Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of droplet digital PCR and conventional quantitative PCR for measuring EGFR gene mutation

Early detection of epidermal growth factor receptor (EGFR) mutation, particularly EGFR T790M mutation, is of clinical significance. The aim of the present study was to compare the performances of amplification refractory mutation system-based quantitative polymerase chain reaction (ARMS-qPCR) and droplet digital polymerase chain reaction (ddPCR) approaches in the detection of EGFR mutation and explore the feasibility of using ddPCR in the detection of samples with low mutation rates. EGFR gene mutations in plasmid samples with different T790M mutation rates (0.1–5%) and 10 clinical samples were detected using the ARMS-qPCR and ddPCR approaches. The results demonstrated that the ARMS-qPCR method stably detected the plasmid samples (6,000 copies) with 5 and 1% mutation rates, while the ddPCR approach reliably detected those with 5% (398 copies), 1% (57 copies), 0.5% (24 copies) and 0.1% (average 6 copies) mutation rates. For the 10 clinical samples, the results for nine samples by the ARMS-qPCR and ddPCR methods were consistent; however, the sample N006, indicated to be EGFR wild-type by ARMS-qPCR, was revealed to have a clear EGFR T790M mutation with seven copies of mutant alleles in a background of 6,000 wild-type copies using ddPCR technology. This study demonstrates the feasibility of applying the ddPCR system to detect EGFR mutation and identified the advantage of ddPCR in the detection of samples with a low EGFR mutation abundance, particularly the secondary EGFR T790M resistance mutation, which enables early diagnosis before acquired resistance to tyrosine kinase inhibitors becomes clinically detectable.
Risk Taking with Variable Resources: a Field and a Laboratory Experiment

Abstract Background: Theoretical predictions and experimental findings concerning the relationship between risk taking and accumulated resources are contradictory. In contrast to laboratory experiments, studies conducted in an ecologically valid environment allow for the evaluation of available resources and the motivational impact of potentially serious consequences for risk taking. Objective: Our aim was to (i) examine the influence of available resources on risk taking in an ecologically valid field experiment; and (ii) to compare “real life” and laboratory experiments assessing risk taking. Method: To reproduce real decisions involving real stakes, the students were asked to choose between exam questions representing different levels of difficulty. Available resources of the students were defined as the amount of points accumulated during the semester. In parallel, the laboratory experiments were conducted to assess risk taking in a laboratory setting. Results: The two experimental setups yielded different results. In the field experiment, risk taking decreased with the available resources, whereas the laboratory experiments suggested an inverse tendency. The influence of contextual effects was only prominent in the field experiment.Conclusion: The results of the field experiment support the variable risk preference model, whereas the risk-sensitivity theory could only be validated in the laboratory setting.
Correlation between the serum and tissue levels of oxidative stress markers and the extent of inflammation in acute appendicitis

OBJECTIVES: To determine the serum and tissue levels of markers of impaired oxidative metabolism and correlate these levels with the histopathology and Alvarado score of acute appendicitis patients. METHOD: Sixty-five acute appendicitis patients (mean age, 31.4±12.06 years; male/female, 30/35) and 30 healthy control subjects were studied. The Alvarado score was recorded. Serum samples were obtained before surgery and 12 hours postoperatively to examine the total antioxidant status, total oxidant status, paraoxonase, stimulated paraoxonase, arylesterase, catalase, myeloperoxidase, ceruloplasmin, oxidative stress markers (advanced oxidized protein products and total thiol level) and ischemia-modified albumin. Surgical specimens were also evaluated. RESULTS: The diagnoses were acute appendicitis (n = 37), perforated appendicitis (n = 8), phlegmonous appendicitis (n = 12), perforated+phlegmonous appendicitis (n = 4), or no appendicitis (n = 4). The Alvarado score of the acute appendicitis group was significantly lower than that of the perforated+phlegmonous appendicitis group (p = 0.004). The serum total antioxidant status, total thiol level, advanced oxidized protein products, total oxidant status, catalase, arylesterase, and ischemia-modified albumin levels were significantly different between the acute appendicitis and control groups. There was no correlation between the pathological extent of acute appendicitis and the tissue levels of the markers; additionally, there was no correlation between the tissue and serum levels of any of the parameters. CONCLUSIONS: The imbalance of oxidant/antioxidant systems plays a role in the pathogenesis acute appendicitis. The Alvarado score can successfully predict the presence and extent of acute appendicitis.
Patterns for Human-oriented Information Presentation Shape Associativity Structure

Introduction Humans interchange information using textual and graphical forms of representation. For an efficient information interchange human specific abilities in information perception, retrieval and recognition have to be considered. Key aspects in perception, retrieval and recognition of information are: • Shape Human information perception is based on spatial cues. Geometric shapes and patterns are the basic form of information which humans visually perceive. The optic nerves are extensions of the brain. Geometric shapes and visual patterns trigger information perception and processing in a direct way. • Associativity Human information perception is associative. New information has to be included into an existing associative net of known information. The relationships between information items are especially important. • Structure The process of perceiving information consists of building up relations of information items to existing ones in our associative memory. Integrating information in the associative net of known information relies on internal structures, which are modified, completed and even newly built. The quest for structure is a way to deal with the mass of information pouring into us and therefore enlarging and completing our knowledge. The rationale of the patterns in this collection refer directly or indirectly to these key aspects. The patterns of this collection can be applied in a wide range of situations where information has to be represented and interchanged: from writing papers to preparing talks or performing a creative process of capturing ideas. As introducing examples the structure of this document and the relationships between the patterns are represented here in two fundamental ways: graphically and textual. • Graphical Visualization of the Relationships between the Pattens Figure 1 provides an overview of this pattern collection as a map. A directed graph illustrates the patterns and the relations between them.
Security and insurance management in networks with heterogeneous agents

Computer users express a strong desire to prevent attacks and to reduce the losses from computer and information security breaches. However, security compromises are common and widespread and highly damaging. Next to attackers' increased sophistication, a root cause for the harm inflicted is that users often fail to optimally protect their resources or to recover gracefully from a security breach. We argue that users often underestimate the strong mutual dependence between their security strategies and the economic environment (e.g., threat model) in which these choices are made and evaluated. This misunderstanding weakens the effectiveness of users' security investments, and is compounded by heterogeneity within the user population, in some cases further reducing incentives for cooperation and coordination. We study how economic agents invest into security in five different economic environments, that are characteristic of different threat models. We consider generalized models of traditional public goods games (e.g., total effort and weakest link) and two recently proposed games (e.g., weakest target game). Agents may split their contributions between a public good (protection) and a private good (self-insurance). Our analysis centers on how agents respond to incentives when important parameters of the game (i.e., loss probability, loss magnitude, and cost of technology) are heterogeneous in the agent population. We also highlight key differences to the case of homogeneous decision makers. For example, security investments may become substantially more sensitive to the size of the network. We extend our results to discuss important modes of intervention.
Reduced kidney function and outcome in acute ischaemic stroke: relationship to arterial hypertension and diabetes.

BACKGROUND Stroke is a dangerous long-term complication of kidney failure, yet its occurrence early in disease is poorly characterized. Our aim was to investigate the association of reduced kidney function, hypertension and diabetes with acute ischaemic stroke and the outcome thereof. METHODS In this prospective cohort study, the association of reduced kidney function, hypertension and diabetes with stroke and 2-year all-cause mortality was investigated. Glomerular filtration rate (eGFR) was estimated by the simplified Modification of Diet in Renal Disease formula in 13 365 consecutive patients (671 with acute ischaemic stroke) admitted to our clinical facility over a 12-month period. RESULTS Ischaemic stroke, after adjustment for age and gender, was significantly associated with eGFR <60 mL/min/1.73m(2) [odds ratio (OR) 1.53, 95% confidence interval (CI) 1.30-1.81], hypertension (2.77, 95% CI 2.33-3.28) and diabetes (1.30, 95% CI 1.04-1.63). Multivariate analysis of interaction indicated the absence of an additive effect between eGFR, hypertension and diabetes, on the risk of stroke. Age and gender-adjusted survival analysis by Cox regression showed an association of mortality with reduced eGFR alone (HR = 4.29, 95% CI 1.02-19.60). CONCLUSIONS In patients acutely admitted to hospital, reduced kidney function, hypertension and diabetes are independently associated with ischaemic stroke, but do not exert a synergic effect. After hospital discharge, mortality is strongly associated with reduced eGFR but with neither hypertension nor diabetes.
Estimating the Ultimate Bounds and Positively Invariant Sets for a Class of General Lorenz-type New Chaotic Systems

To estimate the ultimate bound and positively invariant set of a dynamic system is an important but quite challenging task. In this paper, we attempt to investigate the ultimate bounds and positively invariant sets for a class of more general Lorenz-type new chaotic systems. We derive some ellipsoidal estimates of the globally exponentially attractive set and positively invariant set of the general Lorenz-type new system for all the positive values of its parameters via the generalized Lyapunov function theory. Furthermore, the estimations derived here contain the results given in as special cases and can lead to a series of new estimations.
Optimal Additive Composition of Abstraction-based Admissible Heuristics

We describe a procedure that takes a classical planning task, a forward-search state, and a set of abstraction-based admissible heuristics, and derives an optimal additive composition of these heuristics with respect to the given state. Most importantly, we show that this procedure is polynomial-time for arbitrary sets of all known to us abstraction-based heuristics such as PDBs, constrained PDBs, merge-and-shrink abstractions, fork-decomposition structural patterns, and structural patterns based on tractable constraint optimization.
A Survey of z > 5.7 Quasars in the Sloan Digital Sky Survey. IV. Discovery of Seven Additional Quasars

We present the discovery of seven quasars at z > 5.7, selected from ∼2000 deg2 of multicolor imaging data of the Sloan Digital Sky Survey. The new quasars have redshifts z from 5.79 to 6.13. Five are selected as part of a complete flux-limited sample in the SDSS northern Galactic cap; two have larger photometric errors and are not part of the complete sample. One of the new quasars, SDSS J1335+3533 (z = 5.93), exhibits no emission lines; the 3 σ limit on the rest-frame equivalent width of the Lyα+N V line is 5 Å. It is the highest redshift lineless quasar known and could be a gravitational lensed galaxy, a BL Lac object, or a new type of quasar. Two new z > 6 quasars, SDSS 1250+3130 (z = 6.13) and SDSS J1137+3549 (z = 6.01), show deep Gunn-Peterson absorption gaps in Lyα. These gaps are narrower than the complete Gunn-Peterson absorption troughs observed among quasars at z > 6.2 and do not have complete Lyβ absorption.
Robotic mechanism for soil penetration inspired by plant root

In this paper we propose a soil penetration robotic system inspired by low friction penetration strategies in plant roots. Growth of cells at the root tip deforms soil, while sloughing cells in the cap create an interface between root and soil to reduce root-soil friction during penetration. A simple prototype, inspired by these root features and based on a tubular shaft and a soft continuum skin, was developed. The skin is kept inside the shaft and slips out and slides on its external body. This outward movement of the skin opens the soil in front of the tip and helps the system to penetrate. The skin covering the external body of shaft imitates the role of sloughing cells and provides low-friction interface between soil and shaft. Interaction between the external skin and soil gives to the system self-anchorage capabilities for the penetration. The performances of our robotic system were characterized during penetration in granular soils. The skin-soil interaction was found to be fundamental for 1) displacing the soil in front of the tip and 2) preventing backward movements of the robot by anchoring the posterior body to the soil. In order to exploit these effects some artificial hairs were added along the skin. The increased hair density (0.012 hairs/mm2) resulted in higher penetration depth of robot (about 30%).
Optimizing the Placement of Integration Points in Multi-hop Wireless Networks

Efficient integration of a multi-hop wireless network with the Internet is an important research problem. In a wireless neighborhood network, a few Internet Transit Access Points (ITAPs), serving as gateways to the Internet, are deployed across the neighborhood; houses are equipped with low-cost antennas, and form a multi-hop wireless network among themselves to cooperatively route traffic to the Internet through the ITAPs. For both these applications, placement of integration points between the wireless and wired network is a critical determinant of system performance and resource usage. In this paper, we explore the placement problem under three wireless link models. For each link model, we develop algorithms to make informed placement decisions based on neighborhood layouts, user demands, and wireless link characteristics. We also extend our algorithms to provide fault tolerance and handle significant workload variation. We evaluate our placement algorithms and show that our algorithms yield close to optimal solutions over a wide range of scenarios we have considered.
In Situ Hybridization of SP-A mRNA in Adult Human Conducting Airways

In our study, surfactant protein (SP)-A was characterized in adult human trachea and bronchi. SP-A mRNA and protein were localized to serous cells in submucosal glands by in situ hybridization and immunohistochemistry, respectively. A 2.2 kb SP-A mRNA transcript was detected in tracheal tissues by Northern blot analysis. Primer extension analysis and gene-specific reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the predominance of SP-A2 mRNA. However, using nested PCR, we also detected low amounts of SP-A1 mRNA in the tracheal tissues. A ∼35 kDa SP-A immunoreactive protein was detected in the tracheal tissues by immunoblot analysis and was shown to be modified by the addition of N-linked oligosaccharides. We conclude that submucosal glands in the conducting airways produce a novel SP-A protein with a molecular weight and post-translational modification similar to the SP-A produced in the distal lung. We speculate that this SP-A2 protein, like other serous secretions from airway submucosal glands, functions in local antimicrobial host defense mechanisms in the conducting airways.
Prostaglandin Promotion of Osteocyte Gap Junction Function through Transcriptional Regulation of Connexin 43 by Glycogen Synthase Kinase 3/β-Catenin Signaling

ABSTRACT Gap junction intercellular communication in osteocytes plays an important role in bone remodeling in response to mechanical loading; however, the responsible molecular mechanisms remain largely unknown. Here, we show that phosphoinositide-3 kinase (PI3K)/Akt signaling activated by fluid flow shear stress and prostaglandin E2 (PGE2) had a stimulatory effect on both connexin 43 (Cx43) mRNA and protein expression. PGE2 inactivated glycogen synthase kinase 3 (GSK-3) and promoted nuclear localization and accumulation of β-catenin. Knockdown of β-catenin expression resulted in a reduction in Cx43 protein. Furthermore, the chromatin immunoprecipitation (ChIP) assay demonstrated an association of β-catenin with the Cx43 promoter, suggesting that β-catenin could regulate Cx43 expression at the level of gene transcription. We have previously reported that PGE2 activates cyclic AMP (cAMP)-protein kinase A (PKA) signaling and increases Cx43 and gap junctions. Interestingly, the activation of PI3K/Akt appeared to be independent of the activation of PKA, whereas both PI3K/Akt and PKA signaling inactivated GSK-3 and increased β-catenin translocation. Together, these results suggest that shear stress, through PGE2 release, activates both PI3K/Akt and cAMP-PKA signaling, which converge through the inactivation of GSK-3, leading to the increase in nuclear accumulation of β-catenin. β-Catenin binds to the Cx43 promoter, stimulating Cx43 expression and functional gap junctions between osteocytes.
Relationship between delta‐like and proneural bHLH genes during chick retinal development

Notch signaling in the retina maintains a pool of progenitor cells throughout retinogenesis. However, two Notch‐ligands from the Delta‐like gene family, Dll1 and Dll4, are present in the developing retina. To understand their relationship, we characterized Dll1 and Dll4 expression with respect to proliferating progenitor cells and newborn neurons in the chick retina. Dll4 matched the pattern of neural differentiation. By contrast, Dll1 was primarily expressed in progenitor cells. We compared Dll1 and Dll4 kinetic profiles with that of the transiently up‐regulated cascade of proneural basic helix–loop–helix (bHLH) genes after synchronized progenitor cell differentiation, which suggested a potential role for Ascl1 in the regulation of Delta‐like genes. Gain‐of‐function assays demonstrate that Ascl1 does influence Delta‐like gene expression and Notch signaling activity. These data suggest that multiple sources of Notch signaling from newborn neurons and progenitors themselves coordinate retinal histogenesis. Developmental Dynamics 237:1565–1580, 2008. © 2008 Wiley‐Liss, Inc.
Who is Afraid of the Friedman Rule?

We explore the connection between optimal monetary policy and heterogeneity among agents. We utilize a standard monetary economy with two types of agents that differ in the marginal utility they derive from real money balances-a framework that produces a nondegenerate stationary distribution of money holdings. Without type-specific fiscal policy, we show that the zero-nominal-interest-rate policy (the Friedman rule) does not maximize type-specific welfare; further, it may not maximize aggregate ex ante social welfare. Indeed one or, more surprisingly, both types of agents may benefit if the central bank deviates from the Friedman rule.
Predicting P-Glycoprotein-Mediated Drug Transport Based On Support Vector Machine and Three-Dimensional Crystal Structure of P-glycoprotein

Human P-glycoprotein (P-gp) is an ATP-binding cassette multidrug transporter that confers resistance to a wide range of chemotherapeutic agents in cancer cells by active efflux of the drugs from cells. P-gp also plays a key role in limiting oral absorption and brain penetration and in facilitating biliary and renal elimination of structurally diverse drugs. Thus, identification of drugs or new molecular entities to be P-gp substrates is of vital importance for predicting the pharmacokinetics, efficacy, safety, or tissue levels of drugs or drug candidates. At present, publicly available, reliable in silico models predicting P-gp substrates are scarce. In this study, a support vector machine (SVM) method was developed to predict P-gp substrates and P-gp-substrate interactions, based on a training data set of 197 known P-gp substrates and non-substrates collected from the literature. We showed that the SVM method had a prediction accuracy of approximately 80% on an independent external validation data set of 32 compounds. A homology model of human P-gp based on the X-ray structure of mouse P-gp as a template has been constructed. We showed that molecular docking to the P-gp structures successfully predicted the geometry of P-gp-ligand complexes. Our SVM prediction and the molecular docking methods have been integrated into a free web server (http://pgp.althotas.com), which allows the users to predict whether a given compound is a P-gp substrate and how it binds to and interacts with P-gp. Utilization of such a web server may prove valuable for both rational drug design and screening.
Bounding Cache-Related Preemption Delay for Real-Time Systems

Cache memory is used in almost all computer systems today to bridge the ever increasing speed gap between the processor and main memory. However, its use in multitasking computer systems introduces additional preemption delay due to the reloading of memory blocks that are replaced during preemption. This cache-related preemption delay poses a serious problem in realtime computing systems where predictability is of utmost importance. We propose an enhanced technique for analyzing and thus bounding the cache-related preemption delay in fixed-priority preemptive scheduling focusing on instruction caching. The proposed technique improves upon previous techniques in two important ways. First, the technique takes into account the relationship between a preempted task and the set of tasks that execute during the preemption when calculating the cache-related preemption delay. Second, the technique considers the phasing of tasks to eliminate many infeasible task interactions. These two features are expressed as constraints of a linear programming problem whose solution gives a guaranteed upper bound on the cache-related preemption delay. This paper also compares the proposed technique with previous techniques using randomly generated task sets. The results show that the improvement on the worst-case response time prediction by the proposed technique over previous techniques ranges between 5 percent and 18 percent depending on the cache refill time when the task set utilization is 0.6. The results also show that as the cache refill time increases, the improvement increases, which indicates that accurate prediction of cache-related preemption delay by the proposed technique becomes increasingly important if the current trend of widening speed gap between the processor and main memory continues.