bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclin E Overexpression Sensitizes Triple-Negative Breast Cancer to Wee1 Kinase Inhibition
Authors: Chen Xian , Low Kwang-Huei , Alexander Angela , Jiang Yufeng , Karakas Cansu , Hess Kenneth R. , Carey Jason P.W. , Bui Tuyen N. , Vijayaraghavan Smruthi , Evans Kurt W. , Yi Min , Ellis D. Christian , Cheung Kwok-Leung , Ellis Ian O. , Fu Siqing , Meric-Bernstam Funda , Hunt Kelly K. , Keyomarsi Khandan 
Published: September 2018

Abstract

Purpose:
Poor prognosis in triple-negative breast cancer (TNBC) is due to an aggressive phenotype and lack of biomarker-driven targeted therapies. Overexpression of cyclin E and phosphorylated-CDK2 are correlated with poor survival in patients with TNBC, and the absence of CDK2 desensitizes cells to inhibition of Wee1 kinase, a key cell-cycle regulator. We hypothesize that cyclin E expression can predict response to therapies, which include the Wee1 kinase inhibitor, AZD1775.

Experimental Design:
Mono- and combination therapies with AZD1775 were evaluated in TNBC cell lines and multiple patient-derived xenograft (PDX) models with different cyclin E expression profiles. The mechanism(s) of cyclin E–mediated replicative stress were investigated following cyclin E induction or CRISPR/Cas9 knockout by a number of assays in multiple cell lines.

Results:
Cyclin E overexpression (i) is enriched in TNBCs with high recurrence rates, (ii) sensitizes TNBC cell lines and PDX models to AZD1775, (iii) leads to CDK2-dependent activation of DNA replication stress pathways, and (iv) increases Wee1 kinase activity. Moreover, treatment of cells with either CDK2 inhibitors or carboplatin leads to transient transcriptional induction of cyclin E (in cyclin E–low tumors) and result in DNA replicative stress. Such drug-mediated cyclin E induction in TNBC cells and PDX models sensitizes them to AZD1775 in a sequential treatment combination strategy.
Conclusions:Cyclin E is a potential biomarker of response (i) for AZD1775 as monotherapy in cyclin E–high TNBC tumors and (ii) for sequential combination therapy with CDK2 inhibitor or carboplatin followed by AZD1775 in cyclin E–low TNBC tumors.
Synergistic Interaction Between Zinc and Reactive Oxygen Species Amplifies Ischemic Brain Injury in Rats
Authors: Zhao Yongmei , Yan Feng , Yin Jie , Pan Rong , Shi Wenjuan , Qi Zhifeng , Fang Yalan , Huang Yuyou , Li Sen , Luo Yumin , Ji Xunming , Liu Ke Jian 
Published: September 2018

Background and Purpose—
Although intracellular zinc accumulation has been shown to contribute to neuronal death after cerebral ischemia, the mechanism by which zinc keeps on accumulating to cause severe brain damage remains unclear. Herein the dynamic cause-effect relationships between zinc accumulation and reactive oxygen species (ROS) production during cerebral ischemia/reperfusion are investigated.

Methods—
Rats were treated with zinc chelator, ROS scavenger, mitochondria-targeted ROS inhibitor, or NADPH oxidase inhibitor during a 90-minute middle cerebral artery occlusion. Cytosolic labile zinc, ROS level, cerebral infarct volume, and neurological functions were assessed after ischemia/reperfusion.

Results—
Zinc and ROS were colocalized in neurons, leading to neuronal apoptotic death. Chelating zinc reduced ROS production at 6 and 24 hours after reperfusion, whereas eliminating ROS reduced zinc accumulation only at 24 hours. Furthermore, suppression of mitochondrial ROS production reduced the total ROS level and brain damage at 6 hours after reperfusion but did not change zinc accumulation, indicating that ROS is produced mainly from mitochondria during early reperfusion and the initial zinc release is upstream of ROS generation after ischemia. Suppression of NADPH oxidase decreased ROS generation, zinc accumulation, and brain damage only at 24 hours after reperfusion, indicating that the majority of ROS is produced by NADPH oxidase at later reperfusion time.

Conclusions—
This study provides the direct evidence that there exists a positive feedback loop between zinc accumulation and NADPH oxidase–induced ROS production, which greatly amplifies the damaging effects of both. These findings reveal that different ROS-generating source contributes to ischemia-generated ROS at different time, underscoring the critical importance of spatial and temporal factors in the interaction between ROS and zinc accumulation, and the consequent brain injury, after cerebral ischemia/reperfusion.
Wall Shear Stress and T1 Contrast Ratio Are Associated With Embolic Signals During Carotid Exposure in Endarterectomy
Authors: Oshida Sotaro , Mori Futoshi , Sasaki Makoto , Sato Yuiko , Kobayshi Masakazu , Yoshida Kenji , Fujiwara Shunrou , Ogasawara Kuniaki 
Published: September 2018

Background and Purpose—
The frictional force because of blood flow may dislodge masses present on the surface of a plaque. Such frictional force is calculated as wall shear stress (WSS) using computational fluid dynamics. The aims of the present study were to determine whether, in addition to carotid plaque intensity on T1-weighted magnetic resonance (MR) imaging, WSS calculated using computational fluid dynamics analysis for carotid arteries is associated with development of an embolism during exposure of carotid arteries during carotid endarterectomy.

Methods—
One hundred patients with internal carotid artery stenosis (≥70%) underwent carotid plaque imaging with MR, and 54 patients with a vulnerable plaque (intraplaque hemorrhage or lipid/necrotic core) displayed as a high-intensity lesion underwent additional cervical 3-dimensional MR angiography. The maximum value of WSS within the most severe stenotic segment of the internal carotid artery was calculated using MR angiography. Transcranial Doppler monitoring of microembolic signals (MES) in the ipsilateral middle cerebral artery was performed during carotid endarterectomy.

Results—

Although none of the 46 patients with a nonvulnerable carotid plaque had MES during exposure of carotid arteries, 24 of the 54 patients with a vulnerable carotid plaque (44%) had MES. Logistic regression analysis showed that higher plaque intensity (
P
=0.0107) and higher WSS (
P
=0.0029) were significantly associated with the development of MES. When both cutoff points of plaque intensity and WSS in the receiver operating characteristic curves for predicting development of MES were combined, specificity (from 63% to 93%) and positive predictive value (from 66% to 90%) became greater than those for plaque intensity alone.

Conclusions—
In addition to carotid plaque intensity on T1-weighted MR imaging, WSS calculated using computational fluid dynamics analysis for carotid arteries is associated with development of an embolism during exposure of carotid arteries during carotid endarterectomy.
The Politics and Poetics of Madness in Ḥasan Blāsim’s The Madman of Freedom Square
Authors: Al-Masri Khaled 
Published: September 2018

Abstract
Iraqi writer Ḥasan Blāsim’s debut collection of short stories, Majnūn sāḥat al-ḥurriyyah (The Madman of Freedom Square), is centrally concerned with states and expressions of madness arising from the traumatic violence that consumed Iraq during, between, and after the first and second Gulf wars. The experiences of refugees and their search for asylum are frequently highlighted. Focusing on select stories, this article identifies and explores four types of madness in Blāsim’s fiction: contained madness, a structural dichotomy between madness and sanity that is established through a nested narrative structure in which a fantastical inner story is framed and retold by an apparently reliable external narrator; madness of the body, in which a traumatized character experiences a transformation, or disintegration, of his human form; gendered madness, in which madness is a response to patriarchal violence and oppression; and destabilizing madness, a subversion of contained madness in which the boundaries between sanity and madness, reality and fantasy, become indistinguishable. Drawing on theories of literary madness advanced by Shoshana Felman and others, the article argues that Blāsim’s iterations of madness and trauma serve to expand reality, rather than distort it, ultimately depicting the horror of wartime Iraq and the lives of its refugees in a way that rational storytelling simply cannot capture.
Extratropical Cyclogenesis Changes in Connection with Tropospheric ENSO Teleconnections to the North Atlantic: Role of Stationary and Transient Waves
Authors: Schemm Sebastian , Rivière Gwendal , Ciasto Laura M. , Li Camille 
Published: September 2018

AbstractThis study investigates mechanisms for changes in wintertime extratropical cyclogenesis over North America and the North Atlantic during different phases of El Niño–Southern Oscillation (ENSO). Insights into the relationship between the ENSO–North Atlantic teleconnection and the cyclogenesis changes are provided by diagnosing the relative roles of stationary wave propagation and transient eddies in setting cyclogenesis-conducive large-scale circulation anomalies. During La Niña winters, Rocky Mountain and Greenland cyclogenesis are enhanced, while Gulf Stream cyclogenesis is reduced. Diagnostics suggest that stationary waves of tropical origin work in tandem with transient eddies to amplify the ridge over the northeastern Pacific, establishing background flow anomalies that favor Rocky Mountain cyclogenesis; downstream, more transient eddies with an anticyclonic tilt push the North Atlantic jet poleward, favoring cyclogenesis near Greenland, while contributions from stationary waves are small. During central Pacific El Niño winters, the cyclogenesis situation is essentially the opposite: Rocky Mountain and Greenland cyclogenesis are reduced, while Gulf Stream cyclogenesis is enhanced. The analyses are consistent with stationary waves and transient eddies acting to weaken the climatological ridge over the northeastern Pacific, creating a more zonal Pacific jet; downstream, transient eddies with a cyclonic tilt push the North Atlantic jet equatorward, favoring Gulf Stream cyclogenesis. Anomalies in cyclogenesis frequencies, and the relative roles of transient and stationary waves, during eastern Pacific El Niño winters are associated with larger uncertainties.
An integrated design of self-care textile wearables: exploration of thermal-stimuli effects and drug delivery function
Authors: Wai Cheung Tin , Yang Chenxiao , Li Li 
Published: September 2018

Fiber technology has become increasingly essential in various industries, such as the fashion clothing, medical, cosmetic and upholstery industries. It can be used to overcome some existing challenges of textile–skin interaction in response to medical functions. This research aims to study the thermal-stimuli effects and biological performances of drug delivery textiles so as to develop a personal self-care textile that is wearable for a wide range of adaptive medical treatments. The proposed study is interdisciplinary and focuses on the following: (1) developing a long-term continuous self-care drug delivery textile wearable for patients by using different textile materials and structure layering; (2) examining the loading capability of synthetic staple crimped hollow fibers in the assembly of the non-woven structure; (3) comparing the drug loading performance between direct infiltration with magnetic stirring and vacuum loading; (4) observing the thermal distribution of the thermal-stimuli drug delivery textile layers. Designing a specially made textile wearable for breast cancer patients (i.e. a bra for females and a sweatshirt/pullover for males) is a conceptual example of the proposed self-care textile wearable. Silver-coated conductive yarns were fabricated into hollow fiber-based non-woven fabrics for thermal stimulation. Significant drug delivery through the non-wovens was shown by the anti-breast cancer analysis. Drugs in different phases, liquid and crystal solid, could be carried by the lumens of the hollow fibers. If the proposed study is successfully commercialized, it will be a great technological breakthrough in preparing a future generation of drug delivery medical textiles. A variety of medical applications can hence be provided and it could also be an alternative for topical healthcare.
A study of linear PMSM driven ropeless elevators
Authors: So Albert , Chan WL 
Published: September 2018

In recent years, buildings have become taller and wider. The conventional approach of one roped elevator car per hoistway seems increasingly impractical. The idea of ropeless elevators using linear motors was proposed more than 30 years ago, but it was merely treated as wishful thinking by the industry at that time due to lots of safety concerns. And discussion by the industry has mainly been qualitative in nature. In recent years, an international manufacturer announced the development of a prototype and the world's first installation may probably be open to public before the end of 2018. So far, academic studies have mainly focused on the study of linear motors with generic applications, while this paper focuses on the performance of the motor drive from an elevator's point of view. In this paper, we investigate the mechanism of the drive, and the linear permanent magnet synchronous motor and, by discretizing the equations of the full mathematical model, we fine tune the parameters and design suitable controllers. We evaluate its performance by computer simulation, based on the necessary kinematics of a real elevator, so as to arrive at some design guidelines. Finally, the most critical safety concern, i.e. free fall during a total power failure, is quantitatively studied by short circuiting all motor windings. Methods to achieve a reasonably constant and low descending speed, have been studied with parameters estimated analytically, and are verified by simulation. For the sake of illustrating the concept as an initial trial, simplified circuit models, controllers and sensors are all assumed as being ideal. It is hoped that this paper will stimulate the research interest of both the academic world and the industry, while the inclusion of more losses, armature reactions, and imperfections, etc., could be tackled in a further study. Practical application: The application of one roped elevator car in taller and wider buildings seems increasingly impractical. This paper considers the analysis of the application of ropeless elevators using linear motors focusing on the performance of the motor drive from an elevator's point of view. A basic mathematical framework is developed to study and design the controllers and drive of a multi-car elevator system by using linear permanent magnet synchronous motors with emphasis on the elevator performance as a whole system. The paper is aimed at stimulating research interest to drive the appropriate analysis and application of linear permanent magnet synchronous motor driven ropeless elevators.
Worsening Knee Osteoarthritis Features on Magnetic Resonance Imaging 1 to 5 Years After Anterior Cruciate Ligament Reconstruction
Authors: Patterson Brooke E. , Culvenor Adam G. , Barton Christian J. , Guermazi Ali , Stefanik Joshua J. , Morris Hayden G. , Whitehead Timothy S. , Crossley Kay M. 
Published: September 2018

Background: An anterior cruciate ligament (ACL) injury is a well-established risk factor for the long-term development of radiographic osteoarthritis (OA). However, little is known about the early degenerative changes (ie, <5 years after injury) of individual joint features (ie, cartilage, bone marrow), which may be reversible and responsive to interventions. Purpose: To describe early degenerative changes between 1 and 5 years after ACL reconstruction (ACLR) on magnetic resonance imaging (MRI) and explore participant characteristics associated with these changes. Study Design: Case-control study; Level of evidence, 3. Methods: Seventy-eight participants (48 men; median age, 32 years; median body mass index [BMI], 26 kg/m2) underwent 3.0-T MRI at 1 and 5 years after primary hamstring autograft ACLR. Early tibiofemoral and patellofemoral OA features were assessed with the MRI Osteoarthritis Knee Score. The primary outcome was worsening (ie, incident or progressive) cartilage defects, bone marrow lesions (BMLs), osteophytes, and meniscal lesions. Logistic regression with generalized estimating equations evaluated participant characteristics associated with worsening features. Results: Worsening of cartilage defects in any compartment occurred in 40 (51%) participants. Specifically, worsening in the patellofemoral and medial and lateral tibiofemoral compartments was present in 34 (44%), 8 (10%), and 10 (13%) participants, respectively. Worsening patellofemoral and medial and lateral tibiofemoral BMLs (14 [18%], 5 [6%], and 10 [13%], respectively) and osteophytes (7 [9%], 8 [10%], and 6 [8%], respectively) were less prevalent, while 17 (22%) displayed deteriorating meniscal lesions. Worsening of at least 1 MRI-detected OA feature, in either the patellofemoral or tibiofemoral compartment, occurred in 53 (68%) participants. Radiographic OA in any compartment was evident in 5 (6%) and 16 (21%) participants at 1 and 5 years, respectively. A high BMI (>25 kg/m2) was consistently associated with elevated odds (between 2- and 5-fold) of worsening patellofemoral and tibiofemoral OA features. Conclusion: High rates of degenerative changes occur in the first 5 years after ACLR, particularly the development and progression of patellofemoral cartilage defects. Older patients with a higher BMI may be at particular risk and should be educated about this risk.
Clinical Outcomes of Multifocal Osteochondral Allograft Transplantation of the Knee: An Analysis of Overlapping Grafts and Multifocal Lesions
Authors: Cotter Eric J. , Hannon Charles P. , Christian David R. , Wang Kevin C. , Lansdown Drew A. , Waterman Brian R. , Frank Rachel M. , Cole Brian J. 
Published: September 2018

Background: There is a paucity of literature regarding the outcomes of adjacent-plug osteochondral allograft transplantation (OCA) for irregular or ovoid lesions and multifocal OCA for multicompartmental, focal lesions. Purpose: To quantify the survival of multiplug OCA for larger, high-grade chondral lesions with the “snowman” technique versus that of multicompartmental or bipolar OCA. Study Design: Case series; Level of evidence, 4. Methods: All patients who underwent primary, multiplug OCA for large unicondylar, multicompartmental (eg, bipolar patellofemoral and condylar, bicondylar), or bipolar chondral defects (ie, patellofemoral) with a minimum 2-year follow-up by a single surgeon from April 1, 2003, to April 1, 2015, were analyzed. Failure was defined as revision OCA, conversion to arthroplasty, or gross appearance of graft degeneration on second-look arthroscopic surgery. Results: Twenty-six patients (28 knees) were identified, with 22 patients (24 knees; 50% female; mean age, 31.9 ± 9.1 years) having at least 2-year clinical follow-up (85.7%). Nine patients (9 knees) underwent isolated, condylar OCA with the snowman technique and had a mean follow-up of 7.4 ± 3.6 years (range, 1.38-11.14 years), while 13 additional patients (15 knees) underwent multifocal OCA and had a mean follow-up of 6.4 ± 3.9 years (range, 2.07-12.38 years). Reoperations were common, with 44.4% (n = 4) of the snowman group and 20.0% (n = 3) of the multifocal group undergoing at least 1 reoperation. There were 3 failures (33.3%) in the snowman group at a mean 7.7 ± 5.5 years and 1 failure (6.7%) in the multifocal group at 4.5 ± 0.0 years, with all undergoing secondary total knee arthroplasty. Patients who underwent snowman OCA demonstrated significant postoperative improvement in the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscore and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) overall score ( P < .05 for both). Patients who underwent multifocal OCA demonstrated significant improvement in the International Knee Documentation Committee score; KOOS symptoms, activities of daily living, sport, and quality of life subscores; WOMAC stiffness, function, and overall subscores; and 12-Item Short Form Health Survey physical component summary score ( P < .05 for all). Conclusion: Patients who underwent unicondylar, multiplug OCA using the snowman technique demonstrated inferior clinical outcomes, higher reoperation rates, and greater failure rates than those who underwent isolated single-graft transplantation. By contrast, multifocal OCA may be a viable knee preservation technique for young, active patients with multicompartmental chondral disease, leading to improved clinical outcomes and low reoperation and failure rates at midterm follow-up.
Polystyrene-Organoclay Nanocomposites Prepared via In-Situ Emulsion Polymerization
Authors: Mocan M. , Uyanık N. 
Published: September 2018

In this study, polystyrene-clay nanocomposites (PSNC's) were prepared via in-situ bulk and in-situ emulsion polymerization. The effect of organoclay and the architecture of surfactant were investigated. For the investigation of the effect of surfactant, organoclays were synthesized containing clay modifiers having different structures. Trimethylhexadecyl ammonium chloride, dimethylbenzylhexadecyl ammonium chloride and dimethylbenzyl(4-vinyl) hexadecyl ammonium chloride, which is synthesized in laboratory, modified clays were synthesized. Pristine polystyrene (PS) was synthesized by bulk and emulsion polymerization for comparison, and PSNC's containing 3 wt.% organoclays were prepared by both these polymerization methods. Structural analysis of synthesized surfactant was identified by Nuclear Magnetic Resonance (NMR) Spectrometer. The interlayer spacing of silicate layers and the morphology of samples were examined by using the X-ray Diffraction (XRD) Spectrometer and Scanning Electron Microscopy (SEM) images, respectively. Thermal properties of nanocomposites were determined by Thermogravimetric analyzer (TGA) and Differential Scanning Calorimeter (DSC). It is observed that organoclays and PS were compatible to each other and each organoclay could form a nanocomposite structure with PS. PSNC's exhibited better properties than pristine PS. Nanocomposites prepared by in-situ emulsion polymerization resulted with better thermal properties and higher interlayer distances than that prepared by in-situ bulk polymerization. In order to improve some properties of PS such as thermal stability, preparation of PSNC's by in-situ emulsion polymerization has been suggested.
Modified Pet Fibres for Metal Ion and Dye Removal from Aqueous Media
Authors: Abdouss Majid , Shoushtari Ahmad Mousavi , Shamloo Nasrin , Haji Aminoddin 
Published: September 2018

In this study, poly(ethylene terephthalate) (PET) fibres were modified with methacrylic acid (MAA) to provide new chelating fibres. Benzoyl peroxide (BPO) was used as initiator. To increase the grafting yield, a pretreatment with formaldehyde was done, which increased the efficiency of grafting treatment by connecting –CH2OH groups to the fibres' polymeric chains. The effect of reaction parameters including methacrylic acid concentration, benzoyl peroxide concentration, reaction time and temperature on grafting yield were studied. The extent of fibre modification was characterized with FT-IR spectroscopy, thermo-gravimetric analysis (TGA) and SEM. The ability of modified fibres to adsorb Cu2+ and Pb2+ ions from aqueous media was determined using atomic absorption spectroscopy. The results confirmed that the methacrylic acid grafted PET fibres could remove Cu2+ and Pb2+ ions from water efficiently. Also, the modified fibre was used for basic dye adsorption from water and showed a great capacity for removal of cationic dyes from aqueous media.