bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A40: Twist1 activation in muscle progenitor cells during development or adulthood causes severe muscle loss reminiscent of human cancer cachexia
Authors: Parajuli Parash , Kumar Santosh , Loumaye Audrey , Singh Purba , Eragamreddy Sailaja , Nguyen Thien Ly , Ozkan Seval , Razzaqe Mohammed S. , Prunier Céline , Thissen Jean-Paul , Atfi Azeddine
Published: May 2018

Cancer cachexia is characterized by extreme skeletal muscle loss that results in high morbidity and mortality. The incidence of cachexia varies among tumor types, being lowest in sarcomas, whereas 90% of pancreatic ductal adenocarcinoma (PDAC) patients experience severe weight loss. How these tumors trigger muscle depletion is still unfolding. Serendipitously, we found that overexpression of Twist1 in mouse muscle progenitor cells, either constitutively during development or inducibly in adult animals, caused severe muscle atrophy with features reminiscent of cachexia. Using several genetic mouse models of PDAC, we detected a massive increase in Twist1 expression in muscle undergoing cachexia. In cancer patients, elevated levels of Twist1 are associated with greater degrees of muscle wasting. Both genetic and pharmacologic inactivation of Twist1 in muscle progenitor cells afforded substantial protection against cancer-mediated cachexia, which translated into meaningful survival benefits, implicating Twist1 as a possible target for attenuating muscle cachexia in cancer patients.

Citation Format: Parash Parajuli, Santosh Kumar, Audrey Loumaye, Purba Singh, Sailaja Eragamreddy, Thien Ly Nguyen, Seval Ozkan, Mohammed S. Razzaqe, Céline Prunier, Jean-Paul Thissen, Azeddine Atfi. Twist1 activation in muscle progenitor cells during development or adulthood causes severe muscle loss reminiscent of human cancer cachexia [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A40.
Abstract B01: A genetically engineered mouse model of de novo bone metastasis
Authors: Arriaga Juan Martin , Abate-Shen Cory
Published: May 2018

The primary metastatic site of prostate cancer is the bone, which is associated with high morbidity and mortality. Despite this fact, very few genetically engineered mouse models recapitulate this phenotype, hindering our ability to model and understand the molecular drivers of bone metastasis. Our laboratory has generated a highly metastatic mouse model of castration-resistant prostate cancer based on the monoallelic loss of function of Nkx3.1, biallelic deletion of Pten, and oncogenic mutation of Kras in the prostate, termed the NPK model. By tracking these tumors with a bright fluorescent reporter, we now show that these tumors metastasize to bone with a penetrance of ~45% and display a bone distribution similar to that of human cancer. This model has thus allowed us to comprehensively profile the molecular alterations of bone metastatic lesions compared to the primary tumor and other metastatic sites. We found that differential gene expression profiles comparing bone metastases with primary tumors differ from those comparing lung metastases with primary tumors, suggesting that different biologic principles underlie metastasis to these two organ sites. Furthermore, gene-expression profiling demonstrated significant overlap with human bone metastases at the gene, master regulator, and pathway levels. Even though expression of the androgen receptor (AR) is maintained in the primary tumor and most lung metastases, bone lesions are AR-, without evidence of neuroendocrine (NE) differentiation, pointing to an AR-, NE- prostate cancer subtype, which is increasingly frequent in human prostate cancer. These results lay the groundwork for understanding the molecular drivers and pathways that are important for bone metastatic spread and may hopefully aid in selecting appropriate molecular targets to combat the metastatic disease.

Citation Format: Juan Martin Arriaga, Cory Abate-Shen. A genetically engineered mouse model of de novo bone metastasis [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr B01.
Abstract B11: Foxm1 mediates maintenance and progression of mouse lung tumor driven by oncogenic Kras
Authors: Chao Sheng-Yang , Li Chien-Cheng , Liang Sheng-Kai , Chiu Yi-Shiuan , Lin Yi-Kai , Hsu Chia-Chan , Chen Jen-Kun , Tsou Tsui-Chun , Wang I-Ching
Published: May 2018

Oncogenic mutation of Kras gene is one of the major causes of non-small cell lung cancer (NSCLC), and there is no effective chemotherapy agent available for targeting cancers harboring oncogenic Kras mutations. Hence, identifying new downstream molecular targets of KRAS signaling is critical for improving current therapeutic outcomes. Previous research has demonstrated that increased activity and expression of Forkhead box M1 (FOXM1) transcription factor are associated with poor prognosis in NSCLC patients. We and others have reported that FOXM1 regulates gene transcription network of cell cycle, angiogenesis, epithelial-to-mesenchymal transition (EMT), cell migration, and cancer stemness. Deletion of Foxm1 alleles in respiratory epithelial cells diminished the lung tumor initiation in SPC-rtTA/tetO-KrasG12D/Foxm1-/- mice; however, whether Foxm1 is critical for Kras mutant tumor maintenance and progression remains unclear. Herein, we report that intratracheal (IT) injected adenoviral Ad-Cre to CCSP-rtTA/tetO-KrasG12D/Foxm1fl/fl mice that bear induced KRAS mutant lung tumors, causing 75% of preexisting lung tumor regression as detected by micro-computed tomography (μCT). IT treatment with Ad-Cre that mediated genetically deletion of Foxm1 alleles in lungs, resulted in reduced proliferation of tumor cells. Moreover, in vitro disruption of FOXM1 expression by shRNA diminished cell proliferation on plate and anchorage-independent growth in soft agar of KRAS-mutated lung cancer NCI-H23 as well as KRASG12D-transformed BEAS-2B cells. Accordingly, these results demonstrated that Foxm1 is critical for oncogenic KRAS signaling pathway in both maintenance and progression of lung adenocarcinoma, suggesting that Foxm1 could be a potential therapeutic target to improve the outcome of KRAS mutant lung cancer treatment.

Citation Format: Sheng-Yang Chao, Chien-Cheng Li, Sheng-Kai Liang, Yi-Shiuan Chiu, Yi-Kai Lin, Chia-Chan Hsu, Jen-Kun Chen, Tsui-Chun Tsou, I-Ching Wang. Foxm1 mediates maintenance and progression of mouse lung tumor driven by oncogenic Kras [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr B11.
Abstract B33: CRISPR/Cas9 generation of Ret and Ntrk1 fusion oncogenes and novel in vitro sgRNA screening method
Authors: Schubert Laura , Le Anh T. , Malkoski Stephen P. , Nemenoff Raphael , Doebele Robert C.
Published: May 2018

Chromosomal rearrangements of ALK, RET, ROS1, and NTRK1 collectively represent approximately 10% of oncogenic drivers in lung adenocarcinoma. These rearrangements result in the aberrant expression and constitutive activation of a chimeric fusion kinase, which promotes growth, proliferation and survival of the cancer cell. CRISPR/Cas9 technology can now be employed to generate these chromosomal rearrangements both in vitro and in vivo. sgRNAs can be designed to target the Cas9 endonuclease to introns within the 5′ and 3′ gene partners of the rearrangement. A unique advantage of this approach is that it is compatible with immunocompetent mouse models. We have developed a novel in vitro screening strategy to identify sgRNAs that successfully generated the intended rearrangements. Ba/F3 cells are a murine B-cell cell line whose proliferation is normally dependent on the exogenous addition of the cytokine interleukin 3 (IL3), but can be rendered IL3 independent if an oncogenic alteration is introduced. We hypothesized that IL3-independence in Ba/F3 cells could be used as a method to select for cells that had successfully created chromosomal rearrangements leading to oncogenic fusions. This strategy eliminates the need for single cell cloning to confirm that successful CRISPR genome editing has occurred. We transfected Ba/F3 cells with pairs of sgRNAs within the PX330 Cas9 containing plasmid and then withdrew IL3. Cells that became IL3 independent were tested for rearrangements. Using this screening system, we successfully generated Kif5b-Ret, Trim24-Ret, and Tpm3-Ntrk1 rearrangements in Ba/F3 cells. These rearrangements were confirmed using PCR or RT-PCR and sequencing using fusion-specific primers. Additionally, the Ret rearrangements and Ntrk1 rearrangements were far more sensitive to RET and TRK inhibitors, respectively, than parental Ba/F3 cells, further confirming that the Ba/F3 cells' growth was now dependent on signaling from the fusion kinase. RET protein expression was also detected with Western blotting in the two Ret rearranged Ba/F3 cell lines. Our future plans are to introduce adenovirus containing validated sgRNAs into immune-competent mice, and confirm that they generate tumors with the intended rearrangements.

Citation Format: Laura Schubert, Anh T. Le, Stephen P. Malkoski, Raphael Nemenoff, Robert C. Doebele. CRISPR/Cas9 generation of Ret and Ntrk1 fusion oncogenes and novel in vitro sgRNA screening method [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr B33.
Abstract B38: In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis
Authors: Roper Jatin , Tammela Tuomas , Cetinbas Naniye Malli , Akkad Adam , Roghanian Ali , Rickelt Steffen , Almeqdadi Mohammad , Wu Katherine , Oberli Matthias , Sánchez-Rivera Francisco , Park Yoona , Liang Xu , Eng George , Taylor Martin S. , Azimi Roxana , Kedrin Dmitriy , Neupane Rachit , Beyaz Semir , Sicinska Ewa T. , Suarez Yvelisse , Yoo James , Chen Lillian , Zukerberg Lawrence , Katajisto Pekka , Deshpande Vikram , Bass Adam , Tsichlis Philip N. , Lees Jacqueline , Langer Robert , Hynes Richard O. , Chen Jianzhu , Bhutkar Arjun J. , Jacks Tyler , Yilmaz Ömer H.
Published: May 2018

In vivo interrogation of the function of genes implicated in tumorigenesis is limited by the need to generate and cross germline mutant mice. Here we describe approaches to model colorectal cancer (CRC) and metastasis that rely on in situ gene editing and orthotopic organoid transplantation in mice without cancer-predisposing mutations. Autochthonous tumor formation is induced by CRISPR/Cas9-based editing of the Apc and Trp53 tumor suppressor genes in colon epithelial cells and by orthotopic transplantation of Apc-edited colon organoids. ApcΔ/Δ;KrasG12D/+;Trp53Δ/Δ (AKP) mouse colon organoids and human CRC organoids engraft in the distal colon and metastasize to the liver. Finally, we apply the orthotopic transplantation model to characterize the clonal dynamics of Lgr5+ stem cells and demonstrate sequential activation of an oncogene in established colon adenomas. These experimental systems enable rapid in vivo characterization of cancer-associated genes and reproduce the entire spectrum of tumor progression and metastasis.

Citation Format: Jatin Roper, Tuomas Tammela, Naniye Malli Cetinbas, Adam Akkad, Ali Roghanian, Steffen Rickelt, Mohammad Almeqdadi, Katherine Wu, Matthias Oberli, Francisco Sánchez-Rivera, Yoona Park, Xu Liang, George Eng, Martin S. Taylor, Roxana Azimi, Dmitriy Kedrin, Rachit Neupane, Semir Beyaz, Ewa T. Sicinska, Yvelisse Suarez, James Yoo, Lillian Chen, Lawrence Zukerberg, Pekka Katajisto, Vikram Deshpande, Adam Bass, Philip N. Tsichlis, Jacqueline Lees, Robert Langer, Richard O. Hynes, Jianzhu Chen, Arjun J. Bhutkar, Tyler Jacks, Ömer H. Yilmaz. In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr B38.
Abstract B44: Lysyl oxidases suppress pancreatic cancer progression and inhibit FAK and ERK signaling
Authors: Shields Mario , Maguin Pascal , Giuliano Christopher , Dallas Sarah , Wilkinson John Erby , Egeblad Mikala
Published: May 2018

Pancreatic cancer carries a dismal prognosis, as most patients present with locally advanced and metastatic disease at time of diagnosis. High levels of type I collagen extracellular matrix in pancreatic tumor specimens are associated with poor survival and resistance to therapy. Furthermore, the expression of lysyl oxidases (LOXs), enzymes that mediate cross-linking and linearization of collagen type I, correlate with poor prognosis in breast and pancreatic cancer. However, a clinical trial targeting LOX-like (LOXL) 2 in pancreatic cancer did not show any survival benefits, pointing to a limited understanding of the context in which these enzymes function in cancer progression.

To understand how collagen structure influences cancer cell behavior, we used host mice that expressed GFPtopaz fused to collagen type I and performed intravital microscopy after orthotopic injection of fluorescently labeled cancer cells (derived from the KPC mouse models of pancreatic cancer). Strikingly, we observed that invasive cancer cells migrated out of the tumors on linear type I collagen. Surprisingly, inhibition of LOX and LOXL2, using a pharmacologic inhibitor or shRNA-mediated knockdown, had the opposite results of what we expected with increased metastasis, collagen linearization, and focal adhesion kinase (FAK) activity. Indicating a mechanism independently of collagen crosslinking, LOX inhibition promoted invasion and increased FAK and Ras/ERK-MAPK signaling in vitro, when cells were grown on plastic. We demonstrated that the FAK activity was required for the increased metastasis induced by LOX inhibition, using a clinical stage pharmacologic inhibitor. Our data highlight that LOXs in pancreatic cancer play an important role in suppression of the ERK and FAK signaling pathways, and metastasis. Indeed, the earliest report of lysyl oxidase function in cancer was as a tumor suppressor in Ras transformed cells.

Citation Format: Mario Shields, Pascal Maguin, Christopher Giuliano, Sarah Dallas, John Erby Wilkinson, Mikala Egeblad. Lysyl oxidases suppress pancreatic cancer progression and inhibit FAK and ERK signaling [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr B44.
Abstract IA09: Metabolic recycling in cancer
Authors: Haigis Marcia
Published: May 2018

Metabolic reprogramming is a hallmark of cancer that supports the rapid proliferation and survival of tumor cells. While many studies have focused on identifying pathways involved in increased fuel usage, such as glucose and glutamine uptake and metabolism, the fate of metabolic waste products has been little investigated. Ammonia is a ubiquitous by-product of cellular metabolism, long thought to be a toxic waste product. Here we will discuss ammonia recycling to support cellular biomass and proliferation in breast cancer.

Citation Format: Marcia Haigis. Metabolic recycling in cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr IA09.
Antenatal Workup of Early Megacystis and Selection of Candidates for Fetal Therapy
Authors: Fontanella Federica , Duin Leonie , Adama van Scheltema Phebe N. , Cohen-Overbeek Titia E. , Pajkrt Eva , Bekker Mireille , Willekes Christine , Bax Caroline J. , Oepkes Dick , Bilardo Catia M.
Published: May 2018

Objective: To investigate the best criteria for discriminating fetuses with isolated posterior urethral valves from those theoretically not eligible for fetal treatment because of complex megacystis, high chance of spontaneous resolution, and urethral atresia. Methods: A retrospective national study was conducted in fetuses with megacystis detected before 17 weeks’ gestation (early megacystis). Results: In total, 142 cases with fetal megacystis were included in the study: 52 with lower urinary tract obstruction, 29 with normal micturition at birth, and 61 with miscellaneous syndromal associations, chromosomal and multiple structural abnormalities (complex megacystis). Only a nuchal translucency > 95th centile, and not a longitudinal bladder diameter ≤15 mm (p = 0.24), significantly increased the risk of complex megacystis (p < 0.01). Cases with a high chance of spontaneous resolution were identified by using the cut-off of 12 mm, as demonstrated in a previous study, and the finding of an associated umbilical cord cyst carried a high-risk of urethral atresia (odds ratio: 15; p = 0.026), an unfavorable condition for antenatal treatment. An algorithm encompassing these three criteria demonstrated good accuracy in selecting fetuses theoretically eligible for fetal treatment (specificity 73%; sensitivity 92%). Conclusions: Cases theoretically eligible for early fetal therapy are those with normal nuchal translucency, a longitudinal bladder diameter > 12 mm, and without ultrasound evidence of umbilical cord cysts.
Effect of Air Pollution on Exacerbations of Bronchiectasis in Badalona, Spain, 2008–2016
Authors: Garcia-Olivé Ignasi , Stojanovic Zoran , Radua Joaquim , Rodriguez-Pons Laura , Martinez-Rivera Carlos , Ruiz Manzano Juan
Published: May 2018

Introduction: Air pollution has been widely associated with respiratory diseases. Nevertheless, the association between air pollution and exacerbations of bronchiectasis has been less studied. Objective: To analyze the effect of air pollution on exacerbations of bronchiectasis. Methods: This was a retrospective observational study conducted in Badalona. The number of daily hospital admissions and emergency room visits related to exacerbation of bronchiectasis (ICD-9 code 494.1) between 2008 and 2016 was obtained. We used simple Poisson regressions to test the effects of daily mean temperature, SO2, NO2, CO, and PM10 levels on bronchiectasis-related emergencies and hospitalizations on the same day and 1–4 days after. All p values were corrected for multiple comparisons. Results: SO2 was significantly associated with an increase in the number of hospitalizations (lags 0, 1, 2, and 3). None of these associations remained significant after correcting for multiple comparisons. The number of emergency room visits was associated with higher levels of SO2 (lags 0–4). After correcting for multiple comparisons, the association between emergency room visits and SO2 levels was statistically significant for lag 0 (p = 0.043), lag 1 (p = 0.018), and lag 3 (p = 0.050). Conclusions: The number of emergency room visits for exacerbation of bronchiectasis is associated with higher levels of SO2.
Testis-Sparing Surgery in Patients with Germ Cell Cancer: Indications and Clinical Outcome
Authors: Pfister David , Paffenholz Pia , Haidl Friederike
Published: May 2018

Testicular cancer affects mainly young men between 20 and 30 years of age. Due to the availability of effective chemotherapy, the majority of patients are cured. Despite an increased risk of metachronous testicular cancer, it should be carefully considered whether immediate orchiectomy is indicated. This mini review gives an account of the available literature on testis-sparing surgery in patients with unilateral or bilateral synchronous or metachronous testicular cancer.
Endothelial Progenitor Cells and Kidney Diseases
Authors: Ozkok Abdullah , Yildiz Alaattin
Published: May 2018

Endothelial progenitor cells (EPC) are bone marrow derived or tissue-resident cells that play major roles in the maintenance of vascular integrity and repair of endothelial damage. Although EPCs may be capable of directly engrafting and regenerating the endothelium, the most important effects of EPCs seem to be depended on paracrine effects. In recent studies, specific microvesicles and mRNAs have been found to mediate the pro-angiogenic and regenerative effects of EPCs on endothelium. EPC counts have important prognostic implications in cardiovascular diseases (CVD). Uremia and inflammation are associated with lower EPC counts which probably contribute to increased CVD risks in patients with chronic kidney disease. Beneficial effects of the EPC therapies have been shown in studies performed on different models of CVD and kidney diseases such as acute and chronic kidney diseases and glomerulonephritis. However, lack of a clear definition and specific marker of EPCs is the most important problem causing difficulties in interpretation of the results of the studies investigating EPCs.
A functional Variant (Rs35592567) in TP63 at 3q28 is Associated with Gastric Cancer Risk via Modifying its Regulation by MicroRNA-140
Authors: Lu Chaomin , Yang Yongwei , Ma Siyue
Published: May 2018

Background/Aims: TP63 was believed to play an important role in the development of many malignancies, while the polymorphisms located at the miRNA binding sites within the 3’UTR of TP63 mRNA may interfere with its expression. In this study, we aimed to study the role of TP63 regulation in the tumorigenesis of gastric cancer (GC). Methods: Computational and luciferase analysis were used to search and confirm the target of miR-140. Real-time PCR, western-blot, MTT assay, and flow cytometry cell cycle analysis were utilized to explore the molecular pathway of miR-140 involved in the progression of GC. Results: TP63 was identified as a direct target gene of miR-140. In HT-29 cells over-expressing miR-140, the luciferase activity was decreased when the cells were transfected with wild-type TP63 3’UTR, but remained unchanged when the cells were transfected with mutant 1 and mutant 2 TP63 3’UTR. In addition, the level of TP63 in HT-29 cells transfected with miR-140 mimic was evidently down-regulated, whereas the level of TP63 in HT-29 cells transfected with miR-140 inhibitor was significantly up-regulated. Furthermore, based on the results from MTT assay and flow cytometry cell cycle analysis, HT-29 cells transfected with miR-140 mimics were associated with significantly higher viability compared to the cells transfected with the control plasmid, suggesting that an increased expression of miR-140 protected HT-29 cells against apoptosis. Finally, when miR-140 expression was high, the number of cells at the G1 phase was notably increased, accompanied by a remarkably diminished number of cells at the S phase. Conclusions: The rs35592567 polymorphism in TP63 affected the expression of TP63 by interfering with its interaction with miR-140, and could serve as an explanation for the increased risk of GC.
Therapeutic Effect of CD4+CD25+ Regulatory T Cells Amplified In Vitro on Experimental Autoimmune Neuritis in Rats
Authors: Wang Feng-Jie , Cui Dan , Qian Wei-Dong
Published: May 2018

Background/Aims: This study aimed to explore whether the adoptive transfusion of autologous CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) has a therapeutic effect on Experimental autoimmune neuritis (EAN) model rats, and it provides new experimental and theoretical bases for the immunotherapy of Guillain-Barre syndrome (GBS). Methods: CD4+CD25+ Tregs were sorted from the spleens of rats using immunomagnetic bead separation techniques combined with flow cytometry. Their in vitro inhibitory function was determined using a lymphocyte proliferation inhibition test, and their purity was confirmed by flow cytometry. Cells were stimulated using CD3/CD28 monoclonal antibodies and were cultured in culture medium containing interleukin 2 (IL-2), transforming growth factor-β (TGF-β) and rapamycin. After 15 days of amplification, CD4+CD25+ Tregs were collected and transfused into EAN model rats. Changes in the pathology and electron microscopical morphology of rat sciatic nerves in the normal group, untreated group, low-dose group (2 × 107) and high-dose group (4 × 107) were observed, and the expression of CD4+CD25+FOXP3 in peripheral blood in the four groups of rats was detected by flow cytometry. Results: Compared with rats in the untreated group, rats in the treatment groups had significantly reduced infiltration of inflammatory cells in the sciatic nerve, as well as myelin and axonal damage. Additionally, the CD4+CD25+ Tregs levels in peripheral blood were significantly higher than those in the untreated group (P< 0. 05). Moreover, the therapeutic effect became more significant with an increase in the dose of adoptive transfusion. Conclusion: Adoptive transfusion of CD4+CD25+ Tregs into EAN model rats has significant therapeutic effects.
Preliminary Reflections on Art and Society
Authors: Wagner Christiane
Published: May 2018

Este artigo apresenta uma síntese das interpretações da teoria do Belo e da mimésis renovando-se e encontrando como ponto de referência, perpassando a tradição ocidental, ao lado da beleza ideal, o mundo da experiência concreta da arte, vivido pelo indivíduo em sociedade. Sendo o sentido sócio-histórico a base para a representa- ção e a interpretação da arte, principal referência para as experiências imaginárias e reais no processo de autonomia da arte e do cidadão. Este processo é tratado desde as belas-artes até o momento em que o critério da autenticidade da arte transforma as relações de produção artística e função social com a modernidade. E, finalmente, discute-se a arte contemporânea face ao valor cultural como progresso de ordem política e social ao encontro do ideal da “democratização da arte”
Joint Effect of Carotid Plaque and C‐Reactive Protein on First‐Ever Ischemic Stroke and Myocardial Infarction?
Authors: Eltoft Agnethe , Arntzen Kjell Arne , Wilsgaard Tom , Hansen John‐Bjarne , Mathiesen Ellisiv B. , Johnsen Stein Harald
Published: May 2018

Background

The joint effect of atherosclerosis and CRP (C‐reactive protein) on risk of ischemic stroke (
IS
) and myocardial infarction (
MI
) has been sparsely studied. The aim of this study was to explore whether
CRP
mediates the risk of events in subjects with prevalent carotid plaque, examine synergism, and test whether
CRP
and carotid plaque add to risk prediction beyond traditional risk factors.

Methods and Results

CRP
and carotid total plaque area (
TPA
) were measured in 10 109 participants in the Tromsø Study from 1994 to 2008. Incident
IS
(n=671) and
MI
(n=1079) were registered until December 31, 2013. We calculated hazard ratios (HRs) of
MI
and
IS
according to categories of
CRP
(<1, 1–3, and >3 mg/L) and plaque status (no plaque and
TPA
below and above median) in Cox proportional hazard models with time‐varying covariates. Multivariable‐adjusted
CRP
>3 versus <1 mg/L was associated with risk of
IS
(
HR
, 1.84; 95% confidence interval, 1.49–2.26) and
MI
(
HR,
1.46; 95% confidence interval, 1.23–1.73).
TPA
above median versus no plaque was associated with risk for
IS
(
HR
, 1.65; 95% confidence interval, 1.36–2.01) and
MI
(
HR
, 1.64; 95% confidence interval, 1.41–1.92). In participants with plaque, adjustment for
CRP
minimally attenuated the risk estimates. The highest incidence rates for
MI
and
IS
were seen in the group with both
CRP
>3 mg/L and TPA is above the median.
TPA
and
CRP
combined added to risk prediction beyond traditional risk factors.

Conclusions

The simultaneous presence of subclinical atherosclerosis and elevated
CRP
was associated with increased risk of
IS
and
MI
. The combined assessment of subclinical atherosclerosis and inflammatory biomarkers may improve cardiovascular disease risk stratification.
The Ottoman Empire and the Crimean Khanate in the North Caucasus: A Case Study of Ottoman-Crimean Relations in the Mid-Sixteenth Century
Authors: Yaşar Murat , Oh Chong Jin
Published: May 2018

Focusing on Ottoman and Crimean policies and their involvement in the North Caucasus in the second half of the sixteenth century as a case study, this paper sheds light on the nature of the political arrangement between the Ottoman empire and the Crimean khanate in this period. Agreeing with scholars who argue that the Crimean khanate’s relationship with the Ottoman empire cannot be classified as vassalage, the present article treats the North Caucasus as a newly emerging borderland and a ‘micro north’ to better understand the framework in which the Crimean khanate functioned as a unit within the Ottoman system.
The acoustics of primary and secondary stress in Modern Hebrew
Authors: Cohen Evan-Gary , Silber-Varod Vered , Amir Noam
Published: May 2018

This study investigates the acoustic realization of primary and secondary stress in polysyllabic words in Modern Hebrew (MH). The study focuses on the production of target words embedded in a meaningful carrier sentence, with three primary stress types: ultimate, penultimate and antepenultimate stress. We measured the duration, intensity and F0 of each vowel. Results show that duration is the sole reliable cue for stress in MH, and that there is no phonetic realization of secondary stress in MH, and therefore no true surface alternating pattern. These findings may have phonological implications regarding the prosodic organization of language, and provide a solid basis for future studies on the perception of primary and secondary stress by speakers.
Akkadian substrate words and meanings surfacing in Neo-Aramaic
Authors: Mutzafi Hezy
Published: May 2018

The present article concerns twelve cases of Akkadian lexical influences on Aramaic that are not manifest until the modern period. These are added to several cases already discussed in scholarly works, and include ten substrate words and two loan translations, all in North-Eastern Neo-Aramaic (NENA), and in one case of loan translation apparently also in Western Neo-Aramaic (assuming a westward diffusion of the innovation involved). As most Akkadian lexical influences which surface in Neo-Aramaic are confined to NENA, it seems that the main reasons for the lack of their attestation in pre-modern Aramaic is the strictly vernacular nature of the remote progenitor of NENA, and the fact that the history of this dialect group is not attested.
Plural addressee marker and grammaticalization in Barayin
Authors: Lovestrand Joseph
Published: May 2018

This article describes two distinct but related grammaticalization paths in Barayin, an East Chadic language. One path is from a first-person plural pronoun to a first-person dual pronoun. Synchronically, the pronominal forms in Barayin with first-person dual number must now be combined with a plural addressee enclitic, nà, to create a first-person plural pronoun. This path is identical to what has been documented in Philippine-type languages. The other path is from a first-person dative suffix to a suffix dedicated to first-person hortative. This path of grammaticalization has not been discussed in the literature. It occurred in several related languages, and each case results in a hortative form with a dual subject. Hortative forms with a plural subject are created by adding a plural addressee marker to the dual form. The plural addressee marker in Chadic languages is derived from a second-person pronominal.
Molecular data allow to elucidate the taxonomic placement of some Umbelliferae from Middle Asia and Afghanistan (Pinacantha, Ladyginia, Peucedanum mogoltavicum)
Authors: DEGTJAREVA GALINA V. , PIMENOV MICHAEL G. , SAMIGULLIN TAHIR H.
Published: May 2018

The systematic position of three Apiaceae-Apioideae taxa, Pinacantha porandica, Ladyginia bucharica and Peucedanum mogoltavicum, from Middle Asia and Afghanistan, is clarified based on nrITS DNA sequence data. In the molecular phylogenetic tree, the monotypic Pinacantha is placed in unresolved position within the Ferulinae. Although there is no morphological information on essential characters, we propose a new position of Pinacantha porandica within the genus Ferula. As a result a new combination Ferula porandica is proposed, with a new section Pinacantha to accommodate it. The attribution of Peucedanum mogoltavicum to Ferula has been confirmed, its correct name being Ferula lithophila. The genus Ladyginia should not be included in Ferula, its closest relatives being Mozaffariania and Glaucosciadium from the Glaucosciadium Clade.
Exostoma ericinum, a new glyptosternine catfish from southwestern China (Teleostei: Siluriformes: Sisoridae)
Authors: NG HEOK HEE
Published: May 2018

A new species of glyptosternine catfish in the genus Exostoma is described in this study. The new species, E. ericinum, is known from the upper Dayingjiang (=Taping River) drainage in southwestern China and is distinguished from congeners in having an unique combination of the following characters: 42–44 vertebrae; parallel striae on anterolateral surfaces of lips and lower surface of maxillary barbel; interorbital distance 26–31% HL; preanal length 67.7–70.5% SL; body depth at anus 10.4–12.0% SL (1.4–1.9 times in caudal peduncle depth); length of adipose-fin base 39.5–43.0% SL; lacking an incision at posterior extremity of adipose-fin base; caudal peduncle length 23.2–26.2% SL; caudal peduncle depth 5.7–7.9% SL; and caudal-fin lobes with slightly concave posterior margin.
Soil Moisture Drought in Europe: A Compound Event of Precipitation and Potential Evapotranspiration on Multiple Time Scales
Authors: Manning Colin , Widmann Martin , Bevacqua Emanuele , Van Loon Anne F. , Maraun Douglas , Vrac Mathieu
Published: May 2018

Compound events are extreme impacts that depend on multiple variables that need not be extreme themselves. In this study, we analyze soil moisture drought as a compound event of precipitation and potential evapotranspiration (PET) on multiple time scales related to both meteorological drought and heat waves in wet, transitional, and dry climates in Europe during summer. Drought indices that incorporate PET to account for the effect of temperature on drought conditions are sensitive to global warming. However, as evapotranspiration (ET) is moisture limited in dry climates, the use of such drought indices has often been criticized. We therefore assess the relevance of the contributions of both precipitation and PET to the estimation of soil moisture drought. Applying a statistical model based on pair copula constructions to data from FluxNet sites in Europe, we find at all sites that precipitation exerts the main control over soil moisture drought. At wet sites PET is additionally required to explain the onset, severity, and persistence of drought events over different time scales. At dry sites, where ET is moisture limited in summer, PET does not improve the estimation of soil moisture. In dry climates, increases in drought severity measured by indices incorporating PET may therefore not indicate further drying of soil but the increased availability of energy that can contribute to other environmental hazards such as heat waves and wildfires. We therefore highlight that drought indices including PET should be interpreted within the context of the climate and season in which they are applied in order to maximize their value.
Blended induction program for electronic engineering freshmen
Authors: Dayawansa Indra , Wijenayake Chamith , Edussooriya Chamira , Samarasekara Thusitha , Karunasekara Chamanthi , Dias Dileeka , Samarasinghe Kithsiri , Kulasekere Chulantha , Rodrigo Ranga , Dayananda Nuwan
Published: May 2018

This paper presents learning and teaching experiences gathered from an induction program conducted at the Department of Electronic and Telecommunication Engineering, University of Moratuwa, Sri Lanka for newly enrolled undergraduate students. The induction program, named as the pre-academic term, was an experimental effort to explore the applicability of blended leaning concepts to enhance the learning experience of Engineering freshmen, while enabling smooth transition from high school to university education. In addition to standard lectures, an integral part of the program was in-class demonstrations, where electronic circuits were assembled from scratch on a printed circuit board and demonstrated using a projected camera during the lectures. Organization, learning objectives, brief description of the example projects are presented along with a summary of formal student feedback. More than 85% of the freshmen indicated that the induction program helped them to smoothly begin the university education. A qualitative assessment in the laboratory work indicated that about 98% of the students successfully completed the assigned hands-on activities.
Predictive Accuracy of Sentiment Analytics for Tourism: A Metalearning Perspective on Chinese Travel News
Authors: Fu Yu , Hao Jin-Xing , (Robert) Li Xiang , Hsu Cathy H.C.
Published: May 2018

Sentiment analytics, as a computational method to extract emotion and detect polarity, has gained increasing attention in tourism research. However, issues regarding how to properly apply sentiment analytics are seldom addressed in the tourism literature. This study addresses such methodological challenges by employing the metalearning perspective to examine the design effects on predictive accuracy using a sentiment analysis experiment for Chinese travel news. Our results reveal strong interactions among key design factors of sentiment analytics on predictive accuracy; accordingly, this study formulates a metalearning framework to improve predictive accuracy for computational tourism research. Our study attempts to highlight and improve the methodological relevance and appropriateness of sentiment analytics for future tourism studies.
Video Data Analysis: A Methodological Frame for a Novel Research Trend
Authors: Nassauer Anne , Legewie Nicolas M.
Published: May 2018

Since the early 2000s, the proliferation of cameras, whether in mobile phones or CCTV, led to a sharp increase in visual recordings of human behavior. This vast pool of data enables new approaches to analyzing situational dynamics. Application is both qualitative and quantitative and ranges widely in fields such as sociology, psychology, criminology, and education. Despite the potential and numerous applications of this approach, a consolidated methodological frame does not exist. This article draws on various fields of study to outline such a frame, what we call video data analysis (VDA). We discuss VDA’s research agenda, methodological forebears, and applications, introduce an analytic tool kit, and discuss criteria for validity. We aim to establish VDA as a methodological frame and an interdisciplinary analytic approach, thereby enhancing efficiency and comparability of studies, and communication among disciplines that employ VDA. This article can serve as a point of reference for current and future practitioners, reviewers, and interested readers.
Megan’s Law 20 Years Later: An Empirical Analysis and Policy Review
Authors: Zgoba Kristen M. , Jennings Wesley G. , Salerno Laura M.
Published: May 2018

This present study examines the sexual and general recidivism rates of 547 convicted sex offenders released before and after the enactment of Megan’s Law in New Jersey. Presenting the longest Megan’s Law evaluation, participants were followed for an average of 15 years after release (range = 10-29 years). Bivariate and multivariate logistic regression equations were estimated to identify covariates significantly associated with both sexual and general recidivism. Group-based trajectories of general recidivism within the 10 years post–prison release were also estimated and compared according to pre–Megan’s Law and post–Megan’s Law release status. No differences in recidivism rates were noted between the cohorts, but differences emerged in the offending trajectories of the high-risk group of offenders within 10 years of release. These results highlight the lack of impact that sex offender registration and notification (SORN) laws have on sexual and general reoffending rates postrelease.
The Influence of Sentence Length on the Commission of Serious and Violent Prison Infractions by Female Inmates
Authors: Reidy Thomas J. , Sorensen Jon R.
Published: May 2018

This study examined the relationship between sentence length and time to commission of serious and violent disciplinary infractions by female inmates divided into short (2 years or less), intermediate (2-8 years), and long-term (8 or more years) groups. Relying on the intermediate-term group as a referent, a Cox regression model demonstrated that short-term inmates were most likely, and long-term inmates least likely, to commit serious and violent infractions across monthly time intervals during the 2-year study period. All three groups exhibited a low base rate of violent behavior directed toward inmates and staff. Predictors associated with the time to commission of serious and violent acts included age, education, mental health, and custody level. Findings point to the potential for over-classification to more secure custody assignments for some inmates, particularly for long-term female prisoners. Policy, institutional, and clinical implications are discussed, including the need for specialized programming and mental health treatment.
The Spiritual Authority of Literature in a Secular Age
Authors: Coleman Dawn
Published: May 2018

This essay argues that literary studies has a vital role to play in secular studies through its analysis of literary texts, whose intricate representations of the subjective experience of secularity often defy historical narratives and social science theories. Drawing on Boaz Huss’s definition of spirituality as a phenomenon intimately linked to the dissolution of the mind/body dualism under late capitalism, the essay maintains that literary texts from at least the nineteenth century forward assert a spiritual authority essential to the study of secularity and to contemporary self-reflection.
Post-secular Nature and the New Nature Writing
Authors: Hampton Alexander J. B.
Published: May 2018

With the turn of the twenty-first century, a group of writers began rehabilitating British nature writing and the voice of the individual interacting with it, producing what has become collectively known as the new nature writing. This examination considers how this literature represents a post-secular re-conceptualization of our relationship to nature. The new nature writing challenges a key element of the secular social imaginary, namely the subject-centered, immanence-bound, disenchanted representation of nature, which sets the self over and above nature, destabilizing existing dichotomies, and generating a multiplicity of hybridized possibilities that re-conceptualize our relationship to nature.
Effects of Monoclonal Antibodies against Nerve Growth Factor on Healthy Bone and Joint Tissues in Mice, Rats, and Monkeys: Histopathologic, Biomarker, and Microcomputed Tomographic Assessments
Authors: Gropp Kathryn E. , Carlson Cathy S. , Evans Mark G. , Bagi Cedo M. , Reagan William J. , Hurst Susan I. , Shelton David L. , Zorbas Mark A.
Published: May 2018

Tanezumab, an anti-nerve growth factor (NGF) antibody, is in development for management of chronic pain. During clinical trials of anti-NGF antibodies, some patients reported unexpected adverse events requiring total joint replacements, resulting in a partial clinical hold on all NGF inhibitors. Three nonclinical toxicology studies were conducted to evaluate the effects of tanezumab or the murine precursor muMab911 on selected bone and joint endpoints and biomarkers in cynomolgus monkeys, Sprague-Dawley rats, and C57BL/6 mice. Joint and bone endpoints included histology, immunohistochemistry, microcomputed tomography (mCT) imaging, and serum biomarkers of bone physiology. Responses of bone endpoints to tanezumab were evaluated in monkeys at 4 to 30 mg/kg/week for 26 weeks and in rats at 0.2 to 10 mg/kg twice weekly for 28 days. The effects of muMab911 at 10 mg/kg/week for 12 weeks on selected bone endpoints were determined in mice. Tanezumab and muMab911 had no adverse effects on any bone or joint parameter. There were no test article–related effects on bone or joint histology, immunohistochemistry, or structure. Reversible, higher osteocalcin concentrations occurred only in the rat study. No deleterious effects were observed in joints or bones in monkeys, rats, or mice administered high doses of tanezumab or muMab911.
Development of Human‐Derived Cell Culture Lines for Recurrent Respiratory Papillomatosis
Authors: Attra James , Hsieh Li‐En , Luo Linda , Mo Jun Qin , Brigger Matthew , Liu Yu‐Tsueng , Pransky Seth
Published: May 2018

Recurrent respiratory papillomatosis (RRP) is mainly caused by human papillomavirus (HPV) 6 and 11. While various adjuvant therapies have been reported, no effective therapy has been documented to universally “cure” this disease. In the era of precision medicine, it would be valuable to identify effective intervention based on drug sensitivity testing and/or molecular analysis. It is essential to be able to successfully carry out in vitro culture and expand tumor cells directly from patients to accomplish this goal. Here we report the result of successful culture of HPV‐infected cell lines (success rate 70%, 9/13) that express the E6/E7 RNA transcript, using pathologic tissue biopsies from patients treated at our institution. The availability of such a system would enable ex vivo therapeutic testing and disease modeling.
The Politics of Skilled Immigration: Explaining the Ups and Downs of the US H-1B Visa Program
Authors: Kennedy Andrew
Published: May 2018

The United States has long been a magnet for skilled immigrants, but its openness to these immigrants has varied considerably over time. Focusing on the H-1B visa program, this article explains why the program’s annual cap has risen and fallen from the mid-1990s to the present. Whereas recent studies of skilled immigration policy have focused on struggles between capital and labor, this article contends that US policy also reflects a struggle between capital and citizen groups — one that has changed considerably over the past two decades. The findings challenge recent work on skilled immigration and US immigration policy.
An Alternative Model of Politics? Prospects and Problems of Jane Bennett’s Vital Materialism
Authors: Lemke Thomas
Published: May 2018

This article discusses the basic arguments and important achievements of Jane Bennett’s vital materialism, as well as some problems and limitations of this theoretical perspective. It first analyzes the ontological underpinnings of Bennett’s materialist account and presents two examples she uses to illustrate the notion of a ‘force of things’. The paper then addresses central conceptual and analytic problems of Bennett’s account. The notion of an all-encompassing ‘vitality of matter’ is insufficient to explain the relationality of matter; it is also empirically limited and provides only a selective account of agency. These shortcomings and limitations affect the political perspectives of Bennett’s version of vital materialism. I conclude that there is a tendency in her work to displace political considerations by invoking new ethical responsibilities and sensibilities. Being attentive to the vitality of things translates into a systematic blindness concerning the inequalities, asymmetries and hierarchies enacted in vital materializations.