bluuebunny/crossref_metadata_2025 huggingface dataset:
Rescuing language education from the neoliberal disaster: Culturometric predictions and analyses of future policy
Authors: Boufoy-Bastick Béatrice
Published: March 2015

Over the last three decades neoliberal government policies have spread successfully around the world with disastrous effects on the social infrastructures of many countries. Neoliberal policies move vast amounts of public money into private hands increasing the gap between rich and poor and decimating social support services for the majority of the population. Along with health and transport, government-funded education is also among the most devastated public services. Yet, in representative democracies, these policies are initially supported by the misguided self-interests of those most deleteriously affected – lecturers, teachers, students and their families, communities and institutions. This paper analyses this effect on language education through the culturometric definition of cultural identity – a concept originally inextricably bound with the teaching of languages – examining language ‘spin’ used in achieving neoliberal policy acceptance, focusing here on the current spin of ‘diversity’. By tracing western government resourcing of value changes in language education through their international change events over the last three decades we show – in contradiction to neoliberal policy documents such as the ‘Common European Framework of Reference for Languages: Learning, teaching, assessment’ – how the potential diversity for student educational outcomes of language education has shrunk under neoliberal education governance to the single option of ‘employee-ment’ – the identity of an ideal employee. We evidence how culture has been stripped from language education and replaced by training employee-ment skills to current policy compliancy standards. To recover from this disaster we then deconstruct cultural diversity in language education to deduce policy amendments to the Common European Framework that would authentically increase cultural diversity as it is valued by the international community of language educators. We conclude by extrapolating the past three decades of changes in resourcing language education towards two possible futures – a future predicated on the employee-ment values of the current common framework and a future predicted by the deduced policy amendments to the framework for authentically enhancing cultural diversity through language education.
The Effects of Counseling on the Retention and Academic Performance of Underprepared Freshmen
Authors: Cholewa Blaire , Ramaswami Soundaram
Published: March 2015

Higher education administrators, faculty, and staff expend great effort to increase the academic success and retention of college freshmen. Underprepared college freshmen are of particular concern given their high risk for dropping out. While interventions such as specific orientation programs, remedial/developmental coursework, and special advisement are utilized to increase retention of these students, one area that appears promising is the provision of counseling. Therefore, the purpose of this study was to examine the impact of individual counseling, grade point average (GPA), and failing remedial and other courses on underprepared freshmen's retention rates. Analysis of variance and logistic regression analyses revealed that counseling for 3 to 4 hours in the fall had a positive impact on fall GPA, and failing fall remedial courses was the most significant predictor of whether a student was retained or not. However, in the spring, GPA, the number of credits completed, and the number of remedial courses taken were the best predictors.
“Sisters in the Collective Struggle”
Authors: Macías Kelly
Published: March 2015

As the conversation on the state of modern Black America deepens in the wake of the Trayvon Martin tragedy and increased violence affecting young Black males, acknowledging historical and present structures that serve to disenfranchise the Black community remain largely focused on boys and men. Yet, to fully examine the impact of White supremacy, patriarchy, and violence on Black lives, it is necessary to remove the culture of silence that permeates the discussion of how oppression is experienced by Black females. In this article, I explore the ways in which society encourages misogynoir (anti-Black misogyny) by reinforcing the marginalization of Black females and their status as the keepers of Black life. A dialogue about Black life, which does not speak to the troubles of Black women, is incomplete. Giving voice to their struggles, in the context of discussing the collective Black experience, is a part of the larger fight for peace, justice, and equality.
Ain’t That a Shame? Trayvon’s Trauma Revealed Through the Theatre of TNT
Authors: Martinson Karen Jean , Jackson Gennifer
Published: March 2015

Just days after the George Zimmerman verdict, the Truth N Trauma (TNT) Theatre Ensemble, comprised entirely of African American actors, performed the devised piece The Only Way Out Is the Way Through. Wearing a hoodie and holding a package of Skittles, the ensemble’s only male actor delivered a monologue that spoke eloquently about the threats that young Black men face. By briefly embodying the figure of Trayvon Martin, this performance interrogated the perceived dangers of Black masculinity to reveal that the deadly violence levied against Black men is not an aberration, but rather is the norm. This article seeks to locate the death of Trayvon Martin historically, tracking similarities in the murders and trials of Trayvon Martin and Emmett Till. It then focuses on the monologue, interrogating its themes, its creation, and its effect in performance to discuss the multiple narratives surrounding Black masculinity that emerge through it, narratives which speak truth to the dominant discourse that normalizes the murder of Black boys. Finally, it demonstrates how theatre is an arena in which such divisive issues can be explored, deconstructed, and transformed into a vehicle for social change.
A Comparative Descriptive Study of Characteristics of Early- and Late-Onset Dementia Family Caregivers
Authors: Ducharme Francine , Lachance Lise , Kergoat Marie-Jeanne , Coulombe Renée , Antoine Pascal , Pasquier Florence
Published: March 2015

Characteristics of early- and late-onset dementia family caregivers were described and compared. Based on a theoretical model of role transition, data were collected through structured interviews from 48 caregivers of adults with Alzheimer’s disease or a related dementia older than the age of 70 and 48 caregivers of similarly diagnosed adults younger than the age of 60. A significantly higher proportion of caregivers of younger adults were spouses and gainfully employed compared with those of older adults; they had more years of schooling, took care of a person with more severe impairments, received more help, perceived themselves as better prepared to deal with future needs, and better informed about services. They did not differ from caregivers of older adults in terms of psychological distress, role confidence, self-efficacy, and social support. This study highlights differences and similarities to be considered in the development of services tailored to the specific needs of each group.
“The Poison That Ruined the Nation”: Native American Men—Alcohol, Identity, and Traditional Healing
Authors: Matamonasa-Bennett Arieahn
Published: March 2015

Alcoholism and destructive drinking patterns are serious social problems in many Native American reservation and urban communities. This qualitative study of men from a single Great Lakes reservation community examined the social, cultural, and psychological aspects of their alcohol problems through their life stories. The men were in various stages of recovery and sobriety, and data collection consisted of open-ended interviews and analysis utilizing principles and techniques from grounded theory and ethnographic content analysis. Alcoholism and other serious social problems facing Native American communities need to be understood in the sociocultural and historical contexts of colonization and historical grief and trauma. This study suggests that for Native American men, there are culturally specific perspectives on alcohol that have important implications for prevention and treatment of alcohol abuse. The participants’ narratives provided insight into the ways reconnecting with traditional cultural values (retraditionalization) helped them achieve sobriety. For these men, alcohol was highly symbolic of colonization as well as a protest to it. Alcohol was a means for affirming “Indian” identity and sobriety a means for reaffirming traditional tribal identity. Their narratives suggested the ways in which elements of traditional cultural values and practices facilitate healing in syncretic models and Nativized treatment. Understanding the ways in which specific Native cultural groups perceive their problems with drinking and sobriety can create more culturally congruent, culturally sensitive, and effective treatment approaches and inform future research.
Exercise in the management of persons with multiple sclerosis
Authors: Giesser Barbara S.
Published: March 2015

For decades, persons with multiple sclerosis (MS) were counseled to avoid excessive physical activity and exercise because of concerns about worsening disease activity. Recent studies indicate that, not only can those with MS tolerate physical exercise, but that it is helpful in managing symptoms, preventing complications and comorbidities, and may possibly have neuroprotective actions. This article reviews previous studies on the effects of different exercise protocols in people with MS, and provides summaries of suggested exercise regimens that may be appropriate and beneficial for this patient population.
Technique Tip
Authors: Sullivan Martin , Panti Juan Paulo
Published: March 2015

The combination of a dorsal approach to the plantar plate with a Weil’s metatarsal osteotomy has been shown to provide an adequate exposure for plantar plate repair. However, soft tissues in a restricted area of the metatarsophalangeal joint could present as a technical difficulty during suture retrieval during repair of the plantar plate. The purpose of this article is to describe the use of the McGlamry elevator for assistance in the retrieval of sutures through the proximal phalanx.

Level of Evidence: Level V: Expert opinion
Targeting deubiquitinase activity with a novel small-molecule inhibitor as therapy for B-cell malignancies
Authors: Peterson Luke F. , Sun Hanshi , Liu Yihong , Potu Harish , Kandarpa Malathi , Ermann Monika , Courtney Stephen M. , Young Matthew , Showalter Hollis D. , Sun Duxin , Jakubowiak Andrzej , Malek Sami N. , Talpaz Moshe , Donato Nicholas J.
Published: March 2015

Key Points

Deubiquitinases Usp9x and Usp24 regulate Mcl-1 and myeloma cell survival. Small-molecule–mediated Usp9x/Usp24 inhibition induces apoptosis and blocks myeloma tumor growth in vivo.
The IL-33/ST2 axis augments effector T-cell responses during acute GVHD
Authors: Reichenbach Dawn K. , Schwarze Vincent , Matta Benjamin M. , Tkachev Victor , Lieberknecht Elisabeth , Liu Quan , Koehn Brent H. , Pfeifer Dietmar , Taylor Patricia A. , Prinz Gabriele , Dierbach Heide , Stickel Natalie , Beck Yvonne , Warncke Max , Junt Tobias , Schmitt-Graeff Annette , Nakae Susumu , Follo Marie , Wertheimer Tobias , Schwab Lukas , Devlin Jason , Watkins Simon C. , Duyster Justus , Ferrara James L. M. , Turnquist Heth R. , Zeiser Robert , Blazar Bruce R.
Published: March 2015

Key Points

IL-33 and ST2 expression are increased post-conditioning and with GVHD, resulting in increased T-cell activation via the IL-33/ST2 axis. Infusion of ST2-Fc protein exploits sST2’s function as a negative regulator of acute GVHD inhibiting pro-inflammatory cytokines.
Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide
Authors: McCurdy Shannon R. , Kanakry Jennifer A. , Showel Margaret M. , Tsai Hua-Ling , Bolaños-Meade Javier , Rosner Gary L. , Kanakry Christopher G. , Perica Karlo , Symons Heather J. , Brodsky Robert A. , Gladstone Douglas E. , Huff Carol Ann , Pratz Keith W. , Prince Gabrielle T. , Dezern Amy E. , Gojo Ivana , Matsui William H. , Borrello Ivan , McDevitt Michael A. , Swinnen Lode J. , Smith B. Douglas , Levis Mark J. , Ambinder Richard F. , Luznik Leo , Jones Richard J. , Fuchs Ephraim J. , Kasamon Yvette L.
Published: March 2015

Key Points

Nonmyeloablative, related HLA-haploidentical BMT utilizing high-dose posttransplantation cyclophosphamide has a favorable safety profile. Risk-stratified relapse and survival outcomes with this approach are comparable to those of HLA-matched BMT.
Granulocyte colony-stimulating factor reprograms bone marrow stromal cells to actively suppress B lymphopoiesis in mice
Authors: Day Ryan B. , Bhattacharya Deepta , Nagasawa Takashi , Link Daniel C.
Published: March 2015

Key Points

G-CSF suppresses B lymphopoiesis at multiple stages of development. G-CSF reprograms bone marrow stromal cells to inhibit their production of B-cell trophic factors.
Effect of single-walled carbon nanotubes on tumor cells viability and formation of multicellular tumor spheroids
Authors: Yakymchuk Olena M , Perepelytsina Olena M , Dobrydnev Alexey V , Sydorenko Mychailo V
Published: March 2015

This paper describes the impact of different concentrations of single-walled carbon nanotubes (SWCNTs) on cell viability of breast adenocarcinoma, MCF-7 line, and formation of multicellular tumor spheroids (MTS). Chemical composition and purity of nanotubes is controlled by Fourier transform infrared spectroscopy. The strength and direction of the influence of SWCNTs on the tumor cell population was assessed by cell counting and measurement of the volume of multicellular tumor spheroids. Effect of SWCNTs on the formation of multicellular spheroids was compared with the results obtained by culturing tumor cells with ultra dispersed diamonds (UDDs). Our results demonstrated that SWCNTs at concentrations ranging from 12.5 to 50 μg/ml did not have cytotoxic influence on tumor cells; instead, they had weak cytostatic effect. The increasing of SWCNTs concentration to 100 to 200 μg/ml stimulated proliferation of tumor cells, especially in suspension fractions. The result of this influence was in formation of more MTS in cell culture with SWCNTs compared with UDDs and control samples. In result, the median volume of MTS after cultivation with SWCNTs at 100 to 200 μg/ml concentrations is 3 to 5 times greater than that in samples which were incubated with the UDDs and is 2.5 times greater than that in control cultures. So, if SWCNTs reduced cell adhesion to substrate and stimulated formation of tumor cell aggregates volume near 7 · 10−3 mm3, at the same time, UDDs reduced adhesion and cohesive ability of cells and stimulated generation of cell spheroids volume no more than 4 · 10−3 mm3. Our results could be useful for the control of cell growth in three-dimensional culture.

PACS

61. 46 + w; 61.48 + c; 61.48De; 87.15-v; 87.64-t
Properties of Sodium Currents in Neonatal and Young Adult Mouse Superficial Dorsal Horn Neurons
Authors: Tadros Melissa A , Farrell Kristen E , Graham Brett A , Brichta Alan M , Callister Robert J
Published: March 2015

Background

Superficial dorsal horn (SDH) neurons process nociceptive information and their excitability is partly determined by the properties of voltage-gated sodium channels. Recently, we showed the excitability and action potential properties of mouse SDH neurons change markedly during early postnatal development. Here we compare sodium currents generated in neonate (P0-5) and young adult (≥P21) SDH neurons.

Results

Whole cell recordings were obtained from lumbar SDH neurons in transverse spinal cord slices (CsF internal, 32°C). Fast activating and inactivating TTX-sensitive inward currents were evoked by depolarization from a holding potential of −100 mV. Poorly clamped currents, based on a deflection in the IV relationship at potentials between −60 and −50 mV, were not accepted for analysis. Current density and decay time increased significantly between the first and third weeks of postnatal development, whereas time to peak was similar at both ages. This was accompanied by more subtle changes in activation range and steady state inactivation. Recovery from inactivation was slower and TTX-sensitivity was reduced in young adult neurons.

Conclusions

Our study suggests sodium channel expression changes markedly during early postnatal development in mouse SDH neurons. The methods employed in this study can now be applied to future investigations of spinal cord sodium channel plasticity in murine pain models.
Reviewer Acknowledgement 2014
Authors: Menz Hylton B , Potter Mike
Published: March 2015

Contributing reviewers

The Editors of Journal of Foot and Ankle Research would like to thank all our reviewers who have contributed to the journal in Volume 7 (2014).
Prolonged mechanical ventilation–induced neuroinflammation affects postoperative memory dysfunction in surgical mice
Authors: Chen Chang , Zhang Zongze , Chen Ting , Peng Mian , Xu Xing , Wang Yanlin
Published: March 2015

Introduction

Patients undergoing surgery frequently develop neuropsychological disturbances, including cognitive decline or memory impairment, and routine clinical procedures such as mechanical ventilation (MV) may affect acute-phase brain outcome. We aimed to investigate the effect of the prolonged MV on postoperative memory dysfunction in surgical mice.

Methods

Male C57BL/6 mice were randomly divided into the following three groups: (1) The control group (group C) comprised anesthetized, unventilated animals; (2) the surgery group (subgroups S1h, S3h and S6h) was unventilated animals that underwent surgery under general anesthesia; and (3) the MV group (subgroups MV1h, MV3h and MV6h) was made up of animals under MV for 1 hour, 3 hours or 6 hours after surgery. Separate cohorts of animals were tested for memory function with fear conditioning tests or were killed at 6 hours, 1 day or 3 days postsurgery or post-MV to examine levels systemic and hippocampal interleukin (IL)-1β, IL-6 and tumor necrosis factor α (TNFα), and assessed synaptic structure and microglial activation. Nuclear factor κB (NF-κB) p65, cytochrome c, cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) activation were analyzed by Western blotting.

Results

The MV6h group showed increased CD11b-immunopositive cells, synapse degeneration, cytochrome c release, cleaved caspase-3 and cleaved PARP-1 activation after surgery, as well as a decrease in freezing time after surgery. At 6 hours and 1 day post-MV, MV6h increased NF-κB activation and levels of systemic and hippocampal IL-1β, IL-6 and TNFα after surgery.

Conclusions

Prolonged MV after surgery further aggravates cognitive decline that may stem from upregulation of hippocampal IL-1β, IL-6 and TNFα, partially via activation of gliocytes in the surgical mouse hippocampus.
A systematic review of implementation strategies for assessment, prevention, and management of ICU delirium and their effect on clinical outcomes
Authors: Trogrlić Zoran , van der Jagt Mathieu , Bakker Jan , Balas Michele C , Ely E Wesley , van der Voort Peter HJ , Ista Erwin
Published: March 2015

Introduction

Despite recommendations from professional societies and patient safety organizations, the majority of ICU patients worldwide are not routinely monitored for delirium, thus preventing timely prevention and management. The purpose of this systematic review is to summarize what types of implementation strategies have been tested to improve ICU clinicians’ ability to effectively assess, prevent and treat delirium and to evaluate the effect of these strategies on clinical outcomes.

Method

We searched PubMed, Embase, PsychINFO, Cochrane and CINAHL (January 2000 and April 2014) for studies on implementation strategies that included delirium-oriented interventions in adult ICU patients. Studies were suitable for inclusion if implementation strategies’ efficacy, in terms of a clinical outcome, or process outcome was described.

Results

We included 21 studies, all including process measures, while 9 reported both process measures and clinical outcomes. Some individual strategies such as “audit and feedback” and “tailored interventions” may be important to establish clinical outcome improvements, but otherwise robust data on effectiveness of specific implementation strategies were scarce. Successful implementation interventions were frequently reported to change process measures, such as improvements in adherence to delirium screening with up to 92%, but relating process measures to outcome changes was generally not possible. In meta-analyses, reduced mortality and ICU length of stay reduction were statistically more likely with implementation programs that employed more (six or more) rather than less implementation strategies and when a framework was used that either integrated current evidence on pain, agitation and delirium management (PAD) or when a strategy of early awakening, breathing, delirium screening and early exercise (ABCDE bundle) was employed. Using implementation strategies aimed at organizational change, next to behavioral change, was also associated with reduced mortality.

Conclusion

Our findings may indicate that multi-component implementation programs with a higher number of strategies targeting ICU delirium assessment, prevention and treatment and integrated within PAD or ABCDE bundle have the potential to improve clinical outcomes. However, prospective confirmation of these findings is needed to inform the most effective implementation practice with regard to integrated delirium management and such research should clearly delineate effective practice change from improvements in clinical outcomes.
Granulocytic immune infiltrates are essential for the efficient formation of breast cancer liver metastases
Authors: Tabariès Sébastien , Ouellet Véronique , Hsu Brian E , Annis Matthew G , Rose April AN , Meunier Liliane , Carmona Euridice , Tam Christine E , Mes-Masson Anne-Marie , Siegel Peter M
Published: March 2015

Introduction

Breast cancer cells display preferences for specific metastatic sites including the bone, lung and liver. Metastasis is a complex process that relies, in part, on interactions between disseminated cancer cells and resident/infiltrating stromal cells that constitute the metastatic microenvironment. Distinct immune infiltrates can either impair the metastatic process or conversely, assist in the seeding, colonization and growth of disseminated cancer cells.

Methods

Using in vivo selection approaches, we previously isolated 4T1-derived breast cancer cells that preferentially metastasize to these organs and tissues. In this study, we examined whether the propensity of breast cancer cells to metastasize to the lung, liver or bone is associated with and dependent on distinct patterns of immune cell infiltration. Immunohistocytochemistry and immunohistofluorescence approaches were used to quantify innate immune cell infiltrates within distinct metastases and depletion of Gr1+ (Ly-6C and Ly-6G) or specifically Ly-6G+ cells was performed to functionally interrogate the role of Ly-6G+ infiltrates in promoting metastasis to these organs.

Results

We show that T lymphocytes (CD3+), myeloid-derived (Gr-1+) cells and neutrophils (Ly-6G+ or NE+) exhibit the most pronounced recruitment in lung and liver metastases, with markedly less recruitment within bone metastatic lesions. Interestingly, these infiltrating cell populations display different patterns of localization within soft tissue metastases. T lymphocytes and granulocytic immune infiltrates are localized around the periphery of liver metastases whereas they were dispersed throughout the lung metastases. Furthermore, Gr-1+ cell-depletion studies demonstrate that infiltrating myeloid-derived cells are essential for the formation of breast cancer liver metastases but dispensable for metastasis to the lung and bone. A specific role for the granulocytic component of the innate immune infiltrate was revealed through Ly-6G+ cell-depletion experiments, which resulted in significantly impaired formation of liver metastases. Finally, we demonstrate that the CD11b+/Ly-6G+ neutrophils that infiltrate and surround the liver metastases are polarized toward an N2 phenotype, which have previously been shown to enhance tumor growth and metastasis.

Conclusions

Our results demonstrate that the liver-metastatic potential of breast cancer cells is heavily reliant on interactions with infiltrating Ly-6G+ cells within the liver microenvironment.
Calling genotypes from public RNA-sequencing data enables identification of genetic variants that affect gene-expression levels
Authors: Deelen Patrick , Zhernakova Daria V , de Haan Mark , van der Sijde Marijke , Bonder Marc Jan , Karjalainen Juha , van der Velde K Joeri , Abbott Kristin M , Fu Jingyuan , Wijmenga Cisca , Sinke Richard J , Swertz Morris A , Franke Lude
Published: March 2015

Background

RNA-sequencing (RNA-seq) is a powerful technique for the identification of genetic variants that affect gene-expression levels, either through expression quantitative trait locus (eQTL) mapping or through allele-specific expression (ASE) analysis. Given increasing numbers of RNA-seq samples in the public domain, we here studied to what extent eQTLs and ASE effects can be identified when using public RNA-seq data while deriving the genotypes from the RNA-sequencing reads themselves.

Methods

We downloaded the raw reads for all available human RNA-seq datasets. Using these reads we performed gene expression quantification. All samples were jointly normalized and subjected to a strict quality control. We also derived genotypes using the RNA-seq reads and used imputation to infer non-coding variants. This allowed us to perform eQTL mapping and ASE analyses jointly on all samples that passed quality control. Our results were validated using samples for which DNA-seq genotypes were available.

Results

4,978 public human RNA-seq runs, representing many different tissues and cell-types, passed quality control. Even though these data originated from many different laboratories, samples reflecting the same cell type clustered together, suggesting that technical biases due to different sequencing protocols are limited. In a joint analysis on the 1,262 samples with high quality genotypes, we identified cis-eQTLs effects for 8,034 unique genes (at a false discovery rate ≤0.05). eQTL mapping on individual tissues revealed that a limited number of samples already suffice to identify tissue-specific eQTLs for known disease-associated genetic variants. Additionally, we observed strong ASE effects for 34 rare pathogenic variants, corroborating previously observed effects on the corresponding protein levels.

Conclusions

By deriving and imputing genotypes from RNA-seq data, it is possible to identify both eQTLs and ASE effects. Given the exponential growth of the number of publicly available RNA-seq samples, we expect this approach will become especially relevant for studying the effects of tissue-specific and rare pathogenic genetic variants to aid clinical interpretation of exome and genome sequencing.
Peripheral and central effects of γ-secretase inhibition by semagacestat in Alzheimer’s disease
Authors: Doody Rachelle S , Raman Rema , Sperling Reisa A , Seimers Eric , Sethuraman Gopalan , Mohs Richard , Farlow Martin , Iwatsubo Takeshi , Vellas Bruno , Sun Xiaoying , Ernstrom Karin , Thomas Ronald G , Aisen Paul S ,   for the Alzheimer’s Disease Cooperative Study
Published: March 2015

Introduction

The negative efficacy study examining the γ-secretase inhibitor semagacestat in mild to moderate Alzheimer’s disease (AD) included a number of biomarkers of the disease as well as safety outcomes. We analyzed these data to explore relationships between drug exposure and pharmacodynamic effects and to examine the correlations among outcome measures.

Methods

The study was a multicenter, randomized, placebo-controlled trial of two dose regimens of semagacestat and a placebo administered for 18 months to individuals with mild to moderate AD. Changes in measures of central and peripheral drug activity were compared between the three treatment groups using one-way analysis of variance. The relationship between changes in each of the outcome measures and measures of drug exposure and peripheral pharmacodynamic effect were assessed using Spearman’s correlation coefficient.

Results

Assignment to the active treatment arms was associated with reduction in plasma amyloid-β (Aβ) peptides, increase in ventricular volume, decrease in cerebrospinal fluid phosphorylated tau (p-tau) and several other laboratory measures and adverse event categories. Within the active arms, exposure to drug, as indicated by area under the concentration curve (AUC) of blood concentration, was associated with reduction in plasma Aβ peptides and a subset of laboratory changes and adverse event rates. Ventricular volume increase, right hippocampal volume loss and gastrointestinal symptoms were related to change in plasma Aβ peptide but not AUC, supporting a link to inhibition of γ-secretase cleavage of the amyloid precursor protein. Cognitive decline correlated with ventricular expansion and reduction in p-tau.

Conclusion

These findings may inform future studies of drugs targeting secretases involved in Aβ generation.

Trial registration

ClinicalTrials.gov Identifier: NCT00594568. Registered 11 January 2008.
Novel 89Zr cell labeling approach for PET-based cell trafficking studies
Authors: Bansal Aditya , Pandey Mukesh K , Demirhan Yunus E , Nesbitt Jonathan J , Crespo-Diaz Ruben J , Terzic Andre , Behfar Atta , DeGrado Timothy R
Published: March 2015

Background

With the recent growth of interest in cell-based therapies and radiolabeled cell products, there is a need to develop more robust cell labeling and imaging methods for in vivo tracking of living cells. This study describes evaluation of a novel cell labeling approach with the positron emission tomography (PET) isotope 89Zr (T
1/2 = 78.4 h). 89Zr may allow PET imaging measurements for several weeks and take advantage of the high sensitivity of PET imaging.

Methods

A novel cell labeling agent, 89Zr-desferrioxamine-NCS (89Zr-DBN), was synthesized. Mouse-derived melanoma cells (mMCs), dendritic cells (mDCs), and human mesenchymal stem cells (hMSCs) were covalently labeled with 89Zr-DBN via the reaction between the NCS group on 89Zr-DBN and primary amine groups present on cell surface membrane protein. The stability of the label on the cell was tested by cell efflux studies for 7 days. The effect of labeling on cellular viability was tested by proliferation, trypan blue, and cytotoxicity/apoptosis assays. The stability of label was also studied in in vivo mouse models by serial PET scans and ex vivo biodistribution following intravenous and intramyocardial injection of 89Zr-labeled hMSCs. For comparison, imaging experiments were performed after intravenous injections of 89Zr hydrogen phosphate (89Zr(HPO4)2).

Results

The labeling agent, 89Zr-DBN, was prepared in 55% ± 5% decay-corrected radiochemical yield measured by silica gel iTLC. The cell labeling efficiency was 30% to 50% after 30 min labeling depending on cell type. Radioactivity concentrations of labeled cells of up to 0.5 MBq/106 cells were achieved without a negative effect on cellular viability. Cell efflux studies showed high stability of the radiolabel out to 7 days. Myocardially delivered 89Zr-labeled hMSCs showed retention in the myocardium, as well as redistribution to the lung, liver, and bone. Intravenously administered 89Zr-labeled hMSCs also distributed primarily to the lung, liver, and bone, whereas intravenous 89Zr(HPO4)2 distributed to the liver and bone with no activity in the lung. Thus, the in vivo stability of the radiolabel on the hMSCs was evidenced.

Conclusions

We have developed a robust, general, and biostable 89Zr-DBN-based cell labeling strategy with promise for wide applications of PET-based non-invasive in vivo cell trafficking.
Expression and functional validation of heat-labile enterotoxin B (LTB) and cholera toxin B (CTB) subunits in transgenic rice (Oryza sativa)
Authors: Soh Ho Seob , Chung Ha Young , Lee Hyun Ho , Ajjappala Hemavathi , Jang Kyoungok , Park Jong-Hwa , Sim Joon-Soo , Lee Gee Young , Lee Hyun Ju , Han Young Hee , Lim Jae Wook , Choi Inchan , Chung In Sik , Hahn Bum-Soo
Published: March 2015

We expressed the heat-labile enterotoxin B (LTB) subunit from enterotoxigenic Escherichia coli and the cholera toxin B (CTB) subunit from Vibrio cholerae under the control of the rice (Oryza sativa) globulin (Glb) promoter. Binding of recombinant LTB and CTB proteins was confirmed based on GM1-ganglioside binding enzyme-linked immunosorbent assays (GM1-ELISA). Real-time PCR of three generations (T3, T4, and T5) in homozygous lines (LCI-11) showed single copies of LTB, CTB, bar and Tnos. LTB and CTB proteins in rice transgenic lines were detected by Western blot analysis. Immunogenicity trials of rice-derived CTB and LTB antigens were evaluated through oral and intraperitoneal administration in mice, respectively. The results revealed that LTB- and CTB-specific IgG levels were enhanced in the sera of intraperitoneally immunized mice. Similarly, the toxin-neutralizing activity of CTB and LTB in serum of orally immunized mice was associated with elevated levels of both IgG and IgA. The results of the present study suggest that the combined expression of CTB and LTB proteins can be utilized to produce vaccines against enterotoxigenic strains of Escherichia coli and Vibrio cholera, for the prevention of diarrhea.
Reactive scheduling based on actual logistics data by applying simulation-based optimization
Authors: Szczesny Kamil , König Markus
Published: March 2015

Background

A reasonable management and monitoring of construction projects requires accurate construction schedules. Accuracy depends highly on availability of reliable actual logistics data. Such data contain information about available material, equipment, personnel, updated delivery dates, and other data on site conditions. However, such data is often associated with different types of uncertainties due to infrequent collections, varying transport times, or manual assessments. Nonetheless, consideration of these uncertainties is important for evaluating actual data regarding their impact on the overall construction progress. Currently, the integration of such data into construction schedules is a time-consuming, manual and, thus, error-prone process. Therefore, in practice schedules are not updated as often as they should be.

Methods

To ease the handling of actual data and their integration into construction schedules, a reactive construction scheduling approach is presented. The approach is structured into four successive steps. To evaluate and systematically analyze uncertain actual data, fuzzy set theory and α-cut method are incorporated. Thus, actual data can be integrated into discrete-event simulation models. These models are used to perform simulation-based sensitivity analyzes, which evaluate impacts on construction schedules. As a result, an actual schedule is generated, such that a target-actual schedule comparison can be performed. If significant deviations or problems are identified, adaption is necessary and a new schedule needs to be generated. Thereby, different restrictions on the target schedule, such as contracted delivery dates, milestones or resource allocation must be considered. To perform this required adaption simulation-based optimization is utilized.

Results

To validate the method and show its advantages, an initial construction schedule example is created. The example is extended to incorporate uncertain actual logistics data. The proposed method shows how efficient actual data can be analyzed to update construction schedules. Further, the results show a competitive adaption of invalid construction schedules, such that contracted milestones, or other project objectives can be achieved.

Conclusion

The presented reactive construction scheduling method has the ability to improve current treatment of uncertain actual logistics data. This helps construction project managers to improve the management and monitoring of construction projects by reducing the time-consuming, error-prone process of updating inconsistent schedules.
Reworking the appraisal framework in ESL research: refining attitude resources
Authors: Ngo Thu , Unsworth Len
Published: March 2015

The Appraisal framework within Systemic Functional Linguistics as a robust tool in language teaching and research has attracted a great deal of interest in recent years. Since its establishment as the most complete account, the framework has been used in a variety of contexts, resulting in a number of refinements, tuning its applicability for specific research purposes such as studies of the evaluative language in research article abstracts, biology experiment reports, wine appreciation and student narrative writing. This article proposes additional refinements, particularly to the system of Attitude, informed by research into the deployment of evaluative resources in spoken discourse by postgraduate students in small group discussions in English and in Vietnamese. The refinements were required to account for the range of evaluative language used in discussions of topics including personal experiences of living and studying in Australia, academic experiences at Australian universities, and opinion about one’s professional standing. These refinements contribute to the ongoing development of the Appraisal framework and provide a resource for enhancing the effectiveness of expressions of evaluative stance for speakers of English as a second or additional language.
On the reliability of N-body simulations
Authors: Boekholt Tjarda , Portegies Zwart Simon
Published: March 2015

The general consensus in the N-body community is that statistical results of an ensemble of collisional N-body simulations are accurate, even though individual simulations are not. A way to test this hypothesis is to make a direct comparison of an ensemble of solutions obtained by conventional methods with an ensemble of true solutions. In order to make this possible, we wrote an N-body code called , that uses arbitrary-precision arithmetic. In combination with the Bulirsch-Stoer method, is able to obtain converged solutions, which are true up to a specified number of digits.

We perform simulations of democratic 3-body systems, where after a sequence of resonances and ejections, a final configuration is reached consisting of a permanent binary and an escaping star. We do this with conventional double-precision methods, and with ; both have the same set of initial conditions and initial realisations. The ensemble of solutions from the conventional simulations is compared directly to that of the converged simulations, both as an ensemble and on an individual basis to determine the distribution of the errors.

We find that on average at least half of the conventional simulations diverge from the converged solution, such that the two solutions are microscopically incomparable. For the solutions which have not diverged significantly, we observe that if the integrator has a bias in energy and angular momentum, this propagates to a bias in the statistical properties of the binaries. In the case when the conventional solution has diverged onto an entirely different trajectory in phase-space, we find that the errors are centred around zero and symmetric; the error due to divergence is unbiased, as long as the time-step parameter, $\eta\le2^{-5}$
η
≤

2

−
5

and when simulations which violate energy conservation by more than 10% are excluded. For resonant 3-body interactions, we conclude that the statistical results of an ensemble of conventional solutions are indeed accurate.
Adaptive techniques for clustered N-body cosmological simulations
Authors: Menon Harshitha , Wesolowski Lukasz , Zheng Gengbin , Jetley Pritish , Kale Laxmikant , Quinn Thomas , Governato Fabio
Published: March 2015

ChaNGa is an N-body cosmology simulation application implemented using Charm++. In this paper, we present the parallel design of ChaNGa and address many challenges arising due to the high dynamic ranges of clustered datasets. We propose optimizations based on adaptive techniques. We evaluate the performance of ChaNGa on highly clustered datasets: a $z \sim0$
z
∼
0
snapshot of a 2 billion particle realization of a 25 Mpc volume, and a 52 million particle multi-resolution realization of a dwarf galaxy. For the 25 Mpc volume, we show strong scaling on up to 128K cores of Blue Waters. We also demonstrate scaling up to 128K cores of a multi-stepping run of the 2 billion particle simulation. While the scaling of the multi-stepping run is not as good as single stepping, the throughput at 128K cores is greater by a factor of 2. We also demonstrate strong scaling on up to 512K cores of Blue Waters for two large, uniform datasets with 12 and 24 billion particles.
Cyclic Shear Behavior of Gypsum Board-to-Steel Stud Screw Connections in Nonstructural Walls
Authors: Rahmanishamsi Esmaeel , Soroushian Siavash , Maragakis Manos
Published: March 2015

Gypsum steel-stud partition walls are composed of light-gauge, cold-formed steel studs, and gypsum boards attached with self-drilling screws. Previous experimental studies on the seismic performance of these walls have shown widespread failure of gypsum-to-stud connections (GSCs), initiated at very low amplitude excitation. The failure of GSCs resulted in loss of strength and stiffness of the partition walls. A series of component tests has been conducted at University of Nevada, Reno to evaluate the shear force and displacement capacities of GSCs. Fastener spacing (center to center and also center to edge), loading protocol (monotonic or cyclic), and stud thickness were varied between specimens. The test data were then used to develop fragility curves for shear capacities of GSCs in terms of displacements. Additionally, a series of nonlinear GSC hinge models were proposed and validated using component experimental data.
Brg1 modulates enhancer activation in mesoderm lineage commitment
Authors: Alexander Jeffrey M. , Hota Swetansu K. , He Daniel , Thomas Sean , Ho Lena , Pennacchio Len A. , Bruneau Benoit G.
Published: March 2015

The interplay between different levels of gene regulation in modulating developmental transcriptional programs, such as histone modifications and chromatin remodeling, is not well understood. Here, we show that the chromatin remodeling factor Brg1 is required for enhancer activation in mesoderm induction. In an embryonic stem cell-based directed differentiation assay, the absence of Brg1 results in a failure of cardiomyocyte differentiation and broad deregulation of lineage-specific gene expression during mesoderm induction. We find that Brg1 co-localizes with H3K27ac at distal enhancers and is required for robust H3K27 acetylation at distal enhancers that are activated during mesoderm induction. Brg1 is also required to maintain Polycomb-mediated repression of non-mesodermal developmental regulators, suggesting cooperativity between Brg1 and Polycomb complexes. Thus, Brg1 is essential for modulating active and repressive chromatin states during mesoderm lineage commitment, in particular the activation of developmentally important enhancers. These findings demonstrate interplay between chromatin remodeling complexes and histone modifications that, together, ensure robust and broad gene regulation during crucial lineage commitment decisions.
SNPfisher: tools for probing genetic variation in laboratory-reared zebrafish
Authors: Butler Matthew G. , Iben James R. , Marsden Kurt C. , Epstein Jonathan A. , Granato Michael , Weinstein Brant M.
Published: March 2015

Single nucleotide polymorphisms (SNPs) are the benchmark molecular markers for modern genomics. Until recently, relatively few SNPs were known in the zebrafish genome. The use of next-generation sequencing for the positional cloning of zebrafish mutations has increased the number of known SNP positions dramatically. Still, the identified SNP variants remain under-utilized, owing to scant annotation of strain specificity and allele frequency. To address these limitations, we surveyed SNP variation in three common laboratory zebrafish strains using whole-genome sequencing. This survey identified an average of 5.04 million SNPs per strain compared with the Zv9 reference genome sequence. By comparing the three strains, 2.7 million variants were found to be strain specific, whereas the remaining variants were shared among all (2.3 million) or some of the strains. We also demonstrate the broad usefulness of our identified variants by validating most in independent populations of the same laboratory strains. We have made all of the identified SNPs accessible through ‘SNPfisher’, a searchable online database (snpfisher.nichd.nih.gov). The SNPfisher website includes the SNPfisher Variant Reporter tool, which provides the genomic position, alternate allele read frequency, strain specificity, restriction enzyme recognition site changes and flanking primers for all SNPs and Indels in a user-defined gene or region of the zebrafish genome. The SNPfisher site also contains links to display our SNP data in the UCSC genome browser. The SNPfisher tools will facilitate the use of SNP variation in zebrafish research as well as vertebrate genome evolution.
Wnt5aandWnt11regulate mammalian anterior-posterior axis elongation
Authors: Andre Philipp , Song Hai , Kim Wantae , Kispert Andreas , Yang Yingzi
Published: March 2015

Mesoderm formation and subsequent anterior-posterior (A-P) axis elongation are fundamental aspects of gastrulation, which is initiated by formation of the primitive streak (PS). Convergent extension (CE) movements and epithelial-mesenchymal transition (EMT) are important for A-P axis elongation in vertebrate embryos. The evolutionarily conserved planar cell polarity (PCP) pathway regulates CE, and Wnts regulate many aspects of gastrulation including CE and EMT. However, the Wnt ligands that regulate A-P axis elongation in mammalian development remain unknown. Wnt11 and Wnt5a regulate axis elongation in lower vertebrates, but only Wnt5a, not Wnt11, regulates mammalian PCP signaling and A-P axis elongation in development. Here, by generating Wnt5a; Wnt11 compound mutants, we show that Wnt11 and Wnt5a play redundant roles during mouse A-P axis elongation. Both genes regulate trunk notochord extension through PCP-controlled CE of notochord cells, establishing a role for Wnt11 in mammalian PCP. We show that Wnt5a and Wnt11 are required for proper patterning of the neural tube and somites by regulating notochord formation, and provide evidence that both genes are required for the generation and migration of axial and paraxial mesodermal precursor cells by regulating EMT. Axial and paraxial mesodermal precursors ectopically accumulate in the PS at late gastrula stages in Wnt5a−/−; Wnt11−/− embryos and these cells ectopically express epithelial cell adhesion molecules. Our data suggest that Wnt5a and Wnt11 regulate EMT by inducing p38 (Mapk14) phosphorylation. Our findings provide new insights into the role of Wnt5a and Wnt11 in mouse early development and also in cancer metastasis, during which EMT plays a crucial role.
The Housing Market (s) of San Diego
Authors: Landvoigt Tim , Piazzesi Monika , Schneider Martin
Published: March 2015

This paper uses an assignment model to understand the cross section of house prices within a metro area. Movers’ demand for housing is derived from a life-cycle problem with credit market frictions. Equilibrium house prices adjust to assign houses that differ by quality to movers who differ by age, income, and wealth. To quantify the model, we measure distributions of house prices, house qualities, and mover characteristics from micro-data on San Diego County during the 2000s boom. The main result is that cheaper credit for poor households was a major driver of prices, especially at the low end of the market. (JEL D14, D91, R21, R31)