bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gridlock and Innovation in Global Governance: The Partial Transnational Solution
Authors: Hale Thomas , Held David 
Published: May 2012

AbstractThe political institutions that manage transborder problems are changing, offering new avenues around the inadequacies of the existing multilateral order. Several trends in global politics – for example the emergence of new powers, the growing challenge of collective action problems and the complexity of institutions that seek to address them – have made it increasingly difficult to govern transnational problems through multilateral cooperation. Global priorities ranging from climate change, to the Doha trade round, to financial stability are faced with gridlock. But even as ‘traditional’ intergovernmental institutions stall, new kinds of transborder institutions are emerging alongside them. These institutions bring new kinds of actors, public and private, into global governance, and deploy innovative governance ‘technologies’ to make rules and provide public goods. We evaluate these new institutions in the areas of financial and environmental governance. While no panacea, we argue that innovative institutional forms offer a partial solution for the challenges of contemporary interdependence.Policy Implications
Gridlock in many international negotiations and multinational institutions can hobble intergovernmental agreements. New kinds of governance arrangements may help meet some of the governance gaps that multilateral institutions are failing to fill.
Scholars have only begun to catalogue the new forms of global governance that play an increasingly prominent role in world politics.
We must also strive to explain these changes and study their implications. Together, these tasks form an important future research agenda.
Policy makers should familiarize themselves with the full range of transborder governance institutions. These include transgovernmental networks, multistakeholder initiatives, voluntary regulations and innovative tools for adjudication and financing. Such instruments may offer functional benefits over more ‘traditional’ governance arrangements, especially when political factors constrain the latter.
While new governance institutions may represent at best a partial solution to the challenges of transborder cooperation, their adaptability and flexibility suggest a significant contribution nonetheless.
Synergies between Energy Efficiency and Energy Access Policies and Strategies
Authors: Pachauri Shonali , Ürge‐Vorsatz Diana , LaBelle Michael 
Published: May 2012

AbstractPolicies to improve energy access and energy efficiency are often discussed, designed and assessed in isolation from each other. In this paper, we highlight possible synergies in these two domains of policy making by looking specifically at some key household end uses that are the first to be met once improved access has been provided. By building in efficiency considerations at the very inception of activities aimed at improving access, effective energy supply available is potentially increased, the level of energy services that can be provided by the existing capacity and infrastructure or from existing budgets available is also enhanced, and the potential for reducing the cost for those populations for which cost has the highest consideration is also improved. In particular, we recommend two areas where policy maybe leveraged to benefit both access and efficiency objectives, first in the setting of standards, labels and codes and second coupling energy subsidies for access with rebates or grants for more efficient end use devices.
Retrospective study of cytologic features of well‐differentiated hepatocellular carcinoma in dogs
Authors: Masserdotti Carlo , Drigo Michele 
Published: May 2012

BackgroundCytologic diagnosis of hepatocellular carcinoma is possible when hepatocytes have prominent criteria of malignancy, but is problematic when hepatocytes have a relatively normal morphologic appearance.ObjectivesThe aim of this study was to determine the cytologic features of histologically confirmed well‐differentiated hepatocellular carcinomas (WD‐HCC) in dogs to develop reasonable criteria for an accurate diagnosis when obvious criteria of malignancy in hepatocytes are lacking.MethodsSlides of ultrasound‐guided fine‐needle aspirates of 15 histologically confirmed WD‐HCC in dogs were evaluated retrospectively using a scoring system (0–3) established for 33 cytologic features. For comparison, 15 cytologic samples of non‐nodular non‐neoplastic liver were evaluated using the same criteria. Statistical analysis included multiple hypothesis testing using the Benjamini–Hochberg method or false discovery rate control to correct for multiple comparisons.ResultsThe most significant and useful cytologic features in the diagnosis of canine WD‐HCC were dissociation of hepatocytes, acinar or palisading arrangements of neoplastic cells, and the presence of naked nuclei and capillaries, together with mild anisocytosis, anisokaryosis, multinuclearity, and increased N:C ratios.ConclusionsCytologic features of canine WD‐HCC were determined. Further studies are warranted to compare these cytologic criteria among WD‐HCC, hepatomas, and hyperplastic nodules and to examine co‐variance of the 33 cytologic features.
Oral therapy for type 1 diabetes mellitus using a novel immunomodulator, FTY720 (fingolimod), in combination with sitagliptin, a dipeptidyl peptidase‐4 inhibitor, examined in non‐obese diabetic mice
Authors: Tsuji Takumi , Yoshida Yuya , Fujita Tetsuro , Kohno Takeyuki 
Published: May 2012

AbstractAims/Introduction:  The therapeutic effectiveness against type 1 diabetes mellitus of a novel immunomodulator, FTY720 (fingolimod), in combination with sitagliptin, a dipeptidyl peptidase‐4 inhibitor, was examined in the non‐obese diabetic (NOD) mouse model.Materials and Methods:  Female NOD mice that had developed type 1 diabetes mellitus spontaneously were divided into four groups according to which therapy they received: (i) FTY720 (0.1 mg/kg, orally, six times a week) plus sitagliptin (1 mg/kg, orally, six times a week); (ii) FTY720 (0.1 mg/kg, orally, six times a week); (iii) sitagliptin (1 mg/kg, orally, six times a week); and (iv) the vehicle (water) alone. Therapeutic efficacy was evaluated in terms of survival rate, ratio of insulin‐positive β‐cells/total islet area, extent of islet inflammation (insulitis score) and blood‐glucose level.Results:  The therapeutic administration of FTY720 plus sitagliptin significantly improved survival (83% at 70 days after onset, P < 0.05) compared with sitagliptin alone (17%) or vehicle alone (0%). The fasting‐blood glucose level, the ratio of insulin‐positive β‐cells/total islet area and the insulitis score in the surviving mice, which had been treated with FTY720 plus sitagliptin, were improved to the normal levels as in age‐matched NOD mice with normoglycemia.Conclusions:  Combination therapy with FTY720 and sitagliptin is a promising candidate for type 1 diabetes mellitus treatment, and might allow the treatment of type 1 diabetes mellitus with only oral agents. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00218.x, 2012)
Dipeptidyl‐peptidase IV inhibitor is effective in patients with type 2 diabetes with high serum eicosapentaenoic acid concentrations
Authors: Senmaru Takafumi , Fukui Michiaki , Kobayashi Kanae , Iwase Hiroya , Inada Shinobu , Okada Hiroshi , Asano Mai , Yamazaki Masahiro , Hasegawa Goji , Nakamura Naoto , Iwasaki Masahiro , Yabe Daisuke , Kurose Takeshi , Seino Yutaka 
Published: May 2012

AbstractAims/Introduction:  Eicosapentaenoic acid (EPA) stimulates glucagon‐like peptide‐1 (GLP‐1) secretion in mice. We investigated the relationship between serum EPA concentrations and the efficacy of dipeptidyl‐peptidase IV (DPP‐4) inhibitor in patients with type 2 diabetes.Materials and Methods:  Serum EPA concentrations were measured in 62 consecutive patients with type 2 diabetes who were newly given DPP‐4 inhibitor as a monotherapy or as an add‐on therapy to oral hypoglycemic agents. The dosage of oral hypoglycemic agents was maintained during the observation period. After 24 weeks of treatment with DPP‐4 inhibitor, we evaluated the relationships between a decrease in hemoglobin A1c from baseline and serum EPA concentrations, as well as age, sex, body mass index (BMI), hemoglobin A1c at baseline and usage of antidiabetic concomitant drugs.Results:  Hemoglobin A1c was significantly decreased from 8.1 ± 1.1% to 7.2 ± 1.0% by DPP‐4 inhibitor. A decrease in hemoglobin A1c correlated with BMI (r = −0.396, P = 0.0013), age (r = 0.275, P = 0.0032), hemoglobin A1c at baseline (r = 0.490, P < 0.0001) and log EPA (r = 0.285, P = 0.0246). Multiple regression analysis showed that BMI (β = −0.419, P = 0.0002), hemoglobin A1c at baseline (β = 0.579, P < 0.0001) and log EPA (β = 0.220, P = 0.0228) were independent determinants of decrease in hemoglobin A1c.Conclusions:  DPP‐4 inhibitor is effective in patients with type 2 diabetes with high serum EPA concentrations. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00220.x	, 2012)
Control of breathing and blood pressure by parafacial neurons in conscious rats
Authors: Takakura Ana C. , Moreira Thiago S. , De Paula Patrícia M. , Menani José V. , Colombari Eduardo 
Published: May 2012

New Findings
What is the central question of this study?The main purpose of the present manuscript was to investigate the cardiorespiratory responses to hypoxia or hypercapnia in conscious rats submitted to neuronal blockade of the parafacial region. We clearly showed that the integrity of parafacial region is important for the respiratory responses elicited by peripheral and central chemoreflex activation in freely behavior rats.
What is the main finding and its importance?Since the parafacial region is part of the respiratory rhythm generator, they are essential for postnatal survival, which is probably due to their contribution to chemoreception in conscious rats.
The retrotrapezoid nucleus (RTN), located in the parafacial region, contains glutamatergic neurons that express the transcriptor factor Phox2b and that are suggested to be central respiratory chemoreceptors. Studies in anaesthetized animals or in vitro have suggested that RTN neurons are important in the control of breathing by influencing respiratory rate, inspiratory amplitude and active expiration. However, the contribution of these neurons to cardiorespiratory control in conscious rats is not clear. Male Holtzman rats (280–300 g, n= 6–8) with bilateral stainless‐steel cannulae implanted into the RTN were used. In conscious rats, the microinjection of the ionotropic glutamatergic agonist NMDA (5 pmol in 50 nl) into the RTN increased respiratory frequency (by 42%), tidal volume (by 21%), ventilation (by 68%), peak expiratory flow (by 24%) and mean arterial pressure (MAP, increased by 16 ± 4, versus saline, 3 ± 2 mmHg). Bilateral inhibition of the RTN neurons with the GABAA agonist muscimol (100 pmol in 50 nl) reduced resting ventilation (52 ± 34, versus saline, 250 ± 56 ml min−1 kg−1 with absolute values) and attenuated the respiratory response to hypercapnia and hypoxia. Muscimol injected into the RTN slightly reduced resting MAP (decreased by 13 ± 7, versus saline, increased by 3 ± 2 mmHg), without changing the effects of hypercapnia or hypoxia on MAP and heart rate. The results suggest that RTN neurons activate facilitatory mechanisms important to the control of ventilation in resting, hypoxic or hypercapnic conditions in conscious rats.
Online database of clinical MR and ultrasound images of brain tumors
Authors: Mercier Laurence , Del Maestro Rolando F. , Petrecca Kevin , Araujo David , Haegelen Claire , Collins D. Louis 
Published: May 2012

Purpose:One of the important challenges in the field of medical imaging is finding real clinical images with which to validate new image processing algorithms. This is particularly true for tracked 3D ultrasound images of the brain.Methods:In 2010, pre‐ and postoperative magnetic resonance and intraoperative ultrasound images were acquired from brain tumor patients involved in the authors' imaging study at the Montreal Neurological Institute.Results:These data are available online at the Montreal Neurological Institute's Brain Images of Tumors for Evaluation database, termed here the MNI BITE database. It contains ultrasound and magnetic resonance images from 14 patients. Each patient underwent a preoperative and a postoperative T1‐weighted magnetic resonance scan with gadolinium enhancement, and multiple intraoperative B‐mode images were acquired before and after resection. Corresponding features were manually selected in some image pairs for validation. All images are in MINC format, the file format used at the authors' institute for image processing. The MINC tools are available for free download at packages.bic.mni.mcgill.ca.Conclusions:This is the first online database of its kind. These images can be used by image processing scientists as well as clinicians wishing to compare findings from magnetic resonance and ultrasound imaging.
Development of an automated region of interest selection method for 3D surface monitoring of head motion
Authors: Kang H. J. , Grelewicz Z. , Wiersma R. D. 
Published: May 2012

Purpose:To simplify the often complex and user‐dependent manual region of interest (ROI) selection process for head motion monitoring, an automatic ROI selection method was developed.Methods:The automatic ROI selection algorithm calculated the displacements and velocities of 3D surface points between a temporally correlated 3D image series and a reference image. Only facial surfaces satisfying certain spatial and temporal criteria were selected. The algorithm was tested on five healthy volunteers instructed to perform different types of facial movements for a total of 27 real‐time image sets (40–120 images for each image set).Results:The algorithm detected and excluded surface areas affected by different types of local facial movements that were independent of actual net head motion. Eye, eyebrow, and mandible motion were most commonly detected as being independent of head motion and were excluded from the final ROI. For 3D images taken with substantial facial or whole head motion, either most of the facial area was excluded or only small areas with random patterns were included in the final ROI. Surface image registration using iterative closest point (ICP) methods showed more stable real‐time head tracking using the automatically selected ROI than manual user defined ROIs.Conclusions:The automatic selection method successfully found ROIs stable over time for tracking head motion by excluding locally varying facial motions. By automating the ROI selection process, it is feasible that the time and complexity of current ROI definition can be reduced, together with user‐dependent registration errors.
Voxel‐wise uncertainty in CT substitute derived from MRI
Authors: Johansson Adam , Karlsson Mikael , Yu Jun , Asklund Thomas , Nyholm Tufve 
Published: May 2012

Purpose:In an earlier work, we demonstrated that substitutes for CT images can be derived from MR images using ultrashort echo time (UTE) sequences, conventional T2 weighted sequences, and Gaussian mixture regression (GMR). In this study, we extend this work by analyzing the uncertainties associated with the GMR model and the information contributions from the individual imaging sequences.Methods:An analytical expression for the voxel‐wise conditional expected absolute deviation (EAD) in substitute CT (s‐CT) images was derived. The expression depends only on MR images and can thus be calculated along with each s‐CT image. The uncertainty measure was evaluated by comparing the EAD to the true mean absolute prediction deviation (MAPD) between the s‐CT and CT images for 14 patients. Further, the influence of the different MR images included in the GMR model on the generated s‐CTs was investigated by removing one or more images and evaluating the MAPD for a spectrum of predicted radiological densities.Results:The largest EAD was predicted at air‐soft tissue and bone‐soft tissue interfaces. The EAD agreed with the MAPD in both these regions and in regions with lower EADs, such as the brain. Two of the MR images included in the GMR model were found to be mutually redundant for the purpose of s‐CT generation.Conclusions:The presented uncertainty estimation method accurately predicts the voxel‐wise MAPD in s‐CT images. Also, the non‐UTE sequence previously used in the model was found to be redundant.
Fur-Regulated Iron Uptake System of Edwardsiella ictaluri and Its Influence on Pathogenesis and Immunogenicity in the Catfish Host
Authors: Santander Javier , Golden Greg , Wanda Soo-Young , Curtiss Roy 
Published: May 2012

ABSTRACT

The ability of bacterial pathogens to take up iron from the host during infection is necessary for their multiplication within the host. However, host high-affinity iron binding proteins limit levels of free iron in fluids and tissues. To overcome this deficiency of iron during infection, bacterial pathogens have developed iron uptake systems that are upregulated in the absence of iron, typically tightly controlled by the ferric uptake regulator (Fur) protein. The iron uptake system of
Edwardsiella ictaluri
, a host-restricted pathogen of channel catfish (
Ictalurus punctatus
) and the main pathogen of this fish in aquaculture, is unknown. Here we describe the
E. ictaluri
Fur protein, the iron uptake machinery controlled by Fur, and the effects of
fur
gene deletion on virulence and immunogenicity in the fish host. Analysis of the
E. ictaluri
Fur protein shows that it lacks the N-terminal region found in the majority of pathogen-encoded Fur proteins. However, it is fully functional in regulated genes encoding iron uptake proteins.
E. ictaluri
grown under iron-limited conditions upregulates an outer membrane protein (HemR) that shows heme-hemoglobin transport activity and is tightly regulated by Fur.
In vivo
studies showed that an
E. ictaluri
Δ
fur
mutant is attenuated and immune protective in zebrafish (
Danio rerio
) and catfish (
Ictalurus punctatus
), triggering systemic immunity. We conclude that an
E. ictaluri
Δ
fur
mutant could be an effective component of an immersion-oral vaccine for the catfish industry.
Design of Meningococcal Factor H Binding Protein Mutant Vaccines That Do Not Bind Human Complement Factor H
Authors: Pajon Rolando , Beernink Peter T. , Granoff Dan M. 
Published: May 2012

ABSTRACT
Meningococcal factor H binding protein (fHbp) is a human species-specific ligand for the complement regulator, factor H (fH). In recent studies, fHbp vaccines in which arginine at position 41 was replaced by serine (R41S) had impaired fH binding. The mutant vaccines elicited bactericidal responses in human fH transgenic mice superior to those elicited by control fHbp vaccines that bound human fH. Based on sequence similarity, fHbp has been classified into three variant groups. Here we report that although R41 is present in fHbp from variant groups 1 and 2, the R41S substitution eliminated fH binding only in variant group 1 proteins. To identify mutants in variant group 2 with impaired fH binding, we generated fHbp structural models and predicted 63 residues influencing fH binding. From these, we created 11 mutants with one or two amino acid substitutions in a variant group 2 protein and identified six that decreased fH binding. Three of these six mutants retained conformational epitopes recognized by all six anti-fHbp monoclonal antibodies (MAbs) tested and elicited serum complement-mediated bactericidal antibody titers in wild-type mice that were not significantly different from those obtained with the control vaccine. Thus, fHbp amino acid residues that affect human fH binding differ across variant groups. This result suggests that fHbp sequence variation induced by immune selection also affects fH binding motifs via coevolution. The three new fHbp mutants from variant group 2, which do not bind human fH, retained important epitopes for eliciting bactericidal antibodies and may be promising vaccine candidates.
The
Clostridium difficile spo0A
Gene Is a Persistence and Transmission Factor
Authors: Deakin Laura J. , Clare Simon , Fagan Robert P. , Dawson Lisa F. , Pickard Derek J. , West Michael R. , Wren Brendan W. , Fairweather Neil F. , Dougan Gordon , Lawley Trevor D. 
Published: May 2012

ABSTRACT

Clostridium difficile
is a major cause of chronic antibiotic-associated diarrhea and a significant health care-associated pathogen that forms highly resistant and infectious spores. Spo0A is a highly conserved transcriptional regulator that plays a key role in initiating sporulation in
Bacillus
and
Clostridium
species. Here, we use a murine model to study the role of the
C. difficile spo0A
gene during infection and transmission. We demonstrate that
C. difficile spo0A
mutant derivatives can cause intestinal disease but are unable to persist within and effectively transmit between mice. Thus, the
C. difficile
Spo0A protein plays a key role in persistent infection, including recurrence and host-to-host transmission in mice.
Role of Mouse Peptidoglycan Recognition Protein PGLYRP2 in the Innate Immune Response to Salmonella enterica Serovar Typhimurium Infection
In Vivo
Authors: Lee Jooeun , Geddes Kaoru , Streutker Catherine , Philpott Dana J. , Girardin Stephen E. 
Published: May 2012

ABSTRACT

Peptidoglycan recognition proteins (PGRPs) are a family of innate pattern recognition molecules that bind bacterial peptidoglycan. While the role of PGRPs in
Drosophila
innate immunity has been extensively studied, how the four mammalian PGRP proteins (PGLYRP1 to PGLYRP4) contribute to host defense against bacterial pathogens
in vivo
remains poorly understood. PGLYRP1, PGLYRP3, and PGLYRP4 are directly bactericidal
in vitro
, whereas PGLYRP2 is an
N
-acetylmuramyl-
l
-alanine amidase that cleaves peptidoglycan between the sugar backbone and the peptide stem. Because PGLYRP2 cleaves muramyl peptides detected by host peptidoglycan sensors Nod1 and Nod2, we speculated that PGLYRP2 may act as a modifier of Nod1/Nod2-dependent innate immune responses. We investigated the role of PGLYRP2 in
Salmonella enterica
serovar Typhimurium-induced colitis, which is regulated by Nod1/Nod2 through the induction of an early Th17 response. PGLYRP2 did not contribute to expression of Th17-associated cytokines, interleukin-22 (IL-22)-dependent antimicrobial proteins, or inflammatory cytokines. However, we found that
Pglyrp2
-deficient mice displayed significantly enhanced inflammation in the cecum at 72 h postinfection, reflected by increased polymorphonuclear leukocyte (PMN) infiltration and goblet cell depletion.
Pglyrp2
expression was also induced in the cecum of
Salmonella
-infected mice, and expression of green fluorescent protein under control of the
Pglyrp2
promoter was increased in discrete populations of intraepithelial lymphocytes. Lastly,
Nod2
−/−
Pglyrp2
−/−
mice displayed increased susceptibility to infection at 24 h postinfection compared to
Pglyrp2
−/−
mice, which correlated with increased PMN infiltration and submucosal edema. Thus, PGLYRP2 plays a protective role
in vivo
in the control of
S
. Typhimurium infection through a Nod1/Nod2-independent mechanism.