bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting MDM2 for novel molecular therapy: Beyond oncology
Authors: Wang Wei , Qin Jiang‐Jiang , Rajaei Mehrdad , Li Xin , Yu Xiaoyi , Hunt Courtney , Zhang Ruiwen 
Published: October 2019

AbstractThe murine double minute 2 (MDM2) oncogene exerts major oncogenic activities in human cancers; it is not only the best‐documented negative regulator of the p53 tumor suppressor, but also exerts p53‐independent activities. There is an increasing interest in developing MDM2‐based targeted therapies. Several classes of MDM2 inhibitors have been evaluated in preclinical models, with a few entering clinical trials, mainly for cancer therapy. However, noncarcinogenic roles for MDM2 have also been identified, demonstrating that MDM2 is involved in many chronic diseases and conditions such as inflammation and autoimmune diseases, dementia and neurodegenerative diseases, heart failure and cardiovascular diseases, nephropathy, diabetes, obesity, and sterility. MDM2 inhibitors have been shown to have promising therapeutic efficacy for treating inflammation and other nonmalignant diseases in preclinical evaluations. Therefore, targeting MDM2 may represent a promising approach for treating and preventing these nonmalignant diseases. In addition, a better understanding of how MDM2 works in nonmalignant diseases may provide new biomarkers for their diagnosis, prognostic prediction, and monitoring of therapeutic outcome. In this review article, we pay special attention to the recent findings related to the roles of MDM2 in the pathogenesis of several nonmalignant diseases, the therapeutic potential of its downregulation or inhibition, and its use as a biomarker.
Analysis of the impact of chronic corticosteroid use on free flap reconstruction
Authors: Weisberger Joseph S. , Oleck Nicholas C. , Ayyala Haripriya S. , Malhotra Radhika , Lee Edward S. 
Published: October 2019

AbstractBackgroundSystemic corticosteroids negatively impact wound healing, potentially increasing postoperative wound complication rates. In this study, the authors utilize the American College of Surgeons (ACS) National Surgical Quality Improvement (NSQIP) database to investigate the impact of chronic steroid usage on postoperative complications following microvascular free tissue transfer procedures.MethodsThe ACS NSQIP database was queried for all free flap procedures performed between 2005 and 2016. Patients with a history of chronic steroid use (n = 159) were compared to patients with no history of chronic steroid use (n = 3,405). The two cohorts were compared by univariate analysis, followed by multivariate binary logistic regression for all complications noted to be statistically significant on univariate analysis.ResultsPatients treated with systemic corticosteroids were more likely to be smokers, have a history of diabetes, hypertension, bleeding disorders, hypoalbuminemia, anemia, and have a wound infection at time of surgery. There were increased rates of bleeding requiring transfusion (37.7 vs. 27.5% p = .005), overall surgical complications (48.4 vs. 36.7%, p = .003) and overall complication rates (56.0 vs. 42.3%, p = .001) in these patients. On multivariate analysis, chronic steroid use was not associated with increased risk of surgical complications (OR = 2.540, p = .056, 95% CI 0.975–6.622), overall complications (OR = 2.303, p = .086, 95% CI 0.888–5.973), or wound complications. However, chronic steroid usage conferred nearly a four times increased risk for major bleeding complications (OR = 3.995, p = .009, 95% CI 1.415–11.279).ConclusionChronic corticosteroid use does not increase rates of wound complications, reoperation, or readmission. However, this population may be at increased risk for major bleeding requiring blood transfusion following free flap reconstruction.
Experimental characterization of magnetically focused electron contamination at the surface of a high‐field inline MRI‐linac
Authors: Roberts Natalia F. , Patterson Elizabeth , Jelen Urszula , Causer Trent , Holloway Lois , Liney Gary , Lerch Michael , Rosenfeld Anatoly B. , Cutajar Dean , Oborn Bradley M. , Metcalfe Peter 
Published: October 2019

PurposeThe fringe field of the Australian MRI‐linac causes contaminant electrons to be focused along the central axis resulting in a high surface dose. This work aims to characterize this effect using Gafchromic film and high‐resolution detectors, MOSkinTM and microDiamond. The secondary aim is to investigate the influence of the inline magnetic field on the relative dose response of these detectors.MethodsThe Australian MRI‐linac has the unique feature that the linac is mounted on rails allowing for measurements to be performed at different magnetic field strengths while maintaining a constant source‐to‐surface distance (SSD). Percentage depth doses (PDD) were collected at SSD 1.82 m in a solid water phantom positioned in a low magnetic field region and then at isocenter of the MRI where the magnetic field is 1 T. Measurements for a range of field sizes were taken with the MOSkinTM, microDiamond, and Gafchromic® EBT3 film. The detectors’ relative responses at 1 T were compared to the near 0 T PDD beyond the region of electron contamination, that is, 20 mm depth. The near surface measurements inside the MRI bore were compared among the different detectors.ResultsSkin dose in the MRI, as measured with the MOSkinTM, was 104.5% for 2.1 × 1.9 cm2, 185.6% for 6.1 × 5.8 cm2, 369.1% for 11.8 × 11.5 cm2, and 711.1% for 23.5 × 23 cm2. The detector measurements beyond the electron contamination region showed agreement between the relative response at 1 T and near 0 T. Film was in agreement with both detectors in this region further demonstrating their relative response is unaffected by the magnetic field.ConclusionsExperimental characterization of the high electron contamination at the surface was performed for a range of field sizes. The relative response of MOSkinTM and microDiamond detectors, beyond the electron contamination region, were confirmed to be unaffected by the 1‐T inline magnetic field.
Chemical‐shift encoding–based water–fat separation with multifrequency fat spectrum modeling in spin‐lock MRI
Authors: Chen Weitian , Karampinos Dimitrios C. 
Published: October 2019

PurposeChemical exchange saturation transfer is used commonly to generate MRI contrast based on the chemical exchange effect. The spin‐lock techniques can also be used to probe the chemical exchange and other molecular motion processes in tissues. The presence of fat can cause errors in spin‐lock MRI. Signals from fat are typically suppressed based on spectral selectivity or T1 nulling approaches in spin‐lock imaging. However, these methods cannot be used to suppress fat signals from multiple fat peaks. To address this problem, we report chemical‐shift encoding–based water–fat separation approaches with multifrequency fat spectrum modeling.MethodsBoth the conventional spin‐lock and the adiabatic continuous‐wave constant‐amplitude spin lock (ACCSL) with multi‐echo acquisitions are investigated for chemical‐shift encoding–based water–fat separation in spin‐lock imaging. A comparison is made of reconstructions based on 3 models: a single‐peak fat spectrum model, a standard precalibrated proton density 6‐peak fat spectrum model, and the self‐calibrated relaxation‐dependent 3‐peak fat spectrum model. Comparisons were performed using Bloch simulations, phantom, and in vivo experiments at 3 T.ResultsConventional spin‐lock acquisitions cannot be used for reliable water–fat separation with a multipeak fat spectrum model. Water–fat separation based on ACCSL acquisitions achieves superior performance compared with the use of conventional spin‐lock acquisitions. The best result is achieved from ACCSL acquisition with self‐calibrated relaxation‐dependent multipeak fat spectrum modeling.ConclusionThe ACCSL acquisition can be used for chemical‐shift encoding–based water–fat separation with multipeak fat spectrum modeling. This approach has the potential to improve quantitative analysis using spin‐lock MRI for assessing the biochemical properties of tissues.
Longitudinal 16‐year study of dominant intermediate CMT type C neuropathy
Authors: Pan Yi , Kafaie Jafar , Thomas Florian P. 
Published: October 2019

AbstractBackgroundDominant‐intermediate Charcot–Marie‐Tooth neuropathy subtype C (DI‐CMTC) is associated with mutations in the YARS gene. The aim of this study is to investigate the long‐term natural history of the disease.MethodsIn a 5‐generation DI‐CMTC family, we compared data from 2016 to that of 2000 in 13 of 21 original participants.ResultsFive women and 8 men were examined. While most symptoms and signs progressed, only gait progression was statistically significant (P = .016). The median CMT Neuropathy Score was 6.08 in 2000 and 11 in 2016 (P = .001). Quality of life (QOL) deteriorated in mobility (P = .008), pain/discomfort (P = .011), and anxiety/depression (P = .014). Median and ulnar compound muscle action potential amplitudes decreased from 9.35 ± 2.90 mV to 6.0 ± 2.9 mV (P = .002), and from 9.24 ± 2.10 mV to 6.06 ± 1.81 mV (P = .004), respectively, whereas motor nerve conduction velocities remained unchanged.ConclusionsDI‐CMTC in this family is a slowly progressive disease with axonal degeneration, deteriorating mobility and QOL.
Two‐step simulation approach for laser shock peening
Authors: Pozdnyakov Vasily , Keller Sören , Kashaev Nikolai , Klusemann Benjamin , Oberrath Jens 
Published: October 2019

AbstractLaser shock peening (LSP) is a surface modification technique to introduce compressive residual stresses (RS) with a high magnitude in the near surface region of the material. Due to non‐linear interactions (e.g. laser absorption by plasma, shock wave propagation, etc.) and a high number of parameters, it is difficult to study and optimize the process based on experiments alone. Therefore, a two‐step simulation approach is proposed in this paper, where two models are combined, because one model of the complete process is difficult to derive, due to the different characteristics of the plasma formation and the shock wave propagation in the material. On one hand, a global model including plasma and shock wave descriptions is applied for the LSP of an aluminium sample with water confinement. The numerical solution of this model, applied for a 3×3 mm2 focus size, 5 J and 20 ns (full width at half maximum (FWHM)) laser pulse, allows to determine the temporal plasma pressure evolution on the material surface. On the other hand, a finite element simulation is used to calculate the RS distribution within the target material, where the plasma pressure is applied as a surface loading for the aluminium alloy AA2198‐T3. The simulated residual stresses are fitted to measurements via parameter variation of the global model. The identified values and the two‐step simulation approach can be used in future work to predict stress states of materials after LSP for various process parameters variations.
Association behavior of bile salts binary mixtures in an aqueous system: A tensiometric and fluorometric study
Authors: Azum Naved , Rub Malik Abdul , Asiri Abdullah M. 
Published: October 2019

AbstractBile salts are steroidal surfactants consisting of 2 to 12 monomers to form a micelle. The most important physiological property of bile salts is the solubilization of cholesterol. The bile salts make mixed micelle with phospholipids that enhance the bile salts ability to solubilize cholesterol. The mixed micelle formation in aqueous solution between two bile salts (sodium taurocholate [NaTC] and sodium deoxycholate [NaDC]) mixtures has been studied by tensiometric and fluorometric studies. The nonideal mixing behavior was examined for mixed systems, and synergism was found for the current mixed systems. Rubingh and Rosen models were used to analyze the bile salt‐bile salt binary mixtures, and the interaction parameters, as well as mixed micelle compositions at bulk and interface, have been computed as well as discussed one by one. The values of
were achieved to be negative for all studied systems. In the solution mixtures, as the content of NaTC increases, the formation of micelles becomes slightly less favorable.
Comparison of backbone dynamics of the p50 dimerization domain of NFκB in the homodimeric transcription factor NFκB1 and in its heterodimeric complex with RelA (p65)
Authors: Kohl Bastian , Granitzka Vanessa , Singh Amrinder , Quintas Pedro , Xiromeriti Elli , Mörtel Fabian , Wright Peter E. , Kroon Gerard , Dyson H. Jane , Stoll Raphael 
Published: October 2019

AbstractThe nuclear factor of kappa light polypeptide gene enhancer in B‐cells (NFκB) transcription factors play a critical role in human immune response. The family includes homodimers and heterodimers of five component proteins, which mediate different transcriptional responses and bind preferentially to different DNA sequences. Crystal structures of DNA complexes show that the dimers of the Rel‐homology regions are structurally very similar. Differing DNA sequence preference together with structural similarity suggests that the dimers may differ in their dynamics. In this study, we present the first near‐complete 15N, 13Cα/β, and HN backbone resonance assignments of two dimers of the dimerization domain (DD) of the NFκB1 (p50) protein (residues 241–351): the homodimer of two p50 domains and a heterodimer of the p50 DD with the p65 DD. As expected, the two dimers behave very similarly, with chemical shift differences between them largely concentrated in the dimer interface and attributable to specific differences in the amino acid sequences of p50 and p65. A comparison of the picosecond‐nanosecond dynamics of the homo‐ and heterodimers also shows that the environment of p50 is similar, with an overall slightly reduced correlation time for the homodimer compared to the heterodimer, consistent with its slightly smaller molecular weight. These results demonstrate that NMR spectroscopy can be used to explore subtle changes in structure and dynamics that have the potential to give insights into differences in specificity that can be exploited in the design of new therapeutic agents.
A seamless filter for daily to seasonal forecasts, with applications to Iran and Brazil
Authors: Bürger Gerd 
Published: October 2019

AbstractA digital filter is introduced which treats the problem of predictability versus time averaging in a continuous, seamless manner. This seamless filter (SF) is characterized by a unique smoothing rule that determines the strength of smoothing in dependence on lead time. The rule needs to be specified beforehand, either by expert knowledge or by user demand. As a result, skill curves are obtained that allow a predictability assessment across a whole range of time‐scales, from daily to seasonal, in a uniform manner. The SF is applied to downscaled SEAS5 ensemble forecasts for two focus regions in or near the tropical belt, the river basins of the Karun in Iran and the São Francisco in Brazil. Both are characterized by strong seasonality and semi‐aridity, so that predictability across various time‐scales is in high demand. Among other things, it is found that from the start of the water year (autumn), areal precipitation is predictable with good skill for the Karun basin two and a half months ahead; for the São Francisco it is only one month, longer‐term prediction skill is just above the critical level.
Ultrasensitive Field‐Effect Biosensors Enabled by the Unique Electronic Properties of Graphene
Authors: Zhang Xiaoyan , Jing Qiushi , Ao Shen , Schneider Grégory F. , Kireev Dmitry , Zhang Zhengjun , Fu Wangyang 
Published: October 2019

AbstractThis review provides a critical overview of current developments on nanoelectronic biochemical sensors based on graphene. Composed of a single layer of conjugated carbon atoms, graphene has outstanding high carrier mobility and low intrinsic electrical noise, but a chemically inert surface. Surface functionalization is therefore crucial to unravel graphene sensitivity and selectivity for the detection of targeted analytes. To achieve optimal performance of graphene transistors for biochemical sensing, the tuning of the graphene surface properties via surface functionalization and passivation is highlighted, as well as the tuning of its electrical operation by utilizing multifrequency ambipolar configuration and a high frequency measurement scheme to overcome the Debye screening to achieve low noise and highly sensitive detection. Potential applications and prospectives of ultrasensitive graphene electronic biochemical sensors ranging from environmental monitoring and food safety, healthcare and medical diagnosis, to life science research, are presented as well.
Europium and Acetate Co‐doping Strategy for Developing Stable and Efficient CsPbI2Br Perovskite Solar Cells
Authors: Yang Shaomin , Zhao Huan , Han Yu , Duan Chenyang , Liu Zhike , Liu Shengzhong (Frank) 
Published: October 2019

AbstractAll‐inorganic perovskite solar cells have developed rapidly in the last two years due to their excellent thermal and light stability. However, low efficiency and moisture instability limit their future commercial application. The mixed‐halide inorganic CsPbI2Br perovskite with a suitable bandgap offers a good balance between phase stability and light harvesting. However, high defect density and low carrier lifetime in CsPbI2Br perovskites limit the open‐circuit voltage (Voc < 1.2 V), short‐circuit current density (Jsc < 15 mA cm−2), and fill factor (FF < 75%) of CsPbI2Br perovskite solar cells, resulting in an efficiency below 14%. For the first time, a CsPbI2Br perovskite is doped by Eu(Ac)3 to obtain a high‐quality inorganic perovskite film with a low defect density and long carrier lifetime. A high efficiency of 15.25% (average efficiency of 14.88%), a respectable Voc of 1.25 V, a reasonable Jsc of 15.44 mA cm−2, and a high FF of 79.00% are realized for CsPbI2Br solar cells. Moreover, the CsPbI2Br solar cells with Eu(Ac)3 doping demonstrate excellent air stability and maintain more than 80% of their initial power conversion efficiency (PCE) values after aging in air (relative humidity: 35–40%) for 30 days.
Interfacial behavior between normal substrate and green ultra‐high‐performance fiber‐reinforced concrete under elevated temperatures
Authors: Abo Sabah Saddam H. , Zainal Nur L. , Muhamad Bunnori Norazura , Megat Johari Megat A. , Hassan Mohd H. 
Published: October 2019

AbstractThis study assesses the effects of elevated temperatures (100, 200, 300, 400, and 500°C) on the bonding behavior of normal concrete (NC) substrate as old concrete and the new Green Universiti Sains Malaysia Reinforced Concrete (GUSMRC) as a repair material through slant shear, pull‐off, splitting tensile, and flexural tests. Sandblasting (SB) and grinding (GR) surface treatments were employed to enhance the bond strength of the NC/GUSMRC composite. The research also evaluates the mechanical characteristics of the GUSMRC mix which 50% of its content is ultrafine palm oil fuel ash prior to and after the exposure to elevated temperatures. The results showed degradation in the mechanical properties of the monolithic GUSMRC and the bonding strength of the NC/GUSMRC composite after exposure to elevated temperatures; however, the bonding quality is excellent. Moreover, the SB surface treatment enhanced the interfacial bonding more than the GR surface treatment before and after elevated temperature exposure.
To Honor and Inform: Addressing Cultural Humility in Intercultural Music Teacher Education in Canada
Authors: Dolloff Lori-Anne 
Published: October 2019

AbstractIn this chapter I address the need for reshaping the way we think about Indigenous inclusion in the intercultural curriculum. While Canada has prided itself on its multicultural heritage, the nation’s relationship with the First Peoples – First Nations, Inuit and Métis – has been immoral, genocidal and assimilationist. The 2015 publication of the findings of the Truth and Reconciliation Commission’s Calls to Action details a way forward from the colonial patriarchy of the past. Education in general, and music education in particular are charged with finding ways to incorporate Indigenous knowledge, perspectives and history into the curriculum. After an introduction to the issues of the marginalization of Indigenous voices I discuss several arts-based curricular and extra-curricular initiatives that reframe intercultural music education. I propose that developing cultural humility in music teacher education will be a step forward in the decolonization of our teaching and learning spaces. This includes a move from generic cultural competencies toward an attitude of ‘Cultural Humility’. Cultural Humility is discussed as an attitude toward engagement with peoples of cultures other than one’s own. The stance is based on life-long, self-reflective inquiry, and seeks to disrupt the power imbalance that defines ‘othering’, seeking to establish partnerships and collaboration.
Easterly wave contributions to seasonal rainfall over the tropical Americas in observations and a regional climate model
Authors: Dominguez Christian , Done James M. , Bruyère Cindy L. 
Published: October 2019

AbstractEasterly waves (EWs) are important moisture carriers and their variability can impact the total May–November rainfall, defined as seasonal precipitation, over the Tropical Americas. The contribution of EWs to the seasonal precipitation is explored over the tropical Americas using rain gauge stations, reanalysis data and a regional model ensemble during the 1980–2013 period. In the present study, EWs are found to produce up to 50% of seasonal rainfall mainly over the north of South America and contribute substantially to interannual regional rainfall variability. An observational analysis shows that the El Niño Southern Oscillation (ENSO) affects EW frequency and therefore, their contribution to seasonal rainfall. In recent years, tropical cyclone (TC) activity over the Main Development Region (MDR) of the tropical North Atlantic has a negative impact on regional seasonal precipitation over northern South America. High TC activity over MDR corresponds to below-normal precipitation because it reduces the EW activity reaching northern South America through the recurving of TC tracks. Recurving TC tracks redirect moisture away from the tropical belt and into the mid-latitudes. However, this relationship only holds under neutral ENSO conditions and the positive phase of the Atlantic Multidecadal Oscillation. A 10-member regional model multi-physics ensemble simulation for the period 1990–2000 was analyzed to show the relationships are robust to different representations of physical processes. This new understanding of seasonal rainfall over the tropical Americas may support improved regional seasonal and climate outlooks.