bluuebunny/crossref_metadata_2025 huggingface dataset:
The truth aboutin vitroculture ofCryptosporidiumspecies
Authors: Karanis Panagiotis
Published: November 2017

Cryptosporidiumresearch has focused on the development of infection control, and effective therapy that has thus far been hampered by the inability to cultureCryptosporidium in vitro. Other limitations include inadequate animal models, cumbersome screening procedures for chemotherapeutic approaches and a lack of tools for genetic manipulation. These limitations can, however, be eased by the improvement and focused development ofin vitrocultivation. The ability to culture relevantCryptosporidiumisolatesin vitroand to propagate the life cycle stages that are responsible for causing disease in an infected host is still a critical link. This ability will facilitate other relevant approaches, e.g., the ability to knockout genes and the application of broader screening for drug discoveries and vaccine developments, in combination with new discoveries on the parasite's basic biology, genetic manipulation and new life cycle stages. Success in this effort represents an essential step towards significant progress in the control of cryptosporidiosis.
High-throughput sequencing of kDNA amplicons for the analysis ofLeishmaniaminicircles and identification of Neotropical species
Authors: KOCHER ARTHUR , VALIÈRE SOPHIE , BAÑULS ANNE-LAURE , MURIENNE JÉRÔME
Published: November 2017

Leishmaniakinetoplast DNA contains thousands of small circular molecules referred to as kinetoplast DNA (kDNA) minicercles. kDNA minicircles are the preferred targets for sensitiveLeishmaniadetection, because they are present in high copy number and contain conserved sequence blocks in which polymerase chain reaction (PCR) primers can be designed. On the other hand, the heterogenic nature of minicircle networks has hampered the use of this peculiar genomic region for strain typing. The characterization ofLeishmaniaminicirculomes used to require isolation and cloning steps prior to sequencing. Here, we show that high-throughput sequencing of single minicircle PCR products allows bypassing these laborious laboratory tasks. The 120 bp long minicircle conserved region was amplified by PCR from 18Leishmaniastrains representative of the major species complexes found in the Neotropics. High-throughput sequencing of PCR products enabled recovering significant numbers of distinct minicircle sequences from each strain, reflecting minicircle class diversity. Minicircle sequence analysis revealed patterns that are congruent with current hypothesis ofLeishmaniarelationships. Then, we show that a barcoding-like approach based on minicircle sequence comparisons may allow reliable identifications ofLeishmaniaspp. This work opens up promising perspectives for the study of kDNA minicercles and a variety of applications inLeishmaniaresearch.
The exoteric/esoteric divide and Schellenberg's Sceptical Religion
Authors: DUMSDAY TRAVIS
Published: November 2017

In a ground-breaking series of books, Canadian philosopher J. L. Schellenberg (2005d; 2007b; 2009; 2013a) has developed a systematic non-theistic, non-naturalist philosophy of religion. One of the core claims within his system is that given our limited evidence (and limited capabilities for assessing what evidence we do have), scepticism concerning the truth of religious propositions is at present the only warranted epistemic response. In this article I draw attention to a potential complication for Schellenberg's assessment of the pragmatic implications of this evidential situation, a complication arising from the distinction between exoteric and esoteric religion.
The humanness of artificial non-normative personalities
Authors: Clark Kevin B.
Published: November 2017

Technoscientific ambitions for perfecting human-like machines, by advancing state-of-the-art neuromorphic architectures and cognitive computing, may end in ironic regret without pondering the humanness of fallible artificial non-normative personalities. Self-organizing artificial personalities individualize machine performance and identity through fuzzy conscientiousness, emotionality, extraversion/introversion, and other traits, rendering insights into technology-assisted human evolution, robot ethology/pedagogy, and best practices against unwanted autonomous machine behavior.
The importance of motivation and emotion for explaining human cognition
Authors: Güss C. Dominik , Dörner Dietrich
Published: November 2017

Lake et al. discuss building blocks of human intelligence that are quite different from those of artificial intelligence. We argue that a theory of human intelligence has to incorporate human motivations and emotions. The interaction of motivation, emotion, and cognition is the real strength of human intelligence and distinguishes it from artificial intelligence.
Autonomous development and learning in artificial intelligence and robotics: Scaling up deep learning to human-like learning
Authors: Oudeyer Pierre-Yves
Published: November 2017

Autonomous lifelong development and learning are fundamental capabilities of humans, differentiating them from current deep learning systems. However, other branches of artificial intelligence have designed crucial ingredients towards autonomous learning: curiosity and intrinsic motivation, social learning and natural interaction with peers, and embodiment. These mechanisms guide exploration and autonomous choice of goals, and integrating them with deep learning opens stimulating perspectives.
Intelligent machines and human minds
Authors: Spelke Elizabeth S. , Blass Joseph A.
Published: November 2017

The search for a deep, multileveled understanding of human intelligence is perhaps the grand challenge for 21st-century science, with broad implications for technology. The project of building machines that think like humans is central to meeting this challenge and critical to efforts to craft new technologies for human benefit.
Crossmodal lifelong learning in hybrid neural embodied architectures
Authors: Wermter Stefan , Griffiths Sascha , Heinrich Stefan
Published: November 2017

Lake et al. point out that grounding learning in general principles of embodied perception and social cognition is the next step in advancing artificial intelligent machines. We suggest it is necessary to go further and consider lifelong learning, which includes developmental learning, focused on embodiment as applied in developmental robotics and neurorobotics, and crossmodal learning that facilitates integrating multiple senses.
A usage-based cognitive linguistic (re-)interpretation of priming evidence
Authors: Günther Franziska
Published: November 2017

Usage-based cognitive linguistic (UBCL) theories offer a unifying interpretation of the different (structural vs. [more] lexical) priming effects reported by Branigan & Pickering (B&P), and they provide an ideal basis for explaining contextual influences on priming. However, they also call into question B&P's claim that priming “provides evidence that is directly informative about mental representation” (sect. 1.5, para. 1).
What structural priming can and cannot reveal
Authors: Koring Loes , Reuland Eric
Published: November 2017

The nature of mental representations of linguistic expressions in relation to the time course from intention to articulation is a major issue. We discuss Branigan & Pickering's (B&P's) proposal to use structural priming to tap into this process. We show that their interpretation of their findings cannot be maintained. We reinterpret these results and suggest a revision of their conclusions.
Structural priming is not a Royal Road to representations
Authors: Meyer Antje S.
Published: November 2017

Branigan & Pickering (B&P) propose that the structural priming paradigm is a Royal Road to linguistic representations of any kind, unobstructed by influences of psychological processes. In my view, however, they are too optimistic about the versatility of the paradigm and, more importantly, its ability to provide direct evidence about the nature of stored linguistic representations.
Setting the empirical record straight: Acceptability judgments appear to be reliable, robust, and replicable
Authors: Sprouse Jon , Almeida Diogo
Published: November 2017

Branigan & Pickering (B&P) advocate the use of syntactic priming to investigate linguistic representations and argue that it overcomes several purported deficiencies of acceptability judgments. While we recognize the merit of drawing attention to a potentially underexplored experimental methodology in language science, we do not believe that the empirical evidence supports B&P's claims about acceptability judgments. We present the relevant evidence.
Pivotal Politics and the ideological content of Landmark Laws
Authors: Gray Thomas R. , Jenkins Jeffery A.
Published: November 2017

The Pivotal Politics model (Krehbiel) has significantly influenced the study of American politics, but its core empirical prediction – that the size of the gridlock interval is negatively related to legislative productivity – has not found strong empirical support. We argue that previous research featured a disconnect between the exclusively ideological theory and tests that relied on outcome variables that were not purely ideological. We remedy this by dividing landmark laws (Mayhew) into two counts – those that invoke ideological preferences and those that do not – and uncover results consistent with Pivotal Politics’ core prediction: the size of the gridlock interval is negatively related to the production of ideological legislation. We also find that the size of the gridlock zone is positively related to the production of nonideological legislation. These results hold up in the face of various sensitivity analyses and robustness checks. We further show that Pivotal Politics explains variation in ideological legislation better than alternative theories based on partisan agenda control.
Obstacle avoidance control of a human-in-the-loop mobile robot system using harmonic potential fields
Authors: Ton C. , Kan Z. , Mehta S. S.
Published: November 2017

This paper considers applications where a human agent is navigating a semi-autonomous mobile robot in an environment with obstacles. The human input to the robot can be based on a desired navigation objective, which may not be known to the robot. Additionally, the semi-autonomous robot can be programmed to ensure obstacle avoidance as it navigates the environment. A shared control architecture can be used to appropriately fuse the human and the autonomy inputs to obtain a net control input that drives the robot. In this paper, an adaptive, near-continuous control allocation function is included in the shared controller, which continuously varies the control effort exerted by the human and the autonomy based on the position of the robot relative to obstacles. The developed control allocation function facilitates the human to freely navigate the robot when away from obstacles, and it causes the autonomy control input to progressively dominate as the robot approaches obstacles. A harmonic potential field-based non-linear sliding mode controller is developed to obtain the autonomy control input for obstacle avoidance. In addition, a robust feed-forward term is included in the autonomy control input to maintain stability in the presence of adverse human inputs, which can be critical in applications such as to prevent collision or roll-over of smart wheelchairs due to erroneous human inputs. Lyapunov-based stability analysis is presented to guarantee finite-time stability of the developed shared controller, i.e., the autonomy guarantees obstacle avoidance as the human navigates the robot. Experimental results are provided to validate the performance of the developed shared controller.
DOMINANCE, PROFICIENCY, AND SPANISH HERITAGE SPEAKERS’ PRODUCTION OF ENGLISH AND SPANISH VOWELS
Authors: Shea Christine
Published: November 2017

This study examines how dominance and proficiency relate to Spanish heritage speaker vowel productions. Participants’ normalized vowel measurements were compared to nonheritage native speakers of Spanish and English using the Pillai score, an output of Multivariate Analysis of Variances (MANOVAs) that allows comparisons across distributions of two or more dependent variables. With Pillai scores as the dependent variable, we created two multiple regression models for each language, one with factors related to dominance, one with factors related to proficiency. We use commonality analysis (variance partitioning) to determine the unique and shared contribution of each variable to the regression models. The results showed different patterns of unique and shared variance across English and Spanish for the factors related to dominance and also for proficiency. Given this, we maintain that it is important to preserve dominance and proficiency as separate but related constructs when considering heritage speaker linguistic data.
Do executive functions explain the covariance between internalizing and externalizing behaviors?
Authors: Hatoum Alexander S. , Rhee Soo Hyun , Corley Robin P. , Hewitt John K. , Friedman Naomi P.
Published: November 2017

This study examined whether executive functions (EFs) might be common features of internalizing and externalizing behavior problems across development. We examined relations between three EF latent variables (a common EF factor and factors specific to updating working memory and shifting sets), constructed from nine laboratory tasks administered at age 17, to latent growth intercept (capturing stability) and slope (capturing change) factors of teacher- and parent-reported internalizing and externalizing behaviors in 885 individual twins aged 7 to 16 years. We then estimated the proportion of intercept–intercept and slope–slope correlations predicted by EF as well as the association between EFs and a common psychopathology factor (P factor) estimated from all 9 years of internalizing and externalizing measures. Common EF was negatively associated with the intercepts of teacher-rated internalizing and externalizing behavior in males, and explained 32% of their covariance; in the P factor model, common EF was associated with the P factor in males. Shifting-specific was positively associated with the externalizing slope across sex. EFs did not explain covariation between parent-rated behaviors. These results suggest that EFs are associated with stable problem behavior variation, explain small proportions of covariance, and are a risk factor that that may depend on gender.
Language Ideologies and Minority Language Education: Lessons from Brittany for Kashubia
Authors: Dołowy-Rybińska Nicole , Hornsby Michael
Published: November 2017

In many situations of minority language education, the focus has been on gains in the absolute numbers of speakers, with the result that less attention has been paid to the processes and linguistic outcomes associated with students in these educational programmes. In this article, we initiate a discussion on the revitalization situations in Brittany and Kashubia from a comparative perspective. In particular, we look at the different models of education in each of these regions and examine ethnographic data that highlight the attempts of students to attain legitimate ‘speakerhood’ of the minority languages in question. In particular, we take into the consideration the difficulties associated with these situations of attempted additive multilingualism when the general trend, among the majority populations, is toward standardized monolingualism. By way of a conclusion, we attempt to evaluate the different educational systems in both regions in terms of the production of future generations of ‘successful’ Kashubian and Breton speakers by examining the various language ideologies that are apparent in both situations of language revitalization.
The shelf space and strategic placement of healthy and discretionary foods in urban, urban-fringe and rural/non-metropolitan Australian supermarkets
Authors: Cameron Adrian J
Published: November 2017

Objective

Supermarkets are a key influence on eating behaviours, but it is unknown if the promotion of food within stores varies on a geographic gradient from urban, to urban-fringe and non-metropolitan areas. The present study aimed to assess the shelf space and strategic placement of healthy and discretionary foods in each of urban, urban-fringe and non-metropolitan Australian supermarkets.

Design/Setting

In-store audits were conducted in stores from one of the two major Australian supermarket chains in urban (n19), urban-fringe (n20) and non-metropolitan (n26) areas of Victoria. These audits examined selected food items (crisps/chips, chocolate, confectionery, soft drinks/sodas, fruits and vegetables) and measured the shelf space and the proportion of end-of-aisle and cash register displays containing these products. Store size was measured as the sum of aisle length. Differences in the supermarket food environment with respect to location were assessed, before and after adjustment for neighbourhood socio-economic position.

Results

The strategic placement of discretionary foods was commonly observed in all supermarkets. Adjusting for store size (larger in urban-fringe and rural areas), urban stores had greater shelf space devoted to fruits and vegetables, and less checkouts with soft drinks, than urban-fringe and rural/non-metropolitan areas. Differences remained following adjustment for neighbourhood socio-economic position. No clear pattern was observed for end-of-aisle displays, or the placement of chocolate and confectionery at checkouts.

Conclusions

The shelf space of healthy and discretionary foods in urban-fringe and rural stores parallels the prevalence of overweight and obesity in these areas. Interventions in urban-fringe and rural stores targeting the shelf space of healthy foods and the placement of soft drinks at key displays may be useful obesity prevention initiatives.
Variation in pre-harvest sprouting tolerance and fresh seed germination in mungbean (Vigna radiata L.) genotypes
Authors: Lamichaney Amrit , Katiyar Pradip Kumar , Laxmi Vijay , Pratap Aditya
Published: November 2017

Mungbean seeds, despite being protected inside the pod, are susceptible to pre-harvest sprouting (PHS) following rainfall due to lack of fresh seed dormancy (FSD), which deteriorates the quality of the seed/grain produced. Therefore, development of mungbean cultivars with short (10–15 days) period of FSD has become important to curtail losses incurred by PHS. In this study, we investigated variations in PHS, fresh seed germination (FSG) and activity of α-amylase enzyme in diverse mungbean genotypes. There was a wide variation in PHS tolerance and FSG among 163 genotypes examined and 14 genotypes were found to be tolerant (<20%) to PHS. Seed germination in a pod, a measure used to evaluate PHS, varied from 7.14% in germplasm accession Chamu 4 to 82.52% in cultivated variety IPM 2–3. There was a marked increase in α-amylase activity in genotypes showing high FSG and PHS, especially at 48 and 72 h after germination as compared with PHS tolerant genotypes. Therefore, α-amylase can be used as an effective biochemical marker to evaluate a large number of mungbean genotypes for FSD and PHS. Also, the variation in seed germinability as found in this study could be further used for mungbean improvement programme.
Current Treatment Concepts for Stress Urinary Incontinence
Authors: Rautenberg Oliver , Zivanovic Irena , Kociszewski Jacek , Kuszka Andrzej , Münst Julia , Eisele Lilly , Viereck Nicole , Walser Claudia , Gamper Marianne , Viereck Volker
Published: November 2017

Aktuelle Behandlungskonzepte bei Belastungsinkontinenz

Zusammenfassung. Eine Belastungsinkontinenz sollte immer zuerst konservativ behandelt werden. Schon eine Gewichtsreduktion, Hormonpräparate, Physiotherapie, Beckenbodentraining und/oder die Anwendung von Pessaren können zum Erfolg führen. Nach Ausschöpfen dieser Therapien werden heute Inkontinenzoperationen mit meist sehr guten Heilungschancen (ca. 80–90 %) angeboten. Der operative Goldstandard ist die suburethrale Schlingeneinlage. Die Pelvic-Floor-Sonografie liefert dazu sehr wichtige Hinweise zur Wahl der Operationstechnik und zur Behebung von Komplikationen. Ferner bildet die intra- oder paraurethrale Injektion von Bulking Agents eine vielversprechende, wenig invasive operative Alternative. In diesem Artikel werden Behandlungskonzepte, prä-, intra- und postoperative Untersuchungen, Wahl der Operationsmethode, operationstechnische Details für den Operationserfolg sowie Vorbeugung und Behandlung von Komplikationen diskutiert.
Circular RNA expression is suppressed by androgen receptor (AR)-regulated adenosine deaminase that acts on RNA (ADAR1) in human hepatocellular carcinoma
Authors: Shi Liang , Yan Peijian , Liang Yuelong , Sun Yin , Shen Jiliang , Zhou Senjun , Lin Hui , Liang Xiao , Cai Xiujun
Published: November 2017

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy as a result of complex genetic and epigenetic alterations. HCC is characterized by a clear gender disparity for which there is lack of a clear mechanistic understanding. Androgen receptor (AR) is thought to be critical for such bias. Meanwhile, the potential function of circular RNA (circRNA), regulated by RNA editing enzyme, remained largely unknown in malignancy till now. By utilizing circRNA microarray survey coupled with in vitro analysis, we analyzed the influence of AR on circRNA expression in HCC. Our results indicated that AR could suppress circRNA expression by upregulating ADAR1 p110. Such effect is because AR served as a transcriptional activator of ADAR1 promoter. More significantly, data collected from our center strongly suggest that ADAR1 expression can effectively predict HCC patients’ prognosis and an abnormal overexpression of ADAR1 is positively correlated with AR in HCC. In addition, we found CircARSP91 (hsa_circ_0085154), one of the circRNAs downregulated by AR in an ADAR1-dependent manner, could inhibit HCC tumor growth both in vitro and in vivo. These findings highlight the fact that AR as a contributing factor for gender disparity in HCC can cause complex consequences though regulation of circRNA expression. Better understanding of the roles of circRNA during HCC initiation and progression will provide a novel angle to develop potential HCC therapies.
Reassessment of chitosanase substrate specificities and classification
Authors: Weikert Tobias , Niehues Anna , Cord-Landwehr Stefan , Hellmann Margareta J. , Moerschbacher Bruno M.
Published: November 2017

Chitosanases can be used to produce partially acetylated chitosan oligosaccharides (paCOS) for different applications, provided they are thoroughly characterized. However, recent studies indicate that the established classification system for chitosanases is too simplistic. Here, we apply a highly sensitive method for quantitatively sequencing paCOS to reassess the substrate specificities of the best-characterized class I–III chitosanases. The enzymes’ abilities to cleave bonds at GlcNAc residues positioned at subsite (−1) or (+1), on which the classification system is based, vary especially when the substrates have different fractions of acetylation (F
A
). Conflicts with the recent classification are observed at higher F
A
, which were not investigated in prior specificity determinations. Initial analyses of pectin-degrading enzymes reveal that classifications of other polysaccharide-degrading enzymes should also be critically reassessed. Based on our results, we tentatively suggest a chitosanase classification system which is based on specificities and preferences of subsites (−2) to (+2).
MafB is a critical regulator of complement component C1q
Authors: Tran Mai Thi Nhu , Hamada Michito , Jeon Hyojung , Shiraishi Risako , Asano Keigo , Hattori Motochika , Nakamura Megumi , Imamura Yuki , Tsunakawa Yuki , Fujii Risa , Usui Toshiaki , Kulathunga Kaushalya , Andrea Christina-Sylvia , Koshida Ryusuke , Kamei Risa , Matsunaga Yurina , Kobayashi Makoto , Oishi Hisashi , Kudo Takashi , Takahashi Satoru
Published: November 2017

The transcription factor MafB is expressed by monocytes and macrophages. Efferocytosis (apoptotic cell uptake) by macrophages is important for inhibiting the development of autoimmune diseases, and is greatly reduced inMafb-deficient macrophages. Here, we show the expression of the first protein in the classical complement pathway C1q is important for mediating efferocytosis and is reduced inMafb-deficient macrophages. The efferocytosis defect inMafb-deficient macrophages can be rescued by adding serum from wild-type mice, but not by adding serum from C1q-deficient mice. By hemolysis assay we also show that activation of the classical complement pathway is decreased inMafb-deficient mice. In addition, MafB overexpression induces C1q-dependent gene expression and signals that induce C1q genes are less effective in the absence of MafB. We also show thatMafb-deficiency can increase glomerular autoimmunity, including anti-nuclear antibody deposition. These results show that MafB is an important regulator of C1q.
Structurally triggered metal-insulator transition in rare-earth nickelates
Authors: Mercy Alain , Bieder Jordan , Íñiguez Jorge , Ghosez Philippe
Published: November 2017

Rare-earth nickelates form an intriguing series of correlated perovskite oxides. Apart from LaNiO3, they exhibit on cooling a sharp metal-insulator electronic phase transition, a concurrent structural phase transition, and a magnetic phase transition toward an unusual antiferromagnetic spin order. Appealing for various applications, full exploitation of these compounds is still hampered by the lack of global understanding of the interplay between their electronic, structural, and magnetic properties. Here we show from first-principles calculations that the metal-insulator transition of nickelates arises from the softening of an oxygen-breathing distortion, structurally triggered by oxygen-octahedra rotation motions. The origin of such a rare triggered mechanism is traced back in their electronic and magnetic properties, providing a united picture. We further develop a Landau model accounting for the metal-insulator transition evolution in terms of the rare-earth cations and rationalizing how to tune this transition by acting on oxygen rotation motions.
Intensification of terrestrial carbon cycle related to El Niño–Southern Oscillation under greenhouse warming
Authors: Kim Jin-Soo , Kug Jong-Seong , Jeong Su-Jong
Published: November 2017

The El Niño/Southern Oscillation (ENSO) drives interannual variation in the global carbon cycle. However, the relationship between ENSO and the carbon cycle can be modulated by climate change due to anthropogenic forcing. We show herein that the sensitivity of the terrestrial carbon flux to ENSO will be enhanced under greenhouse warming by 44% ( ± 15%), indicating a future amplification of carbon–climate interactions. Separating the contributions of the changes in carbon sensitivity reveals that the response of land surface temperature to ENSO and the sensitivity of gross primary production to local temperature are significantly enhanced under greenhouse warming, thereby amplifying the ENSO–carbon-cycle coupling. In a warm climate, depletion of soil moisture increases temperature response in a given ENSO event. These findings suggest that the ENSO-related carbon cycle will be enhanced by hydroclimate changes caused by anthropogenic forcing.
The combination of CHK1 inhibitor with G-CSF overrides cytarabine resistance in human acute myeloid leukemia
Authors: Di Tullio Alessandro , Rouault-Pierre Kevin , Abarrategi Ander , Mian Syed , Grey William , Gribben John , Stewart Aengus , Blackwood Elizabeth , Bonnet Dominique
Published: November 2017

Cytarabine (AraC) represents the most effective single agent treatment for AML. Nevertheless, overriding AraC resistance in AML remains an unmet medical need. Here we show that the CHK1 inhibitor (CHK1i) GDC-0575 enhances AraC-mediated killing of AML cells both in vitro and in vivo, thus abrogating any potential chemoresistance mechanisms involving DNA repair. Importantly, this combination of drugs does not affect normal long-term hematopoietic stem/progenitors. Moreover, the addition of CHK1i to AraC does not generate de novo mutations and in patients’ samples where AraC is mutagenic, addition of CHK1i appears to eliminate the generation of mutant clones. Finally, we observe that persistent residual leukemic cells are quiescent and can become responsive to the treatment when forced into cycle via granulocyte colony-stimulating factor (G-CSF) administration. This drug combination (AraC+CHK1i+G-CSF) will open the doors for a more efficient treatment of AML in the clinic.
Checkpoint kinase 1 is essential for normal B cell development and lymphomagenesis
Authors: Schuler Fabian , Weiss Johannes G. , Lindner Silke E. , Lohmüller Michael , Herzog Sebastian , Spiegl Simon F. , Menke Philipp , Geley Stephan , Labi Verena , Villunger Andreas
Published: November 2017

Checkpoint kinase 1 (CHK1) is critical for intrinsic cell cycle control and coordination of cell cycle progression in response to DNA damage. Despite its essential function, CHK1 has been identified as a target to kill cancer cells and studies using Chk1 haploinsufficient mice initially suggested a role as tumor suppressor. Here, we report on the key role of CHK1 in normal B-cell development, lymphomagenesis and cell survival. Chemical CHK1 inhibition induces BCL2-regulated apoptosis in primary as well as malignant B-cells and CHK1 expression levels control the timing of lymphomagenesis in mice. Moreover, total ablation of Chk1 in B-cells arrests their development at the pro-B cell stage, a block that, surprisingly, cannot be overcome by inhibition of mitochondrial apoptosis, as cell cycle arrest is initiated as an alternative fate to limit the spread of damaged DNA. Our findings define CHK1 as essential in B-cell development and potent target to treat blood cancer.
Watt-level 10-gigahertz solid-state laser enabled by self-defocusing nonlinearities in an aperiodically poled crystal
Authors: Mayer A. S. , Phillips C. R. , Keller U.
Published: November 2017

Femtosecond modelocked lasers with multi-gigahertz pulse repetition rates are attractive sources for all applications that require individually resolvable frequency comb lines or high sampling rates. However, the modelocked laser architectures demonstrated so far have several issues, including the need for single-mode pump lasers, limited output power, Q-switching instabilities and challenging cavity geometries. Here, we introduce a technique that solves these issues. In a two-dimensionally patterned quasi-phase-matching (QPM) device, we create a large, low-loss self-defocusing nonlinearity, which simultaneously provides SESAM-assisted soliton modelocking in the normal dispersion regime and suppresses Q-switching induced damage. We demonstrate femtosecond passive modelocking at 10-GHz pulse repetition rates from a simple straight laser cavity, directly pumped by a low-cost highly spatially multimode pump diode. The 10.6-GHz Yb:CaGdAlO4 (Yb:CALGO) laser delivers 166-fs pulses at 1.2 W of average output power. This enables a new class of femtosecond modelocked diode-pumped solid-state lasers with repetition rates at 10 GHz and beyond.
Exposure to Violence Accelerates Epigenetic Aging in Children
Authors: Jovanovic Tanja , Vance L. Alexander , Cross Dorthie , Knight Anna K. , Kilaru Varun , Michopoulos Vasiliki , Klengel Torsten , Smith Alicia K.
Published: November 2017

Epigenetic processes, including DNA methylation, change reliably with age across the lifespan, such that DNA methylation can be used as an “epigenetic clock”. This epigenetic clock can be used to predict age and age acceleration, which occurs when methylation-based prediction of age exceeds chronological age and has been associated with increased mortality. In the current study we examined epigenetic age acceleration using saliva samples collected from children between ages 6–13 (N = 101). Children’s exposure to neighborhood violence and heart rate during a stressful task were assessed. Age acceleration was associated with children’s direct experience of violence (p = 0.004) and with decreased heart rate (p = 0.002). Children who were predicted to be older than their chronological age had twice as much violence exposure as other children and their heart rate was similar to that of adults. The results remained significant after controlling for demographic variables, such as sex, income and education. This is the first study to show the effects of direct violence exposure on epigenetic aging in children using salivary DNA. Although longitudinal studies are needed to determine whether accelerated epigenetic aging leads to adverse health outcomes later in life, these data point to DNA methylation during childhood as a putative biological mechanism.
Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration
Authors: Facchinello Nicola , Tarifeño-Saldivia Estefania , Grisan Enrico , Schiavone Marco , Peron Margherita , Mongera Alessandro , Ek Olivier , Schmitner Nicole , Meyer Dirk , Peers Bernard , Tiso Natascia , Argenton Francesco
Published: November 2017

Type 2 diabetes (T2D) is a disease characterized by impaired insulin secretion. The Wnt signaling transcription factor Tcf7l2 is to date the T2D-associated gene with the largest effect on disease susceptibility. However, the mechanisms by which TCF7L2 variants affect insulin release from β-cells are not yet fully understood. By taking advantage of a tcf7l2 zebrafish mutant line, we first show that these animals are characterized by hyperglycemia and impaired islet development. Moreover, we demonstrate that the zebrafish tcf7l2 gene is highly expressed in the exocrine pancreas, suggesting potential bystander effects on β-cell growth, differentiation and regeneration. Finally, we describe a peculiar vascular phenotype in tcf7l2 mutant larvae, characterized by significant reduction in the average number and diameter of pancreatic islet capillaries. Overall, the zebrafish Tcf7l2 mutant, characterized by hyperglycemia, pancreatic and vascular defects, and reduced regeneration proves to be a suitable model to study the mechanism of action and the pleiotropic effects of Tcf7l2, the most relevant T2D GWAS hit in human populations.
Two opposite size effects of hardness at real nano-scale and their distinct origins
Authors: Yang Rong , Zhang Qun , Xiao Pan , Wang Jun , Bai Yilong
Published: November 2017

Although it has been well known that hardness of metals obtained with conical indenter remains a constant of about 3 times yield strength in conventional tests, and hardness will show a size effect of increasing hardness with decreasing indentation depth in micro-scale beyond 100 nm, the nano-indentation hardness experiments within 100 nm indentation depth usually show a large deviation and unclear trends. We report the cross-validated experimental and numerical results of two opposite depth-dependences of hardness at real nano-scale. That is to say, the indentation size effect (ISE) of hardness of single-crystal copper shows a rapid increase and then a slow decrease with increasing indentation depth within 100 nm depth. All of the results were coss-checked by means of both elaborated nano-indentation experiments with calibrated indenter tips and large scale molecular dynamics (MD) simulations. Further analysis of the MD results and experimental data reveal that the two opposite ISE of nano-hardness should be attributed to the finite roundness of the indenter tip and the intrinsic transition governing property of the material.
Destructive influence of interlayer coupling on Heider balance in bilayer networks
Authors: Górski Piotr J. , Kułakowski Krzysztof , Gawroński Przemysław , Hołyst Janusz A.
Published: November 2017

We consider the problem of Heider balance in a link multiplex, i.e. a special multiplex where coupling exists only between corresponding links. Numerical simulations and analytical calculations demonstrate that the presence of such interlayer connections hinders the emergence of the Heider balance. The effect is especially pronounced when the interactions between layers are negative, similarly as in antiferromagnetically coupled spin layers. The larger is the network, the narrower is the region of coupling parameters where the Heider balance can exist. If the interlayer couplings are of opposite signs and are strong enough, then the link dynamics can be reduced to the system of weakly coupled harmonic oscillators. For large strongly-coupled networks and randomly chosen initial conditions the probability of attaining the Heider balance decreases with the network size N as $${2}^{-{N}^{2}/2}$$

2

−

N

2

/
2

. Our finding can explain a lack of the Heider balance in many social systems, where multilayer structures mediate social interactions.
Encapsulation of primary dopaminergic neurons in a GDNF-loaded collagen hydrogel increases their survival, re-innervation and function after intra-striatal transplantation
Authors: Moriarty Niamh , Pandit Abhay , Dowd Eilís
Published: November 2017

Poor graft survival limits the use of primary dopaminergic neurons for neural repair in Parkinson’s disease. Injectable hydrogels have the potential to significantly improve the outcome of such reparative approaches by providing a physical matrix for cell encapsulation which can be further enriched with pro-survival factors. Therefore, this study sought to determine the survival and efficacy of primary dopaminergic grafts after intra-striatal delivery in a glial-derived neurotrophic factor (GDNF)-loaded collagen hydrogel in a rat model of Parkinson’s disease. After intra-striatal transplantation into the lesioned striatum, the GDNF-enriched collagen hydrogel significantly improved the survival of dopaminergic neurons in the graft (5-fold), increased their capacity for striatal re-innervation (3-fold), and enhanced their functional efficacy. Additional studies suggested that this was due to the hydrogel’s ability to retain GDNF in the microenvironment of the graft, and to protect the transplanted cells from the host immune response. In conclusion, the encapsulation of dopaminergic neurons in a GDNF-loaded hydrogel dramatically increased their survival and function, providing further evidence of the potential of biomaterials for neural transplantation and brain repair in neurodegenerative diseases such as Parkinson’s disease.
Changes in cardiac arrest patients’ temperature management after the publication of 2015 AHA guidelines for resuscitation in China
Authors: Du Lanfang , Ge Baolan , Ma Qingbian , Yang Jianzhong , Chen Fengying , Mi Yuhong , Zhu Huadong , Wang Cong , Li Yan , Zhang Hongbo , Yang Rongjia , Guan Jian , Zhang Yixiong , Jin Guiyun , Zhu Haiyan , Xiong Yan , Wang Guoxing , Zhu Zhengzhong , Zhang Haiyan , Zhang Yun , Zhu Jihong , Li Jie , Lan Chao , Xiong Hui
Published: November 2017

A survey was performed to assess the current management of targeted temperature management (TTM) in patients following cardiac arrest (CA) and whether healthcare providers will change target temperature after publication of 2015 American Heart Association guidelines for resuscitation in China. 52 hospitals were selected from whole of China between August to November 2016. All healthcare providers in EMs and/or ICUs of selected hospitals participated in the study. 1952 respondents fulfilled the survey (86.8%). TTM in CA patients was declared by 14.5% of physicians and 6.7% of the nurses. Only 4 of 64 departments, 7.8% of physicians and 5.7% of the nurses had implemented TH for CA patients. Since the publication of 2015 AHA guidelines, 33.6% of respondents declared no modification of target temperature, whereas 51.5% declared a target temperature’s change in future practice. Respondents were more likely to choose 35∼36 °C-TTM (54.7%) after guidelines publication, as compared to that before guidelines publication they preferred 32∼34 °C-TTM (54.0%). TTM for CA patients was still in the early stage in China. Publication of 2015 resuscitation guidelines did have impact on choice of target temperature among healthcare providers. They preferred 35∼36 °C-TTM after guidelines publication.
Femtosecond to picosecond transient effects in WSe
2
observed by pump-probe angle-resolved photoemission spectroscopy
Authors: Liu Ro-Ya , Ogawa Yu , Chen Peng , Ozawa Kenichi , Suzuki Takeshi , Okada Masaru , Someya Takashi , Ishida Yukiaki , Okazaki Kozo , Shin Shik , Chiang Tai-Chang , Matsuda Iwao
Published: November 2017

Time-dependent responses of materials to an ultrashort optical pulse carry valuable information about the electronic and lattice dynamics; this research area has been widely studied on novel two-dimensional materials such as graphene, transition metal dichalcogenides (TMDs) and topological insulators (TIs). We report herein a time-resolved and angle-resolved photoemission spectroscopy (TRARPES) study of WSe2, a layered semiconductor of interest for valley electronics. The results for below-gap optical pumping reveal energy-gain and -loss Floquet replica valence bands that appear instantaneously in concert with the pump pulse. Energy shift, broadening, and complex intensity variation and oscillation at twice the phonon frequency for the valence bands are observed at time scales ranging from the femtosecond to the picosecond and beyond. The underlying physics is rich, including ponderomotive interaction, dressing of the electronic states, creation of coherent phonon pairs, and diffusion of charge carriers – effects operating at vastly different time domains.
Genome-wide analysis shows that RNase G plays a global role in the stability of mRNAs in Stenotrophomonas maltophilia
Authors: Bernardini Alejandra , Martínez José L.
Published: November 2017

Gene expression is determined by critical processes such as RNA synthesis and degradation. Ribonucleases participate in the coordinated and differential decay of messenger RNAs. We describe a suitable method of normalization and calculation of mRNAs half-life values quantified by RNA-Seq. We determined the mRNA half-lives of more than 2000 genes in Stenotrophomonas maltophilia D457 and in an isogenic RNase G deficient mutant. Median half-lives were 2,74 and 3 min in the wild-type and the rng-deficient strain, respectively. The absence of RNase G resulted in an overall enhancement of mRNA half-life times, showing that many RNAs are targets of RNase G in S. maltophilia. Around 40 genes are likely to be regulated directly by RNase G since their half-lives were more than two-fold higher in the rng-deficient mutant. Gene length, GC content or expression levels did not correlate with mRNAs lifetimes, although groups of genes with different functions showed different RNA half-lives. Further, we predicted 1542 gene pairs to be part of the same operons in S. maltophilia. In contrast to what was described for other bacteria, our data indicate that RNase G has a global role in mRNA stability and consequently in the regulation of S. maltophilia gene expression.
Energy expenditure estimation from respiration variables
Authors: Gilgen-Ammann Rahel , Koller Marcel , Huber Céline , Ahola Riikka , Korhonen Topi , Wyss Thomas
Published: November 2017

The aim of this study was to develop and cross-validate two models to estimate total energy expenditure (TEE) based on respiration variables in healthy subjects during daily physical activities. Ninety-nine male and female subjects systematically varying in age (18–60 years) and body mass index (BMI; 17–36 kg*m−2) completed eleven aerobic activities with a portable spirometer as the criterion measure. Two models were developed using linear regression analyses with the data from 67 randomly selected subjects (50.0% female, 39.9 ± 11.8 years, 25.1 ± 5.2 kg*m−2). The models were cross-validated with the other 32 subjects (49% female, 40.4 ± 10.7 years, 24.7 ± 4.6 kg*m−2) by applying equivalence testing and Bland-and-Altman analyses. Model 1, estimating TEE based solely on respiratory volume, respiratory rate, and age, was significantly equivalent to the measured TEE with a systematic bias of 0.06 kJ*min−1 (0.22%) and limits of agreement of ±6.83 kJ*min−1. Model 1 was as accurate in estimating TEE as Model 2, which incorporated further information on activity categories, heart rate, sex, and BMI. The results demonstrated that respiration variables and age can be used to accurately determine daily TEE for different types of aerobic activities in healthy adults across a broad range of ages and body sizes.
Phospholipase A2-Responsive Phosphate Micelle-Loaded UCNPs for Bioimaging of Prostate Cancer Cells
Authors: Sharipov Mirkomil , Tawfik Salah M. , Gerelkhuu Zayakhuu , Huy Bui The , Lee Yong-Ill
Published: November 2017

We report the effective synthesis of biocompatible upconversion nanoparticles (UCNP)-loaded phosphate micelles and successful delivery of UCNPs to prostate cancer cells via secreted phospholipase A2 (sPLA-2) enzyme cleavage of the loaded micelles for the first time. The activity of the (sPLA-2) enzyme toward the synthesized micelles was investigated and confirmed by LC-MS. TEM results showed that the micelles have a size distribution of 80 to 150 nm, whereas UCNP-loaded micelles range from 200 to 350 nm, indicating the successful loading of UCNPs. The selective release of UCNPs to prostate cancer cells rather than other cells, specifically cervical cancer cells, was observed and confirmed by a range of bioimaging studies. Moreover, cytotoxicity assays confirmed the biocompatibility of the UCNP-loaded micelles.
Metformin transiently inhibits colorectal cancer cell proliferation as a result of either AMPK activation or increased ROS production
Authors: Mogavero Angela , Maiorana Maria Valeria , Zanutto Susanna , Varinelli Luca , Bozzi Fabio , Belfiore Antonino , Volpi Chiara C. , Gloghini Annunziata , Pierotti Marco A. , Gariboldi Manuela
Published: November 2017

Metformin is a widely used and well-tolerated anti-diabetic drug that can reduce cancer risk and improve the prognosis of certain malignancies. However, the mechanism underlying its anti-cancer effect is still unclear. We studied the anti-cancer activity of metformin on colorectal cancer (CRC) by using the drug to treat HT29, HCT116 and HCT116 p53−/− CRC cells. Metformin reduced cell proliferation and migration by inducing cell cycle arrest in the G0/G1 phase. This was accompanied by a sharp decrease in the expression of c-Myc and down-regulation of IGF1R. The anti-proliferative action of metformin was mediated by two different mechanisms: AMPK activation and increase in the production of reactive oxygen species, which suppressed the mTOR pathway and its downstream targets S6 and 4EBP1. A reduction in CD44 and LGR5 expression suggested that the drug had an effect on tumour cells with stem characteristics. However, a colony formation assay showed that metformin slowed the cells’ ability to form colonies without arresting cell growth, as confirmed by absence of apoptosis, autophagy or senescence. Our finding that metformin only transiently arrests CRC cell growth suggests that efforts should be made to identify compounds that combined with the biguanide can act synergistically to induce cell death.