bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B38: Ewing sarcoma regression without GVHD by allo-MHC/CHM1 specific T cells
Authors: Thiel Uwe , Schober Sebastian J. , Einspieler Ingo , Kirschner Andreas , Schirmer David , Gall Katja , Schmidt Oxana , Grunewald Thomas G. P. , Sorensen Poul H. , Richter Guenther H. S. , Luettichau Irene Teichert von , Busch Dirk H. , Burdach Stefan
Published: August 2018

Background: Chondromodulin-I (CHM1) sustains malignancy in Ewing sarcoma (ES). Refractory ES carries a dismal prognosis and patients with bone-marrow (BM) metastases do not survive irrespective of therapy. We assessed HLA-A*02:01/CHM1 specific allorestricted T-cell receptor (TCR) wild-type and transgenic cytotoxic (CD8+) T cells against ES.

Patients and Methods: Three refractory HLA-A2+ ES patients were treated with HLA-A*02:01/peptide specific allorepertoire-derived (i.e., allorestricted) CD8+ T cells. Patient #1 received up to 4.8 x 105/kg body weight HLA-A*02:0 allorestricted donor-derived wild type CD8+ T cells. Patient #2 received up to 8.2 x 106/kg HLA-A*02:01 donor-derived and patient #3 up to 6 x 106/kg autologous allorestricted TCR transgenic CD8+ T cells. All patients were treated with the same TCR complementary determining region 3 allorecognition sequence for CHM1 peptide 319 (CHM1319).

Findings: HLA-A*02:01/CHM1319 specific allorestricted CD8+ T cells showed specific in vitro lysis of all patient-derived ES cell lines. Therapy was well tolerated and did not cause graft-versus-host disease (GVHD). Patients #1 and #3 showed slow progression, whereas patient #2, while having BM involvement, showed partial metastatic regression associated with T-cell homing to involved lesions. CHM1319 TCR transgenic T cells could be tracked in his BM for weeks.

Interpretation: HLA-A*02:01/antigen specific allorestricted T cells proliferate in vivo without causing GVHD. CHM1319 TCR transgenic T cells home to affected BM and are associated with partial disease regression.

Funding: Wilhelm Sander-Stiftung (2006.109.1), Else Kröner-Stiftung (GR & SB; P31/08//A123/07), BMBF (GR, UT and SB, TranSarNet 01GM1104B; SB, PROVABES 01KT1311) and Cura Placida Children's Cancer Research Foundation. PHS is funded by the Excellenzinitiative at TUM/CCC Munich.

Citation Format: Uwe Thiel, Sebastian J. Schober, Ingo Einspieler, Andreas Kirschner, David Schirmer, Katja Gall, Oxana Schmidt, Thomas G. P. Grunewald, Poul H. Sorensen, Guenther H. S. Richter, Irene Teichert von Luettichau, Dirk H. Busch, Stefan Burdach. Ewing sarcoma regression without GVHD by allo-MHC/CHM1 specific T cells [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr B38.
Abstract IA13: Dynamic cell populations are responsible for sarcoma propagating potential
Authors: Tang Jackie , David Kirsch , Alman Benjamin
Published: August 2018

Self-renewal can maintain tumor viability and play a role in recurrence and metastasis, yet little is known about the control of self-renewal in sarcomas. We previously found that cells that exclude Hoechst dye (side population or SP cells) are enriched for tumor propagating potential in serial transplantations in a variety of sarcoma types, and thus might be enriched for renewal capacity. Here we used a mouse in which soft tissue sarcomas were driven by Trp53 deletion and Kras overexpression to trace individual clones of cells. Expression of a confetti allele or expression of barcoding in the Rosa26 locus was used to trace clones. Tumors were observed in situ in the mice, and in serial translations. Intravital microscopy in transplantations of tumors from mice expressing the confetti allele was also undertaken. While there were multiple fluorescent colors in the primary tumors, over time a dominant clone was apparent. This usually arises from a small population of cells in the early tumor. This finding was verified with serial intravital microscopy, as well as tracing the clones using barcoding. SP cells were sorted from the tumors and found to be significantly enriched for tumor propagating potential as demonstrated using serial transplantations. Over multiple transplantations, the fluorescent color expressed by cells that sorted to the SP, and were enhanced for tumor propagating potential, changed. This suggests that the tumor propagating population is dynamic, rather than being limited to a specific clone. Barcoding in additional experiments showed the same result. This was further verified by genetically expressing different-colored fluorescent markers in SP and non-SP cells. While at a given time the SP expressed one fluorescent color, over serial transplantations, they expressed different colors. Taken together, this shows that the small subpopulation of cells that are enhanced for tumor propagating potential are not derived from the same clone, but a dynamic population that changes over time. Similar to findings in human sarcoma SP cells, RNA sequencing data showed that the murine SP cells were enhanced for Wnt and Notch signaling, even in different clones over time from the same initial population. Blocking these pathways suppresses the tumor propagating potential. Thus, epigenetic changes that activate Wnt and Notch in dynamic cell populations derived from different clones in the initial tumor are likely responsible for enhancing tumor propagating potential and for cells to achieve an SP cell phenotype.

Citation Format: Jackie Tang, Kirsch David, Benjamin Alman. Dynamic cell populations are responsible for sarcoma propagating potential [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA13.
Abstract IA19: Emerging genetic mechanisms in undifferentiated round cell sarcomas
Authors: Antonescu Cristina
Published: August 2018

Undifferentiated round cell sarcomas (URCS) occurring in pediatric and young adults are defined by a primitive morphology reminiscent of Ewing sarcoma, but lack the canonical EWSR1-ETS gene fusion. More than >90% of EWSR1-negative URCS are instead characterized by either a CIC-DUX4 fusion or a genetic abnormality involving BCOR. The latter group includes intra-chromosomal paracentric inversions (BCOR-CCNB3), inter-chromosomal fusions (BCOR-MAML3), or BCOR internal tandem duplications (ITD). Irrespective of their variable mechanism for dysregulation, the tumors share a similar phenotype and a BCOR upregulation at transcriptional and protein levels. In contrast, CIC-DUX4 URCS are characterized by a distinct transcriptional upregulation of PEA3 transcription factors (ETV1/4/5). For practical and treatment purposes, URCS have been regarded as “Ewing sarcoma-like” and have been managed similarly to the Ewing sarcoma family of tumors, despite their poor chemotherapy responses and aggressive clinical behavior. Alternatively these tumors are grouped by default in an “undifferentiated sarcoma category,” with their clinical management being often biased. Despite the wide spectrum of genetic abnormalities, the unifying concept is that the various gene partners or ITDs disrupt the C-terminal repressor domains of both CIC and BCOR, resulting in an oncogenic transcriptional activation of target genes. In URCS with BCOR ITD, the ITD sequences located at the C-terminal may affect the PUFD domain conformation of the BCOR protein, which might interfere with PCGF1 binding and thus could affect the PRC1-related epigenetic modifications.

Citation Format: Cristina Antonescu. Emerging genetic mechanisms in undifferentiated round cell sarcomas [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA19.
Abstract IA24: Identification of therapies for plexiform neurofibromas, a precursor of malignant peripheral nerve sheath tumors
Authors: Clapp D. Wade
Published: August 2018

Plexiform neurofibromas (PNs) are complex nerve and soft tissue tumors that affect 25-50% of individuals with neurofibromatosis type 1 (NF1), the most common genetic disease in man with a predisposition to cancer. PNs cause lifelong morbidity ranging from deformity to paralysis and mortality due to organ compression, and progress to MPNST in ~8-13% of patients. The generation of genetically engineered mouse models that closely recapitulate the development of human plexiform neurofibromas has allowed our laboratory and others to pursue genetic and pharmacologic studies to identify novel therapies. Genetic and adoptive transfer studies conducted by our lab in collaboration with Dr. Luis Parada identified a key role for c-kit/kit-ligand in tumor initiation and progression. These data led to a clinical trial administering imatinib mesylate to target aberrant stem cell factor (SCF)/c-kit signaling in the tumor microenvironment, which induced the only objective clinical responses ever obtained in a therapeutic clinical trial in pNF. Based on the observation that young children with head, neck, and airway tumors were most likely to have partial tumor regression, a registration trial in this patient population is currently being pursued. Further, additional phase 2 trials using other receptor tyrosine kinases that include c-kit are under way as well. More recently, studies in GEM models informed clinical trials of MEK inhibitors led by Dr. Brigitte Widemann (Pediatric Branch of NCI) to directly inhibit aberrant Ras signaling in PN cells. Studies are ongoing to extend these promising initial clinical findings to investigate the developmental, molecular, and pharmacokinetic effects of c-kit and MEK inhibition alone and in combination in preclinical models. Specifically, studies to explore adaptive responses to MEK inhibition monotherapy in mice and patients treated with selumetinib via integrated exome, RNAseq, and kinome studies in pre- and post-treatment tumor tissue are under way.

Citation Format: D. Wade Clapp. Identification of therapies for plexiform neurofibromas, a precursor of malignant peripheral nerve sheath tumors [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA24.
Abstract PR06: Functional genomics of CIC-DUX4 fusions in zebrafish recapitulates the spectrum of human CIC-rearranged cancers
Authors: Watson Sarah , Kendall Genevieve C. , Murchison Whitney A. , Delattre Olivier , Tirode Franck , Amatruda James F.
Published: August 2018

CIC-DUX4 sarcomas are aggressive soft-tissue malignancies characterized by frequent metastases and poor survival. Histologically, CIC-DUX4 sarcomas resemble Ewing sarcomas but do not express EWS-FLI1 or other FET-ETS fusion genes typical of Ewing sarcoma. The tumors arise from chromosomal translocations that fuse the transcriptional repressor CIC with the homeodomain-containing protein DUX4, creating an aberrant transcription factor. However, the critical targets of CIC-DUX4 have been only partly described, the cell of origin and mechanism of transformation are unknown, and animal models of the disease are lacking. Owing to this poor biologic understanding, patients with CIC-DUX4 sarcomas are treated with the same regimens used for classical Ewing sarcoma, despite generally poor outcomes.

To comprehensively address these problems, we are taking a cross-species comparative oncology approach via analysis of human CIC-DUX4 sarcomas and genetically engineered in vivo zebrafish models. Human CIC-DUX4 transgenes exerted strong effects on zebrafish embryonic development. Beginning at 5 weeks of age, almost 40% of injected animals developed invasive, rapidly growing tumors. Strikingly, two classes of tumors emerged: small round blue cell sarcomas developed in soft tissues including the trunk musculature and the ventral abdomen, and CNS-PNETs arose in the head. This recapitulates the spectrum of human tumors with CIC gene rearrangements. To further understand the molecular mechanisms of tumorigenesis, we performed RNASeq on zebrafish CIC-DUX4 sarcoma and zebrafish EWS-FLI1 sarcomas alongside human tumors and nonmalignant tissues. This analysis revealed pathways conserved between fish and human, including RAS-MAPK signaling, and highlighted the central importance of ETV4 in this disease. Further studies established ETV4 as a valuable new marker of the human disease. Taken together these findings demonstrate that CIC-DUX4 expression is sufficient to promote the development of tumors, give insight into the cellular origins of CIC-DUX4 tumors, and provide a valuable new animal model for translational research.

Citation Format: Sarah Watson, Genevieve C. Kendall, Whitney A. Murchison, Olivier Delattre, Franck Tirode, James F. Amatruda. Functional genomics of CIC-DUX4 fusions in zebrafish recapitulates the spectrum of human CIC-rearranged cancers [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr PR06.
Abstract PR09: Modeling the tumor microenvironment in sarcoma: The impact on MPNST biology and chemotherapeutic response
Authors: Dodd Rebecca , Lee Chang-Lung , Overton Mary , Huang Wesley , Eward William , Ingram Davis , Cordona Diana , Lazar Alexander , Kirsch David
Published: August 2018

NF1 haploinsufficiency is a hallmark of neurofibromatosis Type 1 and is critical for neurofibroma development. The role of the supporting stroma (endothelial cells, immune cells, fibroblasts, etc.) in the development of patient neurofibromas is well established. However, the impact of NF1 haploinsufficiency on MPNST biology is less clear. Sporadic MPNSTs arise in patients with NF1 wild-type stroma (NF1 +/+), while NF1-associated MPNSTs arise in neurofibromatosis patients with NF1 haploinsufficient stroma (NF1 -/+). Patients with NF1-associated MPNSTs have worse outcome than patients with sporadic MPNSTs, but the cause of this difference is under debate. To define the impact of stromal genetics on tumor biology, we have developed unique mouse models that reflect the genetics of patient-associated MPNSTs.

Using paired littermate mice, we model the genetic status of NF1 in the tumor microenvironment of different MPNST patient populations. We use Adenovirus-Cre injections to generate MPNSTs in NF1 Flox/Flox; CDKN2A Flox/Flox and NF1 Null/Flox; CDKN2A Flox/Flox paired littermate mice to model tumors from NF1 wild-type and NF1-assoicated patients, respectively. We find that NF1 haploinsufficiency (NF1 +/- stroma) accelerates tumor onset, which is accompanied by an increase in immune cells comprising CD11B+ cells, monocytes, and mast cells. Furthermore, mast cells are also enriched in human NF1-associated MPNSTs. We used these mouse models in a preclinical trial to examine how the tumor microenvironment influences response to multiagent chemotherapy and found that the stromal NF1 status does not impact the response of MPNSTs to chemotherapy. Taken together, these studies help clarify the role of the NF1 haploinsufficient tumor microenvironment in MPNSTs.

This abstract is also being presented as Poster B15.

Citation Format: Rebecca Dodd, Chang-Lung Lee, Mary Overton, Wesley Huang, William Eward, Davis Ingram, Diana Cordona, Alexander Lazar, David Kirsch. Modeling the tumor microenvironment in sarcoma: The impact on MPNST biology and chemotherapeutic response [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr PR09.
A Broad Test Based on Fluorescent-Multiplex PCR for Noninvasive Prenatal Diagnosis of Cystic Fibrosis
Authors: Guissart Claire , Tran Mau Them Frédéric , Debant Vanessa , Viart Victoria , Dubucs Charlotte , Pritchard Victoria , Rouzier Cécile , Boureau-Wirth Amandine , Haquet Emmanuelle , Puechberty Jacques , Bieth Eric , Khau Van Kien Philippe , Brechard Marie-Pierre , Raynal Caroline , Girardet Anne , Claustres Mireille , Koenig Michel , Vincent Marie-Claire
Published: August 2018

Background: Analysis of cell-free fetal DNA in maternal plasma is very promising for early diagnosis of monogenic diseases. However, it has been limited by the need to set up patient- or disease-specific custom-made approaches. Here we propose a universal test based on fluorescent multiplex PCR and size fragment analysis for an indirect diagnosis of cystic fibrosis (CF). Methods: The test, based on haplotyping, includes nine intra- and extragenic short tandem repeats of the CFTR locus, the coamplification of p.Phe508del (the most frequent mutation in CF patients worldwide), and a specific SRY sequence. The assay is able to determine the inherited paternal allele. Results: Our simple approach was successfully applied to 30 couples and provided clear results from the maternal plasma. The mean rate of informative markers was sufficient to propose it for use in indirect diagnosis. Conclusions: This noninvasive prenatal diagnosis test, focused on indirect diagnosis of CF, offers many advantages over current methods: it is simple, rapid, and cost-effective. It allows for the testing of a large number of couples with high risk of CF, whatever the familial mutation of the CFTR gene. It provides an alternative method to reduce the number of invasive tests.
Biomarkers for Antidepressant Efficacy of Electroconvulsive Therapy: An Exploratory Cerebrospinal Fluid Study
Authors: Kranaster Laura , Hoyer Carolin , Aksay Suna S. , Bumb J. Malte , Müller Norbert , Zill Peter , Schwarz Markus J. , Moll Natalie , Lutz Beat , Bindila Laura , Zerr Inga , Schmitz Matthias , Blennow Kaj , Zetterberg Henrik , Haffner Dieter , Leifheit-Nestler Maren , Ozbalci Cagakan , Janke Christoph , Thiel Manfred , Sartorius Alexander
Published: August 2018

Background: No candidate biomarkers based on cerebrospinal fluid (CSF) have been identified as prognostic factors in patients with major depression treated with electroconvulsive therapy (ECT), yet. Method: Following different underlying hypotheses, we analysed baseline CSF levels of markers of neurodegeneration (tau proteins, β-amyloids and neurogranin), elements of the innate immune system (interleukin [IL]-6, neopterin, soluble CD14, soluble CD163, migration inhibitory factor and monocyte chemotactic protein 1), endocannabinoids, sphingolipids and Klotho before ECT in patients with depression (n = 12) to identify possible correlations with the clinical antidepressant response to ECT. Results: Correlation with the reduction of the depressive symptoms could be observed especially for markers of neurodegeneration and elements of the innate immune system. Differences for CSF levels of several markers were found between the groups of responders and non-responders at the trend level. Limitations: The sample size is small and the ­distribution of responders and non-responders is uneven. Conclusions: It is this first study on CSF biomarkers for antidepressant efficacy of ECT warrants further research regarding the mechanism of ECT and personalized antidepressant therapy.
Finally, a Minimally Invasive Option for Intrahepatic Inferior Vena Cava Invasion by Hepatocellular Carcinoma
Authors: Soule Erik , Matteo Jerry
Published: August 2018

Background: Major vessel invasion is a late manifestation of hepatocellular carcinoma, which may directly result in mortality if left untreated. Surgical resection may be an option for select patients; however, surgery may be contraindicated. Contraindications include multifocal disease, poor liver reserve, inability to tolerate surgery, and patient preference. Cryoablation is a minimally invasive therapy utilized for treating hepatic neoplasms by subjecting them to extreme cold temperatures. The “thermal sink” effect describes cryoablation near flowing blood such as that found in high volumes within major vascular structures. Thermodynamics dictates that proximity to the flowing intravascular compartment will decrease ice formation, and therefore, tumor destruction. Methods: This report describes a novel palliative technique to induce temporary cessation of the blood flow in the intrahepatic inferior vena cava (IVC), thus enabling the operator to perform cryoablation targeting invasive cancer within. Results: Adequate ablation using this technique allowed a patient with IVC invasion 9 months of survival. Conclusion: Quality of life during this time was maximized, as recovery time from this procedure is minimal.
SRGN Promotes Colorectal Cancer Metastasis as a Critical Downstream Target of HIF-1α
Authors: Xu Yang , Xu Jie  , Yang Yanfang , Zhu Lei , Li Xubin , Zhao Weipeng
Published: August 2018

Background/Aims: The chondroitin sulfate proteoglycan serglycin (SRGN), a hematopoietic cell granule proteoglycan, has been implicated in promoting tumor metastasis; however, the underlying mechanisms remain to be elucidated. The present study aimed to investigate the SRGN gene expression and its regulation as downstream signaling of hypoxia-inducible transcription factor 1 alpha (HIF-1α) in colorectal cancer (CRC) cells and tissues. Methods: The expression of SRGN was analyzed in CRC specimens for its correlation with progression and metastasis. Using chromatin-immunoprecipitation (ChIP), quantitative real-time PCR, Western blot, and transwell assay, the functional role and underlying mechanism of SRGN in CRC metastasis were elucidated. Thus, this study provides evidence of a critical role of SRGN in metastatic progression of CRC. Results: Our results indicated that SRGN overexpression was significantly associated with poor prognosis in CRC specimens. SRGN overexpression promoted CRC cell migration and invasion in vitro; however, SRGN depletion exhibited contrasting effects. Mechanistic investigations revealed that HIF-1α regulated SRGN transcription via physically binding to a hypoxia response element in its promoter region. Conclusions: In conclusion, we demonstrated that dysregulated HIF-1α/SRGN signaling promotes CRC progression and metastasis. SRGN may serve as a potential candidate therapeutic target for metastatic CRC.
Endometrial prostaglandin F2α in vitro production and its modulation regarding dominant follicle position in cattle
Authors: Bressan Fabiana Fernandes , Membrive Claudia Maria Bertan , Goissis Marcelo Demarchi , Marques Vanessa Belentani , Cunha Pauline Martins da , Binelli Mario
Published: August 2018

Prostaglandin F2α (PGF2α) determines luteolysis in cattle, and the ability to manipulate its endogenous synthesis is indispensible for large-scale animal breeding. Estradiol (E2) and progesterone (P4) modulate several molecular pathways in endometrial cells, including the synthesis of PGF2α; however, its specific mechanisms are still not totally known. This study investigated the production in vitro and possible modulation of endometrial PGF2α due to a local effect of endogenous E2 in the ipsilateral uterine horn (UH) containing the dominant follicle (DF) or from P4 in ipsilateral horn containing the corpus luteum (CL). The PGF2α stimulators oxytocin (OT) and phorbol 12,13-dibutyrate (PDBu) were incubated with endometrial explants, and PGF2α content was measured. For that, cycling cows were synchronized, the development of DF and CL was examined by ultrasonography and on the seventh day of the estrous cycle, endometrial explants were collected and cultured in medium supplemented with 10-6 M PDBu or 10-6 M OT or non-supplemented. Media samples were collected immediately after treatment and 60 min later. Radioimmunoassay showed that the PGF2α content of the UH ipsilateral to the DF was 49% less than that of the contralateral UH (8.22 ± 0.95 vs. 12.24 ± 0.95 pg/mL/mg tissue, respectively; P < 0.01). However, the PGF2α levels did not differ between the UHs as a function of the CL position (9.46 ± 0.95 vs. 11 ± 0.95 pg/mL/mg; P > 0.05). The cellular stimulators promoted an increase in PGF2α synthesis (P < 0.02), and the effects differed among the animals (P < 0.04). The PGF2a production was higher in the explants treated with PDBu rather than OT (13.68 ± 1.16 vs. 10.01 ± 1.16 pg/mL/mg tissue, respectively; P < 0.05). In conclusion, PGF2α synthesis is modulated by the presence of the DF (local E2) but not the CL (local P4), and both PDBu and OT stimulated PGF2a synthesis.
‘Render to Caesar’
Authors: Tounsel Christopher
Published: August 2018

This article examines the relationship between missions and the government during the late colonial and early independence era in Sudan. I approach the matter of religious liberty by looking at missionaries’ references to Scripture and their understandings of the roles of Church and State during a period of political change. Acknowledgments that Christians are called to ‘render to Caesar’ were coupled by defiance to the government’s aim to inculcate Islam in the South. Mission articulations of religious thought allow for a useful comparison to the liberationist religious rhetoric that Southern Sudanese Christians fashioned during the First Civil War. Missionaries were co-architects of political theology during an era of sociopolitical change.
Drought and Land-Cover Conditions in the Great Plains
Authors: Tollerud Heather , Brown Jesslyn , Loveland Tom , Mahmood Rezaul , Bliss Norman
Published: August 2018

Land–atmosphere interactions play a critical role in the Earth system, and a better understanding of these interactions could improve weather and climate models. The interaction among drought, vegetation productivity, and land cover is of particular significance. In a semiarid environment, such as the U.S. Great Plains, droughts can have a large influence on the productivity of agriculture and grasslands, with serious environmental and economic impacts. Here, we used the vegetation drought response index (VegDRI) drought indicator to investigate the response of vegetation to weather and climate for land-cover types in the Great Plains in the United States from 1989 to 2012. We found that analysis that focused on land-cover types within ecoregion divisions provided substantially more and land-cover-based detail on the timing and intensity of drought than did summarizing across the entire Great Plains region. In the northern Great Plains, VegDRI measured more frequent drought impacts on vegetation in the western ecoregions than in the eastern ecoregions. Across the ecoregions of the Great Plains, drought impacts on vegetation were more commonly found in grassland than in cropland. For example, in the “Northwestern Great Plains” ecoregion (which encompasses areas of Montana, Wyoming, North Dakota, South Dakota, and Nebraska), grassland and nonirrigated cropland were observed in VegDRI to have historical fractional drought coverages in the growing season of 17% and 11%, respectively.
Ensemble-Based Atmospheric Reanalysis Using a Global Coupled Atmosphere–Ocean GCM
Authors: Komori Nobumasa , Enomoto Takeshi , Miyoshi Takemasa , Yamazaki Akira , Kuwano-Yoshida Akira , Taguchi Bunmei
Published: August 2018

Ensemble-based atmospheric data assimilation (DA) systems are sometimes afflicted with an underestimation of the ensemble spread near the surface caused by the use of identical boundary conditions for all ensemble members and the lack of atmosphere–ocean interaction. To overcome these problems, a new DA system has been developed by replacing an atmospheric GCM with a coupled atmosphere–ocean GCM, in which atmospheric observational data are assimilated every 6 h to update the atmospheric variables, whereas the oceanic variables are subject to no direct DA. Although SST suffers from the common biases among many coupled GCMs, two months of a retrospective analysis–forecast cycle reveals that the ensemble spreads of air temperature and specific humidity in the surface boundary layer are slightly increased and the forecast skill in the midtroposphere is rather improved by using the coupled DA system in comparison with the atmospheric DA system. In addition, surface atmospheric variables over the tropical Pacific have the basinwide horizontal correlation in ensemble space in the coupled DA system but not in the atmospheric DA system. This suggests the potential benefit of using a coupled GCM rather than an atmospheric GCM even for atmospheric reanalysis with an ensemble-based DA system.
Emotions and identity work: Emotions as discursive resources in the constitution of junior professionals’ identities
Authors: Ahuja Sumati , Heizmann Helena , Clegg Stewart
Published: August 2018

For junior professionals, notions of professional identity established during their education are often called into question in the early stages of their professional careers. The workplace gives rise to identity challenges that manifest in significant emotional struggles. However, although extant literature highlights how emotions trigger and accompany identity work, the constitutive role of emotions in identity work is under-researched. In this article, we analyse how junior professionals mobilize emotions as discursive resources for identity work. Drawing on an empirical study of junior architects employed in professional service firms, we examine how professional identities, imbued with varying forms of discipline and agency, are discursively represented. The study makes two contributions to the literature on emotions and identity work. First, we identify three key identity work strategies ( idealizing, reframing and distancing) that are bound up in junior architects’ emotion talk. We suggest that these strategies act simultaneously as a coping mechanism and as a disciplinary force in junior architects’ efforts to constitute themselves as professionals. Second, we argue that identity work may not always lead to the accomplishment of a positive sense of self but can express a sense of disillusionment that leads to the constitution of dejected professional identities.
Assessment of the Stability of von Willebrand Profile Clotting Factors and Platelet Dense Granule Testing Following Air Transport
Authors: Mai Denise Bichuyen , Smith Mary R. , Gunning William T.
Published: August 2018

The purpose of this study was to determine the reliability of test results dependent upon blood and plasma sample stability when shipped by airfreight courier for reference laboratory assessment. Of particular interest was evaluation of von Willebrand profile assays and platelet dense granule storage pool analysis. Peripheral venous blood was obtained from healthy volunteers. von Willebrand factor (VWF) activity, VWF antigen, and factor VIII coagulant activity assays were performed immediately following venipuncture with additional aliquots of plasma frozen and stored at −70°C for subsequent analysis 48 hours later. One frozen aliquot was shipped via airfreight for analysis 48 hours later, with another frozen aliquot that remained on-site. Blood was also collected to enumerate platelet dense granules to determine whether shipment would affect results. Statistical analysis of all test results demonstrated significant correlation between immediately assayed samples and samples that were stored for 48 hours at −70°C ( P < .0001), or frozen and shipped on dry ice ( P < .0001) for analysis upon return to our laboratory. No difference was found in the mean number of platelet dense granules between samples retained in our laboratory or samples analyzed upon return of shipment ( P = .751).
Tracking Affective Labour for Agility in the Quantified Workplace
Authors: Moore Phoebe V
Published: August 2018

Sensory and tracking technologies are being introduced into workplaces in ways Taylor and the Gilbreths could only have imagined. New work design experiments merge wellness with productivity to measure and modulate the affective and emotional labour of resilience that is necessary to survive the turbulence of the widespread incorporation of agile management systems, in which workers are expected to take symbolic direction from machines. The Quantified Workplace project was carried out by one company that fitted sensory algorithmic devices to workers’ computers and bodies, which, this article argues, identify workers’ so-called agility and reveal management practices that track affective and emotional labour, categorized in the project as stress, subjective productivity and wellbeing. Capital’s accelerated attempts to capture more areas of work and workers’ capacities facilitate the conversion of labour power into a source of value but also results in alienation and abstraction. Participants’ resistance to participation in the Quantified Workplace reveals tensions in the labour process when affect is measured in processes of corporate change.
A survey of intrusion detection on industrial control systems
Authors: Hu Yan , Yang An , Li Hong , Sun Yuyan , Sun Limin
Published: August 2018

The modern industrial control systems now exhibit an increasing connectivity to the corporate Internet technology networks so as to make full use of the rich resource on the Internet. The increasing interaction between industrial control systems and the outside Internet world, however, has made them an attractive target for a variety of cyber attacks, raising a great need to secure industrial control systems. Intrusion detection technology is one of the most important security precautions for industrial control systems. It can effectively detect potential attacks against industrial control systems. In this survey, we elaborate on the characteristics and the new security requirements of industrial control systems. After that, we present a new taxonomy of intrusion detection systems for industrial control systems based on different techniques: protocol analysis based, traffic mining based, and control process analysis based. In addition, we analyze the advantages and disadvantages of different categories of intrusion detection systems and discuss some future developments of intrusion detection systems for industrial control systems, in order to promote further research on intrusion detection technology for industrial control systems.
Enabling smart behavior through automatic service composition for Internet of Things–based Smart Homes
Authors: Santofimia Maria J , Villa David , Aceña Oscar , del Toro Xavier , Trapero Cristian , Villanueva Felix J , Lopez Juan Carlos
Published: August 2018

This article presents an Internet of Things architecture for Smart Homes that specifically targets service composition and reconfiguration as enablers for the actuation and smart behavior capabilities. To this end, the main challenge that has to be addressed is the support to a seamless integration, composition, and reconfiguration of Internet of Things objects. Two enabling technologies are proposed here: a planning strategy based on a common-sense reasoning approach for service composition and a virtual-network protocol for Inter-Domain Messaging. The planner will identify the services that, properly connected, will cater for arisen, and therefore, unexpected needs. The virtual-network protocol will provide the support for this interconnection to take place in a transparent and orthogonal manner. This is particularly important to enable autonomous systems to instantiate composite services. To demonstrate the capabilities of the resulting framework, two use cases are presented, which under real circumstances demonstrate the potential of the proposed approach.
Study on windbreak performance of tree canopy by numerical simulation method
Authors: Jian Zhang , Bo Li , Mingyue Wang
Published: August 2018

When airflow fly over trees, a shelter area will be generated at downstream area, and wind speed in the region will be reduced correspondingly. In order to analyze the windbreak performance of tree canopy, porous media method and additional source term are explored to simulate by computational fluid dynamics. Based on the given method, windbreak performance of trees with different canopy porosity, canopy shapes and distances between trees is investigated in detail, and characteristics of wind flow on the downstream of tree are shown. Results showed that small canopy porosity does not always mean good performance of windbreak, especially for the lower part. Canopy shapes only affect wind speed in the wake range. In these regions, windbreak performance of tree depends on the thickness of canopy. When distance is beyond 3H (H is the height of tree), wind speed becomes uniform at the downstream of tree and spacing can be equivalent to the porosity. But, for the region close to tree, trees with spacing cannot provide effective windshield. These simulations of tree canopy windbreak performance are conducted. All the results of the new model show better canopy flow characteristics through the field.
Visual Estimation of Dupuytren’s Flexion Contractures—A Prospective Comparative Trial
Authors: Corkum Joseph P. , Gillis Joshua A. , Tang David T.
Published: August 2018

Purpose:

Surgeons and resident physicians in a clinic setting often visually estimate Dupuytren flexion contractures of the hand to follow disease progression and decide on management. No previous study has compared visual estimates with a standardized instrument to ensure measurement reliability.

Methods:

Consecutive patients consulted for Dupuytren flexion contractures of the hand had individual joint contractures estimated in degrees (°) by both a resident physician and staff surgeon. Estimates were compared with goniometer measurements to generate intraclass correlation coefficients (ICCs), and residents and surgeons were compared based on their accuracy.

Results:

Twenty-eight patients enrolled in this study, which provided a total of 80 hand joints for analysis. Resident physicians achieved an ICC of 0.42, which indicates poor reliability. The hand surgeon achieved an ICC of 0.86, which indicates high reliability. The surgeon also had better accuracy than the residents.

Conclusion:

Hand surgeons should be mindful of the limitations of visual estimates of Dupuytren flexion contractures, particularly when conducted by trainees. Joint angle measurements taken for the purposes of research should be done with a goniometer at minimum.
Multidimensional family therapy in adolescents with a cannabis use disorder: long-term effects on delinquency in a randomized controlled trial
Authors: van der Pol Thimo M. , Hendriks Vincent , Rigter Henk , Cohn Moran D. , Doreleijers Theo A. H. , van Domburgh Lieke , Vermeiren Robert R. J. M.
Published: August 2018

Background

Substance use and delinquency are considered to be mutual risk factors. Previous studies have shown that multidimensional family therapy (MDFT) is effective in tackling both conditions on the short term. The current study examines the long-term effects of MDFT on criminal offending.

Methods

109 adolescents with cannabis use disorder and comorbid problem behavior were randomly assigned to either MDFT or cognitive behavioral therapy (CBT). Police arrest data were collected for 6 years: 3 years prior to and 3 years after treatment entry. Using survival analysis and repeated measure General Linear Models (rmGLM), the two treatment groups were compared on number of arrests, type of offence, and severity of offence. Moderator analyses looking at age, disruptive behavior disorders, history of crimes, family functioning, and (severe) cannabis use were conducted (rmGLM).

Results

While police arrest rates increased in the 3 years before treatment, the rates decreased substantially after the start of both treatments. No differences were found between the treatment groups with respect to either time to first offence from the start of the treatment or changes in frequency or severity of offending over time. A treatment effect trend favoring MDFT was found for property offending in the subgroup of adolescents with high baseline-severity of cannabis use.

Conclusions

Across a follow-up period of 3 years, MDFT and CBT were similarly effective in reducing delinquency in adolescents with a cannabis use disorder.

Trial registration ISRCTN51014277, Registered 17 March 2010—Retrospectively registered, http://www.isrctn.com/ISRCTN51014277
Endocrine Deficiency As a Function of Radiation Dose to the Hypothalamus and Pituitary in Pediatric and Young Adult Patients With Brain Tumors
Authors: Vatner Ralph E. , Niemierko Andrzej , Misra Madhusmita , Weyman Elizabeth A. , Goebel Claire P. , Ebb David H. , Jones Robin M. , Huang Mary S. , Mahajan Anita , Grosshans David R. , Paulino Arnold C. , Stanley Takara , MacDonald Shannon M. , Tarbell Nancy J. , Yock Torunn I.
Published: August 2018

Purpose

There are sparse data defining the dose response of radiation therapy (RT) to the hypothalamus and pituitary in pediatric and young adult patients with brain tumors. We examined the correlation between RT dose to these structures and development of endocrine dysfunction in this population.

Materials and Methods

Dosimetric and clinical data were collected from children and young adults (< 26 years of age) with brain tumors treated with proton RT on three prospective studies (2003 to 2016). Deficiencies of growth hormone (GH), thyroid hormone, adrenocorticotropic hormone, and gonadotropins were determined clinically and serologically. Incidence of deficiency was estimated using the Kaplan-Meier method. Multivariate models were constructed accounting for radiation dose and age.

Results

Of 222 patients in the study, 189 were evaluable by actuarial analysis, with a median follow-up of 4.4 years (range, 0.1 to 13.3 years), with 31 patients (14%) excluded from actuarial analysis for having baseline hormone deficiency and two patients (0.9%) because of lack of follow-up. One hundred thirty patients (68.8%) with medulloblastoma were treated with craniospinal irradiation (CSI) and boost; most of the remaining patients (n = 56) received involved field RT, most commonly for ependymoma (13.8%; n = 26) and low-grade glioma (7.4%; n = 14). The 4-year actuarial rate of any hormone deficiency, growth hormone, thyroid hormone, adrenocorticotropic hormone, and gonadotropin deficiencies were 48.8%, 37.4%, 20.5%, 6.9%, and 4.1%, respectively. Age at start of RT, time interval since treatment, and median dose to the combined hypothalamus and pituitary were correlated with increased incidence of deficiency.

Conclusion

Median hypothalamic and pituitary radiation dose, younger age, and longer follow-up time were associated with increased rates of endocrinopathy in children and young adults treated with radiotherapy for brain tumors.
Highly Selective Transfer Hydrogenation of Carbonyl Compounds Using La2O3
Authors: Natsir Taufik Abdillah , Hara Takayoshi , Ichikuni Nobuyuki , Shimazu Shogo
Published: August 2018

In the present study, we used rare earth oxides for the catalytic transfer hydrogenation of carbonyl compounds. Pre-treated La2O3 showed better catalytic performance than various rare earth oxides for the reduction of carbonyl compounds. Reaction conditions, precursors, and donor hydrogen sources were also investigated to optimize the hydrogen transfer to furfural in 2-propanol. La2O3 provided a conversion of different carbonyl compounds and selectivity to the corresponding alcohols up to 100% and 99%, respectively. We also investigated a plausible mechanism using in situ IR and found that furfural was adsorbed on the catalyst surface in a different adsorption mode. Meanwhile, La(OH)3, a hydroxide derivative of La2O3 formed during the reaction, was also catalytically active.
Combinatorial interplay of RNA-binding proteins tunes levels of mitochondrial mRNA in trypanosomes
Authors: Dixit Sameer , Lukeš Julius
Published: August 2018

MRP1/2 is a heteromeric protein complex that functions in the trypanosomatid mitochondrion as part of the RNA editing machinery, which facilitates multiple targeted insertions and deletions of uridines. MRP1/2 was shown to interact with MRB8170, which initiates RNA editing by marking pre-edited mRNAs, while TbRGG2 is required for its efficient progression on pan-edited mRNAs. Both MRP1/2 and TbRGG2 are capable of modulating RNA–RNA interactions in vitro. As determined by using iCLIP and RIP-qPCR, RNAs bound to MRP1/2 are characterized and compared with those associated with MRB8170 and TbRGG2. We provide evidence that MRP1 and MRB8170 have correlated binding and similar RNA crosslinking peak profiles over minimally and never-edited mRNAs. Our results suggest that MRP1 assists MRB8170 in RNA editing on minimally edited mRNAs.
Contextualization of Wasathiyah Values in Haji Sulong’s thoughts for Islamic Education Renewal in South Thailand
Authors: Sumarni Sri
Published: August 2018

Since Pattani region entered into a nation state of Thailand there have been various policies of assimilation toward the people of Southern Thailand. Until the present time, this policy has caused a conflict to both sides. The main problem is not about religious issues, but the ethnicity to maintain Malay-Muslim identity from Thai-Buddhist threats. Efforts to understand each other's identity, both Malay-Islamic and Thai-Buddhist can be continuously explored, such as: Islamic values ​​as ummatan wasathan and Buddha’s Majjhima-patipada oriented to the idea of ​​"middle way". Efforts to understand each other can be done through education starting from Early Childhood Education to Higher Education. Efforts to understand both identities can also be done by a figure, such as Haji Sulong. Haji Sulong's struggle was initially prioritized the renewal of the Islamic Education System in Pattani, both the management and the curriculum. But along with the royal policy that continues to pressure the people of Southern Thailand, Haji Sulong also plunged into the political world. Haji Sulong heroic values ​​can be a transformative spirit for the people of South Thailand, such as: (1) Innovative value, (2) Caring values, (3) Values ​​of love/empathy, (4) Prudence, (5) The value of self-control, (6) The value of justice, (7) The value of courage, and etc.
Effect of Yttrium Oxide Dispersion on the Microstructure and Properties of Tungsten Heavy Alloys
Authors: Gnanasambandam Prabhu , Kumar Arockia , Nandy Tapash Kumar
Published: August 2018

Tungsten heavy alloys are considered as two phase composites with 88 to 97 wt% tungsten interspersed in a matrix of relatively low melting elements such as nickel, iron and cobalt. The mechanical properties of these alloys are greatly influenced by the microstructural features such as tungsten grain size, tungsten-tungsten contiguity and matrix volume fraction. Oxide dispersion strengthening (ODS), refinement of tungsten grain size, cyclic heat treatment, addition of alloying elements like Cr, Mo, and Co are some of the methods investigated to improve the microstructural features and thereby the mechanical properties of tungsten heavy alloys. Among these methods ODS has been considered as a promising processing technique since the tungsten grain size observed in ODS alloys is finer compared to the conventional alloys and more importantly the dynamic fracture mode changes from adiabatic shear band to brittle fracture. The present study is mainly focused on investigating the effect of 0.3 wt% yttrium oxide (Y2O3) dispersion on the microstructure and consequently the tensile properties of 90W-6Ni-2Fe-2Co alloy. With 0.3 wt%Y2O3, the ODS alloy (89.7W-6Ni-2Fe-2Co-0.3Y2O3) is processed by two-stage sintering with subsequent thermo-mechanical treatment which includes vacuum heat treatment and swaging. ODS alloy and the conventional alloy (without oxides) are compared based on the microstructures and tensile properties obtained after liquid phase sintering and after final processing.