bluuebunny/crossref_metadata_2025 huggingface dataset:
Design, Synthesis and Biological Evaluation of Pyridin‐3‐yl pyrimidines as Potent Bcr‐Abl Inhibitors
Authors: Pan Xiaoyan , Dong Jinyun , Gao Hongping , Wang Fang , Zhang Yanmin , Wang Sicen , Zhang Jie
Published: December 2013

A series of pyridin‐3‐yl pyrimidines was synthesized and evaluated for their Bcr‐Abl inhibitory and anticancer activity. The preliminary results indicated that some compounds were promising anticancer agents. Compounds A2, A8, and A9 exhibited potent Bcr‐Abl inhibitory activity, suggesting that aniline containing halogen substituents might be important for biological activity. Molecular docking was carried out to investigate the binding mode of them with Bcr‐Abl. Details of synthesis and SAR studies of these compounds are described.
SOX‐10 expression in cutaneous myoepitheliomas and mixed tumors
Authors: Naujokas Agne , Charli‐Joseph Yann , Ruben Beth S. , Yeh Iwei , LeBoit Philip E. , McCalmont Timothy H. , Pincus Laura B.
Published: December 2013

Background

SOX‐10 expression can be demonstrated by immunohistochemistry in salivary gland myoepitheliomas, but its expression in cutaneous myoepitheliomas and in cutaneous mixed tumors with prominent myoepithelial cells has not been studied.

Methods

We assessed the staining pattern of SOX‐10 in five cutaneous myoepitheliomas and six cutaneous mixed tumors with a prominent myoepithelial component among both the myoepithelial cells and cells lining lumens. In addition, we examined the staining of S100, microphthalmia‐associated transcription factor (MiTF), keratin cocktail, HMK903, smooth muscle actin (SMA) and epithelial membrane antigen (EMA).

Results

SOX‐10 positivity was seen in three of five (60%) cutaneous myoepitheliomas and in the myoepithelial cells of all cutaneous mixed tumors. SOX‐10 expression on the cells lining the glandular structures in mixed tumors was variable. All myoepitheliomas and mixed tumors stained positively with S100 and negatively with MiTF. Pan‐keratin, HMK903, SMA and EMA showed variable expression.

Conclusions

SOX‐10 is a relatively reliable marker for staining cutaneous myoepitheliomas. Cutaneous myoepitheliomas are notoriously difficult to diagnose, and the addition of SOX‐10 to the repertoire of stains that can label this tumor is of practical utility. These results further support that cutaneous myoepitheliomas and cutaneous mixed tumors exist on a morphologic and immunophenotypic spectrum.
Costs and benefits linked to developments in cognitive control
Authors: Blackwell Katharine A. , Munakata Yuko
Published: December 2013

Developing cognitive control over one's thoughts, emotions, and actions is a fundamental process that predicts important life outcomes. Such control begins in infancy, and shifts during development from a predominantly reactive form (e.g. retrieving task‐relevant information when needed) to an increasingly proactive form (e.g. maintaining task‐relevant information in anticipation of needing it). While such developments are generally viewed as adaptive, cognitive abilities can also involve trade‐offs, such that the benefits of developing increasingly proactive control may come with associated costs. In two experiments, we test for such cognitive trade‐offs in children who are transitioning to proactive control. We find that proactive control predicts expected benefits in children's working memory, but is also associated with predicted costs in disproportionately slowing children under conditions of distraction. These findings highlight unique advantages and disadvantages of proactive and reactive control, and suggest caution in attempting to alter their balance during development.
Prosthesis Migration after Percutaneous Aortic Valve Implantation
Authors: Sozzi Fabiola B. , Eker Armand , Bourlon Francois , Habib Yacoub , Civaia Filippo , Alexandrescu Clara , Dreyfus Gilles , Dor Vincent
Published: December 2013

Mini‐Abstract

A 91‐year‐old man with severe symptomatic aortic stenosis underwent a transfemoral aortic valve (Edwards Sapien XT23) implantation. Migration of the prosthesis into the left ventricular outflow tract occurred a week after. An urgent successful subsequent open heart surgery for device retrieval and prosthesis replacement was performed.
Psychometric validation of the Spanish version of the Dundee Ready Education Environment Measure applied to dental students
Authors: Tomás I. , Casares‐De‐Cal M. A. , Aneiros A. , Abad M. , Ceballos L. , Gómez‐Moreno G. , Hidalgo J. J. , Llena C. , López‐Jornet P. , Machuca M. C. , Monticelli F. , Palés J.
Published: December 2013

Aim

To carry out a psychometric evaluation of the Spanish‐language version of the Dundee Ready Education Environment Measure (DREEM) applied to dental students.

Methods

A total of 1,391 students from nine Spanish public schools of dentistry responded to the DREEM questionnaire. To analyse the reliability of the DREEM questionnaire, the internal consistency was assessed and a ‘test‐retest’ carried out. Validity was evaluated through analysis of item response rate, floor and ceiling effects, corrected item‐total and item‐subscale correlations and factor structure. A confirmatory factor analysis was performed to analyse the structure of the original DREEM scale.

Results

Cronbach's alpha coefficient for the ‘Educational Climate’ (EC) global scale was 0.92. In the subscales, the ‘observed’ Cronbach's alpha coefficients ranged between 0.57 and 0.79 and were higher than the ‘expected’ ones; except for the Social subscale. In the DREEM questionnaire, all of the corrected correlation coefficients between the items and the EC global scale, and the items and their corresponding subscales, were >0.2; except for items 50 and 17. All goodness‐of‐fit indices of confirmatory factor analysis showed acceptable values (close to one or zero, depending on the case), and there was consistency in the results.

Conclusions

The Spanish‐language version of the DREEM questionnaire is a reliable and valid instrument for analysing the EC for dental students and its factor structure is supported by the data. Although our findings indicate that the DREEM may be as culturally independent as was originally stated, more research should be directed at verifying the factor structure in various languages and cultural environments.
Immunophenotypic analysis of T‐acute lymphoblastic leukemia. A CD5‐based ETP‐ALL perspective of non‐ETP T‐ALL
Authors: Chopra Anita , Bakhshi Sameer , Pramanik Suman Kumar , Pandey Ravindra Mohan , Singh Saroj , Gajendra Smeeta , Gogia Ajay , Chandramohan Jagan , Sharma Atul , Kumar Lalit , Seth Rachna , Rai Sandeep , Kumar Rajive
Published: December 2013

T‐cell antigens [CD5,CD1a,CD8] define early T‐cell precursor acute lymphoblastic leukemia (ETP‐ALL). To understand immature T‐ALL of which ETP‐ALL is part, we used these antigens to subcategorize non‐ETP T‐ALL for examining expression of myeloid/stem cell antigens (M/S) and clinical features. Using CD5 (+/−) to start categorization, we studied 69 routinely immunophenotyped patients with T‐ALL. CD5− was a homogenous (CD8,CD1a)− M/S+ ETP‐ALL group (n = 9). CD5+ cases were (CD8,CD1a)− pre‐T‐ALL (n = 22) or (CD8,CD1a)+ (n = 38) thymic/cortical T‐ALL; M/S+ 20/22 (90.91%) in former and 22/38 (57.89%) in latter (P = 0.007). ETP‐ and pre‐T‐ALL together (CD1a−,CD5−/+ immature T‐ALL group) were nearly always M/S+ (29/31; 93.55%). In multivariate analysis, only ETP‐ALL predicted poor overall survival (P = 0.02). We conclude (i) CD5 negativity in T‐ALL almost always means ETP‐ALL. CD1a and CD8 negativity, as much as CD5, marks immaturity in T‐ALL, and the CD5+/−/CD1a−/CD8− immature T‐ALL group needs further study to understand the biology of the T‐ALL–myeloid interface. (ii) ETP‐ALL patients may be pre‐T‐ALL if CD2+; CD2+, conversely, CD5−/CD1a−/CD8− pre‐T ALL patients are ETP‐ALL. (iii) Immunophenotypic workup of T‐ALL must not omit CD1a, CD5, CD8 and CD2, and positivity of antigens should preferably be defined as recommended for ETP‐ALL, so that this entity can be better evaluated in future studies of immature T‐ALL, a group to which ETP‐ALL belongs. (iv) ETP‐ALL has poor prognosis.
Zoledronic acid in the management of bone disease as a consequence of multiple myeloma: a review
Authors: Alegre Adrián , Gironella Mercedes , Bailén Alicia , Giraldo Pilar
Published: December 2013

Background

Multiple myeloma (MM) is a haematological cancer associated with organ damage, essentially bone damage. MM continues to be considered an incurable disease and requires significant therapeutic resources.

Aim

This manuscript presents a literature review of the utility of zoledronic acid (zoledronate) in the management of bone disease in MM.

Discussion

The clinical benefit of bisphosphonates in the prevention and treatment of bone disease in MM has been demonstrated in the last 10 years. A recent network meta‐analysis has evaluated 20 randomised clinical trials with nearly 7000 patients with myeloma enrolled and confirms the role of these agents in the prevention of pain, bone fractures and other skeletal‐related events (SRE) in MM. However, their role on survival remains unclear. Zoledronate has shown significant reductions in SRE compared with placebo or other agents with acceptable tolerability, and recent studies have shown antitumoural effects for this agent, with a marginal survival benefit demonstrated in MM.

Conclusions

Zoledronate prevents SRE in MM and presents a marginal survival benefit that deserves further investigation in controlled studies. Current clinical guidelines should be followed regarding the appropriate use of zoledronate in MM, to enhance its effects and to minimise its potential toxicity.
Continuation of deferiprone therapy in patients with mild neutropenia may not lead to a more severe drop in neutrophil count
Authors: El‐Beshlawy Amal M. , El‐Alfy Mohsen S. , Sari Teny T. , Chan Lee L. , Tricta Fernando
Published: December 2013

Approximately 6% of patients with thalassemia receiving deferiprone develop neutropenia. Present practice is to monitor absolute neutrophil count (ANC) weekly and to interrupt treatment at the first sign of neutropenia, lest continuation lead to progressive neutrophil reduction. In a 6‐month study evaluating the safety and efficacy of a liquid form of deferiprone in 100 children, ANC was initially checked weekly for all patients. For individuals experiencing mild neutropenia, deferiprone was continued but monitoring was increased to daily until resolution. Therapy was to be suspended only if the episode was prolonged or if it worsened. Four patients experienced single episodes of mild neutropenia, and two others each experienced two episodes. All eight episodes resolved within 4–7 d despite continued therapy. (One patient later developed agranulocytosis and had treatment terminated.) This study showed that not all cases of mild neutropenia during deferiprone therapy develop into agranulocytosis, and suggests that many may not be caused by deferiprone. Transient declines in ANC to levels defined as neutropenic are common even in healthy individuals, particularly children; and it could be that the frequent monitoring of ANC mandated during deferiprone therapy may reveal cases of transient neutropenia that would otherwise have gone undetected and resolved on their own without clinical consequences. In patients with thalassemia, several factors increase the probability of a transient fall in ANC. These findings raise the question of whether deferiprone should be routinely stopped in cases of mild neutropenia, provided that such patients have their ANC monitored more frequently during the neutropenic episode.
Alpha‐thalassaemia and response to hydroxyurea in sickle cell anaemia
Authors: Darbari Deepika S. , Nouraie Mehdi , Taylor James G. , Brugnara Carlo , Castro Oswaldo , Ballas Samir K.
Published: December 2013

Background

Hydroxyurea (HU) reduces vaso‐occlusive crises (VOC) and other complications of sickle cell anaemia (SCA). Alpha‐thalassaemia is a known modifier of SCA. Studies on the efficacy of HU in SCA patients with α‐thalassaemia have yielded varying results.

Objective

To determine the effect of α‐thalassaemia in response to HU therapy in the Multicenter Study of Hydroxyurea (MSH) cohort.

Methods

We compared the laboratory parameters and VOC incidence in the MSH cohort stratified by the presence or the absence of α‐thalassaemia.

Results

Hydroxyurea showed significant (P = 0.001 for all baseline vs. follow‐up comparisons) treatment effect on red cell indices irrespective of α‐globin gene deletion. The magnitude of the HU‐related changes was similar for mean corpuscular volume (MCV) (no α‐thalassaemia 13 fl and α‐thalassaemia 13 fl) and mean corpuscular haemoglobin (MCH) (no α‐thalassaemia 4 pg and α‐thalassaemia 4 pg) in both groups. Foetal haemoglobin (HbF) and F‐cells also increased significantly with HU treatment in both groups. Total haemoglobin increased after HU treatment in both groups, but the increase was smaller and not statistically significant in patients with α‐thalassaemia. In contrast, HU‐related reduction in VOCs was more pronounced in patients with α‐thalassaemia (VOC incidence rate ratio HU/placebo: 0.63 for α‐thalassaemia and 0.54 for no α‐thalassaemia (P for interaction 0.003).

Conclusion

Hydroxyurea decreases VOCs in SCA patients with and without α‐thalassaemia, and the degree of VOC reduction was more pronounced in the patients with alpha‐thalassaemia. Despite the lower baseline values, changes in standard laboratory parameters such as MCV and HbF percent remain useful in monitoring HU therapy in the presence of α‐thalassaemia.
Detection of alpha(0)‐thalassemia South‐East Asian‐type deletion by droplet digital PCR
Authors: Pornprasert Sakorn , Prasing Watcharee
Published: December 2013

Background

The α(0)‐thalassemia South‐East Asian (SEA)‐type deletion is the most common genetic disorder in the Asian population. Couples who are both carriers have a 25% chance of conceiving Bart's hydrops fetalis. Therefore, results from carrier screening and prenatal diagnosis frequently need to be available rapidly. The aim of this study was to implement a droplet digital polymerase chain reaction (ddPCR) for diagnosis of α(0)‐thalassemia SEA‐type deletion.

Methods

The wild‐type α‐globin gene allele and α(0)‐thalassemia SEA allele were quantified in DNA samples of 20 normal individuals, 15 samples with α(0)‐thalassemia SEA trait, and 8 samples with Bart's hydrops fetalis using the ddPCR. The DNA copy number of wild‐type α‐globin gene allele and α(0)‐thalassemia SEA allele was then calculated using the Quantasoft analysis software.

Results

The mean ± standard deviation (SD) ratio of wild‐type α‐globin gene allele and α(0)‐thalassemia SEA allele among normal individuals, samples with α(0)‐thalassemia SEA trait, and Bart's hydrops fetalis were clearly distinguished with levels of 1.78 ± 0.49, 0.85 ± 0.14, and 0.03 ± 0.03, respectively.

Conclusion

The ddPCR may be one alternative technology available for routine clinical diagnosis of α(0)‐thalassemia SEA‐type deletion and prenatal diagnosis of Bart's hydrops fetalis.
Management of erythropoiesis: cross‐sectional study of the relationships between erythropoiesis and nutrition, physical features, and adiponectin in 3519 Japanese people
Authors: Kohno Kei , Narimatsu Hiroto , Shiono Yosuke , Suzuki Ikuko , Kato Yuichi , Fukao Akira , Kubota Isao , Ueno Yoshiyuki , Kayama Takamasa , Kato Takeo
Published: December 2013

Although erythroid abnormalities (anemia and polycythemia) are commonly observed pathological conditions, not much information about borderline abnormalities is available. In this study, a cross‐sectional study to analyze the relationships between erythropoiesis and nutrition, physical features, and laboratory test findings was conducted in middle‐aged and older men and women. The study included 3519 Japanese people (1579 men and 1940 women), age 40 years and over. Analysis of variance showed that the group with a tendency to anemia was older, had a lower body mass index and diastolic blood pressure, and had higher serum adiponectin and creatinine. Multiple regression analysis showed that adiponectin, triglycerides, and total protein were common factors that affected erythropoiesis in both men and women. Hepatic, renal, and cardiac functions were also factors involved in erythropoiesis in men and in postmenopausal women. In addition, nutrient factors such as alcohol, vitamins, and carbohydrates were also significantly involved in erythropoiesis in men, but there were no significant nutrient factors involved in erythropoiesis in either premenopausal or postmenopausal women. This study showed that factors that influence erythropoiesis differ between men, premenopausal women, and postmenopausal women, and it suggested that appropriately modifying erythropoiesis management for each group of people is essential.
Neurosystems: brain rhythms and cognitive processing
Authors: Cannon Jonathan , McCarthy Michelle M. , Lee Shane , Lee Jung , Börgers Christoph , Whittington Miles A. , Kopell Nancy
Published: December 2013

Neuronal rhythms are ubiquitous features of brain dynamics, and are highly correlated with cognitive processing. However, the relationship between the physiological mechanisms producing these rhythms and the functions associated with the rhythms remains mysterious. This article investigates the contributions of rhythms to basic cognitive computations (such as filtering signals by coherence and/or frequency) and to major cognitive functions (such as attention and multi‐modal coordination). We offer support to the premise that the physiology underlying brain rhythms plays an essential role in how these rhythms facilitate some cognitive operations.
Hypothalamic hamartoma: Is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis
Authors: Scholly Julia , Valenti Maria‐Paola , Staack Anke M. , Strobl Karl , Bast Thomas , Kehrli Pierre , Steinhoff Bernhard J. , Hirsch Edouard
Published: December 2013

Gelastic seizures associated with hypothalamic hamartomas (HHs) are a clinicoradiologic syndrome presenting with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, electroencephalography (EEG) abnormalities, precocious puberty, behavioral disturbances, and progressive cognitive deterioration. Surgery in adults provides seizure freedom in only one third of patients. The poor results of epilepsy surgery could be explained by an extrahypothalamic epileptogenic zone. The existence of an independent, secondary epileptogenic area with persistent seizures after resection of the presumably primary lesion supports the concept of a “hypothalamic plus” epilepsy. “Hypothalamic plus” epilepsy could be related to either an extrahypothalamic structural lesion (visible on magnetic resonance imaging [MRI] or on neuropathology) or if the former is absent, to a functional alteration with enhanced epileptogenic properties due to a process termed secondary epileptogenesis. We report two patients with gelastic seizures with HH (gelastic seizures isolated or associated with dyscognitive seizures of temporal origin). Both patients underwent two‐step surgery: first an endoscopic resection of the HH, followed at a later time by temporal lobectomy. Both patients became seizure‐free only after the temporal lobectomy. In both cases, neuropathology failed to demonstrate a significant structural lesion in the temporal lobe. To our knowledge, for the first time, these two cases suggest the existence of independent secondary epileptogenesis in humans.
Resecting the epileptogenic tuber: What happens in the long term?
Authors: Shahid Asim
Published: December 2013

Tuberous sclerosis complex (TSC) is an autosomal dominant, neurocutaneous disorder causing benign noninvasive lesions in multiple organ systems. Cognitive delays and neuropsychiatric disorders such as autism are common. Epilepsy is very common and is associated with single or multiple epileptogenic cortical tubers. More than half of these individuals will become medically refractory over time. For these patients, epilepsy surgery with resection of the epileptogenic tuber or tubers not only can render a select patient population seizure‐free, but also improvesIQand cognitive behaviors over time.
The functional relevance of polyploidization in the skin
Authors: Trakala Marianna , Malumbres Marcos
Published: December 2013

Cell proliferation and differentiation are tightly coupled through the regulation of the cell division cycle. To preserve specific functional properties in differentiated cells, distinct variants of the basic mitotic cell cycle are used in various mammalian tissues, leading to the formation of polyploid cells. In this issue of Experimental Dermatology, Gandarillas and Freije discuss the evidences for polyploidization in keratinocytes, a process whose physiological relevance is now becoming evident. A better evaluation of these unconventional cell cycles is required not only to improve our understanding of the development and structure of the epidermis but also for future therapies against skin diseases.
Nuclear Raf‐1 kinase regulates the CXCR5 promoter by associating with NFATc3 to drive retinoic acid‐induced leukemic cell differentiation
Authors: Geil Wendy M. , Yen Andrew
Published: December 2013

Novel functions of signaling molecules have been revealed in studies of cancer stem cells. Retinoic acid (RA) is an embryonic morphogen and stem cell regulator that controls the differentiation of a patient‐derived leukemic cell line, HL‐60, which is composed of progenitor cells with bipotent myelo‐monocytic differentiation capability. RA treatment of HL‐60 cells causes unusually long‐lasting mitogen‐activated protein kinase signaling, with the cells exhibiting the beginning of G0 cell cycle arrest and functional differentiation by 48 h after treatment with RA. This event coincides with the nuclear translocation of Raf‐1, phosphorylated at serine 621. The present study shows how the novel localization of Raf‐1 to the nucleus results in transcriptional changes that contribute to the differentiation of HL‐60 cells induced by RA. We find that nuclear pS621 Raf‐1 associates with NFATc3 near its cognate binding site in the promoter of CXCR5, a gene that must be up‐regulated to drive RA‐induced differentiation. NFATc3 becomes immunoprecipitable with anti‐phosphoserine serum, and CXCR5 is transcriptionally up‐regulated upon RA‐induced differentiation. Inhibiting the pS621 Raf‐1/NFATc3 association with PD98059 inhibits these processes and cripples RA‐induced differentiation. In this novel paradigm for Raf‐1 and RA function, Raf‐1 has a role in driving the nuclear signaling of RA‐induced differentiation of leukemic progenitor cells.

Structured digital abstract

NFATc3 physically interacts with Raf-1 by coimmunoprecipitation (1, 2)
Increased energy maize production reduces farmland bird diversity
Authors: Sauerbrei Ralf , Ekschmitt Klemens , Wolters Volkmar , Gottschalk Thomas K.
Published: December 2013

Producing energy crops as an alternative to fossil fuels in order to reduce CO2 emissions will lead to large‐scale changes in agricultural landscapes. Here, we quantify the potential impact of an increase in maize fields on the diversity of farmland birds by means of high resolution (25 × 25 m) land‐use scenarios. We generated scenarios in which the area of maize production in Germany increases from presently 2.6 to 2.9, 3.6 and 4.3 million ha, corresponding to the energy crop production targets of the German Renewable Energy Act for the years 2020, 2035 and 2050. To test the mitigating potential of conservation measures, each scenario was generated in a standard version and a landscape protection version, with the latter excluding valuable farmland areas from being converted into maize fields. Nine species of farmland birds belonging to the governmental indicator scheme for sustainable land‐use in Germany were modelled for the six nation‐wide scenarios. The models predicted that only the Northern Lapwing and the Little Owl might profit from extended maize production. Despite this, the total number of breeding pairs of the indicator species was predicted to decline by about 0.4 million breeding pairs in the most intensive scenario. Protection of valuable farmland did not mitigate these negative effects in the models. Our findings suggest that increased production of energy crops conflicts with conservation of biological diversity.
The microbiome and regulation of mucosal immunity
Authors: McDermott Andrew J. , Huffnagle Gary B.
Published: December 2013

The gastrointestinal tract is a mucosal surface constantly exposed to foreign antigens and microbes, and is protected by a vast array of immunologically active structures and cells. Epithelial cells directly participate in immunological surveillance and direction of host responses in the gut and can express numerous pattern recognition receptors, including Toll‐like receptor 5 (TLR5), TLR1, TLR2, TLR3, TLR9, and nucleotide oligomerization domain 2, as well as produce chemotactic factors for both myeloid and lymphoid cells following inflammatory stimulation. Within the epithelium and in the underlying lamina propria resides a population of innate lymphoid cells that, following stimulation, can become activated and produce effector cytokines and exert both protective and pathogenic roles during inflammation. Lamina propria dendritic cells play a large role in determining whether the response to a particular antigen will be inflammatory or anti‐inflammatory. It is becoming clear that the composition and metabolic activity of the intestinal microbiome, as a whole community, exerts a profound influence on mucosal immune regulation. The microbiome produces short‐chain fatty acids, polysaccharide A, α‐galactosylceramide and tryptophan metabolites, which can induce interleukin‐22, Reg3γ, IgA and interleukin‐17 responses. However, much of what is known about microbiome–host immune interactions has come from the study of single bacterial members of the gastrointestinal microbiome and their impact on intestinal mucosal immunity. Additionally, evidence continues to accumulate that alterations of the intestinal microbiome can impact not only gastrointestinal immunity but also immune regulation at distal mucosal sites.
Human cell‐based artificial antigen‐presenting cells for cancer immunotherapy
Authors: Butler Marcus O. , Hirano Naoto
Published: December 2013

Adoptive T‐cell therapy, where anti‐tumor T cells are first prepared in vitro, is attractive since it facilitates the delivery of essential signals to selected subsets of anti‐tumor T cells without unfavorable immunoregulatory issues that exist in tumor‐bearing hosts. Recent clinical trials have demonstrated that anti‐tumor adoptive T‐cell therapy, i.e. infusion of tumor‐specific T cells, can induce clinically relevant and sustained responses in patients with advanced cancer. The goal of adoptive cell therapy is to establish anti‐tumor immunologic memory, which can result in life‐long rejection of tumor cells in patients. To achieve this goal, during the process of in vitro expansion, T‐cell grafts used in adoptive T‐cell therapy must be appropriately educated and equipped with the capacity to accomplish multiple, essential tasks. Adoptively transferred T cells must be endowed, prior to infusion, with the ability to efficiently engraft, expand, persist, and traffic to tumor in vivo. As a strategy to consistently generate T‐cell grafts with these capabilities, artificial antigen‐presenting cells have been developed to deliver the proper signals necessary to T cells to enable optimal adoptive cell therapy.
TCR repertoires of intratumoral T‐cell subsets
Authors: Linnemann Carsten , Mezzadra Riccardo , Schumacher Ton N. M.
Published: December 2013

The infiltration of human tumors by T cells is a common phenomenon, and over the past decades, it has become increasingly clear that the nature of such intratumoral T‐cell populations can predict disease course. Furthermore, intratumoral T cells have been utilized therapeutically in clinical studies of adoptive T‐cell therapy. In this review, we describe how novel methods that are either based on T‐cell receptor (TCR) sequencing or on cancer exome analysis allow the analysis of the tumor reactivity and antigen‐specificity of the intratumoral TCR repertoire with unprecedented detail. Furthermore, we discuss studies that have started to utilize these techniques to probe the link between cancer exomes and the intratumoral TCR pool. Based on the observation that both the cancer epitope repertoire and intratumoral TCR repertoire appear highly individual, we outline strategies, such as ‘autologous TCR gene therapy’, that exploit the tumor‐resident TCR repertoire for the development of personalized immunotherapy.
Die Empfehlung für einen nationalen sozialen Basisschutz: Kann ein sechsseitiges Dokument den Kurs der Sozialgeschichte ändern?
Authors: Cichon Michael
Published: December 2013

Auszug

Im Juni 2012 machte die globale Gemeinschaft einen wichtigen Schritt hin zur festen Verankerung des Sozialschutzes als Teil nationaler und globaler Entwicklungsstrategien. Die Internationale Arbeitskonferenz verabschiedete 2012 einstimmig die Empfehlung über nationalen sozialen Basisschutz (Nr. 202), die dem Menschenrecht auf soziale Sicherheit einen konkreten Inhalt gibt. Dieser Artikel betrachtet die Empfehlung im Licht der historischen und politischen Entwicklung von Standards, beschreibt das Auftauchen des Konzepts eines sozialen Basisschutzes und analysiert den Inhalt der neuen Empfehlung sowie einige ihrer politischen Knackpunkte. Sodann wird untersucht, ob dieses neue Instrument das Potenzial hat, die soziale Realität in den 185 Mitgliedsstaaten der IAO zu verändern. Der Artikel kommt zum Schluss, dass die Verabschiedung der Empfehlung eine noch nie dagewesene Demonstration guten Willens und eines weitreichenden globalen Konsenses im Bereich der Sozialpolitik darstellt. Wenn jedoch Raum für einen Wandel der nationalen Sozialpolitiken geschaffen werden soll, dann muss diese Kampagne für ein Mindestmaß an sozialer Sicherheit für alle fortgeführt werden, und sie muss auf der internationalen Agenda gehalten werden. Am Ende des Artikels werden Strategien aufgezählt, die von der globalen Koalition hinter dieser Kampagne verfolgt werden müssen, wenn die soziale Sicherheit ein unabdingbares Ziel nationaler und internationaler Entwicklungsstrategien bleiben oder werden soll.
Finanzierung des sozialen Basisschutzes: Gedanken zum finanzpolitischen Spielraum
Authors: Harris Elliott
Published: December 2013

Auszug

Die Effizienz des Sozialschutzes im Kampf gegen Armut und Bedürftigkeit, bei der Abfederung von Schocks, der Verringerung sozialer Ungleichheit und der Förderung von langfristigem Wachstum ist bewiesen, doch effiziente Systeme der sozialen Sicherung sind in vielen Entwicklungsländern sowie in Ländern mit geringem Einkommen seit geraumer Zeit ein unbezahlbarer Luxus. Das Konzept eines Sockels der sozialen Sicherung besteht in der Einrichtung eines garantierten Minimums an sozialer Sicherheit zu einem vernünftigen Preis, auch in einem Umfeld knapper Ressourcen; ein Sockel, der als Plattform für die graduelle Einführung eines umfassenden Systems der sozialen Sicherheit dient. Die Einführung und Aufrechterhaltung eines solchen Sockels bzw. seine Ausdehnung setzt die gegenwärtige und zukünftige Mobilisierung von Haushaltsmitteln voraus. Der vorliegende Artikel argumentiert, dass bei der Schaffung des dafür notwendigen finanzpolitischen Spielraums zunächst die Vorhersehbarkeit sorgfältig analysiert werden muss, ferner auch die Auswirkungen gegenwärtiger Finanzierungsentscheidungen auf die längerfristige finanzielle Tragfähigkeit von Steuern und Schulden, die gesamtwirtschaftliche Stabilität, Ungleichheit, Armutsminderung und das Wachstum und somit auf den zukünftigen finanziellen Spielraum. Aus dieser Perspektive untersucht der Artikel die Auswirkungen der Schaffung von Haushaltsmitteln durch die zusätzliche Bereitstellung von Ressourcen innerhalb des Landes, ferner durch Neuzuweisung von Ausgaben oder Effizienzsteigerung, Reduzierung des Schuldendienstes oder externe Finanzierungsquellen. Er präsentiert auch eine breite Palette von Maßnahmen zu einem vernünftigen Preis, die auf langfristig tragbare Art und Weise in Ländern mit unterschiedlichen Einkommens‐ und Entwicklungsniveaus getroffen worden sind, sowohl mit eigenen Ressourcen als auch mit externer Finanzierung.
'Between a Rock and a Hard Place': The Coalition, the Davies Commission and the Wicked Issue of Airport Expansion
Authors: GRIGGS STEVEN , HOWARTH DAVID
Published: December 2013

In 2010, the Conservative‐Liberal Democrat Coalition placed a moratorium on airport expansion in the south‐east of England. In office, however, it has faced a sustained political campaign from supporters of the aviation industry and expansion, leading to the appointment in September 2012 of the Davies Commission on airport capacity. This paper critically evaluates this nascent policy reversal in aviation policy, analysing the political backlash in favour of expansion and the political mediation of such demands by the Coalition. It argues that while the shifting political context has placed new pressures on the coalition, its current difficulties cannot be divorced from the continued resonance of the logic of aviation expansion embedded in British institutions at the end of the Second World War. The paper concludes with an assessment of the challenges facing the Davies Commission, the coalition and campaigners, when set against the continued ‘grip’ of aviation on our collective consciousness.
What Is It About Politicians?
Authors: WRIGHT TONY
Published: December 2013

Why do people dislike politicians and could anything be done about it? Drawing upon survey evidence, it is argued that the twin charge against politicians is that they are engaged in a kind of game and that they are a political class out of touch with real life. These charges are examined and found to have at least some merit. Remedies would involve a change in political behaviour; and measures to widen political recruitment. The consequences of not making such changes will be a further erosion of political trust. Constitutional change is less important in tackling dislike of politicians than alterations in political behaviour.
Rawls's Difference Principle as Compensation for Social Immobility
Authors: MACHIN DEAN
Published: December 2013

Outside academia, John Rawls's theory of justice—justice as fairness—has had little impact. This article is part of a broader project to rectify this. I offer a distinctive, second‐best, argument for Rawls's difference principle. The difference principle requires that inequalities in income and wealth are justified only if they benefit society's least‐advantaged citizens. My paper argues that, slightly‐modified, the difference principle is an excellent principle of redress in light of the UK's continued failure to give all citizens fair career chances. I show how we might realize the difference principle at the level of policy through tax rate reductions or negative tax rates. I conclude that if you don't want to accept the second‐best argument for the difference principle you must get serious about giving all citizens fair career chances. As I suggest, this task is extremely difficult.
Religion and the Scottish Independence Referendum
Authors: BONNEY NORMAN
Published: December 2013

The Scottish independence referendum debate, like the Act of Union of 1707, has significant religious dimensions. The Act gave special recognition through the monarch to the Presbyterian Church of Scotland. The Church, a national church, has not yet declared a position on independence, but is seeking to protect its existing privileges whatever the result. The Roman Catholic Church, recognised by the Scottish Parliament, unlike its formal rejection by the UK Parliament and monarchy, symbolically associates itself with the case for independence. Paradoxically, Catholics supporting independence subject themselves, in their religious lives, to an authoritarian foreign power. The SNP Scottish Government attempts to draw Roman Catholic support for independence from its traditional support base in the Labour Party by cultivating a sense of religious grievance that is not justified by the evidence. Old religious divisions are still relevant but non‐religion is growing fast and resulting in new perspectives on the independence debate.
Bovine thoracoscopy: Surgical technique and normal anatomy
Authors: Scharner Doreen , Dorn Katja , Brehm Walter
Published: December 2013

Objective

To describe a surgical technique for thoracoscopy and report visible anatomy within the thoracic cavity of standing cattle.

Study design

Prospective study.

Animals

Adult clinically healthy Holstein–Friesian cows (n = 15).

Methods

Each cow had four thoracoscopic examinations. Initially, the left hemithorax was examined after passive lung collapse, then again 24 hours later after CO2insufflation. The right hemithorax was examined 24 hours later after passive lung collapse and again 24 hours later after CO2insufflation.

Results

CO2insufflation did not significantly improve visibility within the pleural space. Collapsed lung, aorta, esophagus, diaphragm, and azygos vein were readily viewed; however, the pericardial region was not consistently visible. Minor laceration of the lung occurred in 1 cow with adhesions, otherwise there were no intra‐ or postoperative complications. All cows recovered without signs of discomfort. No local swelling or emphysema occurred at the portals.

Conclusions

Thoracoscopy can be safely performed on healthy standing cattle.
Plasma Arc Welding of TiB2–20 vol% TiC
Authors: King Derek S. , Hilmas Greg E. , Fahrenholtz William G.
Published: December 2013

Ceramics consisting of titanium diboride with titanium carbide additions were fusion welded to produce continuous joins. A welding current of 135 A, welding speed of 8 cm/min, and plasma flow rate of 0.75 L/min were combined with a preheat temperature of ~1450°C to fusion weld coupons of TiB2 containing 20 vol% TiC with a thickness of 4 mm. The resulting fusion zone (FZ) was 3.9 mm deep at the center of the joint and 10.4 mm wide. During cooling of the melt pool, four distinct regions of crystal growth and nucleation were observed due to thermal gradients. Regions at the top and bottom of the FZ exhibited smaller TiB2 crystals due to higher nucleation rates whereas regions in the middle of the FZ showed higher growth rates, with TiB2 crystals up to 1.2 mm in length. Thermal gradients also affected cooling of the eutectic phase, causing a cellular structure to appear in the cooled eutectic. Plasma arc welding was a viable method for joining diboride‐based ceramics.
Structural Influence on the Thermal Conversion of Self‐Catalyzed HfB2/ZrB2 Sol–Gel Precursors by Rapid Ultrasonication of Oxychloride Hydrates
Authors: Walker Luke S. , Corral Erica L.
Published: December 2013

Sol–gel precursors to HfB2 and ZrB2 are processed by high‐energy ultrasonication of Hf,Zr oxychloride hydrates, triethyl borate, and phenolic resin to form precipitate‐free sols that turn into stable gels with no catalyst addition. Both precursor concentration and structure (a sol or a gel) are found to influence the synthesis of the diboride phase at high temperature. Decreasing sol concentration increases powder surface area from 3.6 to 6.8 m2/g, whereas heat‐treating a gel leads to residual oxides and carbides. Particles are either fine spherical particles, unique elongated rods, and/or platelets, indicating particle growth with directional coarsening. Investigation of the conversion process to ZrB2 indicates that a multistep reaction is likely taking place with: (1) ZrC formation, (2) ZrC reacts with B2O3 or ZrC reacts with B2O3 and C to form ZrB2. At low temperatures, ZrC formation is limiting, while at higher temperatures the reaction of ZrC to ZrB2 becomes rate limiting. ZrC is found to be a direct reducing agent for B2O3 at low temperature (~1200°C) to form ZrB2 and ZrO2, whereas at high temperatures (~1500°C) it reacts with B2O3 and C to form pure ZrB2.
Local Ordering Around Tetrahedral Co2+ in Silicate Glasses
Authors: Hunault Myrtille , Calas Georges , Galoisy Laurence , Lelong Gérald , Newville Matthew
Published: December 2013

Alkali lime silicate glasses containing 5 wt% of CoO were investigated by Co K‐edge XANES and EXAFS and optical absorption spectroscopy. Our results reveal the presence of tetrahedral Co2+ connected with the glass network, with a IVCo–O–Si angle of 134°. Changing the alkali from K+ to Na+ induces an increase of the local disorder around Co2+, as shown by a decrease of the contribution from the second neighbors in the EXAFS signal. We propose two models for interpreting the structure of the second shell of neighbors. Our results provide a structural basis for rationalizing the optical properties of Co2+ species in glasses.
Highly Transparent Mg0.27Al2.58O3.73N0.27 Ceramic Prepared by Pressureless Sintering
Authors: Liu Xiao , Wang Hao , Tu Bingtian , Wang Weimin , Fu Zhengyi
Published: December 2013

A novel aluminum magnesium oxynitride transparent ceramic with the chemical formula Mg0.27Al2.58O3.73N0.27 was firstly prepared by pressureless sintering of fine single‐phase powders at 1875°C for 24 h in nitrogen atmosphere. The ceramic was fully dense with the average grain size of 57.5 μm. The sample showed excellent in‐line transmission from the visible to middle‐infrared wavelengths with the maximum transmittance of 84%, which could be attributed to rare pores in the sintering body. The material also exhibited good mechanical properties of Vickers hardness (13.39 ± 0.18 GPa), fracture toughness (2.46 ± 0.3 MPa/m1/2), and flexural strength (274 ± 6 MPa).
Large Electrostrictive Strain in (Bi0.5Na0.5)TiO3–BaTiO3–(Sr0.7Bi0.2)TiO3 Solid Solutions
Authors: Shi Jing , Fan Huiqing , Liu Xiao , Bell Andrew J.
Published: December 2013

Relaxor ferroelectrics (0.94 − x)(Bi0.5Na0.5)TiO3–0.06BaTiO3−x(Sr0.7Bi0.2□0.1)TiO3 (BNT–BT–xSBT) (0 ≤ x ≤ 0.5), were prepared by a solid‐state reaction process, and their structures were characterized by the transmission electron microscopy and Raman spectroscopy. The BNT–BT–0.3SBT has a very high electrostrictive strain S = 0.152% with hysteresis‐free behavior, much more than the reported S in other ferroelectrics. S–P2 profiles perfectly follow the quadratic relation, which indicates a purely electrostrictive effect with a high electrostrictive coefficient (Q11) of 0.0297 m4/C2. Even, its Q11 keeps at a high level in the temperature range from ambient temperature to 180°C. The field‐induced large electrostrictive strain of BNT–BT–0.3SBT was attributed to the existence of ferroelectric nanodomains.
Eu‐,Tb‐, and Dy‐Doped Oxyfluoride Silicate Glasses for LED Applications
Authors: Zhu Chaofeng , Wang Jia , Zhang Meimei , Ren Xiaorong , Shen Jianxing , Yue Yuanzheng
Published: December 2013

Luminescence glass is a potential candidate for the light‐emitting diodes (LEDs) applications. Here, we study the structural and optical properties of the Eu‐, Tb‐, and Dy‐doped oxyfluoride silicate glasses for LEDs by means of X‐ray diffraction, photoluminescence spectra, Commission Internationale de L'Eclairage (CIE) chromaticity coordinates, and correlated color temperatures (CCTs). The results show that the white light emission can be achieved in Eu/Tb/Dy codoped oxyfluoride silicate glasses under excitation by near‐ultraviolet light due to the simultaneous generation of blue, green, yellow, and red‐light wavelengths from Tb, Dy, and Eu ions. The optical performances can be tuned by varying the glass composition and excitation wavelength. Furthermore, we observed a remarkable emission spectral change for the Tb3+ single‐doped oxyfluoride silicate glasses. The 5D3 emission of Tb3+ can be suppressed by introducing B2O3 into the glass. The conversion of Eu3+ to Eu2+ takes place in Eu single‐doped oxyfluoride aluminosilicate glasses. The creation of CaF2 crystals enhances the conversion efficiency. In addition, energy transfers from Dy3+ to Tb3+ and Tb3+ to Eu3+ ions occurred in Eu/Tb/Dy codoped glasses, which can be confirmed by analyzing fluorescence spectra and energy level diagrams.
Enhanced Luminescence of Ca14Mg2Si8O28+δN4−δ:Eu2+Phosphors by Codoping Ce3+, Mn2+ for White LEDs and Their Energy‐Transfer Mechanism
Authors: Unithrattil Sanjith , Lee Kyoung Hwa , Im Won Bin
Published: December 2013

The Eu2+, M‐codoped(M = Ce3+, Mn2+) phosphor powders were prepared by a solid‐state reaction. The addition of Ce3+ in the Eu2+ sites in partially nitridated bredigite‐structure phosphor(CMSN) remarkably enhances the luminescent intensity by ~180% through sensitized luminescence. Dual band emission was observed for Eu, Mn‐codoped CMSN through energy transfer from Eu2+ to Mn2+. Ce3+–Eu2+ and Eu2+–Mn2+ energy‐transfer mechanism was investigated through decay profile analysis using Inokuti–Hirayama model and energy‐transfer parameters are determined. Interaction mechanism was identified as dipole–dipole interaction. In addition, phosphor in glass plates was prepared using the phosphor and its feasibility in white LED application was studied and is presented.
Crystallization of Stoichiometric SbSI Glass
Authors: Savytskii Dmytro , Sanders Marisa , Golovchak Roman , Knorr Brian , Dierolf Volkmar , Jain Himanshu
Published: December 2013

Congruent crystallization of antimony sulphoiodide (SbSI) glass of stoichiometric composition, which is prepared successfully for the first time using rapid melt‐quenching, has been investigated using differential scanning calorimetry (DSC). The results for glass powder show a glass transition at 127°C and two separate exothermal peaks with maxima around 140°C and 190°C. The ratio of the intensities of the exothermal peak at ~190°C to the peak at ~140°C increases as the particle size and heating rate are increased, but their total enthalpy remains constant at 62 ± 2 J/g for all DSC runs. Surface heating of the glass induced by a 520 nm CW laser shows two contracted regions: needle‐like crystalline formations at low temperature and bulk crystallization at high temperature. The observed phenomena and DSC results suggest two different kinds of crystallization of the SbSI phase: one‐dimensional crystallization at low temperature which starts from the sample surface and three‐dimensional bulk crystallization that continues the transformation to crystalline state at higher temperatures. The origin of the two different crystallizations can be traced to the strong anisotropy of the SbSI crystal structure due to the weak van der Waals interaction between covalent‐ionic chains (Sb2S2I2)n.
In Situ Mechanical Properties of Chamotte Particulate Reinforced, Potassium Geopolymer
Authors: Musil Sean S. , Kriven Waltraud M.
Published: December 2013

Geopolymers are an inorganic polymeric material composed of alumina, silica, and alkali metal oxides. Monolithic geopolymer is brittle and susceptible to dehydration cracking at elevated temperatures. The addition of a reinforcing phase not only improves strength and toughness but also maintains the structural integrity of the material at elevated temperatures. For this study, potassium‐based geopolymer (KGP) is reinforced with varying weight percent of chamotte particles. Chamotte is kaolinite grade clay calcined at 1350°C to produce 38% crystalline mullite, as well as metastable cristobalite and quartz. The chemical composition of the chamotte is almost identical to that of the metakaolin used to create the geopolymer, however, its crystalline nature prevents reactivity with the caustic potassium silicate solution and it remains as a particulate reinforcement. Flexural strength is evaluated at room temperature and in situ at elevated temperatures to just below the leucite crystallization temperature. Reinforcement with 25 wt% chamotte has shown a two‐fold increase in room‐temperature flexural strength. Flexural strength is also evaluated at room temperature after heating above the leucite crystallization temperature to determine if the chamotte aids in maintaining structural integrity during the volumetric contraction and destructive transformation from cubic to tetragonal symmetry upon forming leucite.