bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hookworm Excretory/Secretory Products Induce Interleukin-4 (IL-4)+IL-10+CD4+T Cell Responses and Suppress Pathology in a Mouse Model of Colitis
Authors: Ferreira Ivana , Smyth Danielle , Gaze Soraya , Aziz Ammar , Giacomin Paul , Ruyssers Nathalie , Artis David , Laha Thewarach , Navarro Severine , Loukas Alex , McSorley Henry J. 
Published: April 2013

ABSTRACTEvidence from human studies and mouse models shows that infection with parasitic helminths has a suppressive effect on the pathogenesis of some inflammatory diseases. Recently, we and others have shown that some of the suppressive effects of hookworms reside in their excretory/secretory (ES) products. Here, we demonstrate that ES products of the hookwormAncylostoma caninum(AcES) suppress intestinal pathology in a model of chemically induced colitis. This suppression was associated with potent induction of a type 2 cytokine response characterized by coexpression of interleukin-4 (IL-4) and IL-10 by CD4+T cells, downregulation of proinflammatory cytokine expression in the draining lymph nodes and the colon, and recruitment of alternatively activated (M2) macrophages and eosinophils to the site of ES administration. Protease digestion and heat denaturation of AcES resulted in impaired induction of CD4+IL-4+IL-10+cell responses and diminished ability to suppress colitis, indicating that protein component(s) are responsible for some of the immunosuppressive effects of AcES. Identification of the specific parasite-derived molecules responsible for reducing pathology during chemically induced colitis could lead to the development of novel therapeutics for the treatment of human inflammatory bowel disease.
Identification of a Peptide-Based Neutralizer That Potently Inhibits Both Shiga Toxins 1 and 2 by Targeting Specific Receptor-Binding Regions
Authors: Tsutsuki Kazue , Watanabe-Takahashi Miho , Takenaka Yasuaki , Kita Eiji , Nishikawa Kiyotaka 
Published: April 2013

ABSTRACT

Shiga toxin (Stx) is a major virulence factor of enterohemorrhagic
Escherichia coli
that occasionally causes fatal systemic complications. We recently developed a tetravalent peptide (PPP-tet) that neutralizes the cytotoxicity of Stx2 using a multivalent peptide library approach. In this study, we used this technique to identify a series of tetravalent peptides that bound to Stx1, another major Stx family member, with high affinity by targeting one receptor-binding site of the B subunit. One peptide, MMA-tet, markedly inhibited Stx1 and Stx2 cytotoxicity with greater potency than PPP-tet. After forming a complex with Stx1 through its specific receptor-binding region, MMA-tet did not affect vesicular transport of the toxin to the endoplasmic reticulum but substantially rescued inhibition of the protein synthesis induced by Stx1. Oral application of MMA-tet protected mice from a fatal dose of an
E. coli
O157:H7 strain producing both toxins. MMA-tet may be a promising therapeutic agent against the infection.
Heterozygosity at the A625C Polymorphic Site of the MyD88 Gene Is Associated with Mycobacterium bovis Infection in Cattle
Authors: Capparelli Rosanna , De Chiara Francesco , Nocerino Nunzia , Medaglia Chiara , Di Costanzo Rosa , Ramunno Luigi , Capuano Federico , Casalinuovo Francesco , Di Matteo Antonio , Iannelli Domenico 
Published: April 2013

ABSTRACT

The study demonstrates that in cattle, animals heterozygous at the MyD88 A625C polymorphic marker have a 5-fold reduced risk for active pulmonary tuberculosis (odds ratio [OR] = 0.19;
P
= 6 × 10
−12
). The reduced risk, however, does not extend to animals with latent pulmonary tuberculosis (OR = 0.83;
P
= 0.40). Heterozygosity at the A625C single nucleotide polymorphism is associated with intermediate levels of tumor necrosis factor alpha, gamma interferon, and nitric oxide synthase (NOS). Accordingly, deficiency as well as overexpression of proinflammatory cytokines or NOS favor tuberculosis, while heterozygosity provides the animals with the optimal level of inflammation.
Towards testing a two-Higgs-doublet model with maximal CP symmetry at the LHC: Monte Carlo event generator implementation
Authors: Brehmer J. , Lendermann V. , Maniatis M. , Nachtmann O. , Schultz-Coulon H.-C. , Stamen R. 
Published: April 2013

AbstractA Monte Carlo event generator is implemented for a two-Higgs-doublet model with maximal CP symmetry, the MCPM. The model contains five physical Higgs bosons; the ρ′, behaving similarly to the standard-model Higgs boson, two extra neutral bosons h′ and h″, and a charged pair H±. The special feature of the MCPM is that, concerning the Yukawa couplings, the bosons h′, h″ and H± couple directly only to the second-generation fermions but with strengths given by the third-generation-fermion masses. Our event generator allows the simulation of the Drell–Yan-type production processes of h′, h″ and H± in proton–proton collisions at LHC energies. Also the subsequent leptonic decays of these bosons into the μ+μ−, μ+νμ and $\mu^{-} \bar{\nu}_{\mu}$ channels are studied as well as the dominant background processes. We estimate the integrated luminosities needed in pp collisions at center-of-mass energies of 8 and 14 TeV for significant observations of the Higgs bosons h′, h″ and H± in these muonic channels.
EFFECTS OF SIMVASTATIN ON FEMORAL BIOMECHANICS IN OVARIECTOMIZED RATS
Authors: JIAN XIAOCHONG , CHEN JIANG , ZHANG LINLIN , YAN FUHUA , ZENG YANJUN 
Published: April 2013

Objective: To investigate the effect of simvastatin on the biomechanical characteristics of the femur in ovariectomized rats. Material and methods: Fifty-four female Sprague-Dawley rats, aged three months old, were randomly divided into three groups: sham-operated group ( SHAM; n = 18), ovariectomized group (OVX; n = 18), and ovariectomized with simvastatin treatment group (OVX+SIM; n = 18). Eight weeks after being ovariectomized, simvastatin was administered orally at 5 mg/kg each day in the OVX + SIM group. The animals were sacrificed at either four or 12 weeks after administration and femurs were obtained. Biomechanical parameters were measured by the three-point bending test. Results: There were no significant differences in the maximal strain and flexibility strain between the OVX and OVX + SIM groups at either four or 12 weeks after administration (p > 0.05). In contrast, significant differences in flexibility loading at four weeks and in maximal loading, flexibility loading, and the coefficient of bending ductility between the OVX and OVX + SIM groups at either four or 12 weeks (p < 0.05 and p < 0.01, respectively). Intergroup comparisons showed that maximal loading and flexibility loading have significant differences in the OVX + SIM group (p < 0.01). Conclusion: Simvastatin shows potential in promoting bone remodeling, changing bone micro-architecture, and influencing the integration and distribution ratio of organic and inorganic constituents in bone tissue of ovariectomized rats. In addition, a longer time of administration with simvastatin could enhance the femoral strength.
Squamous Dysplasia—The Precursor Lesion for Esophageal Squamous Cell Carcinoma
Authors: Taylor Philip R. , Abnet Christian C. , Dawsey Sanford M. 
Published: April 2013

Abstract
Esophageal squamous cell carcinoma (ESCC) accounts for 80% of all esophageal cancers worldwide, and esophageal squamous dysplasia (ESD) is the only histopathology that predicts the development of ESCC. The prevalence of ESD parallels rates of invasive ESCC and is typically found in 25% or more of adults above the age of 35 years in populations in north central China, where risk for ESCC is among the highest in the world. Results of chemoprevention and early detection studies to prevent progression of ESD suggest that these approaches, coupled with emerging endoscopic therapies, offer promise for the prevention of esophageal cancer mortality in high-risk populations. Future research on ESD and ESCC should focus on finding additional modifiable risk factors and on identifying biomarkers to incorporate into early detection strategies. Cancer Epidemiol Biomarkers Prev; 22(4); 540–52. ©2013 AACR.
Precursors to Lymphoproliferative Malignancies
Authors: Goldin Lynn R. , McMaster Mary L. , Caporaso Neil E. 
Published: April 2013

AbstractWe review monoclonal B-cell lymphocytosis (MBL) as a precursor to chronic lymphocytic leukemia and monoclonal gammopathy of undetermined significance (MGUS) as a precursor to plasma cell disorders. These conditions are present in the general population and increase with age. These precursors aggregate with lymphoproliferative malignancies in families suggesting shared inheritance. MBL and MGUS may share some of the same risk factors as their related malignancies but data are limited. Although these conditions are characterized by enhanced risk for the associated malignancy, the majority of individuals with these conditions do not progress to malignancy. A key focus for current work is to identify markers that predict progression to malignancy. Cancer Epidemiol Biomarkers Prev; 22(4); 533–9. ©2013 AACR.
Human Papillomavirus Infection and the Multistage Carcinogenesis of Cervical Cancer
Authors: Schiffman Mark , Wentzensen Nicolas 
Published: April 2013

Abstract
This short review outlines our understanding of cervical cancer precursors, concentrating on the central etiologic role of persistent human papillomavirus infection. The stages of cervical carcinogenesis are better understood than for most other major cancers, providing a successful cancer etiology and prevention model. Cancer Epidemiol Biomarkers Prev; 22(4); 553–60. ©2013 AACR.
GSK-3α Promotes Oncogenic KRAS Function in Pancreatic Cancer via TAK1–TAB Stabilization and Regulation of Noncanonical NF-κB
Authors: Bang Deepali , Wilson Willie , Ryan Meagan , Yeh Jen Jen , Baldwin Albert S. 
Published: April 2013

AbstractMutations in KRAS drive the oncogenic phenotype in a variety of tumors of epithelial origin. The NF-κB transcription factor pathway is important for oncogenic RAS to transform cells and to drive tumorigenesis in animal models. Recently, TGF-β–activated kinase 1 (TAK1), an upstream regulator of IκB kinase (IKK), which controls canonical NF-κB signaling, was shown to be important for chemoresistance in pancreatic cancer and for regulating KRAS-mutant colorectal cancer cell growth and survival. Here, we show that mutant KRAS upregulates glycogen synthase kinase 3α (GSK-3α), leading to its interaction with TAK1 to stabilize the TAK1–TAB complex to promote IKK activity. In addition, GSK-3α is required for promoting critical noncanonical NF-κB signaling in pancreatic cancer cells. Pharmacologic inhibition of GSK-3 suppresses growth of human pancreatic tumor explants, consistent with the loss of expression of oncogenic genes such as c-myc and TERT. These data identify GSK-3α as a key downstream effector of oncogenic KRAS via its ability to coordinately regulate distinct NF-κB signaling pathways.Significance: GSK-3α functions to promote IKK/NF-κB activity downstream of oncogenic KRAS via stabilization and activation of the TAK1/TAB complex and to promote noncanonical NF-κB activity via control of nuclear levels of NF-κB2. Inhibition of GSK-3 strongly suppresses growth of human pancreatic tumor explants with downregulation of certain oncogenic NF-κB target genes such as c-myc and TERT. Cancer Discov; 3(6); 690–703. ©2013 AACR.This article is highlighted in the In This Issue feature, p. 591
Prevalence and Predictors of Ischemia and Outcomes in Outpatients With Diabetes Mellitus Referred for Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging
Authors: Bourque Jamieson M. , Patel Chetan A. , Ali Mohamed M. , Perez Margarita , Watson Denny D. , Beller George A. 
Published: April 2013

Background—
The prevalence of ischemia and its prediction of events are unclear in outpatients with diabetes mellitus in the modern era of intensive medical management. We sought to identify the prevalence of ischemia, subsequent cardiac events, and impact of sex, stress type, and symptom status on these findings in a cohort of stable outpatients with diabetes mellitus referred for single-photon emission computed tomography myocardial perfusion imaging (MPI).

Methods and Results—

The study cohort included 575 consecutive outpatients with diabetes mellitus who underwent quantitative, gated single-photon emission computed tomography MPI. Clinical information, stress MPI variables, and cardiac events were prospectively collected and analyzed. The study population was at intermediate risk of coronary artery disease or had known coronary artery disease (40.3%); 29% of patients were asymptomatic at the time of stress testing. Scintigraphic ischemia and significant (≥10%) left ventricular ischemia were present in 126 patients (21.9%) and 29 patients (5.0%), respectively, and <1% of patients had early revascularization. The risk of ischemia was increased >2-fold by male sex (
P
<0.001), but was not impacted by pharmacological stress (
P
=0.15) or presence of symptoms (
P
=0.89). During a median 4.4 years follow-up, the rate of cardiac death/nonfatal myocardial infarction was moderate at 2.6%/y (cardiac death 0.8%/y) in the total cohort, but was 5.7%/y in those with ischemia (
P
<0.001). Pharmacological stress predicted a higher cardiac event rate (
P
<0.001) but symptoms did not (
P
=0.55).

Conclusions—
This cohort of stable outpatients with diabetes mellitus referred for single-photon emission computed tomography had low rates of significant ischemia and early revascularization; an initially low cardiac event rate increased after 2 years. Independent predictors of cardiac death/nonfatal myocardial infarction were known coronary artery disease, pharmacological stress, and MPI ischemia. Nearly one third of those with events had a normal MPI, indicating a need for improved risk stratification.
Relative Status and Well-Being: Evidence from U.S. Suicide Deaths
Authors: Daly Mary C. , Wilson Daniel J. , Johnson Norman J. 
Published: April 2013

AbstractWe assess the importance of interpersonal income comparisons using data on suicide deaths. We examine whether suicide risk is related to others' income, holding own income and other individual and environmental factors fixed. We estimate models of the suicide hazard using two independent data sets: the National Longitudinal Mortality Study and the National Center for Health Statistics' Multiple Cause of Death Files combined with the 5% Public Use Micro Sample of the 1990 decennial census. Results from both data sources show that, controlling for own income and individual characteristics, individual suicide risk rises with others' income.
Sex Ratios and Crime: Evidence from China
Authors: Edlund Lena , Li Hongbin , Yi Junjian , Zhang Junsen 
Published: April 2013

Abstract
Since the introduction of the one-child policy in China in 1979, many more boys than girls have been born, foreshadowing a sizable bride shortage. What do young men unable to find wives do? This paper focuses on criminality, an asocial activity that has seen a marked rise since the mid-1990s. Exploiting province-year level variation, we find an elasticity of crime with respect to the sex ratio of 16- to 25-year-olds of 3.4, suggesting that male sex ratios can account for one-seventh of the rise in crime. We hypothesize that adverse marriage market conditions drive this association.
Knowledge Spillovers from Research Universities: Evidence from Endowment Value Shocks
Authors: Kantor Shawn , Whalley Alexander 
Published: April 2013

Abstract
We estimate the local spillovers from research university activity in a sample of urban counties. Our approach uses the interaction between university endowment values and stock market shocks over time for identification. We find statistically significant local spillover effects from university activity. The effects are significantly larger when local universities are more research intensive or local firms are technologically close to universities. Our results suggest that the longer-term effects that universities have on their local economies may grow over time as the composition of local industries adjusts to take advantage of the heterogeneous knowledge spillovers we identify.
Dynamic Hierarchical Factor Models
Authors: Moench Emanuel , Ng Serena , Potter Simon 
Published: April 2013

AbstractThis paper uses multilevel factor models to characterize within- and between-block variations as well as idiosyncratic noise in large dynamic panels. Block-level shocks are distinguished from genuinely common shocks, and the estimated block-level factors are easy to interpret. The framework achieves dimension reduction and yet explicitly allows for heterogeneity between blocks. The model is estimated using an MCMC algorithm that takes into account the hierarchical structure of the factors. The importance of block-level variations is illustrated in a four-level model estimated on a panel of 445 series related to different categories of real activity in the United States.
Printing and Protestants: An Empirical Test of the Role of Printing in the Reformation
Authors: Rubin Jared 
Published: April 2013

Abstract
The causes of the Protestant Reformation have long been debated. This paper seeks to revive and econometrically test the theory that the spread of the Reformation is linked to the spread of the printing press. I test this theory by analyzing data on the spread of the press and the Reformation at the city level. An econometric analysis that instruments for omitted variable bias with a city's distance from Mainz, the birthplace of printing, suggests that cities with at least one printing press by 1500 were at minimum 29 percentage points more likely to be Protestant by 1600.
Does Enforcement of Intellectual Property Rights Matter in China? Evidence from Financing and Investment Choices in the High-Tech Industry
Authors: Ang James S , Cheng Yingmei , Wu Chaopeng 
Published: April 2013

Abstract
Using a unique and rich database of high-technology firms in China, we show that effective enforcement of intellectual property rights at the provincial level is critical in encouraging financing and investing in R&D. Better enforcement of intellectual property (IP) rights positively affects firms' ability to acquire new external debt and allows firms to invest in more R&D, generate more innovation patents, and produce more sales from new products. Our results suggest that facilitating financing and investing in R&D are the channels through which better IP rights enforcement can affect economic growth.
Comparing Treatments across Labor Markets: An Assessment of Nonexperimental Multiple-Treatment Strategies
Authors: Flores Carlos A. , Mitnik Oscar A. 
Published: April 2013

AbstractWe study the effectiveness of nonexperimental strategies in adjusting for comparison group differences when using data from several programs, each implemented at a different location, to compare their effect if implemented at alternative locations. First, we adjust for individual characteristics differences simultaneously across all groups using unconfoundedness-based and conditional difference-in-difference methods for multiple treatments. Second, we adjust for differences in local economic conditions and stress their role after program participation. Our results show that it is critical to have sufficient overlap across locations in both dimensions and illustrate the difficulty of adjusting for local economic conditions that differ greatly across locations.
Expectations and Economic Fluctuations: An Analysis Using Survey Data
Authors: Leduc Sylvain , Sill Keith 
Published: April 2013

Abstract
Using survey-based measures of future U.S. economic activity from the Livingston Survey and the Survey of Professional Forecasters, we study how changes in expectations and their interaction with monetary policy contribute to fluctuations in macroeconomic aggregates. We find that changes in expected future economic activity are a quantitatively important driver of economic fluctuations: a perception that good times are ahead typically leads to a significant rise in current measures of economic activity and inflation. We also find that the short-term interest rate rises in response to expectations of good times as monetary policy tightens.
Self-Selection and International Migration: New Evidence from Mexico
Authors: Kaestner Robert , Malamud Ofer 
Published: April 2013

AbstractThis paper examines the selection of Mexican migrants to the United States using novel data with rich premigration characteristics that include permanent migrants, return migrants, and migrating households. Results indicate that Mexican migrants are more likely to be young, male, and from rural areas compared to nonmigrants, but they are similar to nonmigrants in cognitive ability and health. Migrants are selected from the middle of the education distribution. Male Mexican migrants are negatively selected on earnings, and this result is largely explained by differential returns to labor market skill between the United States and Mexico rather than proxies for differential costs of migration.
The Effect of Health Insurance on Emergency Department Visits: Evidence from an Age-Based Eligibility Threshold
Authors: Anderson Michael L. , Dobkin Carlos , Gross Tal 
Published: April 2013

AbstractHealth insurance affects the rate at which individuals visit hospitals and emergency departments (EDs). We identify the causal effect of losing health insurance using a regression discontinuity design. We compare individuals just before and after their twenty third birthday, which insurers have used as a cutoff after which students are no longer eligible for their parents' health insurance: 1.5% of young adults lose their health insurance upon turning 23, and this transition leads to a 1.6% decrease in ED visits and a 0.8% decrease in hospital stays. We discuss why these estimates are larger than those observed among teenage populations.