bluuebunny/crossref_metadata_2025 huggingface dataset:
Identity, repression, and the threat of ethnic conflict in a strong state
Authors: Mele Christine S , Siegel David A
Published: May 2017

Faced with repression from a strong state, one might expect minority ethnic groups to attempt to assimilate into the dominant group to make themselves seem less threatening. However, this conceptualization of threat elides its tactical components. Oppressed minority groups, even under strong states, may engage in anti-state operations in order to reduce the repression they face, and these operations may succeed with greater likelihood the more they assimilate. Anticipating this, strategic states may be more likely to preemptively raise repression in the face of assimilation in order to reduce this threat. Our model formalizes this logic, illustrating that it can be optimal for the minority group to differentiate even when doing so is strictly detrimental to mobilization. Differentiation is more likely to obtain when increased repression is more costly to the group and when the group’s anti-state operations are more capable of compelling the state to substantially reduce repression.
Experimental study on the model-based control of a 2-degree-of-freedom spherical parallel robot camera stabilizer based on multi-thread programming concept
Authors: Safaryazdi Alireza , Zarei Mojtaba , Abolghasemi Omid , Tale Masouleh Mehdi
Published: May 2017

This article aims at proposing a real-time controller for a camera stabilizer using a 2-degree-of-freedom spherical parallel robot with simultaneous display of the control results using multi-threading programming concept. The main contribution of this article can be regarded as employing (a) a 2-degree-of-freedom spherical parallel robot as a camera stabilizer, (b) introducing approximated model and Jacobian model, and (c) using multi-thread programming in order to create equal conditions for comparing accuracy of designed controllers and simultaneous controlling and running of graphical user interface. The experimental setup consists of a 2-degree-of-freedom spherical parallel robot in which a camera is attached to its end-effector plus a 3-degree-of-freedom passive rotational platform, which provide the possibility to apply random perturbations on the base of the foregoing 2-degree-of-freedom spherical parallel robot. At the end-effector of the robot, a 6-degree-of-freedom sensor is installed which sends rotational data to a micro controller, wirelessly. To this end, transceiver boards are constructed to create connection between PC controller and micro-controller. A PC controller is designed in order to ensure that the installed cameras orientation will remain fixed for a prescribed orientation. In this regard, a controller without encoder and a Jacobian-based controller are employed for the under study spherical 2-degree-of-freedom parallel robot. Then, multi-thread programming is used to eliminate complexities of controller structures. Based on the experimental results obtained by implementing both controller, outputs are compared and mean error of each control method and the related RMSE are reported for the sake of proposing the most promising controller.
Experimental and numerical analysis of repaired stiffened carbon fiber-reinforced plastics panels under compression
Authors: Dong Dalong , Zhou Xiang , Wang Hai , Jiang Xiaowei
Published: May 2017

Stiffened carbon fiber reinforced plastics (CFRP) panels have been widely used in the aerospace industry due to their high weight-specific mechanical properties but they are also susceptible to impact damage. Therefore, the research on the effects of various defects and repair methods on the damaged stiffened CFRP panels is of paramount importance. This paper presents an experimental and numerical study on the compression behavior of stiffened CFRP panels containing two types of initial defects with three repair methods i.e. mechanical repair, adhesively bonded repair, and scarf patch repair. Quasi-static compression mechanical tests were first performed on physical specimens. The buckling and post-buckling behaviors of the specimens were analyzed through experimental results. The finite element models were developed and validated through experimental results, based on which parametric studies on the influences of various delamination and repairing parameters to the load-carrying capacity of the stiffened CFRP panel were performed. The experimental and numerical results reported in this paper can serve as a general guideline for the selection of the most suitable repair method for various defected stiffened CFRP panels.
Conflict Management in Illicit Drug Cryptomarkets
Authors: Morselli Carlo , Décary-Hétu David , Paquet-Clouston Masarah , Aldridge Judith
Published: May 2017

Illegal drug markets have been described as “stateless” systems. Drug dealers, moreover, are commonly considered to have a predilection toward the use of violence to resolve disputes arising from dealing activities. While some studies have undermined this popular perception, new trends surrounding the distribution of illegal drugs via online channels (drug cryptomarkets) have shifted the transactional setting from the physical to virtual realm, thus decreasing the likelihood of violent resolution outcomes even further. This article examines conflict management strategies within cryptomarkets by coding discussion forums between vendors and buyers. Violence, as expected, is absent. Strategies more likely reflect alternatives that have been recognized in conflict management research within and beyond illegal market settings: tolerance, avoidance, ostracism, third-party intervention, negotiation, and threats. The overall setting from which such resolutions emerge is clearly not subject to formal regulations, but our analyses illustrate the multitude of informal social control mechanisms that are consistently at play and which underlie the self-regulatory and communal processes that are firmly in place.
Artists, Temporality, and the Governance of Collaborative Place-Making
Authors: Bain Alison L. , Landau Friederike
Published: May 2017

Place-making is a policy exercise rooted in a politics of both space and time. By examining the temporal sequencing of discursive relations and governance networks in the cultural redevelopment of Güterbahnhof Moabit in Berlin, this article demonstrates the fallacy of place-making via artist proxy. It documents the hidden expectations of artist stakeholders and the overextension of their capacities in their municipally delegated and self-assumed roles as “strategic” and “collaborative” partners with local government in place-making processes. It argues that contrary to collaborative and participatory governance ideals, artists are often singularly responsibilized by civic leaders to realize place-narratives for a community rather than with them, which creates a fundamental barrier to community engagement.
Amended Safety Assessment of Isethionate Salts as Used in Cosmetics
Authors: Burnett Christina L. , Heldreth Bart , Bergfeld Wilma F. , Belsito Donald V. , Hill Ronald A. , Klaassen Curtis D. , Liebler Daniel C. , Marks James G. , Shank Ronald C. , Slaga Thomas J. , Snyder Paul W. , Andersen F. Alan
Published: May 2017

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) rereviewed the safety of 12 isethionate salts as used in cosmetics and concluded that these ingredients are safe in the present practices of use and concentration, when formulated to be nonirritating. These isethionate salts are reported to function mostly as surfactants and cleansing agents in cosmetic products. The Panel reviewed the available animal and clinical data as well as information from previous CIR reports. Although there are data gaps, the shared chemical core structure, expected similarities in physicochemical properties, and similar functions and concentrations in cosmetics enabled grouping these ingredients and reading across the available toxicological data to support the safety assessment of each ingredient.
Tg.rasH2 Mice and not CByB6F1 Mice Should Be Used for 28-Day Dose Range Finding Studies Prior to 26-Week Tg.rasH2 Carcinogenicity Studies
Authors: Paranjpe Madhav G. , Belich Jessica , Vidmar Tom J. , Elbekai Reem H. , McKeon Marie , Brown Caren
Published: May 2017

Our recent retrospective analysis of data, collected from 29 Tg.rasH2 mouse carcinogenicity studies, determined how successful the strategy of choosing the high dose for the 26-week studies was based on the estimated maximum tolerated dose (EMTD) derived from earlier 28-day dose range finding (DRF) studies conducted in CByB6F1 mice. Our analysis demonstrated that the high doses applied at EMTD in the 26-week Tg.rasH2 studies failed to detect carcinogenic effects. To investigate why the dose selection process failed in the 26-week carcinogenicity studies, the initial body weights, terminal body weights, body weight gains, food consumption, and mortality from the first 4 weeks of 26-week studies with Tg.rasH2 mice were compared with 28-day DRF studies conducted with CByB6F1 mice. Both the 26-week and the earlier respective 28-day studies were conducted with the exact same vehicle, test article, and similar dose levels. The analysis of our results further emphasizes that the EMTD and subsequent lower doses, determined on the basis of the 28-day studies in CByB6F1 mice, may not be an accurate strategy for selecting appropriate dose levels for the 26-week carcinogenicity studies in Tg.rasH2 mice. Based on the analysis presented in this article, we propose that the Tg.rasH2 mice and not the CByB6F1 mice should be used in future DRF studies. The Tg.rasH2 mice demonstrate more toxicity than the CByB6F1 mice, possibly because of their smaller size compared to CByB6F1 mice. Also, the Tg.rasH2 males appear to be more sensitive than the female Tg.rasH2 mice.
Is There a Dark Side of Ambidexterity? Implications of Dueling Sales and Service Orientations
Authors: Gabler Colin B. , Ogilvie Jessica L. , Rapp Adam , Bachrach Daniel G.
Published: May 2017

This study examines how employee customer and selling orientations, and their interaction, impact frontline employees’ (FLEs) pursuit of service and sales-related performance outcomes. Applying a job demands-resources lens, we advance a model that explores service-sales ambidexterity at the individual level. Polynomial regression and response surface analysis are used to assess how varying levels of customer and selling orientation relate to FLE outcomes. Our findings indicate that commitment to service quality and sales performance are highest when employees are singularly focused on one or the other. However, when required to be ambidextrous—that is, when employees must maintain a dual focus—these outcomes begin to suffer as employees are unclear of their role in the organization. While ambidextrous employees experience role conflict, they are also more likely to use creativity in their selling activities. These positive and negative consequences of ambidexterity underscore both the potential risks and rewards of a dual orientation on the front line.
Histologic Sequelae of Apical Hypertrophic Cardiomyopathy: Dystrophic Calcification
Authors: Saba Shahryar G , Makaryus John N , Rahmani Navid , Jadonath Ram
Published: May 2017

We present cardiac computed tomography (CT) findings demonstrating apical hypertrophic cardiomyopathy with dystrophic calcification of the left ventricular apex. The absence of significant epicardial coronary artery disease demonstrated by coronary CT angiography suggests that increased wall tension and decreased microvascular perfusion over time account for the dyskinetic apical myocardium, rather than myocardial infarction secondary to atherosclerotic plaque rupture. These observations support CT as the imaging modality of choice to visualize the deposition of calcium in injured myocardial tissue, a recognized occurrence in chronically infarcted myocardium.
Cognitive impairment and clinical characteristics in patients with chronic obstructive pulmonary disease
Authors: Cleutjens Fiona A H M , Spruit Martijn A , Ponds Rudolf W H M , Vanfleteren Lowie E G W , Franssen Frits M E , Gijsen Candy , Dijkstra Jeanette B , Wouters Emiel F M , Janssen Daisy J A
Published: May 2017

We aimed to investigate (1) the relationship between cognitive impairment (CI) and disease severity and (2) the potential differences in exercise performance, daily activities, health status, and psychological well-being between patients with and without CI. Clinically stable chronic obstructive pulmonary disease (COPD) patients, referred for pulmonary rehabilitation, underwent a neuropsychological examination. Functional exercise capacity (6-minute walk test [6MWT]), daily activities (Canadian Occupational Performance Measure [COPM]), health status (COPD Assessment Test [CAT]) and St George’s Respiratory Questionnaire-COPD specific [SGRQ-C]), and psychological well-being (Hospital Anxiety and Depression Scale [HADS], Beck Depression Inventory [BDI], and Symptom Checklist 90 [SCL-90]) were compared between patients with and without CI. Of 183 COPD patients (mean age 63.6 (9.4) years, FEV1 54.8 (23.0%) predicted), 76 (41.5%) patients had CI. The prevalence was comparable across Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1–4 (44.8%, 40.0%, 41.0%, 43.5%, respectively, p = 0.97) and GOLD groups A–D (50.0%, 44.7%, 33.3%, 40.2%, respectively, p = 0.91). Patients with and without CI were comparable for demographics, smoking status, FEV1% predicted, mMRC, 6MWT, COPM, CAT, HADS, BDI, and SCL-90 scores. Clinical characteristics of COPD patients with and without CI are comparable. Assessment of CI in COPD, thus, requires an active case-finding approach.
Recording Intimacy, Reviewing Spectacle: The Emergence of Video in the American Home
Authors: Spaulding Hannah
Published: May 2017

This article traces the discourses surrounding home video-recording technologies, from their emergence in the mid-1960s to their popularity in the mid-1990s. Through an analysis of newspapers, magazines, and advertisements, this article contends that video’s history has been shaped by two seemingly opposed visions of the medium: one which embraced it as a tool for intimacy, and another that condemned it as a harbinger of spectacle. Ultimately, I argue that these two seemingly contradictory views actually share similar convictions and emerge in response to crises and conditions of American capitalism. In their attempt to grapple with video, they condemn commercial television, defend a nostalgic vision of home and family, and in so doing reveal the instability of intimacy and persistence of spectacle at the heart of American domestic life.
TPACK and Teachers of Spanish: Development of a Theory-Based Joint Display in a Mixed Methods Research Case Study
Authors: Bustamante Carolina
Published: May 2017

This article describes the development of a joint display in a mixed methods research case study, using a theoretical framework as the start point. A case study of professional development on Web 2.0 technologies for teachers of Spanish illustrates how the qualitative results from interviews, observations, and documents, and quantitative results from pre, post, and follow-up surveys were integrated via a joint display using the TPACK model. The discussion focuses on the role of joint displays in data merging and how they facilitate the representation of fit of data integration, enriching the results in convergent designs.
How Much Volume of Local Anesthesia and How Long Should You Wait After Injection for an Effective Wrist Median Nerve Block?
Authors: Lovely Lyndsay M. , Chishti Yasmin Z. , Woodland Jennifer L. , Lalonde Donald H.
Published: May 2017

Background: Many surgeons and emergentologists use non–ultrasound-guided wrist nerve blocks. There is little evidence to guide the ideal volume of local anesthesia or how long we should wait after injection before performing pain-free procedures. This pilot study examined time to maximal anesthesia to painful needle stick in 14 volunteer participants receiving bilateral wrist blocks of 6 versus 11 mL of local. Methods: One surgeon performed all 14 bilateral wrist median nerve blocks in participants who remained blinded until after bandages were applied to their wrist. No one could see which wrist received the larger 11-mL volume injection versus the 6-mL block. Blinded sensory assessors then measured perceived maximal numbness time and numbness to needle stick pain in the fingertips of the median nerve distribution. Results: Failure to get a complete median nerve block occurred in seven of fourteen 6-mL wrist blocks versus failure in only one of fourteen 11-mL blocks. Perceived maximal numbness occurred at roughly 40 minutes after injection, but actual numbness to painful needle stick took around 100 minutes. Conclusions: Incomplete median nerve numbness occurred with both 6- and 11-mL non–ultrasound-guided blocks at the wrist. In those with complete blocks, it took a surprisingly long time of 100 minutes for maximal anesthesia to occur to painful needle stick stimuli to the fingertips of the median nerve distribution. Non–ultrasound-guided median nerve blocks at the wrist as described in this article lack reliability and take too long to work.
Meningioma embolization with the pressure cooker technique using Squid 12
Authors: Szatmáry Zoltán , Hillman Jan , Finitsis Stephanos
Published: May 2017

Background

Preoperative meningioma embolization may be performed with microparticles or liquid embolic agents. The pressure cooker technique (PCT) has recently been described for the embolization of brain arteriovenous malformations (AVMs).

Case

We present the case of a 73-year-old woman with a large frontal interhemispheric meningioma that was successfully preoperatively embolized with the PCT using Squid 12, a new ethyl-vinyl alcohol copolymer embolic agent. The PCT presents considerable advantages relative to conventional embolization techniques such as deeper and faster tumor penetration and embolization of tumors with difficult vascular access, and retrograde feeling of pial afferents may be achieved.

Conclusions

The use of the PCT with Squid 12 may potentially increase the effectiveness of meningioma embolization, increase tumor devascularization and improve outcomes of surgical resection.
Building coherence for instructional improvement through professional development
Authors: Stosich Elizabeth Leisy , Bocala Candice , Forman Michelle
Published: May 2017

This study explores how six school leadership teams in a rural district in California responded to professional development (PD) designed to strengthen leadership practices and organizational conditions in schools for improving teaching and learning. Specifically, the PD was intended to address the problem of practice identified by the schools: teachers needed to learn to work in new ways to support students in meeting the Common Core State Standards (CCSS). Researchers used design-based implementation research (DBIR) to understand the connection between the design and implementation of the PD model and the impact on participating schools. Findings suggest that in developing PD programs, three challenges need to be addressed in designing experiences for educators that strengthen their capabilities to lead instructional improvement: maintaining the connection between organizational processes and instructional practice; approaching school leadership team collaboration as joint work; and utilizing a developmental approach to improvement. The article concludes by exploring the potential of DBIR for designing and refining models for school leaders’ professional learning.
Tweeting from the past: Commemorating the Anzac Centenary @ABCNews1915
Authors: Sumartojo Shanti
Published: May 2017

This article argues that the digital world has introduced new complexities to state commemoration of the past and public engagement with those efforts. It focuses on how national narratives are transmitted by and through particular digital lieux de mémoire; on how the archival trace of the past is presented as lively and emergent, even when the people it represents are long dead; and the implications for the temporalities of national history and memory of new digital forms of state commemoration. To make these arguments, it draws on the April 2015 ‘live tweeting’ by the Australian Broadcasting Corporation of the Anzac landing on the Gallipoli peninsula. It will use material from Twitter handle @ABCNews1915 to trace some of the links between state commemoration and the digital world, a relationship that has become more urgent in light of the increasing use of social media to articulate state-sponsored history and to communicate between states and individuals.
Patient-Centered Care in Small Primary Care Practices in New York City: Recognition Versus Reality
Authors: Paul Margaret M. , Albert Stephanie L. , Mijanovich Tod , Shih Sarah C. , Berry Carolyn A.
Published: May 2017

Background: The Primary Care Information Project (PCIP) is a program administered by the New York City Department of Health and Mental Hygiene to help primary care providers adopt a fully functional electronic health record (EHR) and focus on population health. PCIP also offers practices assistance with the National Committee for Quality Assurance (NCQA) patient-centered medical home (PCMH) recognition application. The objectives of this study were to assess the presence of key dimensions of PCMH among PCIP practices with 5 or fewer providers and to determine whether and to what extent NCQA recognition was related to the presence of these dimensions. Methods: Analyses relied on data collected from a comprehensive practice assessment survey of PCIP practices administered in summer 2012. The survey was developed to assess discrete dimensions of the PCMH model and other practice characteristics. The study population includes practices for which survey results were available among PCIP practices with 5 or fewer providers (63% response rate; n = 83). Results: At the time of survey, 57% of practices had received some level of NCQA recognition (n = 47). Practices with recognition scored significantly higher on several dimensions, including whole person orientation, team-based care, care coordination and integration, and quality and safety. Conclusions: Results indicate that very small urban practices in New York City are implementing many key features of PCMH. In general, practices with NCQA recognition scored higher on PCMH constructs and domains relative to practices without recognition; however, there is room for improvement on construct and domain scores in both groups.
Turning Classroom Failure Into Student Success: The Value of Integrating Resiliency Building Activities in the Academic Classroom
Authors: Berg Patricia , Pietrasz Carol
Published: May 2017

Millennials are a unique generational cohort populating the classroom, leaving university professors with the challenge of appropriately preparing them for the chaotic workforce. One challenge is their lower levels of resiliency. When faced with setbacks, Millennials tend to give up instead of bouncing back. This lack of resiliency is negatively affecting their academic success as well as causing a decrease in job performance, lack of career success, and lack of organizational retention. This article will help readers (a) develop a deeper understanding of Millennials’ unique traits and behaviors, (b) develop a deeper awareness of resiliency, and (c) use two experiential classroom exercises that can help university professors increase resiliency awareness in the classroom.
T cells lacking HDAC11 have increased effector functions and mediate enhanced alloreactivity in a murine model
Authors: Woods David M. , Woan Karrune V. , Cheng Fengdong , Sodré Andressa L. , Wang Dapeng , Wu Yongxia , Wang Zi , Chen Jie , Powers John , Pinilla-Ibarz Javier , Yu Yu , Zhang Ya , Wu Xuefeng , Zheng Xiaoyan , Weber Jeffrey , Hancock Wayne W. , Seto Edward , Villagra Alejandro , Yu Xue-Zhong , Sotomayor Eduardo M.
Published: May 2017

Key Points

T cells from HDAC11KO mice have increased effector functions and mediate more rapid and potent GVHD. HDAC11 associates with the Eomes and Tbet gene promoter regions in resting cells and disassociates upon activation.
KRASG12D expression in lung-resident myeloid cells promotes pulmonary LCH-like neoplasm sensitive to statin treatment
Authors: Kamata Tamihiro , Giblett Susan , Pritchard Catrin
Published: May 2017

Key Points

KRASG12D expression in mouse lung myeloid cells induces pulmonary LCH-like neoplasms. KRASG12D-induced LCH-like neoplasms are sensitive to in vivo treatment with 3-hydroxy-3-methylglutaryl coenzyme A inhibitor atorvastatin.
Central nervous system involvement in acute lymphoblastic leukemia is mediated by vascular endothelial growth factor
Authors: Münch Vera , Trentin Luca , Herzig Julia , Demir Salih , Seyfried Felix , Kraus Johann M. , Kestler Hans A. , Köhler Rolf , Barth Thomas F. E. , te Kronnie Geertruy , Debatin Klaus-Michael , Meyer Lüder H.
Published: May 2017

Key Points

Xenografted ALL cells faithfully recapitulate CNS leukemia and are characterized by high expression of VEGF, mediating CNS entry of ALL cells. VEGF captured by bevacizumab in vivo specifically reduces CNS leukemia, providing a novel strategy to target CNS involvement in ALL.
Essential role for histone deacetylase 11 (HDAC11) in neutrophil biology
Authors: Sahakian Eva , Chen Jie , Powers John J , Chen Xianghong , Maharaj Kamira , Deng Susan L , Achille Alex N , Lienlaf Maritza , Wang Hong Wei , Cheng Fengdong , Sodré Andressa L , Distler Allison , Xing Limin , Perez-Villarroel Patricio , Wei Sheng , Villagra Alejandro , Seto Ed , Sotomayor Eduardo M , Horna Pedro , Pinilla-Ibarz Javier
Published: May 2017

Epigenetic changes in chromatin structure have been recently associated with the deregulated expression of critical genes in normal and malignant processes. HDAC11, the newest member of the HDAC family of enzymes, functions as a negative regulator of IL-10 expression in APCs, as previously described by our lab. However, at the present time, its role in other hematopoietic cells, specifically in neutrophils, has not been fully explored. In this report, for the first time, we present a novel physiologic role for HDAC11 as a multifaceted regulator of neutrophils. Thus far, we have been able to demonstrate a lineage-restricted overexpression of HDAC11 in neutrophils and committed neutrophil precursors (promyelocytes). Additionally, we show that HDAC11 appears to associate with the transcription machinery, possibly regulating the expression of inflammatory and migratory genes in neutrophils. Given the prevalence of neutrophils in the peripheral circulation and their central role in the first line of defense, our results highlight a unique and novel role for HDAC11. With the consideration of the emergence of new, selective HDAC11 inhibitors, we believe that our findings will have significant implications in a wide range of diseases spanning malignancies, autoimmunity, and inflammation.
Involvement of cell surface 90 kDa heat shock protein (HSP90) in pattern recognition by human monocyte-derived macrophages
Authors: Bzowska Małgorzata , Nogieć Anna , Bania Krystian , Zygmunt Magdalena , Zarębski Mirosław , Dobrucki Jerzy , Guzik Krzysztof
Published: May 2017

Heat shock proteins (HSPs) are typical intracellular chaperones which also appear on the cell surface and in extracellular milieu. HSP90, which chaperones many proteins involved in signal transduction, is also a regular component of LPS-signaling complexes on Mϕ. As LPS is a prototypical PAMP, we speculated that HSP90 is engaged in pattern recognition by professional phagocytes. In this report, we provide the first evidence, to our knowledge, of the geldanamycin (Ge)-inhibitable HSP90 on the surface of live monocyte-derived Mϕs (hMDMs). Using cytometry and specific Abs, we showed both HSP90 isoforms (α and β) on the surface of human monocytes and hMDMs. The cell-surface HSP90 pool was also labeled with cell-impermeable Ge derivatives. Confocal analysis of hMDMs revealed that HSP90-inhibitor complexes were rapidly clustered on the cell surface and recycled through the endosomal compartment. This finding suggests that the N-terminal (ATPase) domain of HSP90 is exposed and accessible from the extracellular space. To study the role of cell-surface HSP90 in pattern recognition, we used pathogen (PAMPs)- or apoptotic cell-associated molecular patterns (ACAMPs). We showed that blocking the cell-surface HSP90 pool leads to a dramatic decrease in TNF production by monocytes and hMDMs exposed to soluble (TLRs-specific ligands) and particulate [bacteria Staphylococcus aureus (SA) and Porphyromonas gingivalis (PG)] PAMPs. Surprisingly, in hMDMs the functional cell-surface HSP90 was not necessary for the engulfment of either apoptotic neutrophils or bacteria. The presented data suggest that the cell-surface HSP90 is a “signaling complex chaperone,” with activity that is essential for cytokine response but not for target engulfment by Mϕ.
The blood-borne sialyltransferase ST6Gal-1 is a negative systemic regulator of granulopoiesis
Authors: Dougher Christopher W L , Buffone Alexander , Nemeth Michael J , Nasirikenari Mehrab , Irons Eric E , Bogner Paul N , Lau Joseph T Y
Published: May 2017

Responding to systemic demands in producing and replenishing end-effector blood cells is predicated on the appropriate delivery and interpretation of extrinsic signals to the HSPCs. The data presented herein implicate the systemic, extracellular form of the glycosyltransferase ST6Gal-1 in the regulation of late-stage neutrophil development. ST6Gal-1 is typically a membrane-bound enzyme sequestered within the intracellular secretory apparatus, but an extracellular form is released into the blood from the liver. Both human and murine HSPCs, upon exposure to extracellular ST6Gal-1 ex vivo, exhibited decreased proliferation, diminished expression of the neutrophilic primary granule protein MPO, and decreased appearance of CD11b+ cells. HSPC suppression was preceded by decreased STAT-3 phosphorylation and diminished C/EBPα expression, without increased apoptosis, indicating attenuated G-CSF receptor signaling. A murine model to raise systemic ST6Gal-1 level was developed to examine the role of the circulatory enzyme in vivo. Our results show that systemic ST6Gal-1 modified the cell surface of the GMP subset of HSPCs and decreased marrow neutrophil reserves. Acute airway neutrophilic inflammation by LPS challenge was used to drive demand for new neutrophil production. Reduced neutrophil infiltration into the airway was observed in mice with elevated circulatory ST6Gal-1 levels. The blunted transition of GMPs into GPs in vitro is consistent with ST6Gal-1-attenuated granulopoiesis. The data confirm that circulatory ST6Gal-1 is a negative systemic regulator of granulopoiesis and moreover suggest a clinical potential to limit the number of inflammatory cells by manipulating blood ST6Gal-1 levels.
Francisella novicida inhibits spontaneous apoptosis and extends human neutrophil lifespan
Authors: Kinkead Lauren C , Fayram Drew C , Allen Lee-Ann H
Published: May 2017

Francisella novicida is a Gram-negative bacterium that is closely related to the highly virulent facultative intracellular pathogen, Francisella tularensis. Data published by us and others demonstrate that F. tularensis virulence correlates directly with its ability to impair constitutive apoptosis and extend human neutrophil lifespan. In contrast, F. novicida is attenuated in humans, and the mechanisms that account for this are incompletely defined. Our published data demonstrate that F. novicida binds natural IgG that is present in normal human serum, which in turn, elicits NADPH oxidase activation that does not occur in response to F. tularensis. As it is established that phagocytosis and oxidant production markedly accelerate neutrophil death, we predicted that F. novicida may influence the neutrophil lifespan in an opsonin-dependent manner. To test this hypothesis, we quantified bacterial uptake, phosphatidylserine (PS) externalization, and changes in nuclear morphology, as well as the kinetics of procaspase-3, -8, and -9 processing and activation. To our surprise, we discovered that F. novicida not only failed to accelerate neutrophil death but also diminished and delayed apoptosis in a dose-dependent, but opsonin-independent, manner. In keeping with this, studies of conditioned media (CM) showed that neutrophil longevity could be uncoupled from phagocytosis and that F. novicida stimulated neutrophil secretion of CXCL8. Taken together, the results of this study reveal shared and unique aspects of the mechanisms used by Francisella species to manipulate neutrophil lifespan and as such, advance understanding of cell death regulation during infection.
Myeloid-derived cells in prostate cancer progression: phenotype and prospective therapies
Authors: Lopez-Bujanda Zoila , Drake Charles G
Published: May 2017

Prostate cancer is the second most common cause of cancer mortality in men in the United States. As is the case for other tumor types, accumulating evidence suggests an important role for myeloid-derived cells in the promotion and progression of prostate cancer. Here, we briefly describe myeloid-derived cells that interact with tumor cells and what is known about their immune suppressive function. We next discuss new evidence for tumor cell–mediated myeloid infiltration via the PI3K/PTEN/AKT signaling pathway and an alternative mechanism for immune evasion that may be regulated by an endoplasmic reticulum stress response. Finally, we discuss several interventions that target myeloid-derived cells to treat prostate cancer.
Comparative exploration of multidimensional flow cytometry software: a model approach evaluating T cell polyfunctional behavior
Authors: Spear Timothy T , Nishimura Michael I , Simms Patricia E
Published: May 2017

Advancement in flow cytometry reagents and instrumentation has allowed for simultaneous analysis of large numbers of lineage/functional immune cell markers. Highly complex datasets generated by polychromatic flow cytometry require proper analytical software to answer investigators’ questions. A problem among many investigators and flow cytometry Shared Resource Laboratories (SRLs), including our own, is a lack of access to a flow cytometry-knowledgeable bioinformatics team, making it difficult to learn and choose appropriate analysis tool(s). Here, we comparatively assess various multidimensional flow cytometry software packages for their ability to answer a specific biologic question and provide graphical representation output suitable for publication, as well as their ease of use and cost. We assessed polyfunctional potential of TCR-transduced T cells, serving as a model evaluation, using multidimensional flow cytometry to analyze 6 intracellular cytokines and degranulation on a per-cell basis. Analysis of 7 parameters resulted in 128 possible combinations of positivity/negativity, far too complex for basic flow cytometry software to analyze fully. Various software packages were used, analysis methods used in each described, and representative output displayed. Of the tools investigated, automated classification of cellular expression by nonlinear stochastic embedding (ACCENSE) and coupled analysis in Pestle/simplified presentation of incredibly complex evaluations (SPICE) provided the most user-friendly manipulations and readable output, evaluating effects of altered antigen-specific stimulation on T cell polyfunctionality. This detailed approach may serve as a model for other investigators/SRLs in selecting the most appropriate software to analyze complex flow cytometry datasets. Further development and awareness of available tools will help guide proper data analysis to answer difficult biologic questions arising from incredibly complex datasets.
Correlation analysis for spread-spectrum induced-polarization signal processing in electromagnetically noisy environments
Authors: Liu Weiqiang , Chen Rujun , Cai Hongzhu , Luo Weibin , Revil André
Published: May 2017

In induced-polarization (IP) surveys, the raw data are usually distorted significantly by the presence of electromagnetic (EM) interferences, including cultural noise. Several methods have been proposed to improve the signal-to-noise ratio of these data. However, signal processing in an electromagnetically noisy environment is still a challenging problem. We have determined a new and simple technique based on the analysis of the correlation between the measured potential and the injected primary current signals. This processing is applied to the data acquired using a new frequency-domain IP method called the spread-spectrum induced-polarization (SSIP) approach. In this approach, we use a pseudorandom m-sequence (also called the maximum length sequence) for the injected primary current. One of the advantages of this sequence is to be essentially spectrally flat in a given frequency range. Therefore, complex resistivity can be determined simultaneously at various frequencies. A new SSIP data set is acquired in the vicinity of Baiyin mine, Gansu Province, China. The correlation between potential difference and transmitting current signals for each period can be used to assess data quality. Only when the correlation coefficient between the two signals is greater than 0.5 can the SSIP data be used for subsequent processing and tomography. We determine what threshold value should be used for the correlation coefficient to extract high-quality apparent complex resistivity data and eliminate EM-contaminated data. We then compare the pseudosections with and without using the correlation analysis. When the correlation analysis is used, the noisy data are filtered out, and the target anomaly obtained through tomography is clearly enhanced. The inversion results of the apparent complex resistivity (amplitude and phase) for the survey area are consistent with some independent geologic and drilling information regarding the position of the ore body demonstrating the effectiveness of the approach.
A micro ocean-bottom E-field receiver
Authors: Chen Kai , Deng Ming , Luo Xianhu , Wu Zhongliang
Published: May 2017

Ocean-bottom electromagnetic (EM) receivers are used to record EM signals for marine magnetotelluric and controlled-source EM offshore data acquisition. These marine EM data are used for offshore gas hydrate and petroleum exploration. Although many conventional receivers are used for offshore data acquisition, they have deficiencies, such as a large size, high cost, and low operational efficiency. To address these limitations, we have developed a micro ocean-bottom E-field (micro-OBE) receiver. It reduces costs and deck-space use, while providing improved horizontal resolution and operational efficiency. Based on conventional receiver specifications, including low noise levels, low power consumption, and low clock-drift error, we reduced the receiver size, provided a low-cost release mechanism, integrated an acoustic telemetry module, improved the operational efficiency, and reduced the field acquisition cost. The resulting micro-OBE is comprised of a compact nylon frame, 17 inch glass sphere, logging system, batteries, recovery beacon, burn-wire release mechanism, transducer, electrode, red flag, and anchor (which eliminates the heavy and expensive acoustic release). It has no alloy aluminum press case, and it contains a minimal number of glass spheres, watertight cables, and connectors. Its size is [Formula: see text] (not including the electrode arm, red flag, and anchor). Its weight in air is 70 kg. It has a noise level of [Formula: see text] (Hz) at 8 Hz, and it provides 33 days of battery lifetime. Offshore data acquisition was performed to evaluate the micro-OBE field performance during an offshore gas-hydrate experiment. Our results indicate that the receiver effectively functioned throughout the operation and offshore data acquisition. Micro-OBE was thus verified as providing a low cost, compact size, and high operational efficiency.
A novel experimental rat model of peripheral nerve scarring: reliably mimicking post-surgical complications and recurring adhesions
Authors: Lemke Angela , Penzenstadler Carina , Ferguson James , Lidinsky Dominika , Hopf Rudolf , Bradl Monika , Redl Heinz , Wolbank Susanne , Hausner Thomas
Published: May 2017

Inflammation, fibrosis and perineural adhesions with the surrounding tissue are common pathological processes following nerve injury and surgical interventions on peripheral nerves in human patients. Furthermore, these signs can reoccur following external neurolysis, currently the most common surgical treatment, thus leading to renewed nerve function impairment and chronic pain. To enable a successful evaluation of new therapeutic approaches, it is crucial to use a reproducible animal model that mimics the main clinical symptoms occurring in human patients. However, a clinically relevant model combining both histological and functional alterations has not been published to date. For this reason, we developed a reliable rat model, which exhibits the essential pathological processes of peripheral nerve scarring.

In our study, we present a novel method for the induction of nerve scarring by applying glutaraldehyde-containing glue, known to cause nerve injury in humans. After a three-week contact period with the sciatic nerve in female Sprague Dawley rats, we could demonstrate severe intra- and perineural scarring that resulted in grade 3 adhesions and major impairments in the electrophysiological peak amplitude compared to sham control (p=0.0478). Immunohistochemical analysis of the nerve structure revealed vigorous nerve inflammation and recruitment of T cells and macrophages. Also, distinct nerve degeneration was determined by immunostaining. These pathological alterations were further reflected in significant functional deficiencies as determined by the analysis of relevant gait parameters as well as the quantification of the sciatic functional index starting at week 1 post-operatively (p<0.01). Moreover, with this model we could, for the first time, demonstrate not only the primary formation, but also the recurrence of severe adhesions one week after glue removal, imitating a major clinical challenge. As a comparison, we tested an already published model for generating perineural fibrotic adhesions, which however did not result in significant pathological changes.

Taken together, we established an easily reproducible and reliable rat model for peripheral nerve scarring which allows for the effective testing of new therapeutic strategies.
An alternative surgical approach reduces variability following filament induction of experimental stroke in mice
Authors: Trotman-Lucas M. , Kelly M. E. , Janus J. , Fern R. , Gibson C. L.
Published: May 2017

Animal models are critical for understanding the pathology of stroke and investigating potential treatments. However, in vivo stroke models are associated, particularly in mice, with high variability in lesion volume. We investigated whether a surgical refinement where reperfusion is not reliant on the Circle of Willis reduced outcome variability. Mice underwent 60 minutes of transient middle cerebral artery occlusion avoiding ligation of the external carotid artery. During reperfusion the common carotid artery was either ligated (standard approach), or it was repaired to allow re-establishment of blood flow through the common carotid artery. All mice underwent MRI scanning for assessment of infarct volume, apparent diffusion coefficient and fractional anisotropy along with terminal assessment of infarct volume by TTC staining. Repairing the common carotid artery following middle cerebral artery occlusion enhanced reperfusion (P<0.01) and reduced the variability seen in both total (histological analysis, P =0.008; T2-weighted MRI, P=0.015) and core (diffusion tensor imaging MRI scanning, P=0.043) lesion volume. Avoiding external carotid artery ligation may improve animal wellbeing, through reduced weight loss, while using an alternative surgical approach which enabled reperfusion through the common carotid artery decreased the variability in lesion volume seen within groups.
Viral delivery of C9ORF72 hexanucleotide repeat expansions in mice lead to repeat length dependent neuropathology and behavioral deficits.
Authors: Herranz-Martin Saul , Chandran Jayanth , Lewis Katherine , Mulcahy Padraig , Higginbottom Adrian , Walker Callum , Valenzuela Isabel Martinez-Pena y , Jones Ross A. , Coldicott Ian , Iannitti Tommaso , Akaaboune Mohammed , El-Khamisy Sherif F. , Gillingwater Thomas H. , Shaw Pamela J. , Azzouz Mimoun
Published: May 2017

Intronic GGGGCC repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Two major pathologies stemming from the hexanucleotide RNA expansions (HREs) have been identified in postmortem tissue: intracellular RNA foci and repeat-associated non-ATG dependent (RAN) dipeptides, though it is unclear how these and other hallmarks of disease contribute to the pathophysiology of neuronal injury. Here we generated two novel lines of mice that overexpress either 10 pure or 102 interrupted G4C2 repeats mediated by adeno-associated virus (AAV) and characterized relevant pathology and disease-related behavioral phenotypes. Similar levels of intracellular RNA foci developed in both lines of mice, but only mice expressing 102 repeats generated c9-RAN pathology, neuromuscular junction (NMJ) abnormalities, dispersal of the hippocampal CA1, enhanced apoptosis, and deficits in gait and cognition. Neither line of mice, however, showed extensive TAR DNA-binding protein 43 (TDP-43) pathology or neurodegeneration. Our data suggests that RNA foci pathology is not a good predictor of c9-RAN dipeptide formation, and that RAN dipeptides and NMJ dysfunction are drivers of c9-disease pathogenesis. These AAV-mediated models of C9orf72 ALS/FTD will be useful tools for studying disease pathophysiology and developing new therapeutic approaches.
The Notion of the Diameter of Mereological Ball in Tarski's Geometry of Solids
Authors: Sitek Grzegorz
Published: May 2017

In  the paper "Full development of Tarski's geometry of solids" Gruszczyński and Pietruszczak have obtained the full development of Tarski’s geometry of solids that was sketched in [14, 15]. In this paper 1 we introduce in Tarski’s theory the notion of congruence of mereological balls and then the notion of diameter of mereological ball. We prove many facts about these new concepts, e.g., we give a characterization of mereological balls in terms of its center and diameter and we prove that the set of all diameters together with the relation of inequality of diameters is the dense linearly ordered set without the least and the greatest element.
Benefits conditionality for disabled people: stylised facts from a review of international evidence and practice
Authors: Geiger Ben Baumberg
Published: May 2017

While behavioural conditionality for disability benefit claimants has been increasing, there is little evidence on its implementation or impacts. This article summarises existing studies, alongside an international review based on 140 documents and 38 expert interviews, into four ‘stylised facts’: (1) requirements for disability benefit claimants are common, but sanctioning is rare; (2) assessment and support are critical for implementing conditionality; (3) limited but robust existing evidence suggests that sanctioning may have zero or even negative impacts on work-related outcomes for disabled people; and (4) individual case studies suggest that sanctioning can lead to destitution and affect mental health.