bluuebunny/crossref_metadata_2025 huggingface dataset:
Sialic Acid Blockade Suppresses Tumor Growth by Enhancing T-cell–Mediated Tumor Immunity
Authors: Büll Christian , Boltje Thomas J. , Balneger Natasja , Weischer Sarah M. , Wassink Melissa , van Gemst Jasper J. , Bloemendal Victor R. , Boon Louis , van der Vlag Johan , Heise Torben , den Brok Martijn H. , Adema Gosse J.
Published: April 2018

Sialic acid sugars on the surface of cancer cells have emerged as potent immune modulators that contribute to the immunosuppressive microenvironment and tumor immune evasion. However, the mechanisms by which these sugars modulate antitumor immunity as well as therapeutic strategies directed against them are limited. Here we report that intratumoral injections with a sialic acid mimetic Ac53FaxNeu5Ac block tumor sialic acid expression in vivo and suppress tumor growth in multiple tumor models. Sialic acid blockade had a major impact on the immune cell composition of the tumor, enhancing tumor-infiltrating natural killer cell and CD8+ T-cell numbers while reducing regulatory T-cell and myeloid regulatory cell numbers. Sialic acid blockade enhanced cytotoxic CD8+ T-cell–mediated killing of tumor cells in part by facilitating antigen-specific T-cell–tumor cell clustering. Sialic acid blockade also synergized with adoptive transfer of tumor-specific CD8+ T cells in vivo and enhanced CpG immune adjuvant therapy by increasing dendritic cell activation and subsequent CD8+ T-cell responses. Collectively, these data emphasize the crucial role of sialic acids in tumor immune evasion and provide proof of concept that sialic acid blockade creates an immune-permissive tumor microenvironment for CD8+ T-cell–mediated tumor immunity, either as single treatment or in combination with other immune-based intervention strategies.

Significance: Sialic acid sugars function as important modulators of the immunosuppressive tumor microenvironment that limit potent antitumor immunity.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3574/F1.large.jpg. Cancer Res; 78(13); 3574–88. ©2018 AACR.
A Rationally Designed Fully Human EGFRvIII:CD3-Targeted Bispecific Antibody Redirects Human T Cells to Treat Patient-derived Intracerebral Malignant Glioma
Authors: Gedeon Patrick C. , Schaller Teilo H. , Chitneni Satish K. , Choi Bryan D. , Kuan Chien-Tsun , Suryadevara Carter M. , Snyder David J. , Schmittling Robert J. , Szafranski Scott E. , Cui Xiuyu , Healy Patrick N. , Herndon James E. , McLendon Roger E. , Keir Stephen T. , Archer Gary E. , Reap Elizabeth A. , Sanchez-Perez Luis , Bigner Darell D. , Sampson John H.
Published: April 2018

Purpose: Conventional therapy for malignant glioma fails to specifically target tumor cells. In contrast, substantial evidence indicates that if appropriately redirected, T cells can precisely eradicate tumors. Here we report the rational development of a fully human bispecific antibody (hEGFRvIII-CD3 bi-scFv) that redirects human T cells to lyse malignant glioma expressing a tumor-specific mutation of the EGFR (EGFRvIII).

Experimental Design: We generated a panel of bispecific single-chain variable fragments and optimized design through successive rounds of screening and refinement. We tested the ability of our lead construct to redirect naïve T cells and induce target cell–specific lysis. To test for efficacy, we evaluated tumor growth and survival in xenogeneic and syngeneic models of glioma. Tumor penetrance following intravenous drug administration was assessed in highly invasive, orthotopic glioma models.

Results: A highly expressed bispecific antibody with specificity to CD3 and EGFRvIII was generated (hEGFRvIII-CD3 bi-scFv). Antibody-induced T-cell activation, secretion of proinflammatory cytokines, and proliferation was robust and occurred exclusively in the presence of target antigen. hEGFRvIII-CD3 bi-scFv was potent and target-specific, mediating significant lysis of multiple malignant glioma cell lines and patient-derived malignant glioma samples that heterogeneously express EGFRvIII. In both subcutaneous and orthotopic models, well-engrafted, patient-derived malignant glioma was effectively treated despite heterogeneity of EGFRvIII expression; intravenous hEGFRvIII-CD3 bi-scFv administration caused significant regression of tumor burden (P < 0.0001) and significantly extended survival (P < 0.0001). Similar efficacy was obtained in highly infiltrative, syngeneic glioma models, and intravenously administered hEGFRvIII-CD3 bi-scFv localized to these orthotopic tumors.

Conclusions: We have developed a clinically translatable bispecific antibody that redirects human T cells to safely and effectively treat malignant glioma. On the basis of these results, we have developed a clinical study of hEGFRvIII-CD3 bi-scFv for patients with EGFRvIII-positive malignant glioma. Clin Cancer Res; 24(15); 3611–31. ©2018 AACR.
Insulin-Like Growth Factor 2 mRNA-Binding Protein 3 is a Novel Post-Transcriptional Regulator of Ewing Sarcoma Malignancy
Authors: Mancarella Caterina , Pasello Michela , Ventura Selena , Grilli Andrea , Calzolari Linda , Toracchio Lisa , Lollini Pier-Luigi , Donati Davide Maria , Picci Piero , Ferrari Stefano , Scotlandi Katia
Published: April 2018

Purpose: Large-scale sequencing studies have indicated that besides genomic alterations, the posttranscriptional regulation of gene expression or epigenetic mechanisms largely influences the clinical behavior of Ewing sarcoma. We investigated the significance of the RNA-binding protein IGF2BP3 in the regulation of Ewing sarcoma aggressiveness.

Experimental Design: Explorative study was performed in 14 patients with localized Ewing sarcoma using RNA sequencing. Next, 128 patients with localized Ewing sarcoma were divided into two cohorts. In the training set, 29 Ewing sarcoma samples were analyzed using Affymetrix GeneChip arrays. In the validation set, 99 Ewing sarcoma samples were examined using qRT-PCR. Patient-derived cell lines and experimental models were used for functional studies.

Results:Univariate and multivariate analyses indicated IGF2BP3 as a potent indicator of poor prognosis. Furthermore, ABCF1 mRNA was identified as a novel partner of IGF2BP3. Functional studies indicated IGF2BP3 as an oncogenic driver and ABCF1 mRNA as a sponge that by binding IGF2BP3, partly repressed its functions. The combined evaluation of IGF2BP3 and ABCF1 could identify different patient outcomes—high IGF2BP3 and low ABCF1 levels indicated poor survival (25%), whereas low IGF2BP3 and high ABCF1 levels indicated favorable survival (85.5%). The bromodomain and extraterminal domain inhibitor (BETi) JQ1 decreased IGF2BP3 expression, modified the expression of its validated targets and inhibited the capability of Ewing sarcoma cells to grow under anchorage-independent conditions.

Conclusions: The combined assessment of IGF2BP3 and ABCF1 predicts recurrence in Ewing sarcoma patients. Thus, for patients with high expression of IGF2BP3 and poor probability of survival, the use of BETis should be clinically evaluated. Clin Cancer Res; 24(15); 3704–16. ©2018 AACR.
Targeting the Proteasome-Associated Deubiquitinating Enzyme USP14 Impairs Melanoma Cell Survival and Overcomes Resistance to MAPK-Targeting Therapies
Authors: Didier Robin , Mallavialle Aude , Ben Jouira Rania , Domdom Marie Angela , Tichet Mélanie , Auberger Patrick , Luciano Frédéric , Ohanna Mickael , Tartare-Deckert Sophie , Deckert Marcel
Published: April 2018

Advanced cutaneous melanoma is one of the most challenging cancers to treat because of its high plasticity, metastatic potential, and resistance to treatment. New targeted therapies and immunotherapies have shown remarkable clinical efficacy. However, such treatments are limited to a subset of patients and relapses often occur, warranting validation of novel targeted therapies. Posttranslational modification of proteins by ubiquitin coordinates essential cellular functions, including ubiquitin-proteasome system (UPS) function and protein homeostasis. Deubiquitinating enzymes (DUB) have been associated to multiple diseases, including cancer. However, their exact involvement in melanoma development and therapeutic resistance remains poorly understood. Using a DUB trap assay to label cellular active DUBs, we have observed an increased activity of the proteasome-associated DUB, USP14 (Ubiquitin-specific peptidase 14) in melanoma cells compared with melanocytes. Our survey of public gene expression databases indicates that high expression of USP14 correlates with melanoma progression and with a poorer survival rate in metastatic melanoma patients. Knockdown or pharmacologic inhibition of USP14 dramatically impairs viability of melanoma cells irrespective of the mutational status of BRAF, NRAS, or TP53 and their transcriptional cell state, and overcomes resistance to MAPK-targeting therapies both in vitro and in human melanoma xenografted mice. At the molecular level, we find that inhibition of USP14 rapidly triggers accumulation of poly-ubiquitinated proteins and chaperones, mitochondrial dysfunction, ER stress, and a ROS production leading to a caspase-independent cell death. Our results provide a rationale for targeting the proteasome-associated DUB USP14 to treat and combat melanomas. Mol Cancer Ther; 17(7); 1416–29. ©2018 AACR.
Vancomycin-Associated Acute Kidney Injury with a Steep Rise in Serum Creatinine
Authors: Velez Juan Carlos Q. , Obadan Ndidiamaka O. , Kaushal Amit , Alzubaidi Mohammed , Bhasin Bhavna , Sachdev Sachin H. , Karakala Nithin , Arthur John M. , Nesbit Ross M. , Phadke Gautam M.
Published: April 2018

Background: Vancomycin-associated (VA) acute kidney injury (AKI) is being increasingly recognized. A distinct pattern of rapid rise in serum creatinine (sCr) during VA-AKI has occasionally been observed. However, such scenarios remain underreported. Methods: We conducted an online survey at the American Society of Nephrology Communities forum and reviewed publications of VA-AKI via PubMed or Google searching for cases of precipitous AKI (those with rise in sCr ≥1.5 mg/dL/day) attributable to vancomycin. Results: We identified 12 original cases compiled from 6 different hospitals and 4 published cases (n = 16; 38% women, age 43.5 ± 16 years, weight 108 ± 23 kg, body mass index 35 ± 7 kg/m2) of precipitous AKI observed shortly after large cumulative doses of VA (8.8 ± 5 g). The median steepest 24-h rise in sCr was 2.6 mg/dL (range 1.5–3.5 mg/dL) and the slope of the initial 48-h sCr rise was greater than that of a control AKI (non-VA, n = 48) group (2.03 ± 0.1 vs. 0.62 ± 0.0 mg/dL/day; p < 0.0001). The steep rise in sCr in the VA-AKI was not accompanied by anuria. Overt rhabdomyolysis was absent in all cases. Further, in 3 precipitous VA-AKI cases, simultaneous serum cystatin C values did not rise precipitously, suggesting that the reductions in glomerular filtration rate were overestimated by the sCr increase. Conclusions: VA-AKI can manifest with a precipitous rise in sCr shortly after a high cumulative dose of vancomycin. True toxic tubular injury overrepresented by the sCr rise is postulated.
Coexisting Heart Failure and Chronic Obstructive Pulmonary Disease: Report of Two Cases Treated with Indacaterol/Glycopyrronium
Authors: Cosentino Eugenio Roberto , Degli Esposti Daniela , Miceli Rinaldo , Bentivenga Crescenzio , Landolfo Matteo , Ricci Iamino Ilaria , Spinardi Luca , Magri Gianluigi , Borghi Claudio
Published: April 2018

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, and it is associated with a high economic burden. Heart failure shares some general symptoms with COPD; thus, diagnosing COPD is difficult in subjects with a history of heart failure, and spi­rometry is mandatory for confirmation. Moreover, COPD is a highly prevalent comorbidity negatively impacting the outcome of heart failure patients. We document here the treatment with indacaterol/glycopyrronium in 2 patients with concomitant COPD and heart failure. Overall, the combination of indacaterol and glycopyrronium resulted in a reciprocal potentiation with a maximal bronchodilatory effect.
A Case of Ventricular Fibrillation in a Frail Patient with Chronic Obstructive Pulmonary Disease, Obstructive Sleep Apnea Syndrome, and Electrolytic Disorder
Authors: Marchitto Nicola , Mauti Monica , Andreozzi Simona , Pannozzi Alberto , Dalmaso Serenella G. , Raimondi Gianfranco
Published: April 2018

Chronic obstructive pulmonary disease (COPD) is associated with an increased cardiovascular risk, although the pathophysiological mechanisms responsible for this interdependence are not completely known. For instance, the increased sympathetic activity may be implied. The severity of COPD correlates with various arrhythmic manifestations such as atrial fibrillation, atrial flutter, and either sustained or nonsustained ventricular tachycardia. COPD and obstructive sleep apnea syndrome may increase the overall cardiovascular risk, especially in elderly patients. Additionally, electrolytic disorders may precipitate cardiac rhythm disturbances and thus cause important arrhythmic consequences such as ventricular fibrillation, as reported in our clinical case. We discuss here the possible treatment of this association of pathological conditions on the basis of a single case we have successfully treated, and provide a brief review of the available literature regarding cardiovascular comorbidities in COPD patients.
The Timing of Initiating Complementary Feeding in Preterm Infants and Its Effect on Overweight: A Systematic Review
Authors: Vissers Karin M. , Feskens Edith J.M. , van Goudoever Johannes B. , Janse Arieke J.
Published: April 2018

Background: What is the appropriate time to start complementary feeding for preterm infants? The answer to this question is yet under debate. The timing of initiating complementary feeding may be associated with overweight in term infants. This systematic review aimed to study the effect of the timing of initiating complementary feeding on overweight in preterm infants. Predefined search items included preterm infants, complementary feeding, overweight, and their synonyms. Summary: The search identified 15,749 articles, of which 5 articles were included. Three studies presented data of randomized controlled trials and 2 studies were cohort studies. Two randomized controlled trials found no significant difference in body mass index (BMI) Z-score between the intervention groups at 12 months of age. One randomized controlled trial presented a significant greater mean rate of growth in length per week until 12 months in the preterm weaning strategy-group compared with the current best practices. One observational study concluded that each month the infants received complementary food later, the Z-score for length and weight was reduced by 0.1. Key Messages: No clear conclusion could be drawn from the included studies. This review illustrates the need for further research to access the effect of the timing of initiating complementary feeding on overweight in preterm infants.
DeSanto-Shinawi Syndrome: First Case in South America
Authors: Vanegas Sara , Ramirez-Montaño Diana , Candelo Estephania , Shinawi Marwan , Pachajoa Harry
Published: April 2018

Pathogenic variants in WAC are uncommon causes of developmental delay and neurobehavioral phenotypes. The clinical features associated with WAC haploinsufficiency include recognizable dysmorphic facial features that were recently delineated as DeSanto-Shinawi syndrome (DESSH; OMIM 616708). Additional clinical features include hypotonia, hearing and vision abnormalities, gastrointestinal problems, and behavioral difficulties. Here, we report a case of a 4-year-old Colombian male patient with typical dysmorphic facial features, developmental delay, hyperactivity, and recurrent respiratory infections. His immune workup revealed hypogammaglobulinemia, and clinical exome sequencing revealed a novel intronic variant in WAC (c.1437+1G>A). To the best of our knowledge, this is the first case of DESSH in South America, underlining the accumulating evidence of the significant role of WAC haploinsufficiency in neurobehavioral phenotypes. Although this report suggested the potential involvement of WAC in immune regulation, additional reports are required to confirm our observations.
Disorders of Lipid Metabolism in Chronic Kidney Disease
Authors: Bulbul Mustafa C.  , Dagel Tuncay , Afsar Baris , Ulusu Nuray N. , Kuwabara Masanari , Covic Adrian , Kanbay Mehmet
Published: April 2018

Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD). One of the most important pathophysiological mechanisms for CVD in patients with CKD is the widespread and possibly accelerated formation of atherosclerotic plaques due to hyperlipidemia, uremic toxins, inflammation, oxidative stress, and endothelial dysfunction. Recent studies showed that the level of oxidized low-density lipoprotein cholesterol increases, and that high-­density lipoprotein cholesterol dysfunction occurs as kidney function declines and inflammation becomes more prevalent. In this review, we aimed to discuss the effect of kidney dysfunction, oxidative stress, and inflammation on lipid ­profile.
Identification of a New Candidate Locus for Ebstein Anomaly in 1p36.2
Authors: Miranda-Fernández Marta-Catalina , Ramírez-Oyaga Silvia , Restrepo Carlos M. , Huertas-Quiñones Victor-Manuel , Barrera-Castañeda Magally , Quero Rossi , Hernández-Toro Camilo-José , Tamar Silva Claudia , Laissue Paul , Cabrera Rodrigo
Published: April 2018

Ebstein anomaly (EA) is a rare congenital heart defect (CHD) with a poorly characterized genetic etiology. However, some EA patients carry deletions in 1p36, all of which have been reported to carry distal deletions and share loss of the PRDM16 gene, which is currently considered the most likely candidate for EA development in this region. Here, we report a patient with an 11.96-Mb proximal 1p36 deletion, without loss of PRDM16, who presented with EA and a proximal deletion phenotype. This finding suggests that PRDM16 loss is not required for the development of EA in 1p36 deletions and that the loss of an additional proximal locus in 1p36 is also likely associated with EA. Our data suggest that a distal locus containing the SKI gene and a proximal locus containing the CHD-associated genes RERE and UBE4B are the most probable etiological factors for EA in patients with 1p36 deletion syndrome.
Immunotherapy of Colon Cancer
Authors: Stein Alexander , Folprecht Gunnar
Published: April 2018

In contrast to other tumour types inhibitors of PD-1/-L1 or CTLA 4 have not yet shown relevant efficacy in unselected colorectal cancer. Based on the high mutational burden, deficient mismatch repair (dMMR) or microsatellite instable (MSI-H) tumours are yet the only subgroup, which is amenable to checkpoint inhibition. These tumours show relevant and durable responses in the refractory setting by PD-1/-L1 +/- CTLA 4 inhibition. Thus, ongoing phase 3 trials in this subgroup evaluate immunotherapy in the adjuvant setting as well as in the first line metastatic setting with or without chemotherapy. For the by far larger subgroup of non-dMMR/MSI-H patients (95% in the metastatic setting) combination regimen are urgently required, either with chemotherapy and/or molecular targeting drugs, local ablative treatments or other immunotherapeutic agents (e.g. CEA-TCB).
Leucine-Rich Repeat Kinase 2 in Parkinson’s Disease: Updated from Pathogenesis to Potential Therapeutic Target
Authors: Chen Jinhua , Chen Ying , Pu Jiali
Published: April 2018

Background: Parkinson’s disease (PD) is characterized by the selective loss of dopaminergic neurons in the midbrain. The pathogenesis of PD is not fully understood but is likely caused by a combination of genetic and environmental factors. Several genes are associated with the onset and progression of familial PD. There is increasing evidence that leucine-rich repeat kinase 2 (LRRK2) plays a significant role in PD pathophysiology. Summary: Many studies have been conducted to elucidate the functions of LRRK2 and identify effective LRRK2 inhibitors for PD treatment. In this review, we discuss the role of LRRK2 in PD and recent progress in the use of LRRK2 inhibitors as therapeutic agents. Key Messages: LRRK2 plays a significant role in the pathophysiology of PD, and pharmacological inhibition of LRRK2 has become one of the most promising potential therapies for PD. Further research is warranted to determine the functions of LRRK2 and expand the applications of LRRK2 inhibitors in PD treatment.
Biliary Tract Cancer: Implicated Immune-Mediated Pathways and Their Associated Potential Targets
Authors: Tariq Noor-ul-Ain , Vogel Arndt , McNamara Mairead G. , Valle Juan W.
Published: April 2018

There is a well-established link between biliary tract cancers (BTC) and chronic inflammatory conditions such as primary sclerosing cholangitis, chronic cholecystitis, chronic cholelithiasis, liver fluke-associated infestations, and chronic viral hepatic infections. These associated risk factors highlight the potential for development of immune-modulatory agents in this poor-prognostic disease group with limited treatment options. Clinical trials have evaluated the role of immune cells, inflammatory biomarkers, vaccines, cytokines, adoptive cell therapy, and immune checkpoint inhibitors in patients with BTC. Although these have demonstrated the importance of the immune environment in BTC, currently none of the immune-based therapies have been approved for use in this disease group. The role of immunomodulatory agents is a developing field and has yet to find its way ‘from bench to bedside' in BTC.
High Glucose-Induced Reactive Oxygen Species Stimulates Human Mesenchymal Stem Cell Migration Through Snail and EZH2-Dependent E-Cadherin Repression
Authors: Oh Ji Young , Choi Gee Euhn , Lee Hyun Jik , Jung Young Hyun , Ko So Hee , Chae Chang Woo , Kim Jun Sung , Kim Seo Yihl , Lim Jae Ryong , Lee Chang-Kyu , Han Ho Jae
Published: April 2018

Background/Aims: Glucose plays an important role in stem cell fate determination and behaviors. However, it is still not known how glucose contributes to the precise molecular mechanisms responsible for stem cell migration. Thus, we investigate the effect of glucose on the regulation of the human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) migration, and analyze the mechanism accompanied by this effect. Methods: Western blot analysis, wound healing migration assays, immunoprecipitation, and chromatin immunoprecipitation assay were performed to investigate the effect of high glucose on hUCB-MSC migration. Additionally, hUCB-MSC transplantation was performed in the mouse excisional wound splinting model. Results: High concentration glucose (25 mM) elicits hUCB-MSC migration compared to normal glucose and high glucose-pretreated hUCB-MSC transplantation into the wound sites in mice also accelerates skin wound repair. We therefore elucidated the detailed mechanisms how high glucose induces hUCB-MSC migration. We showed that high glucose regulates E-cadherin repression through increased Snail and EZH2 expressions. And, we found high glucose-induced reactive oxygen species (ROS) promotes two signaling; JNK which regulates γ–secretase leading to the cleavage of Notch proteins and PI3K/Akt signaling which enhances GSK-3β phosphorylation. High glucose-mediated JNK/Notch pathway regulates the expression of EZH2, and PI3K/Akt/GSK-3β pathway stimulates Snail stabilization, respectively. High glucose enhances the formation of EZH2/Snail/HDAC1 complex in the nucleus, which in turn causes E-cadherin repression. Conclusion: This study reveals that high glucose-induced ROS stimulates the migration of hUCB-MSC through E-cadherin repression via Snail and EZH2 signaling pathways.
C-Met-Activated Mesenchymal Stem Cells Rescue Ischemic Damage via Interaction with Cellular Prion Protein
Authors: Han Yong-Seok , Yun Seung Pil , Lee Jun Hee , Kwon Seung-Hwan , Kim SangMin , Hur Jin , Lee Sang Hun
Published: April 2018

Background/Aims: Stem cell transplantation has emerged as a promising therapeutic strategy, but the exact mechanisms by which stem cells exposed to hypoxic conditions increase the survival rate and rescue ischemic injury at the graft site are not well known. In this study, we aimed to determine if c-Met-activated mesenchymal stem cells (MSCs) pre-exposed to hypoxia promote therapeutic efficacy when transplanted to ischemic models, and whether c-Met interacts with cellular prion protein (PrPC) present in the ischemic tissue. Methods: Western blot analysis was performed to determine the expression levels of PrPC, C-caspase-3, and C-PARP-1, as well as the phosphorylation of Akt, p38, JNK, and BAX. A co-immunoprecipitation assay was performed to show that PrPC binds with c-Met in vitro. An adhesion assay was performed to explore the alterations in MSCs attached to myoblasts (in vitro), and an invasion assay was performed to determine the effect on MSC invasion capacity upon interaction with myoblast-induced c-Met and PrPC. CD31-positive capillaries and αSMA-positive arterioles in in vivo hindlimb ischemic tissue were quantified by immunofluorescence staining. The level of apoptosis in the tissue of each group was assessed by quantifying the number of C-caspase-3-positive cells. Finally, laser Doppler technology was utilized to detect the enhanced angiogenic effects in vivo. Results: We showed that hypoxic conditions increased PrPC levels in vivo (hindlimb ischemic tissue) and in vitro (myoblasts) and increased c-Met levels in MSCs. To identify the relationship between c-Met from MSCs and PrPC from myoblasts, we used a co-culturing system with myoblasts and MSCs pre-exposed to hypoxia. Hypoxia increased the phosphorylation of mitogen-activated protein kinases. Transplantation of hypoxia-pre-exposed MSCs to the ischemic site increased anti-apoptosis and enhanced the survival and proliferation of transplanted MSCs in a murine hindlimb model, resulting in improved functional recovery of the ischemic tissue. All the aforementioned effects were inhibited by the pretreatment of MSCs with the c-Met-neutralizing antibody Conclusion: c-Met-activated MSCs pre-exposed to hypoxia interact with PrPC at the site of ischemic injury to increase the efficiency of MSC transplantation. Hence, our study demonstrated that c-Met is a potential target for MSC-based therapies.
Novel Scheme for Minimal Iterative PSO Algorithm for Extending Network Lifetime of Wireless Sensor Network
Authors: P Hemavathi , A. N. Nandakumar
Published: April 2018

Clustering is one of the operations in the wireless sensor network that offers both streamlined data routing services as well as energy efficiency. In this viewpoint, Particle Swarm Optimization (PSO) has already proved its effectiveness in enhancing clustering operation, energy efficiency, etc. However, PSO also suffers from a higher degree of iteration and computational complexity when it comes to solving complex problems, e.g., allocating transmittance energy to the cluster head in a dynamic network. Therefore, we present a novel, simple, and yet a cost-effective method that performs enhancement of the conventional PSO approach for minimizing the iterative steps and maximizing the probability of selecting a better clustered. A significant research contribution of the proposed system is its assurance towards minimizing the transmittance energy as well as receiving energy of a cluster head. The study outcome proved proposed a system to be better than conventional system in the form of energy efficiency.
An Internal Current Controlled BLDC Motor Drive Supplied with PV Fed High Voltage Gain DC-DC Converter
Authors: Raja Sekhar G. G. , Banakara Basavaraja
Published: April 2018

The paper presents an efficient speed control of brushless DC (BLDC) motor drive for photo-voltaic (PV) system fed system. A high-gain DC-DC converter is employed in the system to boost the PV system low output voltage to a level required for the drive system. High-gain DC-DC converter is operated in closed-loop mode to attain accurate and steady output. The converter (VSI) for BLDC is switched at fundamental frequency and thus reducing high frequency switching losses. Internal current control method is developed and employed for the speed control of PV fed BLDC motor. The appropriateness of the internal current controller for the speed control of PV fed BLDC motor is verified for increamental speed with fixed torque and decreamental speed with fixed torque operating conditions. The system is developed and results are developed using MATLAB/SIMULINK software
Model to Evaluate the Performance of Building Integrated Photovoltaic Systems using Matlab/Simulink
Authors: Camacho Castro Julian Andres , Aristizabal Cardona Andres Julian
Published: April 2018

This article describes a mathematical model implemented in Matlab/Simulink to evaluate the performance of building integrated photovoltaic systems (BIPVS). The proposed methodology allows to model independently the solar panel, the photovoltaic (pv) generator, inverter and the grid to integrate them into a single model in Simulink in order to evaluate the performance of the complete system. The validation of the model was made on a BIPV system of 6 kWp installed in a building at the Universidad de Bogotá Jorge Tadeo Lozano in Bogota, Colombia. The results indicate that there is a correlation greater than 0.9 between DC and AC power generated by the BIPV system and calculated by the model proposed for any weather condition.
A Comprehensive Analysis of Partial Shading Effect on Output Parameters of a Grid-connected PV System
Authors: Mirazizi H. Rahimi , Shafiyi M. A.
Published: April 2018

One of the issues of grid-connected photovoltaic systems is the effect of the partial shading on the key parameters and performance of the system. In practice, a share of the entire PV panel may shadded because of the various reasons, inevitably. In this case, the key parameters of the system output are affected with respect to the shading extent and paradigm. In this paper, the effects of the various partial shading patterns on the ouput of the system are examined. This is performed by deriving relevant equations and appropriate modeling of the system and defining different scenarios. The analysis on the system performance is carried out on the dominant output parameters including panel voltage, panel power, and total harmonic distortion (THD) of the inverter. Also, the study considers the effect of using bypass diodes in the panels or not. Addintionally, to compare derived conclusions, the study is implementd on a practical system. The set up is made up of a 7-level multi-level inverter, a Z-source converter, and 1 kW lateral circuitry. The real world test results of the study demonstrate a negligible deviation compared to the simulation results.
Gravitational-Search Algorithm for Optimal Controllers Design of Doubly-fed Induction Generator
Authors: Albatran Saher , Alomoush Muwaffaq I. , Koran Ahmed M.
Published: April 2018

Recently, the Gravitational-Search Algorithm (GSA) has been presented as a promising physics-inspired stochastic global optimization technique. It takes its derivation and features from laws of gravitation. This paper applies the GSA to design optimal controllers of a nonlinear system consisting of a doubly-fed induction generator (DFIG) driven by a wind turbine. Both the active and the reactive power are controlled and processed through a back-to-back converter. The active power control loop consists of two cascaded proportional integral (PI) controllers. Another PI controller is used to set the q-component of the rotor voltage by compensating the generated reactive power. The GSA is used to simultaneously tune the parameters of the three PI controllers. A time-weighted absolute error (ITAE) is used in the objective function to stabilize the system and increase its damping when subjected to different disturbances. Simulation results will demonstrate that the optimal GSA-based coordinated controllers can efficiently damp system oscillations under severe disturbances. Moreover, simulation results will show that the designed optimal controllers obtained using the GSA perform better than the optimal controllers obtained using two commonly used global optimization techniques, which are the Genetic Algorithm (GA) and Particle Swarm Optimization (PSO).
CMOS Temperature Sensor with Programmable Temperature Range for Biomedical Applications
Authors: Setiabudi Agung , Tamura Hiroki , Tanno Koichi
Published: April 2018

A CMOS temperature sensor circuit with programmable temperature range is proposed for biomedical applications. The proposed circuit consists of temperature sensor core circuit and programmable temperature range digital interface circuit. Both circuits are able to be operated at 1.0 V. The proposed temperature sensor circuit is operated in weak inversion region of MOSFETs. The proposed digital interface circuit converts current into time using Current-to-Time Converter (ITC) and converts time to digital data using counter. Temperature range can be programmed by adjusting pulse width of the trigger and clock frequency of counter. The proposed circuit was simulated using HSPICE with 1P, 5M, 3-wells, 0.18-μm CMOS process (BSIM3v3.2, LEVEL53). From the simulation of proposed circuit, temperature range is programmed to be 0 °C to 100 °C, it is obtained that resolution of the proposed circuit is 0.392 °C with -0.89/+0.29 °C inaccuracy and the total power consumption is 22.3 μW in 25 °C. 
An Investigation towards Effectiveness in Image Enhancement Process in MPSoC
Authors: H. R. Archana , K. S. Vasundara Patel
Published: April 2018

Image enhancement has a primitive role in the vision-based applications. It involves the processing of the input image by boosting its visualization for various applications. The primary objective is to filter the unwanted noises, clutters, sharpening or blur. The characteristics such as resolution and contrast are constructively altered to obtain an outcome of an enhanced image in the bio-medical field. The paper highlights the different techniques proposed for the digital enhancement of images. After surveying these methods that utilize Multiprocessor System-on-Chip (MPSoC), it is concluded that these methodologies have little accuracy and hence none of them are efficiently capable of enhancing the digital biomedical images.
Development of a Condition Monitoring Algorithm for Industrial Robots based on Artificial Intelligence and Signal Processing Techniques
Authors: Jaber Alaa Adulhady , Bicker Robert
Published: April 2018

Signal processing plays a significant role in building any condition monitoring system. Many types of signals can be used for condition monitoring of machines, such as vibration signals, as in this research; and processing these signals in an appropriate way is crucial in extracting the most salient features related to different fault types. A number of signal processing techniques can fulfil this purpose, and the nature of the captured signal is a significant factor in the selection of the appropriate technique. This chapter starts with a discussion of the proposed robot condition monitoring algorithm. Then, a consideration of the signal processing techniques which can be applied in condition monitoring is carried out to identify their advantages and disadvantages, from which the time-domain and discrete wavelet transform signal analysis are selected.
O cotidiano e a história em Brasília e Brasília, um dia em fevereiro
Authors: Lima Tatiana Hora Alves de
Published: April 2018

Os documentários Brasília, um dia em fevereiro (1996), de Maria Augusta Ramos, e Brasília (2011), de Cao Guimarães, apresentam outras visadas sobre Brasília, distantes das grandes narrativas da história e atentos ao cotidiano da cidade. Esses filmes criam uma estética da familiarização num lugar concebido a partir de uma utopia arquitetônica que apresenta uma estética do estranhamento em edifícios monumentais. Não se trata de desistoricizar a capital, mas cristalizar a história em imagens, à procura de vestígios do passado impregnados no espaço e no presente.
A planta redescoberta: um relato do encontro da ayahuasca com o povo Yudjá
Authors: Lima Tânia Stolze
Published: April 2018

Oferecendo-se mais como uma fala do que um artigo, este texto é um relato etnográfico sobre um movimento de recriação do xamanismo que tem animado o povo Yudjá nos últimos cinco anos e que foi deslanchado por seu encontro com a ayahuasca. A fim de desdobrar o meu próprio encontro com esse encontro, procuro criar uma vizinhança ou afinidade entre o movimento Yudjá, o conceito deleuze-guattariano de agenciamentos e certos movimentos que animam a ecosofia guattariana e as cosmopolíticas stengersianas.
Entrevivendo em suspensão
Authors: Simonetti Cristián
Published: April 2018

Inspirado pelo trabalho etnográfico com mergulhadores profissionais, cujas habi lidades e tecnologia são relevantes para o modo como astronautas treinam na terra e sobrevivem no espaço sideral, este artigo teoriza sobre o que significa para humanos viver em suspensão. Eu argumento que encontros científicos com ambientes extraterrestres são marcados pela coexistência de tropos de superfície e suspensão, que falam de modos contrastantes de corporizar e conceber vida extrema. O contraste entre os tropos de superfície e suspensão ressoa profundamente com, sugiro, alguns dos desafios que os extremófilos – organismos que vicejam em ambientes extremos – apresentam para visões neodarwinistas de evolução. Eu concluo salientando as relações emaranhadas entre sentir e pensar que existem na conceitualização de relações ambientais.
Macacos também choram, ou esboço para um conceito ameríndio de espécie
Authors: Garcia Uirá
Published: April 2018

Este artigo discute parte das práticas de conhecimento relativas aos animais e à caça de macacos entre os Guajá, considerando o processo de destruição de seus territórios. O artigo explicita conexões feitas e refeitas continuamente, em um regime que relaciona humanos e animais, sem, no entanto, recorrer à ideia de que caça e criação seriam formas complementares de relação com os animais. Sugiro que as maneiras como humanos e bugios vivem juntos talvez encontre aqui outra forma de pensar a própria ideia de “espécie”. O desafio a mais do artigo está em refletir, a partir dessa “noção indígena de espécie”, como poderíamos pensar outros fenômenos, por exemplo, o surto de febre amarela experimentado no Sudeste brasileiro no ano de 2017.
Apresentação do dossiê – Cosmopolitropicália: diplomacia animista em São Paulo
Authors: Skafish Peter
Published: April 2018

Em meados do outono passado em São Paulo, mais de 200 estudantes e pesquisadores desafiaram o retrocesso político e econômico de uma forma particularmente audaciosa: eles se deixaram conduzir por uma famosa bruxa em uma dança ritual e canto invocatório realizados em espiral, com o intuito de regenerar a terra em que a cidade foi construída. Starhawk, uma americana ecofeminista, ativista antiglobalização e wicca, foi convidada ao lado do líder indígena Ailton Krenak e de  antropólogos estrangeiros e brasileiros para a universidade de São Paulo para a sexta conferência bianual da ReACT (Reunião de Antropologia da Ciência e da Tecnologia). O objetivo de todos era tratar do tema da conferência, o entreviver – um neologismo que se refere ao problema apontado por grupos indígenas latino-americanos sobre como podem (e se podem) os modernos cosmopolitanos e os seres não humanos coexistir de forma bem-sucedida dentro e através de seus respectivos e com frequência bastante divergentes meios político-ecológicos.
O dia em que virei índio – a identificação ontológica com o outro como metamorfose descolonizadora
Authors: Taddei Renzo
Published: April 2018

Este texto combina reflexões sobre as dificuldades encontradas em meu trabalho etnográf ico junto à Fundação Cacique Cobra Coral, em especial no que diz respeito a transformações na forma como a alteridade foi vivida ao longo do processo etnográfico, com críticas de antropólogos indígenas à antropologia e suas práticas, de modo a fazer com que elementos da pesquisa etnográfica iluminem, na medida do possível, dimensões pouco compreendidas das referidas críticas. O texto então busca oferecer algumas reflexões sobre os impactos do aparecimento de todo um contingente de antropólogos declaradamente “animistas” dentro de um contexto em que a antropologia tacitamente reproduz, em algumas de suas práticas, o naturalismo materialista das ciências ditas “duras”.
Relationship Between Emergency Medical Services Response Time and Bystander Intervention in Patients With Out‐of‐Hospital Cardiac Arrest
Authors: Goto Yoshikazu , Funada Akira , Goto Yumiko
Published: April 2018

Background

The response time of emergency medical services (
EMS
) is an important determinant of survival after out‐of‐hospital cardiac arrest. We sought to identify upper limits of
EMS
response times and bystander interventions associated with neurologically intact survival.

Methods and Results

We analyzed the records of 553 426 patients with out‐of‐hospital cardiac arrest in a Japanese registry between 2010 and 2014. The primary study end point was 1‐month neurologically intact survival (Cerebral Performance Category scale 1 or 2). Increased
EMS
response time was associated with significantly decreased adjusted odds of 1‐month neurologically intact survival (adjusted odds ratio [
aOR
] for each 1‐minute increase, 0.89; 95% confidence interval [
CI
], 0.89–0.90), although this relationship was modified by bystander interventions. The bystander interventions and the ranges of
EMS
response times that were associated with increased adjusted 1‐month neurologically intact survival were as follows: bystander defibrillation, from ≤2 minutes (
aOR
, 3.10 [95%
CI
, 1.25–7.31]) to 13 minutes (
aOR
, 5.55 [95%
CI
, 2.66–11.2]); bystander conventional cardiopulmonary resuscitation, from 3 minutes (
aOR
1.48 [95%
CI
, 1.02–2.12]) to 11 minutes (
aOR
2.41 [95%
CI
, 1.61–3.56]); and bystander chest‐compression‐only cardiopulmonary resuscitation, from ≤2 minutes (
aOR
1.57 [95%
CI
, 1.01–2.25]) to 11 minutes (
aOR
1.92 [95%
CI
, 1.45–2.56]). However, the increase in neurologically intact survival of those receiving bystander interventions became statistically insignificant compared with no bystander interventions when the
EMS
response time was outside these ranges.

Conclusions

The upper limits of the
EMS
response times associated with improved 1‐month neurologically intact survival were 13 minutes when bystanders provided defibrillation (typically with cardiopulmonary resuscitation) and 11 minutes when bystanders provided cardiopulmonary resuscitation without defibrillation.
Field Observations and Modeling of Surfzone Sensible Heat Flux
Authors: MacMahan Jamie , Thornton Ed , Koscinski Jessica , Wang Qing
Published: April 2018

Surfzone sensible heat flux (HS,SZ) obtained through direct eddy-covariance estimates was measured at four different sandy beach sites along Monterey Bay, California. The HS,SZ source region is estimated from a footprint probability distribution function (pdf) model and is only considered when at least 70% of the footprint pdf occupies the surfzone. The measured HS,SZ is 2 times the modeled interfacial sensible heat (HS,int) using COARE3.5. A formulation for estimating sensible heat flux from spray droplets (HS,spray) generated during depth-limited wave breaking is developed. The sea-spray generation function for droplet radii ranging over 0.1 < ro < 1000 μm is based on self-similar spectra of spray droplets measured from the surfzone forced by the average depth-limited breaking wave dissipation across the surfzone. However, it is shown that the size of the spume droplets that contribute to HS,spray is limited owing to the relatively short residence time in air as the droplets fall to the sea surface during wave breaking. The addition of the surfzone-modeled HS,spray to the COARE3.5 HS,int gives values similar to the observed surfzone HS,SZ, highlighting the importance of depth-limited wave-breaking processes to sensible heat flux. Measured HS,SZ values are an order of magnitude larger than simultaneous open ocean observations.
Assessing Hurricane Rainfall Mechanisms Using a Physics-Based Model: Hurricanes Isabel (2003) and Irene (2011)
Authors: Lu Ping , Lin Ning , Emanuel Kerry , Chavas Daniel , Smith James
Published: April 2018

We examine a recently developed physics-based tropical cyclone rainfall (TCR) model and apply it to assess the mechanisms that dominate the magnitude and spatial distribution of TC rainfall, with Hurricanes Isabel (2003) and Irene (2011) as study cases. We evaluate the TCR model using Weather and Research Forecasting (WRF) Model simulations. TCR-generated rainfall fields for the two storms compare well with WRF estimates in terms of both azimuthal mean and spatial distributions. When coupled with a hydrologic model, TCR generates flood peaks over the Delaware River basin for Irene as accurately as WRF. TCR accounts for four major rainfall mechanisms: surface frictional convergence, vortex stretching, interaction of the storm with topography, and interaction of the storm with large-scale baroclinity. We show that these rainfall mechanisms affected the rainfall pattern differently for Isabel and Irene. Frictional convergence is the dominant factor, while other mechanisms are also significant. The frictional convergence depends on the boundary layer formulation, which is relatively simple in TCR and may require calibration of boundary layer parameters. Furthermore, we find that the TC rainfall distribution is strongly dependent on the temporal and spatial variation of the TC wind field, mediated by the physical mechanisms represented by TCR. When coupled with various analytical wind models, TCR generally captures the rainfall distribution, with the Holland wind model performing the best. Given its high computational efficiency, TCR can be coupled with an analytical wind model, a hydrological model, and a TC climatology model to generate large numbers of synthetic events to assess the risk associated with TC rainfall and inland flooding.
Development and Validation of a Long-Term, Global, Terrestrial Sensible Heat Flux Dataset
Authors: Siemann Amanda L. , Chaney Nathaniel , Wood Eric F.
Published: April 2018

Sensible heat flux is a turbulent flux driving interactions between the Earth’s surface and the atmosphere, propelling local and regional climate. While turbulent fluxes are measured in situ, global scales require estimates at larger spatial scales, which can be made using remotely sensed satellite data. This study uses a first-order approximation to calculate the unconstrained hourly, terrestrial, 0.5°-resolution sensible heat flux using a land surface temperature consistent with the High Resolution Infrared Radiation Sounder (HIRS) retrievals, six reanalysis-based air temperature products, and a dataset of Zilitinkevich empirical constant Czil values. This sensible heat flux dataset is constrained using the daily Bowen ratio and available energy, to produce nine constrained, daily products. All resulting global, terrestrial averages are within the uncertainty range of ±6.3 W m−2 from the 38.8 W m−2 global annual average previously reported in the literature. The product constrained with the net radiation using the Moderate Resolution Infrared Spectroradiometer (MODIS) albedo and air temperature from the National Centers for Environmental Protection (NCEP) Climate Forecast System Reanalysis (CFSR) performs closest to the FLUXNET ground observations in the monthly analysis. These sensible heat flux estimates should be used for benchmarking global climate models at monthly or annual scales, and improvements should be made to the accuracy of input variables, particularly the temperature gradient, Czil estimates, and the roughness length.