bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the Sugen5416/hypoxia/normoxia model of pulmonary arterial hypertension.
Authors: Joshi Sachindra Raj , Dhagia Vidhi , Gairhe Salina , Edwards John G. , McMurtry Ivan F. , Gupte Sachin A.
Published: July 2016

Heart failure, a major cause of morbidity and mortality in patients with pulmonary arterial hypertension (PAH), is an outcome of complex biochemical processes. In this study, we determined changes in microRNAs (miRs) in the right and left ventricles of normal and PAH rats. Using an unbiased quantitative miR microarray analysis, we found 1) miR-21-5p, miR-31-5 and 3p, miR-140-5 and 3p, miR-208b-3p, miR-221-3p, miR-222-3p, miR-702-3p, and miR-1298 were upregulated (>2-fold; P < 0.05) in the right ventricle (RV) of PAH compared with normal rats; 2) miR-31-5 and 3p, and miR-208b-3p were upregulated (>2-fold; P < 0.05) in the left ventricle plus septum (LV+S) of PAH compared with normal rats; 3) miR-187-5p, miR-208a-3p, and miR-877 were downregulated (>2-fold; P < 0.05) in the RV of PAH compared with normal rats; and 4) no miRs were up- or downregulated with >2-fold in LV+S compared with RV of PAH and normal. Upregulation of miR-140 and miR-31 in the hypertrophic RV was further confirmed by quantitative PCR. Interestingly, compared with control rats, expression of mitofusin-1 (MFN1), a mitochondrial fusion protein that regulates apoptosis, and which is a direct target of miR-140, was reduced in the RV relative to LV+S of PAH rats. We found a correlation between increased miR-140 and decreased MFN1 expression in the hypertrophic RV. Our results also demonstrated that upregulation of miR-140 and downregulation of MFN1 correlated with increased RV systolic pressure and hypertrophy. These results suggest that miR-140 and MFN1 play a role in the pathogenesis of PAH-associated RV dysfunction.

Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/mir140-and-right-heart-hypertrophy/ .
4D intravital microscopy uncovers critical strain differences for the roles of PECAM and CD99 in leukocyte diapedesis
Authors: Sullivan David P. , Watson Richard L. , Muller William A.
Published: July 2016

Leukocyte transendothelial migration (TEM) is an essential component of the inflammatory response. In vitro studies with human cells have demonstrated that platelet/endothelial cell adhesion molecule (PECAM) functions upstream of CD99 during TEM; however, results in vivo with mice have been apparently contradictory. In this study we use four-dimensional (4D) intravital microscopy to demonstrate that the site and order of function of PECAM and CD99 in vivo are dependent on the strain of mice. In FVB/n mice, PECAM functions upstream of CD99, as in human cells in vitro, and blocking antibodies against either molecule arrest neutrophils before they traverse the endothelium. However, in C57BL/6 mice, PECAM and CD99 appear to function at a different step, as the same antibodies arrest leukocyte migration through the endothelial basement membrane. These results are the first direct comparison of PECAM and CD99 function in different murine strains as well as the first demonstration of the sequential function of PECAM and CD99 in vivo.
The von Hippel-Lindau Chuvash mutation in mice alters cardiac substrate and high-energy phosphate metabolism
Authors: Slingo Mary , Cole Mark , Carr Carolyn , Curtis Mary K. , Dodd Michael , Giles Lucia , Heather Lisa C. , Tyler Damian , Clarke Kieran , Robbins Peter A.
Published: July 2016

Hypoxia-inducible factor (HIF) appears to function as a global master regulator of cellular and systemic responses to hypoxia. HIF pathway manipulation is of therapeutic interest; however, global systemic upregulation of HIF may have as yet unknown effects on multiple processes. We used a mouse model of Chuvash polycythemia (CP), a rare genetic disorder that modestly increases expression of HIF target genes in normoxia, to understand what these effects might be within the heart. An integrated in and ex vivo approach was employed. Compared with wild-type controls, CP mice had evidence (using in vivo magnetic resonance imaging) of pulmonary hypertension, right ventricular hypertrophy, and increased left ventricular ejection fraction. Glycolytic flux (measured using [3H]glucose) in the isolated contracting perfused CP heart was 1.8-fold higher. Net lactate efflux was 1.5-fold higher. Furthermore, in vivo 13C-magnetic resonance spectroscopy (MRS) of hyperpolarized [13C1]pyruvate revealed a twofold increase in real-time flux through lactate dehydrogenase in the CP hearts and a 1.6-fold increase through pyruvate dehydrogenase. 31P-MRS of perfused CP hearts under increased workload (isoproterenol infusion) demonstrated increased depletion of phosphocreatine relative to ATP. Intriguingly, no changes in cardiac gene expression were detected. In summary, a modest systemic dysregulation of the HIF pathway resulted in clear alterations in cardiac metabolism and energetics. However, in contrast to studies generating high HIF levels within the heart, the CP mice showed neither the predicted changes in gene expression nor any degree of LV impairment. We conclude that the effects of manipulating HIF on the heart are dose dependent.
Effect of PEEP, blood volume, and inspiratory hold maneuvers on venous return
Authors: Berger David , Moller Per W. , Weber Alberto , Bloch Andreas , Bloechlinger Stefan , Haenggi Matthias , Sondergaard Soren , Jakob Stephan M. , Magder Sheldon , Takala Jukka
Published: July 2016

According to Guyton's model of circulation, mean systemic filling pressure (MSFP), right atrial pressure (RAP), and resistance to venous return (RVR) determine venous return. MSFP has been estimated from inspiratory hold-induced changes in RAP and blood flow. We studied the effect of positive end-expiratory pressure (PEEP) and blood volume on venous return and MSFP in pigs. MSFP was measured by balloon occlusion of the right atrium (MSFPRAO), and the MSFP obtained via extrapolation of pressure-flow relationships with airway occlusion (MSFPinsp_hold) was extrapolated from RAP/pulmonary artery flow (QPA) relationships during inspiratory holds at PEEP 5 and 10 cmH2O, after bleeding, and in hypervolemia. MSFPRAOincreased with PEEP [PEEP 5, 12.9 (SD 2.5) mmHg; PEEP 10, 14.0 (SD 2.6) mmHg, P = 0.002] without change in QPA[2.75 (SD 0.43) vs. 2.56 (SD 0.45) l/min, P = 0.094]. MSFPRAOdecreased after bleeding and increased in hypervolemia [10.8 (SD 2.2) and 16.4 (SD 3.0) mmHg, respectively, P < 0.001], with parallel changes in QPA. Neither PEEP nor volume state altered RVR ( P = 0.489). MSFPinsp_holdoverestimated MSFPRAO[16.5 (SD 5.8) vs. 13.6 (SD 3.2) mmHg, P = 0.001; mean difference 3.0 (SD 5.1) mmHg]. Inspiratory holds shifted the RAP/QPArelationship rightward in euvolemia because inferior vena cava flow (QIVC) recovered early after an inspiratory hold nadir. The QIVCnadir was lowest after bleeding [36% (SD 24%) of preinspiratory hold at 15 cmH2O inspiratory pressure], and the QIVCrecovery was most complete at the lowest inspiratory pressures independent of volume state [range from 80% (SD 7%) after bleeding to 103% (SD 8%) at PEEP 10 cmH2O of QIVCbefore inspiratory hold]. The QIVCrecovery thus defends venous return, possibly via hepatosplanchnic vascular waterfall.
αVβ3 Integrin-Targeted Radionuclide Therapy with 64Cu-cyclam-RAFT-c(-RGDfK-)4
Authors: Jin Zhao-Hui , Furukawa Takako , Degardin Mélissa , Sugyo Aya , Tsuji Atsushi B. , Yamasaki Tomoteru , Kawamura Kazunori , Fujibayashi Yasuhisa , Zhang Ming-Rong , Boturyn Didier , Dumy Pascal , Saga Tsuneo
Published: July 2016

The transmembrane cell adhesion receptor αVβ3 integrin (αVβ3) has been identified as an important molecular target for cancer imaging and therapy. We have developed a tetrameric cyclic RGD (Arg-Gly-Asp) peptide–based radiotracer 64Cu-cyclam-RAFT-c(-RGDfK-)4, which successfully captured αVβ3-positive tumors and angiogenesis by PET. Here, we subsequently evaluated its therapeutic potential and side effects using an established αVβ3-positive tumor mouse model. Mice with subcutaneous U87MG glioblastoma xenografts received single administrations of 37 and 74 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4 (37 MBq/nmol), peptide control, or vehicle solution and underwent tumor growth evaluation. Side effects were assessed in tumor-bearing and tumor-free mice in terms of body weight, routine hematology, and hepatorenal functions. Biodistribution of 64Cu-cyclam-RAFT-c(-RGDfK-)4 with ascending peptide doses (0.25–10 nmol) and with the therapeutic dose of 2 nmol were determined at 3 hours and at various time points (2 minutes–24 hours) postinjection, respectively, based on which radiation-absorbed doses were estimated. The results revealed that 64Cu-cyclam-RAFT-c(-RGDfK-)4 dose dependently slowed down the tumor growth. The mean tumor doses were 1.28 and 1.81 Gy from 37 and 74 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4, respectively. Peptide dose study showed that the tumor uptake of 64Cu-cyclam-RAFT-c(-RGDfK-)4 dose dependently decreased at doses ≥1 nmol, indicating a saturation of αVβ3 with the administered therapeutic doses (1 and 2 nmol). Combined analysis of the data from tumor-bearing and tumor-free mice revealed no significant toxicity caused by 37–74 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4. Our study demonstrates the therapeutic efficacy and safety of 64Cu-cyclam-RAFT-c(-RGDfK-)4 for αVβ3-targeted radionuclide therapy. 64Cu-cyclam-RAFT-c(-RGDfK-)4 would be a promising theranostic drug for cancer imaging and therapy. Mol Cancer Ther; 15(9); 2076–85. ©2016 AACR.
Phosphoproteomics Reveals MAPK Inhibitors Enhance MET- and EGFR-Driven AKT Signaling in KRAS-Mutant Lung Cancer
Authors: Kim Jae-Young , Welsh Eric A. , Fang Bin , Bai Yun , Kinose Fumi , Eschrich Steven A. , Koomen John M. , Haura Eric B.
Published: July 2016

Pathway inhibition of the RAS-driven MAPK pathway using small-molecule kinase inhibitors has been a key focus for treating cancers driven by oncogenic RAS, yet significant clinical responses are lacking. Feedback reactivation of ERK driven by drug-induced RAF activity has been suggested as one of the major drug resistance mechanisms, especially in the context of oncogenic RAS. To determine whether additional adaptive resistance mechanisms may coexist, we characterized global phosphoproteomic changes after MEK inhibitor selumetinib (AZD6244) treatment in KRAS-mutant A427 and A549 lung adenocarcinoma cell lines employing mass spectrometry–based phosphoproteomics. We identified 9,075 quantifiable unique phosphosites (corresponding to 3,346 unique phosphoproteins), of which 567 phosphosites were more abundant and 512 phosphosites were less abundant after MEK inhibition. Selumetinib increased phosphorylation of KSR-1, a scaffolding protein required for assembly of MAPK signaling complex, as well as altered phosphorylation of GEF-H1, a novel regulator of KSR-1 and implicated in RAS-driven MAPK activation. Moreover, selumetinib reduced inhibitory serine phosphorylation of MET at Ser985 and potentiated HGF- and EGF-induced AKT phosphorylation. These results were recapitulated by pan-RAF (LY3009120), MEK (GDC0623), and ERK (SCH772984) inhibitors, which are currently under early-phase clinical development against RAS-mutant cancers. Our results highlight the unique adaptive changes in MAPK scaffolding proteins (KSR-1, GEF-H1) and in RTK signaling, leading to enhanced PI3K–AKT signaling when the MAPK pathway is inhibited.

Implications: This study highlights the unique adaptive changes in MAPK scaffolding proteins (KSR-1, GEF-H1) and in RTK signaling, leading to enhanced PI3K/AKT signaling when the MAPK pathway is inhibited. Mol Cancer Res; 14(10); 1019–29. ©2016 AACR.
Cell-free DNA (cfDNA): Clinical Significance and Utility in Cancer Shaped By Emerging Technologies
Authors: Volik Stanislav , Alcaide Miguel , Morin Ryan D. , Collins Colin
Published: July 2016

Precision oncology is predicated upon the ability to detect specific actionable genomic alterations and to monitor their adaptive evolution during treatment to counter resistance. Because of spatial and temporal heterogeneity and comorbidities associated with obtaining tumor tissues, especially in the case of metastatic disease, traditional methods for tumor sampling are impractical for this application. Known to be present in the blood of cancer patients for decades, cell-free DNA (cfDNA) is beginning to inform on tumor genetics, tumor burden, and mechanisms of progression and drug resistance. This substrate is amenable for inexpensive noninvasive testing and thus presents a viable approach to serial sampling for screening and monitoring tumor progression. The fragmentation, low yield, and variable admixture of normal DNA present formidable technical challenges for realization of this potential. This review summarizes the history of cfDNA discovery, its biological properties, and explores emerging technologies for clinically relevant sequence-based analysis of cfDNA in cancer patients. Molecular barcoding (or Unique Molecular Identifier, UMI)-based methods currently appear to offer an optimal balance between sensitivity, flexibility, and cost and constitute a promising approach for clinically relevant assays for near real-time monitoring of treatment-induced mutational adaptations to guide evidence-based precision oncology. Mol Cancer Res; 14(10); 898–908. ©2016 AACR.
Genomic Integration of High-Risk HPV Alters Gene Expression in Oropharyngeal Squamous Cell Carcinoma
Authors: Walline Heather M. , Komarck Christine M. , McHugh Jonathan B. , Bellile Emily L. , Brenner J. Chad , Prince Mark E. , McKean Erin L. , Chepeha Douglas B. , Wolf Gregory T. , Worden Francis P. , Bradford Carol R. , Carey Thomas E.
Published: July 2016

High-risk HPV (hrHPV) is the leading etiologic factor in oropharyngeal cancer. HPV-positive oropharyngeal tumors generally respond well to therapy, with complete recovery in approximately 80% of patients. However, it remains unclear why some patients are nonresponsive to treatment, with 20% of patients recurring within 5 years. In this study, viral factors were examined for possible clues to differences in tumor behavior. Oropharynx tumors that responded well to therapy were compared with those that persisted and recurred. Viral oncogene alternate transcripts were assessed, and cellular sites of viral integration were mapped and sequenced. Effects of integration on gene expression were assessed by transcript analysis at the integration sites. All of the tumors demonstrated active viral oncogenesis, indicated by expression of HPV E6 and E7 oncogenes and alternate E6 splicing. In the responsive tumors, HPV integration occurred exclusively in intergenic chromosome regions, except for one tumor with viral integration into TP63. Each recurrent tumor exhibited complex HPV integration patterns into cancer-associated genes, including TNFRSF13B, SCN2A, SH2B1, UBE2V2, SMOC1, NFIA, and SEMA6D. Disrupted cellular transcripts were identified in the region of integration in four of the seven affected genes.

Implications: Integration of transcriptionally active hrHPV into cellular intergenic regions associates with tumor behavior by altering gene expression. Mol Cancer Res; 14(10); 941–52. ©2016 AACR.
Mechanism, Consequences, and Therapeutic Targeting of Abnormal IL15 Signaling in Cutaneous T-cell Lymphoma
Authors: Mishra Anjali , La Perle Krista , Kwiatkowski Sonya , Sullivan Laura A. , Sams Gregory H. , Johns Jessica , Curphey Douglas P. , Wen Jing , McConnell Kathleen , Qi Jun , Wong Henry , Russo Giandomenico , Zhang Jianying , Marcucci Guido , Bradner James E. , Porcu Pierluigi , Caligiuri Michael A.
Published: July 2016

Cutaneous T-cell lymphoma (CTCL) is the most common type of primary cutaneous lymphoma. Here, we report that patients with CTCL show increased IL15 in a clinical stage–dependent manner. Mechanistically, we show that ZEB1 is a transcriptional repressor of IL15 in T cells and that hypermethylation of the ZEB1 binding region within the IL15 promoter, as seen in patients with CTCL, prevents ZEB1 binding and causes increased transcription of IL15. Using a transgenic mouse model of IL15, we provide evidence that overexpression of IL15 induces a spontaneous CTCL that mimics the human neoplasm. Excessive autocrine production of IL15 in T cells inhibits an HDAC1-mediated negative autoregulatory loop, resulting in the upregulation of HDAC1 and HDAC6 and transcriptional induction of the onco-miR-21. Interruption of IL15 downstream signaling with isotype-specific HDAC inhibitors halts (HDAC1) or significantly delays (HDAC6) the progression of CTCL in vivo and provides preclinical evidence supporting a hierarchical model of oncogenic signaling in CTCL.

Significance: To date, CTCL pathogenesis remains unknown, and there are no curative therapies. Our findings not only demonstrate a critical role for IL15-mediated inflammation in cutaneous T-cell lymphomagenesis, but also uncover a new oncogenic regulatory loop in CTCL involving IL15, HDAC1, HDAC6, and miR-21 that shows differential sensitivity to isotype-specific HDAC inhibitors. Cancer Discov; 6(9); 986–1005. ©2016 AACR.

This article is highlighted in the In This Issue feature, p. 932
Association of Exome Sequences With Cardiovascular Traits Among Blacks in the Jackson Heart Study
Authors: Peloso Gina M. , Lange Leslie A. , Varga Tibor V. , Nickerson Deborah A. , Smith Joshua D. , Griswold Michael E. , Musani Solomon , Polfus Linda M. , Mei Hao , Gabriel Stacey , Quarells Rakale Collins , Altshuler David , Boerwinkle Eric , Daly Mark J. , Neale Benjamin , Correa Adolfo , Reiner Alex P. , Wilson James G. , Kathiresan Sekar
Published: July 2016

Background—

The correlation of null alleles with human phenotypes can provide insight into gene function in humans. In individuals of African ancestry, we set out to identify null and damaging missense variants, and test these variants for association with a range of cardiovascular phenotypes.

Methods and Results—

We performed whole-exome sequencing in 3223 black individuals from the Jackson Heart Study and found a total of 729 666 variant sites with minor allele frequency <5%, including 17 263 null variants and 49 929 missense variants predicted to be damaging by in silico algorithms. We tested null and damaging missense variants within each gene for association with 36 cardiovascular traits. We found 3 associations that met our prespecified level of significance (α=1.1×10
−7
). Null and damaging missense variants in
PCSK9
were associated with 36 mg/dL lower low-density lipoprotein cholesterol (
P
=3×10
−21
). Three individuals in their 50s with complete PCSK9 deficiency (each compound heterozygote for
PCSK9
p.Y142X and p.C679X) were identified, with one having a coronary artery calcification score in the 83rd percentile despite a low-density lipoprotein cholesterol of 32 mg/dL. A damaging missense variant in
HBQ1
(p.G52A) was associated with a 2 pg/cell lower mean corpuscular hemoglobin (
P
=9×10
−13
) and rare damaging missense variants in
VPS13A
with higher red blood cell distribution width (
P
=9.9×10
–8
).

Conclusions—

A limited number of null/damaging alleles with a large effect on cardiovascular traits were detectable in ≈3000 black individuals.
Effect of collection tube type and freeze–thaw cycles on myeloperoxidase concentrations in blood samples of acute coronary syndrome patients
Authors: Naz Saima , Ghafoor Farkhanda , Iqbal Imran Akhtar
Published: July 2016

Background

Myeloperoxidase has shown potential as a marker for prognosis of coronary artery disease, but presently little is known about preanalytical handling of samples for quantifying myeloperoxidase. The present study was conducted to evaluate the effect of collection tube and freeze–thaw cycles on myeloperoxidase concentrations.

Methods

Acute coronary syndrome patients ( n = 88) were enrolled after obtaining written informed consent from coronary care unit of a tertiary care hospital (January 2012–June 2014). About 5 mL venous blood was collected from patients and divided into serum, lithium heparin, ethylenediaminetetraacetic acid and sodium citrate tubes. Except serum, all tubes were kept on ice immediately after collection. Samples were centrifuged at −4℃, separated immediately after centrifugation and stored at −40℃ until analysis. Myeloperoxidase was quantified by in-house and commercial assays and re-quantified after five freeze–thaw cycles.

Results

Myeloperoxidase concentrations, (serum samples) determined by commercial and in-house assays correlated well (r = 0.946) ( P < 0.001) and were higher in serum samples. Within plasma, myeloperoxidase concentrations were slightly higher in ethylenediaminetetraacetic acid (307.7 ± 52.1) and lower in lithium heparin (290.3 ± 49.2) and sodium citrate (221.4 ± 40.3) but not statistically significant. Correlation between myeloperoxidase concentrations (in-house enzyme-linked immunosorbent assay) after first cycle and fifth freeze–thaw cycle dropped to r = 0.448 ( P < 0.001).

Conclusion

Myeloperoxidase concentrations are comparable in three types of plasma tubes when samples are placed on ice immediately, centrifuged at low temperatures and separated immediately after centrifugation. Multiple freeze–thaw cycles have an effect on myeloperoxidase and should be avoided for quantifying myeloperoxidase.
Measurement of titanium in hip-replacement patients by inductively coupled plasma optical emission spectroscopy
Authors: Harrington Chris F , McKibbin Craig , Rahanu Monika , Langton David , Taylor Andrew
Published: July 2016

Background

Patients with metal-on-metal hip replacements require testing for cobalt and chromium. There may also be a need to test for titanium, which is used in the construction of the femoral stem in total hip replacements. It is not possible to use quadrupole inductively coupled plasma mass spectrometry due to interferences.

Methods

Titanium was measured using inductively coupled plasma optical emission spectroscopy using the emission line at 336.1 nm and Y (internal standard) at 371.0 nm. Internal quality control materials were prepared for blood and serum and concentrations assigned using a sector field-inductively coupled plasma mass spectrometer. A candidate whole blood certified reference material was also evaluated.

Results

The method had detection and quantitation limits of 0.6 and 1.9 µg/L, respectively. The respective bias (%) and measurement uncertainty ( U) (k = 2) were 3.3% and 2.0 µg/L (serum) and − 1.0% and 1.4 µg/L (whole blood). The respective repeatability and intermediate precision (%) were 5.1% and 10.9% (serum) and 2.4% and 8.6% (whole blood). The concentration of titanium was determined in patients’ samples, serum (median = 2.4 µg/L, n = 897) and whole blood (median = 2.4 µg/L, n = 189). Serum is recommended for monitoring titanium in patients, since the concentration is higher than in whole blood and the matrix less problematic. In hip fluid samples, the concentrations were much higher (mean 58.5 µg/L, median 5.1 µg/L, n = 83).

Conclusions

A method based on inductively coupled plasma optical emission spectroscopy was developed and validated for measuring titanium in clinical samples.
Assessing oral presentation skills in Electrical Engineering: Developing a valid and reliable rubric
Authors: Galván-Sánchez Inmaculada , Verano-Tacoronte Domingo , González-Betancor Sara M , Fernández-Monroy Margarita , Bolívar-Cruz Alicia
Published: July 2016

Oral presentation is one of the most important transversal competences for the professional career of Electrical Engineers. To develop and assess this competence, scoring rubrics are useful academic tools. The main purpose of this study is to contribute to the understanding of the learning and assessment of oral presentation skills of future Electrical Engineers by using a scoring rubric as a teaching resource. A pilot experiment was carried out in the 2011/2012 academic year in a course in the ninth semester of Electrical Engineering studies with 64 students. In order to acquire the oral competence, students had to present a marketing plan for an industrial electrical project in front of an audience. Feedback was collected in meetings held with teachers and students after the presentations. As a result, the need to review the rubric was detected, in order to make its use easier. The rubric’s design was improved. In the 2012/2013 academic year, 86 students participated in a new experiment using the improved rubric in the same subject. Intra-rater consistency was shown by the scale’s reliability, measured with Cronbach’s alpha. Regarding inter-rater consistency, two procedures were used: holistic and analytic. The holistic procedure revealed a positive and relatively high correlation between the global scores given by each of the two raters. The analytic procedure showed an acceptable level of inter-rater consensus. Through a questionnaire, quantitative data were collected reflecting students’ satisfaction with the use of the improved scoring rubric. The results reveal the rubric promotes students’ learning by providing them with a clear orientation to improve their performance on current academic assignments and in future professional situations. So, the analyses show that the proposed rubric is valid, reliable and, suitable to teach and assess oral presentations in a simulated professional scenario for Electrical Engineers.
Challenges and coping strategies of East Asian graduate students in the United States
Authors: Park Hyejoon , Lee Meng-Jung , Choi Ga-Young , Zepernick Janet S
Published: July 2016

This study uses qualitative analysis of semi-structured interviews to explore the adjustment challenges encountered by international graduate students during their study at US universities, and the protective factors most associated with successful adjustment. Nine students from China, Korea, and Taiwan, attending a Midwestern university, participated in the study. Language barriers and discrimination were the primary challenges reported; the factors most associated with successful adjustment were personal perception, social support, strong mentoring relationships, religious belief, and use of campus services. Implications for providing effective assistance for international graduate students are discussed.
Family policy for all South African families
Authors: Rabe Marlize
Published: July 2016

The ‘White Paper of Families in South Africa’ is critically analysed in this article. It is shown that although family diversity is acknowledged in the aforementioned document, certain implications of the document undermine such professed diversity, not all caretakers of children are acknowledged and supported, and financially vulnerable families are not strengthened. Instead, narrow ideals of family life are at times promoted, suggesting middle-class heterosexual values. It is argued here that the realities of family life should be accepted as such and family in different forms should be supported consistently, not subtly pushed to conform to restricted interpretations of what families should be like.
Social Movements and State Repression in India
Authors: Das Raju J
Published: July 2016

State repression is particularly likely when social movements target property relations that cause ordinary citizens to suffer. Whether these movements are violent, and whether the state is a liberal democracy is a contingent matter. This is illustrated by India’s ‘Maoist movement’ (which is also known as the Naxalite movement because it originated in an area called Naxalbari, located in India’s West Bengal State). Where necessary, sections of this movement use violent methods to fight for justice for aboriginal peoples and peasants. This strategy, which the author, incidentally, does not endorse, has been seen by the state as the greatest internal military threat to it. Such a perception invites state violence. What is often under-emphasized or ignored is that the movement is an economic, political and ideological threat, and not just a military threat, and it is so through its localized alternative developmental activities, and this is also a reason for the state’s violent response to it.
Marginalized Identities and Spaces
Authors: Salenius Sirpa
Published: July 2016

James Baldwin’s stories concentrate on racially and sexually marginalized identities placed within cosmopolitan capitals (Paris and New York). In such novels as Another Country, Baldwin explores antonyms, contrasting ideals and ideologies, and the formation of nonconforming relationships. Individual desire and external social pressure create a complex tension that pulls white and black, homo- and heterosexual characters toward and away from each other. Space repeatedly appears as reflective of the inner landscapes of the characters who are intricately linked to the space in which they act. Similar tensions that characterize their inner conflicts appear also in the concept of cosmopolitanism that defines the cities they inhabit. Indeed, a cosmopolitan world citizen, who is at home everywhere but not belonging anywhere, is torn between opposing forces, between inclusion and exclusion. Similarly, Baldwin’s fiction examines inclusion and exclusion, steering, however, away from simplified constructions of centrality and marginality.
Explaining Mainstream Success
Authors: Wiebold Loralie L. , Spiller Marwin
Published: July 2016

The bulk of sociological work examines African American men who are young, unemployed, and poorly educated. In contrast, we offer a nuanced look at Black men living and working in mainstream society—men in the American mainstream although not always identifying as middle class. From 25 in-depth interviews, our data show an apparent contradiction. We find that men account for their success through their individual choices and declared personal motivation to succeed. Yet, throughout their interviews, these men revealed ways they were exposed to critical interactions and opportunities to a larger social network that provided them with tools for mainstream success. In talking about their experiences, these men shared instances in which their racial identity was questioned.
Vibration analysis of bi-stable composite cross-ply laminates using refined shape functions
Authors: Firouzian-Nejad A , Ziaei-Rad S , Moore M
Published: July 2016

In this article, static and dynamic responses of cross-ply bi-stable composite plates were studied. To accurately predict the natural frequencies and snap-through load, a set of higher order shape functions were proposed. In static analysis, the stable configurations, the deflection of corners, and the midpoint of the plate were calculated. For dynamic analysis, Hamilton’s principle is used to provide approximate solutions to the vibration problem under study. The responses of the plate under ramp and harmonic applied forces were determined, the effect of shape functions on the prediction of the first natural frequency of the plate and the required force for snap-through were investigated. A finite element model is also developed to study the static and vibration characteristics of bi-stable composite plate. The qualitative and quantitative comparisons between the finite element method results and those obtained from the present analysis are generally good and satisfactory. The developed analytical model can also be used for parametric study and further design modification.
microRNA-21 Contributes to Orthodontic Tooth Movement
Authors: Chen N. , Sui B.D. , Hu C.H. , Cao J. , Zheng C.X. , Hou R. , Yang Z.K. , Zhao P. , Chen Q. , Yang Q.J. , Jin Y. , Jin F.
Published: July 2016

microRNAs could be mechanosensitive and emerge as critical posttranscriptional regulators in the bone-remodeling process. During orthodontic tooth movement (OTM), the application of mechanical force induces alveolar bone remodeling, but whether microRNAs respond to orthodontic force and contribute to OTM is unknown. microRNA-21 (miR-21) has been previously reported in vitro to mediate stretch-induced osteogenic differentiation of periodontal ligament stem cells and support osteoclast differentiation. In this study, the authors show that miR-21 responded to orthodontic force in periodontal tissue in a dose- and time-dependent manner and regulated the osteogenesis of human periodontal ligament stem cells following OTM. Using mmu-miR-21-deficient (miR-21-/-) mice, the authors discovered that mmu-miR-21 deficiency inhibited OTM and prevented force-induced maxillary bone loss. The authors found that miR-21-/- mice showed a normal skeletal phenotype in development and a similar alveolar bone formation rate to wild-type mice postnatally. During OTM, mmu-miR-21 regulated force-induced alveolar osteoblastogenesis in the tensile side, while no effects were detected in the compressive side. However, miR-21-/- mice showed inhibited alveolar osteoclastogenesis when compared with wild-type mice. During OTM, mmu-miR-21 deficiency blocked alveolar bone resorption in both the compressive and tensile sides. To dissect the mechanism by which miR-21 regulates alveolar bone remodeling, the authors screened the reported functional targets of miR-21 and found that periodontal expression of programmed cell death 4 ( Pdcd4) was inhibited following OTM. Furthermore, mmu-miR-21 deficiency removed the suppression of Pdcd4 at both the mRNA and protein levels in the periodontium, resulting in upregulation of the downstream effector C-fos. Further analysis of OTM under lipopolysaccharide-induced periodontal inflammation showed that mmu-miR-21 mediated lipopolysaccharide (LPS)-accelerated OTM and that mmu-miR-21 deficiency blocked lipopolysaccharide-induced maxillary bone loss. In summary, these findings reveal a previously unrecognized mechanism that a microRNA can modulate OTM and alveolar bone remodeling under both normal and inflammatory microenvironments in vivo.
Pain Mechanisms and Centralized Pain in Temporomandibular Disorders
Authors: Harper D.E. , Schrepf A. , Clauw D.J.
Published: July 2016

Until recently, most clinicians and scientists believed that the experience of pain is perceptually proportional to the amount of incoming peripheral nociceptive drive due to injury or inflammation in the area perceived to be painful. However, many cases of chronic pain have defied this logic, leaving clinicians perplexed as to how patients are experiencing pain with no obvious signs of injury in the periphery. Conversely, there are patients who have a peripheral injury and/or inflammation but little or no pain. What makes some individuals experience intense pain with minimal peripheral nociceptive stimulation and others experience minimal pain with serious injury? It is increasingly well accepted in the scientific community that pain can be generated and maintained or, through other mechanisms, suppressed by changes in the central nervous system, creating a complete mismatch between peripheral nociceptive drive and perceived pain. In fact, there is no known chronic pain condition where the observed extent of peripheral damage reproducibly engenders the same level of pain across individuals. Temporomandibular disorders (TMDs) are no exception. This review focuses on the idea that TMD patients range on a continuum—from those whose pain is generated peripherally to those whose pain is centralized (i.e., generated, exacerbated, and/or maintained by central nervous system mechanisms). This article uses other centralized chronic pain conditions as a guide, and it suggests that the mechanistic variability in TMD pain etiology has prevented us from adequately treating many individuals who are diagnosed with the condition. As the field moves forward, it will be imperative to understand each person’s pain from its own mechanistic standpoint, which will enable clinicians to deliver personalized medicine to TMD patients and eventually provide relief in even the most recalcitrant cases.
The Concept of Magnitude and What It Tells Us About How Struggling Students Learn Fractions
Authors: Woodward John
Published: July 2016

This commentary summarizes emerging research into fractions instruction for students who are at risk for failure. Each of the three articles emphasizes a measure conception of fractions. Teaching fractions as measurement helps students learn the magnitude of rational numbers. However, measurement is only part of the way that students should conceptualize fractions. Instruction also needs to emphasize fractions as division. The article also draws attention to the teaching qualifications of those who typically instruct at-risk students in Tier 2 and 3 settings. More often than not, these individuals lack the pedagogical content knowledge needed to adapt instruction and address student misconceptions. This is a critical issue going forward as the field attempts to balance procedural understanding with key underlying fractional ideas such a measurement and division.
Social Justice and Teacher Education
Authors: Mills Carmen , Ballantyne Julie
Published: July 2016

Teachers play a crucial role in promoting more equitable educational outcomes for marginalized students from low socio-economic backgrounds. Correspondingly, there is a clear warrant for preservice teacher education to work toward the development of teachers who are socially just in their beliefs and practices. This article comprises a systematic review locating empirical research at the intersection of social justice—as it is variously defined within the literature—and teacher education published in peer-reviewed journals within the last 10 years. We explore the focus, design, and findings of the research identified as a basis for recommending future research in the field. By taking stock of the current state of the field and articulating questions that remain under-researched and research approaches under-utilized, we are better placed to move beyond revisiting familiar research terrain.
Ethnic Diversity, Social Trust and the Moderating Role of Subnational Integration Policy
Authors: Gundelach Birte , Manatschal Anita
Published: July 2016

Increasing ethnic diversity and whether or not it impacts on social trust are highly debated topics. Numerous studies report a negative relationship between diversity and trust, particularly in the United States. A growing body of follow-up studies has examined the extent to which these findings can be transferred to Europe, but the results remain inconclusive. Moving beyond the discussion of the mere existence or absence of diversity effects on trust, this study is concerned with the moderation of this relationship. It addresses the neglected role of subnational integration policies influencing the impact of diversity on trust. Empirical tests not only indicate that integration policies moderate the relationship but also suggest that the influence of policies varies substantively according to the specific policy aspect under consideration.
More Choice for Better Choosers: Political Freedom, Autonomy, and Happiness
Authors: Bavetta Sebastiano , Patti Dario Maimone Ansaldo , Miller Peter , Navarra Pietro
Published: July 2016

A substantial literature finds that freedom in the sense of an expanded opportunity set is positively related to happiness. A contrasting literature, however, finds that an excess of choice can have socially undesirable outcomes. We test the effect of two types of freedom—autonomy and political—on happiness using five waves of World Values Survey data (1981–2008). We find evidence supporting the claim that equipping people with the tools to direct the course of their lives (i.e. increasing autonomy freedom) incentivizes the desire to investigate alternatives (e.g. political parties) before making a decision. The effect of freedoms on happiness is diminished in contexts where individuals have less experience with evaluating alternatives, such as in authoritarian or transitional countries.
How Stable Is Political Parties’ Issue Ownership? A Cross-Time, Cross-National Analysis
Authors: Seeberg Henrik Bech
Published: July 2016

Research on issue ownership is accelerating and so is its use in studies of voting and party behaviour. Yet we do not know how stable issue ownership is. Does it describe a solid, persistent association between a party and an issue in the eyes of the electorate, or does it describe a more fluid and fragile issue reputation of a party among the electorate? Theoretical and empirical work suggests both stability and variability in issue ownership. To get closer to an answer, this article presents and analyses unprecedented comprehensive data on issue ownership. The analysis identifies stability rather than change in issue ownership over time and similarity more than difference across countries, and therefore suggests that issue ownership is a general and long-term rather than a local and short-term phenomenon. The implications for how voters perceive parties are important.
Doodling the Nerves: Surfacing Language Anxiety Experiences in an English Language Classroom
Authors: Siagto-Wakat Geraldine
Published: July 2016

This qualitative study explored the use of doodling to surface experiences in the psychological phenomenon of language anxiety in an English classroom. It treated the doodles of 192 freshmen from a premier university in Northern Luzon, Philippines. Further, it made use of phenomenological reduction in analysing the data gathered. Findings reveal that doodling can be an effective tool in surfacing experiences of a psychological phenomena, such as language anxiety, although this may not be generalizable. The gathered doodles show that English language learners go through shimming and shaming experiences, specifically, buffing, baffling, shutting, sweating and shivering, and shattering. The findings of the study can benefit teachers for they can use doodling, a non-verbal tool, in generating the classroom experiences of their students. More so, the anxiety experiences unveiled in this study will help language teachers realize the impact of language anxiety on English language learners.
Effect of projectile nose geometry on the critical velocity and failure of yarn subjected to transverse impact
Authors: Hudspeth Matthew , Chu Jou-mei , Jewell Emily , Lim BoonHim , Ytuarte Ernest , Tsutsui Waterloo , Horner Suzanne , Zheng James , Chen Weinong
Published: July 2016

Three different types of yarn have been subjected to transverse impact experiments in efforts to gain an understanding of local yarn failure and to provide input parameters for future transverse yarn impact simulations. Dupont™ Kevlar® KM2, DSM Dyneema® SK76, and AuTx® from JSC Kamenskvolokno were selected as representative materials, as the former two are commonly implemented into bullet resistant panels and the latter is a promising material for future impact resistant fabrics. In order to assess the effect of projectile nose shape on the critical rupture velocity range for each yarn type, three missile geometries have been implemented, namely a 0.30 caliber rounded head, a 0.30 caliber chisel nosed fragment simulation projectile (FSP), and a high-carbon steel razor blade. As opposed to one single velocity wherein yarn behavior transitions from transverse wave development to immediate local failure, a range is defined wherein progressive filament failure is detected with increasing impact velocities. Such ranges are determined for all yarn types using the three projectile geometries yielding critical velocity transition regions of increasing value when impacting via razor blade, FSP, and round projectile heads, accordingly. In addition, post-mortem fracture surfaces recovered from impact experiments have been imaged so as to elucidate the mechanism of failure throughout the range of velocities tested for each projectile type and yarn material and said fracture surfaces correlate well with impact velocity and projectile nose geometry.
Neighbourhood artistic disaffiliation in Hamilton, Ontario, Canada
Authors: Bain Alison L
Published: July 2016

This article argues that the creative drive of cultural workers to envision alternative urban futures and to make real changes in neighbourhoods in the urban present, while politically powerful and imaginatively seductive to urban decision-makers, contains destructive impulses. Such a drive can challenge, but also reinforce, the established social order and unequal power relations. This article critically examines the spatial politics of creative destruction that can unfold in the place-making wake of cultural workers. A case study is used from the mid-sized, industrial city of Hamilton of a deprived inner-city neighbourhood that is informally being reimagined as an arts district. In this neighbourhood, some cultural workers selectively practice middle-class disaffiliation. Individual acts of avoidance, control and destruction function as withdrawal strategies to help minimise the negative externalities of crime and social disorder and to realise a vision of this neighbourhood in their own image.
Comparative Process Tracing
Authors: Bengtsson Bo , Ruonavaara Hannu
Published: July 2016

This article introduces comparative process tracing (CPT) as a two-step methodological approach that combines theory, chronology, and comparison. For each studied case, the processes leading “from A to B” are reconstructed and analyzed in terms of ideal-type social mechanisms and then compared by making use of the identified mechanisms and ideal-type periodization. Central elements of CPT are path dependence, critical junctures and focal points, social mechanisms, context, periodization, and counterfactual analysis. The CPT approach is described, discussed, and compared with more formal and deterministic forms of process tracing, which are found to be less fruitful for systematic comparison.
Religion and Development: Understanding their Relationship with Reference to Hinduism: A Study Marking the Centenary of Weber’s Religions of India
Authors: Srivastava Vinay Kumar
Published: July 2016

An interesting debate in social science pertains to the relationship between religion and economy, particularly the areas of economic development. Both these aspects are so different that they are often approached with a streak of scepticism. Religion is expected to drive one away from this world, engaging one with supra-empirical and spiritual concerns, and it is to its amelioration that the process of development devotes itself. This relationship of religion and development being polar opposites was challenged in Max Weber’s comparative religious studies. Since then, it has generated an animated debate whether the cultural and symbolic ingredients present in Protestant ethics were found in other religious traditions. This article submits that religion, ‘in and by itself’, is neutral. So malleable it is to interpretations by people and their institutions at different points of time that it can be defined as promoting economic enterprise at one time, and at another, its pursuit may be situated as antithetical to economy.
Triple Exclusion of Dalits in Land Ownership in Kerala
Authors: Yadu C.R. , Vijayasuryan C.K.
Published: July 2016

As a community, dalits are found to be at the lowest level of land ownership in Kerala. This article argues that this abysmal status of land ownership is the result of three exclusionary processes. Dalits were historically excluded from land ownership due to the caste system. Second, they were consistently excluded from the process of land reforms in a significant way. Lastly, the current trends in land market activities tend to exclude them from land ownership. This article shows how social inequality in land ownership in Kerala, known to be a progressive state, remains high. Dalits lag far behind in land ownership as compared to the upper castes reinforcing the fact that the land–caste nexus still dominates in Kerala.