bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring Longevity Risk: An Application to the Royal Canadian Mounted Police Pension Plan
Authors: Boyer M. Martin , Mejza Joanna , Stentoft Lars 
Published: March 2014

AbstractAn employer that sets up a defined benefit pension plan promises to periodically pay a certain sum to each participant starting at some future date and continuing until death. Although both the future beneficiary and the employer can be asked to finance the plan throughout the beneficiary's career, any shortcoming of funds in the future is often the employer's responsibility. It is therefore essential for the employer to be able to predict with a high degree of confidence the total amount that will be required to cover its future pension obligations. Applying mortality forecasting models to the case of the Royal Canadian Mounted Police pension plan, we illustrate the importance of mortality forecasting to value a pension fund's actuarial liabilities. As future survival rates are uncertain, pensioners may live longer than expected. We find that such longevity risk represents approximately 2.8 percent of the total liability ascribable to retired pensioners (as measured by the relative value at risk at the 95th percentile) and 2.5 percent of the total liabilities ascribable to current regular contributors. Longevity risk compounds the model risk associated with not knowing what is the true mortality model, and we estimate that model risk represents approximately 3.2 percent of total liabilities. The compounded longevity risk therefore represents almost 6 percent of the pension plan's total liabilities.
Designing an Enterprise Risk Management Curriculum for Business Studies: Insights From a Pilot Program
Authors: Acharyya Madhu , Brady Chris 
Published: March 2014

AbstractThe latest financial crises have highlighted the centrality of managing risks across organizations. Internationally, Basel II/III, The Volcker Rule of the Dodd–Frank Act, and Vickers’ Ring‐Fence all propose stronger management of risk across banks and greater oversight of executive compensation to mitigate generic risk. Given this situation, it might be assumed that academia would also view risk as a central concern for its business programs. It seems not. There is a little evidence that academic curricula are being specifically designed to address this issue. This article examines an Enterprise Risk Management curriculum delivered to graduate student cohorts over 3 consecutive years. Four criteria were used to develop the new curriculum. First, it should take a holistic view of risk; second, the theories related to risk needed to be transformed from individual to group level; third, the dynamics of risk due to market factors needed to be understood; and finally, the way firms respond to crises needed to be observed and embedded in the curriculum.
HLA‐G +3142 polymorphism as a susceptibility marker in two rheumatoid arthritis populations in Brazil
Authors: Veit T. D. , de Lima C. P. S. , Cavalheiro L. C. , Callegari‐Jacques S. M. , Brenol C. V. , Brenol J. C. T. , Xavier R. M. , da Cunha Sauma M. F. L. , dos Santos E. J. M. , Chies J. A. B. 
Published: March 2014

AbstractIn this study, we sought to investigate the genetic influence of two HLA‐G 3′‐untranslated region (3′‐UTR) polymorphisms – 14 bp (rs66554220) and +3142C>G (rs1063320) and their compounding haplotypes in susceptibility to rheumatoid arthritis (RA) in a two‐region Brazilian study comprising of 539 patients and 489 controls. All subjects were polymerase chain reaction (PCR) genotyped for the referred polymorphisms and logistic regression models controlling for sex, city and age were performed. Homozygozity for the +3142G allele was associated with an increased risk of RA [odds ratio (OR) = 1.45, 95% confidence interval (CI) = 1.075–1.959, PBonf = 0.030], whereas no association was observed for the 14 bp polymorphism. Haplotype comparisons between patients and controls showed a decreased frequency of the delC haplotype in patients (OR = 0.70, 95% CI = 0.521–0.946, PBonf = 0.040), which remained significant in the rheumatoid factor (RF)‐positive group (OR = 0.66, 95% CI = 0.482–0.900, PBonf = 0.018), but not in the RF‐negative group. These results corroborate the hypothesis of an involvement of HLA‐G in the susceptibility of RA. The +3142G allele is associated with haplotype lineages that share high identity and are regarded as low producers. The presence of the G allele in homozygosis could be responsible for a low HLA‐G expression profile that could favor the triggering of RA.
RhHB1 mediates the antagonism of gibberellins to ABA and ethylene during rose (Rosa hybrida) petal senescence
Authors: Lü Peitao , Zhang Changqing , Liu Jitao , Liu Xiaowei , Jiang Guimei , Jiang Xinqiang , Khan Muhammad Ali , Wang Liangsheng , Hong Bo , Gao Junping 
Published: March 2014

SummaryRose (Rosa hybrida) is one of the most important ornamental plants worldwide; however, senescence of its petals terminates the ornamental value of the flower, resulting in major economic loss. It is known that the hormones abscisic acid (ABA) and ethylene promote petal senescence, while gibberellins (GAs) delay the process. However, the molecular mechanisms underlying the antagonistic effects amongst plant hormones during petal senescence are still unclear. Here we isolated RhHB1, a homeodomain‐leucine zipper I transcription factor gene, from rose flowers. Quantitative RT‐PCR and GUS reporter analyses showed that RhHB1 was strongly expressed in senescing petals, and its expression was induced by ABA or ethylene in petals. ABA or ethylene treatment clearly accelerated rose petal senescence, while application of the gibberellin GA3 delayed the process. However, silencing of RhHB1 delayed the ABA‐ or ethylene‐mediated senescence, and resulted in higher petal anthocyanin levels and lower expression of RhSAG12. Moreover, treatment with paclobutrazol, an inhibitor of GA biosynthesis, repressed these delays. In addition, silencing of RhHB1 blocked the ABA‐ or ethylene‐induced reduction in expression of the GA20 oxidase encoded by RhGA20ox1, a gene in the GA biosynthetic pathway. Furthermore, RhHB1 directly binds to the RhGA20ox1 promoter, and silencing of RhGA20ox1 promoted petal senescence. Eight senescence‐related genes showed substantial differences in expression in petals after treatment with GA3 or paclobutrazol. These results suggest that RhHB1 mediates the antagonistic effect of GAs on ABA and ethylene during rose petal senescence, and that the promotion of petal senescence by ABA or ethylene operates through an RhHB1–RhGA20ox1 regulatory checkpoint.
Analysis and Optimization of an Electrohydraulic Power Pack for Use in a Fully-Active Vehicle Suspension Through the Use of Computational Fluid Dynamics
Authors: O’Shea Colin , Xia Yanjun , Lowry Sam 
Published: February 2014

Shock absorbers are essential to vehicle comfort and handling. Most shock absorbers use passive or “semi-active” valves to produce reactive force with limited ride benefits while dissipating hydraulic power as heat. Fully-active suspensions can fundamentally eliminate the discomfort of bumps and provide superior handling and safety. Existing active suspensions consume large amounts of power and are expensive and unwieldy. If these challenges are addressed, fully-active suspensions could revolutionize the ride control industry.
A compact and full-active suspension system, GenShock, is being developed by Levant Power. The patented system relies upon an electrohydraulic power pack coupled with a gerotor motor/pump. Energy consumption is minimized by regenerative harvesting from suspension dynamics. The system is based around a proprietary electrohydraulic motor/pump mechanism that can both semi-actively damp body and wheel motion while recovering energy, and actuate to drive the wheel and chassis.
This article describes the use of computational fluid dynamics (CFD) in the development and optimization of hydraulic components in GenShock. The CFD software PumpLinx enabled the complex non-linear GenShock system to be simulated within 5% of experimental tests, and enabled a threefold increase in system efficiency. Parametric simulations predict the torque, power, leakage behavior, and hydrodynamics of the system including effects of aeration and cavitation. Detailed analysis and correlations between experimental data and simulations are presented.
Planting by the Moon: Medieval Science and New Age Religion
Authors: Krug Rebecca 
Published: February 2014

The purpose of this essay is to distinguish between late medieval and New Age responses to astrology in the realm of gardening. Medieval garden writers took a practical approach to gardening and understood astrological gardening as fundamentally true but less relevant than empirically observable aspects of seed germination and plant growth. In contrast, New Age writers invest gardening with philosophical and spiritual significance, drawing on an understanding of astrology as ancient wisdom that can bring greater self-understanding. New Age gardening is a practice engaged with the symbolic value of interaction with nature for the individual as a member of a community.
Movement Demands of Elite Rugby League Players during Australian National Rugby League and European Super League Matches
Authors: Twist Craig , Highton Jamie , Waldron Mark , Edwards Emma , Austin Damien , Gabbett Tim J. 
Published: February 2014

Purpose:This study compared the movement demands of players competing in matches from the elite Australian and European rugby league competitions.Methods:Global positioning system devices were used to measure 192 performances of forwards, adjustables, and outside backs during National Rugby League (NRL; n = 88) and European Super League (SL; n = 104) matches. Total and relative distances covered overall and at low (0–3.5 m/s), moderate (3.6–5 m/s), and high (>5 m/s) speeds were measured alongside changes in movement variables across the early, middle, and late phases of the season.Results:The relative distance covered in SL matches (95.8 ± 18.6 m/min) was significantly greater (P < .05) than in NRL matches (90.2 ± 8.3 m/min). Relative low-speed activity (70.3 ± 4.9 m/min vs 75.5 ± 18.9 m/min) and moderate-speed running (12.5 ± 3.3 m m/min vs 14.2 ± 3.8 m/min) were highest (P < .05) in the SL matches, and relative high-speed distance was greater (P < .05) during NRL matches (7.8 ± 2.1 m/min vs 6.1 ± 1.7 m/min).Conclusions:NRL players have better maintenance of high-speed running between the first and second halves of matches and perform less low- and moderate-speed activity, indicating that the NRL provides a higher standard of rugby league competition than the SL.
Evidence of Clonal Expansion in the Genome of a Multidrug-Resistant Mycobacterium tuberculosis Clinical Isolate from Peru
Authors: Galarza M. , Tarazona D. , Borda V. , Agapito J. C. , Guio H. 
Published: February 2014

ABSTRACT

We report the genome sequence of
Mycobacterium tuberculosis
INS-MDR from Peru, a multidrug-resistant tuberculosis (MDR-TB) and Latin American-Mediterranean (LAM) lineage strain. Our analysis showed mutations related to drug resistance in the
rpoB
(D516V),
katG
(S315T),
kasA
(G269S), and
pncA
(Q10R) genes. Our evidence suggests that INS-MDR may be a clonal expansion related to the African strain KZN 1435.
PARK2 and proinflammatory/anti-inflammatory cytokine gene interactions contribute to the susceptibility to leprosy: a case–control study of North Indian population
Authors: Chopra Rupali , Kalaiarasan Ponnusamy , Ali Shafat , Srivastava Amit K , Aggarwal Shweta , Garg Vijay K , Bhattacharya Sambit N , Bamezai Rameshwar N K 
Published: February 2014

ObjectivesCytokines and related molecules in immune-response pathways seem important in deciding the outcome of the host–pathogen interactions towards different polar forms in leprosy. We studied the role of significant and functionally important single-nucleotide polymorphisms (SNPs) in these genes, published independently from our research group, through combined interaction with an additional analysis of the in silico network outcome, to understand how these impact the susceptibility towards the disease, leprosy.DesignThe study was designed to assess an overall combined contribution of significantly associated individual SNPs to reflect on epistatic interactions and their outcome in the form of the disease, leprosy. Furthermore, in silico approach was adopted to carry out protein–protein interaction study between PARK2 and proinflammatory/anti-inflammatory cytokines.SettingPopulation-based case–control study involved the data of North India. Protein–protein interaction networks were constructed using cytoscape.ParticipantsStudy included the data available from 2305 Northern Indians samples (829 patients with leprosy; 1476 healthy controls), generated by our research group.Primary and secondary outcome measuresFor genotype interaction analysis, all possible genotype combinations between selected SNPs were used as an independent variable, using binary logistic regression with the forward likelihood ratio method, keeping the gender as a covariate.ResultsInteraction analysis between PARK2 and significant SNPs of anti-inflammatory/proinflammatory cytokine genes, including BAT1 to BTNL2-DR spanning the HLA (6p21.3) region in a case–control comparison, showed that the combined analysis of: (1) PARK2, tumour necrosis factor (TNF), BTNL2-DR, interleukin (IL)-10, IL-6 and TGFBR2 increased the risk towards leprosy (OR=2.54); (2) PARK2, BAT1, NFKBIL1, LTA, TNF-LTB, IL12B and IL10RB provided increased protection (OR=0.26) in comparison with their individual contribution.ConclusionsEpistatic SNP–SNP interactions involving PARK2 and cytokine genes provide an additive risk towards leprosy susceptibility. Furthermore, in silico protein–protein interaction of PARK2 and important proinflammatory/anti-inflammatory molecules indicate that PARK2 is central to immune regulation, regulating the production of different cytokines on infection.
Endovascular treatment of tandem vascular occlusions in acute ischemic stroke
Authors: Puri Ajit S , Kühn Anna L , Kwon Hyon-Jo , Khan Muhib , Hou Samuel Y , Lin Eugene , Chueh Juyu , van der Bom Imramsjah MJ , Dabus Guilherme , Linfante Italo , Gounis Matthew J , Wakhloo Ajay K 
Published: February 2014

Background and purposeTandem vascular occlusions are an important cause of acute ischemic stroke (AIS) and present unique treatment challenges. We report our experience of managing a subset of AIS patients with extracranial vascular stenting/angioplasty and intracranial revascularization.MethodsConsecutive patients who presented at three centers with AIS from tandem vascular occlusions confirmed by brain and neck CT imaging were included in the study. We retrospectively analyzed the patient demographics, National Institute of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score at the time of admission, treatment strategy, angiographic results using the Thrombolysis In Cerebral Infarction (TICI) score, and clinical and imaging follow-up.ResultsTwenty-eight patients were included. The mean NIHSS score at admission was 18. Extracranial carotid occlusions with a concomitant middle cerebral artery occlusion were seen in 89.3% of patients (n=25) and vertebral artery combined with basilar artery lesions in 10.7% (n=3). An antegrade approach (ie, treatment of the extracranial lesion first) was used in 24 patients (85.7%). Proximal occlusion recanalization was achieved usually with a stent (n=27; 96.4%). Pursuant to intracranial revascularization techniques, ≥TICI 2A recanalization was seen in 96.4% of patients. An mRS score of ≤2 at 90 days was achieved in 56.5% of patients.ConclusionsOur study shows preliminary data from three centers on recanalization of tandem occlusions in patients presenting with AIS. There was a preference to revascularize the proximal occlusion using a stent followed by distal recanalization with mechanical thrombectomy, intra-arterial thrombolysis or a combination of these. This approach has low periprocedural complications and can achieve an excellent angiographic and clinical outcome.
On Some Numbers Related to Extremal Combinatorial Sum Problems
Authors: Petrassi D. 
Published: March 2014

Let n, d, and r be three integers such that 1≤r, d≤n. Chiaselotti (2002) defined γn,d,r as the minimum number of the nonnegative partial sums with d summands of a sum ∑1=1nai≥0, where a1,…,an are n real numbers arbitrarily chosen in such a way that r of them are nonnegative and the remaining n-r are negative. Chiaselotti (2002) and Chiaselotti et al. (2008) determine the values of γn,d,r for particular infinite ranges of the integer parameters n, d, and r. In this paper we continue their approach on this problem and we prove the following results: (i) γ(n,d,r)≤(rd)+(rd-1) for all values of n, d, and r such that (d-1)/dn-1≤r≤(d-1)/dn; (ii) γd+2,d,d=d+1.
LIMD2 Is a Small LIM-Only Protein Overexpressed in Metastatic Lesions That Regulates Cell Motility and Tumor Progression by Directly Binding to and Activating the Integrin-Linked Kinase
Authors: Peng Hongzhuang , Talebzadeh-Farrooji Mehdi , Osborne Michael J. , Prokop Jeremy W. , McDonald Paul C. , Karar Jayashree , Hou Zhaoyuan , He Mei , Kebebew Electron , Orntoft Torben , Herlyn Meenhard , Caton Andrew J. , Fredericks William , Malkowicz Bruce , Paterno Christopher S. , Carolin Alexandra S. , Speicher David W. , Skordalakes Emmanuel , Huang Qihong , Dedhar Shoukat , Borden Katherine L.B. , Rauscher Frank J. 
Published: March 2014

Abstract
Proteins that communicate signals from the cytoskeleton to the nucleus are prime targets for effectors of metastasis as they often transduce signals regulating adhesion, motility, and invasiveness. LIM domain proteins shuttle between the cytoplasm and the nucleus, and bind to partners in both compartments, often coupling changes in gene expression to extracellular cues. In this work, we characterize LIMD2, a mechanistically undefined LIM-only protein originally found to be overexpressed in metastatic lesions but absent in the matched primary tumor. LIMD2 levels in fresh and archival tumors positively correlate with cell motility, metastatic potential, and grade, including bladder, melanoma, breast, and thyroid tumors. LIMD2 directly contributes to these cellular phenotypes as shown by overexpression, knockdown, and reconstitution experiments in cell culture models. The solution structure of LIMD2 that was determined using nuclear magnetic resonance revealed a classic LIM-domain structure that was highly related to LIM1 of PINCH1, a core component of the integrin-linked kinase–parvin–pinch complex. Structural and biochemical analyses revealed that LIMD2 bound directly to the kinase domain of integrin-linked kinase (ILK) near the active site and strongly activated ILK kinase activity. Cells that were null for ILK failed to respond to the induction of invasion by LIMD2. This strongly suggests that LIMD2 potentiates its biologic effects through direct interactions with ILK, a signal transduction pathway firmly linked to cell motility and invasion. In summary, LIMD2 is a new component of the signal transduction cascade that links integrin-mediated signaling to cell motility/metastatic behavior and may be a promising target for controlling tumor spread. Cancer Res; 74(5); 1390–403. ©2014 AACR.
A Specific STAT3-Binding Peptide Exerts Antiproliferative Effects and Antitumor Activity by Inhibiting STAT3 Phosphorylation and Signaling
Authors: Kim Daejin , Lee In-Hyun , Kim Sunghyun , Choi Minsuk , Kim Hyungjun , Ahn Sukyung , Saw Phei Er , Jeon Hyungsu , Lee Yumi , Jon Sangyong 
Published: February 2014

Abstract
STAT3 promotes the survival, proliferation, metastasis, immune escape, and drug resistance of cancer cells, making its targeting an appealing prospect. However, although multiple inhibitors of STAT3 and its regulatory or effector pathway elements have been developed, bioactive agents have been somewhat elusive. In this report, we report the identification of a specific STAT3-binding peptide (APTSTAT3) through phage display of a novel “aptide” library. APTSTAT3 bound STAT3 with high specificity and affinity (∼231 nmol/L). Addition of a cell-penetrating motif to the peptide to yield APTSTAT3-9R enabled uptake by murine B16F1 melanoma cells. Treatment of various types of cancer cells with APTSTAT3-9R blocked STAT3 phosphorylation and reduced expression of STAT targets, including cyclin D1, Bcl-xL, and survivin. As a result, APTSTAT3-9R suppressed the viability and proliferation of cancer cells. Furthermore, intratumoral injection of APTSTAT3-9R exerted potent antitumor activity in both xenograft and allograft tumor models. Our results offer a preclinical proof-of-concept for APTSTAT3 as a tractable agent for translation to target the broad array of cancers harboring constitutively activated STAT3. Cancer Res; 74(8); 2144–51. ©2014 AACR.
IL-10: Master Switch from Tumor-Promoting Inflammation to Antitumor Immunity
Authors: Oft Martin 
Published: March 2014

AbstractHuman cancer is characterized by deficits in antigen-specific immunity and intratumoral CD8+ T cells. On the other hand, inflammatory macrophages and mediators of chronic inflammation are highly prevalent in patients with late-stage cancer. Intratumoral T-cell deficiency and chronic inflammation have been linked independently to a poor prognosis in patients with cancer, and therapeutic approaches to overcome either pathology separately are in clinical testing. The anti-inflammatory cytokine interleukin (IL)-10 suppresses macrophage and proinflammatory Th17 T-cell responses by inhibiting the inflammatory cytokines IL-6 and IL-12/23. Corroborating the anti-inflammatory action of IL-10, deficiency in IL-10 leads to a stimulation of inflammatory responses and inflammatory bowel disease. The anti-inflammatory role of IL-10 fostered the assumption that IL-10 undermines the immune response to cancer. However, mice and humans deficient in IL-10 signaling develop tumors spontaneously and at high rates. Overexpression of IL-10 in models of human cancer or treatment with a pegylated IL-10 (PEG-IL-10) led to tumor rejection and long-lasting tumor immunity. IL-10 stimulates cytotoxicity of CD8+ T cells and the expression of IFN-γ in CD8+ T cells. IL-10–induced tumor rejections are dependent on the expression of IFN-γ and granzymes in tumor-resident CD8+ T cells and the upregulation of MHC molecules. These findings reconcile earlier clinical data, which showed that recombinant IL-10 increased IFN-γ and granzymes in the blood of treated individuals. PEG-IL-10 is therefore a unique therapeutic agent, which simultaneously stimulates antitumor immunity and inhibits tumor-associated inflammation. Cancer Immunol Res; 2(3); 194–9. ©2014 AACR.