bluuebunny/crossref_metadata_2025 huggingface dataset:
A Challenging Case of Acute Mercury Toxicity
Authors: Nayfeh Ali , Kassim Thamer , Addasi Noor , Alghoula Faysal , Holewinski Christopher , Depew Zachary
Published: February 2018

Background. Mercury exists in multiple forms: elemental, organic, and inorganic. Its toxic manifestations depend on the type and magnitude of exposure. The role of colonoscopic decompression in acute mercury toxicity is still unclear. We present a case of acute elemental mercury toxicity secondary to mercury ingestion, which markedly improved with colonoscopic decompression. Clinical Case. A 54-year-old male presented to the ED five days after ingesting five ounces (148 cubic centimeters) of elemental mercury. Examination was only significant for a distended abdomen. Labs showed elevated serum and urine mercury levels. An abdominal radiograph showed radiopaque material throughout the colon. Succimer and laxatives were initiated. The patient had recurrent bowel movements, and serial radiographs showed interval decrease of mercury in the descending colon with interval increase in the cecum and ascending colon. Colonoscopic decompression was done successfully. The colon was evacuated, and a repeat radiograph showed decreased hyperdense material in the colon. Three months later, a repeat radiograph showed no hyperdense material in the colon. Conclusion. Ingested elemental mercury can be retained in the colon. Although there are no established guidelines for colonoscopic decompression, our patient showed significant improvement. We believe further studies on this subject are needed to guide management practices.
Intermittent Control for Cluster‐Delay Synchronization in Directed Networks
Authors: Zhang Jianbao , Wang Yi , Ma Zhongjun , Qiu Jianlong , Alsaadi Fawaz
Published: February 2018

We investigate cluster‐delay synchronization of a directed network possessing cluster structures by designing an intermittent control protocol. Based on Lyapunov stability theory, we proved that synchronization can be realized for oscillators in the same cluster and cluster‐delay synchronization can be realized for the whole network. By simplifying the obtained sufficient conditions, we carry out a succinct and utilitarian corollary. In addition, comparative researches are carried out to show the differences and the usefulness of the obtained results with respect to other similar controllers from the recent literature. Finally we provide two numerical examples to show the effectiveness of the control schemes.
Vegetarian Diet and Cardiometabolic Risk among Asian Indians in the United States
Authors: Misra Ranjita , Balagopal Padmini , Raj Sudha , Patel Thakor G.
Published: February 2018

Research studies have shown that plant-based diets confer cardiovascular and metabolic health benefits. Asian Indians (AIs) in the US (who have often followed plant-based diets) have elevated risk for chronic diseases such as diabetes, metabolic syndrome, and obesity suggesting ethnic vulnerability that imply genetic and/or lifestyle causative links. This study explored the association between this ethnic group and diabetes, obesity, and metabolic syndrome after controlling for demographics, acculturation, family history of diabetes, and lifestyle and clinical risk factors. The sample comprised of 1038 randomly selected adult AIs in seven US sites. Prevalence and metabolic syndrome was estimated, and obesity was calculated using the WHO Asian criteria. Multivariate analysis included multinomial logistic regression. The mean age and length of residency in the US were 47 and 18.5 years, respectively. The majority of respondents were vegetarians (62%) and educated. A vegetarian lifestyle was associated with females, food label users, respondents with poor/fair current health status, less acculturated, and those who reported their diet had not changed after coming to the US. Vegetarian status was a protective factor and lowered the risk for diabetes but not for metabolic syndrome and obesity in the regression model. Results provide a firm basis for educational programs.
International Network Performance and Security Testing Based on Distributed Abyss Storage Cluster and Draft of Data Lake Framework
Authors: Cha ByungRae , Park Sun , Kim JongWon , Pan SungBum , Shin JuHyun
Published: February 2018

The megatrends and Industry 4.0 in ICT (Information Communication & Technology) are concentrated in IoT (Internet of Things), BigData, CPS (Cyber Physical System), and AI (Artificial Intelligence). These megatrends do not operate independently, and mass storage technology is essential as large computing technology is needed in the background to support them. In order to evaluate the performance of high-capacity storage based on open source Ceph, we carry out the network performance test of Abyss storage with domestic and overseas sites using KOREN (Korea Advanced Research Network). And storage media and network bonding are tested to evaluate the performance of the storage itself. Additionally, the security test is demonstrated by Cuckoo sandbox and Yara malware detection among Abyss storage cluster and oversea sites. Lastly, we have proposed the draft design of Data Lake framework in order to solve garbage dump problem.
Dedolomitization Potential of Fluids from Gypsum-to-Anhydrite Conversion: Mass Balance Constraints from the Late Permian Zechstein-2-Carbonates in NW Germany
Authors: Hallenberger M. , Reuning L. , Schoenherr J.
Published: February 2018

The Zechstein-2-Carbonates represent one of the most prolific hydrocarbon systems of Central Europe. Carbonate reservoir quality is primarily controlled by mineralogy, with dolomite representing moderate-to-good porosities and calcite commonly representing low porosities. Current models suggest that this calcite is the result of a basin-wide phase of dedolomitization. The calcium (Ca) source for the dedolomites is thought to be derived from the fluids liberated during gypsum-to-anhydrite conversion. We present an easy-to-use and generally applicable template to estimate the dedolomitization potential of these fluids. Depending on reaction stoichiometry, salinity, and temperature, we estimate that between2.8⁎10−3 m3and6.2⁎10−3 m3of calcite may replace dolomite for each m3of anhydrite created. Within the constraints dictated by the environment of the late Permian Zechstein basin, we estimate that about5⁎10−3 m3of dedolomite is created for each m3of anhydrite. Mass balance constraints indicate that fluids derived from gypsum-to-anhydrite conversion account for less than 1% of the observed dedolomite in most of the studied industry wells from northern Germany.
Identifying Elastic and Viscoelastic Material Parameters by Means of a Tikhonov Regularization
Authors: Diebels Stefan , Scheffer Tobias , Schuster Thomas , Wewior Aaron
Published: February 2018

For studying the interaction of displacements, stresses, and acting forces for elastic and viscoelastic materials, it is of utmost importance to have a decent mathematical model available. Usually such a model consists of a coupled set of nonlinear differential equations together with appropriate boundary conditions. However, since the different material classes vary significantly with respect to their physical and mechanical behavior, the parameters which appear in these equations are unknown and therefore have to be determined before the equations can be used for further investigations or simulations. It is this very step which is addressed in this article where we consider elastic as well as viscoelastic material behavior. The idea is to compute the parameters as solutions of a minimization problem for Tikhonov functionals. Tikhonov regularization is a well-established solution technique for tackling inverse problems. On the one hand, it assures a computation that is stable with respect to noisy input data, and on the other hand, it involves desired a priori information on the solution. In this article we develop problem adapted Tikhonov functionals and prove that a Tikhonov regularization improves the accuracy especially when the underlying system is ill-conditioned.
Searching for Clinically Relevant Biomarkers in Geriatric Oncology
Authors: Katsila Theodora , Patrinos George P. , Kardamakis Dimitrios
Published: February 2018

Ageing, which is associated with a progressive decline and functional deterioration in multiple organ systems, is highly heterogeneous, both inter- and intraindividually. For this, tailored-made theranostics and optimum patient stratification become fundamental, when decision-making in elderly patients is considered. In particular, when cancer incidence and cancer-related mortality and morbidity are taken into account, elderly patient care is a public health concern. In this review, we focus on oncogeriatrics and highlight current opportunities and challenges with an emphasis on the unmet need of clinically relevant biomarkers in elderly cancer patients. We performed a literature search on PubMed and Scopus databases for articles published in English between 2000 and 2017 coupled to text mining and analysis. Considering the top insights, we derived from our literature analysis that information knowledge needs to turn into knowledge growth in oncogeriatrics towards clinically relevant biomarkers, cost-effective practices, updated educational schemes for health professionals (in particular, geriatricians and oncologists), and awareness of ethical issues. We conclude with an interdisciplinary call to omics, geriatricians, oncologists, informatics, and policy-makers communities thatBig Datashould be translated into decision-making in the clinic.
Automatic Lateralization of Temporal Lobe Epilepsy Based on MEG Network Features Using Support Vector Machines
Authors: Wu Ting , Chen Duo , Chen Qiqi , Zhang Rui , Zhang Wenyu , Li Yuejun , Zhang Ling , Liu Hongyi , Wan Suiren , Jiang Tianzi , Zhang Junpeng
Published: February 2018

Correct lateralization of temporal lobe epilepsy (TLE) is critical for improving surgical outcomes. As a relatively new noninvasive clinical recording system, magnetoencephalography (MEG) has rarely been applied for determining lateralization of unilateral TLE. Here we propose a framework for using resting‐state brain‐network features and support vector machine (SVM) for TLE lateralization based on MEG. We recruited 15 patients with left TLE, 15 patients with right TLE, and 15 age‐ and sex‐matched healthy controls. The lateralization problem was then transferred into a series of binary classification problems, including left TLE versus healthy control, right TLE versus healthy control, and left TLE versus right TLE. Brain‐network features were extracted for each participant using three network metrics (nodal degree, betweenness centrality, and nodal efficiency). A radial basis function kernel SVM (RBF‐SVM) was employed as the classifier. The leave‐one‐subject‐out cross‐validation strategy was used to test the ability of this approach to overcome individual differences. The results revealed that the nodal degree performed best for left TLE versus healthy control and right TLE versus healthy control, with accuracy of 80.76% and 75.00%, respectively. Betweenness centrality performed best for left TLE versus right TLE with an accuracy of 88.10%. The proposed approach demonstrated that MEG is a good candidate for solving the lateralization problem in unilateral TLE using various brain‐network features.
Mutual Coupling Reduction of E-Shaped MIMO Antenna with Matrix of C-Shaped Resonators
Authors: Alsultan Raghad Ghalib Saadallah , Ögücü Yetkin Gölge
Published: February 2018

E-shaped multiple-input-multiple-output (MIMO) microstrip antenna systems operating in WLAN and WiMAX bands (between 5 and 7.5 GHz) are proposed with enhanced isolation features. The systems are comprised of two antennas that are placed parallel and orthogonal to each other, respectively. According to the simulation results, the operating frequency of the MIMO antenna system is 6.3 GHz, and mutual coupling is below −18 dB in a parallel arrangement, whereas they are 6.4 GHz and −25 dB, respectively, in the orthogonal arrangement. The 2 × 3 matrix of C-shaped resonator (CSR) is proposed and placed between the antenna elements over the substrate, to reduce the mutual coupling and enhance the isolation between the antennas. More than 30 dB isolation between the array elements is achieved at the resonant frequency for both of the configurations. The essential parameters of the MIMO array such as mutual coupling, surface current distribution, envelop correlation coefficient (ECC), diversity gain (DG), and the total efficiency have been simulated to verify the reliability and the validity of the MIMO system in both parallel and orthogonal configurations. The experimental results are also provided and compared for the mutual coupling with simulated results. An adequate match between the measured and simulated results is achieved.
Vγ4+ T Cells: A Novel IL-17-ProducingγδT Subsets during the Early Phase of Chlamydial Airway Infection in Mice
Authors: Sun Li-da , Qiao Sai , Wang Yue , Pang Gao-ju , Zha Xiao-yu , Liu Teng-Li , Zhao Hui-Li , Liang Ju-You , Zheng Ning-bo , Tan Lu , Zhang Hong , Bai Hong
Published: February 2018

Our previous studies showed thatγδT cells provided immune protection against Chlamydialmuridarum(Cm), an obligate intracellular strain of chlamydia trachomatis, lung infection by producing abundant IL-17. In this study, we investigated the proliferation and activation of lungγδT cell subsets, specifically the IL-17 and IFNγproduction by them following Cm lung infection. Our results found that fiveγδT cell subsets, Vγ1+ T, Vγ2+ T, Vγ4+ T, Vγ5+ T, and Vγ6+ T, expressed in lungs of naïve mice, while Cm lung infection mainly induced the proliferation and activation of Vγ4+ T cells at day 3 p.i., following Vγ1+ T cells at day 7 p.i. Cytokine detection showed that Cm lung infection induced IFNγsecretion firstly by Vγ4+ T cells at very early stage (day 3) and changed to Vγ1+ T cells at midstage (day 7). Furthermore, Vγ4+ T cell is the mainγδT cell subset that secretes IL-17 at the very early stage of Cm lung infection and Vγ1+ T cell did not secrete IL-17 during the infection. These findings provide in vivo evidence that Vγ4+T cells are the major IL-17 and IFNγ-producingγδT cell subsets at the early period of Cm lung infection.
Multiclass Informative Instance Transfer Learning Framework for Motor Imagery-Based Brain-Computer Interface
Authors: Hossain Ibrahim , Khosravi Abbas , Hettiarachchi Imali , Nahavandi Saeid
Published: February 2018

A widely discussed paradigm for brain-computer interface (BCI) is the motor imagery task using noninvasive electroencephalography (EEG) modality. It often requires long training session for collecting a large amount of EEG data which makes user exhausted. One of the approaches to shorten this session is utilizing the instances from past users to train the learner for the novel user. In this work, direct transferring from past users is investigated and applied to multiclass motor imagery BCI. Then, active learning (AL) driven informative instance transfer learning has been attempted for multiclass BCI. Informative instance transfer shows better performance than direct instance transfer which reaches the benchmark using a reduced amount of training data (49% less) in cases of 6 out of 9 subjects. However, none of these methods has superior performance for all subjects in general. To get a generic transfer learning framework for BCI, an optimal ensemble of informative and direct transfer methods is designed and applied. The optimized ensemble outperforms both direct and informative transfer method for all subjects except one in BCI competition IV multiclass motor imagery dataset. It achieves the benchmark performance for 8 out of 9 subjects using average 75% less training data. Thus, the requirement of large training data for the new user is reduced to a significant amount.
Laminin 521 Stabilizes the Pluripotency Expression Pattern of Human Embryonic Stem Cells Initially Derived on Feeder Cells
Authors: Albalushi Halima , Kurek Magdalena , Karlsson Leif , Landreh Luise , Kjartansdóttir Kristín Rós , Söder Olle , Hovatta Outi , Stukenborg Jan-Bernd
Published: February 2018

Human embryonic stem (hES) cells represent an important tool to study early cell development. The previously described use of human recombinant laminin (LN) 521 represented a step forward in generating clinically safe culture conditions. To test the short-term effect of LN521 on cultured hES cells, five male hES cell lines were cultured on human foreskin fibroblasts (hFFs), Matrigel, LN521, and LN121 and characterized by qPCR, immunofluorescence analysis, as well as their potential for three-germ layer differentiation. Variations in gene expression related to pluripotency, stemness, and testicular cells at different passages and culture conditions were evaluated by qPCR. All cell lines expressed pluripotency markers at protein and RNA level and were able to differentiate into cell types of the three germ layers after being cultured on LN521 for nine passages. Reduction in variation of pluripotency marker expression could be observed after culturing the cells on LN521 for nine passages. hES cells cultured on LN521 exhibited less differentiation, faster cell growth, and attachment when compared to hES cells cultured on LN121 or Matrigel. Our results indicate a positive effect of LN521 in stabilizing pluripotency gene expression and might be the first step towards more controllable and robust culture conditions for hES cells.
Metastases to Both Parotid Glands Six and Twelve Years after Resection of Renal Cell Carcinoma
Authors: Franzen Achim M. , Glitzky Shirrell , Moganti Ashok , Lippek Frank , Coordes Annekatrin
Published: February 2018

Metastases of renal cell carcinoma (RCC) involving the parotid gland are very rare. We present to our knowledge the first case of a 74-year-old woman with metastases of an RCC which affected both parotid glands six and twelve years following curative therapy.
Candida krusei Empyema Thoracis: A Community-Acquired Infection Requiring a High Index of Suspicion
Authors: Bukamur Hazim , Ahmed Waseem , Numan Yazan , Shahoub Ibrahim , Zeid Fuad
Published: February 2018

Empyema thoracis is a serious condition characterized by the accumulation of purulent fluid in the pleural cavity, typically following a pneumonia, subdiaphragmatic abscess, or esophageal rupture. Fungal empyema thoracis is a rare form of this condition with especially high mortality, in which the most frequently isolated fungus is Candida spp. This article presents a 74-year-old female with Candida krusei pneumonia and a complicated hospital course, initially presenting with nausea, vomiting, and dysphagia. She was initially suspected to have community-acquired pneumonia and was started on azithromycin and ceftriaxone. Worsening respiratory function led to the diagnosis of hydropneumothorax. Pleural fluid and an independent sample of pus and pleural tissue grew Candida krusei, giving the diagnosis of fungal empyema. With further respiratory deterioration, the patient was intubated and switched to piperacillin/tazobactam and micafungin. Decortication with extensive pleural peel and removal of foul-smelling pus and food particles within the chest was performed. This further lead to confirmation of esophageal perforation, and she was started on voriconazole and meropenem. After developing septic shock, the patient was managed with phenylephrine and vasopressin. Finally, after improving she was weaned off pressors and extubated, followed by an esophagogastroduodenoscopy (EDG) with pneumatic balloon dilation and WallFlex stent placement. This patient’s case demonstrated an example of empyema thoracis, which required a high index of suspicion since the presentation was with a community-acquired infection. Candida empyema thoracis may be a complication of operation, gastroesophageal fistula, and spontaneous esophageal rupture. On the other hand, the course of this patient’s hospital stay progressed from esophageal perforation to Candida krusei pneumonia, empyema, and pneumothorax. Thus, community-acquired fungal empyema should be considered in patients with respiratory symptoms and suspected esophageal perforation; nevertheless, after a diagnosis of fungal empyema, esophageal perforation should also be ruled out in addition to other causes like pneumonia, subphrenic abscess, and hematogenous spread. Improved communication between clinicians and microbiologists can lead to early diagnosis and a reduction in the morbidity and mortality of this condition.
Salivary Levels of IL-6 and IL-17 Could Be an Indicator of Disease Severity in Patients with Calculus Associated Chronic Periodontitis
Authors: Batool Husniah , Nadeem Ahmed , Kashif Muhammad , Shahzad Faheem , Tahir Romeeza , Afzal Nadeem
Published: February 2018

Background/Purpose. Chronic periodontitis is an inflammatory disease of gums that causes loss of supporting structures of teeth, that is, gingiva, periodontal ligament, cementum, and alveolar bone. Levels of various cytokines in the serum, gingival tissues, and gingival crevicular fluid in patients with chronic periodontitis have been studied, but limited data are available on the level of cytokines in saliva. Therefore, a study was designed to determine levels of salivary IL-6 and IL-17 in patients with calculus associated chronic periodontitis. Materials and Methods. It was a comparative, cross-sectional study that is comprised of 41 healthy controls and 41 calculus associated chronic periodontitis patients (CP patients). According to the degree of attachment loss, CP patients were subcategorized as mild (CAL 1-2 mm), moderate (CAL 3-4 mm), and severe (CAL > 5 mm) forms of periodontitis. Salivary levels of IL-6 and IL-17 were determined using enzyme-linked immunosorbent assay (ELISA) technique. Data was analyzed using SPSS 20.0. Results. Between healthy controls and CP patients (moderate and severe disease), a statistically significant difference was observed in the concentrations of IL-6 and IL-17. In CP patients, the highest mean ± SD of salivary IL-6 and IL-17 was observed in severe CP, followed by moderate and mild CP. Regarding level of IL-6, a statistically significant difference was observed between mild and severe disease and between moderate and severe subcategories of CP patients. Similarly, statistically significant difference was observed in the level of IL-17 between mild and moderate, mild and severe disease, and moderate and severe disease. Conclusion. The levels of salivary IL-6 and IL-17 were increased significantly in calculus associated CP patients as compared to healthy controls and these levels increased with the progression of CP. Clinical Significance. Salivary levels of IL-6 and IL-17 may help in the subcategorization of CP.
An Improved EMD‐Based Dissimilarity Metric for Unsupervised Linear Subspace Learning
Authors: Yu Xiangchun , Yu Zhezhou , Pang Wei , Li Minghao , Wu Lei
Published: February 2018

We investigate a novel way of robust face image feature extraction by adopting the methods based on Unsupervised Linear Subspace Learning to extract a small number of good features. Firstly, the face image is divided into blocks with the specified size, and then we propose and extract pooled Histogram of Oriented Gradient (pHOG) over each block. Secondly, an improved Earth Mover’s Distance (EMD) metric is adopted to measure the dissimilarity between blocks of one face image and the corresponding blocks from the rest of face images. Thirdly, considering the limitations of the original Locality Preserving Projections (LPP), we proposed the Block Structure LPP (BSLPP), which effectively preserves the structural information of face images. Finally, an adjacency graph is constructed and a small number of good features of a face image are obtained by methods based on Unsupervised Linear Subspace Learning. A series of experiments have been conducted on several well‐known face databases to evaluate the effectiveness of the proposed algorithm. In addition, we construct the noise, geometric distortion, slight translation, slight rotation AR, and Extended Yale B face databases, and we verify the robustness of the proposed algorithm when faced with a certain degree of these disturbances.
Association of Markers of Proinflammatory Phenotype and Beige Adipogenesis with Metabolic Syndrome in Chinese Centrally Obese Adults
Authors: Leung Wilson K. C. , Yu Angus P. , Lai Christopher W. K. , Siu Parco M.
Published: February 2018

Background. Visceral adiposity is associated with higher productions of C-reactive protein (CRP) and interleukin-6 (IL-6). Inflammation of obese adipose tissues could contribute to systemic metabolic dysregulation, especially thermogenic activity of white adipose tissues, namely, beige adipogenesis, characterized by altered irisin expression. Thus, we investigated the roles of inflammation and adipocyte beiging in Chinese centrally obese (CO) adults with metabolic syndrome (MetS). Methods. This cross-sectional study was conducted on 54 CO and 58 non-CO subjects drawn from 1492 Chinese people with age and sex matched during November 2010 and August 2013. Twenty (37.0%) of the CO subjects fulfilled the IDF worldwide definition of MetS. Serum CRP, IL-6, and irisin levels were examined. Results. Higher CRP and IL-6, but lower irisin, levels were manifested in MetS versus non-MetS subjects with or without CO. Multiple linear regression identified high-density lipoprotein cholesterol level as the only independent risk factor for irisin level. Categorized by median of CRP and IL-6 levels, a lower irisin level was only observed in high CRP group. Conclusion. Under the condition of central obesity, chronic inflammation and impaired beige adipogenesis are associated with MetS in Chinese adults.
Readiness of Sub-Saharan Africa Healthcare Systems for the New Pandemic, Diabetes: A Systematic Review
Authors: Nuche-Berenguer Bernardo , Kupfer Linda E.
Published: February 2018

Background. Effective health systems are needed to care for the coming surge of diabetics in sub-Saharan Africa (SSA). Objective. We conducted a systematic review of literature to determine the capacity of SSA health systems to manage diabetes. Methodology. We used three different databases (Embase, Scopus, and PubMed) to search for studies, published from 2004 to 2017, on diabetes care in SSA. Results. Fifty-five articles met the inclusion criteria, covering the different aspects related to diabetes care such as availability of drugs and diagnostic tools, the capacity of healthcare workers, and the integration of diabetes care into HIV and TB platforms. Conclusion. Although chronic care health systems in SSA have developed significantly in the last decade, the capacity for managing diabetes remains in its infancy. We identified pilot projects to enhance these capacities. The scale-up of these pilot interventions and the integration of diabetes care into existing robust chronic disease platforms may be a feasible approach to begin to tackle the upcoming pandemic in diabetes. Nonetheless, much more work needs to be done to address the health system-wide deficiencies in diabetes care. More research is also needed to determine how to integrate diabetes care into the healthcare system in SSA.
Vector Autoregressive Hierarchical Hidden Markov Models for Extracting Finger Movements Using Multichannel Surface EMG Signals
Authors: Malešević Nebojša , Marković Dimitrije , Kanitz Gunter , Controzzi Marco , Cipriani Christian , Antfolk Christian
Published: February 2018

We present a novel computational technique intended for the robust and adaptable control of a multifunctional prosthetic hand using multichannel surface electromyography. The initial processing of the input data was oriented towards extracting relevant time domain features of the EMG signal. Following the feature calculation, a piecewise modeling of the multidimensional EMG feature dynamics using vector autoregressive models was performed. The next step included the implementation of hierarchical hidden semi‐Markov models to capture transitions between piecewise segments of movements and between different movements. Lastly, inversion of the model using an approximate Bayesian inference scheme served as the classifier. The effectiveness of the novel algorithms was assessed versus methods commonly used for real‐time classification of EMGs in a prosthesis control application. The obtained results show that using hidden semi‐Markov models as the top layer, instead of the hidden Markov models, ranks top in all the relevant metrics among the tested combinations. The choice of the presented methodology for the control of prosthetic hand is also supported by the equal or lower computational complexity required, compared to other algorithms, which enables the implementation on low‐power microcontrollers, and the ability to adapt to user preferences of executing individual movements during activities of daily living.
Mass Spectrometry–Based Proteomics Reveals Potential Roles of NEK9 and MAP2K4 in Resistance to PI3K Inhibition in Triple-Negative Breast Cancers
Authors: Mundt Filip , Rajput Sandeep , Li Shunqiang , Ruggles Kelly V. , Mooradian Arshag D. , Mertins Philipp , Gillette Michael A. , Krug Karsten , Guo Zhanfang , Hoog Jeremy , Erdmann-Gilmore Petra , Primeau Tina , Huang Shixia , Edwards Dean P. , Wang Xiaowei , Wang Xuya , Kawaler Emily , Mani D.R. , Clauser Karl R. , Gao Feng , Luo Jingqin , Davies Sherri R. , Johnson Gary L. , Huang Kuan-lin , Yoon Christopher J. , Ding Li , Fenyö David , Ellis Matthew J. , Townsend R. Reid , Held Jason M. , Carr Steven A. , Ma Cynthia X.
Published: February 2018

Activation of PI3K signaling is frequently observed in triple-negative breast cancer (TNBC), yet PI3K inhibitors have shown limited clinical activity. To investigate intrinsic and adaptive mechanisms of resistance, we analyzed a panel of patient-derived xenograft models of TNBC with varying responsiveness to buparlisib, a pan-PI3K inhibitor. In a subset of patient-derived xenografts, resistance was associated with incomplete inhibition of PI3K signaling and upregulated MAPK/MEK signaling in response to buparlisib. Outlier phosphoproteome and kinome analyses identified novel candidates functionally important to buparlisib resistance, including NEK9 and MAP2K4. Knockdown of NEK9 or MAP2K4 reduced both baseline and feedback MAPK/MEK signaling and showed synthetic lethality with buparlisib in vitro. A complex in/del frameshift in PIK3CA decreased sensitivity to buparlisib via NEK9/MAP2K4–dependent mechanisms. In summary, our study supports a role for NEK9 and MAP2K4 in mediating buparlisib resistance and demonstrates the value of unbiased omic analyses in uncovering resistance mechanisms to targeted therapy.

Significance: Integrative phosphoproteogenomic analysis is used to determine intrinsic resistance mechanisms of triple-negative breast tumors to PI3K inhibition. Cancer Res; 78(10); 2732–46. ©2018 AACR.
JAK2 Inhibitor SAR302503 Abrogates PD-L1 Expression and Targets Therapy-Resistant Non–small Cell Lung Cancers
Authors: Pitroda Sean P. , Stack Melinda E. , Liu Gene-Fu , Song Sui-Sui , Chen Lucy , Liang Hua , Parekh Akash D. , Huang Xiaona , Roach Paul , Posner Mitchell C. , Weichselbaum Ralph R. , Khodarev Nikolai N.
Published: February 2018

Lung cancer is the leading cause of cancer-related deaths worldwide. Approximately 85% of all lung cancers are non–small cell histology [non–small cell lung cancer (NSCLC)]. Modern treatment strategies for NSCLC target driver oncogenes and immune checkpoints. However, less than 15% of patients survive beyond 5 years. Here, we investigated the effects of SAR302503 (SAR), a selective JAK2 inhibitor, on NSCLC cell lines and tumors. We show that SAR is cytotoxic to NSCLC cells, which exhibit resistance to genotoxic therapies, such as ionizing radiation, cisplatin, and etoposide. We demonstrate that constitutive IFN-stimulated gene expression, including an IFN-related DNA damage resistance signature, predicts for sensitivity to SAR. Importantly, tumor cell–intrinsic expression of PD-L1 is IFN-inducible and abrogated by SAR. Taken together, these findings suggest potential dual roles for JAK2 inhibitors, both as a novel monotherapy in NSCLCs resistant to genotoxic therapies, and in tandem with immune checkpoint inhibition. Mol Cancer Ther; 17(4); 732–9. ©2018 AACR.
SOCS3 Is Upregulated and Targeted by miR30a-5p in Allergic Rhinitis
Authors: Zhao Chun Yuan , Wang Wei , Yao Hong Chao , Wang Xin
Published: February 2018

Background: Suppressor of cytokine signaling 1 (SOCS1) and SOCS3 play important roles in T helper cell differentiation, which is involved with the pathologic mechanisms of allergic rhinitis (AR). The aim of this study was to evaluate the expression of SOCS1 and SOCS3 in AR and find their regulatory microRNAs (miRNAs) to provide a basis for the treatment of AR. Methods: The expression of SOCS1 and SOCS3 were analyzed by real-time PCR, immunohistochemistry, and Western blot. The correlative regulatory miRNAs were detected by real-time PCR. Luciferase assays and AR mouse model experiments were applied to identify correlative miRNAs that target SOCS3. Results: SOCS1 and SOCS3 mRNA were upregulated in the nasal mucosa and peripheral blood mononuclear cells of AR compared with controls. The expression of SOCS3 protein was significantly increased in the nasal mucosa of AR. The immunohistochemical staining results showed that SOCS3 was similarly localized in the superficial epithelium, submucosal glands, and vascular endothelium in the nasal mucosa of AR subjects and controls. However, SOCS3 protein was especially localized in the inflammatory cells, such as eosinophils, monocytes, and lymphocytes. Conclusions: SOCS3 was targeted by miR30a- 5p in AR. Further study should be performed to identify the regulatory effect of miR30a-5p in AR, which may provide insights into a new therapeutic strategy.
Humanized Exposures of Cefiderocol, a Siderophore Cephalosporin, Display Sustained in vivo Activity against Siderophore-Resistant Pseudomonas aeruginosa
Authors: Ghazi Islam M. , Monogue Marguerite L. , Tsuji Masakatsu , Nicolau David P.
Published: February 2018

We evaluated the in vivo efficacy of humanized exposures of cefiderocol, a novel siderophore cephalosporin, against a test panel of P. aeruginosa (PSA) previously shown to develop resistance to 2 preclinical candidate siderophores (MB-1 and SMC-3176). In the thigh infection model, the PSA bacterial density in untreated controls grew from 5.54 ± 0.23 to 8.68 ± 0.57 log10 CFU over 24 h. The humanized cefiderocol exposure resulted in >1 log10 CFU reduction in all 8 isolates, while MB-1 and SMC-3176 exhibited variable activity similar to that previously reported. Humanized exposures of cefepime and levofloxacin, acting as positive antimicrobial controls displayed activity consistent with that of the bacterial phenotypic susceptibility profiles. Cefiderocol manifested in vivo efficacy against all PSA isolates including those resistant to cefepime and levofloxacin in contrast to its predecessor siderophore compounds. These preclinical data are supportive of further evaluation of cefiderocol in the treatment of P. aeruginosa.
The True Meaning of the Work of Saturnino Herrán: The False
Critics
Authors: Mérida Carlos
Published: February 2018

The introductory essay places “The True Meaning of the Work of Saturnino Herrán: The False Critics” (1920), a piece of early criticism written by the Guatemalan artist Carlos Mérida during the first year he lived in Mexico City, within the contexts of the cosmopolitan milieu of post-Revolutionary Mexico and the artist's own trajectory. It suggests that the text both demonstrates intellectuals’ interest in questions of form and national art and Mérida's desire to provide a critical framework for his own paintings of indigenous Guatemalan and Mexican women. In “The True Meaning of the Work of Saturnino Herrán: The False Critics,” Mérida lashed out at Mexican critics for praising Herrán as the best and most Mexican painter of the time, arguing, instead that the realism and sentimentalism of Herrán's paintings dishonored national themes by presenting them as picturesque stereotypes. Published in the widely-read magazine El Universal Ilustrado, the text attacks Herrán's paintings and the critics who praise them while also arguing that the predominance of the artist is symptomatic of the predominant problem of the literary nature of Mexican artists’ engagement with autochthonous art and culture.
Does the use of a multi-trait, multi-test approach to measure animal personality yield different behavioural syndrome results?
Authors: Huang Ping , Kimball Rebecca T. , St. Mary Colette M.
Published: February 2018

A multi-trait, multi-test approach to investigate the convergence or discrimination between behavioural tests putatively targeting the same or different animal personality traits has been recommended, yet whether and how the approaches affect the identification of behavioural syndrome(s), the suite of correlated personality traits, requires investigation. Here, we used behavioural measures collected from five commonly used behavioural tests targeting three personality traits, evaluated their convergence/discrimination through exploratory factor analysis (EFA), and then explored whether the identification of syndrome changed based on the approach we used to quantify personality traits. Our results indicated that tests presumably targeting the same personality trait actually measured distinct behavioural aspects. Syndrome defined using correlation changed due to how we identified personality traits, but not when using structural equation models (SEMs). Overall, this study emphasizes that it is critical to clarify the approach and terms we use for ‘personality traits’ in the field of animal personality.
Individual Differences in Self-Rated Impulsivity Modulate the Estimation of Time in a Real Waiting Situation
Authors: Jokic Tijana , Zakay Dan , Wittmann Marc
Published: February 2018

In this study we investigated how individual differences regarding impulsivity and time perspective predict the experience of waiting during a time interval without distraction. Each participant (N = 82) filled out self-report questionnaires on impulsiveness (Barratt Impulsiveness Scale) and time perspective (Zimbardo Time Perspective Inventory). Participants were individually shut into an empty room for exactly 7.5 minutes and afterwards asked to report their subjective impressions regarding the experience of time, self and affective reactions. Correlation analyses showed that being more relaxed and having a positive feeling was related to shorter duration estimates and a perceived faster passage of time. Individual traits of impulsivity, present-hedonistic and present-fatalistic time orientation were associated with relative overestimation of duration and a perceived slower passage of time; future orientation was related to an underestimation of duration and a perceived faster passage of time. Multiple regression models show that impulsivity alone predicts the variance related to time estimation of the waiting period. Multiple path analyses reveal that individuals who are more impulsive are less relaxed while waiting and accordingly overestimate duration and feel a slower passage of time. Negative affect and an impulsive present orientation are related to an overestimation of duration and the feeling of a slower passage of time while waiting.
Cybersickness: a Multisensory Integration Perspective
Authors: Gallagher Maria , Ferrè Elisa Raffaella
Published: February 2018

In the past decade, there has been a rapid advance in Virtual Reality (VR) technology. Key to the user’s VR experience are multimodal interactions involving all senses. The human brain must integrate real-time vision, hearing, vestibular and proprioceptive inputs to produce the compelling and captivating feeling of immersion in a VR environment. A serious problem with VR is that users may develop symptoms similar to motion sickness, a malady calledcybersickness. At present the underlying cause of cybersickness is not yet fully understood. Cybersickness may be due to a discrepancy between the sensory signals which provide information about the body’s orientation and motion: in many VR applications, optic flow elicits an illusory sensation of motion which tells users that they are moving in a certain direction with certain acceleration. However, since users are not actually moving, their proprioceptive and vestibular organs provide no cues of self-motion. These conflicting signals may lead to sensory discrepancies and eventually cybersickness. Here we review the current literature to develop a conceptual scheme for understanding the neural mechanisms of cybersickness. We discuss an approach to cybersickness based on sensory cue integration, focusing on the dynamic re-weighting of visual and vestibular signals for self-motion.
The freshwater shrimp family Euryrhynchidae Holthuis, 1950 (Crustacea: Decapoda: Caridea) revisited, with a taxonomic revision of the genus Euryrhynchus Miers, 1878
Authors: PACHELLE PAULO P.G. , TAVARES MARCOS
Published: February 2018

The present revision is based on the largest sample of Euryrhynchidae Holthuis, 1950 studied to date, with special reference to Euryrhynchus Miers, 1878. The revision confirms the validity of the 8 currently recognized species of Euryrhynchidae and describes 2 new species related to Euryrhynchus amazoniensis Tiefenbacher, 1978: E. taruman sp. nov. and E. tuyuka sp. nov. The species Euryrhynchus amazoniensis, E. burchelli Calman, 1907, E. pemoni Pereira, 1985 and E. wrzesniowskii Miers, 1878 are redescribed and illustrated based on specimens from the type series and additional material. Additional diagnostic characters are proposed to differentiate the species of Euryrhynchus, previously separated only by the armature of the second pereopod carpus and merus.
How Well Does Noah-MP Simulate the Regional Mean and Spatial Variability of Topsoil Water Content in Two Agricultural Landscapes in Southwest Germany?
Authors: Poltoradnev M. , Ingwersen J. , Imukova K. , Högy P. , Wizemann H.-D. , Streck T.
Published: February 2018

The spatial variability of topsoil water content (SWC) is often expressed through the relationship between its spatial mean 〈θ〉 and standard deviation σθ. The present study tests the concept that a reasonably performing land surface model (LSM) should be able to produce σθ–〈θ〉 data pairs that fall into a polygon, spanned by the cloud of observed data and two anchor points: σθ at the permanent wilting point σθ–〈θwp〉 and σθ at saturation σθ–〈θs〉. A state-of-the-art LSM, Noah-MP, was driven by atmospheric forcing data obtained from eddy covariance field measurements in two regions of southwestern Germany, Kraichgau (KR) and Swabian Alb (SA). KR is characterized with deep loess soils, whereas the soils in SA are shallow, clayey, and stony. The simulations series were compared with SWC data from soil moisture networks operating in the two study regions. The results demonstrate that Noah-MP matches temporal 〈θ〉 dynamics fairly well in KR, but performs poorly in SA. The best match is achieved with the van Genuchten–Mualem representation of soil hydraulic functions and site-specific rainfall, soil texture, green vegetation fraction (GVF) and leaf area index (LAI) input data. Nevertheless, most of the simulated σθ–〈θ〉 pairs are located outside the envelope of measurements and below the lower bound, which shows that the model smooths spatial SWC variability. This can be mainly attributed to missing topography and terrain information and inadequate representation of spatial variability of soil texture and hydraulic parameters, as well as the model assumption of a uniform root distribution.
Do High-Frequency Radars Measure the Wave-Induced Stokes Drift?
Authors: Chavanne Cédric
Published: February 2018

High-frequency (HF) radars remotely measure ocean near-surface currents based on the Doppler shift of electromagnetic waves backscattered by surface gravity waves with half the electromagnetic wavelength, called Bragg waves. Since their phase velocity is affected not only by wave–current interactions with vertically sheared mean Eulerian currents but also by wave–wave interactions with all the other waves present at the sea surface, HF radars should measure a quantity related to the Stokes drift in addition to mean Eulerian currents. However, the literature is inconsistent—both theoretically and experimentally—on the specific expression and even on the existence of the Stokes drift contribution to the HF radar measurements. Three different expressions that have been proposed in the literature are reviewed and discussed in light of the relevant published experimental results: 1) the weighted depth-averaged Stokes drift, 2) the filtered surface Stokes drift, and 3) half of the surface Stokes drift. Effective measurement depths for these three expressions are derived for the Phillips wave spectrum. Recent experimental results tend to discard the second expression but are not inconsistent with the first and third expressions. The latter is physically appealing, since it is a quasi-Eulerian quantity that would be measured by a current meter at a fixed horizontal position but allowed to follow the free surface moving vertically up and down with the passage of the waves. A definitive answer will require further experimental investigations.
Effect of morphology on nanoparticle transport and deposition in human upper tracheobronchial airways
Authors: Shang Yidan , Tian Lin , Fan Yaming , Dong Jingliang , Inthavong Kiao , Tu Jiyuan
Published: February 2018

Aerosol transport and deposition in human lungs has attracted considerable attention in the past few years, as it has significant value to the study of toxicity consequence as well as therapeutic potential in occupational health and medical applications. In reproducing human tracheobronchial airways, two approaches were frequently taken: (1) anatomical realistic reconstruction through image scans (e.g. CT and MRI) or cadaver casts and (2) mathematical description using simplified models. Strengths and limitations are primarily focused on accuracy, resolution, repeatability, and computational\physical expenses. While both approaches were reported in literature, detailed comparison of aerosol transport and deposition in the two representations were scarcely performed, largely due to the challenge to acquire comprehensive data from the irregular structured airway replicas (approach 1). To fill the gap, the current study performed a numerical comparison of nanoparticle transport and deposition in human upper tracheobronchial airways by using an anatomical realistic reconstruction (through CT scans) and a mathematically simplified airway model. As the first step, the current study was focused on the variation in breathing airflow pattern and the effect towards fate of the inhaled nanoparticles in human upper tracheobronchial airways. The study provided important information to understand geometric sensitivity of nanoparticle modeling in the human tracheobronchial tree and is of significant value to predict the whole lung uptake of inhaled nanoparticles in the human respiratory system.