bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Basis for Escape of Human Astrovirus from Antibody Neutralization: Broad Implications for Rational Vaccine Design
Authors: Bogdanoff Walter A. , Perez Edmundo I. , López Tomás , Arias Carlos F. , DuBois Rebecca M. 
Published: October 2017

ABSTRACT
Human astroviruses are recognized as a leading cause of viral diarrhea worldwide in children, immunocompromised patients, and the elderly. There are currently no vaccines available to prevent astrovirus infection; however, antibodies developed by healthy individuals during previous infection correlate with protection from reinfection, suggesting that an effective vaccine could be developed. In this study, we investigated the molecular mechanism by which several strains of human astrovirus serotype 2 (HAstV-2) are resistant to the potent HAstV-2-neutralizing monoclonal antibody PL-2 (MAb PL-2). Sequencing of the HAstV-2 capsid genes reveals mutations in the PL-2 epitope within the capsid's spike domain. To understand the molecular basis for resistance from MAb PL-2 neutralization, we determined the 1.35-Å-resolution crystal structure of the capsid spike from one of these HAstV-2 strains. Our structure reveals a dramatic conformational change in a loop within the PL-2 epitope due to a serine-to-proline mutation, locking the loop in a conformation that sterically blocks binding and neutralization by MAb PL-2. We show that mutation to serine permits loop flexibility and recovers MAb PL-2 binding. Importantly, we find that HAstV-2 capsid spike containing a serine in this loop is immunogenic and elicits antibodies that neutralize all HAstV-2 strains. Taken together, our results have broad implications for rational selection of vaccine strains that do not contain prolines in antigenic loops, so as to elicit antibodies against diverse loop conformations.

IMPORTANCE
Human astroviruses (HAstVs) infect nearly every person in the world during childhood and cause diarrhea, vomiting, and fever. In this study, we investigated how several strains of HAstV are resistant to a virus-neutralizing monoclonal antibody. We determined the crystal structure of the capsid protein spike domain from one of these HAstV strains and found that a single amino acid mutation induces a structural change in a loop that is responsible for antibody binding. Our findings reveal how viruses can escape antibody neutralization and provide insight for the rational design of vaccines to elicit diverse antibodies that provide broader protection from infection.
Higher-order gravity and the classical equivalence principle
Authors: Accioly Antonio , Herdy Wallace 
Published: October 2017

As is well known, the deflection of any particle by a gravitational field within the context of Einstein’s general relativity — which is a geometrical theory — is, of course, nondispersive. Nevertheless, as we shall show in this paper, the mentioned result will change totally if the bending is analyzed — at the tree level — in the framework of higher-order gravity. Indeed, to first order, the deflection angle corresponding to the scattering of different quantum particles by the gravitational field mentioned above is not only spin dependent, it is also dispersive (energy-dependent). Consequently, it violates the classical equivalence principle (universality of free fall, or equality of inertial and gravitational masses) which is a nonlocal principle. However, contrary to popular belief, it is in agreement with the weak equivalence principle which is nothing but a statement about purely local effects. It is worthy of note that the weak equivalence principle encompasses the classical equivalence principle locally. We also show that the claim that there exists an incompatibility between quantum mechanics and the weak equivalence principle, is incorrect.
Stick number of tangles
Authors: Huh Youngsik , Lee Jung Hoon , Taniyama Kouki 
Published: October 2017

An [Formula: see text]-string tangle is a pair [Formula: see text] such that [Formula: see text] is a disjoint union of properly embedded [Formula: see text] arcs in a topological [Formula: see text]-ball [Formula: see text]. And an [Formula: see text]-string tangle is said to be trivial (or rational)[Formula: see text], if it is homeomorphic to [Formula: see text] as a pair, where [Formula: see text] is a 2-disk, [Formula: see text] is the unit interval and each [Formula: see text] is a point in the interior of [Formula: see text]. A stick tangle is a tangle each of whose arcs consists of finitely many line segments, called sticks. For an [Formula: see text]-string stick tangle its stick-order is defined to be a nonincreasing sequence [Formula: see text] of natural numbers such that, under an ordering of the arcs of the tangle, each [Formula: see text] denotes the number of sticks constituting the [Formula: see text]th arc of the tangle. And a stick-order [Formula: see text] is said to be trivial, if every stick tangle of the order [Formula: see text] is trivial. In this paper, restricting the [Formula: see text]-ball [Formula: see text] to be the standard 3-ball, we give the complete list of trivial stick-orders.
Individualized tracking of self-directed motor learning in group-housed mice performing a skilled lever positioning task in the home cage
Authors: Silasi Gergely , Boyd Jamie D. , Bolanos Federico , LeDue Jeff M. , Scott Stephen H. , Murphy Timothy H. 
Published: October 2017

Skilled forelimb function in mice is traditionally studied through behavioral paradigms that require extensive training by investigators and are limited by the number of trials individual animals are able to perform within a supervised session. We developed a skilled lever positioning task that mice can perform within their home cage. The task requires mice to use their forelimb to precisely hold a lever mounted on a rotary encoder within a rewarded position to dispense a water reward. A Raspberry Pi microcomputer is used to record lever position during trials and to control task parameters, thus making this low-footprint apparatus ideal for use within animal housing facilities. Custom Python software automatically increments task difficulty by requiring a longer hold duration, or a more accurate hold position, to dispense a reward. The performance of individual animals within group-housed mice is tracked through radio-frequency identification implants, and data stored on the microcomputer may be accessed remotely through an active internet connection. Mice continuously engage in the task for over 2.5 mo and perform ~500 trials/24 h. Mice required ~15,000 trials to learn to hold the lever within a 10° range for 1.5 s and were able to further refine movement accuracy by limiting their error to a 5° range within each trial. These results demonstrate the feasibility of autonomously training group-housed mice on a forelimb motor task. This paradigm may be used in the future to assess functional recovery after injury or cortical reorganization induced by self-directed motor learning. NEW & NOTEWORTHY We developed a low-cost system for fully autonomous training of group-housed mice on a forelimb motor task. We demonstrate the feasibility of tracking both end-point, as well as kinematic performance of individual mice, with each performing thousands of trials over 2.5 mo. The task is run and controlled by a Raspberry Pi microcomputer, which allows for cages to be monitored remotely through an active internet connection.
Experience-dependent trends in CA1 theta and slow gamma rhythms in freely behaving mice
Authors: Gereke Brian J. , Mably Alexandra J. , Colgin Laura Lee 
Published: October 2017

CA1 place cells become more anticipatory with experience, an effect thought to be caused by NMDA receptor-dependent plasticity in the CA3–CA1 network. Theta (~5–12 Hz), slow gamma (~25–50 Hz), and fast gamma (~50–100 Hz) rhythms are thought to route spatial information in the hippocampal formation and to coordinate place cell ensembles. Yet, it is unknown whether these rhythms exhibit experience-dependent changes concurrent with those observed in place cells. Slow gamma rhythms are thought to indicate inputs from CA3 to CA1, and such inputs are thought to be strengthened with experience. Thus, we hypothesized that slow gamma rhythms would become more evident with experience. We tested this hypothesis using mice freely traversing a familiar circular track for three 10-min sessions per day. We found that slow gamma amplitude was reduced in the early minutes of the first session of each day, even though both theta and fast gamma amplitudes were elevated during this same period. However, in the first minutes of the second and third sessions of each day, all three rhythms were elevated. Interestingly, theta was elevated to a greater degree in the first minutes of the first session than in the first minutes of later sessions. Additionally, all three rhythms were strongly influenced by running speed in dynamic ways, with the influence of running speed on theta and slow gamma changing over time within and across sessions. These results raise the possibility that experience-dependent changes in hippocampal rhythms relate to changes in place cell activity that emerge with experience. NEW & NOTEWORTHY We show that CA1 theta, slow gamma, and fast gamma rhythms exhibit characteristic changes over time within sessions in familiar environments. These effects in familiar environments evolve across repeated sessions.
Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805
Authors: Jilaveanu Lucia B. , Puligandla Maneka , Weiss Sarah A. , Wang Xin Victoria , Zito Christopher , Flaherty Keith T. , Boeke Marta , Neumeister Veronique , Camp Robert L. , Adeniran Adebowale , Pins Michael , Manola Judith , DiPaola Robert S. , Haas Naomi B. , Kluger Harriet M. 
Published: October 2017

Abstract
Purpose: Increased vascularity is a hallmark of renal cell carcinoma (RCC). Microvessel density (MVD) is one measurement of tumor angiogenesis; however, its utility as a biomarker of outcome is unknown. ECOG-ACRIN 2805 (E2805) enrolled 1,943 resected high-risk RCC patients randomized to adjuvant sunitinib, sorafenib, or placebo. We aimed to determine the prognostic and predictive role of MVD in RCC.
Experimental Design: We obtained pretreatment primary RCC nephrectomy tissues from 822 patients on E2805 and constructed tissue microarrays. Using quantitative immunofluorescence, we measured tumor MVD as the area of CD34-expressing cells. We determined the association with disease-free survival (DFS), overall survival (OS), treatment arm, and clinicopathologic variables.
Results: High MVD (above the median) was associated with prolonged OS for the entire cohort (P = 0.021) and for patients treated with placebo (P = 0.028). The association between high MVD and OS was weaker in patients treated with sunitinib or sorafenib (P = 0.060). MVD was not associated with DFS (P = 1.00). On multivariable analysis, MVD remained independently associated with improved OS (P = 0.013). High MVD correlated with Fuhrman grade 1–2 (P &lt; 0.001), clear cell histology (P &lt; 0.001), and absence of necrosis (P &lt; 0.001) but not with gender, age, sarcomatoid features, lymphovascular invasion, or tumor size.
Conclusions: High MVD in resected high-risk RCC patients is an independent prognostic, rather than predictive, biomarker of improved OS. Further studies should assess whether incorporating MVD into clinical models will enhance our ability to predict outcome and if low MVD can be used for selection of high-risk patients for adjuvant therapy trials. Clin Cancer Res; 24(1); 217–23. ©2017 AACR.
Changes in Statin Adherence Following an Acute Myocardial Infarction Among Older Adults: Patient Predictors and the Association With Follow‐Up With Primary Care Providers and/or Cardiologists
Authors: Hickson Ryan P. , Robinson Jennifer G. , Annis Izabela E. , Killeya‐Jones Ley A. , Korhonen Maarit Jaana , Cole Ashley L. , Fang Gang 
Published: October 2017

Background

Hospitalizations for acute myocardial infarctions (
AMI
s) are associated with changes in statin adherence. It is unclear to what extent adherence changes, which patients are likely to change, and how post‐discharge follow‐up is associated with statin adherence change.

Methods and Results

This retrospective study used Medicare data for all fee‐for‐service beneficiaries 66 years and older with an
AMI
hospitalization in 2008–2010 and statin use before their index
AMI
. Multivariable multinomial logistic regression models (odds ratio [
OR
] and 99% confidence interval [
CI
]) were applied to assess associations between both patient characteristics and follow‐up with a primary care provider and/or cardiologist with the outcome of statin adherence change (increase or decrease) from the 6‐month pre‐ to 6‐month post‐
AMI
periods. Of 113 296 patients, 64.0% had no change in adherence, while 19.7% had increased and 16.3% had decreased adherence after
AMI
hospitalization. Black and Hispanic patients were more likely to have either increased or decreased adherence than white patients. Patients who required coronary artery bypass graft surgery (
OR
, 1.34; 99%
CI,
1.21–1.49) or percutaneous transluminal coronary angioplasty/stent procedure (
OR,
1.25; 99%
CI
, 1.17–1.32) during their index hospitalization were more likely to have increased adherence. Follow‐up with a primary care provider was only mildly associated with increased adherence (
OR
, 1.08; 99%
CI
, 1.00–1.16), while follow‐up with a cardiologist (OR, 1.15; 99%
CI
, 1.05–1.25) or both provider types (
OR
, 1.21; 99%
CI
, 1.12–1.30) had stronger associations with increased adherence.

Conclusions

Post‐
AMI
changes in statin adherence varied by patient characteristics, and improved adherence was associated with post‐discharge follow‐up care, particularly with a cardiologist or both a primary care provider and a cardiologist.
Limitations of a Purely Salvation-historical Approach to Biblical Theology
Authors: Lockett Darian 
Published: October 2017

Abstract
A salvation-historical approach to biblical theology emphasizes the historical and progressive nature of revelation such that the Bible’s primary meaning is (too often) reduced to its reference to the sequential events of a special (salvation) history. After offering a general description of the development of the salvation-historical approach to biblical theology, the essay considers the representative example of D. A. Carson. Then, noting the criticisms of Hans Frei, Karl Barth, and Brevard Childs, the paper argues that limiting one’s biblical theology to a salvation-historical approach replaces Christ as the subject matter of both Testaments with “the temporally distinct and ordered stages of the history of salvation.” Although the insights of a redemptive-historical biblical theology are important, when taken as the exclusive methodology for biblical theology it risks flattening the relationship between the two Testaments and missing Scripture’s theological subject matter.
Out-of-Cloud Convective Turbulence: Estimation Method and Impacts of Model Resolution
Authors: Barber Katelyn A. , Mullendore Gretchen L. , Alexander M. Joan 
Published: October 2017

AbstractConvectively induced turbulence (CIT) poses both a serious threat to aviation operations and a challenge to forecasting applications. CIT generation and propagation processes occur on scales between 10 and 1000 m and therefore are best treated with high-resolution cloud-resolving models. However, high-resolution model simulations are computationally expensive, limiting their operational use. In this study, summertime convection in the North Dakota region is simulated over a 1-week period using a variety of model setups that are similar to those utilized in operational and research applications. Eddy dissipation rate and Ellrod index, both popular turbulence metrics, are evaluated across various model resolutions and compared with pilot reports from aircraft. The Ellrod index was found to be extremely sensitive to model resolution and overestimated turbulence intensity. The variability of turbulence values with respect to model resolution and distance away from convection is also examined. Turbulence probability was found to be the greatest when farther than 20 mi (32.2 km) away from convective cores. Model resolution was found to influence the intensity of predicted turbulence, and the model setup with the highest horizontal and vertical resolution predicted the highest turbulence values. However, the influence on turbulence intensity of vertical resolution and convective properties, such as storm depth, was found to be minimal for 3-km horizontal grid spacing.
Playwork in prison as a mechanism to support family health and well-being
Authors: Woodall James , Kinsella Karina 
Published: October 2017

Objective: The health of the prison population is of increasing concern, given the disproportionate rates of ill health in this population. Moreover, the challenges faced by prisoners’ families and their children are also becoming more apparent, with prisoners’ children being more likely than other children to experience mental and emotional health problems and more likely to go to prison themselves. Prison visits are an integral part of institutional structures and are a key way by which families stay in contact and mitigate against the negative effects of family separation. This paper focuses particularly on the impact of prison play visits as an alternative to ‘standard’ visiting procedures. Design: Cross-sectional qualitative study. Setting: A male prison in Northern England. Method: Telephone interviews with six prison visitors who had regularly participated in a play visit, plus a focus group with five prisoners. Results: The paper identifies play visits as a useful way to maintain family well-being as they ‘mimic’, albeit temporarily, domestic life. This is reported to be beneficial for future family outcomes and in enabling children to adjust to parental incarceration. Play visits improve levels of intimacy, which is beneficial for the mental and emotional health of both prisoners and their children. Conclusion: The paper argues for a more holistic notion of prisoner health that sees family connections as a key part of supporting health and well-being.
Calf Muscle Performance Deficits Remain 7 Years After an Achilles Tendon Rupture
Authors: Brorsson Annelie , Grävare Silbernagel Karin , Olsson Nicklas , Nilsson Helander Katarina 
Published: October 2017

Background: Optimizing calf muscle performance seems to play an important role in minimizing impairments and symptoms after an Achilles tendon rupture (ATR). The literature lacks long-term follow-up studies after ATR that describe calf muscle performance over time. Purpose: The primary aim was to evaluate calf muscle performance and patient-reported outcomes at a mean of 7 years after ATR in patients included in a prospective, randomized controlled trial. A secondary aim was to evaluate whether improvement in calf muscle performance continued after the 2-year follow-up. Study Design: Cohort study; Level of evidence, 2. Methods: Sixty-six subjects (13 women, 53 men) with a mean age of 50 years (SD, 8.5 years) were evaluated at a mean of 7 years (SD, 1 year) years after their ATR. Thirty-four subjects had surgical treatment and 32 had nonsurgical treatment. Patient-reported outcomes were evaluated with Achilles tendon Total Rupture Score (ATRS) and Physical Activity Scale (PAS). Calf muscle performance was evaluated with single-leg standing heel-rise test, concentric strength power heel-rise test, and single-legged hop for distance. Limb Symmetry Index (LSI = injured side/healthy side × 100) was calculated for side-to-side differences. Results: Seven years after ATR, the injured side showed decreased values in all calf muscle performance tests ( P < .001-.012). Significant improvement in calf muscle performance did not continue after the 2-year follow-up. Heel-rise height increased significantly ( P = .002) between the 1-year (10.8 cm) and the 7-year (11.5 cm) follow-up assessments. The median ATRS was 96 (of a possible score of 100) and the median PAS was 4 (of a possible score of 6), indicating minor patient-reported symptoms and fairly high physical activity. No significant differences were found in calf muscle performance or patient-reported outcomes between the treatment groups except for the LSI for heel-rise repetitions. Conclusion: Continued deficits in calf muscle endurance and strength remained 7 years after ATR. No continued improvement in calf muscle performance occurred after the 2-year follow-up except for heel-rise height.
Dihydrofolate Reductase Inhibition. A Study in the Use of X-ray Crystallography, Molecular Graphics, and Quantitative Structure-Activity Relations in Drug Design
Authors: Hansch Corwin 
Published: October 2017

Substituent constants and regression analyses are used to formulate quantitative structure-activity relationships (QSAR) for the inhibition by 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3-X-phenyl)- s-triazines of purified dihydrofolate reductase (DHFR) from L. casei cells, bovine liver, and murine leukemia cells (L5178Y). The QSAR for the activity of the triazines on purified DHFR is compared with the QSAR for their action on L. casei cell culture and murine L5178Y cell culture. The QSAR for action on purified DHFR is similar to that on wild type cells; however, the QSAR for these cells differs remarkably from QSAR for both types of cells that are resistant to methotrexate (MTX).The conclusion from these analyses is that cells resistant to MTX protect themselves from this highly hydrophilic drug by developing a hydrophobic barrier. Our understanding of DHFR interaction with drugs is rapidly increasing via QSAR, and X-ray crystallography, combined with the new molecular graphics of Langridge's group, promises to expedite the process. The value of three-dimensional color graphics is discussed, with the aid of color stereo views of L. casei and E. coli DHFR.
Evaluation of Appropriateness and Interpretation of Serum Theophylline Assays
Authors: Sargenti Christine , Zelman Lawrence , Beauclair Therese , Garrard Elwyn , Boehm Ralph 
Published: October 2017

A drug utilization review of serum theophylline assays was undertaken to: (1) evaluate the prescriben' usage and interpretation of serum theophylline levels (STLs), and (2) calculate the cost of inappropriate assays. Criteria for appropriate use and interpretation were defined by an audit committee and approved by the chief medical resident. STLs were evaluated on medicine patients for a one-month period. Results of 102 levels ordered showed that 47 percent were inappropriate. The reasons cited most often for inappropriateness were: (1) previously-known STLs with no reason to expect a change in subsequent levels (26 percent); and (2) STLs drawn prior to steady state (12 percent). None of the levels evaluated had a request entered for the sampling time to be recorded. STLs were interpreted with the same degree of accuracy regardless of whether they were ordered appropriately. Results from this study suggest significant cost savings can be realized if physicians' ordering habits are corrected.