bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of the LMO2 oncogene through a somatically acquired neomorphic promoter in T-cell acute lymphoblastic leukemia
Authors: Rahman Sunniyat , Magnussen Michael , León Theresa E. , Farah Nadine , Li Zhaodong , Abraham Brian J. , Alapi Krisztina Z. , Mitchell Rachel J. , Naughton Tom , Fielding Adele K. , Pizzey Arnold , Bustraan Sophia , Allen Christopher , Popa Teodora , Pike-Overzet Karin , Garcia-Perez Laura , Gale Rosemary E. , Linch David C. , Staal Frank J. T. , Young Richard A. , Look A. Thomas , Mansour Marc R. 
Published: March 2017

Key Points
Recurrent intronic mutations that create probable MYB, ETS1, and RUNX1 binding sites occur at the LMO2 promoter in some T-ALL patients. CRISPR/Cas9-mediated disruption of the mutant MYB site in PF-382 cells markedly downregulates LMO2 expression.
Infiltration of effector regulatory T cells predicts poor prognosis of diffuse large B-cell lymphoma, not otherwise specified
Authors: Nakayama Shoko , Yokote Taiji , Akioka Toshikazu , Hiraoka Nobuya , Nishiwaki Uta , Miyoshi Takuji , Iwaki Kazuki , Takayama Ayami , Masuda Yuki , Hatooka Jun , Fujimoto Mayumi , Nishimura Yasuichiro , Tsuji Motomu 
Published: March 2017

Key PointsIn the patients with DLBCL, NOS, a high infiltration of FOXP3-positive cells in tumor was associated with a better prognosis. However, a high infiltration of FOXP3/CTLA-4 double-positive cells, which are eTregs, was associated with a worse prognosis.
Measuring Cochlear Duct Length – a historical analysis of methods and results
Authors: Koch Robert W. , Ladak Hanif M. , Elfarnawany Mai , Agrawal Sumit K. 
Published: March 2017

Background Cochlear Duct Length (CDL) has been an important measure for the development and advancement of cochlear implants. Emerging literature has shown CDL can be used in preoperative settings to select the proper sized electrode and develop customized frequency maps. In order to improve post-operative outcomes, and develop new electrode technologies, methods of measuring CDL must be validated to allow usage in the clinic. Purpose The purpose of this review is to assess the various techniques used to calculate CDL and provide the reader with enough information to make an informed decision on how to conduct future studies measuring the CDL. Results The methods to measure CDL, the modality used to capture images, and the location of the measurement have all changed as technology evolved. With recent popularity and advancement in computed tomography (CT) imaging in place of histologic sections, measurements of CDL have been focused at the lateral wall (LW) instead of the organ of Corti (OC), due to the inability of CT to view intracochlear structures. After analyzing results from methods such as directly measuring CDL from histology, indirectly reconstructing the shape of the cochlea, and determining CDL based on spiral coefficients, it was determined the three dimensional (3D) reconstruction method is the most reliable method to measure CDL. 3D reconstruction provides excellent visualization of the cochlea and avoids errors evident in other methods. Due to the number of varying methods with varying accuracies, certain guidelines must be followed in the future to allow direct comparison of CDL values between studies. Conclusion After summarizing and analyzing the interesting history of CDL measurements, the use of standardized guidelines and the importance of CDL for future cochlear implant developments is emphasized for future studies.
Neutrophils as active regulators of the immune system in the tumor microenvironment
Authors: Shaul Merav E , Fridlender Zvi G 
Published: March 2017

Abstract
In recent years, the role of immune cells in tumor progression has been a matter of increasing interest. Neutrophils constitute an important portion of the immune cells infiltrating the tumor microenvironment. Traditionally viewed as the first line of defense against infections, it is now well accepted that neutrophils also have an important role in multiple aspects of cancer biology. Multiple and heterogeneous neutrophil subsets have been identified in tumors and in circulation. Evidence from many studies now supports the notion that tumor-associated neutrophils (TANs) show functional plasticity driven by multiple factors present in the tumor microenvironment. In this review, we first concisely discuss the pro-tumor vs. anti-tumor nature of neutrophils in cancer, their functional plasticity, and the mechanisms that regulate neutrophil polarization. We then expand on the various crosstalks and mutual effects between TANs and other tumor-infiltrating immune cell types, emphasizing the active role of neutrophils as regulators of the immune system, promoting or inhibiting the establishment of a permissive tumor microenvironment. Finally, the possible modulation of cancer-related neutrophils by therapies directed toward immune checkpoints is discussed briefly.
Complex electrical conductivity changes associated with hydrous pyrolysis maturation of the Woodford Shale
Authors: Woodruff William F. , Lewan Michael D. , Revil André , Torres-Verdín Carlos 
Published: March 2017

Hydrous closed-system pyrolysis experiments were performed on five pairs of chert cubes from the Woodford Shale aliquots under uniaxial confinement at various prescribed thermal maturities. These thermal maturities represent each of the phases of organic-matter (OM) catagenesis under hydrous conditions: immature kerogen at low thermal stress (125°C for 72 h), low and peak bitumen generation with increasing thermal stress (300°C and 330°C for 72 h), cracking of bitumen to oil and gas at higher thermal stresses (330°C and 360°C for 72 h), and cracking of some oil at the highest experimental conditions (400°C for 72 h). We measured the spectra of the complex electrical conductivity tensor (in the frequency range 10 mHz to 45 kHz) of these 10 aliquots to capture the effects of thermal maturation by hydrous pyrolysis. Results indicate that surface conduction of polar-rich bitumens has a significant effect on their complex electrical conductivity. The OM of a source rock is considered a negligible cause of cation-exchange capacity (CEC), whose parameters influence surface and quadrature conductivity components of the complex electrical conductivity tensor. Part of this CEC was reactivated during the hydrous closed-system pyrolysis experiments. The conspicuous absence of a decrease in electrical conductivity with bitumen and oil generation in the chert cubes recovered from the hydrous-pyrolysis experiments does not agree with the observed increases of well-log resistivity in the natural maturation of some source rocks. Contraction of OM at the contacts with mineral grains is considered a partial cause of this discrepancy, which occurs during the cooling of the experiments to room temperature when no mechanical compaction is applied. Mineral-grain supported rocks such as the chert we studied appear to be especially prone to such a phenomenon.
A Phase 2A randomized, double-blind, placebo-controlled pilot trial of GM604 in patients with Amyotrophic Lateral Sclerosis (ALS Protocol GALS-001) and a single compassionate patient treatment (Protocol GALS-C)
Authors: Kindy Mark , Lupinacci Paul , Chau Raymond , Shum Tony , Ko Dorothy 
Published: March 2017

Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that lacks effective treatment options. Genervon has discovered and developed GM604 (GM6) as a potential ALS therapy. GM6 has been modeled upon an insulin receptor tyrosine kinase binding motoneuronotrophic factor within the developing central nervous system. Methods This was a 2-center phase 2A, randomized, double-blind, placebo-controlled pilot trial with 12 definite ALS patients diagnosed within 2 years of disease onset. Patients received 6 doses of GM604 or placebo, administered as slow IV bolus injections (3x/week, 2 consecutive weeks). Objectives were to assess the safety and efficacy of GM604 based on ALSFRS-R, FVC and selected biomarkers (TDP-43, Tau and SOD1, pNFH). This report also includes results of compassionate treatment protocol GALS-C for an advanced ALS patient. Results Definite ALS patients were randomized to one of two treatment groups (GM604, n = 8; placebo, n = 4). 2 of 8 GM604-treated patients exhibited mild rash, but otherwise adverse event frequency was similar in treated and placebo groups. GM604 slowed functional decline (ALSFRS-R) when compared to a historical control (P = 0.005). At one study site, a statistically significant difference between treatment and control groups was found when comparing changes in respiratory function (FVC) between baseline and week 12 (P = 0.027). GM604 decreased plasma levels of key ALS biomarkers relative to the placebo group (TDP-43, P = 0.008; Tau, P = 0.037; SOD1, P = 0.009). The advanced ALS patient in compassionate treatment demonstrated improved speech, oral fluid consumption, mouth suction with GM604 treatment and biomarker improvements. Conclusions We observed favorable shifts in ALS biomarkers and improved functional measures during the Phase 2A study as well as in an advanced ALS patient. Although a larger trial is needed to confirm these findings, the present data are encouraging and support GM604 as an ALS drug candidate.
A survey of working conditions within biomedical research in the United Kingdom
Authors: Riddiford Nick 
Published: March 2017

Background: Many recent articles have presented a bleak view of career prospects in biomedical research in the US. Too many PhDs and postdocs are trained for too few research positions, creating a “holding-tank” of experienced senior postdocs who are unable to get a permanent position. Coupled with relatively low salaries and the high levels of pressure to publish in top-tier academic journals, this has created a toxic environment that is perhaps responsible for a recently observed decline in biomedical postdocs in the US, the so-called “postdocalypse”. Methods: In order to address the gulf of information relating to working habits and attitudes of UK-based biomedical researchers, a survey was conducted and analysed to examine discrete profiles for three major career stages: the PhD, the postdoc and the principal investigator. Results: Overall, the data presented here echoes trends observed in the US: Scientists in the UK feel disillusioned with academic research, due to the low chance of getting a permanent position and the long hours required at the bench. Also like the US, large numbers of researchers at each distinct career stage are considering leaving biomedical research altogether. Conclusions: There are several systemic flaws in the academic scientific research machine – for example to continual overproduction of PhDs and the lack of stability in the early-mid stages of a research career - that are slowly being addressed in countries such as the US and Germany. This data suggests that similar flaws also exist in the UK, with a large proportion of respondents concerned about their future in research. To avoid lasting damage to the biomedical research agenda in the UK, addressing such concerns should be a major priority.
A comparative analysis of the factors driving film cycles: Italian and American zombie film production, 1978–82
Authors: Platts Todd K. 
Published: March 2017

Abstract
This study shines light on the general factors involved in film cycle development and non-development through a focus on Dawn of the Dead’s (Romero, 1978/79) influence in the Italian and US film markets. Four factors, commercial success, sociopolitical events and broader social currents, supporting cultural phenomena and ephemera, and industrial compatibility, are comparatively assessed with respect to the Italian zombie cycle from 1978 to 1981 and the lack of an American cycle from the same period. The comparative approach advanced in the article properly historicizes the development of zombie cinema after one of its landmark films. Moreover, while the approach is applied to late 1970s/early 1980s zombie cinema, it offers a general analytic for future film cycle scholarship.
Longitudinal Changes in Component Processes of Working Memory
Authors: Rieckmann Anna , Pudas Sara , Nyberg Lars 
Published: March 2017

AbstractWorking memory (WM) entails maintenance and manipulation of information in the absence of sensory input. This study investigated the trajectories and neural basis of these component processes of WM functions in aging. Longitudinal human functional magnetic resonance imaging (fMRI) data are presented from 136 older individuals (55–80 years) who were scanned at baseline and again 4 years later. We obtained evidence that age-related changes in parietal and frontal components of the WM core network are dissociable in terms of their role in maintenance of perceptual representations and further manipulation of this information, respectively. Individual difference analyses in performance subgroups showed that only prefrontal changes in fMRI activation were accompanied by changes in performance, but parietal brain activity was related to study dropout. We discuss the results in terms of possible neurobiological causes underlying separable aging-related declines in inferior parietal cortex and lateral prefrontal cortex that differentially affect WM functions.
Functional and structural insight into properdin control of complement alternative pathway amplification
Authors: Pedersen Dennis V , Roumenina Lubka , Jensen Rasmus K , Gadeberg Trine AF , Marinozzi Chiara , Picard Capucine , Rybkine Tania , Thiel Steffen , Sørensen Uffe BS , Stover Cordula , Fremeaux‐Bacchi Veronique , Andersen Gregers R 
Published: March 2017

AbstractProperdin (FP) is an essential positive regulator of the complement alternative pathway (AP) providing stabilization of the C3 and C5 convertases, but its oligomeric nature challenges structural analysis. We describe here a novel FP deficiency (E244K) caused by a single point mutation which results in a very low level of AP activity. Recombinant FP E244K is monomeric, fails to support bacteriolysis, and binds weakly to C3 products. We compare this to a monomeric unit excised from oligomeric FP, which is also dysfunctional in bacteriolysis but binds the AP proconvertase, C3 convertase, C3 products and partially stabilizes the convertase. The crystal structure of such a FP‐convertase complex suggests that the major contact between FP and the AP convertase is mediated by a single FP thrombospondin repeat and a small region in C3b. Small angle X‐ray scattering indicates that FP E244K is trapped in a compact conformation preventing its oligomerization. Our studies demonstrate an essential role of FP oligomerization in vivo while our monomers enable detailed structural insight paving the way for novel modulators of complement.
PNPLA3 and RNF7 Gene Variants are Associated with the Risk of Developing Liver Fibrosis and Cirrhosis in an Eastern European Population
Authors: Kupcinskas Juozas , Valantiene Irena , Varkalaitė Greta , Steponaitiene Ruta , Skieceviciene Jurgita , Sumskiene Jolanta , Petrenkiene Vitalija , Kondrackiene Jurate , Kiudelis Gediminas , Lammert Frank , Kupcinskas Limas 
Published: March 2017

Background & Aims: Genome-wide association studies have revealed an association between the risk of developing liver fibrosis or cirrhosis and the single nucleotide polymorphisms (SNPs) of the PNPLA3, RNF7, MERTK and PCSK7 genes. We aimed to validate these results in an Eastern European population.Methods: We evaluated the associations between the PNPLA3 (rs738409), RNF7 (rs16851720), MERTK (rs4374383) and PCSK7 (rs236918) variants and liver fibrosis and cirrhosis in a series of consecutive patients recruited at the Department of Gastroenterology, Lithuanian University of Health Sciences Hospital, during the period 2012-2015. The study included 317 individuals with liver cirrhosis, 154 individuals with liver fibrosis, and 498 controls. The studied SNPs were determined using RT-PCR TaqMan assays.Results: MERTK and PCSK7 SNPs were not associated with liver fibrosis or cirrhosis. The PNPLA3 SNP rs738409 was associated with a higher risk of developing liver fibrosis (aOR: 1.65, P=0.001) and cirrhosis (aOR: 1.92, P=5.57*10-7). PNPLA3 genotypes were also associated with higher risk of developing liver fibrosis and cirrhosis in dominant (aOR: 1.98, P=2.20*10-5; aOR: 1.67, P=0.008, respectively) and recessive (aOR: 3.94, P=5.16*10-5; aOR: 3.02, P=0.003, respectively) models. RNF7 rs16851720 was associated with liver cirrhosis comparing CC vs. AA + CA genotypes (aOR: 0.26, P=0.020).Conclusion: Our study showed that PNPLA3 rs738409 and RNF7 rs16851720 confer an increased risk of developing liver fibrosis and cirrhosis in this Eastern European population, while the MERTK and PCSK7 SNPs are not associated with these conditions.Abbreviations: GWAS: Genome-wide association studies; HBV: hepatitis B virus; HCV: hepatitis C virus; HH: hereditary hemochromatosis; MERTK: proto-oncogene tyrosine-protein kinase MER; NAFLD: non-alcoholic fatty liver disease; PCSK7: proprotein convertase 7; PNPLA3: patatin-like phospholipase domain containing 3; RNF7: SAG sensitive to apoptosis gene; SNP: single nucleotide polymorphism.
The Effectiveness of Cooperative Learning Strategy through English Village for Teaching Speaking Skill
Authors: Hengki Hengki , Jabu Baso , Salija Kisman 
Published: March 2017

This study has five main purposes (1) to investigate the effectiveness of Cooperative Learning (CL) strategy through English Village (EC) for teaching speaking in communicative language function (2) to investigate the effectiveness of teaching speaking in transactional language function (3) to know the significance change on self confidence after being taught through English Village EV using CL strategy. (4) to know the significance change on self interest (5) to know the significance change on self regulation. The study was experimental by using one-group pretest-posttest design. The target population of this study was, in fact, is all students of English education department of private university or colleges in Indonesia. However, while the accessible population was only students of English department at the Islamic university of Kalimantan. The result of dependent t-test turned out to confirm that CL strategy through EV is effective to teach speaking skill for both, communicative and academic language function. The result of Wilcoxon test turn out to confirm that CL strategy through English is in significance change of the students’ internal factors.
L’ENSEIGNEMENT DU FRANÇAIS LANGUE-CULTURE : REPRÉSENTATIONS, ENJEUX ET CHOIX
Authors: BENTAYEB Razika 
Published: March 2017

RÉSUMÉ. S’il est légitime que chaque langue-culture en tant que système ait ses défenseurs qui veillent à la préserver en gagnant plus d’espace par rapport à d’autres systèmes, la classe du français langue étrangère, dans le contexte algérien, se présente comme un des lieux de rencontre des langues-cultures, d’échanges mais aussi de tensions, voulu par les politiques comme un lieu de défense et de préservation. Sachant que l’institution éducative algérienne veille à la formation de la personnalité des apprenants en prenant en charge en premier lieu les valeurs identitaires qui se déploient à travers la notion d’algérianité; ainsi préserver la culture des apprenants c’est préserver l’algérianité de ces derniers. Mais, en quoi et comment peut-elle contribuer à la préservation des intérêts identitaires nationaux à travers l’enseignement d’une langue étrangère à savoir le FLE ? Les résultats de l’analyse du manuel scolaire de français de la 3ème AS ont démontré que l’institution éducative algérienne propose un enseignementapprentissage du français langue étrangère réduit de sa substance culturel alors que les didacticiens insistent plus que jamais sur le fait que l’on ne peut enseigner-apprendre une langue sans sa culture. Mots-clés : FLE, l’écart, institution éducative, manuel scolaire, représentation. ABSTRACT. While it is legitimate that each language-culture as a system has its defender who are careful to preserve it by gaining more space compared to other systems, the class of French as a foreign language, in the Algerian context, presents itself as one of the meeting places of languages and cultures, exchanges but also tensions, wanted by politicians as a place of defense and preservation. Knowing that the Algerian educational institution is concerned with the formation of personality, which is the first component of the overall profile, learners in the first name in charge first of all of the identity values deployed through the notion of Algerianism; Thus preserving the culture of the learners is preserving the algerianity of the latter. However, what and how can it contribute to the preservation of national identity interests through the teaching of a foreign language, the FLE? The results of the analysis of the French textbook of the third ASE showed that the educational institution proposes a teaching-learning of the FLE reduced of its cultural substance whereas the didacticians insist that one can not teach- Learn a language without her culture. Keywords : educational institution, FLE, gap, representation, textbook
CONCEVOIR UN COURS HYBRIDE EN FRANÇAIS DES AFFAIRES
Authors: KAMÉNOVA Svetla 
Published: March 2017

RÉSUMÉ. Les nouvelles réalités mondiales nous placent dans un contexte d’enseignement/apprentissage hétérogène. La recrudescence des mouvements migratoires, la mobilité interuniversitaire, la conciliation études-travail-famille, par exemple, modifient le profil des classes qui sont dorénavant constituées d’étudiants aux niveaux de connaissances divers, aux parcours éducatifs variés, aux styles d’apprentissage différents. Quelles seraient les solutions didactiques pour gérer l’hétérogénéité en classe? Le mode hybride s’en avère une, avec sa flexibilité et son efficacité surtout pour les apprenants adultes. Hyperliens, vidéos, forums de discussion, collaborations en direct et différé sont quelques-uns des outils multimédias que nous utilisons dans notre cours mixte « Le français des affaires » de l’Université Concordia (Canada) et grâce auxquels les participants profitent de la variété des profils présents dans la classe. Ce mode comporte aussi des contraintes : accorder plus de temps tant pour le professeur que pour les étudiants, établir une complémentarité nécessaire entre séances en présentiel et à distance, posséder une dextérité technique. Mots-clés : apprentissage/enseignement, étudiant-acteur, formule hybride, hétérogénéité, TIC. ABSTRACT. The new global realities create a heterogeneous teaching/learning context. The resurgence of migratory movements, inter-university mobility, and the school-workfamily balance, for example, modify the composition of classes, which are henceforth made up of students with varying levels of knowledge, varied educational backgrounds, and different learning styles. What are the didactic solutions for managing heterogeneity in the classroom? The blended mode, with its flexibility and effectiveness especially for adult learners, is one of them. Hyperlinks, videos, discussion forums, online and offline collaborations are some of the multimedia tools we use in our “Business French” class at Concordia University (Canada), where participants benefit from the variety of student profiles. This mode also has constraints: the need to allow more time for both professor and students, the need to establish complementarity between face-to-face and online sessions, and the requirement of technical skills. Keywords: blended learning, heterogeneity, ICT, learning/teaching, student-actor.