bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppressive Effects of Chronic Stress on Influenza Virus Protection after Vaccination with Plasmid DNA-Encoded Nucleoprotein
Authors: Nezam Fatemeh Sadat , Hosseini Seyed Masoud , Kheiri Masoumeh Tavassoti , Abdoli Asghar , Memarnejadian Arash , Shenagari Mohammad , Gholami Shima , Sohani Hesam , Rahmatollahi Hamidreza , Jamali Abbas
Published: March 2015

Background: Influenza is a highly infectious and acute respiratory disease caused by an infection of the host respiratory tract mucosa by the influenza virus. The use of DNA vaccines that express conserved genes such as nucleoprotein (NP) represents a new method of vaccination against influenza. In this study, the effect of chronic stress on the efficiency of this type of vaccine has been evaluated in a mouse model. Methods: The NP DNA vaccine was administered intradermally 3 times on days 0, 3 and 6 to stressed and nonstressed male BALB/c mice. Two weeks after the last immunization, half of these mice were challenged with A/Puerto Rico/8/34 (PR8) influenza virus and were weighed for 12 days, and their mortality rate was assessed during this period. The cellular immune response of the other half of the mice was evaluated by cytotoxicity assay. Results: The results indicate a significant reduction in the cytotoxic T-lymphocyte response of stressed mice in comparison with unstressed mice. Also, the percentage of weight loss and mortality after the challenge in stressed mice was significantly increased compared to the other group. Conclusion: These results indicate that the NP DNA vaccine is not able to induce any effective cytotoxic T-lymphocyte response against influenza virus in stressed mice and cannot induce protective immunity against influenza infection in this group of mice.
AMH and AMHR2 Polymorphisms and AMH Serum Level Can Predict Assisted Reproduction Outcomes: A Cross-Sectional Study
Authors: Peluso Carla , Fonseca Fernando L.A. , Gastaldo Guilherme G. , Christofolini Denise M. , Cordts Emerson Barchi , Barbosa Caio P. , Bianco Bianca
Published: March 2015

Background: In human assisted reproduction, the ovarian response to exogenous recombinant Follicle-stimulating Hormone (FSH) therapy is variable and difficult to predict. The standard protocol of ovarian hyperstimulation can result in satisfactory response; however, an unsatisfactory response necessitates FSH dose adjustment or results in ovarian hyperstimulation syndrome (OHSS). Polymorphisms in AMH and AMHR2 genes appear to affect hormone biological activities, thus affecting follicle recruitment and development, leading to infertility. We aimed to evaluate AMH and AMHR2 polymorphisms in infertile women, and correlate those findings with AMH, FSH and estradiol serum level response to controlled ovarian hyperstimulation (COH), as well as assisted reproduction outcomes. Methods: A cross-sectional study comprising 186 infertile women that underwent one cycle of high complexity assisted reproductive treatment. Blood samples were collected and a TaqMan assay was used for AMH G146T/rs10407022 and AMHR2 A-482G/rs2002555, A10G/rs11170555, C1749G/rs2071558 and G4952A/rs3741664 genotyping, and FSH, estradiol and AMH levels were measured. The findings were correlated to human reproduction outcomes. Results: AMH rs10407022 and AMHR2 rs2002555 polymorphisms were not associated with hormonal measurements, whereas AMHR2 rs11170555 and rs3741664 were positively associated with AMH, estradiol and FSH levels. The genotype distribution of AMH and AMHR2 genes according to Controlled Ovarian Hyperstimulation did not show a positive association. However, an association with AFC, degree of oocyte maturation (allele G of AMHR2 rs2071558) the number of embryos produced (alleles T and G of AMH rs10407022 and AMHR2 rs2002555, respectively) and frozen embryo (allele G of AMHR2 rs11170555) were found to be statistically associated. Considering COH, serum AMH and AFC were a positive predictor to OHSS. Regarding serum AMH and assisted reproduction outcomes, a positive correlation with all variables studied was found. Comparing AFC and AMH as predictors of human reproduction outcomes, the AFC was less effective than serum AMH. Considering pregnancy rates, no marker was positively associated. Conclusion: AMHR2 polymorphisms were associated with estradiol, AMH and FSH measurements, as well as number and quality of embryos, while AMH polymorphisms was associated with number of embryos produced. Serum AMH was correlated with nearly all variables analyzed in assisted reproductive treatment, demonstrating that it represents a better biomarker of OHSS and human reproduction outcomes compared to AMH and AMHR2 polymorphisms.
Intensified Surveillance for Early Detection of Breast Cancer in High-Risk Patients
Authors: Bick Ulrich
Published: March 2015

Efforts for early detection of breast cancer play an important role in the care of high-risk women. This will include both women with a pathological mutation in one of the known breast cancer susceptibility genes as well as women with a high breast cancer risk based on family history only. Due to the much higher incidence of breast cancer in premenopausal women with a genetic predisposition or a familial background, to be most effective, imaging-based breast surveillance should start at an age as early as 25-30 years. There is now ample evidence that magnetic resonance imaging (MRI) is by far the most sensitive imaging modality in young high-risk women. With high-risk multimodality screening at least 30% of breast cancers will be detected primarily by MRI and would have been missed at regular screening without MRI. Therefore, most high-risk breast surveillance programs now offer annual MRI to eligible high-risk women from age 25 to 30, usually supplemented by regular mammography starting at least from age 40. The inclusion of clinical breast exam (CBE) and/or ultrasound in the high-risk surveillance has little impact on the detection of additional cancers, but may improve compliance and reduce unnecessary call-backs for nonspecific findings on MRI. To reduce advanced stage interval cancers, especially in BRCA1/2 mutation carriers, some programs offer additional semiannual CBE and/or ultrasound or alternate MRI and mammography every 6 months. How long regular MRI should be continued in high-risk women is a matter of considerable debate. It appears feasible that MRI can safely be discontinued even in BRCA1/2 mutation carriers between the age of 60 and 70, especially if mammographic breast density is low. Even though several cohort studies have now demonstrated a very favorable stage distribution of breast cancers found in women undergoing high-risk surveillance with MRI, data on long-term survival and mortality in these patients is still rare.
A Sequence Kernel Association Test for Dichotomous Traits in Family Samples under a Generalized Linear Mixed Model
Authors: Yan Qi , Tiwari Hemant K. , Yi Nengjun , Gao Guimin , Zhang Kui , Lin Wan-Yu , Lou Xiang-Yang , Cui Xiangqin , Liu Nianjun
Published: March 2015

Objective: The existing methods for identifying multiple rare variants underlying complex diseases in family samples are underpowered. Therefore, we aim to develop a new set-based method for an association study of dichotomous traits in family samples. Methods: We introduce a framework for testing the association of genetic variants with diseases in family samples based on a generalized linear mixed model. Our proposed method is based on a kernel machine regression and can be viewed as an extension of the sequence kernel association test (SKAT and famSKAT) for application to family data with dichotomous traits (F-SKAT). Results: Our simulation studies show that the original SKAT has inflated type I error rates when applied directly to family data. By contrast, our proposed F-SKAT has the correct type I error rate. Furthermore, in all of the considered scenarios, F-SKAT, which uses all family data, has higher power than both SKAT, which uses only unrelated individuals from the family data, and another method, which uses all family data. Conclusion: We propose a set-based association test that can be used to analyze family data with dichotomous phenotypes while handling genetic variants with the same or opposite directions of effects as well as any types of family relationships.
Parkinson's Disease and Restless Legs Syndrome
Authors: Ylikoski Ari , Martikainen Kirsti , Partinen Markku
Published: March 2015

Aims: Various sleep-related complications are common in Parkinson's disease (PD). The prevalence of restless legs syndrome (RLS) and its association with other symptoms were studied. Methods: Altogether, 1,447 Parkinson patients, aged 43-89, participated in a questionnaire study. Results: The response rate was 59.0% and of these, 68% returned fully answered questionnaires (n = 577). RLS occurred in 20.3% of the PD subjects. In patients with RLS, the symptoms occurred in 81.9% at least once weekly. The degree of severity was moderate in 42.7%, severe in 23.9% and very severe in 15.4%. Daytime sleepiness, fatigue, chronic insomnia, sleep maintenance insomnia, intense dreaming, and low quality of life were more common in patients with RLS than in patients without RLS. The occurrence of early onset RLS (onset ≤ age of 45 years) was 4.2%. The occurrences of late onset (>45 years) drug naïve RLS and late onset RLS (with dopaminergic medication) were 5.4 and 10.4%, respectively. Conclusion: In patients with PD, the early onset of RLS resembles idiopathic RLS with typical gender distribution and familial trait. Late onset of RLS is more common than idiopathic RLS.
Second-Line Treatment of Advanced Urothelial Cancer with Paclitaxel and Everolimus in a German Phase II Trial (AUO Trial AB 35/09)
Authors: Niegisch Günter , Retz Margitta , Thalgott Mark , Balabanov Stefan , Honecker Friedemann , Ohlmann Carsten Henning , Stöckle Michael , Bögemann Martin , vom Dorp Frank , Gschwend Jürgen , Hartmann Arndt , Ohmann Christian , Albers Peter
Published: March 2015

Objective: The efficacy of second-line treatment after failure of platinum-based chemotherapy in patients with advanced urothelial cancer is limited. Based on encouraging preclinical and clinical phase I data, we evaluated the safety and efficacy of the combination of paclitaxel and everolimus in these patients. Methods: In this trial, patients having failed to respond to prior platinum-based combination treatment of urothelial cancer were treated with paclitaxel (175 mg/m2 i.v., 3-weekly) and the mTOR-inhibitor everolimus (10 mg p.o., once daily). The patients were treated until tumor progression or until a maximum of 6 cycles was completed. A one-stage design was used to evaluate the objective response rate (ORR) as the primary endpoint. Results: A total of 27 patients (67% male; median age 63 years) were enrolled. The most frequent grade III/IV toxicities were anemia (28%), peripheral neuropathy (28%), and fatigue (24%). No treatment-related deaths were reported. Complete and partial remissions were observed in 0/24 and 3/24 patients eligible for efficacy analysis, respectively (ORR 13%). Progression-free survival was 2.9 months [95% confidence interval (95% CI) 1.9-4.2], and the median overall survival was 5.6 months (95% CI 4.8-10.2). Conclusion: The combination of paclitaxel and everolimus has not achieved the expected efficacy in second-line treatment of urothelial cancer and should not be further explored.
NLRC4 Inflammasome Is an Important Regulator of Interleukin-18 Levels in Patients With Acute Coronary Syndromes
Authors: Johansson Åsa , Eriksson Niclas , Becker Richard C. , Storey Robert F. , Himmelmann Anders , Hagström Emil , Varenhorst Christoph , Axelsson Tomas , Barratt Bryan J. , James Stefan K. , Katus Hugo A. , Steg Philippe Gabriel , Syvänen Ann-Christine , Wallentin Lars , Siegbahn Agneta
Published: March 2015

Background—

Interleukin 18 (IL-18) promotes atherosclerotic plaque formation and is increased in patients with acute coronary syndromes. However the relative contribution of genetic variants to the IL-18 levels has not been fully determined.

Methods and Results—

Baseline plasma IL-18 levels were measured in 16 633 patients with acute coronary syndrome, of whom 9340 had genetic data that passed genotype quality control. A 2-stage genome-wide association study was performed, followed by combined analyses using >10 million genotyped or imputed genetic markers. Single nucleotide polymorphisms at 3 loci (
IL18, NLRC4
, and
MROH6
) were identified (
P
<3.15×10
−8
) in the discovery cohort (n=3777) and replicated in the remaining patients (n=5563). In the pooled data (discovery+replication cohort), 7 independent associations, in 5 chromosomal regions, were associated with IL-18 levels (minimum
P
=6.99×10
–72
). Six single nucleotide polymorphisms are located in predicted promoter regions of which one disrupts a transcription factor binding site. One single nucleotide polymorphism in
NLRC4
is a rare missense variant, predicted to be deleterious to the protein. Altogether, the identified genetic variants explained 8% of the total variation in IL-18 levels in the cohort.

Conclusions—

Our results show that genetic variants play an important role in determining IL-18 levels in patients with acute coronary syndrome and we have identified genetic variants located in the IL-18 gene (
IL18
) or close to genes that are involved in procaspase-1 activation (
NLRC4
and
CARD16
,
CARD17
, and
CARD18
). These associations also highlight the importance of the NLRC4 inflammasome for IL-18 production in acute coronary syndrome patients.
Aortic Disease Presentation and Outcome Associated With
ACTA2
Mutations
Authors: Regalado Ellen S. , Guo Dong-chuan , Prakash Siddharth , Bensend Tracy A. , Flynn Kelly , Estrera Anthony , Safi Hazim , Liang David , Hyland James , Child Anne , Arno Gavin , Boileau Catherine , Jondeau Guillaume , Braverman Alan , Moran Rocio , Morisaki Takayuki , Morisaki Hiroko , Pyeritz Reed , Coselli Joseph , LeMaire Scott , Milewicz Dianna M.
Published: March 2015

Background—

ACTA2
mutations are the major cause of familial thoracic aortic aneurysms and dissections. We sought to characterize these aortic diseases in a large case series of individuals with
ACTA2
mutations.

Methods and Results—

Aortic disease, management, and outcome associated with the first aortic event (aortic dissection or aneurysm repair) were abstracted from the medical records of 277 individuals with 41 various
ACTA2
mutations. Aortic events occurred in 48% of these individuals, with the vast majority presenting with thoracic aortic dissections (88%) associated with 25% mortality. Type A dissections were more common than type B dissections (54% versus 21%), but the median age of onset of type B dissections was significantly younger than type A dissections (27 years versus 36 years). Only 12% of aortic events were repair of ascending aortic aneurysms, which variably involved the aortic root, ascending aorta, and aortic arch. Overall, cumulative risk of an aortic event at age 85 years was 0.76 (95% confidence interval, 0.64–0.86). After adjustment for intrafamilial correlation, sex and race, mutations disrupting p.R179 and p.R258 were associated with significantly increased risk for aortic events, whereas p.R185Q and p.R118Q mutations showed significantly lower risk of aortic events compared with other mutations.

Conclusions—

ACTA2
mutations are associated with high risk of presentation with an acute aortic dissection. The lifetime risk for an aortic event is only 76%, suggesting that additional environmental or genetic factors play a role in expression of aortic disease in individuals with
ACTA2
mutations.
Seeing the Same Words Differently: The Time Course of Automaticity and Top–Down Intention in Reading
Authors: Strijkers Kristof , Bertrand Daisy , Grainger Jonathan
Published: March 2015

We investigated how linguistic intention affects the time course of visual word recognition by comparing the brain's electrophysiological response to a word's lexical frequency, a well-established psycholinguistic marker of lexical access, when participants actively retrieve the meaning of the written input (semantic categorization) versus a situation where no language processing is necessary (ink color categorization). In the semantic task, the ERPs elicited by high-frequency words started to diverge from those elicited by low-frequency words as early as 120 msec after stimulus onset. On the other hand, when categorizing the colored font of the very same words in the color task, word frequency did not modulate ERPs until some 100 msec later (220 msec poststimulus onset) and did so for a shorter period and with a smaller scalp distribution. The results demonstrate that, although written words indeed elicit automatic recognition processes in the brain, the speed and quality of lexical processing critically depends on the top–down intention to engage in a linguistic task.
Preconscious Prediction of a Driver's Decision Using Intracranial Recordings
Authors: Perez Omri , Mukamel Roy , Tankus Ariel , Rosenblatt Jonathan D. , Yeshurun Yehezkel , Fried Itzhak
Published: March 2015

While driving, we make numerous conscious decisions such as route and turn direction selection. Although drivers are held responsible, the neural processes that govern such decisions are not clear. We recorded intracranial EEG signals from six patients engaged in a computer-based driving simulator. Patients decided which way to turn (left/right) and subsequently reported the time of the decision. We show that power modulations of gamma band oscillations (30–100 Hz) preceding the reported time of decision (up to 5.5 sec) allow prediction of decision content with high accuracy (up to 82.4%) on a trial-by-trial basis, irrespective of subsequent motor output. Moreover, these modulations exhibited a spatiotemporal gradient, differentiating left/right decisions earliest in premotor cortices and later in more anterior and lateral regions. Our results suggest a preconscious role for the premotor cortices in early stages of decision-making, which permits foreseeing and perhaps modifying the content of real-life human choices before they are consciously made.
The Devil Is in the Detail: Brain Dynamics in Preparation for a Global–Local Task
Authors: Leaver Echo E. , Low Kathy A. , DiVacri Assunta , Merla Arcangelo , Fabiani Monica , Gratton Gabriele
Published: March 2015

When analyzing visual scenes, it is sometimes important to determine the relevant “grain” size. Attention control mechanisms may help direct our processing to the intended grain size. Here we used the event-related optical signal, a method possessing high temporal and spatial resolution, to examine the involvement of brain structures within the dorsal attention network (DAN) and the visual processing network (VPN) in preparation for the appropriate level of analysis. Behavioral data indicate that the small features of a hierarchical stimulus (local condition) are more difficult to process than the large features (global condition). Consistent with this finding, cues predicting a local trial were associated with greater DAN activation. This activity was bilateral but more pronounced in the left hemisphere, where it showed a frontal-to-parietal progression over time. Furthermore, the amount of DAN activation, especially in the left hemisphere and in parietal regions, was predictive of subsequent performance. Although local cues elicited left-lateralized DAN activity, no preponderantly right activity was observed for global cues; however, the data indicated an interaction between level of analysis (local vs. global) and hemisphere in VPN. They further showed that local processing involves structures in the ventral VPN, whereas global processing involves structures in the dorsal VPN. These results indicate that in our study preparation for analyzing different size features is an asymmetric process, in which greater preparation is required to focus on small rather than large features, perhaps because of their lesser salience. This preparation involves the same DAN used for other attention control operations.
Effects of Eddy Vorticity Forcing on the Mean State of the Kuroshio Extension
Authors: Delman Andrew S. , McClean Julie L. , Sprintall Janet , Talley Lynne D. , Yulaeva Elena , Jayne Steven R.
Published: March 2015

Eddy–mean flow interactions along the Kuroshio Extension (KE) jet are investigated using a vorticity budget of a high-resolution ocean model simulation, averaged over a 13-yr period. The simulation explicitly resolves mesoscale eddies in the KE and is forced with air–sea fluxes representing the years 1995–2007. A mean-eddy decomposition in a jet-following coordinate system removes the variability of the jet path from the eddy components of velocity; thus, eddy kinetic energy in the jet reference frame is substantially lower than in geographic coordinates and exhibits a cross-jet asymmetry that is consistent with the baroclinic instability criterion of the long-term mean field. The vorticity budget is computed in both geographic (i.e., Eulerian) and jet reference frames; the jet frame budget reveals several patterns of eddy forcing that are largely attributed to varicose modes of variability. Eddies tend to diffuse the relative vorticity minima/maxima that flank the jet, removing momentum from the fast-moving jet core and reinforcing the quasi-permanent meridional meanders in the mean jet. A pattern associated with the vertical stretching of relative vorticity in eddies indicates a deceleration (acceleration) of the jet coincident with northward (southward) quasi-permanent meanders. Eddy relative vorticity advection outside of the eastward jet core is balanced mostly by vertical stretching of the mean flow, which through baroclinic adjustment helps to drive the flanking recirculation gyres. The jet frame vorticity budget presents a well-defined picture of eddy activity, illustrating along-jet variations in eddy–mean flow interaction that may have implications for the jet’s dynamics and cross-frontal tracer fluxes.
Use of an Electromagnetic Device Compared With Chest X‐ray to Confirm Nasogastric Feeding Tube Position in Critical Care
Authors: Bear Danielle E. , Champion Alice , Lei Katie , Smith John , Beale Richard , Camporota Luigi , Barrett Nicholas A.
Published: March 2015

Background: Insertion of nasogastric feeding tubes (NGTs) is common in critical care. However, misplacement is frequent and can carry a significant morbidity. Current methods to confirm position of NGTs are not reliable in this setting. We retrospectively compared the position of NGTs using an electromagnetically guided nasogastric tube (e‐NGT) with that demonstrated by chest x‐ray (CXR), the proportion of lung placements avoided, and the time taken to establish enteral feeding. Methods: This was a retrospective, observational study undertaken in a tertiary referral, adult intensive care unit between February 2006 and November 2013. Patients were included if they had a radiologically confirmed NGT. All CXRs were independently reviewed by an intensivist to determine position, and a subset of patients had their e‐NGT image independently reviewed for quality control. Statistical analysis was in the form of sensitivity and specificity and descriptive where indicated. Results: In total, 121 NGT placements in 113 patients were analyzed. We found a sensitivity of 98% (95% confidence interval [CI], 93.9%–99.7%) and a specificity of 100% (95% CI, 48.0%–100.0%) when using the e‐NGT compared with CXR. In the subset of 51 independently reviewed e‐NGT images, 9 lung placements were avoided. The mean (SD) time from e‐NGT placement to CXR was 185 (264.4) minutes and to feeding was 404 (77.8) minutes. Conclusion: When placed by a dedicated team, e‐NGT allowed immediate detection of tube misplacement. As such, if used as the sole method for determining NGT position, e‐NGTs minimize feeding delay and the need for multiple CXRs with subsequent cost savings.
Helping Teachers Help Themselves
Authors: Patton Kevin , Parker Melissa , Tannehill Deborah
Published: March 2015

For school administrators to facilitate impactful teacher professional development, a shift in thinking that goes beyond the acquisition of new skills and knowledge to helping teachers rethink their practice is required. Based on review of the professional development literature and our own continued observations of professional development, this scholarly article synthesizes findings and presents core features of effective professional development, including what those features might look like in practice. Strategies for teachers, administrators, and schools to begin to engage in meaningful professional development experiences are presented and discussed.
Reduction of acid rock drainage using steel slag in cover systems over sulfide rock waste piles
Authors: de Almeida Rodrigo Pereira , Leite Adilson do Lago , Borghetti Soares Anderson
Published: March 2015

The extraction of gold, coal, nickel, uranium, copper and other earth-moving activities almost always leads to environmental damage. In metal and coal extraction, exposure of sulfide minerals to the atmosphere leads to generation of acid rock drainage (ARD) and in underground mining to acid mine drainage (AMD) due to contamination of infiltrating groundwater. This study proposes to develop a reactive cover system that inhibits infiltration of oxygen and also releases alkalinity to increase the pH of generated ARD and attenuate metal contaminants at the same time. The reactive cover system is constructed using steel slag, a waste product generated from steel industries. This study shows that this type of cover system has the potential to reduce some of the adverse effects of sulfide mine waste disposal on land. Geochemical and geotechnical characterization tests were carried out. Different proportions of sulfide mine waste and steel slag were studied in leachate extraction tests. The best proportion was 33% of steel slag in dry weight. Other tests were conducted as follows: soil consolidation, saturated permeability and soil water characteristic curve. The cover system was numerically modeled through unsaturated flux analysis using Vadose/w. The solution proposed is an oxygen transport barrier that allows rain water percolation to treat the ARD in the waste rock pile. The results showed that the waste pile slope is an important factor and the cover system must have 5 m thickness to achieve an acceptable effectiveness.
Mercuric chloride induced hepatotoxic and hematologic changes in rats
Authors: Uzunhisarcikli Meltem , Aslanturk Ayse , Kalender Suna , Apaydin Fatma Gokce , Bas Hatice
Published: March 2015

This study focuses on investigating the possible protective effect of sodium selenite (Na2SeO3) and/or vitamin E against mercuric chloride (HgCl2)-induced hepatotoxicity in rat. Male rats were given HgCl2 (1 mg/kg body weight (bw)) and HgCl2 plus Na2SeO3 (0.25 mg/kg bw) and/or vitamin E (100 mg/kg bw) daily via gavage for 4 weeks. HgCl2-treated groups had significantly higher white blood cell and thrombocyte counts than the control group. Serum activities of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl-transferase, and lactate dehydrogenase significantly increased and serum levels of total protein, albumin, triglyceride, total cholesterol, and low-density lipoprotein cholesterol significantly decreased in the HgCl2-treated groups compared with control group. Malondialdehyde level significantly increased and superoxide dismutase, catalase, and glutathione peroxidase activities decreased in liver tissue of HgCl2-treated rats. Also, HgCl2 exposure resulted in histopathological changes. Supplementation of Na2SeO3 and/or vitamin E provided partial protection in hematological and biochemical parameters that were altered by HgCl2. As a result, Na2SeO3 and/or vitamin E significantly reduced HgCl2-induced hepatotoxicity, but not protected completely.
What Is the German’s Fatherland?
Authors: Panagiotidis Jannis
Published: March 2015

This article deals with the migration of “ethnic Germans” from socialist Eastern Europe to the GDR in the decades after the Second World War. Post-expulsion resettlement from that region is commonly associated with Aussiedler migration to West Germany. Contesting the idea that East Germany displayed no interest in Eastern European Germans, this article shows that the GDR, which challenged the West German claim to be the sole representative of the German nation, also received ethnic German immigrants, mostly from Poland and the USSR. It argues that the distribution of roles between the two German states, with West Germany being the prime destination for resettlers, was not clear from the outset. It was only after Polish–West German “normalization” in 1970 that the FRG became the almost uncontested “fatherland” for Eastern European Germans. West and East German approaches resembled each other as long as they were predicated on humanitarian family reunification. They diverged as the GDR attempted co-ethnic labor recruitment in Poland in the 1960s. These efforts met with limited success, as East Germany was the weakest link in a cross-bloc “tetradic nexus” with the German minority in Poland, the Polish state, and West Germany. Meanwhile, the GDR authorities eyed grass-roots migration initiatives by Soviet Germans with suspicion, as they undermined the government aspiration to control the movement of people. The article finally argues that movement of labor had no priority in the project of socialist economic integration, which gives reason to suspect a link between limited migration and failed COMECON integration.
Strategic party heterogeneity
Authors: Kernell Georgia
Published: March 2015

Political parties field heterogeneous candidates and send a variety of messages about their policy positions. Yet most voting models maintain that office-seeking parties should enforce intraparty homogeneity and cultivate clear party reputations. This article reconciles theory with reality by identifying a strategic rationale for parties to pursue heterogeneity. I develop a model in which two parties each select a distribution of potential candidates to compete in an upcoming election. The model demonstrates that well-positioned parties should indeed offer homogeneous candidate teams, but that parties with platforms distant from the median voter should cast a wide net. Extensions allow for multiple candidate signals, voters who care about party platforms and candidates’ positions, and voter uncertainty.
The Eleanor Chelimsky Forum
Authors: Feldman Jill , Kelley John
Published: March 2015

In response to Eleanor Chelimsky’s inspiring plenary address 3 years ago, and with generous support from the Robert Wood Johnson Foundation, the Eastern Evaluation Research Society launched the Eleanor Chelimsky Forum at its 2013 Annual Conference. The objective of this annual Forum, which has become a hallmark event in the evaluation world, is to spark meaningful dialogue about the interplay of evaluation theory and practice through open discussion among thought leaders, from practitioners to theorists.
Physiological responses during downhill walking
Authors: Camillo Carlos Augusto , Burtin Chris , Hornikx Miek , Demeyer Heleen , De Bent Kristien , van Remoortel Hans , Osadnik Christian R , Janssens Wim , Troosters Thierry
Published: March 2015

Skeletal muscle quadriceps low-frequency fatigue (LFF) during exercise promotes improvements in exercise capacity with exercise training. In healthy subjects, eccentric muscle work induced by downhill walking (DW) generates higher muscular stress, whilst metabolic cost is lower compared to level walking (LW). We investigated quadriceps LFF and metabolic cost of DW in patients with chronic obstructive pulmonary disease. Ten participants (67 ± 7 years, FEV1 51 ± 15% predicted) performed DW, DW carrying a load (DWL) of 10% body weight via vest and LW, in random order. Quadriceps potentiated twitch force (TWqpot) was assessed before and after each walk, and muscle damage was assessed before and 24 hours after each walk via serum creatine kinase (CK) levels. Ventilation (VE) and oxygen consumption (VO2) were measured via breath-by-breath analysis during each walk. DW and DWL resulted in a greater decrease in TWqpot (−30 ± 14 N in DW, p < 0.05; and −22 ± 16 N in DWL, p < 0.05) compared to LW (−3 ± 21 N, p > 0.05). CK levels only increased 24 hours following DW and DWL ( p < 0.05). DW and DWL showed lower VE and VO2 than LW ( p < 0.05). DW is associated with enhanced quadriceps LFF and lower cardiorespiratory costs than LW. The addition of a chest load to DW does not seem to enhance these effects.
Current challenges in clinical development of “targeted therapies”: the case of acute myeloid leukemia
Authors: Estey Elihu , Levine Ross L. , Löwenberg Bob
Published: March 2015

A fundamental difficulty in testing “targeted therapies” in acute myeloid leukemia (AML) is the limitations of preclinical models in capturing inter- and intrapatient genomic heterogeneity. Clinical trials typically focus on single agents despite the routine emergence of resistant subclones and experience in blast-phase chronic myeloid leukemia and acute promyelocytic leukemia arguing against this strategy. Inclusion of only relapsed-refractory, or unfit newly diagnosed, patients risks falsely negative results. There is uncertainty as to whether eligibility should require demonstration of the putative target and regarding therapeutic end points. Although use of in vivo preclinical models employing primary leukemic cells is first choice, newer preclinical models including “organoids” and combinations of pharmacologic and genetic approaches may better align models with human AML. We advocate earlier inclusion of combinations ± chemotherapy and of newly diagnosed patients into clinical trials. When a drug plausibly targets a pathway uniquely related to a specific genetic aberration, eligibility should begin with this subset, including patients with other malignancies, with subsequent extension to other patients. In other cases, a more open-minded approach to initial eligibility would facilitate quicker identification of responsive subsets. Complete remission without minimal residual disease seems a particularly useful short-term end point. Genotypic and phenotypic studies should be prespecified and performed routinely to distinguish responders from nonresponders.
First-principles calculations of perpendicular magnetic anisotropy in Fe1−x
Co
x
/MgO(001) thin films
Authors: Cai Guanzhi , Wu Zhiming , Guo Fei , Wu Yaping , Li Heng , Liu Qianwen , Fu Mingming , Chen Ting , Kang Junyong
Published: March 2015

The perpendicular magnetic anisotropy (PMA) of Fe1−x
Co
x
thin films on MgO(001) was investigated via first-principles density-functional calculations. Four different configurations were considered based on their ground states: Fe/MgO, Fe12Co4/MgO, Fe10Co6/MgO, and Fe8Co8/MgO. As the Co composition increases, the amplitude of PMA increases first from Fe/MgO to Fe12Co4/MgO, and then decreases in Fe10Co6/MgO; finally, the magnetic anisotropy becomes horizontal in Fe8Co8/MgO. Analysis based on the second-order perturbation of the spin-orbit interaction was carried out to illustrate the contributions from Fe and Co atoms to PMA, and the differential charge density was calculated to give an intuitive comparison of 3d orbital occupancy. The enhanced PMA in Fe12Co4/MgO is ascribed to the optimized combination of occupied and unoccupied 3d states around the Fermi energy from both interface Fe and Co atoms, while the weaker PMA in Fe10Co6/MgO is mainly attributed to the modulation of the interface Co-d

xy
orbital around the Fermi energy. By adjusting the Co composition in Fe1−x
Co
x
, the density of states of transitional metal atoms will be modulated to optimize PMA for future high-density memory application.
Direct patterning of gold nanoparticles using flexographic printing for biosensing applications
Authors: Benson Jamie , Fung Chung Man , Lloyd Jonathan Stephen , Deganello Davide , Smith Nathan Andrew , Teng Kar Seng
Published: March 2015

In this paper, we have presented the use of flexographic printing techniques in the selective patterning of gold nanoparticles (AuNPs) onto a substrate. Highly uniform coverage of AuNPs was selectively patterned on the substrate surface, which was subsequently used in the development of a glucose sensor. These AuNPs provide a biocompatible site for the attachment of enzymes and offer high sensitivity in the detection of glucose due to their large surface to volume ratio. The average size of the printed AuNPs is less than 60 nm. Glucose sensing tests were performed using printed carbon-AuNP electrodes functionalized with glucose oxidase (GOx). The results showed a high sensitivity of 5.52 μA mM−1 cm−2 with a detection limit of 26 μM. We have demonstrated the fabrication of AuNP-based biosensors using flexographic printing, which is ideal for low-cost, high-volume production of the devices.
Effective radiation dose of a MSCT, two CBCT and one conventional radiography device in the ankle region
Authors: Koivisto Juha , Kiljunen Timo , Kadesjö Nils , Shi Xie‐Qi , Wolff Jan
Published: March 2015

Background

The aim of this study was to assess and compare the effective doses (ICRP 103) in the ankle region of X‐ray imaging resulting from a multi slice computed tomography (MSCT) device, two cone beam CT (CBCT) devices and one conventional x‐ray device.

Methods

Organ dose measurements were performed using 20 metal oxide field effect transistor (MOSFET) dosimeters that were placed in a custom made anthropomorphic RANDO ankle phantom. The following scanners were assessed in this study: Siemens Sensation Open 24‐slice MSCT‐scanner (120 kVp, 54 mAs), NewTom 5G CBCT scanner (110 kVp, 2.3 ‐ 59 mAs), Planmed Verity CBCT‐scanner (90 kVp, 48 mAs), Shimadzu FH‐21 HR direct radiography equipment (AP + LAT), (57 kVp, 16 mAs).

Results

Measurements of the MSCT device resulted in 21.4 μSv effective dose. The effective doses of CBCTs were between 1.9 μSv and 14.3 μSv for NewTom 5G and 6.0 μSv for Planmed Verity. Effective doses for the Shimadzu FH‐21 HR conventional radiography were 1.0 μSv (LAT) and 0.5 μSv (AP), respectively.

Conclusions

Compared with a conventional 2D radiographic device, this study showed a 14‐fold effective dose for standard MSCT and 1.3 ‐10 fold effective dose for standard CBCT protocols. CBCT devices offers a 3D view of ankle imaging and exhibited lower effective doses compared with MSCT.
Enhancement of periodontal tissue regeneration by transplantation of osteoprotegerin-engineered periodontal ligament stem cells
Authors: Su Fang , Liu Shi-Sen , Ma Jun-Li , Wang Dong-Sheng , E Ling-Ling , Liu Hong-Chen
Published: March 2015

Introduction

The objective of the present study was to evaluate the capacity of a tissue-engineered complex of human osteoprotegerin (hOPG)-transfected periodontal ligament stem cells (PDLSCs) seeding on beta-tricalcium phosphate (β-TCP) to regenerate alveolar bone defects in New Zealand rabbits.

Methods

PDLSCs were isolated from rabbit periodontal ligament tissues and expanded in vitro to enrich PDLSC numbers, and their proliferative activities and differentiation capability were evaluated under specific induction conditions. Lentiviral vector containing hOPG and enhanced green fluorescent protein (EGFP) was constructed by using Gateway technology and transfected into rabbit PDLSCs. The expression of hOPG was determined with quantitative real-time reverse transcription-polymerase chain reaction and Western blot. The PDLSCs with or without engineered hOPG were seeded on β-TCP scaffolds prior to transplantation. Morphological characterization of cells and materials was done by scanning electron microscope. Twenty rabbits with alveolar bone defects were randomly allocated into four groups and transplanted with β-TCP, PDLSCs/β-TCP, and hOPG-transfected PDLSCs/β-TCP or were left untreated as a control. Animals were sacrificed 12 weeks after operation for histological observation and histomorphometric analysis.

Results

PDLSCs expressed STRO-1 and vementin and favored osteogenesis and adipogenesis in conditioned media. Expressions of hOPG were significantly upregulated after transfection of the lentiviral vector into PDLSCs. PDLSCs attached and spread well on β-TCP, and there was no significant difference in growth of PDLSCs on β-TCP between the hOPG transfection group and the non-transfection group. The histological observation and histomorphometric analysis showed that the hOPG-transfected PDLSCs/β-TCP complex exhibited an earlier mineralization and more bone formation inside the scaffold than control, β-TCP, and PDLSCs/β-TCP complexes. Implantation of hOPG-transfected PDLSCs contributed to new bone formation as determined by EGFP gene expression under circularly polarized light microscopy.

Conclusions

The present study demonstrated the feasibility of β-TCP scaffolds for primary PDLSC culture and expression of hOPG gene in vitro and in vivo, and hOPG-transfected PDLSCs could serve as a potential cell source for periodontal bone regeneration, which may shed light on the potential of systemic hOPG gene therapy in combination with PDLSC tissue engineering as a good candidate in periodontal tissue engineering for alveolar bone regeneration.
Social BIMCloud: a distributed cloud-based BIM platform for object-based lifecycle information exchange
Authors: Das Moumita , Cheng Jack CP , Kumar Srinath S
Published: March 2015

Background

The architecture, engineering and construction (AEC) industry lacks a framework for capturing, managing, and exchanging project, product, and social information over the lifecycle of a building. The current tools have various limitations, such as lack of interoperability, slow to transfer huge building model files, and possibility of data inconsistency.

Methods

In this paper, we present a cloud-based BIM server framework namely Social BIMCloud that facilitates BIM information exchange through dynamic merging and splitting of building models. The data model of Social BIMCloud is based on but not limited to IFC. The data model of Social BIMCloud was further extended to accommodate social interactions, by studying the formal modes of communication in the AEC industry. An object-based approach to capture and manage social interactions in AEC projects through a BIM-based visual user interface was also developed and demonstrated.

Results

Social BIMCloud addresses the issues of inefficient data transfer speed and data inconsistency in a distributed environment by facilitating the storage and partial exchange of integrated nD BIM models. Data interoperability is facilitated through open BIM standards such as IFC and direct integration with construction software. High performance, scalability, fault tolerance, and cost effectiveness are facilitated through data partitioning, data replication strategies, multi-node structures, and pay-per-use tariff systems, respectively, through a cloud-based NoSQL database.

Conclusion

The Social BIMCloud framework helps to develop and exchange BIM models, which are rich in project information such as social interactions, cost, and energy analyses. This framework improves the communication efficiency between project participants, leading to better designs and less rework. The information captured by this framework could also be useful to determine important metrics such as industry trends, relationships among project participants, and user requirements.
Optimal consumer search with prospect utility in hybrid uncertain environment
Authors: Zhou Chi , Tang Wansheng , Zhao Ruiqing
Published: March 2015

This paper studies a consumer search model with prospect utility in a hybrid uncertain environment. Hybrid uncertainty consists of the uncertainty of the consumer’s valuation for each product and the randomness of stockout. An optimal search strategy is designed for the consumer to search or buy a product. The results show that the presence of prospect utility can result in low purchase threshold. By comparative statics, we demonstrate that the consumer’s purchase threshold for low-value product increases with the risk coefficients for gains and losses, while the purchase threshold for high-value product decreases with the risk coefficients for gains and losses. In addition, we find that the consumer who is more sensitive to the loss will search for much less products. Finally, some numerical examples are given to illustrate the relationships between the model without and with prospect utility and further verify the effectiveness and credibility of the conclusions.
Mitochondrial fusion and fission are involved in stress tolerance of Candida glabrata
Authors: Li Shubo , Liu Liming , Chen Jian
Published: March 2015

Background

Recently, cell tolerance toward environmental stresses has become the major problem in the development of industrial microbial fermentation. Acetoin is an important chemical that can be synthesized by microbes. Its toxicity was investigated usingCandida glabrataas the model in this study.

Results

A series of physiological and biochemical experiments demonstrated that the organic solvent acetoin can inhibit cell growth by increasing intracellular reactive oxygen species (ROS) production and inducing damage to mitochondria and cell apoptosis. Integrating RT-PCR experiments, the genesfzo1 anddnm1 were overexpressed to regulate the balance between mitochondrial fusion and fission. Enhancement of mitochondrial fusion was shown to significantly increase cell tolerance toward acetoin stress by inhibiting ROS production and increasing the intracellular adenosine triphosphate (ATP) supply, which was also demonstrated by the addition of citrate.

Conclusions

Regulating mitochondrial fusion-fission may be an alternative strategy for rationally improving the growth performance of eukaryotes under high environmental stress conditions, and also expands our knowledge of the mechanisms of cell tolerance through the processes of energy-related metabolic pathways.
Improving input/output performance in 2D and 3D angle-domain common-image gathers from reverse time migration
Authors: Jin Hu , McMechan George A. , Nguyen Bao
Published: March 2015

We have developed a new method of extracting angle-domain common-image gathers (ADCIGs) from prestack reverse time migration (RTM) that has minimal intermediate storage requirements. To include multipathing, we applied an imaging condition for prestack RTM that uses multiple excitation image times. Instead of saving the full-source snapshots at all time steps, we picked and saved only a few of the highest amplitude arrivals, and their corresponding excitation times, of the source wavefield at each grid point, and we crosscorrelated with the receiver wavefield. When extracting the ADCIGs from RTM, we calculated the source propagation direction from the gradient of the excitation times. The result was that the source time snapshots do not have to be saved or reconstructed during RTM or while extracting ADCIGs. We calculated the receiver propagation direction from Poynting vectors during the receiver extrapolation at each time step and the reflector normal direction by the phase-gradient method. With a new strategy that uses three direction vectors (the source and receiver propagation directions as well as the reflector normal direction), we provided more reliable ADCIGs that are free of low-wavenumber artifacts than any two of them do separately, when the migration velocity model was near to the correct velocity model. The 2D and 3D synthetic tests demonstrated the successful application of the new algorithms with acceptable accuracy, improved storage efficiency, and without an input/output bottleneck.