Miracle-dz/UniFAR-FTUs huggingface dataset:
AST1306, A Novel Irreversible Inhibitor of the Epidermal Growth Factor Receptor 1 and 2, Exhibits Antitumor Activity Both In Vitro and In Vivo

Despite the initial response to the reversible, ATP-competitive quinazoline inhibitors that target ErbB-family, such a subset of cancer patients almost invariably develop resistance. Recent studies have provided compelling evidence that irreversible ErbB inhibitors have the potential to override this resistance. Here, we found that AST1306, a novel anilino-quinazoline compound, inhibited the enzymatic activities of wild-type epidermal growth factor receptor (EGFR) and ErbB2 as well as EGFR resistant mutant in both cell-free and cell-based systems. Importantly, AST1306 functions as an irreversible inhibitor, most likely through covalent interaction with Cys797 and Cys805 in the catalytic domains of EGFR and ErbB2, respectively. Further studies showed that AST1306 inactivated pathways downstream of these receptors and thereby inhibited the proliferation of a panel of cancer cell lines. Although the activities of EGFR and ErbB2 were similarly sensitive to AST1306, ErbB2-overexpressing cell lines consistently exhibited more sensitivity to AST1306 antiproliferative effects. Consistent with this, knockdown of ErbB2, but not EGFR, decreased the sensitivity of SK-OV-3 cells to AST1306. In vivo, AST1306 potently suppressed tumor growth in ErbB2-overexpressing adenocarcinoma xenograft and FVB-2/Nneu transgenic breast cancer mouse models, but weakly inhibited the growth of EGFR-overexpressing tumor xenografts. Tumor growth inhibition induced by a single dose of AST1306 in the SK-OV-3 xenograft model was accompanied by a rapid (within 2 h) and sustained (≥24 h) inhibition of both EGFR and ErbB2, consistent with an irreversible inhibition mechanism. Taken together, these results establish AST1306 as a selective, irreversible ErbB2 and EGFR inhibitor whose growth-inhibitory effects are more potent in ErbB2-overexpressing cells.
Distributed Robust Fixed-Time Consensus for Nonlinear and Disturbed Multiagent Systems

In this paper, the robust fixed-time consensus problem for multiagent systems with nonlinear dynamics and uncertain disturbances under a weighted undirected topology is investigated. Some nonlinear control protocols are proposed under which fixed-time consensus in the considered multiagent systems can be ensured. Compared with the initial-condition based finite-time consensus, it is theoretically shown that any prescribed convergence time for the achievement of consensus can be guaranteed within fixed time regardless of the initial conditions. Furthermore, the achievement of consensus is shown to be robust against bounded uncertain disturbances affecting the agents. Finally, some numerical examples are provided to illustrate the performance and effectiveness of the theoretical results.
Emotional intelligence and clinical performance/retention of nursing students

Objective: This exploratory, quantitative, descriptive study was undertaken to explore the relationship between clinical performance and anticipated retention in nursing students. Methods: After approval by the university′s Human Subjects Committee, a sample of 104 nursing students were recruited for this study, which involved testing with a valid and reliable emotional intelligence (EI) instrument and a self-report survey of clinical competencies. Results: Statistical analysis revealed that although the group average for total EI score and the 6 score subsets were in the average range, approximately 30% of the individual total EI scores and 30% of two branch scores, identifying emotions correctly and understanding emotions, fell in the less than average range. This data, as well as the analysis of correlation with clinical self-report scores, suggest recommendations applicable to educators of clinical nursing students. Conclusions: Registered nurses make-up the largest segment of the ever-growing healthcare workforce. Yet, retention of new graduates has historically been a challenge for the profession. Given the projected employment growth in nursing, it is important to identify factors which correlate with high levels of performance and job retention among nurses. There is preliminary evidence that EI "a nontraditional intelligence measure" relates positively not only with retention of clinical staff nurses, but with overall clinical performance as well.
Intermittent and lateral varying ULVZ structure at the northeastern margin of the Pacific LLSVP

Thin patches with ultralow velocities have been proposed to exist at the core‐mantle boundary (CMB). The detection and mapping of ultralow velocity zones (ULVZs) are difficult, in part, because of limited source‐receiver geometries of seismic phases used in ULVZ modeling. Here we develop a new approach that simultaneously utilizes ScS precursor and postcursor energies to investigate the CMB region for ULVZ structure. We stacked source‐deconvolved ScS waveforms within 1.5° geographic bins to extract ScS precursor and postcursor energies, if present, with ScS effectively removed from waveforms. We investigate the CMB beneath the central Pacific Ocean, and evidence for ULVZs is clearly apparent. Geographic bin stacks possessing similar ScS precursor‐plus‐postcursor behavior are grouped by using cluster analysis to produce more robust waveforms by enhancing the signal‐to‐noise ratios. Synthetic seismograms that demonstrate the amplitude and timing of the ULVZ arrivals are sensitive to ULVZ thickness and internal velocities. To pursue local ULVZ properties we processed 13,850 1‐D synthetic models with various ULVZ thicknesses and internal properties, using the identical ScS‐stripping method as with the data. A best fitting model was found for each geographical bin cluster by using an amplitude‐sensitive cross‐correlation algorithm. While limitations exist due to 1‐D modeling, strong lateral variations are clearly apparent in ULVZ thickness and properties across the large low shear velocity province (LLSVP) margin in our study area. Inside hypothesized LLSVP edges, ULVZs appear to distribute unevenly, suggesting 3‐D variations of convection currents.
Effects in Cats of Inhibition of Nitric Oxide Synthesis on Cerebral Vasodilation and Endothelium‐Derived Relaxing Factor From Acetylcholine

Background and Purpose: We investigated the chemical identity of the endothelium-derived relaxing factor generated by acetylcholine in cerebral microvessels by studying the effects and mechanism of action of inhibitors of nitric oxide synthesis from arginine on the vasodilation and endothelium-derived relaxing factor production induced by topical application of acetylcholine in cerebral arterioles. Methods: We determined cerebral arteriolar dilation and endothelium-derived relaxing factor production by bioassay in anesthetized cats equipped with cranial windows during supervision of 10−7 M acetylcholine before and after administration of either NG-monomethyl L-arginine or NG-nitro-L-arginine, two inhibitors of nitric oxide synthesis. Results: NG-Nitro-L-arginine abolished the vasodilation from acetylcholine and eliminated the production of endothelium-derived relaxing factor in the bioassay experiments. NG-Monomethyl L-arginine had no effect on the response to acetylcholine in the absence of pretreatment. However, after pretreatment with the detergent sodium dodecyl sulfate to increase cell membrane permeability, the inhibitor had effects identical to those of NG-nitro-L-arginine. L-Arginine reversed the effects of the inhibitors of nitric oxide synthesis. Neither inhibitor affected baseline vascular caliber, nor did they generate a vasoconstrictor agent in the bioassay experiments. The two inhibitors of nitric oxide synthesis did not affect the response to nitroprusside or adenosine, showing that the effect on responses to acetylcholine was specific. Also, the blockade of the response to acetylcholine induced by the inhibitors of nitric oxide synthesis was unaffected by treatment with superoxide dismutase and catalase, showing that the effect was not mediated by oxygen radicals. Conclusion: The endothelium-derived relaxing factor generated by acetylcholine in cerebral arterioles of cats is either nitric oxide or a nitric oxide-containing substance. The effect of these inhibitors on the response to acetylcholine is mediated by inhibition of the synthesis of nitric oxide. There is no involvement of radicals, and no vasoconstrictor agent is generated.
Neural transdifferentiation of mesenchymal stem cells – a critical review

The classic concept of stem cell differentiation can be illustrated as driving into a series of one‐way streets, where a given stem cell through generations of daughter cells becomes correspondingly restricted and committed towards a definitive lineage with fully differentiated cells as end points. According to this concept, tissue‐derived adult stem cells can only give rise to cells and cell lineages found in the natural, specified tissue of residence. During the last few years it has, however, been reported that under certain experimental conditions adult stem cells may lose their tissue or germ layer‐specific phenotypes and become reprogrammed to transdifferentiate into cells of other germ layers and tissues. The transdifferentiation process is referred to as “stem cell plasticity”. Mesenchymal stem cells, present in various tissues, including bone marrow, have – besides differentiation into bone, cartilage, smooth muscle and skeletal muscle – also been reported to transdifferentiate into skin, liver and brain cells (neurons and glia). Conversely, neural stem cells have been reported to give rise to blood cells. The actual occurrence of transdifferentiation is currently much debated, but would have immense clinical potential in cell replacement therapy and regenerative medicine. Controlled neural differentiation of human mesenchymal stem cells might thus become an important source of cells for cell therapy of neurodegenerative diseases, since autologous adult mesenchymal stem cells are more easily harvested and effectively expanded than corresponding neural stem cells. This article provides a critical review of the reports of neural transdifferentiation of mesenchymal stem cells, and proposes a set of criteria to be fulfilled for validation of transdifferentiation.
Amygdala hypoactivity to fearful faces in boys with conduct problems and callous-unemotional traits.

OBJECTIVE Although early-onset conduct problems predict both psychiatric and health problems in adult life, little research has been done to index neural correlates of conduct problems. Emerging research suggests that a subgroup of children with conduct problems and elevated levels of callous-unemotional traits may be genetically vulnerable to manifesting disturbances in neural reactivity to emotional stimuli indexing distress. Using functional MRI, the authors evaluated differences in neural response to emotional stimuli between boys with conduct problems and elevated levels of callous-unemotional traits and comparison boys. METHOD Seventeen boys with conduct problems and elevated levels of callous-unemotional traits and 13 comparison boys of equivalent age (mean=11 years) and IQ (mean=100) viewed blocked presentations of fearful and neutral faces. For each face, participants distinguished the sex of the face via manual response. RESULTS Relative to the comparison group, boys with conduct problems and elevated levels of callous-unemotional traits manifested lesser right amygdala activity to fearful faces. CONCLUSIONS This finding is in line with data from studies of adults with antisocial behavior and callous-unemotional traits (i.e., psychopaths), as well as from a recent study of adolescents with callous-unemotional traits, and suggests that the neural substrates of emotional impairment associated with callous-unemotional antisocial behavior are already present in childhood.
Cation Activation of the Basolateral Sodium-Potassium Pump in Turtle Colon

The current generated by electrogenic sodium-potassium exchange at the basolateral membrane of the turtle colon can be measured directly in tissues that have been treated with serosal barium (to block the basolateral potassium conductance) and mucosal amphotericin B (to reduce the cation selectivity of the apical membrane). We studied the activation of this pump current by mucosal sodium and serosal potassium, rubidium, cesium, and ammonium. The kinetics of sodium activation were consistent with binding to three independent sites on the cytoplasmic side of the pump. The pump was not activated by cellular lithium ions. The kinetics of serosal cation activation were consistent with binding to two independent sites with the selectivity Rb > K > Cs > NH4. The properties and kinetics of the basolateral Na/K pump in the turtle colon are at least qualitatively similar to those ofthe well-characterized Na/K-ATPase of the human red blood cell .
Ineffectiveness of Recombinant Interferon-βserine Nasal Drops for Prophylaxis of Natural Colds

Abstract Two randomized, double-blind, placebo-controlled trials during early autumn of 1986 and 1987 evaluated the efficacy and tolerance of recombinant interferon-βserine (rIFN-βser) nasal drops for prevention of natural rhinovirus colds. In 1986, 9 × 106 units of rIFN-βser (139 subjects) or placebo (157) were adminstered once daily except Sundays for 4 w. Rhinovirus colds occurred in 2.8% of rIFN-βser recipients and 6.0% of placebo recipients during the treatment period (52% reduction, P = .3). In 1987, 24 × 106 units of rIFN-βser (186) or placebo (197) were given daily for 25 consecutive days. Rhinovirus colds developed in 6.3% of rIFN-βser recipients and 5.3% of placebo recipients. In each study, illness frequency and number of days with subjective colds did not differ between the groups. Recipients of nasal drops of rIFN-βser at either dosage did not differ in tolerance from placebo recipients. The lack of both prophylactic efficacy and nasal toxicity are in contrast to prior observations with nasal sprays of rIFN-α2b.
Beyond location: hypertext workspaces and non-linear views

With the growth of the Web as a public information resource, users need workspaces to support the collection, evaluation, organization, and annotation of the materials they retrieve. These analytic workspaces should be designed for both the casual and professional analyst, keeping in mind that different environments may be appropriate for each type of use. In this paper, we derive a set of requirements from observations and reports on the use of information workspaces, coupled with observations of people performing analytical tasks. These workspace requirements include: (1) support for performing multiple simultaneous tasks; (2) a variety of activity-based connections to information resources; (3) tailorable and manipulable reduced document representations; and (4) visualizations to help users manage screen space. We explore the trade-offs implied by these requirements using our implementation of multiple focus fisheye views as we have integrated them into the VIKI workspace.
Monte Carlo simulation of influence of reheat temperature on austenite grain growth in C–Mn steel

Abstract The evolution and topology of a two-dimensional austenite grain growth of C–Mn steel are simulated by the Monte Carlo (MC) model during the reheating process. Simulated microstructural maps have been generated in a square lattice (400×400) at various MC steps and temperatures. Normalised grain size distribution has also been computed at different reheating temperatures, assuming a uniform temperature distribution in the slab. Two important model parameters, namely, the grain growth exponent and the model constant, have been estimated to predict the average grain size. The activation energy for grain growth has been calculated using the Arrhenius relationship. The grain growth behaviour as a function of both MC and physical time has been computed, and the effect of temperature on the rate of growth has been analysed. The predicted temporal evolutions of grain growth and model parameters have been validated with the published literature and found to be in good agreement.
Particle swarm optimization for facility layout problems FLP — A comprehensive study

Regarding facility layout problem FLP and its combinatorial problems, a research gap is detected since none of the reviewed papers give a deeper insight into the potential of Particle Swarm Optimization PSO in that particular field. In this paper, a brief introduction for the so far most promising approaches to facility layout related topics, are provided. The succeeding paper will then illustrate some of those, in more detail. Moreover, we examine PSO modifications and extensions that could contribute to optimization methods in FLP; mostly conform to NP-hard combinatorial problems. Future research areas are identified in Construction Site Facility Layout Problems, Multi-Criteria Facility Layout Problems and Dynamic Facility Layout Problems.
The Savage–Hutter avalanche model: how far can it be pushed?

The Savage–Hutter (SH) avalanche model is a depth-averaged dynamical model of a fluid-like continuum implementing the following simplifying assumptions: (i) density preserving, (ii) shallowness of the avalanche piles and small topographic curvatures, (iii) Coulomb-type sliding with bed friction angle δ and (iv) Mohr–Coulomb behaviour in the interior with internal angle of friction φ≥δ and an ad hoc assumption reducing the number of Mohr's circles in three-dimensional stress states to one. We scrutinize the available literature on information regarding these assumptions and thus delineate the ranges of validity of the proposed model equations. The discussion is limited to relatively large snow avalanches with negligible powder snow component and laboratory sand avalanches starting on steep slopes. The conclusion of the analysis is that the SH model is a valid model for sand avalanches, but its Mohr–Coulomb sliding law may have to be complemented for snow avalanches by a second velocity-dependent contribution. For very small snow avalanches and for laboratory avalanches starting on moderately steep and bumpy slopes it may not be adequate.
Bending analysis of functionally graded sandwich plates using a simple four-unknown shear and normal deformations theory

A refined trigonometric higher-order plate theory is presented for bending analysis of simply supported functionally graded ceramic–metal sandwich plates. The effects of transverse shear strains as well as the transverse normal strain are taken into account. The number of unknown functions involved in the present theory is only four as against six or more in case of other shear and normal deformations theories. Several types of the present symmetric and non-symmetric sandwich plates are used. The faces are assumed to be functionally graded through the thickness, while the core layer is still homogeneous and made of an isotropic material. The present refined plate theory is used to derive the field equations of the functionally graded sandwich plates. Numerical results of the present theory are compared with other theories to show the effect of the inclusion of transverse normal strain on the deflections and stresses.
Balancing Multiple and Conflicting Allocation Goals: A Logical Path Forward

At the end of 4 years of consensus building and two public forums, it is disappointing we have not implemented a better allocation algorithm for kidney transplants. However, the process has been instructive, and a clear path forward is evident. The current national allocation system no longer provides an adequate algorithm for allocating an increasingly limited and diverse donor pool of kidneys to an increasingly older group of recipients. This system has resulted in donor kidneys with excellent predicted longevity being transplanted into recipients with poor expected posttransplant survival. Conversely, donor kidneys with poor expected longevity and poor glomerular mass are transplanted into recipients who have a long expected survival. The current donor service areas (DSAs) evolved without design, resulting in widely disparate waiting times in adjacent areas. Attempts by the Organ Procurement Organization (OPO) to improve the allocation system have resulted in 67% of them incorporating variances to the current standard allocation system based on waiting time and human leukocyte antigen DR (HLA DR) matching. It is imperative that we initiate a national allocation system that will standardize allocation and eliminate the alternative allocation systems. Although these variances historically have served an important function to permit regions to test potentially progressive alternative systems, it is time to evaluate the efficacy of these variances. Successful variances should be incorporated into a uniform national algorithm, as was the original intent of allowing the existence of the alternative systems. Ongoing variances are making programming and implementation of any progressive changes to the national system difficult, time consuming, and expensive; further stretching valuable and limited technology resources. Valuable technologic resources that could be applied to other important programs to increase the annual number of kidney transplants, such as kidney paired donation, are drained. The allocation system that is eventually implemented has to be applied to all OPO’s and must permit subsequent modifications based on evolving data collection and correlation with outcomes. It is increasingly evident that this system will have to be transparent, comprehensible for health care workers and transplant candidates, permit potential recipients to have a reasonable estimation of waiting times, permit a smooth transition for the nearly 80 000 people already waiting for kidneys and provide for better matching between the expected longevity of a donor organ with the expected posttransplant survival of the recipient.
Colocalized Neuropeptides Activate a Central Pattern Generator by Acting on Different Circuit Targets

In the presence of descending modulatory inputs, the stomatogastric ganglion (STG) of the lobster Homarus americanusgenerates a triphasic motor pattern, the pyloric rhythm. Red pigment-concentrating hormone (RPCH) and Cancer borealistachykinin-related peptide (CabTRP) are colocalized in a pair of fibers that project into the neuropil of the STG. When the STG was isolated from anterior ganglia modulatory inputs, the lateral pyloric (LP) and pyloric (PY) neurons became silent, whereas the anterior burster (AB) and pyloric dilator (PD) neurons were rhythmically active at a low frequency. Exogenous application of 10−6m RPCH activated the LP neuron but not the PY neurons; 10−6m CabTRP activated the PY neurons but not the LP neuron. The actions of RPCH on the LP neuron and CabTRP on the PY neurons persisted when the rhythmic drive from the PD and AB neurons was removed, suggesting that the LP and PY neurons are direct targets for RPCH and CabTRP respectively. Coapplication of 10−6m RPCH and 10−6m CabTRP elicited triphasic motor patterns with phase relationships resembling those in a preparation with modulatory inputs intact. In summary, cotransmitters acting on different network targets act cooperatively to activate a complete central pattern-generating circuit.
A Practical Architecture for OFDM-Based Decode-and-Forward Physical Layer Network Coding

In physical layer network coding, it has been argued that performance improvements of a few dBs can be achieved by decoding a linear combination of colliding frames at an intermediate relay. The best results have been achieved by directly decoding the necessary linear combination rather than decoding each of the colliding packets, but so far only rather impractical architectures have been proposed. We explore in this paper a more pragmatic approach, where some important problems have been solved. We show by simulation that the proposed system is able to outperform analog network coding, the only other known practical architecture in this area so far, with substantial gains especially when noise amplification at the relay can be particularly detrimental, for instance when spatial diversity is available or large networks are analyzed.