bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Contribution of Skills and Family Background to Educational Mobility
Authors: Rustichini Aldo , Iacono William G. , McGue Matt 
Published: August 2016

AbstractWe study the role of hard and soft skills in economic performance and social mobility in a sample of twins (N = 2,764) from the Minnesota Twin Family Study, combining classical economic models of parental investment with a complete and realistic equilibrium model of genetic transmission of skills. Hard and soft skills have comparable roles in affecting early educational success and college attainment. We then use the information on family background to estimate the determinants of social intergenerational mobility. The transmission of personality characteristics – in particular but not exclusively of intelligence – explains a substantial fraction of upward and downward mobility of children.
Conditional Akaike Information Criteria for a Class of Poisson Mixture Models with Random Effects
Authors: Yu Dalei 
Published: August 2016

AbstractFocusing on the model selection problems in the family of Poisson mixture models (including the Poisson mixture regression model with random effects and zero‐inflated Poisson regression model with random effects), the current paper derives two conditional Akaike information criteria. The criteria are the unbiased estimators of the conditional Akaike information based on the conditional log‐likelihood and the conditional Akaike information based on the joint log‐likelihood, respectively. The derivation is free from the specific parametric assumptions about the conditional mean of the true data‐generating model and applies to different types of estimation methods. Additionally, the derivation is not based on the asymptotic argument. Simulations show that the proposed criteria have promising estimation accuracy. In addition, it is found that the criterion based on the conditional log‐likelihood demonstrates good model selection performance under different scenarios. Two sets of real data are used to illustrate the proposed method.
A double‐mutant collection targeting MAP kinase related genes in Arabidopsis for studying genetic interactions
Authors: Su Shih‐Heng , Krysan Patrick J. 
Published: August 2016

SummaryMitogen‐activated protein kinase cascades are conserved in all eukaryotes. In Arabidopsis thaliana there are approximately 80 genes encoding MAP kinase kinase kinases (MAP3K), 10 genes encoding MAP kinase kinases (MAP2K), and 20 genes encoding MAP kinases (MAPK). Reverse genetic analysis has failed to reveal abnormal phenotypes for a majority of these genes. One strategy for uncovering gene function when single‐mutant lines do not produce an informative phenotype is to perform a systematic genetic interaction screen whereby double‐mutants are created from a large library of single‐mutant lines. Here we describe a new collection of 275 double‐mutant lines derived from a library of single‐mutants targeting genes related to MAP kinase signaling. To facilitate this study, we developed a high‐throughput double‐mutant generating pipeline using a system for growing Arabidopsis seedlings in 96‐well plates. A quantitative root growth assay was used to screen for evidence of genetic interactions in this double‐mutant collection. Our screen revealed four genetic interactions, all of which caused synthetic enhancement of the root growth defects observed in a MAP kinase 4 (MPK4) single‐mutant line. Seeds for this double‐mutant collection are publicly available through the Arabidopsis Biological Resource Center. Scientists interested in diverse biological processes can now screen this double‐mutant collection under a wide range of growth conditions in order to search for additional genetic interactions that may provide new insights into MAP kinase signaling.
Automated survey of 8000 plan checks at eight facilities
Authors: Halabi Tarek , Lu Hsiao‐Ming , Bernard Damian A. , Chu James C. H. , Kirk Michael C. , Hamilton Russell J. , Lei Yu , Driewer Joseph 
Published: August 2016

Purpose:To identify policy and system related weaknesses in treatment planning and plan check work‐flows.Methods:The authors’ web deployed plan check automation solution, PlanCheck, which works with all major planning and record and verify systems (demonstrated here for mosaiq only), allows them to compute violation rates for a large number of plan checks across many facilities without requiring the manual data entry involved with incident filings. Workflows and failure modes are heavily influenced by the type of record and verify system used. Rather than tackle multiple record and verify systems at once, the authors restricted the present survey to mosaiq facilities. Violations were investigated by sending inquiries to physicists running the program.Results:Frequent violations included inadequate tracking in the record and verify system of total and prescription doses. Infrequent violations included incorrect setting of patient orientation in the record and verify system. Peaks in the distribution, over facilities, of violation frequencies pointed to suboptimal policies at some of these facilities. Correspondence with physicists often revealed incomplete knowledge of settings at their facility necessary to perform thorough plan checks.Conclusions:The survey leads to the identification of specific and important policy and system deficiencies that include: suboptimal timing of initial plan checks, lack of communication or agreement on conventions surrounding prescription definitions, and lack of automation in the transfer of some parameters.
Characterization and Evaluation of a Salmonella enterica Serotype Senftenberg Mutant Created by Deletion of Virulence-Related Genes for Use as a Live Attenuated Vaccine
Authors: Kamble Nitin M. , Lee John Hwa 
Published: August 2016

ABSTRACT

Natural infections of chickens with
Salmonella enterica
subsp.
enterica
serovar Senftenberg (
S.
Senftenberg) are characterized by low-level intestinal invasiveness and insignificant production of antibodies. In this study, we investigated the potential effects of
lon
and
cpxR
gene deletions on the invasiveness of
S
. Senftenberg into the intestinal epithelium of chickens and its ability to induce an immune response, conferring protection against
S
. Senftenberg infection. With the allelic exchange method, we developed JOL1596 (Δ
lon
), JOL1571 (Δ
cpxR
), and JOL1587 (Δ
lon
Δ
cpxR
) deletion mutants from wild-type
S
. Senftenberg. Deletion of the
lon
gene from
S
. Senftenberg produced increased frequency of elongated cells, with significantly greater amounts of exopolysaccharide (EPS) than in the
cpxR
-deleted strain and the wild-type strain. The
in vivo
intestinal loop invasion assay showed a significant increase in epithelial invasiveness for JOL1596 (Δ
lon
) and JOL1587 (Δ
lon
Δ
cpxR
), compared to JOL1571 (Δ
cpxR
) and the wild-type strain. Furthermore, the
S
. Senftenberg wild-type and mutant strains were internalized at high levels inside activated abdominal macrophages from chicken. The
in vivo
inoculation of JOL1587 (Δ
lon
Δ
cpxR
) into chickens led to colonization of the liver, spleen, and cecum for a short time. Chickens inoculated with JOL1587 (Δ
lon
Δ
cpxR
) showed significant increases in humoral, mucosal, and cellular immune responses specific to
S
. Senftenberg antigens. Postchallenge, compared to the control group, the JOL1587 (Δ
lon
Δ
cpxR
)-inoculated chickens showed not only lower persistence but also faster clearance of wild-type
S
. Senftenberg from the cecum. We conclude that the increased intestinal invasiveness and colonization of internal organs exhibited by JOL1587 (Δ
lon
Δ
cpxR
) led to the establishment of immunogenicity and conferred protective efficacy against
S
. Senftenberg infections in chickens.
Mutations That Determine Resistance Breaking in a Plant RNA Virus Have Pleiotropic Effects on Its Fitness That Depend on the Host Environment and on the Type, Single or Mixed, of Infection
Authors: Moreno-Pérez Manuel G. , García-Luque Isabel , Fraile Aurora , García-Arenal Fernando 
Published: August 2016

ABSTRACT

Overcoming host resistance in gene-for-gene host-virus interactions is an important instance of host range expansion, which can be hindered by across-host fitness trade-offs. Trade-offs are generated by negative effects of host range mutations on the virus fitness in the original host, i.e., by antagonistic pleiotropy. It has been reported that different mutations in
Pepper mild mottle virus
(PMMoV) coat protein result in overcoming
L
-gene resistance in pepper. To analyze if resistance-breaking mutations in PMMoV result in antagonistic pleiotropy, all reported mutations determining the overcoming of
L

3

and
L

4

alleles were introduced in biologically active cDNA clones. Then, the parental and mutant virus genotypes were assayed in susceptible pepper genotypes with an
L

+

,
L

1

, or
L

2

allele, in single and in mixed infections. Resistance-breaking mutations had pleiotropic effects on the virus fitness that, according to the specific mutation, the host genotype, and the type of infection, single or mixed with other virus genotypes, were antagonistic or positive. Thus, resistance-breaking mutations can generate fitness trade-offs both across hosts and across types of infection, and the frequency of host range mutants will depend on the genetic structure of the host population and on the frequency of mixed infections by different virus genotypes. Also, resistance-breaking mutations variously affected virulence, which may further influence the evolution of host range expansion.

IMPORTANCE
A major cause of virus emergence is host range expansion, which may be hindered by across-host fitness trade-offs caused by negative pleiotropy of host range mutations. An important instance of host range expansion is overcoming host resistance in gene-for-gene plant-virus interactions. We analyze here if mutations in the coat protein of
Pepper mild mottle virus
determining
L
-gene resistance-breaking in pepper have associated fitness penalties in susceptible host genotypes. Results show that pleiotropic effects of resistance-breaking mutations on virus fitness depend on the specific mutation, the susceptible host genotype, and the type of infection, single or mixed, with other virus genotypes. Accordingly, resistance-breaking mutations can have negative, positive, or no pleiotropic effects on virus fitness. These results underscore the complexity of host range expansion evolution and, specifically, the difficulty of predicting the overcoming of resistance factors in crops.
Acute Liver Damage Associated with Innate Immune Activation in a Small Nonhuman Primate Model of Hepacivirus Infection
Authors: Manickam Cordelia , Rajakumar Premeela , Wachtman Lynn , Kramer Joshua A. , Martinot Amanda J. , Varner Valerie , Giavedoni Luis D. , Reeves R. Keith 
Published: August 2016

ABSTRACT

Despite its importance in shaping adaptive immune responses, viral clearance, and immune-based inflammation, tissue-specific innate immunity remains poorly characterized for hepatitis C virus (HCV) infection due to the lack of access to acutely infected tissues. In this study, we evaluated the impact of natural killer (NK) cells and myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells on control of virus replication and virus-induced pathology caused by another, more rapidly resolving hepacivirus, GB virus B (GBV-B), in infections of common marmosets. High plasma and liver viral loads and robust hepatitis characterized acute GBV-B infection, and while viremia was generally cleared by 2 to 3 months postinfection, hepatitis and liver fibrosis persisted after clearance. Coinciding with peak viral loads and liver pathology, the levels of NK cells, mDCs, and pDCs in the liver increased up to 3-fold. Although no obvious numerical changes in peripheral innate cells occurred, circulating NK cells exhibited increased perforin and Ki67 expression levels and increased surface expression of CXCR3. These data suggested that increased NK cell arming and proliferation as well as tissue trafficking may be associated with influx into the liver during acute infection. Indeed, NK cell frequencies in the liver positively correlated with plasma (
R
= 0.698;
P
= 0.015) and liver (
R
= 0.567;
P
= 0.057) viral loads. Finally, soluble factors associated with NK cells and DCs, including gamma interferon (IFN-γ) and RANTES, were increased in acute infection and also were associated with viral loads and hepatitis. Collectively, the findings showed that mobilization of local and circulating innate immune responses was linked to acute virus-induced hepatitis, and potentially to resolution of GBV-B infection, and our results may provide insight into similar mechanisms in HCV infection.

IMPORTANCE
Hepatitis C virus (HCV) infection has created a global health crisis, and despite new effective antivirals, it is still a leading cause of liver disease and death worldwide. Recent evidence suggests that innate immunity may be a potential therapeutic target for HCV, but it may also be a correlate of increased disease. Due to a lack of access to human tissues with acute HCV infection, in this study we evaluated the role of innate immunity in resolving infection with a hepacivirus, GBV-B, in common marmosets. Collectively, our data suggest that NK cell and DC mobilization in acute hepacivirus infection can dampen virus replication but also regulate acute and chronic liver damage. How these two opposing effects on the host may be modulated in future therapeutic and vaccine approaches warrants further study.
Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan
Authors: Liang Yu , Guttman Miklos , Williams James A. , Verkerke Hans , Alvarado Daniel , Hu Shiu-Lok , Lee Kelly K. 
Published: August 2016

ABSTRACT
The envelope glycoprotein (Env) is the major target for HIV-1 broadly neutralizing antibodies (bNAbs). One of the mechanisms that HIV has evolved to escape the host's immune response is to mask conserved epitopes on Env with dense glycosylation. Previous studies have shown that the removal of a particular conserved glycan at N197 increases the neutralization sensitivity of the virus to antibodies targeting the CD4 binding site (CD4bs), making it a site of significant interest from the perspective of vaccine design. At present, the structural consequences that result from the removal of the N197 glycan have not been characterized. Using native-like SOSIP trimers, we examine the effects on antigenicity and local structural dynamics resulting from the removal of this glycan. A large increase in the binding of CD4bs and V3-targeting antibodies is observed for the N197Q mutant in trimeric Env, while no changes are observed with monomeric gp120. While the overall structure and thermostability are not altered, a subtle increase in the flexibility of the variable loops at the trimeric interface of adjacent protomers is evident in the N197Q mutant by hydrogen-deuterium exchange mass spectrometry. Structural modeling of the glycan chains suggests that the spatial occupancy of the N197 glycan leads to steric clashes with CD4bs antibodies in the Env trimer but not monomeric gp120. Our results indicate that the removal of the N197 glycan enhances the exposure of relevant bNAb epitopes on Env with a minimal impact on the overall trimeric structure. These findings present a simple modification for enhancing trimeric Env immunogens in vaccines.

IMPORTANCE
The HIV-1 Env glycoprotein presents a dense patchwork of host cell-derived N-linked glycans. This so-called glycan shield is considered to be a major protective mechanism against immune recognition. While the positions of many N-linked glycans are isolate specific, some are highly conserved and are believed to play key functional roles. In this study, we examine the conserved, CD4 binding site-proximal N197 glycan and demonstrate that its removal both facilitates neutralizing antibody access to the CD4 binding site and modestly impacts the structural dynamics at the trimer crown without drastically altering global Env trimer stability. This indicates that surgical glycosylation site modification may be an effective way of sculpting epitope presentation in Env-based vaccines.
A COMPARISON OF THE LUMBOPELVIC-HIP COMPLEX MOVEMENT PATTERNS IN PEOPLE WITH AND WITHOUT NON-SPECIFIC LOW BACK PAIN DURING AN ACTIVE HIP TEST
Authors: SADEGHISANI MEISSAM , MANSHADI FARIDEH DEHGHAN , KALANTARI KHOSRO KHADEMI , RAHIMI ABBAS , RAFIEI AHMAD REZA , ASNAASHARI ALI , DEHGHAN MORTAZA 
Published: August 2016

The current study aimed to compare the rhythm of complex lumbopelvic-hip movements in subjects with and without low back pain (LBP) during an active hip internal rotation (AHIR) test. Fifteen professional athletes with LBP were recruited in this analytical study and were compared with 20 age-sex matched healthy people with no history of sports-related rotational movements. A 3D optoelectronic motion analysis system recorded the kinematics of all subjects during an AHIR in the prone position. The outcome measures included the values of hip and pelvic rotation across the test, pelvic rotation during the first half of the test and timing of hip/pelvic rotation in the transverse plane. Then, variables were compared between the two groups. The amount of internal hip rotation of the lower extremities, pelvic rotation in either first half of the pathway or throughout whole path length were all significantly higher in subjects with LBP than the healthy group ([Formula: see text]). Additionally, subjects with LBP showed an earlier movement of the lumbopelvic area than healthy group during the task. Asymmetric movement was seen between the right and left sides of the subjects with LBP for lower limb and hip internal rotation (HIR) ROM. The results demonstrated that the athletes with LBP who use more repetitive movements of their trunk and lower extremities during sports, show increased tendency of lumbopelvic rotation motion during AHIR test.
Exercise and Prognosis on the Basis of Clinicopathologic and Molecular Features in Early-Stage Breast Cancer: The LACE and Pathways Studies
Authors: Jones Lee W. , Kwan Marilyn L. , Weltzien Erin , Chandarlapaty Sarat , Sternfeld Barbara , Sweeney Carol , Bernard Philip S. , Castillo Adrienne , Habel Laurel A. , Kroenke Candyce H. , Langholz Bryan M. , Queensberry Charles P. , Dang Chau , Weigelt Britta , Kushi Lawrence H. , Caan Bette J. 
Published: August 2016

Abstract
To investigate whether the impact of postdiagnosis exercise on breast cancer outcomes in women diagnosed with early-stage breast cancer differs on the basis of tumor clinicopathologic and molecular features. Using a prospective design, 6,211 patients with early-stage breast cancer from two large population-based cohort studies were studied. Age-adjusted and multivariable Cox regression models were performed to determine the relationship between exercise exposure (total MET-hours/week) and recurrence and breast cancer–related death for: (i) all patients (“unselected” cohort), and on the basis of (ii) classic clinicopathologic features, (iii) clinical subtypes, (iv) PAM50-based molecular intrinsic subtypes, and (v) individual PAM50 target genes. After a median follow-up of 7.2 years, in the unselected cohort (n = 6,211) increasing exercise exposure was not associated with a reduction in the risk of recurrence (adjusted Ptrend = 0.60) or breast cancer–related death (adjusted Ptrend = 0.39). On the basis of clinicopathologic features, an exercise-associated reduction in breast cancer–related death was apparent for tumors &lt;2 cm [HR, 0.50; 95% confidence interval (CI), 0.34–0.72], well/moderately differentiated tumors (HR, 0.63; 95% CI, 0.43–0.91), and ER-positive tumors (HR, 0.72; 95% CI, 0.53–0.97). Stratification by clinical subtype indicated that the ER+/PR+/HER2−/low-grade clinical subtype was preferentially responsive to exercise (recurrence: adjusted HR, 0.63; 95% CI, 0.45–0.88; breast cancer–related death: adjusted HR, 0.57; 95% CI, 0.37–0.86). The impact of exercise on cancer outcomes appears to differ as a function of pathologic and molecular features in early-stage breast cancer. Cancer Res; 76(18); 5415–22. ©2016 AACR.
In Vivo FRET Imaging of Tumor Endothelial Cells Highlights a Role of Low PKA Activity in Vascular Hyperpermeability
Authors: Yamauchi Fumio , Kamioka Yuji , Yano Tetsuya , Matsuda Michiyuki 
Published: August 2016

Abstract
Vascular hyperpermeability is a pathological hallmark of cancer. Previous in vitro studies have elucidated roles of various signaling molecules in vascular hyperpermeability; however, the activities of such signaling molecules have not been examined in live tumor tissues for technical reasons. Here, by in vivo two-photon excitation microscopy with transgenic mice expressing biosensors based on Förster resonance energy transfer, we examined the activity of protein kinase A (PKA), which maintains endothelial barrier function. The level of PKA activity was significantly lower in the intratumoral endothelial cells than the subcutaneous endothelial cells. PKA activation with a cAMP analogue alleviated the tumor vascular hyperpermeability, suggesting that the low PKA activity in the endothelial cells may be responsible for the tumor-tissue hyperpermeability. Because the vascular endothelial growth factor (VEGF) receptor is a canonical inducer of vascular hyperpermeability and a molecular target of anticancer drugs, we examined the causality between VEGF receptor activity and the PKA activity. Motesanib, a kinase inhibitor for VEGF receptor, activated tumor endothelial PKA and reduced the vascular permeability in the tumor. Conversely, subcutaneous injection of VEGF decreased endothelial PKA activity and induced hyperpermeability of subcutaneous blood vessels. Notably, in cultured human umbilical vascular endothelial cells, VEGF activated PKA rather than decreasing its activity, highlighting the remarkable difference between its actions in vitro and in vivo. These data suggested that the VEGF receptor signaling pathway increases vascular permeability, at least in part, by reducing endothelial PKA activity in the live tumor tissue. Cancer Res; 76(18); 5266–76. ©2016 AACR.
Multivalent Peptoid Conjugates Which Overcome Enzalutamide Resistance in Prostate Cancer Cells
Authors: Wang Yu , Dehigaspitiya Dilani C. , Levine Paul M. , Profit Adam A. , Haugbro Michael , Imberg-Kazdan Keren , Logan Susan K. , Kirshenbaum Kent , Garabedian Michael J. 
Published: August 2016

Abstract
Development of resistance to antiandrogens for treating advanced prostate cancer is a growing concern and extends to recently developed therapeutics, including enzalutamide. Therefore, new strategies to block androgen receptor (AR) function in prostate cancer are required. Here, we report the characterization of a multivalent conjugate presenting two bioactive ethisterone ligands arrayed as spatially defined pendant groups on a peptoid oligomer. The conjugate, named Multivalent Peptoid Conjugate 6 (MPC6), suppressed the proliferation of multiple AR-expressing prostate cancer cell lines including those that failed to respond to enzalutamide and ARN509. The structure–activity relationships of MPC6 variants were evaluated, revealing that increased spacing between ethisterone moieties and changes in peptoid topology eliminated its antiproliferative effect, suggesting that both ethisterone ligand presentation and scaffold characteristics contribute to MPC6 activity. Mechanistically, MPC6 blocked AR coactivator–peptide interaction and prevented AR intermolecular interactions. Protease sensitivity assays suggested that the MPC6-bound AR induced a receptor conformation distinct from that of dihydrotestosterone- or enzalutamide-bound AR. Pharmacologic studies revealed that MPC6 was metabolically stable and displayed a low plasma clearance rate. Notably, MPC6 treatment reduced tumor growth and decreased Ki67 and AR expression in mouse xenograft models of enzalutamide-resistant LNCaP-abl cells. Thus, MPC6 represents a new class of compounds with the potential to combat treatment-resistant prostate cancer. Cancer Res; 76(17); 5124–32. ©2016 AACR.