bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constitutionalism and experimentalist governance
Authors: Kumm Mattias 
Published: September 2012

AbstractThis comment explores how experimentalist governance is connected to wider constitutional questions and makes two claims. First, there are good reasons to believe that experimentalist governance can only flourish in a world where the precepts of liberal democratic constitutionalism have been widely accepted and institutionalized. Experimentalist governance is part and parcel of the world of liberal democratic constitutionalism. Second, it is not only governance in Europe that can be described in experimentalist terms. The concept is also useful to describe the dynamics of European constitutionalism.
Experimentalist governance in the European Union: A commentary
Authors: Verdun Amy 
Published: September 2012

AbstractSabel and Zeitlin's Experimentalist Governance offers an insight into European governance in those cases where the EU institutions do not have clear competence and where member states are not prepared to accept a unified policy on a problem at hand. Experimentalist Governance identifies four steps of action: agree on common goals, have lower levels propose ways to meet goals, then report on their meeting of goals, and, finally, periodically reevaluate the review procedures. By looking at the developments in EU policymaking through the lens of experimentalist governance (EG), one obtains an appreciation of how goals might be achieved that would otherwise not likely have been achieved through the community method. Sabel and Zeitlin highlight how EG can be effective in obtaining results, integrating peers, and incorporating deliberation, and offer a different way to deal with accountability and legitimacy. This article closes by taking the next step, namely, asking what challenges EG poses to democratic processes.
MALDI imaging of post‐mortem human spinal cord in amyotrophic lateral sclerosis
Authors: Hanrieder Jörg , Ekegren Titti , Andersson Malin , Bergquist Jonas 
Published: September 2012

AbstractAmyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressing disease of the central nervous system that is characterized by motor neuron degeneration in the brainstem and the spinal cord. Matrix‐assisted laser desorption/ionization (MALDI) imaging mass spectrometry is an emerging powerful technique that allows for spatially resolved, comprehensive, and specific characterization of molecular species in situ. In this study, we report for the first time the MALDI imaging‐based spatial protein profiling and relative quantification of post‐mortem human spinal cord samples obtained from ALS patients and controls. In normal spinal cord, protein distribution patterns were well in line with histological features. For example, thymosin beta 4, ubiquitin, histone proteins, acyl‐CoA‐binding protein, and macrophage inhibitory factor were predominantly localized to the gray matter. Furthermore, unsupervised statistics revealed a significant reduction of two protein species in ALS gray matter. One of these proteins (m/z 8451) corresponds to an endogenous truncated form of ubiquitin (Ubc 1–76), with both C‐terminal glycine residues removed (Ubc‐T/Ubc 1–74). This region‐specific ubiquitin processing suggests a disease‐related change in protease activity. These results highlight the importance of MALDI mass spectrometry as a versatile approach to elucidate molecular mechanisms of neurodegenerative diseases.
Glutamate decarboxylase‐dependent acid resistance in orally acquired bacteria: function, distribution and biomedical implications of the gadBC operon
Authors: De Biase Daniela , Pennacchietti Eugenia 
Published: September 2012

SummaryFor successful colonization of the mammalian host, orally acquired bacteria must overcome the extreme acidic stress (pH < 2.5) encountered during transit through the host stomach. The glutamate‐dependent acid resistance (GDAR) system is by far the most potent acid resistance system in commensal and pathogenic Escherichia coli, Shigella flexneri, Listeria monocytogenes and Lactococcus lactis. GDAR requires the activity of glutamate decarboxylase (GadB), an intracellular PLP‐dependent enzyme which performs a proton‐consuming decarboxylation reaction, and of the cognate antiporter (GadC), which performs the glutamatein/γ‐aminobutyrateout (GABA) electrogenic antiport. Herein we review recent findings on the structural determinants responsible for pH‐dependent intracellular activation of E. coli GadB and GadC. A survey of genomes of bacteria (pathogenic and non‐pathogenic), having in common the ability to colonize or to transit through the host gut, shows that the gadB and gadC genes frequently lie next or near each other. This gene arrangement is likely to be important to ensure timely co‐regulation of the decarboxylase and the antiporter. Besides the involvement in acid resistance, GABA production and release were found to occur at very high levels in lactic acid bacteria originally isolated from traditionally fermented foods, supporting the evidence that GABA‐enriched foods possess health‐promoting properties.
Estimation of the two‐dimensional presampled modulation transfer function of digital radiography devices using one‐dimensional test objects
Authors: Wells Jered R. , Dobbins James T. 
Published: September 2012

Purpose:The modulation transfer function (MTF) of medical imaging devices is commonly reported in the form of orthogonal one‐dimensional (1D) measurements made near the vertical and horizontal axes with a slit or edge test device. A more complete description is found by measuring the two‐dimensional (2D) MTF. Some 2D test devices have been proposed, but there are some issues associated with their use: (1) they are not generally available; (2) they may require many images; (3) the results may have diminished accuracy; and (4) their implementation may be particularly cumbersome. This current work proposes the application of commonly available 1D test devices for practical and accurate estimation of the 2D presampled MTF of digital imaging systems.Methods:Theory was developed and applied to ensure adequate fine sampling of the system line spread function for 1D test devices at orientations other than approximately vertical and horizontal. Methods were also derived and tested for slit nonuniformity correction at arbitrary angle. Techniques were validated with experimental measurements at ten angles using an edge test object and three angles using a slit test device on an indirect‐detection flat‐panel system [GE Revolution XQ/i (GE Healthcare, Waukesha, WI)]. The 2D MTF was estimated through a simple surface fit with interpolation based on Delaunay triangulation of the 1D edge‐based MTF measurements. Validation by synthesis was also performed with simulated images from a hypothetical direct‐detection flat‐panel device.Results:The 2D MTF derived from physical measurements yielded an average relative precision error of 0.26% for frequencies below the cutoff (2.5 mm−1) and approximate circular symmetry at frequencies below 4 mm−1. While slit analysis generally agreed with the results of edge analysis, the two showed subtle differences at frequencies above 4 mm−1. Slit measurement near 45° revealed radial asymmetry in the MTF resulting from the square pixel aperture (0.2 mm × 0.2 mm), a characteristic which was not necessarily appreciated with the orthogonal 1D MTF measurements. In simulation experiments, both slit‐ and edge‐based measurements resolved the radial asymmetries in the 2D MTF. The average absolute relative accuracy error in the 2D MTF between the DC and cutoff (2.5 mm−1) frequencies was 0.13% with average relative precision error of 0.11%. Other simulation results were similar to those derived from physical data.Conclusions:Overall, the general availability, acceptance, accuracy, and ease of implementation of 1D test devices for MTF assessment make this a valuable technique for 2D MTF estimation.
Complete Genome Sequence of IME13, a Stenotrophomonas maltophilia Bacteriophage with Large Burst Size and Unique Plaque Polymorphism
Authors: Fan Huahao , Huang Yong , Mi Zhiqiang , Yin Xiuyun , Wang Lin , Fan Hang , Zhang Zhiyi , An Xiaoping , Chen Jiankui , Tong Yigang 
Published: September 2012

ABSTRACT

Stenotrophomonas maltophilia
bacteriophage IME13 is a virulent phage with a large burst size, exceeding 3,000, much larger than that of any other stenotrophomonas phage reported before. It showed effective lysis of
Stenotrophomonas maltophilia
. Additionally, the phage IME13 developed at least three obviously different sizes of plaques when a single plaque was picked out and inoculated on a double-layer Luria broth agar plate with its host. Here we announce its complete genome and describe major findings from its annotation.
Genome Sequence of a Novel HIV-1 Circulating Recombinant Form 54_01B from Malaysia
Authors: Ng Kim Tien , Ong Lai Yee , Takebe Yutaka , Kamarulzaman Adeeba , Tee Kok Keng 
Published: September 2012

ABSTRACT

We report here the first novel HIV-1 circulating recombinant form (CRF) 54_01B (CRF54_01B) isolated from three epidemiologically unlinked subjects of different risk groups in Malaysia. These recently sampled recombinants showed a complex genome organization composed of parental subtype B′ and CRF01_AE, with identical recombination breakpoints observed in the
gag
,
pol
, and
vif
genes. Such a discovery highlights the ongoing active generation and spread of intersubtype recombinants involving the subtype B′ and CRF01_AE lineages and indicates the potential of the new CRF in bridging HIV-1 transmission among different risk groups in Southeast Asia.
Functional Redundancy in HIV-1 Viral Particle Assembly
Authors: O'Carroll Ina P. , Crist Rachael M. , Mirro Jane , Harvin Demetria , Soheilian Ferri , Kamata Anne , Nagashima Kunio , Rein Alan 
Published: September 2012

ABSTRACT

Expression of a retroviral Gag protein in mammalian cells leads to the assembly of virus particles.
In vitro
, recombinant Gag proteins are soluble but assemble into virus-like particles (VLPs) upon addition of nucleic acid. We have proposed that Gag undergoes a conformational change when it is at a high local concentration and that this change is an essential prerequisite for particle assembly; perhaps one way that this condition can be fulfilled is by the cooperative binding of Gag molecules to nucleic acid. We have now characterized the assembly in human cells of HIV-1 Gag molecules with a variety of defects, including (i) inability to bind to the plasma membrane, (ii) near-total inability of their capsid domains to engage in dimeric interaction, and (iii) drastically compromised ability to bind RNA. We find that Gag molecules with any one of these defects still retain some ability to assemble into roughly spherical objects with roughly correct radius of curvature. However, combination of any two of the defects completely destroys this capability. The results suggest that these three functions are somewhat redundant with respect to their contribution to particle assembly. We suggest that they are alternative mechanisms for the initial concentration of Gag molecules; under our experimental conditions, any two of the three is sufficient to lead to some semblance of correct assembly.
Functional and evolutionary implications of the cellular composition of the gill epithelium of feeding adults of a freshwater parasitic species of lamprey, Ichthyomyzon unicuspis
Authors: Bartels Helmut , Docker Margaret F. , Fazekas Ursula , Potter Ian C. 
Published: September 2012

This paper provides the first description of the cellular composition of the gill epithelium of feeding adults of Ichthyomyzon unicuspis Hubbs and Trautman, 1937 (silver lamprey), a parasitic species of lamprey that is confined to fresh water. The surface layer of this epithelium consists solely of pavement cells and intercalated mitochondria-rich cells, which are the only cell types found in all freshwater stages of lampreys and thus considered responsible for the uptake of Na+ and Cl– in hypotonic environments. This epithelium does not contain, however, the chloride cells present during the marine parasitic phase of anadromous lamprey species, such as Petromyzon marinus L., 1758 (sea lamprey), and which are responsible for secreting excess Na+ and Cl–. The absence of this cell type in parasitic adults of I. unicuspis also differs from its presence in parasitic adults of landlocked P. marinus and metamorphosing individuals of the exclusively freshwater nonparasitic species Lethenteron appendix (DeKay, 1842) (American brook lamprey), and which thus reflects the retention of a cell type that was crucial for osmoregulation during the marine phase of their respective anadromous parasitic ancestors. The absence of chloride cells in I. unicuspis is consistent with the hypothesis that Ichthyomyzon, which is at or close to the base of the phylogenetic tree for Northern Hemisphere lampreys (Petromyzontidae), evolved in fresh water or has been confined to fresh water for a very long period.
Muscle cellularity, enzyme activities, and nucleic acid content in meagre (Argyrosomus regius)
Authors: Mittakos Ioannis , Ayala M. Dolores , López-Albors Octavio , Grigorakis Kriton , Lenas Dimitrios , Kakali Fotini , Nathanailides Cosmas 
Published: September 2012

Anatomical and biochemical indices of axial muscle growth were monitored in farmed meagre ( Argyrosomus regius (Asso, 1801)), a species with larger ultimate size. Within the first 19 months of a production cycle, body mass exceeded 1300 g. The specific daily growth rate ranged from a winter low of 0.2% to a summer high of 1.3%. Axial muscle RNA:DNA ratio decreased and cytochrome c oxidase levels increased from spring to winter, indicating a metabolic reorganisation of this tissue in response to winter temperature lows. Body mass correlated positively with increased lactate dehydrogenase activity and myofibre size (hypertrophy). The DNA:protein ratio, the myofibre density, and the percentage of small myofibres (0–150 µm2) decreased towards the end of the production cycle. However, small myofibres persisted even after the first 20 months of rearing. Compared with commonly cultivated species in the Mediterranean region, meagre exhibits delayed onset of puberty, larger ultimate size, and growth rate that is supported by the recruitment of new muscle fibres. This is in agreement with the hypothesis of a relationship between ultimate size and muscle growth dynamics.
Radioimmunotherapy of Fibroblast Activation Protein Positive Tumors by Rapidly Internalizing Antibodies
Authors: Fischer Eliane , Chaitanya Krishna , Wüest Thomas , Wadle Andreas , Scott Andrew M. , van den Broek Maries , Schibli Roger , Bauer Stefan , Renner Christoph 
Published: September 2012

Abstract
Purpose: Fibroblast activation protein (FAP) is a serine protease that has emerged as a promising target for cancer therapy, either by direct abrogation of its proinvasive activity or by specific targeting of FAP-expressing cells with cytotoxic immunoconjugates. We aimed to select novel human–mouse cross-reactive antibodies and to test suitability for tumor therapy as radioimmunoconjugates in a preclinical model.
Experimental Design: Human Fab fragments that bind to human and murine FAP were selected from an antibody phage library. Two candidates (ESC11 and ESC14) were engineered into fully human IgG1 antibodies and further characterized. We investigated the intracellular trafficking of ESC11 and ESC14 in live cells by confocal microscopy and analyzed the biodistribution and therapeutic effects of anti-FAP antibodies labeled with the β-emitting radionuclide 177Lu in a melanoma xenograft nude mouse model. Results were compared with vF19, a humanized variant of an anti-FAP antibody that has been previously used in clinical trials.
Results: The two antibodies bound selectively to both human and mouse FAP, with affinities in the low nanomolar range. Binding to FAP-expressing melanoma cells resulted in rapid internalization of FAP-antibody complexes. 177Lu-labeled ESC11 specifically accumulated in melanoma xenografts in vivo, with a higher tumor uptake than ESC14 and vF19. Radioimmunotherapy with 8 MBq 177Lu-labeled anti-FAP antibodies delayed growth of established tumors, whereas 177Lu-ESC11 extended mouse survival more pronounced than 177Lu-ESC14 and 177Lu-vF19.
Conclusion: Our results show the potential of ESC11 and ESC14 as potent radioimmunoconjugates or antibody–drug conjugates for diagnostic and therapeutic use in patients with FAP-expressing tumors. Clin Cancer Res; 18(22); 6208–18. ©2012 AACR.
A Simple New Visualization of Exercise Data Discloses Pathophysiology and Severity of Heart Failure
Authors: Hansen James E. , Sun Xing‐Guo , Stringer William W. 
Published: September 2012

Background
The complexity of cardiopulmonary exercise testing data and their displays tends to make assessment of patients, including those with heart failure, time consuming.

Methods and Results

We postulated that a new single display that uses concurrent values of oxygen uptake / ventilation versus carbon dioxide output / ventilation ratios (

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o
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/

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e

–versus–

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2

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e

), plotted on equal X–Y axes, would better quantify normality and heart failure severity and would clarify pathophysiology. Consecutive

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–versus–

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values from rest to recovery were displayed on X–Y axes for patients with Class II and IV heart failure and for healthy subjects without heart failure. The displays revealed distinctive patterns for each group, reflecting sequential changes in cardiac output, arterial and mixed venous O
2
and CO
2
content differences, and ventilation (

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e

). On the basis of exercise tests of 417 healthy subjects, reference formulas for highest

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and

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, which normally occur during moderate exercise, are presented. Absolute and percent predicted values of highest

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and

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2

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were recorded for 10 individuals from each group: Those of healthy subjects were significantly higher than those of patients with Class II heart failure, and those of patients with Class II heart failure were higher than those of patients with Class IV heart failure. These values differentiated heart failure severity better than peak

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2

, anaerobic threshold, peak oxygen pulse, and

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slopes. Resting

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–versus–

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values were strikingly low for patients with Class IV heart failure, and with exercise, increased minimally or even decreased. With regard to the pathophysiology of heart failure, high

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/

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o

2

values during milder exercise, previously attributed to ventilatory inefficiency, seem to be caused primarily by reduced cardiac output rather than increased

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.

Conclusion

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–versus–

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measurements and displays, extractable from future or existing exercise data, separate the 3 groups (healthy subjects, patients with Class II heart failure, and patients with Class IV heart failure) well and confirm the dominant role of low cardiac output rather than excessive

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e

in heart failure pathophysiology.

(
J Am Heart Assoc
. 2012;1:e001883 doi

:
10.1161/JAHA.112.001883
.)
Impact of Chronic Kidney Disease on Risk of Incident Atrial Fibrillation and Subsequent Survival in Medicare Patients
Authors: Nelson Sarah E. , Shroff Gautam R. , Li Shuling , Herzog Charles A. 
Published: September 2012

Background

Atrial fibrillation (
AF
) and chronic kidney disease (
CKD
) are prevalent in the elderly and are independently associated with increased risk of death. We evaluated risk of incident
AF
with advancing
CKD
and examined the mortality rate associated with
CKD
after incident
AF
in elderly patients.

Methods and Results

This retrospective cohort study used the
M
edicare 5% database. Point‐prevalent
M
edicare enrollees on December 31, 2006, without preexistent
AF
or end‐stage renal disease were followed up for incident
AF
through 2008.
CKD
and
AF
were identified from
International Classification of Diseases, Ninth Revision, Clinical Modification
diagnosis codes. Associations between
CKD
stage and incident
AF
and subsequent risk of death were examined in a Cox proportional‐hazards model. Unadjusted survival after incident
AF
was estimated by the
K
aplan‐
M
eier method.
CKD
was present in 55 962 patients (5.1% of the cohort). Of these, 4952 (8.8%) had
CKD
stages 1 and 2; 19 795 (35.3%), stages 3 to 5; and 31 215 (55.7%), unknown stage. The hazard ratio for incident
AF
in
CKD
stages 3 to 5 was 1.13 (95% confidence interval 1.09 to 1.18). Other stages were not independently associated with incident
AF
. Survival after incident
AF
decreased progressively as
CKD
stage increased (
P
<0.0001). The 1‐year mortality rate for
CKD
stages 3 to 5 with incident
AF
was 35.6%. Adjusted hazard ratios for death after incident
AF
were 1.14 (95% confidence interval 1.00 to 1.30) for
CKD
stages 1 and 2, 1.27 (95% confidence interval 1.20 to 1.35) for
CKD
stages 3 to 5, and 1.29 (95% confidence interval 1.23 to 1.36) for unknown stage.

Conclusions

Advanced
CKD
is associated with increased risk of incident
AF
. In Medicare patients with incident AF, mortality rates are higher for those with advanced CKD than for those without CKD.
Evaluating Cloud Contamination in Clear-Sky MODIS Terra Daytime Land Surface Temperatures Using Ground-Based Meteorology Station Observations
Authors: Williamson Scott N. , Hik David S. , Gamon John A. , Kavanaugh Jeffrey L. , Koh Saewan 
Published: September 2012

Abstract
Environment Canada meteorological station hourly sampled air temperatures Tair at four stations in the southwest Yukon were used to identify cloud contamination in the Moderate Resolution Imaging Spectroradiometer (MODIS) Terra clear-sky daytime land surface temperature (LST) and emissivity daily level-3 global 1-km grid product (MOD11A1, Collection 5) that is not flagged by the MODIS quality algorithm as contaminated. The additional cloud masking used qualitative ground-based sky condition observations, collected at two of the four stations, and coincident MODIS quality flag information. The results indicate that air temperature observed at a variety of discrete spatial locations having different land cover is highly correlated with MODIS LST collected at 1-km grid spacing. Quadratic relationships between LST and air temperature, constrained by ground observations of “clear” sky conditions, show less variability than relationships found under “mainly clear” and “mostly cloudy” sky conditions, and the more clouds observed in the sky coincides with a decreasing y intercept. Analysis of MODIS LST and its associated quality flags show a cold bias (&lt;0°C) in the assignment of the ≤3-K-average LST error, indicating MODIS LST has a maximum average error of ≤2 K over a warm surface (&gt;0°C). Analysis of two observation stations shows that unidentified clouds in MODIS LST are between 13% and 17%, a result that agrees well with previous studies. Analysis of daytime values is important because many processes are dependent on daylight and maximum temperature. The daytime clear-sky LST–Tair relationship observed for the good-quality confirmed cloud-free-sky MODIS LST quality flag can be used to discriminate cloud-contaminated grid cells beyond the standard MODIS cloud mask.