bluuebunny/crossref_metadata_2025_split huggingface dataset:
Re‐adapting T cells for cancer therapy: from mouse models to clinical trials
Authors: Stromnes Ingunn M. , Schmitt Thomas M. , Chapuis Aude G. , Hingorani Sunil R. , Greenberg Philip D. 
Published: December 2013

SummaryAdoptive T‐cell therapy involves the isolation, expansion, and reinfusion of T lymphocytes with a defined specificity and function as a means to eradicate cancer. Our research has focused on specifying the requirements for tumor eradication with antigen‐specific T cells and T cells transduced to express a defined T‐cell receptor (TCR) in mouse models and then translating these strategies to clinical trials. Our design of T‐cell‐based therapy for cancer has reflected efforts to identify the obstacles that limit sustained effector T‐cell activity in mice and humans, design approaches to enhance T‐cell persistence, develop methods to increase TCR affinity/T‐cell functional avidity, and pursue strategies to overcome tolerance and immunosuppression. With the advent of genetic engineering, a highly functional population of T cells can now be rapidly generated and tailored for the targeted malignancy. Preclinical studies in faithful and informative mouse models, in concert with knowledge gained from analyses of successes and limitations in clinical trials, are shaping how we continue to develop, refine, and broaden the applicability of this approach for cancer therapy.
Territory quality affects the relative importance of habitat heterogeneity and interference competition in a long‐lived territorial songbird
Authors: Grünkorn Thomas , Potiek Astrid , Looft Volker , Jonker Rudy M. , Chakarov Nayden , Krüger Oliver 
Published: December 2013

Density‐dependent reproduction is commonly explained by either the habitat heterogeneity (HHH) or individual adjustment (IAH) hypothesis. Under the HHH, high quality territories are assumed to be occupied first. At higher density, occupation of low‐quality territories increases due to lower availability of high‐quality territories, which reduces mean reproductive success. Alternatively, the IAH assumes that increased competition at higher densities reduces reproductive success in all territories. For birds of prey, HHH plays an important role in territorial species, and IAH in socially breeding species. To test the generality of this hypothesis, we studied the mechanism behind density dependence in raven Corvus corax, a long‐lived passerine bird, using long‐term population data from a large number of territories.Population density decreased reproduction, which was explained by increased usage of low quality territories at higher density, supporting the HHH. Density reduced reproduction in low quality territories, but not in high and intermediate quality territories. We additionally compared the explanatory power of different models describing brood size, representing IAH, HHH, or a combination of both. The best model represented a combination of both hypotheses, in which the effect of density depended on territory quality. Our conclusion that both IAH and HHH are supported can be explained by the biology of ravens, where territorial adults not only experience interference competition with other territorial adults, but also with social groups of juveniles and floaters. We conclude that the relative importance of IAH and HHH may depend on variation in territory quality and social structure.
Structural Investigation and Functional Properties of MgxNi1−xFe2O4 Ferrites
Authors: Airimioaei Mirela , Palamaru Mircea‐Nicolae , Iordan Alexandra Raluca , Berthet Patrick , Decorse Claudia , Curecheriu Lavinia , Mitoseriu Liliana 
Published: December 2013

The preparation, structural, microstructural, dielectric, and low temperature magnetic properties of MgxNi1−xFe2O4 (x = 0, 0.17, 0.34, 0.50, 0.66, 0.83, 1) ferrites synthesized by using a self‐combustion sol–gel method is presented. Good insulating properties were found for all the compositions at high frequencies (kHz and MHz range), which might drive the present ceramics as interesting for RF/microwaves applications. By increasing the Mg2+ concentration, the total resistivity strongly increases (from ~106 Ωm for the Ni ferrite to 109 Ωm for the Mg ferrite), corresponding to conductivities in the range 10−9–10−6 S/m at f = 1 Hz. Typical ferrimagnetic character with a small coercivity and saturation magnetization in the range (30–50) Am2/kg, which slightly decreases with increasing the Mg content, were found. On the basis of the combined results from the infrared spectroscopy and XRD analysis, it was shown that the magnetic properties depend on the Mg2+ ions distribution on the octahedral and tetrahedral sites and the experimental saturation magnetization allowed to compute the cation distribution for the MgxNi1−xFe2O4 ferrites.
Sapotaceae biogeography supportsNewCaledonia being an oldDarwinian island
Authors: Swenson Ulf , Nylinder Stephan , Munzinger Jérôme 
Published: December 2013

AbstractAimPanbiogeographers suggest that the biome in New Caledonia is of vicariant origin, dating from the Cretaceous – rather than being the result of repeated dispersal sincec. 37 Ma, when the area is postulated to have re‐emerged afterc. 15 million years of submergence. Distributions of the plant family Sapotaceae were used as a model system to test this, and to elucidate the probabilities of ancestral areas, all phrased in six hypotheses.LocationAustralasia and the Pacific.MethodsWe used a recently published dataset with extensive sampling (168 terminals) from the subfamily Chrysophylloideae and three nuclear ribosomalDNAmarkers. Phylogenetic divergence times and ancestral areas were estimated in a Bayesian framework usingbeast, a relaxed clock method, and with fossil calibration points. Area transition probabilities were modelled using a reversible rate matrix, assigning equal prior probability to each transition between two areas.ResultsOur analyses suggest that Sapotaceae arrived and diversified in New Caledonia nine times during the period 4.2–33.1 Ma. All crown‐node radiations occurred in the Miocene or Pliocene, with stem splits reaching back into the Oligocene. Australia and New Guinea are the most likely source areas for Sapotaceae in New Caledonia, but this archipelago has never acted as a stepping stone for Sapotaceae to disperse into the Pacific.Main conclusionsRepeated dispersal is the only mechanism able to explain the range expansion of Sapotaceae into New Caledonia. The family has successfully colonized the main island nine times since its re‐emergence in the Eocene. We reject the panbiogeographical hypotheses that representatives of Sapotaceae in New Caledonia originated in the Cretaceous, differentiated due to vicariance, and were of Pacific origin. We therefore argue that New Caledonia is an old Darwinian island. The Pacific has been colonized repeatedly and terminal lineages are never older than the islands they inhabit (except for Hawaii). Chrysophylloideae extended across Wallace's Line into Southeast Asia around 20 Ma, when the Australian continent came into juxtaposition with Eurasia.
Long Pacing Pulses Reduce Phrenic Nerve Stimulation in Left Ventricular Pacing
Authors: HJORTSHØJ SØREN , HEATH FINN , HAUGLAND MORTEN , ESCHEN OLE , THØGERSEN ANNA MARGRETHE , RIAHI SAM , TOFT EGON , STRUIJK JOHANNES JAN 
Published: December 2013

Long Pulses in LV PacingIntroductionPhrenic nerve stimulation is a major obstacle in cardiac resynchronization therapy (CRT). Activation characteristics of the heart and phrenic nerve are different with higher chronaxie for the heart. Therefore, longer pulse durations could be beneficial in preventing phrenic nerve stimulation during CRT due to a decreased threshold for the heart compared with the phrenic nerve.We investigated if long pulse durations decreased left ventricular (LV) thresholds relatively to phrenic nerve thresholds in humans.Methods and ResultsEleven patients, with indication for CRT and phrenic nerve stimulation at the intended pacing site, underwent determination of thresholds for the heart and phrenic nerve at different pulse durations (0.3–2.9 milliseconds). The resulting strength duration curves were analyzed by determining chronaxie and rheobase. Comparisons for those parameters were made between the heart and phrenic nerve, and between the models of Weiss and Lapicque as well.In 9 of 11 cases, the thresholds decreased faster for the LV than for the phrenic nerve with increasing pulse duration. In 3 cases, the thresholds changed from unfavorable for LV stimulation to more than a factor 2 in favor of the LV. The greatest change occurred for pulse durations up to 1.5 milliseconds. The chronaxie of the heart was significantly higher than the chronaxie of the phrenic nerve (0.47 milliseconds vs. 0.22 milliseconds [P = 0.029, Lapicque] and 0.79 milliseconds vs. 0.27 milliseconds [P = 0.033, Weiss]).ConclusionLong pulse durations lead to a decreased threshold of the heart relatively to the phrenic nerve and may prevent stimulation of the phrenic nerve in a clinical setting.
Long‐term study of infliximab for psoriasis in daily practice: drug survival depends on combined treatment, obesity and infusion reactions
Authors: Spertino J. , López‐Ferrer A. , Vilarrasa E. , Puig L. 
Published: December 2013

AbstractBackgroundInfiximab has been shown to be highly effective in phase III clinical trials, but limited information is available regarding drug survival and maintenance of efficacy beyond 1 year in real‐life clinical setting.ObjectivesTo analyse the efficacy and safety of infliximab in a large number of patients with a long follow‐up and to identify clinical factors associated with long‐term drug survival.MethodsA retrospective review of patients with moderate‐to‐severe psoriasis treated with infliximab from March 2004 to August 2012 at a tertiary dermatology centre was carried out.ResultsIn total, 63 treatment courses with infliximab were administered to 56 patients. The mean duration of treatment was 31.6 months. The only significant positive predictor of drug survival was combination treatment [hazard ratio (HR) vs. monotherapy 2.90, 95% confidence interval (CI) 1.42–5.92]. Significant negative predictors of drug survival were obesity (HR 0.40, 95% CI 0.19–0.87) and infusion reactions (HR 0.40, 95% CI 0.19–0.87). Infusion reactions occurred in 13 (23%) of our patients and were a reason for discontinuation of treatment in 5.ConclusionsThis retrospective review of a cohort of patients with moderate‐to‐severe psoriasis treated with infliximab in daily practice shows that the PASI75 response rates at 24 and 52 weeks of treatment are similar to those of the pivotal studies, but 37 courses of treatment (59%) had to be discontinued after a median of 12 months. The major cause for discontinuation was loss of response, in 18 cases. Combination treatment, obesity and infusion reactions were found to be predictors of drug survival.
Uncertainty decomposition and reduction in river flood forecasting: Belgian case study
Authors: Van Steenbergen N. , Willems P. 
Published: December 2013

AbstractUncertainty is a key factor to be taken into account in river flood forecasting. Every forecast is subject to several sources of uncertainty. Knowledge on the relative importance of the different sources would be useful to determine the most effective improvement actions to reduce the uncertainty. In this paper, three key uncertainty sources are studied for hydrological flood forecasting in the Belgian case study of the Rivierbeek: model uncertainty, forecasted rainfall uncertainty and uncertainty in the initial conditions. A non‐parametric data‐based approach is used to quantify the total uncertainty in the forecasts. By resimulating in the model historical forecasts with optimal initial conditions and observed rainfall, the uncertainty generated by each of the key sources could be identified. In order to reduce the model uncertainty, which was primarily identified as the most important source of uncertainty, a step‐wise physically based calibration technique was suggested. After recalibration of the model with this technique, a significant reduction of the contribution of the model uncertainty to the total forecast uncertainty could be achieved. Further improvement of the initial conditions, identified as the second most important uncertainty source for short lead times, could be obtained by applying data assimilation. Both uncertainty reduction techniques combined led to a reduction of the total forecast uncertainty with 30% to 40%.
Effects of different head–neck positions on the larynges of ridden horses
Authors: Zebisch A. , May A. , Reese S. , Gehlen H. 
Published: December 2013

SummaryHyperflexion, that is the strong deflection of the horse's head, poll and neck, is a prevalent training technique in equitation. Hyperflexion has come under criticism in recent years for being suspected of affecting the horses' well‐being contrary to animal welfare. The goal of the present study is a comparison between the impacts of different poll‐neck positions on findings in the upper respiratory tract of ridden horses. For this purpose, video recordings of the larynges of 14 horses were taken using an overground endoscope. The videos were recorded at rest and during three different riding phases: firstly, in a stretching posture, secondly, in a working position and, thirdly, in hyperflexion. A comparison between the analyses of the working position and hyperflexion phases revealed a significant reduction in the laryngeal opening area (p = 0.001) with a value of 8.2 ± 5.0%. Furthermore, other parameters of the larynx evaluated also showed a significant diminishment. These changes did not correlate with the age of the horses or their level of education, and they were independent of the individual anatomical conditions of the poll‐neck region. In summary, it can be stated that hyperflexion causes a considerable compression of the larynx.
Methylglyoxal resistance in Bacillus subtilis: contributions of bacillithiol‐dependent and independent pathways
Authors: Chandrangsu Pete , Dusi Renata , Hamilton Chris J. , Helmann John D. 
Published: December 2013

SummaryMethylglyoxal (MG) is a toxic by‐product of glycolysis that damages DNA and proteins ultimately leading to cell death. Protection from MG is often conferred by a glutathione‐dependent glyoxalase pathway. However, glutathione is absent from the low‐GC Gram‐positive Firmicutes, such as Bacillus subtilis. The identification of bacillithiol (BSH) as the major low‐molecular‐weight thiol in the Firmicutes raises the possibility that BSH is involved in MG detoxification. Here, we demonstrate that MG can rapidly and specifically deplete BSH in cells, and we identify both BSH‐dependent and BSH‐independent MG resistance pathways. The BSH‐dependent pathway utilizes glyoxalase I (GlxA, formerly YwbC) and glyoxalase II (GlxB, formerly YurT) to convert MG to d‐lactate. The critical step in this pathway is the activation of the KhtSTU K+ efflux pump by the S‐lactoyl‐BSH intermediate, which leads to cytoplasmic acidification. We show that cytoplasmic acidification is both necessary and sufficient for maximal protection from MG. Two additional MG detoxification pathways operate independent of BSH. The first involves three enzymes (YdeA, YraA and YfkM) which are predicted to be homologues of glyoxalase III that converts MG to d‐lactate, and the second involves YhdN, previously shown to be a broad specificity aldo‐keto reductase that converts MG to acetol.
Search for novel targets of the PII signal transduction protein in Bacteria identifies the BCCP component of acetyl‐CoA carboxylase as a PII binding partner
Authors: Rodrigues Thiago E. , Gerhardt Edileusa C. M. , Oliveira Marco A. , Chubatsu Leda S. , Pedrosa Fabio O. , Souza Emanuel M. , Souza Gustavo A. , Müller‐Santos Marcelo , Huergo Luciano F. 
Published: December 2013

SummaryThe PII family comprises a group of widely distributed signal transduction proteins. The archetypal function of PII is to regulate nitrogen metabolism in bacteria. As PII can sense a range of metabolic signals, it has been suggested that the number of metabolic pathways regulated by PII may be much greater than described in the literature. In order to provide experimental evidence for this hypothesis a PII protein affinity column was used to identify PII targets in Azospirillum brasilense. One of the PII partners identified was the biotin carboxyl carrier protein (BCCP), a component of the acetyl‐CoA carboxylase which catalyses the committed step in fatty acid biosynthesis. As BCCP had been previously identified as a PII target in Arabidopsis thaliana we hypothesized that the PII–BCCP interaction would be conserved throughout Bacteria. In vitro experiments using purified proteins confirmed that the PII–BCCP interaction is conserved in Escherichia coli. The BCCP–PII interaction required MgATP and was dissociated by increasing 2‐oxoglutarate. The interaction was modestly affected by the post‐translational uridylylation status of PII; however, it was completely dependent on the post‐translational biotinylation of BCCP.
Changes in peptidergic neurotransmission during postoperative ileus in rat circular jejunal muscle
Authors: Goetz B. , Benhaqi P. , Glatzle J. , Müller M. H. , Schmitt S. M. , Brändli A. W. , Kreis M. E. , Kasparek M. S. 
Published: December 2013

AbstractBackgroundOur aim was to explore unknown changes in neurotransmission with vasoactive intestinal peptide (VIP) and Substance P (Sub P) during postoperative ileus (POI).MethodsContractile activity of rat circular jejunal muscle strips was studied in five groups (n = 6/group): Naïve controls, sham controls 12 h and 3 days after laparotomy, and rats 12 h, 3 days after induction of POI. Dose‐responses to VIP (10−10–10−7 M), Sub P (3 × 10−10–3 × 10−7 M), and electrical field stimulation (EFS, to study endogenous release of neurotransmitters) were studied with different antagonists. Intestinal transit, inflammatory cells and immunoreactivity for VIP and Sub P were investigated in the bowel wall and cellular Finkel osteo sarcoma expression was determined in vagal afferent and efferent nuclei of the brainstem.Key ResultsPostoperative ileus characterized by delayed intestinal transit and intramural inflammation was associated with an increased inhibitory effect of VIP on contractile activity. A biphasic impact was observed for Sub P with a decrease in its excitatory potential on contractility at 12 h, followed by a later increase 3 days postoperatively. Inhibitory response to EFS was increased, whereas the excitatory response decreased in ileus animals. VIP expression was increased in all postoperative animals while only animals 3 days after ileus induction showed increased Sub P expression in the myenteric plexus. These changes were associated with an activation of afferent but not efferent vagal nuclei in the brain stem.Conclusions & InferencesSpecific, time‐dependent changes in peptidergic neurotransmission with VIP and Sub P occur during POI that are associated with vagal afferent activation, but are independent of the activation of efferent vagal pathways.
ThePseudomonas syringaetypeIIIeffectorHopD1 suppresses effector‐triggered immunity, localizes to the endoplasmic reticulum, and targets theArabidopsis transcription factorNTL9
Authors: Block Anna , Toruño Tania Y. , Elowsky Christian G. , Zhang Chi , Steinbrenner Jens , Beynon Jim , Alfano James R. 
Published: December 2013

SummaryPseudomonas syringaetypeIIIeffectors are known to suppress plant immunity to promote bacterial virulence. However, the activities and targets of these effectors are not well understood.We used genetic, molecular, and cell biology methods to characterize the activities, localization, and target of theHopD1 typeIIIeffector inArabidopsis.HopD1 contributes toP. syringaevirulence inArabidopsis and reduces effector‐triggered immunity (ETI) responses but not pathogen‐associated molecular pattern‐triggered immunity (PTI) responses. Plants expressingHopD1 supported increased growth ofETI‐inducingP. syringaestrains compared with wild‐typeArabidopsis. We show thatHopD1 interacts with the membrane‐tetheredArabidopsis transcription factorNTL9 and demonstrate that this interaction occurs at the endoplasmic reticulum (ER). AP. syringae hopD1mutant andETI‐inducingP. syringaestrains exhibited enhanced growth onArabidopsisntl9mutant plants. Conversely, growth ofP. syringaestrains was reduced in plants expressing a constitutively activeNTL9 derivative, indicating thatNTL9 is a positive regulator of plant immunity. Furthermore,HopD1 inhibited the induction ofNTL9‐regulated genes duringETIbut notPTI.HopD1 contributes toP. syringaevirulence in part by targetingNTL9, resulting in the suppression ofETIresponses but notPTIresponses and the promotion of plant pathogenicity.
Impact of suspected food allergy on emotional distress and family life of parents prior to allergy diagnosis
Authors: Knibb Rebecca C. , Semper Heather 
Published: December 2013

AbstractBackgroundFood allergy is associated with psychological distress in both child and parent. It is unknown whether parental distress is present prior to clinical diagnosis or whether experiences at clinic can reduce any distress present. This study aimed to assess anxiety and depression in parents and the impact of suspected food allergy on the lives of families before and after a visit to an allergy clinic.MethodsOne hundred and twenty‐four parents visiting an allergy clinic for the first time to have their child assessed for food allergy completed a study‐specific questionnaire and the Hospital Anxiety and Depression Scale; 50 parents completed these 4–6 wk later in their own home.ResultsMost parents (86.4%) reported suspected food allergy had an impact on their family life prior to clinic attendance; 76% had made changes to their child's diet. 32.5% of parents had mild‐to‐severe anxiety before their clinic visit; 17.5% had mild‐to‐moderate depression. Post‐clinic, 40% had mild‐to‐severe anxiety; 13.1% had mild‐to‐moderate depression. There were no significant differences in anxiety (p = 0.34) or depression scores (p = 0.09) before and after the clinic visit.ConclusionsAnxiety and depression is present in a small proportion of parents prior to diagnosis of food allergy in their child and this does not reduce in the short term after the clinic visit. Identification of parents at risk of suffering from distress is needed and ways in which we communicate allergy information before and at clinic should be investigated to see if we can reduce distress.