Miracle-dz/UniFAR-FTUs huggingface dataset:
PI3K/mTOR Inhibitor PF-04691502 Antitumor Activity Is Enhanced with Induction of Wild-Type TP53 in Human Xenograft and Murine Knockout Models of Head and Neck Cancer

Purpose: Phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway activation is often associated with altered expression or mutations of PIK3CA, TP53/p73, PTEN, and TGF-β receptors (TGFBR) in head and neck squamous cell carcinomas (HNSCC). However, little is known about how these alterations affect response to PI3K/mTOR–targeted agents. Experimental Design: In this preclinical study, PI3K/Akt/mTOR signaling was characterized in nine HNSCC (UM-SCC) cell lines and human oral keratinocytes. We investigated the molecular and anticancer effects of dual PI3K/mTOR inhibitor PF-04691502(PF-502) in UM-SCC expressing PIK3CA with decreased wild-type TP53, mutant TP53−/+ mutantTGFBR2, and in HNSCC of a conditional Pten/Tgfbr1 double knockout mouse model displaying PI3K/Akt/mTOR activation. Results: UM-SCC showed increased PIK3CA expression and Akt/mTOR activation, and PF-502 inhibited PI3K/mTORC1/2 targets. In human HNSCC expressing PIK3CA and decreased wtTP53 and p73, PF-502 reciprocally enhanced TP53/p73 expression and growth inhibition, which was partially reversible by p53 inhibitor pifithrin-α. Most UM-SCC with wtTP53 exhibited a lower IC50 than those with mtTP53 status. PF-502 blocked growth in G0–G1 and increased apoptotic sub-G0 DNA. PF-502 suppressed tumorigenesis and showed combinatorial activity with radiation in a wild-type TP53 UM-SCC xenograft model. PF-502 also significantly delayed HNSCC tumorigenesis and prolonged survival of Pten/Tgfbr1-deficient mice. Significant inhibition of p-Akt, p-4EBP1, p-S6, and Ki67, as well as increased p53 and TUNEL were observed in tumor specimens. Conclusions: PI3K-mTOR inhibition can enhance TP53/p73 expression and significantly inhibit tumor growth alone or when combined with radiation in HNSCC with wild-type TP53. PIK3CA, TP53/p73, PTEN, and TGF-β alterations are potential modifiers of response and merit investigation in future clinical trials with PI3K-mTOR inhibitors. Clin Cancer Res; 19(14); 3808–19. ©2013 AACR.
A Rhetorical Status Classifier for Legal Text Summarisation

We describe a classifier which determines the rhetorical status of sentences in texts from a corpus of judgments of the UK House of Lords. Our summarisation system is based on the work of Teufel and Moens where sentences are classified for rhetorical status to aid sentence selection. We experiment with a variety of linguistic features with results comparable to Teufel and Moens, thereby demonstrating the feasibility of porting this kind of system to a new domain.
SOMA: A Single Oligonucleotide Mutagenesis and Cloning Approach

Modern biology research requires simple techniques for efficient and restriction site-independent modification of genetic material. Classical cloning and mutagenesis strategies are limited by their dependency on restriction sites and the use of complementary primer pairs. Here, we describe the Single Oligonucleotide Mutagenesis and Cloning Approach (SOMA) that is independent of restriction sites and only requires a single mutagenic oligonucleotide to modify a plasmid. We demonstrate the broad application spectrum of SOMA with three examples. First, we present a novel plasmid that in a standardized and rapid fashion can be used as a template for SOMA to generate GFP-reporters. We successfully use such a reporter to assess the in vivo knock-down quality of morpholinos in Xenopus laevis embryos. In a second example, we show how to use a SOMA-based protocol for restriction-site independent cloning to generate chimeric proteins by domain swapping between the two human hRMD5a and hRMD5b isoforms. Last, we show that SOMA simplifies the generation of randomized single-site mutagenized gene libraries. As an example we random-mutagenize a single codon affecting the catalytic activity of the yeast Ssy5 endoprotease and identify a spectrum of tolerated and non-tolerated substitutions. Thus, SOMA represents a highly efficient alternative to classical cloning and mutagenesis strategies.
The effect of aviation fuel JP-8 and diesel fuel blends on engine performance and exhaust emissions

The article presents bench test results of a four-stroke, four-cylinder, naturally aspirated, DI diesel engine operating with neat JP-8 fuel (J) and its blends with Diesel fuel (D) in following proportions by volume: 90/10 (J+10D), 70/30 (J+D30), 50/ 50 (J+D50), 30/70 (J+D70), and 100% diesel fuel (DF). The purpose of the research was to analyse and compare changes occurred in the autoignition delay, combustion events, engine performance efficiency, emissions, and smoke of the exhaust when running on JP-8 fuel, jet-diesel fuel blends, and diesel fuel at a full (100%) engine load and speed of 1400 min–1 at which maximum torque occurs and rated speed of 2200 min–1. It was found that the start of injection (SOI) and the start of combustion (SOC) occurred earlier in an engine cycle and the autoignition delay decreased by 9.0% and 12.7% due to replacement of aviation JP-8 fuel with diesel fuel at a full load and the latter speeds. Maximum in-cylinder pressure was 6.8% and 4.0% higher when operating with diesel fuel, whereas brake thermal efficiency was 3.3% and 7.7% higher, and brake specific fuel consumption 2.8% and 7.0% lower when using fuel blend J+D50 compared with the respective values measured with neat JP-8 fuel. Emissions of nitric oxide (NO) and nitrogen oxides (NOx) were 13.3% and 13.1% higher from a straight diesel running at speed of 1400 min–1, and 19.0% and 19.5% higher at a higher speed of 2200 min–1. The carbon monoxide (CO) emissions and total unburned hydrocarbons (HC) decreased 2.1 times and by 12.3% when running with fuel blend J+D70 at speed of 2200 min–1 compared with those values measured with jet fuel. Smoke of the exhaust was 53.1% and 1.9% higher when using fuel blend J+D10 than that of 46.9% and 70.0% measured with jet fuel at speeds of 1400 and 2200 min–1. The engine produced 34.5% more smoke from combustion of fuel blend J+D70 at the low speed of 1400 min–1, but smoke converted to be 11.3% lower when operating at a higher speed of 2200 min–1.
Learning in FOL with a Similarity Measure

There are still very few systems performing a Similarity Based Learning and using a First Order Logic (FOL) representation. This limitation comes from the intrinsic complexity of the learning processes in FOL and from the difficulty to deal with numerical knowledge in this representation. In this paper, we show that major learning processes, namely generalization and clustering, can be solved in a homogeneous way by using a similarity measure. As this measure is defined, the similarity computation comes down to a problem of solving a set of equations in several unknowns. The representation language used to express our examples is a subset of FOL allowing to express both quantitative knowledge and a relevance scale on the predicates.
Postanesthetic Emergence Agitation in Pediatric Patients under General Anesthesia

Abstract Objective Postanesthetic emergence agitation is a common problem in pediatric postanesthetic care unit with an incidence ranging from 10 to 80%. This study was done to determine the prevalence of emergence agitation and associated risk factors in pediatric patients who underwent general anesthesia. Methods This cross-sectional descriptive and analytic study was performed on 747 pediatric patients aged 3- 7 years that underwent general anesthesia for various elective surgeries at Bou-Ali Sina Hospital in Sari, Iran between January 2010 and January 2011. A non-probability quota sampling technique was used. The presence of emergence agitation was recorded using Pediatric Anesthesia Emergence Delirium Scale. The factors linked with Emergence Agitation were recorded in a questionnaire. The data were analyzed using SPSS software 16 and independent sample t-test, χ2 and binary logistic regression. P-values less than 0.05 were considered as significant. Findings One hundred thirty-four (17.9%) children had emergence agitation. The most frequent surgical procedures were ENT surgical procedures 315 (42.2%), abdominal surgery 177 (23.7%), orthopedic surgery 137 (18.3%), urology 97 (13%) and ophthalmic surgery 24 (3.2%). Otorhinolaryngological surgical procedures (P=0.001), pain (P<0.05) and induction behavior of children (P<0.005) were associated with higher rates of post anesthetic emergence agitation (P=0.001). Conclusion This study identified the multiple independent risk factors which are associated with emergence agitation in children. To minimize the incidence of postanesthetic emergence agitation, these risk factors should be considered in the routine care by care providers in postanesthetic care unit.
Executing dynamic data-graph computations deterministically using chromatic scheduling

A data-graph computation — popularized by such programming systems as Galois, Pregel, GraphLab, PowerGraph, and GraphChi — is an algorithm that performs local updates on the vertices of a graph. During each round of a data-graph computation, an update function atomically modifies the data associated with a vertex as a function of the vertex's prior data and that of adjacent vertices. A dynamic data-graph computation updates only an active subset of the vertices during a round, and those updates determine the set of active vertices for the next round. This paper introduces PRISM, a chromatic-scheduling algorithm for executing dynamic data-graph computations. PRISM uses a vertex-coloring of the graph to coordinate updates performed in a round, precluding the need for mutual-exclusion locks or other nondeterministic data synchronization. A multibag data structure is used by PRISM to maintain a dynamic set of active vertices as an unordered set partitioned by color. We analyze PRISM using work-span analysis. Let G=(V,E) be a degree-Δ graph colored with Χ colors, and suppose that Q⊆V is the set of active vertices in a round. Define size(Q)=[Q] + Σv∈Qdeg(v), which is proportional to the space required to store the vertices of Q using a sparse-graph layout. We show that a P-processor execution of PRISM performs updates in Q using O(Χ(lg (Q/Χ)+lgΔ)+ lgP) span and Θ(size(Q)+Χ+P) work. These theoretical guarantees are matched by good empirical performance. We modified GraphLab to incorporate PRISM and studied seven application benchmarks on a 12-core multicore machine. PRISM executes the benchmarks 1.2–2.1 times faster than GraphLab's nondeterministic lock-based scheduler while providing deterministic behavior. This paper also presents PRISM-R, a variation of PRISM that executes dynamic data-graph computations deterministically even when updates modify global variables with associative operations. PRISM-R satisfies the same theoretical bounds as PRISM, but its implementation is more involved, incorporating a multivector data structure to maintain an ordered set of vertices partitioned by color.
Feature Aligned Volume Manipulation for Illustration and Visualization

In this paper we describe a GPU-based technique for creating illustrative visualization through interactive manipulation of volumetric models. It is partly inspired by medical illustrations, where it is common to depict cuts and deformation in order to provide a better understanding of anatomical and biological structures or surgical processes, and partly motivated by the need for a real-time solution that supports the specification and visualization of such illustrative manipulation. We propose two new feature aligned techniques, namely surface alignment and segment alignment, and compare them with the axis-aligned techniques which were reported in previous work on volume manipulation. We also present a mechanism for defining features using texture volumes, and methods for computing correct normals for the deformed volume in respect to different alignments. We describe a GPU-based implementation to achieve real-time performance of the techniques and a collection of manipulation operators including peelers, retractors, pliers and dilators which are adaptations of the metaphors and tools used in surgical procedures and medical illustrations. Our approach is directly applicable in medical and biological illustration, and we demonstrate how it works as an interactive tool for focus+context visualization, as well as a generic technique for volume graphics
Characterization of the pre-force-generation state in the actomyosin cross-bridge cycle

Myosin is an actin-based motor protein that generates force by cycling between actin-attached (strong binding: ADP or rigor) and actin-detached (weak binding: ATP or ADP·Pi) states during its ATPase cycle. However, it remains unclear what specific conformational changes in the actin binding site take place on binding to actin, and how these structural changes lead to product release and the production of force and motion. We studied the dynamics of the actin binding region of myosin V by using fluorescence resonance energy transfer (FRET) to monitor conformational changes in the upper-50-kDa domain of the actin binding cleft in the weak and strong actin binding states. Steady-state and lifetime data monitoring the FRET signal suggest that the cleft is in a more open conformation in the weak actin binding states. Transient kinetic experiments suggest that a rapid conformational change occurs, which is consistent with cleft closure before actin-activated phosphate release. Our results have identified a pre-force-generation actomyosin ADP·Pi state, and suggest force generation may occur from a state not yet seen by crystallography in which the actin binding cleft and the nucleotide binding pocket are closed. Computational modeling uncovers dramatic changes in the rigidity of the upper-50-kDa domain in different nucleotide states, which suggests that the intrinsic flexibility of this domain allows myosin motors to accomplish simultaneous tight nucleotide binding (closed nucleotide binding pocket) and high-affinity actin binding (closed actin binding cleft).
Design of a robust stair-climbing compliant modular robot to tackle overhang on stairs

SUMMARY This paper discusses the concept and parameter design of a robust stair-climbing compliant modular robot, capable of tackling stairs with overhangs. Geometry modifications of the periphery of the wheels of our robot helped in tackling overhangs. Along with establishing a concept design, the robust design parameters are set to minimize performance variations. The Grey-based Taguchi method is applied to provide an optimal setting for the design parameters of the robot. The robot prototype is shown to have successfully scaled stairs of varying dimensions, with overhang, thus corroborating the analysis performed.
Concentrations in serum and distribution in tissue of free and liposomal amphotericin B in rats during continuous intralipid infusion

The influences of Intralipid (IL) and 0.45% normal-saline infusions on the concentration in serum and distribution in tissue of amphotericin B (AmpB) and liposomal amphotericin B (L-AmpB) in rats were compared. In animals receiving a continuous IL infusion, concentrations of AmpB in kidneys and lungs were significantly higher, but the concentration of AmpB in serum was significantly lower in animals administered AmpB versus those given L-AmpB. In animals receiving a continuous normal-saline infusion concentrations of AmpB in kidneys and the spleen were significantly higher, but the concentration of AmpB in serum was significantly lower in animals administered AmpB versus those given L-AmpB. These results suggest that the increased total serum cholesterol and high-density lipoprotein cholesterol during the IL infusion decreased the clearance of AmpB from the bloodstream and decreased the L-AmpB concentration in the kidney and lung.
Dimerization of the TATA Binding Protein (*)

The TATA binding protein (TBP) is a central component of all eukaryotic transcription machineries. The recruitment of TBP to the promoter is slow and possibly rate limiting in transcription complex assembly. In an effort to understand the nature of this potential rate-limiting step, we have investigated the physical state of TBP prior to DNA binding. By chemical cross-linking, gel filtration chromatography, and protein affinity chromatography, we find that the conserved carboxyl-terminal DNA binding domain of human TBP dimerizes when not bound to DNA. The data completely support the proposed dimeric structure of plant TBP, previously determined by x-ray crystallography. TBP dimers are quite stable, having an approximate equilibrium dissociation constant (K) in the low nanomolar range. The dimerization interface appears to be dominated by hydrophobic forces, as predicted by the crystal structure. TBP dimers do not bind DNA, but they must dissociate into monomers before stably binding to the TATA box. Dissociation of TBP dimers appears to be relatively slow, and as such has the potential to dictate the kinetics of DNA binding.
Test Scheduling of NoC‐Based SoCs Using Multiple Test Clocks

Network‐on‐chip (NoC) is an emerging design paradigm intended to cope with future systems‐on‐chips (SoCs) containing numerous built‐in cores. Since NoCs have some outstanding features regarding design complexity, timing, scalability, power dissipation and so on, widespread interest in this novel paradigm is likely to grow. The test strategy is a significant factor in the practicality and feasibility of NoC‐based SoCs. Among the existing test issues for NoC‐based SoCs, test access mechanism architecture and test scheduling particularly dominate the overall test performance. In this paper, we propose an efficient NoC‐based SoC test scheduling algorithm based on a rectangle packing approach used for current SoC tests. In order to adopt the rectangle packing solution, we designed specific methods and configurations for testing NoC‐based SoCs, such as test packet routing, test pattern generation, and absorption. Furthermore, we extended and improved the proposed algorithm using multiple test clocks. Experimental results using some ITC’02 benchmark circuits show that the proposed algorithm can reduce the overall test time by up to 55%, and 20% on average compared with previous works. In addition, the computation time of the algorithm is less than one second in most cases. Consequently, we expect the proposed scheduling algorithm to be a promising and competitive method for testing NoC‐based SoCs.
Chain: A Dynamic Double Auction Framework for Matching Patient Agents

In this paper we present and evaluate a general framework for the design of truthful auctions for matching agents in a dynamic, two-sided market. A single commodity, such as a resource or a task, is bought and sold by multiple buyers and sellers that arrive and depart over time. Our algorithm, CHAIN, provides the first framework that allows a truthful dynamic double auction (DA) to be constructed from a truthful, single-period (i.e. static) double-auction rule. The pricing and matching method of the CHAIN construction is unique amongst dynamic-auction rules that adopt the same building block. We examine experimentally the allocative efficiency of CHAIN when instantiated on various single-period rules, including the canonical McAfee double-auction rule. For a baseline we also consider non-truthful double auctions populated with "zero-intelligence plus"-style learning agents. CHAIN-based auctions perform well in comparison with other schemes, especially as arrival intensity falls and agent valuations become more volatile.
Evaluation of microstructures and wear properties of duplex boride coatings

Abstract To improve wear behaviour of AISI 316L austenitic stainless steel, duplex surface treatments, including borochromising, borotitanising or borovanadising, were carried out using the pack cementation method. Chromising, titanising and vanadising treatments were performed at 1050°C for 4 h and then boriding was carried out on all pretreated specimens at 1000°C for 6 h. Optimum properties have been evaluated in borochromised samples, especially in respect to their surface hardness and wear resistance. Examination of the worn surfaces shows that the oxidation fatigue wear mechanism is predominant on wear failure of coated samples.
Performance analysis of curvature scale space for automatic spatial registration of multisensor shorelines

Registration is a fundamental task in image processing used to match two or more images taken at different times, from different sensors or from different viewpoints. Problems that can occur are change over time, occlusion, image noise and differences in image geometry. The authors concentrate on the automatic registation of shorelines extracted from multisensor imagery. The authors examine the use of curvature scale space (CSS) to represent the shape of shorelines. In CSS, curve evolution is studied by smoothing a shape with a Gaussian kernel and computing the curvature at varying levels of detail. A representation can be constructed that is robust to image noise and is scale invariant, allowing the extraction of control points which characterise a shoreline regardless of its original scale. To map a (sub)set of control points unto another set, the authors use relaxation labeling built on constraints of CSS features and sensor geometry.
Microsatellite Instability Predicts Poor Short-Term Survival in Patients with Advanced Breast Cancer after High-Dose Chemotherapy and Autologous Stem-Cell Transplantation

Purpose: The purpose is to define molecular prognostic factors in patients with advanced breast cancer treated with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Experimental Design: Thirty-nine patients with breast cancer and extensive lymph node (level III) and/or systemic metastases from a prospective single-center study of sequential HDCT/ASCT were studied. Microsatellite analysis was performed after laser microdissection using 15 markers selected for sensitive detection of microsatellite instability (MSI) in breast cancer. Exons 5–9 of the P53 gene were directly sequenced. Expression of P53, HER-2/neu, and the mismatch repair proteins hMSH2 and hMLH1 was evaluated by immunohistochemistry. Results: MSI of at least three markers was detected in 13 of 39 patients (33%) and was predominantly found at tetranucleotide markers. All MSI-positive tumors showed normal expression of hMSH2 and hMLH1. Complete sequence analysis of exons 5–9 of the P53gene was successful in 34 cases; 18% (n = 6) revealed a mutation. Overexpression of HER-2/neu and P53 was observed in 7 (22%) and 12 (46%) of 26 evaluated cases, respectively. The presence of MSI strongly correlated with shorter overall survival (OS; P = 0.0004) and progression-free survival (PFS; P = 0.02). None of the other investigated clinical or molecular factors correlated with OS in univariate analyses, with the exception of menopausal status and previous adjuvant chemotherapy. Testing various multivariate Cox regression models, MSI remained a highly significant, independent, and adverse risk factor for OS. Conclusions: MSI is frequent in advanced breast cancer and could be an indicator of chemotherapy resistance and poor prognosis in breast cancer patients treated with HDCT/ASCT.