bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer Neoantigens and Applications for Immunotherapy
Authors: Desrichard Alexis , Snyder Alexandra , Chan Timothy A.
Published: October 2015

Recent advances in immune checkpoint blockade therapy have revolutionized the treatment of cancer. Tumor-specific antigens that are generated by somatic mutation, neoantigens, can influence patient response to immunotherapy and contribute to tumor shrinkage. Recent evidence demonstrating the success of checkpoint blockade immunotherapy in boosting T-cell reactivity against patient-specific neoantigens constitutes a strong rationale for the development of personalized vaccines against these nonself peptides. With the decreasing cost of next-generation sequencing, peptide manufacturing, and improvement of in silico prediction of peptide immunogenicity, it is increasingly important to evaluate the potential use of neoantigens in both diagnosis and treatment. Specifically, these neoantigens could be useful both as predictors of immune checkpoint blockade therapy response and/or incorporated in therapeutic vaccination strategies. Clin Cancer Res; 22(4); 807–12. ©2015 AACR.
Dual Metronomic Chemotherapy with Nab-Paclitaxel and Topotecan Has Potent Antiangiogenic Activity in Ovarian Cancer
Authors: Previs Rebecca A. , Armaiz-Pena Guillermo N. , Lin Yvonne G. , Davis Ashley N. , Pradeep Sunila , Dalton Heather J. , Hansen Jean M. , Merritt William M. , Nick Alpa M. , Langley Robert R. , Coleman Robert L. , Sood Anil K.
Published: October 2015

There is growing recognition of the important role of metronomic chemotherapy in cancer treatment. On the basis of their unique antiangiogenic effects, we tested the efficacy of nab-paclitaxel, which stimulates thrombospondin-1, and topotecan, which inhibits hypoxia-inducible factor 1-α, at metronomic dosing for the treatment of ovarian carcinoma. In vitro and in vivo SKOV3ip1, HeyA8, and HeyA8-MDR (taxane-resistant) orthotopic models were used to examine the effects of metronomic nab-paclitaxel and metronomic topotecan. We examined cell proliferation (Ki-67), apoptosis (cleaved caspase-3), and angiogenesis (microvessel density, MVD) in tumors obtained at necropsy. In vivo therapy experiments demonstrated treatment with metronomic nab-paclitaxel alone and in combination with metronomic topotecan resulted in significant reductions in tumor weight (62% in the SKOV3ip1 model, P < 0.01 and 96% in the HeyA8 model, P < 0.03) compared with vehicle (P < 0.01). In the HeyA8-MDR model, metronomic monotherapy with either cytotoxic agent had modest effects on tumor growth, but combination therapy decreased tumor burden by 61% compared with vehicle (P < 0.03). The greatest reduction in MVD (P < 0.05) and proliferation was seen in combination metronomic therapy groups. Combination metronomic therapy resulted in prolonged overall survival in vivo compared with other groups (P < 0.001). Tube formation was significantly inhibited in RF-24 endothelial cells exposed to media conditioned with metronomic nab-paclitaxel alone and media conditioned with combination metronomic nab-paclitaxel and metronomic topotecan. The combination of metronomic nab-paclitaxel and metronomic topotecan offers a novel, highly effective therapeutic approach for ovarian carcinoma that merits further clinical development. Mol Cancer Ther; 14(12); 2677–86. ©2015 AACR.
Silibinin Preferentially Radiosensitizes Prostate Cancer by Inhibiting DNA Repair Signaling
Authors: Nambiar Dhanya K. , Rajamani Paulraj , Deep Gagan , Jain Anil K. , Agarwal Rajesh , Singh Rana P.
Published: October 2015

Radiotherapy, a frequent mode of cancer treatment, is often restricted by dose-related toxicity and development of therapeutic resistance. To develop a novel and selective radiosensitizer, we studied the radiosensitizing effects and associated mechanisms of silibinin in prostate cancer. The radiosensitizing effect of silibinin with ionizing radiation (IR) was assessed on radioresistant prostate cancer cell lines by clonogenic, cell cycle, cell death, and DNA repair assays. Tumor xenograft growth, immunohistochemical (IHC) analysis of tumor tissues, and toxicity-related parameters were measured in vivo. Silibinin (25 μmol/L) enhanced IR (2.5–10 Gy)-caused inhibition (up to 96%, P < 0.001) of colony formation selectively in prostate cancer cells, and prolonged and enhanced IR-caused G2–M arrest, apoptosis, and ROS production. Mechanistically, silibinin inhibited IR-induced DNA repair (ATM and Chk1/2) and EGFR signaling and attenuated the levels of antiapoptotic proteins. Specifically, silibinin suppressed IR-induced nuclear translocation of EGFR and DNA-PK, an important mediator of DSB repair, leading to an increased number of γ-H2AX (ser139) foci suggesting lesser DNA repair. In vivo, silibinin strongly radiosensitized DU145 tumor xenograft inhibition (84%, P < 0.01) with higher apoptotic response (10-fold, P < 0.01) and reduced repair of DNA damage, and rescued the mice from IR-induced toxicity and hematopoietic injury. Overall, silibinin enhanced the radiotherapeutic response via suppressing IR-induced prosurvival signaling and DSB repair by inhibiting nuclear translocation of EGFR and DNA-PK. Because silibinin is already in phase II clinical trial for prostate cancer patients, the present finding has translational relevance for radioresistant prostate cancer. Mol Cancer Ther; 14(12); 2722–34. ©2015 AACR.
Tumor-Priming Smoothened Inhibitor Enhances Deposition and Efficacy of Cytotoxic Nanoparticles in a Pancreatic Cancer Model
Authors: Roy Chaudhuri Tista , Straubinger Ninfa L. , Pitoniak Rosemarie F. , Hylander Bonnie L. , Repasky Elizabeth A. , Ma Wen Wee , Straubinger Robert M.
Published: October 2015

Most pancreatic adenocarcinoma patients present with unresectable disease and benefit little from chemotherapy. Poor tumor perfusion and vascular permeability limit drug deposition. Previous work showed that Smoothened inhibitors of hedgehog signaling (sHHI) promote neovascularization in spontaneous mouse models of pancreatic cancer (PaCA) and enhance tumor permeability to low-molecular weight compounds. Here, we tested the hypothesis that sHHI can enhance tumor deposition and efficacy of drug-containing nanoparticles consisting of 80 to 100 nm sterically-stabilized liposomes (SSL) containing doxorubicin (SSL-DXR). SCID mice bearing low-passage patient-derived PaCA xenografts (PDX) were pretreated p.o. for 10 days with 40 mg/kg/d NVP-LDE225 (erismodegib), followed by i.v. SSL-DXR. Microvessel density, permeability, perfusion, and morphology were compared with untreated controls, as was SSL deposition and therapeutic efficacy. The sHHI alone affected tumor growth minimally, but markedly increased extravasation of nanoparticles into adenocarcinoma cell–enriched regions of the tumor. Immunostaining showed that sHHI treatment decreased pericyte coverage (α-SMA+) of CD31+ vascular endothelium structures, and increased the abundance of endothelium-poor (CD31−) basement membrane structures (collagen IV+), suggesting increased immature microvessels. SSL-DXR (15 mg/kg) administered after sHHI pretreatment arrested tumor volume progression and decreased tumor perfusion/permeability, suggesting an initial vascular pruning response. Compared with controls, one cycle of 10-day sHHI pretreatment followed by 6 mg/kg SSL-DXR doubled median tumor progression time. Three cycles of treatment with sHHI and SSL-DXR, with a 10-day between-cycle drug holiday, nearly tripled median tumor progression time. Based upon these data, short-term sHHI treatment sequenced with nanoparticulate drug carriers constitutes a potential strategy to enhance efficacy of pancreatic cancer therapy. Mol Cancer Ther; 15(1); 84–93. ©2015 AACR.
Survival Impact of Pulmonary Metastasis as Recurrence of Pancreatic Ductal Adenocarcinoma
Authors: Yamashita Kotaro , Miyamoto Atsushi , Hama Naoki , Asaoka Tadafumi , Maeda Sakae , Omiya Hideyasu , Takami Koji , Doki Yuichiro , Mori Masaki , Nakamori Shoji
Published: October 2015

Aim: This study aimed at investigating the survival impact of pancreatic ductal adenocarcinoma (PDAC) recurrence as pulmonary metastasis. Methods: We performed a retrospective case-control study of 142 patients who underwent curative resection for PDAC at our institution between 2003 and 2012. Clinicopathological features were compared among patients stratified according to the recurrence pattern and pulmonary metastasis treatment strategy. Results: Patients underwent pancreaticoduodenectomy (n = 96), distal (n = 42), or total pancreatectomy (n = 4). At the last follow-up, 99 patients had developed recurrent post-resection PDAC, including 14 cases of isolated pulmonary recurrence. The median overall survival was significantly longer for patients with isolated pulmonary recurrence (40.3 months) than with other metastases (20.9 months; HR 5.85; p = 0.0156). Two patients underwent resection for isolated pulmonary recurrence, and both survived for ∼70 months after primary resection. Conclusion: Patients with first recurrence of PDAC as pulmonary metastasis had a better prognosis than patients with other types of metastases. Moreover, when isolated pulmonary metastasis is controlled for a certain period, pulmonary resection is likely to improve patient survival.
The Coronary Microcirculation in Hamster-to-Rat Cardiac Xenografts
Authors: Geiger Dominik , Buchholz Stefan , Michel Sebastian , Abicht Jan , Reichel Christoph A. , Reichart Bruno , Hagl Christian , Brenner Paolo , Schramm René
Published: October 2015

Background: The aim of this study was to establish a new experimental model to directly analyse the coronary microcirculation in cardiac xenografts. Methods: Intravital fluorescence microscopy (IVM) of the subepicardial microcirculation in heterotopically transplanted hamster-to-rat cardiac xenografts was performed at 30 and 90 min of reperfusion. We quantitatively assessed the microcirculatory perfusion characteristics as well as the interactions of leukocytes and platelets with the endothelium of postcapillary coronary venules in non-sensitised as well as sensitised recipients. Results: In this first experimental IVM study of cardiac xenografts, we successfully visualised the subepicardial microcirculation, i.e. feeding arterioles, nutritive capillaries and draining postcapillary venules, during reperfusion. Leukocyte-endothelial and platelet-endothelial cell interactions could be quantified. In the non-sensitised group, the myocardial microcirculation remained stable during the observation period of 90 min, whereas in the sensitised group, xenografts were rejected immediately. Conclusions: We established a model for the assessment of the microcirculatory dysfunction and inflammation during ischaemia/reperfusion injury in hamster-to-rat cardiac xenografts.
The Structure, Pathogenicity and Immunogenicity of Two Virion Fractions Harvested from Cell Cultures Infected with the CA16 Virus
Authors: Pu Jing , Huang Hongtai , Zhang Ying , Feng Min , Yang Erxia , Che Yanchun , Dong Chenghong , Liao Yun , Liu Longding , Wang Lichun , Wang Jingjing , Li Qihan
Published: October 2015

Objectives: To investigate the biological characteristics of the two types of virion fractions of Coxsackievirus A 16 (CA16), which include the real virion fraction and pseudo-virion fraction in their structure, pathogenicity and immunogenicity. Methods: We obtained the two CA16 virion fractions by density gradient centrifugation. The morphology of virion fractions was analyzed by electron microscopy, while the antigenic characteristics and immunogenicity of two virion fractions were determined by ELISA, SDS-PAGE, Western blot, qRT-PCR, and the mouse model of immune response. Results: The two virion fractions contained the major viral antigen components in their structures, showed similar pathogenicity in a neonatal murine model and were capable of inducing an effective primary immune response in adult mice, regardless of the essential distinction between the two virion fractions, which was the cleavage of VP0 to VP2 and VP4. Conclusions: The two CA16 virion fractions showed antigenicity and immunogenicity with inducing a specific immune response in animals.
Drug Hypersensitivity: How Drugs Stimulate T Cells via Pharmacological Interaction with Immune Receptors
Authors: Pichler Werner J. , Adam Jacqueline , Watkins Stephen , Wuillemin Natascha , Yun James , Yerly Daniel
Published: November 2015

Small chemicals like drugs tend to bind to proteins via noncovalent bonds, e.g. hydrogen bonds, salt bridges or electrostatic interactions. Some chemicals interact with other molecules than the actual target ligand, representing so-called ‘off-target' activities of drugs. Such interactions are a main cause of adverse side effects to drugs and are normally classified as predictable type A reactions. Detailed analysis of drug-induced immune reactions revealed that off-target activities also affect immune receptors, such as highly polymorphic human leukocyte antigens (HLA) or T cell receptors (TCR). Such drug interactions with immune receptors may lead to T cell stimulation, resulting in clinical symptoms of delayed-type hypersensitivity. They are assigned the ‘pharmacological interaction with immune receptors' (p-i) concept. Analysis of p-i has revealed that drugs bind preferentially or exclusively to distinct HLA molecules (p-i HLA) or to distinct TCR (p-i TCR). P-i reactions differ from ‘conventional' off-target drug reactions as the outcome is not due to the effect on the drug-modified cells themselves, but is the consequence of reactive T cells. Hence, the complex and diverse clinical manifestations of delayed-type hypersensitivity are caused by the functional heterogeneity of T cells. In the abacavir model of p-i HLA, the drug binding to HLA may result in alteration of the presenting peptides. More importantly, the drug binding to HLA generates a drug-modified HLA, which stimulates T cells directly, like an allo-HLA. In the sulfamethoxazole model of p-i TCR, responsive T cells likely require costimulation for full T cell activation. These findings may explain the similarity of delayed-type hypersensitivity reactions to graft-versus-host disease, and how systemic viral infections increase the risk of delayed-type hypersensitivity reactions.
S100A12 and the S100/Calgranulins
Authors: Oesterle Adam , Hofmann Bowman Marion A.
Published: October 2015

Atherosclerosis is mediated by local and systematic inflammation. The multiligand receptor for advanced glycation end products (RAGE) has been studied in animals and humans and is an important mediator of inflammation and atherosclerosis. This review focuses on S100/calgranulin proteins (S100A8, S100A9, and S100A12) and their receptor RAGE in mediating vascular inflammation. Mice lack the gene for S100A12, which in humans is located on chromosome 3 between S100A8 and S100A9. Transgenic mice with smooth muscle cell–targeted expression of S100A12 demonstrate increased coronary and aortic calcification, as well as increased plaque vulnerability. Serum S100A12 has recently been shown to predict future cardiovascular events in a longitudinal population study, underscoring a role for S100A12 as a potential biomarker for coronary artery disease. Genetic ablation of S100A9 or RAGE in atherosclerosis-susceptible apolipoprotein E null mice results in reduced atherosclerosis. Importantly, S100A12 and the RAGE axis can be modified pharmacologically. For example, soluble RAGE reduces murine atherosclerosis and vascular inflammation. Additionally, a class of compounds currently in phase III clinical trials for multiple sclerosis and rheumatologic conditions, the quinoline-3-carboxamides, reduce atherosclerotic plaque burden and complexity in transgenic S100A12 apolipoprotein E null mice, but have not been tested with regards to human atherosclerosis. The RAGE axis is an important mediator for inflammation-induced atherosclerosis, and S100A12 has emerged as biomarker for human atherosclerosis. Decreasing inflammation by inhibiting S100/calgranulin-mediated activation of RAGE attenuates murine atherosclerosis, and future studies in patients with coronary artery disease are warranted to confirm S100/RAGE as therapeutic target for atherosclerosis.
HMGB1-Driven Inflammation and Intimal Hyperplasia After Arterial Injury Involves Cell-Specific Actions Mediated by TLR4
Authors: Cai Jingjing , Yuan Hong , Wang Qingde , Yang Huan , Al-Abed Yousef , Hua Zhong , Wang Jiemei , Chen Dandan , Wu Jinze , Lu Ben , Pribis John P. , Jiang Weihong , Yang Kan , Hackam David J. , Tracey Kevin J. , Billiar Timothy R. , Chen Alex F.
Published: October 2015

Objective—

Endoluminal vascular interventions such as angioplasty initiate a sterile inflammatory response resulting from local tissue damage. This response drives the development of intimal hyperplasia (IH) that, in turn, can lead to arterial occlusion. We hypothesized that the ubiquitous nuclear protein and damage-associated molecular pattern molecule, high-mobility group box 1 (HMGB1), is one of the endogenous mediators that activates processes leading to IH after endoluminal injury to the arterial wall. The aim of this study is to investigate whether approaches that reduce the levels of HMGB1 or inhibit its activity suppresses IH after arterial injury.

Approach and Results—

Here, we show that HMGB1 regulates IH in a mouse carotid wire injury model. Induced genetic deletion or neutralization of HMGB1 prevents IH, monocyte recruitment, and smooth muscle cell growth factor production after endoluminal carotid artery injury. A specific inhibitor of HMGB1 myeloid differentiation factor 2–toll-like receptor 4 (TLR4) interaction, P5779, also significantly inhibits IH. HMGB1 deletion is mimicked in this model by global deletion of TLR4 and partially replicated by myeloid-specific deletion of TLR4 but not TLR2 or receptor for advanced glycation endproducts deletion. The specific HMGB1 isoform known to activate TLR4 signaling (disulfide HMGB1) stimulates smooth muscle cell to migrate and produce monocyte chemotactic protein 1/CCL2) via TLR4. Macrophages produce smooth muscle cell mitogens in response to disulfide HMGB1 also in a TLR4/myeloid differentiation primary response gene (88)/Trif-dependent manner.

Conclusions—

These findings place HMGB1 and its receptor, TLR4 as critical regulators of the events that drive the inflammation leading to IH after endoluminal arterial injury and identify this pathway as a possible therapeutic target to limit IH to attenuate damage-associated molecular pattern molecule–mediated vascular inflammatory responses.
Use of Antiplatelet Agents Is Associated With Intraplaque Hemorrhage on Carotid Magnetic Resonance Imaging
Authors: Liem Madieke I. , Schreuder Floris H.B.M. , van Dijk Anouk C. , de Rotte Alexandra A.J. , Truijman Martine T.B. , Daemen Mat J.A.P. , van der Steen Anton F.W. , Hendrikse Jeroen , Nederveen Aart J. , van der Lugt Aad , Kooi M. Eline , Nederkoorn Paul J. ,   Participating centers:, Schreuder A.H.C.M.L. , Koudstaal P.J. , Limburg M. , Weisfelt M. , Korten A.G.G.C. , Saxena R. , van Oostenbrugge R.J. , Mess W.H. , van Orshoven N.P. , Tromp S.C. , Bakker S.L.M. , Kruyt N.D. , de Kruijk J.R. , de Borst G.J. , Meems B.J. , Verhey J.C.B. , Wijnhoud A.D.
Published: October 2015

Background and Purpose—

Intraplaque hemorrhage (IPH), visualized by magnetic resonance imaging, has shown to be associated with the risk of stroke in patients with carotid artery stenosis. The mechanisms of IPH development are poorly understood. In this study, we investigated the association between clinical patient characteristics and carotid IPH on high-resolution magnetic resonance imaging.

Methods—

Patients participate in the Plaque at Risk (PARISK) study. This prospective, multicenter cohort study included patients with recent amaurosis fugax, hemispheric transient ischemic attack, or nondisabling stroke in the internal carotid artery territory and an ipsilateral carotid stenosis of <70%, who were not scheduled for carotid revascularization procedure. One hundred patients, recruited between 2010 and 2012, underwent a 3-T high-resolution carotid magnetic resonance imaging. We documented clinical patient characteristics and performed multivariable logistic regression analysis to investigate their association with IPH.

Results—

IPH was observed in 45 patients (45%) in 1 or both carotid arteries. Male sex and the use of antiplatelet agents before the index event were associated with IPH in univariable analysis. In a multivariable analysis, only previous use of antiplatelet agents was significantly associated with IPH (odds ratio, 2.71; 95% confidence interval, 1.12–6.61). Risk factors of atherosclerotic arterial disease, including a history of symptomatic arterial diseases, were not associated with IPH.

Conclusions—

In this cohort of 100 patients with recently symptomatic carotid stenosis, the previous use of antiplatelet agents is associated with carotid IPH on magnetic resonance imaging. Antiplatelet therapy may increase the risk of IPH, but our findings need to be confirmed in larger patient cohorts. The implications for risk stratification remain to be determined.
The Mogor as Venomous Hydra: Forging the Mughal-Portuguese Frontier
Authors: Flores Jorge
Published: October 2015

The present article seeks to discuss the prevailing ideas and practices of frontier among the Mughals. Concurrently, it considers the ways in which the Portuguese Asian Empire perceived this expanding imperial space. The Mughal emperors engaged in a strong universalistic discourse, which ultimately pointed towards the idea of an infinite Timurid India. To be sure, the Portuguese were hit by this imperial rhetoric, but they rested on intriguing mechanisms of self-legitimacy, like arguing that the Northern white neighbors of the Estado da Índia were newcomers and actually foreigners in India. Additionally, The Portuguese understood the striking difference between Mughal imperial rhetoric and the actual frontier turbulence on the ground and, since the early years of Mughal rule, they sought to identify spaces of demarcation in Gujarat, Bengal and the Deccan.
Contesting Transnational Mobility among New Zealand’s Chinese Migrants from an Economic Perspective新西兰中国跨国移民的跨界经济活动及成因
Authors: Liu Liangni Sally , Lu Jun
Published: October 2015

New Chinese migrants from the People’s Republic of China to New Zealand are renowned for their transnational mobility. Based on an online survey among this group of migrants, this paper aims to explore how economic factors in Chinese transnational migration play out in a way different from that posited by some conventional conceptions in migration studies. For example, compared with the conventional remittance flow that usually takes place from migrant-receiving countries to migrant-sending countries, this research finds a reverse remittance transaction channel among prc migrants. This reverse remittance flow is a manifestation of China’s economic revitalization, which benefited New Zealand, especially in the recent economic crisis. It was also found that economic reasons were not decisive in an immigrant’s decision to settle in New Zealand. However, economic reasons contributed significantly to their on-going movements after arriving in New Zealand. prc immigrants’ deciding to migrate or re-migrate reflects a layering of priorities that measure the short-term goal of maintaining economic livelihood against the longer-term goal of ensuring one’s family’s overall well-being.
Early Chinese-American Society as Portrayed in Chinese Letters of the Ah Louis Family of San Luis Obispo, California, usa早期美国华侨社会：美国加州,圣路易斯-奥比 斯波市-黄安家族的中文信件
Authors: Fetzer Joel
Published: October 2015

This research report presents the English-language translations of several hand-written, Chinese-language letters from the overseas-Chinese Ah Louis family of San Luis Obispo, California. During the late 1800s and early 1900s, when these letters were written, this medium-sized town on the Pacific coast between San Francisco and Los Angeles was home to hundreds of Cantonese immigrants. As unofficial “mayor” of San Luis Obispo’s Chinatown, the Guangdong-born Ah Louis interacted with a wide variety of merchants, employees, friends, family members, and officials. These documents discuss commerce in Chinatown, a legal case about local Chumash Indians, migration between China and the United States, family life in rural Guangdong Province, and labor relations in California, providing a near-unique window into ordinary Chinese-American life around the turn of the twentieth century. Extensive footnotes also place the letters in their historical and cultural context.
Patterns of Dislocation: Judeo-Arabic Syntactic Influence on Modern Hebrew
Authors: Henshke Yehudit
Published: November 2015

This article deals with a phenomenon of Modern Hebrew that exhibits the influence of Judeo-Arabic: the phenomenon of dislocation as found in the Hebrew sociolect of the Israeli periphery, among descendants of Middle Eastern and North African Jews. I call this sociolect Israeli Periphery Hebrew (iph). The article examines the widespread use of dislocation constructions in iph—specifically pronominal dislocation, as well as echo and anchoring constructions—and their unique features. Even though dislocation is typical of spoken language in general, it is argued here that its frequency and unique constructions in iph reflect the influence of the Judeo-Arabic substrate. The article attempts to illuminate the sources and roots of these dislocated constructions.
The Minnesota School and Immigration History at Midwestern Land Grant Universities, 1890–2005
Authors: Gabaccia Donna R.
Published: October 2015

This article offers an alternative genealogy for American immigration history. It traces the origins of the methods and analytical interests of the new social historians of immigration in the 1960s and 1970s to the early work of immigration historians at midwestern land grant universities. At the University of Minnesota, historian Theodore Blegen introduced a long-term legacy of ‘history from the bottom up,’ privileging the building of archives and the building of collaborations among first and second generation academics, ethnic communities and scholarly research.
Migration History as a Transcultural History of Societies
Authors: Hoerder Dirk
Published: October 2015

As ‘ethnic’ history — the nation-to-ethnic-ghetto version of migrant strategies — came to include the process of migration and the socialization, the ‘roots’ of the field were still traced to the Chicago School and Oscar Handlin. European scholarship in the initial stages centred on emigration to North America and followed us approaches. I discuss, to the 1950s, European and Canadian epistemologies of the field and briefly refer to research in other parts of the world. The essays discuss neglected, theoretically and conceptually complex origins of migration studies and history in the us: (1) the Chicago Women’s School of Sociology of Hull House reformers and women economists from the 1880s and the cluster of interdisciplinary scholars at Columbia University (Franz Boas et al.); (2) scholars at the University of Minnesota who included the migrants’ societies of origin; as well as (3) scholars in California (Bogardus, social distance scale) and (4) British Columbia who recovered data collected in the 1920s and read them in modern multicultural perspectives. Against these many threads the emphasis by Chicago scholars, E. Park in particular, and O. Handlin on disorganization and ‘marginal men’ are assessed.
The Naval Research Laboratory Ocean Surface Flux (NFLUX) System: Satellite-Based Turbulent Heat Flux Products
Authors: May Jackie C. , Rowley Clark , Van de Voorde Neil
Published: October 2015

The Naval Research Laboratory ocean surface flux (NFLUX) system provides satellite-based surface state parameter and surface turbulent heat flux fields operationally over the global ocean. These products are presented as an alternative to using numerical weather prediction models—namely, the U.S. Navy Global Environmental Model (NAVGEM)—to provide the surface forcing to operational ocean models. NFLUX utilizes satellite sensor data records from the Special Sensor Microwave Imager/Sounder (SSMIS), the Advanced Microwave Sounding Unit-A (AMSU-A), the Advanced Technology Microwave Sounder (ATMS), and the Advanced Microwave Scanning Radiometer-2 (AMSR-2) sensors as well as satellite environmental data records from WindSat, the Advanced Scatterometers (ASCAT), and the Oceansat scatterometer (OSCAT). The satellite data are processed and translated into estimates of surface specific humidity, surface air temperature, and 10-m scalar wind speed. Two-dimensional variational analyses of quality-controlled satellite data, in combination with an atmospheric-model field, form global gridded surface state parameter fields. Bulk formulas are then applied to produce surface turbulent heat flux fields. Six-hourly analysis fields are created from 1 January 2013 through 31 December 2013. These fields are examined and validated against in situ data and NAVGEM. Overall, the NFLUX fields have a smaller bias, lower or similar root-mean-square error, and increased skill score relative to those of NAVGEM.
Symmetric Instability, Inertial Oscillations, and Turbulence at the Gulf Stream Front
Authors: Thomas Leif N. , Taylor John R. , D’Asaro Eric A. , Lee Craig M. , Klymak Jody M. , Shcherbina Andrey
Published: October 2015

The passage of a winter storm over the Gulf Stream observed with a Lagrangian float and hydrographic and velocity surveys provided a unique opportunity to study how the interaction of inertial oscillations, the front, and symmetric instability (SI) shapes the stratification, shear, and turbulence in the upper ocean under unsteady forcing. During the storm, the rapid rise and rotation of the winds excited inertial motions. Acting on the front, these sheared motions modulate the stratification in the surface boundary layer. At the same time, cooling and downfront winds generated a symmetrically unstable flow. The observed turbulent kinetic energy dissipation exceeded what could be attributed to atmospheric forcing, implying SI drew energy from the front. The peak excess dissipation, which occurred just prior to a minimum in stratification, surpassed that predicted for steady SI turbulence, suggesting the importance of unsteady dynamics. The measurements are interpreted using a large-eddy simulation (LES) and a stability analysis configured with parameters taken from the observations. The stability analysis illustrates how SI more efficiently extracts energy from a front via shear production during periods when inertial motions reduce stratification. Diagnostics of the energetics of SI from the LES highlight the temporal variability in shear production but also demonstrate that the time-averaged energy balance is consistent with a theoretical scaling that has previously been tested only for steady forcing. As the storm passed and the winds and cooling subsided, the boundary layer restratified and the thermal wind balance was reestablished in a manner reminiscent of geostrophic adjustment.
Increased serum IgM, immunodeficiency, and autoimmunity: A clinical series
Authors: Picchianti Diamanti Andrea , Rosado M Manuela , Scarsella Marco , Ceccarelli Sara , Laganà Bruno , D’Amelio Raffaele , Carsetti Rita
Published: November 2015

Background:

Primary immunodeficiencies (PIDs) are generally characterized by recurrent infections; however they may be complicated by other clinical disorders such as allergy, autoimmunity, and lymphoproliferation. In particular, autoimmunity may be the first manifestation of the disease in patients with low serum immunoglobulins (Ig) levels. Here we describe a group of patients that share features of immunodeficiency and autoimmunity.

Materials and Methods:

All patients went through a complete T and B cell subset characterization and a B cell function analysis in the peripheral blood by flow-cytometry. B cell proliferation and plasma cell differentiation was measured, in vitro, after CpG stimulation for 7 days as previously described. Semi-quantitative PCR analysis for AID and UNG expression as well as serum levels of BAFF were carried out in order to better define the diagnosis.

Results:

Immunological and molecular analysis did not lead to the identification of known molecular defect typical of Hyper IgM syndrome. A comparative study of the peripheral blood B cell subsets between patients and healthy donors showed that in patients with autoimmune manifestations all circulating B cells expressed high amounts of surface IgM.

Conclusions:

These results suggest that the increased IgM expression on circulating B cells, reflecting B cell activation, might identify a clinical condition characterized by hyper IgM serum levels of unknown molecular defects, associated with susceptibility to infections and autoimmunity.
Rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3L exhibit distinct phenotypical and functional characteristics
Authors: N’diaye Marie , Warnecke Andreas , Flytzani Sevasti , Abdelmagid Nada , Ruhrmann Sabrina , Olsson Tomas , Jagodic Maja , Harris Robert A , Guerreiro-Cacais Andre Ortlieb
Published: October 2015

Dendritic cells are professional APCs that play a central role in the initiation of immune responses. The limited ex vivo availability of dendritic cells inspires the widespread use of bone marrow-derived dendritic cells as an alternative in research. However, the functional characteristics of bone marrow-derived dendritic cells are incompletely understood. Therefore, we compared functional and phenotypic characteristics of rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3 ligand bone marrow-derived dendritic cells. A comparison of surface markers revealed that FLT3 ligand-bone marrow-derived dendritic cells expressed signal regulatory protein α, CD103, and CD4 and baseline levels of MHC class II, CD40, and CD86, which were highly up-regulated upon stimulation. Conversely, GM-CSF/IL-4-bone marrow-derived dendritic cells constitutively expressed signal regulatory protein α, CD11c, and CD11b but only mildly up-regulated MHC class II, CD40, or CD86 following stimulation. Expression of dendritic cell-associated core transcripts was restricted to FLT3 ligand-bone marrow-derived dendritic cells. GM-CSF/IL-4-bone marrow-derived dendritic cells were superior at phagocytosis but were outperformed by FLT3 ligand-bone marrow-derived dendritic cells at antigen presentation and T cell stimulation in vitro. Stimulated GM-CSF/IL-4-bone marrow-derived dendritic cells secreted more TNF, CCL5, CCL20, and NO, whereas FLT3 ligand-bone marrow-derived dendritic cells secreted more IL-6 and IL-12. Finally, whereas GM-CSF/IL-4-bone marrow-derived dendritic cell culture supernatants added to resting T cell cultures promoted forkhead box p3+ regulatory T cell populations, FLT3 ligand-bone marrow-derived dendritic cell culture supernatants drove Th17 differentiation. We conclude that rat GM-CSF/IL-4-bone marrow-derived dendritic cells and FLT3 ligand-bone marrow-derived dendritic cells are functionally distinct. Our data support the current rationale that FLT3 ligand-bone marrow-derived dendritic cells mostly resemble classic dendritic cells but comprise additional minor subpopulations, whereas GM-CSF/IL-4-bone marrow-derived dendritic cells resemble monocyte-derived inflammatory dendritic cells (iNOS-positive monocyte-derived cells).
The inflammasome NLRP3 plays a protective role against a viral immunopathological lesion
Authors: Gimenez Fernanda , Bhela Siddheshvar , Dogra Pranay , Harvey Lorena , Varanasi Siva Karthik , Jaggi Ujjaldeep , Rouse Barry T
Published: October 2015

Herpes simplex 1 infection of the eye can cause blindness with lesions in the corneal stroma largely attributable to inflammatory events that include components of both adaptive and innate immunity. Several innate immune responses are triggered by herpes simplex 1, but it is unclear how such innate events relate to the subsequent development of stromal keratitis. In this study, we compared the outcome of herpes simplex 1 ocular infection in mice unable to express NLRP3 because of gene knockout (NLRP3−/−) to that of wild-type mice. The NLRP3−/− mice developed more-severe and earlier stromal keratitis lesions and had higher angiogenesis scores than did infected wild-type animals. In addition, NLRP3−/− mice generated an increased early immune response with heightened chemokines and cytokines, including interleukin-1β and interleukin-18, and elevated recruitment of neutrophils. Increased numbers of CD4+ T cells were seen at later stages of the disease in NLRP3−/− animals. Reduction in neutrophils prevented early onset of the disease in NLRP3−/− animals and lowered levels of bioactive interleukin-1β but did not lower bioactive interleukin-18. In conclusion, our results indicate that NLRP3 has a regulatory and beneficial role in herpetic stromal keratitis pathogenesis.
Recruited monocytes modulate malaria-induced lung injury through CD36-mediated clearance of sequestered infected erythrocytes
Authors: Lagassé H A Daniel , Anidi Ifeanyi U , Craig John M , Limjunyawong Nathachit , Poupore Amy K , Mitzner Wayne , Scott Alan L
Published: October 2015

Pulmonary complications occur in a significant percentage of adults and children during the course of severe malaria. The cellular and molecular innate immune mechanisms that limit the extent of pulmonary inflammation and preserve lung function during severe Plasmodium infections remain unclear. In particular, the contributions to pulmonary complications by parasitized erythrocyte sequestration and subsequent clearance from the lung microvasculature by immune cells have not been clearly defined. We used the Plasmodium berghei ANKA-C57BL/6 mouse model of severe malaria to investigate the mechanisms governing the nature and extent of malaria-associated lung injury. We have demonstrated that sequestration of infected erythrocytes on postcapillary endothelial surfaces results in acute lung injury and the rapid recruitment of CCR2+CD11b+Ly6Chi monocytes from the circulation. These recruited cells remain in the lungs as monocyte-derived macrophages and are instrumental in the phagocytic clearance of adherent Plasmodium berghei-infected erythrocytes. In contrast, alveolar macrophages do not play a significant role in the clearance of malaria-infected cells. Furthermore, the results obtained from Ccr2−/−, Cd36−/−, and CD36 bone marrow chimeric mice showed that sequestration in the absence of CD36-mediated phagocytic clearance by monocytes leads to exaggerated lung pathologic features. In summary, our data indicate that the intensity of malaria-induced lung pathologic features is proportional to the steady-state levels of Plasmodium-infected erythrocytes adhering to the pulmonary vasculature. Moreover, the present work has defined a major role of recruited monocytes in clearing infected erythrocytes from the pulmonary interstitium, thus minimizing lung damage.
Are neurological and psychiatric disorders
different?
Authors: David Anthony S. , Nicholson Timothy
Published: November 2015

There have been recent calls to abandon the distinction between neurological
and psychiatric disorders on philosophical and moral grounds. Crossley and
colleagues, in this issue, meta-analyse published structural brain imaging
data and prove that they are different after all – or do they?
Kondratieff Cycles in Developed Economies
Authors: Басовский  , Basovskiy Leonid
Published: October 2015

The objective of this paper is to identify Kondratieff cycles in the developed

economies. Time series spectral analysis of real per capita GDP of the developed

countries and Brazil is performed. Also studied are time series for the period

from the 19th century to 2008. As a result Kondratieff cycles (waves) are found

out in the economic dynamics of all the countries surveyed, except for Finland.

The power of Kondratieff cycles in the economic dynamics is estimated to fall in

the range of 23 to 61% of the total power of all economic cycles with the periods

of 2 to 100 years. The Kondratieff cycles can be found in a number of economies

in the period of 19th — 20th centuries. It allows to distinguish the three moderntime

Kondratieff waves in the said countries and to evaluate productivity of the

fourth, the fifth and the sixth technological modes in their economies. However

in a number of countries the Kondratieff cycles show up only in the 20th century.

So for these countries only one or two modern Kondratieff waves can be clearly

identified, making it possible to evaluate productivity of only the fifth and the

sixth technological modes in their economies.
Tax Control: Theory and Practice
Authors: Жураев  , Zhuraev A.
Published: October 2015

The paper discusses some theoretical and practical aspects of tax control,

which is considered to be one of the key elements of the tax administration. Also

examined are several cases, where business entities deliberately misrepresented

the true state of their affairs to the tax authorities in order to evade payment of

certain types of taxes.
Cluster Analysis of Human Capital Development in a Selected Region (the Example of the Central Federal District of the RF)
Authors: Комарова  , Komarova Anna
Published: October 2015

This paper proposes a set of indicators to evaluate the level of the human capital

development in a given region. Provided are the results of cluster analysis of

several regions within the Central Federal District in terms of development of

human capital. Identified are the key areas of human capital development for

clusters of regions composing the Central Federal District of the RF.
Cumulative Growth in User-Generated Content Production: Evidence from Wikipedia
Authors: Aaltonen Aleksi , Seiler Stephan
Published: October 2015

Open content production platforms typically allow users to gradually create content and react to previous contributions. Using detailed edit-level data across a large number of Wikipedia articles, we investigate how past edits shape current editing activity. We find that cumulative past contributions, embodied by the current article length, lead to significantly more editing activity, while controlling for a host of factors such as popularity of the topic and platform-level growth trends. The magnitude of the effect is large; content growth over an eight-year period would have been 45% lower in its absence. Our findings suggest that other open content production environments are likely to also benefit from similar cumulative growth effects. In the presence of such effects, managerial interventions that increase content are amplified because they trigger further contributions.

Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2015.2253 .

This paper was accepted by Pradeep Chintagunta, marketing.
Comparison of co-existing forestry and reindeer husbandry value chains in northern Sweden
Authors: Berg Staffan , Valinger Erik , Lind Torgny , Suominen Tommi , Tuomasjukka Diana
Published: October 2015

Forestry in MalÃ¥, northern Sweden, coexists with other land uses. Reindeer husbandry is in the area for centuries and requires large areas of grazing land. Competing land uses may threaten the MalÃ¥ Sami village. The aim of the study was to evaluate increased consideration in forest management towards 1) reindeer husbandry, 2) nature and 3) a combination of the two. These scenarios were compared with forest management as it was in 2009. Results indicate that all three scenarios lead to a decrease in annual harvesting volumes of 0.2 to 0.4 million m. Forest industry dominated the economic viability in the area. Forest management adapted to the needs of reindeer husbandry resulted in less potential for yearly harvest, employment and profits from forest industry. On the other hand, it led to an increase in growing stock and consequently the potential for carbon sequestration over time. Indeed the increased sequestration would compensate for all fossil emissions of carbon from the Forest Wood Chain (FWC). The nature scenario had minor effects on economic result and on the emissions of fossil carbon. The combined scenario gave a reduced economic performance for the FWC. A scenario based on forest management accommodating the needs of reindeer husbandry gave the best economic result for the reindeer chain, due to high survival rate of the reindeer. However the economic importance of reindeer husbandry in the region was small compared to the FWC. Results from scenario analysis could serve as a platform for mutual understanding between stakeholders.3
Economic, social and environmental disclosure, a theoretical framework and its application in Vietnam
Authors: TRAN VU Viet Ha , MAI Anh , DOAN Cam Tu , PIG� Beno�t
Published: October 2015

This study focuses on the appraisal of firms performance and on its representation and reporting. Using interviews and inquiries in firms operating in the cement industry in Vietnam, two points are investigated. First, whether firms top executives consider that firms sustainable performance may include economic, social or environmental performance that is not integrated in financial statements. The theoretical framework is the stakeholder theory complemented with the institutional theory. Second, whether economic, social and environmental performance should be disclosed to answer the expectations of the various stakeholders. Therefore, our research contributes to corporate governance studies by focusing on reporting dedicated to all the stakeholders.
The effect of training and competency on employees� organizational commitment at PT. Bank Danamon in Ambon city
Authors: Kuhuparuw Ventje Jeffry , Ferdinandus Sherly
Published: October 2015

This study aims to identify and analyze training, competency, and organizational commitment; It also analyzes the effect of training on organizational commitment, the effect of competency on organizational commitment, the effect of training and compe- tency on organizational commitment at PT Bank Danamon in Ambon City. The method applied is a survey research method to 60 employees of PT Bank Danamon in Ambon. Technical analysis used to test the hypothesis is multiple linear regres- sion.The results indicate that training shows the effect of 89.5%, and competency of 13.0%. Since other factors also are predicted to affect the improvement of organiza- tional commitment in addition to training and competency, it is necessary to include the provision of motivation and clarity of career. From the point of view of the rela- tionship with the employees, both variables are considered as important parts. Leaders are also expected to actively involve in the implementation of the tasks so that interac- tion between leaders and subordinates can be interwined, and this cumulatively helps leaders know the problems faced by employees. Thus, the employees would feel cared for and this subsequently has impact on loyalty to the company or higher commitment.
Income smoothing practices and empirical testing using discretionary accounting changes
Authors: Trisanti Theresia
Published: October 2015

Financial statements of listed firms are analyzed by financial analysts and investors. In this case, the firms may suffer from stock price declines if they do not meet market expectations. Listed firms may not only have incentives to avoid income declines and losses, they also have incentives to meet or beat market expectations in order to pre- vent declines in stock price. Income smoothing (IS) is the intentional dampening of fluctuations about some levels of income that is considered to be normal for a firm. IS manipulation has a clear objective, which is to produce a steadily growing stream of income. In this study, income-smoothing practices of Indonesian listed companies are detected through empirical tests using discretionary accounting changes (DAC) as IS instrument. Sample firms are classified as smoothers and non-smoothers using income smoothing behavior index. Results show that possible motivations of DAC transac- tions are income smoothing. The two independent variables such as external audit quality institutional ownership have significant influence towards IS practices. But, the type of industry has no significant relationship towards IS Practices.