bluuebunny/crossref_metadata_2025 huggingface dataset:
Gametocidal genes ofAegilops: segregation distorters in wheat–Aegilopswide hybridization
Authors: Niranjana M.
Published: June 2017

Aegilops is a genus belonging to the family Poaceace, which have played an indispensible role in the evolution of bread wheat and continues to do so by transferring genes by wide hybridization. Being the secondary gene pool of wheat, gene transfer from Aegilops poses difficulties and segregation distortion is common. Gametocidal genes are the most well characterized class of segregation distorters reported in interspecific crosses of wheat with Aegilops. These “selfish” genetic elements ensure their preferential transmission to progeny at the cost of gametes lacking them without providing any phenotypic benefits to the plant, thereby causing a proportional reduction in fertility. Gametocidal genes (Gc) have been reported in different species of Aegilops belonging to the sections Aegilops (Ae. geniculata and Ae. triuncialis), Cylindropyrum (Ae. caudata and Ae. cylindrica), and Sitopsis (Ae. longissima, Ae. sharonensis, and Ae. speltoides). Gametocidal activity is mostly confined to 2, 3, and 4 homeologous groups of C, S, S1, Ssh, and Mggenomes. Removal of such genes is necessary for successful alien gene introgression and can be achieved by mutagenesis or allosyndetic pairing. However, there are some instances where Gc genes are constructively utilized for development of deletion stocks in wheat, improving genetic variability and chromosome engineering.
Casimir effect for Elko fields
Authors: Pereira S. H. , da Silva J. M. Hoff , dos Santos Rubia
Published: June 2017

The Casimir effect for mass dimension one fermion fields (sometimes called Elko) in (3 + 1) dimensions is obtained using Dirichlet boundary conditions. It is shown that the existence of a repulsive force is four times greater than the case of the scalar field. The precise reason for such differences are highlighted and interpreted, as well as the right parallel of the Casimir effect due to scalar and fermionic fields.
Momentum fractions carried by quarks and gluons in models of proton structure functions at small x
Authors: Choudhury D. K. , Saikia Baishali , Kalita K.
Published: June 2017

In this paper, we report an analysis of partial momentum fractions carried by quarks and gluons in six alternative phenomenological models of proton structure function valid in limited small [Formula: see text] regions: [Formula: see text], [Formula: see text] to 6; the limits being determined by phenomenological range of validity in each model. Since the physics of small [Formula: see text] is not completely understood at this point, we have considered both self-similarity-based as well as QCD-based models. The procedure by which one can determine the applicability ranges in [Formula: see text] and [Formula: see text] of the models is presented. We find that while the self-similarity-based models with linear rise in [Formula: see text] has limited phenomenological ranges of validity, an improved version with linear rise in [Formula: see text] has a wider phenomenological range. We then compare the partial momentum fractions in all the small [Formula: see text] models. Our analysis implies that the role of small [Formula: see text] sea quarks in calculating the second moments of parton distribution is minor one. We have also made a comprehensive comparison of all the phenomenological models considered to the available perturbative QCD, lattice QCD as well as Ads/QCD results.
Active magnetic bearing system based on sliding mode control
Authors: Zhang Yanhong
Published: June 2017

A new sliding mode variable structure control algorithm suitable for active magnetic bearing is proposed, which is widely used for nonlinear control system. The model and controller is designed, simulation and experimental parts are also made, according to the switching function and the sliding mode control law. The current of electromagnet is adjusted to realize stable levitation of the rotor. The experimental result shows that the sliding mode variable structure controller is an effective way for magnetic bearing control, and the active magnetic bearing system is a highly nonlinear and advanced control method that can reduce the setting time and the cost.
Microfluidic networks embedded in a printed circuit board
Authors: Dong Liangwei , Hu Yueli
Published: June 2017

In order to improve the robustness of microfluidic networks in printed circuit board (PCB)-based microfluidic platforms, a new method was presented. A pattern in a PCB was formed using hollowed-out technology. Polydimethylsiloxane was partly filled in the hollowed-out fields after mounting an adhesive tape on the bottom of the PCB, and solidified in an oven. Then, microfluidic networks were built using soft lithography technology. Microfluidic transportation and dilution operations were demonstrated using the fabricated microfluidic platform. Results show that this method can embed microfluidic networks into a PCB, and microfluidic operations can be implemented in the microfluidic networks embedded into the PCB.
The Early Stage of Internal Corporate Venturing: Entrepreneurial Activities in a Large Manufacturing Company
Authors: Abrell Thomas , Karjalainen Toni-Matti
Published: June 2017

What types of activities are conducted in the early stage of internal corporate venturing in a large manufacturing company? To study these activities, we first performed a literature review that led to a conceptual construct of six activity categories and five process stages. Then, we analysed five projects in our case company. Multiple sources produced an extensive body of data. Our subsequent data analysis resulted in a comprehensive categorization of the key activities and multiple insights concerning their impact on the entrepreneurial mindset and innovation culture of the studied company.
Domain Learning and Opportunity Development in a High-Tech Context
Authors: Marvel Matthew R. , Lumpkin G. T.
Published: June 2017

This study draws from learning and opportunity development theories to develop and test a conceptual model of opportunity development. Using a sample of technology entrepreneurs in university incubators we explore the unique and joint effects of prior knowledge and learning on sales expectations and product innovativeness. Results suggest that domain knowledge of technology and demand are of unequal value to opportunity development. Domains of prior knowledge relate differently to outcomes but demand learning relates to sales expectations and product innovativeness. Findings suggest the types and sequence of knowledge are important to understanding opportunity development.
LIFTING CAPACITY AMONG INDIAN MANUAL MATERIALS HANDLERS USING PROGRESSIVE ISOINERTIAL LIFTING EVALUATION
Authors: Girish N. , Iqbal Rauf , Khanzode Vivek
Published: June 2017

Purpose: Weight of the load which is to be lifted and its characteristics are considered to be important risk factors for low back disorders (LBD) among manual material handlers. Determining the amount of load a person can lift is important in minimizing the incidence of LBD. The objective of this study was to determine the lifting capacity, adopting two lifting techniques at two levels among male construction workers using progressive isoinertial lifting evaluation (PILE). Methods: One hundred and forty-three male construction workers with minimum 1 year of work experience and without any acute illnesses participated in this study. Workers were advised to perform PILE using two lifting techniques (stoop and squat) and at two lifting levels (waist and shoulder). Results: The mean lifting capacity was found to be 24.50 [Formula: see text] 5.10, 21.20 [Formula: see text] 5.54, 19.76 [Formula: see text] 4.08 and 17.25 [Formula: see text] 5.18 kg, respectively, for floor to waist-stoop, floor to waist-squat, floor to shoulder-stoop and floor to shoulder-squat categories. The lifting capacity decreased by 19.40% and 18.54% when the vertical distance was increased from waist to shoulder adopting stoop and squat techniques, respectively. Conclusion: Lifting capacity for construction workers has been determined using PILE, and it was found to be more during stoop technique of lifting at floor to waist level.
INFLUENCE OF LEAFLET’S MATRIX STIFFNESS AND FIBER ORIENTATION ON THE OPENING DYNAMICS OF A PROSTHETIC TRILEAFLET HEART VALVE
Authors: AVANZINI ANDREA
Published: June 2017

Biological valves are employed for aortic valve substitution since a long time but there is a growing effort toward the development of new engineered tissues, in which the complex mechanical response of native leaflets is replicated using composite materials consisting of a soft matrix with embedded reinforcing fibers. The main goal of the present study is to investigate the influence that variations on fiber orientation and matrix stiffness may have on valve dynamics. To this aim, a fluid–structure interaction (FSI) model of a trileaflet valve was implemented in which the opening phase was simulated and leaflet matrix stiffness and fiber orientation were varied in the framework of an anisotropic hyperelastic strain energy function. Results show that both parameters may affect significantly transvalvular pressure gradient and effective orifice area (EOA). For the opening phase of the valve examined, less favorable flow conditions were found when preferred fiber orientation is circumferential, due to lower maximum EOA achievable. Such configuration in combination with stiffer matrix may result in significant degradation of valve performances. Overall fiber orientation can potentially be taylored to optimize valve dynamics, provided also structural aspects that may be prominent in the closure phase, are considered.
Site-Specific Self-Catalyzed DNA Depurination: A Biological Mechanism That Leads to Mutations and Creates Sequence Diversity
Authors: Fresco Jacques R. , Amosova Olga
Published: June 2017

Self-catalyzed DNA depurination is a sequence-specific physiological mechanism mediated by spontaneous extrusion of a stem-loop catalytic intermediate. Hydrolysis of the 5′G residue of the 5′GA/TGG loop and of the first 5′A residue of the 5′GAGA loop, together with particular first stem base pairs, specifies their hydrolysis without involving protein, cofactor, or cation. As such, this mechanism is the only known DNA catalytic activity exploited by nature. The consensus sequences for self-depurination of such G- and A-loop residues occur in all genomes examined across the phyla, averaging one site every 2,000–4,000 base pairs. Because apurinic sites are subject to error-prone repair, leading to substitution and short frameshift mutations, they are both a source of genome damage and a means for creating sequence diversity. Their marked overrepresentation in genomes, and largely unchanging density from the lowest to the highest organisms, indicate their selection over the course of evolution. The mutagenicity at such sites in many human genes is associated with loss of function of key proteins responsible for diverse diseases.
Sodium Hypochlorite as Fluorotic Dentin Pretreatment of Two-Step Self-Etch Adhesive with Silver Nanoparticle: Atomic Force Microscope and Adhesive Microtensile Bond Strength Evaluation
Authors: Monjarás-Ávila Ana-Josefina , Zavala-Alonso Norma-Verónica , Martínez-Castañón Gabriel Alejandro , Patiño-Marín Nuria , Flores Daniel Silva-Herzog , Ruíz Facundo
Published: June 2017

The objective of this work was to evaluate the effect of pretreatment with commercial sodium hypochlorite, 5.25%, with a self-etch adhesive (Optibond Versa) in its original formula and with the incorporation of silver nanoparticles (NaAg) on fluorotic dentin. 240 human molars were classified according to fluorosis severity with Thylstrup-Fejerskov Index (TFI) and subdivided into three study subgroups according to the adhesive technique: (1) self-etch (SE) control subgroup; (2) NaOCl/SE subgroup; (3) NaOCl/SE + NaAg subgroup. The nanostructural characteristics were observed by AFM, μTBS was tested, and hybrid layer formation was observed by SEM. One-way analyses of variance (ANOVA) and Tukey-Kramer post hoc tests were used. No statistically significant differences were found in roughness values in any of the subgroups and subgroups studied. Remnants of smear layer were detected in areas devoid of resin tags in SEM images of samples bonded with subgroup 2, in contrast to subgroup 3. No statistically significant difference between any of the results was found in μTBS and a greater number of adhesive failures were observed. The results show that the pretreatment technique of 5.25% NaOCl and the incorporation of NaAg to the self-adhesive system do not produce a surface more adequate for a better adhesion.
Comparison of Inflammation-Based Prognostic Scores in a Cohort of Patients with Resectable Esophageal Cancer
Authors: Jomrich G. , Paireder M. , Gleiss A. , Kristo I. , Harpain L. , Schoppmann S. F.
Published: June 2017

Background. A number of studies have revealed that inflammation-based prognostic scores, such as Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS), and C-reactive protein and albumin ratio (C/A ratio), are associated with poor outcome in cancer patients. However, until now, no study has investigated the role of these prognostic scores in a cohort of neoadjuvant-treated esophageal adenocarcinomas (nEAC) and squamous cell carcinomas (nESCC).Methods. Patients had laboratory measurements within three days before resection. GPS, mGPS, and C/A ratio were tested together with established clinicopathological factors in simple and multiple Cox regression analysis of overall survival (OS) and disease-free survival (DFS).Results. A total of 283 patients (201 EAC and 82 ESCC) with locally advanced esophageal cancer were enrolled. 167 patients received neoadjuvant treatment (59.0%). Simple analysis revealed that there were significant differences in cancer-specific survival in relation to elevated C-reactive protein (p=0.011), lymph node status (p<0.001), UICC stage (p<0.001), and nEAC (p=0.005). mGPS (p=0.024) showed statistical significance in simple analysis. No statistical significance could be found for GPS (p=0.29), mGPS (p=0.16), and C/A ratio (p=0.76) in multiple analysis.Conclusion. The investigated prognostic scores should be used and interpreted carefully, and established factors like histology, including tumor size and differentiation, lymph node involvement, and status of resection margin remain the only reliable prognostic factors for patients suffering from resectable EC.
A Protective Role of Glibenclamide in Inflammation-Associated Injury
Authors: Zhang Gensheng , Lin Xiuhui , Zhang Shufang , Xiu Huiqing , Pan Chuli , Cui Wei
Published: June 2017

Glibenclamide is the most widely used sulfonylurea drug for the treatment of type 2 diabetes mellitus (DM). Recent studies have suggested that glibenclamide reduced adverse neuroinflammation and improved behavioral outcomes following central nervous system (CNS) injury. We reviewed glibenclamide’s anti-inflammatory effects: abundant evidences have shown that glibenclamide exerted an anti-inflammatory effect in respiratory, digestive, urological, cardiological, and CNS diseases, as well as in ischemia-reperfusion injury. Glibenclamide might block KATPchannel, Sur1-Trpm4 channel, and NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation, decrease the production of proinflammatory mediators (TNF-α, IL-1β, and reactive oxygen species), and suppress the accumulation of inflammatory cells. Glibenclamide’s anti-inflammation warrants further investigation.
A Combined Water Extract of Frankincense and Myrrh Alleviates Neuropathic Pain in Mice via Modulation of TRPV1
Authors: Hu Danyou , Wang Changming , Li Fengxian , Su Shulan , Yang Niuniu , Yang Yan , Zhu Chan , Shi Hao , Yu Lei , Geng Xiao , Gu Leying , Yuan Xiaolin , Wang Zhongli , Yu Guang , Tang Zongxiang
Published: June 2017

Frankincense and myrrh are widely used in clinics as a pair of herbs to obtain a synergistic effect for relieving pain. To illuminate the analgesia mechanism of frankincense and myrrh, we assessed its effect in a neuropathic pain mouse model. Transient receptor potential vanilloid 1 (TRPV1) plays a crucial role in neuropathic pain and influences the plasticity of neuronal connectivity. We hypothesized that the water extraction of frankincense and myrrh (WFM) exerted its analgesia effect by modulating the neuronal function of TRPV1. In our study, WFM was verified by UHPLC-TQ/MS assay. In vivo study showed that nociceptive response in mouse by heat and capsaicin induced were relieved by WFM treatment. Furthermore, thermal hypersensitivity and mechanical allodynia were also alleviated by WFM treatment in a chronic constriction injury (CCI) mouse model. CCI resulted in increased TRPV1 expression at both the mRNA and protein levels in predominantly small-to-medium neurons. However, after WFM treatment, TRPV1 expression was reverted in real-time PCR, Western blot, and immunofluorescence experiments. Calcium response to capsaicin was also decreased in cultured DRG neurons from CCI model mouse after WFM treatment. In conclusion, WFM alleviated CCI-induced mechanical allodynia and thermal hypersensitivity via modulating TRPV1.
A Modified Floor Field Model and Pareto Optimum of Pedestrian Evacuation Efficiency
Authors: Xu Yan , Tian Li-Jun , Yong Gui
Published: June 2017

A modified floor field model is proposed to simulate the pedestrian evacuation behavior in a room with multiple exits. The modification relies upon introduction of a so‐called semidynamical floor field which additionally embodies two cognition coefficients related to exit width and pedestrian distribution around exits. The energy consumption and time requirement of evacuees are numerically investigated and the Pareto optimum of evacuation efficiency is obtained by selecting the combinations of the two cognition coefficients.
Mold Alkaloid Cytochalasin D Modifies the Morphology and Secretion of fMLP-, LPS-, or PMA-Stimulated Neutrophils upon Adhesion to Fibronectin
Authors: Galkina Svetlana I. , Fedorova Natalia V. , Serebryakova Marina V. , Arifulin Evgenii A. , Stadnichuk Vladimir I. , Baratova Ludmila A. , Sud’ina Galina F.
Published: June 2017

Neutrophils play an essential role in innate immunity due to their ability to migrate into infected tissues and kill microbes with bactericides located in their secretory granules. Neutrophil transmigration and degranulation are tightly regulated by actin cytoskeleton. Invading pathogens produce alkaloids that cause the depolymerization of actin, such as the mold alkaloid cytochalasin D. We studied the effect of cytochalasin D on the morphology and secretion of fMLP-, LPS-, or PMA-stimulated human neutrophils upon adhesion to fibronectin. Electron microscopy showed that the morphology of the neutrophils adherent to fibronectin in the presence of various stimuli differed. But in the presence of cytochalasin D, all stimulated neutrophils exhibited a uniform nonspread shape and developed thread-like membrane tubulovesicular extensions (cytonemes) measuring 200 nm in diameter. Simultaneous detection of neutrophil secretory products by mass spectrometry showed that all tested stimuli caused the secretion of MMP-9, a key enzyme in the neutrophil migration. Cytochalasin D impaired the MMP-9 secretion but initiated the release of cathepsin G and other granular bactericides, proinflammatory agents. The release of bactericides apparently occurs through the formation, shedding, and lysis of cytonemes. The production of alkaloids which modify neutrophil responses to stimulation via actin depolymerization may be part of the strategy of pathogen invasion.
Experimental Estimation of Journal Bearing Stiffness for Damage Detection in Large Hydrogenerators
Authors: Brito Geraldo Carvalho , Machado Roberto Dalledone , Chaves Neto Anselmo
Published: June 2017

Based on experimental pieces of evidence collected in a set of twenty healthy large hydrogenerators, this article shows that the operating conditions of the tilting pad journal bearings of these machines may have unpredictable and significant changes. This behavior prevents the theoretical determination of bearing stiffness and damping coefficients with an adequate accuracy and makes damage detection difficult. Considering that dynamic coefficients have similar sensitivity to damage and considering that it is easier to monitor bearing stiffness than bearing damping, this article discusses a method to estimate experimentally the effective stiffness coefficients of hydrogenerators journal bearings, using only the usually monitored vibrations, with damage detection purposes. Validated using vibration signals synthesized by a simplified mathematical model that simulates the dynamic behavior of large hydrogenerators, the method was applied to a journal bearing of a 700 MW hydrogenerator, using two different excitations, the generator rotor unbalance and the vortices formed in the turbine rotor when this machine operates at partial loads. The experimental bearing stiffnesses obtained using both excitations were similar, but they were also much lower than the theoretical predictions. The article briefly discusses the causes of these discrepancies, the method’s uncertainties, and the possible improvements in its application.
Numerical Simulations of the Flame of a Single Coaxial Injector
Authors: Zhukov Victor P. , Feil Markus
Published: June 2017

The processes of mixing and combustion in the jet of a shear-coaxial injector are investigated. Two test cases (nonreacting and reacting) are simulated using the commercial computational fluid dynamics code ANSYS CFX. The first test case is an experiment on the mixing in a nonreacting coaxial jet carried out with the use of planar laser induced fluorescence (PLIF). The second test case is an experiment on the visualization of hydrogen-oxygen flame using PLIF of OH in a single injector combustion chamber at pressure of 53 bar. In the first test case, the two-dimensional axisymmetric simulations are performed using the shear-stress turbulence (SST) model. Due to the dominant flow unsteadiness in the second test case, the turbulence is modeled using transient SAS (Scale-Adaptive Simulation) model. The combustion is modeled using the burning velocity model (BVM) while both two- and three-dimensional simulations are carried out. The numerical model agrees with the experimental data very well in the first test case and adequately in the second test case.
MiR-195Inhibits Tumor Growth and Metastasis in Papillary Thyroid Carcinoma Cell Lines by TargetingCCND1andFGF2
Authors: Yin Yali , Hong Shubin , Yu Shuang , Huang Yanrui , Chen Shuwei , Liu Yujie , Zhang Quan , Li Yanbing , Xiao Haipeng
Published: June 2017

Background. MicroRNA (miRNA) dysregulation was commonly seen in papillary thyroid carcinoma (PTC), andmiR-195was verified to be downregulated in PTC by the large data set analysis from The Cancer Genome Atlas (TCGA). Our study aimed to explore the biological functions and the underlying molecular mechanisms ofmiR-195in PTC.Methods. The relative expression ofmiR-195and its target genes were assessed by quantitative RT-PCR assay in 38 pairs of PTC and the adjacent thyroid tissues. Assays were performed to evaluate the effect ofmiR-195on the proliferation, migration, and invasion in PTC cell lines. Moreover, we searched for targets ofmiR-195and explored the possible molecular pathway ofmiR-195in PTC.Results. We found thatmiR-195was downregulated in PTC cell lines and tissues. Overexpression ofmiR-195significantly inhibited cell proliferation, migration, and invasion in K1 and BCPAP cell lines.CCND1andFGF2, which had inverse correlations withmiR-195in clinical specimens, were found to be the direct targets ofmiR-195. Furthermore,miR-195might be involved in PTC tumorigenesis by suppressing the Wnt/β-catenin signaling pathway.Conclusions. These results highlight an important role ofmiR-195in the initiation and progression of PTC and implicate the potential application ofmiR-195in PTC target therapy.
Cytokines in Endocrine Dysfunction of Plasma Cell Disorders
Authors: Feigerlová Eva , Battaglia-Hsu Shyue-Fang
Published: June 2017

Monoclonal gammopathies (MG) are classically associated with lytic bone lesions, hypercalcemia, anemia, and renal insufficiency. However, in some cases, symptoms of endocrine dysfunction are more prominent than these classical signs and misdiagnosis can thus be possible. This concerns especially the situation where the presence of M-protein is limited and the serum protein electrophoresis (sPEP) appears normal. To understand the origin of the endocrine symptoms associated with MG, we overview here the current knowledge on the complexity of interactions between cytokines and the endocrine system in MG and discuss the perspectives for both the diagnosis and treatments for this class of diseases. We also illustrate the role of major cytokines and growth factors such as IL-6, IL-1β, TNF-α, and VEGF in the endocrine system, as these tumor-relevant signaling molecules not only help the clonal expansion and invasion of the tumor cells but also influence cellular metabolism through autocrine, paracrine, and endocrine mechanisms. We further discuss the broader impact of these tumor environment-derived molecules and proinflammatory state on systemic hormone signaling. The diagnostic challenges and clinical work-up are illustrated from the point of view of an endocrinologist.
A Short Review of FDTD‐Based Methods for Uncertainty Quantification in Computational Electromagnetics
Authors: Zygiridis Theodoros T.
Published: June 2017

We provide a review of selected computational methodologies that are based on the deterministic finite‐difference time‐domain algorithm and are suitable for the investigation of electromagnetic problems involving uncertainties. As it will become apparent, several alternatives capable of performing uncertainty quantification in a variety of cases exist, each one exhibiting different qualities and ranges of applicability, which we intend to point out here. Given the numerous available approaches, the purpose of this paper is to clarify the main strengths and weaknesses of the described methodologies and help the potential readers to safely select the most suitable approach for their problem under consideration.
Hypoxia-Induced Downregulation of DUSP-2 Phosphatase Drives Colon Cancer Stemness
Authors: Hou Pei-Chi , Li Yo-Hua , Lin Shih-Chieh , Lin Shau-Chieh , Lee Jenq-Chang , Lin Bo-Wen , Liou Jing-Ping , Chang Jang-Yang , Kuo Ching-Chuan , Liu Yi-Min , Sun H. Sunny , Tsai Shaw-Jenq
Published: June 2017

Cancer stem-like cells (CSC) evolve to overcome the pressures of reduced oxygen, nutrients or chemically induced cell death, but the mechanisms driving this evolution are incompletely understood. Here, we report that hypoxia-mediated downregulation of the dual specificity phosphatase 2 (DUSP2) is critical for the accumulation of CSC in colorectal cancer. Reduced expression of DUSP2 led to overproduction of COX-2–derived prostaglandin E2, which promoted cancer stemness via the EP2/EP4 signaling pathways. Genetic and pharmacological inhibition of PGE2 biosynthesis or signal transduction ameliorated loss-of-DUSP2–induced tumor growth and cancer stemness. Genome-wide profile analysis revealed that genes regulated by DUSP2 were similar to those controlled by histone deacetylase. Indeed, treatment with novel histone deacetylase inhibitors abolished hypoxia-induced DUSP2 downregulation, COX-2 overexpression, cancer stemness, tumor growth, and drug resistance. Our findings illuminate mechanisms of cancer stemness and suggest new cancer therapy regimens. Cancer Res; 77(16); 4305–16. ©2017 AACR.
WEE1 Kinase Inhibitor AZD1775 Has Preclinical Efficacy in LKB1-Deficient Non–Small Cell Lung Cancer
Authors: Richer Amanda L. , Cala Jacqueline M. , O'Brien Kelley , Carson Vashti M. , Inge Landon J. , Whitsett Timothy G.
Published: June 2017

G1–S checkpoint loss contributes to carcinogenesis and increases reliance upon the G2–M checkpoint for adaptation to stress and DNA repair, making G2–M checkpoint inhibition a target for novel therapeutic development. AZD1775, an inhibitor against the critical G2–M checkpoint protein WEE1, is currently in clinical trials across a number of tumor types. AZD1775 and DNA-damaging agents have displayed favorable activity in several preclinical tumor models, often in the molecular context of TP53 loss. Whether AZD1775 efficacy is modulated by other molecular contexts remains poorly understood. The tumor suppressor serine/threonine kinase 11 (LKB1/STK11) is one of the most frequently mutated genes in non–small cell lung cancer (NSCLC) and is commonly comutated with oncogenic KRAS mutations. We investigated the preclinical effects of AZD1775 in the context of KRAS/LKB1 in NSCLC. Using NSCLC cell lines, we found that AZD1775 alone and in combination with DNA-damaging agents (e.g., cisplatin and radiation) decreased tumor cell viability in LKB1-deficient NSCLC cells. In vitro, LKB1 deficiency enhanced DNA damage and apoptosis in response to AZD1775 exposure compared with wild-type LKB1 cells. In a genetically engineered mouse model of mutant Kras with concomitant loss of Lkb1, combined AZD1775 and cisplatin extended overall survival compared with cisplatin alone. Our data suggest that lack of phosphorylation of LKB1 by ATM was involved in AZD1775-mediated cytotoxicity. Collectively, these findings provide a clinical application for AZD1775 with DNA-damaging agents in KRAS/LKB1 NSCLC. Cancer Res; 77(17); 4663–72. ©2017 AACR.
SPIN90 Depletion and Microtubule Acetylation Mediate Stromal Fibroblast Activation in Breast Cancer Progression
Authors: You Eunae , Huh Yun Hyun , Kwon Ahreum , Kim So Hee , Chae In Hee , Lee Ok-Jun , Ryu Je-Hwang , Park Min Ho , Kim Ga-Eon , Lee Ji Shin , Lee Kun Ho , Lee Yong-Seok , Kim Jung-Woong , Rhee Sangmyung , Song Woo Keun
Published: June 2017

Biomechanical remodeling of stroma by cancer-associated fibroblasts (CAF) in early stages of cancer is critical for cancer progression, and mechanical cues such as extracellular matrix stiffness control cell differentiation and malignant progression. However, the mechanism by which CAF activation occurs in low stiffness stroma in early stages of cancer is unclear. Here, we investigated the molecular mechanism underlying CAF regulation by SPIN90 and microtubule acetylation under conditions of mechanically soft matrices corresponding to normal stromal rigidity. SPIN90 was downregulated in breast cancer stroma but not tumor, and this low stromal expression correlated with decreased survival in breast cancer patients. Spin90 deficiency facilitated recruitment of mDia2 and APC complex to microtubules, resulting in increased microtubule acetylation. This increased acetylation promoted nuclear localization of YAP, which upregulated expression of myofibroblast marker genes on soft matrices. Spin90 depletion enhanced tumor progression, and blockade of microtubule acetylation in CAF significantly inhibited tumor growth in mice. Together, our data demonstrate that loss of SPIN90-mediated microtubule acetylation is a key step in CAF activation in low stiffness stroma. Moreover, correlation among these factors in human breast cancer tissue supports the clinical relevance of SPIN90 and microtubule acetylation in tumor development. Cancer Res; 77(17); 4710–22. ©2017 AACR.
Unpaired Extracellular Cysteine Mutations of CSF3R Mediate Gain or Loss of Function
Authors: Zhang Haijiao , Means Sophie , Schultz Anna Reister , Watanabe-Smith Kevin , Medeiros Bruno C. , Bottomly Daniel , Wilmot Beth , McWeeney Shannon K. , Kükenshöner Tim , Hantschel Oliver , Tyner Jeffrey W.
Published: June 2017

Exclusive of membrane-proximal mutations seen commonly in chronic neutrophilic leukemia (e.g., T618I), functionally defective mutations in the extracellular domain of the G-CSF receptor (CSF3R) have been reported only in severe congenital and idiopathic neutropenia patients. Here, we describe the first activating mutation in the fibronectin-like type III domain of the extracellular region of CSF3R (W341C) in a leukemia patient. This mutation transformed cells via cysteine-mediated intermolecular disulfide bonds, leading to receptor dimerization. Interestingly, a CSF3R cytoplasmic truncation mutation (W791X) found on the same allele as the extracellular mutation and the expansion of the compound mutation was associated with increased leukocytosis and disease progression of the patient. Notably, the primary patient sample and cells transformed by W341C and W341C/W791X exhibited sensitivity to JAK inhibitors. We further showed that disruption of original cysteine pairs in the CSF3R extracellular domain resulted in either gain- or loss-of-function changes, part of which was attributable to cysteine-mediated dimer formation. This, therefore, represents the first characterization of unpaired cysteines that mediate both gain- and loss-of-function phenotypes. Overall, our results show the structural and functional importance of conserved extracellular cysteine pairs in CSF3R and suggest the necessity for broader screening of CSF3R extracellular domain in leukemia patients. Cancer Res; 77(16); 4258–67. ©2017 AACR.
A Clinical Score for Predicting Atrial Fibrillation in Patients with Cryptogenic Stroke or Transient Ischemic Attack
Authors: Kwong Calvin , Ling Albee Y. , Crawford Michael H. , Zhao Susan X. , Shah Nigam H.
Published: June 2017

Objectives: Detection of atrial fibrillation (AF) in post-cryptogenic stroke (CS) or transient ischemic attack (TIA) patients carries important therapeutic implications. Methods: To risk stratify CS/TIA patients for later development of AF, we conducted a retrospective cohort study using data from 1995 to 2015 in the Stanford Translational Research Integrated Database Environment (STRIDE). Results: Of the 9,589 adult patients (age ≥40 years) with CS/TIA included, 482 (5%) patients developed AF post CS/TIA. Of those patients, 28.4, 26.3, and 45.3% were diagnosed with AF 1-12 months, 1-3 years, and >3 years after the index CS/TIA, respectively. Age (≥75 years), obesity, congestive heart failure, hypertension, coronary artery disease, peripheral vascular disease, and valve disease are significant risk factors, with the following respective odds ratios (95% CI): 1.73 (1.39-2.16), 1.53 (1.05-2.18), 3.34 (2.61-4.28), 2.01 (1.53-2.68), 1.72 (1.35-2.19), 1.37 (1.02-1.84), and 2.05 (1.55-2.69). A risk-scoring system, i.e., the HAVOC score, was constructed using these 7 clinical variables that successfully stratify patients into 3 risk groups, with good model discrimination (area under the curve = 0.77). Conclusions: Findings from this study support the strategy of looking longer and harder for AF in post-CS/TIA patients. The HAVOC score identifies different levels of AF risk and may be used to select patients for extended rhythm monitoring.
Efficacy and Tolerability of Polyphenon E in “Difficult-to-Treat” Multiple Genital Warts in an HIV-Positive Male Subject
Authors: Grandolfo Mauro , Milani Massimo
Published: June 2017

A 55-year-old man, nonsmoker, with a HIV-positive history came to our attention in February 2017. He was on treatment with StribildTM, 1 capsule daily (150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 245 mg tenofovir disoproxil). The CD4+/CD8+ cellular count was 326/µL (normal values: 404–1,612); the CD3+/CD8+ cellular count was 819/µL (normal values: 220–1,219). The CD4/CD8 ratio was 0.40 (normal value: >1). Several typical genital wart lesions were present at the penis shaft and at the level of the neck and the corona of glans. These lesions were present for 2 years. Several cryotherapy sessions (a total of 10 procedures) had been performed with partial success. At the initial visit a total of 5 lesions were present. Treatment with topical Polyphenon E 10% 3 times a day was prescribed and started. After 1 month of treatment the lesions were reduced to 2. Treatment was very well tolerated. After 8 weeks of treatment no more lesions were observed and therefore a complete clearance was obtained. Local tolerability was evaluated to be very good by the patient.
A Dessensibilização do Cotidiano
Authors: Lima Edson Prudencio de
Published: June 2017

O ensaio fotográfico “A dessensibilização do cotidiano” é uma projeto autoral, com fotos e texto, que busca provocar a reflexão crítica de nossa percepção à dor do outro através de imagens que simbolizem nossa dessensibilização ao sofrimento que nos é próximo. As fotos mostram o cotidiano de um matadouro clandestino no agreste pernambucano, em que a ausência de condições de higiene e segurança e o envolvimento de crianças na lide com a limpeza de membros e órgãos dos animais abatidos são pretextos para uma análise crítica de nossa incapacidade de sensibilização à dor alheia, quando esta nos cerca diariamente, banalizada pela repetição. O texto busca conduzir o olhar e a atenção do observador do choque inicial − causado pela narrativa visual − ao reconhecimento de que o estranhamento causado pelas imagens denuncia de forma constrangedora nossa relação de impassividade diante da dor do outro, presente em nosso cotidiano. Além disso, o texto descreve brevemente o processo acidental da escolha do tema a partir de um recorte humanista, a interação com os fotografados, o dilema da composição fotográfica e sua relação ética e estética. A primeira exposição do projeto A dessensibilização do cotidiano foi realizada em abril de 2015 em um Centro Estudantil em Friburgo, Suíça, com curadoria da fotógrafa Mélanie Baierlé.
Por que canta o Mahku – Movimento dos Artistas Huni Kuin?
Authors: Mattos Amilton Pelegrino de , Huni Kuin Ibã
Published: June 2017

O presente artigo resulta de uma composição dos autores. Os desenhos realizados pelos MAHKU – Movimento dos Artistas Huni Kuin – a partir dos cantos huni meka, cantos do nixi pae (ayahuasca), são motivos para o comentário de Ibã Huni Kuin e sua forma de tradução da linguagem dos cantos que ele denomina “pôr ou colocar no sentido”. Na primeira parte faz-se uma breve apresentação da trajetória do Mahku, retratada no ensaio audiovisual O sonho do nixi pae (Dir. Amilton Mattos, 2015), do trabalho de pesquisa de Ibã e do coletivo de artistas Huni Kuin dentro e fora da universidade
Arquivos e Imagens (Pós) Coloniais: Contribuições Analíticas sobre duas Coleções Fotográficas
Authors: Triana Bruna Nunes da Costa
Published: June 2017

O objetivo do texto é aproximar os gêneros da fotografia etnográfica e documentária, de modo a problematizar a forma como as duas tradições se utilizaram dos discursos sobre “verdade” e “real” vigentes em cada período para conferir inteligibilidade e legitimidade às respectivas práticas. Para tanto, mobilizam-se os acervos fotográficos do português José Augusto da Cunha Moraes (1855-1933) e do moçambicano Ricardo Rangel (1924-2009), a fim de lançar luz sobre convenções técnicas e estéticas estabelecidas em cada momento e que foram incorporadas nas produções fotográficas dos dois artistas. O argumento é de que a crença numa realidade exterior, passível de ser integralmente capturada, seja para fins de produção de conhecimento científico ou de denúncia social, norteou ambas as práticas.
Relações entre Etnografia Face a Face e Imagens do Google Street View: Uma Pesquisa sobre Usuários de Crack nas Ruas do Centro de São Paulo
Authors: Frúgoli Junior Heitor , Chizzolini Bianca Barbosa
Published: June 2017

O ponto de partida do presente artigo foi um trabalho de campo realizado por integrantes do Grupo de Estudos de Antropologia da Cidade (GEAC-USP), no qual foram investigadas redes de relações, sob o enfoque da assim chamada cracolândia como uma modalidade de territorialidade itinerante, num contexto multifacetado e assinalado por variações situacionais (2008-2012). Posteriormente, integrou-se um novo projeto – Plataforma São Paulo – que reunia docentes da Universidade de São Paulo. Tal plataforma conduziu este estudo a estabelecer relações entre textos etnográficos, mapas e imagens (provenientes do Google Street View, de 2010 a 2016) da região da Luz, na área central de São Paulo, espaço investigado durante a pesquisa etnográfica. O objetivo deste artigo é avaliar as possibilidades e limites decorrentes dessa relação específica entre uma experiência etnográfica prévia e o uso posterior de mapas e imagens do Google.
Os possuídos e seus mundos: (auto)biografias visuais em uma tribo diferente das demais
Authors: Laugrand Frédéric , Luce Emmanuel , Melanson Anthony
Published: June 2017

Lançado em 2014 pela Revista Anthropologie et Sociétés, a série Les Possédés et leur mondes (Os Possuídos e seus mundos) é um projeto antropológico em andamento, focado na preservação, valorização e difusão da socioantropologia canadense. A série privilegia a abordagem (auto) biográfica e se volta à memória de professores-pesquisadores do Canadá que publicaram na revista Anthropologie et Sociétés. Os autores a situam dentro de outros projetos relacionados e apresentam em seguida a sua especificidade, objetivos, dispositivos técnicos, primeiras realizações concretas, contribuição à reflexão antropológica e à história intelectual, seus limites e desafios
Bagagem desfeita: a experiência da imigração por artistas congoleses
Authors: Chalcraft Jasper , Segarra Josep Juan , Hikiji Rose Satiko Gitirana
Published: June 2017

Dois artistas congoleses em São Paulo, Yannick Delass e Shambuyi Wetu, encontram-se em performances que registramos e recriamos. Aqui, música e arte são momentos de empoderamento, mudanças sutis na visibilidade e no espaço auditivo das políticas da imigração.
“Olhando pelo olhar do outro” – entrevista com David MacDougall
Authors: Leaha Mihai Andrei
Published: June 2017

David MacDougall é, sem dúvida, a figura mais importante no campo da antropologia visual atualmente. É um cineasta bem conhecido, antropólogo e escritor que contribuiu para o desenvolvimento da antropologia visual, considerada não apenas como um subdomínio da antropologia, mas como um campo de estudo em si, que não depende mais do princípio científico tradicional de investigação antropológica para ser considerado válido.
A Compartimentação do Parque Natural Municipal de Jacarenema Segundo a Hierarquia da Paisagem Proposta por Bertrand
Authors: Pinheiro Carlos Alberto Kuster , Vale Claudia Câmara
Published: June 2017

A zona costeira sofre com graves prejuízos ambientais, sociais e econômicos devido a sua intensa ocupação. As faixas de terras costeiras, extremamente valiosas por seus recursos e logísticas, são densamente povoadas. O Parque Natural Municipal de Jacarenema (PNMJ) localizado na costa leste do município de Vila Velha vem sendo submetido a forte pressão do processo de urbanização. A falta de dados mais relevantes sobre a importância da manutenção deste parque e a carência de informações que o insiram dentro de uma visão sistêmica foram os principais motivos que inspiraram este artigo. O enfoque aqui será o de descrever a distribuição e o atual estado de conservação dos geofácies (nível da hierarquização da paisagem proposta por Bertrand) levando em consideração também a evolução da ocupação da área do entorno do Parque, isto é, o que deveria ser a zona de amortecimento.
A Paisagem na Geografia Física Integrada: Impressões Iniciais Sobre sua Pesquisa no Brasil entre 2006 e 2016
Authors: Neves Carlos Eduardo das , Salinas Eduardo
Published: June 2017

Discute-se de forma contundente nesse século XXI as trajetórias e tendências da Geografia Física Integradora ou Complexa, possibilitando uma avaliação do seu potencial ao estudo de diversas temáticas, com destaque à fragmentação, qualidade e transformação da paisagem, que encontra-se potencialmente degradada pela apropriação inadequada dos recursos e da relação contraditória entre sociedade ↔ natureza. Assim, realiza-se um estudo bibliométrico para reconhecer um primeiro panorama dessa pesquisa desenvolvida pela Geografia brasileira, entre 2006 e 2016, permitindo pensar as trajetórias e tendências do conceito de paisagem. Para isso, coletou-se a produção sobre a temática publicada em 23 periódicos nacionais, os quais foram recuperados de acordo com o estrato do Qualis Capes Periódicos. Buscou-se entender a relevância da paisagem e do seu uso de forma integradora, bem como suas escalas e unidades de análise. Demonstra-se, ainda, a sua relação com o geossistema, entendido como conceito integrador da relação sociedade ↔ natureza. A partir dos resultados, frisa-se o uso da paisagem predominante ligado às pesquisas ambientais, com forte vínculo à escala local, à bacia hidrográfica e à cartografia de distintos complexos paisagísticos. Avista-se, também, a importância da relação entre a paisagem e o geossistema enquanto subsídio ao diagnóstico e prognóstico ambiental. Portanto, o estudo proposto permite uma análise crítica da prática investigativa geográfica, auxiliando na valorização da geodiversidade e do patrimônio natural brasileiro, pois visualiza-se a sociedade ↔ natureza enquanto um par dialético.
Fundamental Cardiovascular Research: Returns on Societal Investment: A Scientific Statement From the American Heart Association
Authors: Hill Joseph A. , Ardehali Reza , Clarke Kimberli Taylor , del Zoppo Gregory J. , Eckhardt Lee L. , Griendling Kathy K. , Libby Peter , Roden Dan M. , Sadek Hesham A. , Seidman Christine E. , Vaughan Douglas E.
Published: June 2017

Recent decades have witnessed robust successes in conquering the acutely lethal manifestations of heart and vascular diseases. Many patients who previously would have died now survive. Lifesaving successes like these provide a tremendous and easily recognized benefit to individuals and society. Although cardiovascular mortality has declined, the devastating impact of chronic heart disease and comorbidities on quality of life and healthcare resources continues unabated. Future strides, extending those made in recent decades, will require continued research into mechanisms underlying disease prevention, pathogenesis, progression, and therapeutic intervention. However, severe financial constraints currently jeopardize these efforts. To chart a path for the future, this report analyzes the challenges and opportunities we face in continuing the battle against cardiovascular disease and highlights the return on societal investment afforded by fundamental cardiovascular research.
Enhancing Spatial Attention and Working Memory in Younger and Older Adults
Authors: Rolle Camarin E. , Anguera Joaquin A. , Skinner Sasha N. , Voytek Bradley , Gazzaley Adam
Published: June 2017

Daily experiences demand both focused and broad allocation of attention for us to interact efficiently with our complex environments. Many types of attention have shown age-related decline, although there is also evidence that such deficits may be remediated with cognitive training. However, spatial attention abilities have shown inconsistent age-related differences, and the extent of potential enhancement of these abilities remains unknown. Here, we assessed spatial attention in both healthy younger and older adults and trained this ability in both age groups for 5 hr over the course of 2 weeks using a custom-made, computerized mobile training application. We compared training-related gains on a spatial attention assessment and spatial working memory task to age-matched controls who engaged in expectancy-matched, active placebo computerized training. Age-related declines in spatial attention abilities were observed regardless of task difficulty. Spatial attention training led to improved focused and distributed attention abilities as well as improved spatial working memory in both younger and older participants. No such improvements were observed in either of the age-matched control groups. Note that these findings were not a function of improvements in simple response time, as basic motoric function did not change after training. Furthermore, when using change in simple response time as a covariate, all findings remained significant. These results suggest that spatial attention training can lead to enhancements in spatial working memory regardless of age.