or overexpression has been correlated with tumor growth, metastasis, and angiogenesis [4,5]. Thus, the design and the discovery of novel Src kinase inhibitors remains critically important. METHODS A series of 1,4-disubstituted 1,2,3-triazoles derivatives were designed and prepared as potential inhibitors for Src kinase. In this manuscript, all of the designed compounds were screened via molecular docking using PLANTS as virtual screening software to identify new inhibitors of Src kinase. Subsequently, all of the screened compounds were synthesized via Huisgen's 1,3-dipolar cycloaddition between terminal alkynes (1) and methyl 2-azidoacetate (2) with Cu(I) in excellent yields at room temperature. RESULTS In the present study, we report the design and the synthesis of a series of 1,4-disubstituted 1,2,3-triazoles involving one pot condensation of methyl 2-azidoacetate and different terminal alkynes. All the synthesized triazoles were characterized by IR, 1 H, 13 C, 19 F NMR, and HRMS. They were investigated as inhibitors of Src kinase. CONCLUSION A series of 1,4-disubstituted 1,2,3-triazole compounds were synthesized through an easy, convenient Cu(I) catalyzed click reaction and evaluated for their Src kinase activity. Compound 3m exhibited significant inhibitory activity against Src Kinase. These results, along with molecular design docking observations, are significant evidence to demonstrate the compound 3m could be optimized as a potential Src kinase inhibitor in further studies.
The Phosphate Transporter Gene OsPht1;4 Is Involved in Phosphate Homeostasis in Rice

A total of 13 phosphate transporters in rice (Oryza sative) have been identified as belonging to the Pht1 family, which mediates inorganic phosphate (Pi) uptake and transport. We report the biological property and physiological role of OsPht1;4 (OsPT4). Overexpressing OsPT4 resulted in significant higher Pi accumulation in roots, straw and brown rice, and suppression of OsPT4 caused decreased Pi concentration in straw and brown rice. Expression of the β-glucuronidase reporter gene driven by the OsPT4 promoter showed that OsPT4 is expressed in roots, leaves, ligules, stamens, and caryopses under sufficient Pi conditions, consistent with the expression profile showing that OsPT4 has high expression in roots and flag leaves. The transcript level of OsPT4 increased significantly both in shoots and roots with a long time Pi starvation. OsPT4 encoded a plasma membrane—localized protein and was able to complement the function of the Pi transporter gene PHO84 in yeast. We concluded that OsPT4 is a functional Pi-influx transporter involved in Pi absorption in rice that might play a role in Pi translocation. This study will enrich our understanding about the physiological function of rice Pht1 family genes.
Control Engineering: New Trends with OO Modelling Approach

The paper deals with two examples, which show the efficiency of OO modelling approach in control engineering. The first example - an optimization of three tank hydraulic control system shows the efficiency of the OO modelling approach in control engineering education. A very efficient environment is the combination of Matlab Simulink and a Modelica based OO environment Dymola. Two different control strategies - PID and cascade control are demonstrated. The second example shows the efficiency of OO modelling approach in an industrial application. DYMOLA-Modelica was efficiently used for studying a pendulum system in a stone wool production technology in a Slovenian company. In this system linear (horizontal) movement of a bottom edge of the pendulum system is a very important technological feature in forming the secondary wool layer. The simulation results showed that it is possible to achieve more appropriate movements with regard to position and velocity
A Multi-kernel Framework for Inductive Semi-supervised Learning

We investigate the beneﬁt of combining both cluster assumption and manifold assumption underlying most of the semi-supervised algorithms using the ﬂexibility and the eﬃciency of multi-kernel learning. The multiple kernel version of Transductive SVM (a cluster assumption based approach) is proposed and it is solved based on DC (Diﬀerence of Convex functions) programming. Promising results on benchmark data sets suggesting the eﬀectiveness of proposed work.
Living on the Edge of Two Changing Worlds: Forecasting the Responses of Rocky Intertidal Ecosystems to Climate Change

Long-term monitoring shows that the poleward range edges of intertidal biota have shifted by as much as 50 km per decade, faster than most recorded shifts of terrestrial species. Although most studies have concentrated on species-range edges, recent work emphasizes how modifying factors such as regional differences in the timing of low tide can overwhelm large-scale climatic gradients, leading to a mosaic of environmental stress. We discuss how changes in the mean and variability in climatic regimes, as modified by local and regional factors, can lead to complex patterns of species distribution rather than simple range shifts. We describe how ecological forecasting may be used to generate explicit hypotheses regarding the likely impacts of different climatic change scenarios on the distribution of intertidal species and how related hindcasting methods can be used to evaluate changes that have already been detected. These hypotheses can then be tested over a hierarchy of temporal and spatial scales using coupled field and laboratory-based approaches.
Annals of the New York Academy of Sciences Mental Imagery in Music Performance: Underlying Mechanisms and Potential Benefits

This paper examines the role of mental imagery in music performance. Self-reports by musicians, and various other sources of anecdotal evidence, suggest that covert auditory, motor, and/or visual imagery facilitate multiple aspects of music performance. The cognitive and motor mechanisms that underlie such imagery include working memory, action simulation, and internal models. Together these mechanisms support the generation of anticipatory images that enable thorough action planning and movement execution that is characterized by efficiency, temporal precision, and biomechanical economy. In ensemble performance, anticipatory imagery may facilitate interpersonal coordination by enhancing online predictions about others' action timing. Overlap in brain regions subserving auditory imagery and temporal prediction is consistent with this view. It is concluded that individual differences in anticipatory imagery may be a source of variation in expressive performance excellence and the quality of ensemble cohesion. Engaging in effortful musical imagery is therefore justified when artistic perfection is the goal.
Learning to live with missing quality-of-life data in advanced-stage disease trials.

In advanced-stage disease, palliation can be the most important objective. Quality-of-life (QoL) outcomes provide an intuitively reasonable way to monitor palliation from the patient’s perspective. However, patients with advanced-stage disease are often unable to complete a series of QoL assessments because of deteriorating health. This introduces a possible bias in a clinical trial because patients who are healthy enough to complete the assessments may not represent the target population. In this issue, Brown et al report QoL outcomes from a non–small-cell lung cancer trial comparing supportive care regimens with and without chemotherapy. The analysis of completers only was based on half the baseline sample, and the proportion of completers differed by treatment arms. Despite comprehensive descriptions of the missing data problems and sensitivity analyses designed to cope with them, considerable uncertainty remains. Uncertainty is inevitable with this degree of missing data, but a few key questions can both sharpen focus and suggest practical steps to limit the impact of missing data.
Inferential Privacy Guarantees for Differentially Private Mechanisms

The correlations and network structure amongst individuals in datasets today---whether explicitly articulated, or deduced from biological or behavioral connections---pose new issues around privacy guarantees, because of inferences that can be made about one individual from another's data. This motivates quantifying privacy in networked contexts in terms of "inferential privacy"---which measures the change in beliefs about an individual's data from the result of a computation---as originally proposed by Dalenius in the 1970's. Inferential privacy is implied by differential privacy when data are independent, but can be much worse when data are correlated; indeed, simple examples, as well as a general impossibility theorem of Dwork and Naor, preclude the possibility of achieving non-trivial inferential privacy when the adversary can have arbitrary auxiliary information. In this paper, we ask how differential privacy guarantees translate to guarantees on inferential privacy in networked contexts: specifically, under what limitations on the adversary's information about correlations, modeled as a prior distribution over datasets, can we deduce an inferential guarantee from a differential one? We prove two main results. The first result pertains to distributions that satisfy a natural positive-affiliation condition, and gives an upper bound on the inferential privacy guarantee for any differentially private mechanism. This upper bound is matched by a simple mechanism that adds Laplace noise to the sum of the data. The second result pertains to distributions that have weak correlations, defined in terms of a suitable "influence matrix". The result provides an upper bound for inferential privacy in terms of the differential privacy parameter and the spectral norm of this matrix.
Evaluation of Defence Mechanisms in Survivable Networks

In this paper we present an environment for evaluating self-healing mechanisms in survivable networks. The work is based on the thesis that system level requirements of integrity and availability can be inherently conflicting, and that the type and level of defence in each particular network should be determined in relation to the particular network’s characteristics. The study shows that defined levels of critical service, intensity of attacks and time to recovery are important ingredients in measuring survivability. The paper presents a preliminary study of defence mechanisms in a telecommunication management network and illustrates how the network survivability is affected by several parameters such as network size, the implemented defence mechanisms, and the accepted trade-off against availability. The presented results are based on a model of the network built on top of the Swarm simulation platform and illustrate a potentially powerful tool in the hand of network security engineers. Keywords—Survivability, Simulation, Intrusion Tolerance, System Security, Security Metrics, Dependability
Empirical estimates of software availability of deployed systems

We consider empirical evaluation of the availability of the deployed software. Evaluation of real systems is more realistic, more accurate, and provides higher level of confidence than simulations, testing, or models. We process and model information gathered from a variety of operational and service support systems to obtain estimates of software reliability and availability. The three principal quantities are the total runtime, the number of outages, and the duration of outages. We consider methods to assess the quality of information in customer support systems, discuss advantages and disadvantages of various sources, consider methods to deal with missing data, and ways to construct bounds on measures that are not directly available. We propose a method to assess empirically software availability and reliability based on information from operational customer support and inventory systems and use a case study of a large communications system to investigate factors affecting software reliability. We find large variations among platforms and releases and find the failure rate to vary over time.
Outage Probability of Cooperative Diversity System with Relay Selection over Shadowed Nakagami-m Fading Channels

Cooperative diversity system have been receiving a lot of attention recently which can significantly improve the system performance. This paper studies a cooperative diversity system with relay selection over shadowed Nakagami-m fading channels. With the help of Hermite integration, we derive a close-form analytical expression for the outage probability. Some numerical results are presented for different Nakagami parameter m, standard deviation of shadowed fading σ, path loss exponent β and cooperative branches number K. The numerical results show that the derived analytical expression can provide very well approximations to the simulation results.
Disruption of ripple‐associated hippocampal activity during rest impairs spatial learning in the rat

The hippocampus plays a key role in the acquisition of new memories for places and events. Evidence suggests that the consolidation of these memories is enhanced during sleep. At the neuronal level, reactivation of awake experience in the hippocampus during sharp‐wave ripple events, characteristic of slow‐wave sleep, has been proposed as a neural mechanism for sleep‐dependent memory consolidation. However, a causal relation between sleep reactivation and memory consolidation has not been established. Here we show that disrupting neuronal activity during ripple events impairs spatial learning. We trained rats daily in two identical spatial navigation tasks followed each by a 1‐hour rest period. After one of the tasks, stimulation of hippocampal afferents selectively disrupted neuronal activity associated with ripple events without changing the sleep‐wake structure. Rats learned the control task significantly faster than the task followed by rest stimulation, indicating that interfering with hippocampal processing during sleep led to decreased learning. © 2009 Wiley‐Liss, Inc.