bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro and In Vivo Characterization of Irreversible Mutant-Selective EGFR Inhibitors That Are Wild-Type Sparing
Authors: Tjin Tham Sjin Robert , Lee Kwangho , Walter Annette O. , Dubrovskiy Aleksandr , Sheets Michael , Martin Thia St. , Labenski Matthew T. , Zhu Zhendong , Tester Richland , Karp Russell , Medikonda Aravind , Chaturvedi Prasoon , Ren Yixuan , Haringsma Henry , Etter Jeff , Raponi Mitch , Simmons Andrew D. , Harding Thomas C. , Niu Deqiang , Nacht Mariana , Westlin William F. , Petter Russell C. , Allen Andrew , Singh Juswinder 
Published: April 2014

Abstract
Patients with non–small cell lung carcinoma (NSCLC) with activating mutations in epidermal growth factor receptor (EGFR) initially respond well to the EGFR inhibitors erlotinib and gefitinib. However, all patients relapse because of the emergence of drug-resistant mutations, with T790M mutations accounting for approximately 60% of all resistance. Second-generation irreversible EGFR inhibitors are effective against T790M mutations in vitro, but retain affinity for wild-type EGFR (EGFRWT). These inhibitors have not provided compelling clinical benefit in T790M-positive patients, apparently because of dose-limiting toxicities associated with inhibition of EGFRWT. Thus, there is an urgent clinical need for therapeutics that overcome T790M drug resistance while sparing EGFRWT. Here, we describe a lead optimization program that led to the discovery of four potent irreversible 2,4-diaminopyrimidine compounds that are EGFR mutant (EGFRmut) selective and have been designed to have low affinity for EGFRWT. Pharmacokinetic and pharmacodynamic studies in H1975 tumor–bearing mice showed that exposure was dose proportional resulting in dose-dependent EGFR modulation. Importantly, evaluation of normal lung tissue from the same animals showed no inhibition of EGFRWT. Of all the compounds tested, compound 3 displayed the best efficacy in EGFRL858R/T790M-driven tumors. Compound 3, now renamed CO-1686, is currently in a phase I/II clinical trial in patients with EGFRmut-advanced NSCLC that have received prior EGFR-directed therapy. Mol Cancer Ther; 13(6); 1468–79. ©2014 AACR.
Deamidated Lipocalin‐2 Induces Endothelial Dysfunction and Hypertension in Dietary Obese Mice
Authors: Song Erfei , Fan Pengcheng , Huang Bosheng , Deng Han‐Bing , Cheung Bernard Man Yung , Félétou Michel , Vilaine Jean‐Paul , Villeneuve Nicole , Xu Aimin , Vanhoutte Paul M. , Wang Yu 
Published: April 2014

Background
Lipocalin‐2 is a proinflammatory adipokine upregulated in obese humans and animals. A pathogenic role of lipocalin‐2 in hypertension has been suggested. Mice lacking lipocalin‐2 are protected from dietary obesity‐induced cardiovascular dysfunctions. Administration of lipocalin‐2 causes abnormal vasodilator responses in mice on a high‐fat diet (HFD).

Methods and Results

Wild‐type and lipocalin‐2 knockout mice were fed with standard chow or HFD. Immunoassays were performed for evaluating the circulating and tissue contents of lipocalin‐2. The relaxation and contraction of arteries were studied using a wire myograph. Blood pressure was monitored with implantable radio telemetry. Dietary obesity promoted the accumulation of lipocalin‐2 protein in blood and arteries. Deficiency of this adipokine protected mice from dietary obesity‐induced elevation of blood pressure. Mass spectrometry analysis revealed that human and murine lipocalin‐2 were modified by polyamination. Polyaminated lipocalin‐2 was rapidly cleared from the circulation. Adipose tissue was a major site for lipocalin‐2 deamidation. The circulating levels and the arterial accumulation of deamidated lipocalin‐2 were significantly enhanced by treatment with linoleic acid (18:2n−6), which bound to lipocalin‐2 with high affinity and prevented its interactions with matrix metalloproteinase 9 (
MMP
9). Combined administration of linoleic acid with lipocalin‐2 caused vascular inflammation and endothelial dysfunction and raised the blood pressure of mice receiving standard chow. A human lipocalin‐2 mutant with cysteine 87 replaced by alanine (C87A) contained less polyamines and exhibited a reduced capacity to form heterodimeric complexes with
MMP
9. After treatment, C87A remained in the circulation for a prolonged period of time and evoked endothelial dysfunction in the absence of linoleic acid.

Conclusions
Polyamination facilitates the clearance of lipocalin‐2, whereas the accumulation of deamidated lipocalin‐2 in arteries causes vascular inflammation, endothelial dysfunction, and hypertension.
Spatial References and Audio-Tactile Interaction in Cross-Modal Dynamic Capture
Authors: Chen Lihan , Wang Qingcui , Bao Ming 
Published: April 2014

In audiotactile dynamic capture, judgment of the direction of an apparent motion stream (such as auditory motion) was impeded (hence ‘captured’) by the presentation of a concurrent, but directionally opposite apparent motion stream (such as tactile motion) from a distractor modality, leading to a cross-modal dynamic capture (CDC) effect. That is to say, the percentage of correct reporting of the direction of the target motion was reduced. Previous studies have revealed the effect of stimulus onset asynchronies (SOAs) and the potential spatial remapping (by adopting a cross-hands posture) in CDC. However, further exploration of the dynamic capture process under different postures was not available due to the fact that only two levels of time asynchronies were employed (either synchronous or with an SOA of 500 ms). This study introduced a broad range of SOAs (−400 ms to 400 ms, tactile stream preceded auditory stream or vice versa) to explore the time course of audio-tactile interaction in CDC with two spatial references — arms-uncrossed or arms-crossed postures. Participants judged the direction of auditory apparent motion with tactile distractors. The results showed that in the arms-uncrossed condition, the CDC effect was prominent when the auditory–tactile events were in the temporal integration window (0–60 ms). However, with a preceding tactile cueing effect of SOA equal to and above 150 ms, the CDC effect was reduced, and no CDC effect was observed with the arms-crossed posture. These results suggest CDC effect is modulated by both cross-modal interaction and the spatial reference (especially for the distractors). The magnitude of the CDC effects in audiotactile interaction may be accounted for by reliability of tactile spatial-temporal information.
A Climatology of 500-hPa Closed Lows in the Northeastern Pacific Ocean, 1948–2011
Authors: Oakley Nina S. , Redmond Kelly T. 
Published: April 2014

AbstractThe northeastern Pacific Ocean is a preferential location for the formation of closed low pressure systems. These slow-moving, quasi-barotropic systems influence vertical stability and sustain a moist environment, giving them the potential to produce or affect sustained precipitation episodes along the west coast of the United States. They can remain motionless or change direction and speed more than once and thus often pose difficult forecast challenges. This study creates an objective climatological description of 500-hPa closed lows to assess their impacts on precipitation in the western United States and to explore interannual variability and preferred tracks. Geopotential height at 500 hPa from the NCEP–NCAR global reanalysis dataset was used at 6-h and 2.5° × 2.5° resolution for the period 1948–2011. Closed lows displayed seasonality and preferential durations. Time series for seasonal and annual event counts were found to exhibit strong interannual variability. Composites of the tracks of landfalling closed lows revealed preferential tracks as the features move inland over the western United States. Correlations of seasonal event totals for closed lows with ENSO indices, the Pacific decadal oscillation (PDO), and the Pacific–North American (PNA) pattern suggested an above-average number of events during the warm phase of ENSO and positive PDO and PNA phases. Precipitation at 30 U.S. Cooperative Observer stations was attributed to closed-low events, suggesting 20%–60% of annual precipitation along the West Coast may be associated with closed lows.
Spatiotemporal Variability and Predictability of Relative Humidity over West African Monsoon Region
Authors: Broman Daniel , Rajagopalan Balaji , Hopson Thomas 
Published: April 2014

Abstract
Spatial and temporal variability of relative humidity over the West African monsoon (WAM) region is investigated. In particular, the variability during the onset and retreat periods of the monsoon is considered. A K-means cluster analysis was performed to identify spatially coherent regions of relative humidity variability during the two periods. The cluster average of the relative humidity provides a robust representative index of the strength and timing of the transition periods between the dry and wet periods. Correlating the cluster indices with large-scale circulation and sea surface temperatures indicates that the land–ocean temperature gradient and the corresponding circulation, tropical Atlantic sea surface temperatures (SSTs), and to a somewhat lesser extent tropical Pacific SSTs all play a role in modulating the timing of the monsoon season relative humidity onset and retreat. These connections to large-scale climate features were also found to be persistent over interseasonal time scales, and thus best linear predictive models were developed to enable skillful forecasts of relative humidity during the two periods at 15–75-day lead times. The public health risks due to meningitis epidemics are of grave concern to the population in this region, and these risks are strongly tied to regional humidity levels. Because of this linkage, the understanding and predictability of relative humidity variability is of use in meningitis epidemic risk mitigation, which motivated this research.
The Early Winter Sea Ice Variability under the Recent Arctic Climate Shift
Authors: Yang Xiao-Yi , Yuan Xiaojun 
Published: April 2014

This study reveals that sea ice in the Barents and Kara Seas plays a crucial role in establishing a new Arctic coupled climate system. The early winter sea ice before 1998 shows double dipole patterns over the Arctic peripheral seas. This pattern, referred to as the early winter quadrupole pattern, exhibits the anticlockwise sequential sea ice anomalies propagation from the Greenland Sea to the Barents–Kara Seas and to the Bering Sea from October to December. This early winter in-phase ice variability contrasts to the out-of-phase relationship in late winter. The mean temperature advection and stationary wave heat flux divergence associated with the atmospheric zonal wave-2 pattern are responsible for the early winter in-phase pattern. Since the end of the last century, the early winter quadrupole pattern has broken down because of the rapid decline of sea ice extent in the Barents–Kara Seas. This remarkable ice retreat modifies the local ocean–atmosphere heat exchange, forcing an anomalous low air pressure over the Barents–Kara Seas. The subsequent collapse of the atmospheric zonal wave-2 pattern is likely responsible for the breakdown of the early winter sea ice quadrupole pattern after 1998. Therefore, the sea ice anomalies in the Barents–Kara Seas play a key role in establishing new atmosphere–sea ice coupled relationships in the warming Arctic.
A Note on the Phillips Spectral Framework for Ocean Whitecaps*
Authors: Banner Michael L. , Zappa Christopher J. , Gemmrich Johannes R. 
Published: April 2014

Abstract
There has been a recent upsurge in interest in quantifying kinematic, dynamic, and energetic properties of wave breaking in the open ocean, especially in severe sea states. The underpinning observational and modeling framework is provided by the seminal paper of O. M. Phillips. In this note, a fundamental issue contributing to the scatter in results between investigators is highlighted. This issue relates to the choice of the independent variable used in the expression for the spectral density of the mean breaking crest length per unit area. This note investigates the consequences of the different choices of independent variable presently used by various investigators for validating Phillips model predictions for the spectral density of the breaking crest length per unit area and the associated spectral breaking strength coefficient. These spectral measures have a central role in inferring the associated turbulent kinetic energy dissipation rate and the momentum flux to the upper ocean from breaking wave observations.
An Eddy Kinetic Energy View of Physical and Dynamical Processes in Distinct Forecast Scenarios for the Extratropical Transition of Two Tropical Cyclones*
Authors: Keller Julia H. , Jones Sarah C. , Harr Patrick A. 
Published: April 2014

Abstract
The extratropical transition (ET) of Hurricane Hanna (2008) and Typhoon Choi-Wan (2009) caused a variety of forecast scenarios in the European Centre for Medium-Range Weather Forecasts (ECMWF) Ensemble Prediction System (EPS). The dominant development scenarios are extracted for two ensemble forecasts initialized prior to the ET of those tropical storms, using an EOF and fuzzy clustering analysis. The role of the transitioning tropical cyclone and its impact on the midlatitude flow in the distinct forecast scenarios is examined by conducting an analysis of the eddy kinetic energy budget in the framework of downstream baroclinic development. This budget highlights sources and sinks of eddy kinetic energy emanating from the transitioning tropical cyclone or adjacent upstream midlatitude flow features. By comparing the budget for several forecast scenarios for the ET of each of the two tropical cyclones, the role of the transitioning storms on the development in downstream regions is investigated. Distinct features during the interaction between the tropical cyclone and the midlatitude flow turned out to be important. In the case of Hurricane Hanna, the duration of baroclinic conversion from eddy available potential into eddy kinetic energy was important for the amplification of the midlatitude wave pattern and the subsequent reintensification of Hanna as an extratropical cyclone. In the case of Typhoon Choi-Wan, the phasing between the storm and the midlatitude flow was one of the most critical factors for the future development.
A Comparison of Ensemble Kalman Filters for Storm Surge Assimilation
Authors: Altaf M. U. , Butler T. , Mayo T. , Luo X. , Dawson C. , Heemink A. W. , Hoteit I. 
Published: April 2014

Abstract
This study evaluates and compares the performances of several variants of the popular ensemble Kalman filter for the assimilation of storm surge data with the advanced circulation (ADCIRC) model. Using meteorological data from Hurricane Ike to force the ADCIRC model on a domain including the Gulf of Mexico coastline, the authors implement and compare the standard stochastic ensemble Kalman filter (EnKF) and three deterministic square root EnKFs: the singular evolutive interpolated Kalman (SEIK) filter, the ensemble transform Kalman filter (ETKF), and the ensemble adjustment Kalman filter (EAKF). Covariance inflation and localization are implemented in all of these filters. The results from twin experiments suggest that the square root ensemble filters could lead to very comparable performances with appropriate tuning of inflation and localization, suggesting that practical implementation details are at least as important as the choice of the square root ensemble filter itself. These filters also perform reasonably well with a relatively small ensemble size, whereas the stochastic EnKF requires larger ensemble sizes to provide similar accuracy for forecasts of storm surge.
Enhanced optical confinement and lasing characteristics of individual urchin-like ZnO microstructures prepared by oxidation of metallic Zn
Authors: Lu Chia-Hao , Chao Tzu-Yang , Chiu Ying-Feng , Tseng Shuo-Yen , Hsu Hsu-Cheng 
Published: April 2014

Abstract
We prepared urchin-like micron-sized ZnO cavities with high optical quality by oxidizing metallic Zn and proposed the mechanism that resulted in the growth of the urchin-like microstructures. The photoluminescence spectra of the ZnO microstructures had a predominant excitonic emission at room temperature. The lasing properties of the urchin-like ZnO microstructures were investigated systematically through excitation power- and size-dependent photoluminescence measurements. The results showed that a low lasing threshold with high quality factors could be achieved because of the high reflectivity of the optical reflectors formed by the tapered nanowires. The unique optical characteristics may facilitate the development of high-efficiency random lasers.
Analysis of the transcriptional networks underpinning the activation of murine macrophages by inflammatory mediators
Authors: Raza Sobia , Barnett Mark W , Barnett-Itzhaki Zohar , Amit Ido , Hume David A , Freeman Tom C 
Published: April 2014

AbstractMacrophages respond to the TLR4 agonist LPS with a sequential transcriptional cascade controlled by a complex regulatory network of signaling pathways and transcription factors. At least two distinct pathways are currently known to be engaged by TLR4 and are distinguished by their dependence on the adaptor molecule MyD88. We have used gene expression microarrays to define the effects of each of three variables—LPS dose, LPS versus IFN-β and -γ, and genetic background—on the transcriptional response of mouse BMDMs. Analysis of correlation networks generated from the data has identified subnetworks or modules within the macrophage transcriptional network that are activated selectively by these variables. We have identified mouse strain-specific signatures, including a module enriched for SLE susceptibility candidates. In the modules of genes unique to different treatments, we found a module of genes induced by type-I IFN but not by LPS treatment, suggesting another layer of complexity in the LPS-TLR4 signaling feedback control. We also observe that the activation of the complement system, in common with the known activation of MHC class 2 genes, is reliant on IFN-γ signaling. Taken together, these data further highlight the exquisite nature of the regulatory systems that control macrophage activation, their likely relevance to disease resistance/susceptibility, and the appropriate response of these cells to proinflammatory stimuli.
Psychiatric resilience: longitudinal twin study
Authors: Amstadter Ananda B. , Myers John M. , Kendler Kenneth S. 
Published: April 2014

BackgroundThe source of variability in people's response to stressful life events is poorly understood.AimsWe examine the genetic and environmental underpinning of resilience (i.e. the difference between the twins' internalising symptoms and their predicted symptoms based on cumulative stressful life events).MethodStressful life event exposure and internalising symptoms were assessed at two time points in 7500 adult twins. Using the residual between actual and predicted internalising symptom total score, twin modelling was conducted for each wave separately and longitudinally.ResultsResilience was found to have a moderate genetic heritability at each wave (~31%). Qualitative gender effects were found. Incorporating error of measurement into the model increased the estimated heritability for the latent construct of resilience (~50%). When measurement error and occasion-specific effects were removed, environmental influences contributed roughly equally to level of resilience.ConclusionsBoth genes and environment influence level of psychiatric resilience, and are largely stable over time. Environmental influences can have an enduring effect on resilience.
Family Perspectives on a Successful Transition to Adulthood for Individuals With Disabilities
Authors: Henninger Natalie A. , Taylor Julie Lounds 
Published: April 2014

Abstract
When researchers evaluate adult outcomes for individuals with intellectual and/or developmental disabilities (IDD), the perspective of families is not always considered. Parents of individuals with IDD (N  =  198) answered an online survey about their definition of a successful transition to adulthood. Content analysis was used to describe themes and ideas present in the responses. Rather than focusing only on developmental tasks of adulthood, such as living independently, being competitively employed, and maintaining friendships, responses reflected a more varied and dynamic view of success in adulthood, taking into account the fit between the person with IDD and his or her environment. As services are developed and implemented for adults with IDD, it is important to consider the full range of goals that families have for their son or daughter's successful transition to adulthood.
What enabled mother and twins to survive 18 minutes after maternal cardiopulmonary arrest?
Authors: Matsuoka Ayumi , Tanaka Masaaki , Dohi Satoshi , Sasaki Hiromasa , Taniguchi Takumi , Inoue Masaki 
Published: April 2014

Abstract
A woman carrying monochorionic twins underwent sudden cardiopulmonary arrest at 31 weeks of gestation due to spontaneous coronary artery dissection in the hospital. The resuscitation techniques, with her uterus manually displaced to her left, were initiated immediately and maternal spontaneous circulation was resumed 18 min later. A cesarean section was performed 2 h after the revival and the patient was kept hypothermic for 24 h. Finally, full recovery of both mother and twins was achieved. As in this case, the resuscitation techniques for pregnant women recommended by the American Heart Association, and therapeutic hypothermia, might be effective and contribute much to the survival and recovery of patients.
Path dependence and routines: a threat to capability development
Authors: Sjödahl Lars E. 
Published: April 2014

Abstract
This article introduces the concept path dependence based on case illustrations mainly from psychiatric health care. The concept path dependence is widely used in economic research, history, social sciences and law, but so far seldom in psychology and health care, although equally applicable here. Two variants of path dependence, one in a narrow sense and one in a broader sense are defined and exemplified by case illustrations from psychiatric health care and patient safety systems.
Home-built Apparatus for Measuring Thermal Conductivity of Glass and Polymer Materials
Authors: Heffner William R. , Demchak Shera , Scruggs John , Pearson Ray 
Published: April 2014

ABSTRACTAs a part of the IMI-NFG’s series of low-cost experiments in glass science [1,2] we have developed a simple home-built apparatus for measuring the thermal conductivity of glassy materials, from polymers to oxide glasses, in the range of 0.1 to 1.5 W/ °C. Our apparatus is inexpensive, relatively easy to construct and accurate enough for students to use for quantitative measurements of their own glass or polymer samples. Standard materials are used to demonstrate good correlation with literature values. We also measured the thermal conductivity of a silica filled epoxy and showed a linear increase with fill fraction to 20%. This simple, low-cost method can provide students and researchers with a much broader access to this important property.