bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resisting democratic backsliding: An essay on Weimar, self-enforcing constitutions, and the Frankfurt School
Authors: CHOUDHRY SUJIT 
Published: March 2018

Abstract:What, if anything, can constitutions do to resist democratic backsliding? The collapse of the Weimar Republic has led scholars of comparative politics to conclude that constitutional forms and institutions can do little to resist the breakdown of democracy and the rise of autocracy. This paper offers a constitutionalist response. The outlines of that answer can be found in decades-old policy documents produced by a set of German émigré scholars during and in the immediate aftermath of the Second World War: Franz Neumann, Herbert Marcuse, and Otto Kirchheimer. The secret reports root constitutional stability in the creation of a framework for bounded partisan pluralist contestation among political parties that track the principal social and economic cleavages, and that is rooted within, and does not seek to overthrow, the underlying political economy. Second, the secret reports highlight the importance of constitutional design in creating a constitutional infrastructure for bounded pluralistic political contestation, especially with respect to the role of political parties. Third, the secret reports suggest a counter-narrative of the German Basic Law as creating a framework for political contestation that reinforces constitutional stability instead of undermining it.
Molecular imaging of glycan chains couples cell-wall polysaccharide architecture to bacterial cell morphology
Authors: Turner Robert D. , Mesnage Stéphane , Hobbs Jamie K. , Foster Simon J. 
Published: March 2018

AbstractBiopolymer composite cell walls maintain cell shape and resist forces in plants, fungi and bacteria. Peptidoglycan, a crucial antibiotic target and immunomodulator, performs this role in bacteria. The textbook structural model of peptidoglycan is a highly ordered, crystalline material. Here we use atomic force microscopy (AFM) to image individual glycan chains in peptidoglycan from Escherichia coli in unprecedented detail. We quantify and map the extent to which chains are oriented in a similar direction (orientational order), showing it is much less ordered than previously depicted. Combining AFM with size exclusion chromatography, we reveal glycan chains up to 200 nm long. We show that altered cell shape is associated with substantial changes in peptidoglycan biophysical properties. Glycans from E. coli in its normal rod shape are long and circumferentially oriented, but when a spheroid shape is induced (chemically or genetically) glycans become short and disordered.
A complex epistatic network limits the mutational reversibility in the influenza hemagglutinin receptor-binding site
Authors: Wu Nicholas C. , Thompson Andrew J. , Xie Jia , Lin Chih-Wei , Nycholat Corwin M. , Zhu Xueyong , Lerner Richard A. , Paulson James C. , Wilson Ian A. 
Published: March 2018

AbstractThe hemagglutinin (HA) receptor-binding site (RBS) in human influenza A viruses is critical for attachment to host cells, which imposes a functional constraint on its natural evolution. On the other hand, being part of the major antigenic sites, the HA RBS of human H3N2 viruses needs to constantly mutate to evade the immune system. From large-scale mutagenesis experiments, we here show that several of the natural RBS substitutions become integrated into an extensive epistatic network that prevents substitution reversion. X-ray structural analysis reveals the mechanistic consequences as well as changes in the mode of receptor binding. Further studies are necessary to elucidate whether such entrenchment limits future options for immune escape or adversely affect long-term viral fitness.
Asymptotic theory of gravity modes in rotating stars
Authors: Prat V. , Mathis S. , Augustson K. , Lignières F. , Ballot J. , Alvan L. , Brun A. S. 
Published: March 2018

Context. Differential rotation has a strong influence on stellar internal dynamics and evolution, notably by triggering hydrodynamical instabilities, by interacting with the magnetic field, and more generally by inducing transport of angular momentum and chemical elements. Moreover, it modifies the way waves propagate in stellar interiors and thus the frequency spectrum of these waves, the regions they probe, and the transport they generate.
Aims. We investigate the impact of a general differential rotation (both in radius and latitude) on the propagation of axisymmetric gravito-inertial waves.
Methods. We use a small-wavelength approximation to obtain a local dispersion relation for these waves. We then describe the propagation of waves thanks to a ray model that follows a Hamiltonian formalism. Finally, we numerically probe the properties of these gravito-inertial rays for different regimes of radial and latitudinal differential rotation.
Results. We derive a local dispersion relation that includes the effect of a general differential rotation. Subsequently, considering a polytropic stellar model, we observe that differential rotation allows for a large variety of resonant cavities that can be probed by gravito-inertial waves. We identify that for some regimes of frequency and differential rotation, the properties of gravito-inertial rays are similar to those found in the uniformly rotating case. Furthermore, we also find new regimes specific to differential rotation, where the dynamics of rays is chaotic.
Conclusions. As a consequence, we expect modes to follow the same trend. Some parts of oscillation spectra corresponding to regimes similar to those of the uniformly rotating case would exhibit regular patterns, while parts corresponding to the new regimes would be mostly constituted of chaotic modes with a spectrum rather characterised by a generic statistical distribution.
Current paediatric orthopaedic practice in hereditary multiple osteochondromas of the forearm: a systematic review
Authors: EL-Sobky Tamer A. , Samir Shady , Atiyya Ahmed Naeem , Mahmoud Shady , Aly Ahmad S. , Soliman Ramy 
Published: March 2018

Introduction: This systematic review aims to answer three research questions concerning the management of hereditary multiple osteochondromas of forearm in children: What is the best available evidence for the currently employed surgical procedures? What patient characteristics are associated with better prognosis? What disease characteristics are associated with better prognosis?
Methods: We searched the literature using three major databases with no publication date restrictions. To enhance search sensitivity and maintain precision we used keywords/subject terms correlating with patient population, problem and interventions. We used strict inclusion/exclusion criteria to improve validity evidence.
Results: The search process yielded 34 eligible studies with a total of 282 patients (315 forearms). We comprehensively analysed study and patient demographics and interventions and outcomes. Eleven studies (32%) had a long-term follow-up and 31 studies (91%) were retrospective. Of the total number of forearms, ulnar lengthening +/− associated procedures was used in 210 forearms (66.7%), isolated osteochondroma excision in 65 forearms (20.6%) and isolated distal radius hemiepiphysiodesis in 15 forearms (4.7%) among others.
Discussion: Ulnar lengthening can restore radiologic anatomy, improve appearance and to a lesser extent objective clinical parameters like joint range of motion on the short/intermediate term. Isolated osteochondroma excision can relief pain and satisfy cosmetic concerns occasionally. There is poor evidence to suggest that surgery improves quality of life or function. Predictors of surgical success in regard to patient and disease characteristics remain elusive. Natural history and prospective randomized control studies where the control group receives no treatment should be rethought. They have the potential for bias control and identification of the ideal surgical candidate. The complex interplay between the confounding variables has undermined the capability of most studies to provide well-grounded evidence to support and generalize their conclusions. Valid quality of life scales should supplement objective outcome measures.
Significance of BRAF V600E Mutation and Cytomorphological Features for the Optimization of Papillary Thyroid Cancer Diagnostics in Cytologically Indeterminate Thyroid Nodules
Authors: Beiša Augustas , Kvietkauskas Mindaugas , Beiša Virgilijus , Stoškus Mindaugas , Ostanevičiūtė Elvyra , Jasiūnas Eugenijus , Griškevičius Laimonas , Šeinin Dmitrij , Šileikytė Auksė , Strupas Kęstutis 
Published: March 2018

Abstract
Background Ultrasound guided fine needle aspiration biopsy with cytologic analysis is an initial step in diagnostic of thyroid nodules. Unfortunately, up to 30% of biopsies are indeterminate and diagnostic surgery is required. The aim of this study was to estimate the diagnostic value of BRAF V600E mutation status combined with cytomorphological features for diagnosis of papillary thyroid cancer (PTC) in cytologically indeterminate thyroid nodules.
Methods A prospective study analyzed patients who had ultrasound suspicious thyroid nodules, underwent fine needle aspiration and cytological examination, and were classified according to the Bethesda system. Patients from indeterminate diagnostic categories were examined for BRAF V600E mutation and 22 cytomorphological features, and underwent thyroid surgery. A binary logistic regression model was used to evaluate the diagnostic utility.
Results A total of 219 patients met study criteria. After histological examination, 77 (35.2%) patients were diagnosed with PTC and 142 (64.8%) with benign nodular thyroid disease. According to logistic regression model, significant features for PTC diagnosis were: liquid colloid consistency, papillary structures, eosinophilic colloid bodies, and BRAF V600E mutation. Risk groups classified by this model have sensitivity of 80.5% (95% CI: 69.9 to 88.7), specificity of 99.3% (95% CI: 96.1 to 100), positive predictive value of 98.4% (95% CI: 89.8 to 99.8), negative predictive value of 90.4% (95% CI: 85.7 to 93.7), and accuracy of 92.7% (95% CI: 88.4 to 95.8) for PTC diagnosis.
Conclusions Evaluation of BRAF V600E mutation status combined with cytomorphological features for diagnosis of PTC in cytologically indeterminate thyroid nodules can significantly improve diagnostic accuracy and reduce the number of diagnostic operations (calculator available at www.ptc-calc.we2host.lt).
Cerebral Salt-Wasting Syndrome in Subarachnoid Hemorrhage: A Primer for Interventional Neuroradiologists
Authors: Rajendran Adhithyan , Kannath Santhosh , Vimala Smitha , Rajan Jayadevan 
Published: March 2018

AbstractHyponatremia due to several causes could occur in subarachnoid hemorrhage (SAH), and cerebral salt-wasting syndrome (CSWS) is one of the frequent causes of hyponatremia in this clinical setting. Appropriate clinical diagnosis is important as the treatment is entirely different in various etiologies. In the present report, the authors highlight various clinical and biochemical parameters that help in the recognition of CSWS and discuss its clinical management using a clinical prototype. As neurointerventional radiologists are becoming increasingly involved in the management of intra-cranial aneurysms and SAH, awareness of this entity and its appropriate management is essential in providing optimal care to these patients.
Effects of Second and Third Generation Oral Contraceptives and their Respective Progestagens on the Coagulation System in the Absence or Presence of the Factor V Leiden Mutation
Authors: Kemmeren J. M. , Meijers J. C. M. , Bouma B. N. , Grobbee D. E. , Algra A. 
Published: March 2018

SummaryCompared to second generation, the use of third generation oral contraceptives has been associated with an increased risk of venous thrombosis especially in women with the factor V Leiden mutation. To find an explanation for these risk differences we investigated the effects of desogestrel- and levonorgestrel-containing oral contraceptives as well as their progestagens separately on the coagulation system in the absence or presence of the factor V Leiden mutation.In a single center, double blind trial, 51 women without and 35 women with the factor V Leiden mutation were randomized to either a second generation (30 µg ethinylestradiol/150 µg levonorgestrel) or a third generation (30 µg ethinylestradiol/150 µg desogestrel) oral contraceptive. After two cycles of use and a wash-out period of 2 menstrual cycles, the participants received the corresponding progestagen-only preparation containing 150 µg levonorgestrel or 150 µg desogestrel. In plasmas of the participating women fragment 1+2, factor V, VII, VIII, IX, X and XI were determined.Both combined oral contraceptives induced a decrease in factor V, whereas the levels of all other coagulant parameters increased. However, in women without the factor V Leiden mutation the effects of desogestrel-containing preparations were significantly different compared to levonorgestrel-containing oral contraceptives for factor V (−8.0; 95% Cl −13.4 to −2.6), factor VIl (26.8; 95% Cl 15.5 to 38.0) and factor IX (−9.6; 95% Cl −16.2 to −3.2). When these women used progestagen-only pills, a differential effect between desogestrel and levonorgestrel was only found for factor IX (−6.5; 95% CI –11.4 to –1.5).In carriers of the factor V Leiden mutation desogestrel-containing oral contraceptives induced more pronounced changes in factor V (−14.2; 95% CI −22.4 to −6.0) and factor VII (36.1; 95% CI 19.7 to 52.6) compared to levonorgestrel-containing oral contraceptives. Comparing desogestrel- and levonorgestrel-only, only for factor V a differential effect was found in these women (−9.5;95% CI –18.3 to –0.6).It appears that desogestrel-containing oral contraceptives have a more pronounced effect on the coagulation system than levonorgestrelcontaining oral contraceptives which may be explained by a less effective compensation of the thrombotic effect of ethinylestradiol by desogestrel.
Topically Administered Macromolecular Heparin Proteoglycans Inhibit Thrombus Growth in Microvascular Anastomoses
Authors: Olsson Eija , Asko-Seljavaara Sirpa , Lassila Riitta 
Published: March 2018

SummaryPreviously, during blood perfusion over collagen-coated surfaces; soluble or immobilized heparin proteoglycans (HEP-PG) have been shown to block thrombus growth. Our aim was to study the antithrombotic effect of locally applied unfractionated heparin (UFH, 1 mg/ml), or rat mast cell-derived HEP-PG (MW 750 kD, 10 µg/ml) compared with saline in early (10 min) and late (3 days) thrombus formation upon anastomosis of rat common femoral arteries. In both semiquantitative scanning electron microscopy (SEM) and quantitative platelet Indium 111 -labeling HEP-PG inhibited thrombus growth in comparison with saline. At 10 min, the extent of thrombosis (scale 1-4) in SEM followed the order: saline (3.2+/-0.8) > UFH (2.8+/-1.0) > HEP-PG (1.8+/-0.8), and also Indium111-positive platelets (106) accumulated on the anastomosed vessel in the same order 14.2 +/-7.2, 10.3 +/-5.0, and 7.7 +/-3.1 (saline vs. HEP-PG, p = 0.03 and 0.05, respectively). At 3 days all HEP-PGtreated vessels remained patent with only small mural thrombi, whereas 2/7 saline and 1/7 UFH-treated anastomoses occluded and showed more thrombosis overall. We conclude that locally administered HEPPG inhibit arterial thrombus growth in anastomosed small-sized arteries and could prevent thrombotic complications in (micro)vascular surgery and arteriovenous shunts.
Non-Inversion Factor VIII Mutations in 80 Hemophilia A Families Including 24 with Alloimmune Responses
Authors: Liu Miao-Liang , Nakaya Shelley , Thompson Arthur 
Published: March 2018

SummaryHeteroduplex screening identified 74 small mutations in the factor VIII genes of 72 families with hemophilia A. In addition, patients from 3 families with high titer inhibitors had partial gene deletions and 5 unrelated families that were negative for heteroduplex formation had a mutation on direct sequencing. The latter had mild hemophilia A with an inhibitor, and sequencing their exon 23 fragments found a transition predicting a recurrent Arg2150 to His. Of 69 distinct mutations (including the 3 partial gene deletions), 47 are novel. Of small mutations, 51 were missense (one possibly a normal variant and two that could also alter splicing) at 39 sites, 13 were small deletions or insertions (3 inframe and one a normal variant in an intron), 13 were nonsense at 12 sites and 2 altered intron splice junctions. In 24 families, at least one affected member had evidence for an alloimmune response to factor VIII; of these, 11 were associated with missense mutations. In 14 families, de novo origin was demonstrated.
Influence of t-PA and u-PA on Adipose Tissue Development in a Murine Model of Diet-Induced Obesity
Authors: Morange P.E. , Bastelica D. , Bonzi M.F. , Van Hoef B. , Collen D. , Juhan-Vague I. , Lijnen H.R. 
Published: March 2018

SummaryTo investigate the potential role of tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA) in development of adipose tissue, we have used a nutritionally induced obesity model in t-PA (t-PA−/−) and u-PA (u-PA−/−) deficient mice. Five week old male wild-type (WT), t-PA−/− or u-PA−/− mice (n = 9 to 16) were fed a high fat diet (HFD, 42% fat). After 16 weeks of HFD, the body weight of t-PA−/− mice was significantly higher than that of WT mice (48 ± 1.1 g vs. 39 ± 2.2 g, p = 0.004). The total weight of the isolated subcutaneous (sc) fat deposit was higher in t-PA−/− than in WT mice (2.4 ± 0.22 g vs. 1.2 ± 0.29 g, p = 0.002), accompanied with higher adipocyte diameters (80 ± 1.7 µm vs. 61 ± 4.7 µm, p < 0.01). These differences were not observed in the intra-abdominal fat deposit. The number of stroma cells in both adipose tissue territories was increased in t-PA−/− as compared to WT mice (2.0 ± 0.13 vs. 1.5 ± 0.10 p = 0.02 and 3.0 ± 0.17 vs 1.6 ± 0.17, p = 0.0001, stroma cells/ adipocytes in sc and intra-abdominal tissue, respectively), partly as a result of an increased number of endothelial cells (192 ± 9 vs. 154 ± 18 p = 0.06 and 108 ± 13 vs. 69 ± 8 p = 0.04 CD31 stained/adipocyte area). In contrast the weight gain and adipose tissue development in u-PA−/− mice was not different from that in WT mice. These data suggest that t-PA but not u-PA plays a role in adipose tissue development.
Differential Effects of Moderate or Heavy Alcohol Consumption on Circulating Adhesion Molecule Levels
Authors: Badía E. , Nicolás J. M. , Fernández-Solá J. , Antúnez E. , Urbano-Márquez A. , Estruch R. , Sacanella E. 
Published: March 2018

SummaryEpidemiological studies suggest that moderate but not heavy alcohol consumption provides protection against coronary heart disease. We assessed the relationship between alcohol consumption and serum levels of adhesion molecules involved in the pathogenesis of early atherosclerosis. One-hundred apparently healthy men with similar cardiovascular risk factors were divided into four groups according to ethanol intake. Moderate drinkers (20-40 g/day) showed lower serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels than abstainers (p <0.05; both), as well as lower serum ICAM-1, VCAM-1 and E-selectin levels than heavy drinkers (p = 0.01; all). The latter also showed higher serum ICAM-1 and E-selectin levels than abstainers (p <0.001; both). We conclude that moderate drinkers show a significant reduction of soluble endothelial adhesion molecule levels compared to abstainers and heavy drinkers, that may contribute to the protective effect of moderate alcohol consumption against atherosclerosis.
Altering Heparin Cofactor II at VAL439 (P6) either Impairs Inhibition of Thrombin or Confers Elastase Resistance
Authors: Cunningham Michael , Bhakta Varsha , Sheffield William 
Published: March 2018

SummaryHeparin cofactor II (HCII) is plasma glycoprotein and thrombin inhibitor of the serpin type previously shown to inhibit thrombin in the absence of its N-terminal 74 amino acids, and to be cleaved by neutrophil elastase (NE) at two sites: I66-F67 and V439-G440, the P6-P5 bond of the reactive center loop. We examined the contribution of Val439 to the reaction of HCII with thrombin and NE. Hexahistidine-tagged HCII proteins lacking residues 1-66 (H6Δ66HCII) containing either the wild-type Val 439 or one of six substitutions were expressed in E. coli. The rates of heparin-catalyzed thrombin inhibition of the V439L, C, or R variants were reduced at least 80-fold compared to wild-type H6Δ66HCII, while those of the F, S, or W variants were largely unchanged. Following controlled exposure to NE in the presence of heparin, these latter variants retained 3.5to 4.5-fold more residual anti-thrombin activity than wild-type H6Δ66HCII treated in the same manner. This resistance arose due to deflection of NE attack from V439-G440 to secondary sites. The F, S, or W V439 variants exhibited a similar or greater degree of NE resistance when re-expressed as full-length hexahistidine-tagged HCII proteins, suggesting that the I66-F67 NE site is not well recognized in non-glycosylated HCII. Of these full-length variants, the V439F was the most active, exhibiting only a 2-fold reduction in its heparin-catalyzed rate of thrombin inhibition. HCII can therefore be made NE-resistant without severely compromising its capacity to inhibit thrombin.
Evidence that the Platelet Integrin αIIbβ3 Is Regulated by the Integrin-Linked Kinase, ILK, in a PI3-Kinase Dependent Pathway
Authors: Noury Malia , Nurden Alan , Pasquet Jean-Max 
Published: March 2018

SummaryPlatelet aggregation is mediated by the integrin αIIbβ3 which is activated by intracellular signals during platelet activation. We have attempted to determine if ILK (“Integrin-Linked Kinase”) is involved in the regulation of αIIbβ3 function. ILK co-immunoprecipitated with β3 in stimulated platelets. Using confocal microscopy, ILK was detected in the cytoplasm of resting platelets. ADP or PMA stimulation led to its translocation to the plasma membrane. In parallel, there was a transient increase in ILK kinase activity, association with and phosphorylation of β3. Inhibition of PI3-kinase by two unrelated inhibitors (wortmannin and LY294002) prevented ILK-related functions. However, it did not prevent the conformational change in αIIbβ3 (shown by PAC-1 binding), although integrin affinity for fibrinogen was decreased as measured using FITC-fibrinogen. Furthermore, aggregate formation was reduced. Thus ILK transiently associates with and phosphorylates β3 in a PI3-kinase dependent manner suggesting that it participates at an intermediate stage in a critical mechanism for assuring large stable aggregates.