bluuebunny/crossref_metadata_2025 huggingface dataset:
Domino effect in a catastrophic solid oxidizer fire
Authors: Ogle Russell A. , Ramirez Juan C. , Hetrick Todd M.
Published: July 2014

This case study examines a succession of three separate fires which occurred in a period of 4 days at an agricultural chemical manufacturing facility. The facility was located in a small chemical park. The succession of fires illustrates the concept of the domino effect: the first fire caused the second fire, and the second fire caused the third. The final fire was responsible for the total destruction of two businesses and the interruption of a third business. Each fire involved the solid oxidizer sodium chlorate. Despite having manufactured agricultural chemicals for over 25 years, the owner and management of the facility had lost their sense of vulnerability to the hazards of sodium chlorate. The fundamental root cause of these fires was the facility owner's inadequate control of the hazards of sodium chlorate. Workers at the facility had little comprehension of the ability of sodium chlorate to cause organic materials to spontaneously ignite. Housekeeping at the facility was poor. And finally, too large of a quantity of sodium chlorate was stored inside the facility, and this large inventory of solid oxidizer was placed adjacent to combustible materials. Simple procedural safeguards would have been sufficient to prevent the ultimate property damage. © 2014 American Institute of Chemical Engineers Process Saf Prog 34: 167–171, 2015
Biomarker driven population enrichment for adaptive oncology trials with time to event endpoints
Authors: Mehta Cyrus , Schäfer Helmut , Daniel Hanna , Irle Sebastian
Published: July 2014

The development of molecularly targeted therapies for certain types of cancers has led to the consideration of population enrichment designs that explicitly factor in the possibility that the experimental compound might differentially benefit different biomarker subgroups. In such designs, enrollment would initially be open to a broad patient population with the option to restrict future enrollment, following an interim analysis, to only those biomarker subgroups that appeared to be benefiting from the experimental therapy. While this strategy could greatly improve the chances of success for the trial, it poses several statistical and logistical design challenges. Because late‐stage oncology trials are typically event driven, one faces a complex trade‐off between power, sample size, number of events, and study duration. This trade‐off is further compounded by the importance of maintaining statistical independence of the data before and after the interim analysis and of optimizing the timing of the interim analysis. This paper presents statistical methodology that ensures strong control of type 1 error for such population enrichment designs, based on generalizations of the conditional error rate approach. The special difficulties encountered with time‐to‐event endpoints are addressed by our methods. The crucial role of simulation for guiding the choice of design parameters is emphasized. Although motivated by oncology, the methods are applicable as well to population enrichment designs in other therapeutic areas. Copyright © 2014 John Wiley & Sons, Ltd.
A study of library migrations in Java
Authors: Teyton Cédric , Falleri Jean‐Rémy , Palyart Marc , Blanc Xavier
Published: July 2014

Software intensively depends on external libraries whose relevance may change during its life cycle. As a consequence, software developers must periodically reconsider the libraries they depend on, and must think about replacing them for more relevant ones. We refer to this practice as library migration. To find the best replacement for their library, they can rely on information over the Web, but they get quickly overwhelmed by the amount of data they gather. Making the right choice in this context constitutes the topic of our work. The solution we propose is to exhibit and mine the library migrations trends computed by performing a study of a large set of software projects. To perform this analysis, we have defined an automatic approach to compute library dependencies and a semi‐automatic approach that identifies library migrations. Then, we propose a deep analysis of the library migration phenomena by performing a descriptive study of a large set of software projects stored on the Githubplatform. Second, based on our descriptive study, we propose a support to developers who want to migrate their libraries. The main result of our study is that recommendations of libraries can be inferred from the analysis of the migration trends. Copyright © 2014 John Wiley & Sons, Ltd.
Type II Interferon Promotes Differentiation of Myeloid-Biased Hematopoietic Stem Cells
Authors: Matatall Katie A. , Shen Ching-Chieh , Challen Grant A. , King Katherine Y.
Published: July 2014

Interferon gamma (IFNγ) promotes cell division of hematopoietic stem cells (HSCs) without affecting the total HSC number. We postulated that IFNγ stimulates differentiation of HSCs as part of the innate immune response. Here, we report that type II interferon signaling is required, both at baseline and during an animal model of LCMV infection, to maintain normal myeloid development. By separately evaluating myeloid-biased and lymphoid-biased HSC subtypes, we found that myeloid-biased HSCs express higher levels of IFNγ receptor and are specifically activated to divide after recombinant IFNγ exposure in vivo. While both HSC subtypes show increased expression of the transcription factor C/EBPβ after infection, only the myeloid-biased HSCs are transiently depleted from the marrow during the type II interferon-mediated immune response to Mycobacterium avium infection, as measured both functionally and phenotypically. These findings indicate that IFNγ selectively permits differentiation of myeloid-biased HSCs during an innate immune response to infection. This represents the first report of a context and a mechanism for discriminate utilization of the alternate HSC subtypes. Terminal differentiation, at the expense of self-renewal, may compromise HSC populations during states of chronic inflammation. Stem Cells  2014;32:3023–3030
Giving Clients a Backstage Experience: A Case of Dramaturgical Trouble in the Professional Performance of Drug Treatment
Authors: Andersen Ditte
Published: July 2014

Professionals who provide drug treatment to young people seek to approach clients as agents of change, i.e., highlight clients' agency and ownership of treatment plans. On the basis of ethnographic data from two treatment institutions in Denmark, this article investigates how everyday interaction organizes clients' experiences in ways that alternately support and contradict this professional ambition. Notably, findings indicate that talk and material arrangements “backstage” make professionals, not clients, appear as the real agents of change. Clients are increasingly encouraged to participate in meetings “backstage,” where treatment is organized, but, contrary to intentions, clients may experience participation as debasing rather than empowering.
Learning English in the Shadows: Understanding Chinese Learners' Experiences of Private Tutoring
Authors: Yung Kevin Wai‐Ho
Published: July 2014

Given that private tutoring has received increasing attention in research as a global educational phenomenon with significant implications for educational practices, it has become necessary for TESOL researchers and practitioners to become aware of its impact on language learning and pedagogy. This study investigated the learning experience and reflections of 14 Chinese learners who had received English private tutoring (EPT) during their secondary education in Hong Kong. Each participant completed a background questionnaire and participated in a one‐to‐one semistructured interview. The analysis revealed participants' ambivalent and paradoxical attitudes toward EPT. Although they considered EPT indispensable for secondary education, they did not regard it as an effective way to increase their English proficiency because of its excessive focus on examination skills instead of the use of English as a language of global communication. The findings were interpreted with reference to contextual conditions where learning for assessment and competitions prevail. This study sheds light on the world of shadow education that exists beyond the boundaries of mainstream classroom settings. Further research on shadow TESOL practices is needed to help researchers and practitioners in TESOL appreciate the unintended consequences of educational changes and their profound impact on learning as mediated by sociocultural conditions.
Arsenic induces apoptosis by the lysosomal‐mitochondrial pathway in INS‐1 cells
Authors: Pan Xiao , Jiang Liping , Zhong Laifu , Geng Chengyan , Jia Li , Liu Shuang , Guan Huai , Yang Guang , Yao Xiaofeng , Piao Fengyuan , Sun Xiance
Published: July 2014

Recently, long term arsenic exposure was considered to be associated with an increased risk of diabetes mellitus. While a relation of cause‐and‐effect between apoptosis of pancreatic β‐cells and arsenic exposure, the precise mechanisms of these events remains unclear. The aim of this study was to explore arsenic‐induced pancreatic β‐cell apoptosis and the mechanisms of through the possible link between lysosomal and the mitochondrial apoptotic pathway. After exposure to 10 μM of arsenic, the reactive oxygen species (ROS) level was significantly increased at 12 h, while the mitochondrial membrane potential was reduced at 24 h and the lysosomal membrane integrity was disrupted at 48 h. A significant increase in protein expression for cytochrome c was also observed using Western blot analysis after exposure to arsenic for 48 h. To further demonstrate that arsenic reduced the lysosomal membrane integrity, cells pretreated with NH4Cl and exposed to arsenic harbored a lower fluorescence increase than cells that were only exposed to arsenic. In addition, apoptosis was mesured using Hoechst 33342/PI dual staining by microscopy and annexin V‐FITC/propidium iodide dual staining by flow cytometry. The results show an increased uptake of the arsenic dose and the cells changed from dark blue to light blue, karyopyknosis, nuclear chromatin condensation, side set or fracture, and a correlation was found between the number of apoptotic cells and arsenic dose. The result of present study suggest that arsenic may induce pancreatic β‐cell apoptosis through activation of the lysosome‐mitochondrial pathway. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 133–141, 2016.
Protective effects of testosterone propionate on reproductive toxicity caused by Endosulfan in male mice
Authors: Wang Na , Xu Ying , Zhou Xian‐Qing , Wu Yan‐Hua , Li Sheng‐Li , Qiao Xin , Li Yan‐Bo , Sun Zhi‐Wei
Published: July 2014

To investigate the protective effect of testosterone propionate (TP) on reproductive toxicity caused by endosulfan in male mice, three group experiments were designed: the control group received 0 and 0, the endosulfan group received 0.8 and 0, and the endosulfan + TP group received 0.8 mg/kg/d endosulfan and 10 mg/kg/d TP, respectively. The results showed that TP significantly prevented the declines of concentration and motility rates in sperm, reduced the rate of sperm abnormalities in epididymis; and antagonized the decreases in spermatogenous cell and sperm numbers in testes induced by endosulfan. TP also decreased the numbers of cavities formed, prevented the decreases of plasma testosterone and androgen receptor (AR) mRNA in testicular tissue, alleviated the increase of LH induced by endosulfan. It is likely that TP relieve the reproductive toxicity by reversing the endosulfan‐induced decreases in testosterone secretion and AR expression that resulted from the alteration of Leydig cell function. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 142–153, 2016.
Hydro-acoustic precursors of gravity waves generated by surface pressure disturbances localised in space and time
Authors: Renzi Emiliano , Dias F.
Published: July 2014

We consider the mechanics of coupled underwater-acoustic and surface-gravity waves generated by surface pressure disturbances in a slightly compressible fluid. We show that pressure changes on the ocean surface, localised in space and time, can induce appreciable underwater compression waves which are precursors of the surface gravity waves. Although the physical properties of acoustic-gravity waves have already been discussed in the literature, such dynamics was not investigated in previous studies. We derive new results for the underwater compression wave field and discuss the dynamics of its generation and propagation. This work could lead to the design of innovative alert systems for coastal flooding management.
Genotype differences in photosynthetic characteristics and nitrogen efficiency of new-type oilseed rape responding to low nitrogen stress
Authors: WANG G. L. , DING G. D. , XU F. S. , CAI H. M. , ZOU J. , YE X. S.
Published: July 2014

New-type oilseed rape (Brassica napus, ArArCcCc) with introgressed exotic subgenomic components from Brassica rapa (ArAr) and Brassica carinata (BcBcCcCc) showed strong heterosis in both vegetative and reproductive growth. The aim of the current study was to analyse the tolerance of the new-type B. napus with different exotic subgenomic contents to low nitrogen (N) stress. Under hydroponic culture and pot experiments, root system parameters, photosynthetic parameters, relative chlorophyll concentration (SPAD values), biomass, seed yield, seed yield components, N concentration and expressions of genes involved in N transport and assimilation were determined with two new-type B. napus genotypes (N-efficient genotype D4-15 and N-inefficient genotype D1-1) under high-N and low-N levels. Furthermore, N accumulation, N transfer efficiency and N use efficiency (NUE) were analysed in the two genotypes. The hydroponic and potted growth tests showed consistent characteristics in N uptake and utilization efficiency at the seedling stage, and N-efficient genotype (D4-15) showed better growth phenotypes across cultured conditions and N levels. Under the low-N condition, D4-15 produced a larger root system and accumulated more N, and had higher N transfer efficiency and NUE than D1-1. Moreover, D4-15 had significantly higher photosynthetic parameters, photosynthetic NUE and expression levels of the N transporter genes, BnNRT1·1, BnNRT2·5, BnNRT2·7 and BnAMT1·1, in roots or leaves, as well as higher seed yield than that of D1-1 under low-N supply. These results indicated that the N-efficient new-type B. napus D4-15 possessed excellent adaptability to low-N stress, which may be attributed to the highly introgressed exotic subgenomic components from B. rapa and B. carinata, suggesting the possibility of identifying high-nutrient-efficiency germplasm from inter-specific hybrids.
INSIDE THE DYNAMICS OF INDUSTRIAL CAPITALISM: THE MASS PRODUCTION OF CARS IN SPAIN, 1950-1985
Authors: FERNÁNDEZ-DE-SEVILLA TOMÀS
Published: July 2014

In 2010 Spain ranked second among EU-15 countries in the manufacture of passenger cars; however, in 1950 the country’s car production had been purely symbolic. Taking as its starting point the trajectories of the enterprises that have shaped the auto industry in Spain, this study explores the sector’s process of development within the interpretative framework proposed by Alfred D. Chandler in Scale and Scope. Until the mid-1970s, SEAT and FASA-Renault, the sector’s first-movers, maintained their position as industry leaders. The entry of Ford and GM in the 1970s was to restructure the industry as it shifted its focus towards exportation to the European Economic Community. Both market share and net profits are used as indicators of the evolution of each car maker.
A walking control strategy combining global sensory reflex and leg synchronization
Authors: Fu Chenglong , Wang Jianmei , Chen Ken , Yu Zhangguo , Huang Qiang
Published: July 2014

Biped walking can be regarded as a global limit cycle whose stability is difficult to verify by only local sensory feedback. This paper presents a control strategy combining global sensory reflex and leg synchronization. The inverted pendulum angle is utilized as global motion feedback to ensure global stability, and joint synchronization between legs is designed to stabilize bifurcations. The proposed strategy can achieve a stable gait and stabilize bifurcations. The robustness of this approach was evaluated against external disturbances. Walking experiments of a biped actuated by pneumatic muscles were conducted to confirm the validity of the proposed method. Instead of tracking predetermined trajectories, this method uses sensory reflexes to activate motor neurons and coincides with the biological idea wherein inessential degrees-of-freedom are barely controlled rather than strictly controlled.
IS THIS THE REAL LIFE? IS THIS JUST FANTASY?
Authors: Grainger David
Published: July 2014

When the late Freddie Mercury penned these words (1), perhaps he had in mind bringing innovative medicines and devices to patients more quickly.
Growth tightness for groups with contracting elements
Authors: YANG WEN-YUAN
Published: July 2014

We establish growth tightness for a class of groups acting geometrically on a geodesic metric space and containing a contracting element. As a consequence, any group with non-trivial Floyd boundary are proven to be growth tight with respect to word metrics. In particular, all non-elementary relatively hyperbolic group are growth tight. This generalizes previous works of Arzhantseva-Lysenok and Sambusetti. Another interesting consequence is that CAT(0) groups with rank-1 elements are growth tight with respect to CAT(0)-metric.
Social contact patterns of school-age children in Taiwan: comparison of the term time and holiday periods
Authors: CHEN S.-C. , YOU Z.-S.
Published: July 2014

School closure is one of the most common interventions in the early weeks of an influenza pandemic. Few studies have investigated social contact patterns and compared individual student contact characteristics during the school term and holiday periods in Taiwan. Here, we conducted a well-used questionnaire survey in a junior high school (grades 7–8) in June 2013. All 150 diary-based effective questionnaires covering conversation and skin-to-skin contact behaviour were surveyed. Two questionnaires for each participant were designed to investigate the individual-level difference of contact numbers per day during the two periods. The questionnaire response rate was 44%. The average number of contacts during term time (20·0 contacts per day) and holiday periods (12·6 contacts per day) were significantly different (P < 0·05). The dominant contact frequencies and duration were everyday contact (89·10%) and contacts lasting less than 5 minutes (37·09%). The greatest differences occurred within the 13–19 years age groups. The result presented in this study provide an indication of the likely reduction in daily contact frequency that might occur if a school closure policy was adopted in the event of an influenza pandemic in Taiwan. Comparing contact patterns during term time and holiday periods, the number of contacts decreased by 40%. This study is the first research to investigate the contact numbers and contact characteristics for school-age children during the school term and a holiday period in Taiwan. With regard to public health, this study could provide the basic contact information and database for modelling influenza epidemics for minimizing the spread of influenza that depends on personal contacts for transmission.
High-fat diet-related stimulation of sweetness desire is greater in women than in men despite high vegetable intake
Authors: Zhou Bei , Yamanaka-Okumura Hisami , Adachi Chisaki , Kawakami Yuka , Katayama Takafumi , Takeda Eiji
Published: July 2014

Objective

To examine the effects of lunches with different dietary energy densities on food preferences between genders.

Design

Randomized crossover study. Participants were administered the following packed test meals once weekly on a specified day during six sessions: control (150 g of rice with a sautéed beef entrée containing 40 g of raw beef and 240 g of vegetables), high-meat/low-rice, low-vegetable, medium-fat/low-vegetable, high-fat and high-fat/low-vegetable meals. Subjective levels of sensory properties were assessed over time using visual analogue scales.

Setting

University of Tokushima Graduate School, Tokushima, Japan.

Subjects

Sixty-five men and sixty-five women matched by age and BMI.

Results

Men showed significantly stronger desires for salty and fatty foods after meals (P<0·05). Women showed a significantly stronger desire for sweetness from 2 h after the low-vegetable meal, and increasing fat content under high-vegetable conditions caused a significant stimulated sweetness desire in women more than in men (P<0·05). Moreover, after a high-meat/low-rice meal with 100 g of rice, sweetness desire was stronger in women (P=0·024), whereas no significant differences in sweetness desire were shown between genders after another low-energy-density control meal with 150 g of rice.

Conclusions

Men had significantly stronger desires for salty and fatty foods, whereas women preferred sweet food after meals. The sweetness desire in women was stimulated by increasing fat content, even with a high vegetable intake. Low rice intake in a low-energy-density diet also caused a relative stimulation of sweetness desire in women.
NONCOMMUTATIVE REAL ALGEBRAIC GEOMETRY OF KAZHDAN’S PROPERTY (T)
Authors: Ozawa Narutaka
Published: July 2014

It is well known that a finitely generated group ${\rm\Gamma}$ has Kazhdan’s property (T) if and only if the Laplacian element ${\rm\Delta}$ in $\mathbb{R}[{\rm\Gamma}]$ has a spectral gap. In this paper, we prove that this phenomenon is witnessed in $\mathbb{R}[{\rm\Gamma}]$. Namely, ${\rm\Gamma}$ has property (T) if and only if there exist a constant ${\it\kappa}>0$ and a finite sequence ${\it\xi}_{1},\ldots ,{\it\xi}_{n}$ in $\mathbb{R}[{\rm\Gamma}]$ such that ${\rm\Delta}^{2}-{\it\kappa}{\rm\Delta}=\sum _{i}{\it\xi}_{i}^{\ast }{\it\xi}_{i}$. This result suggests the possibility of finding new examples of property (T) groups by solving equations in $\mathbb{R}[{\rm\Gamma}]$, possibly with the assistance of computers.
‘Sound Effects (O.K., Music)’: Steve Reich and the Visual Arts in New York City, 1966–1968
Authors: COLE ROSS
Published: July 2014

This article explores Steve Reich's relationship with New York City's downtown artworld during the latter half of the 1960s, aiming to nuance aspects of early minimalism by tracing diachronic connections with the Park Place gallery, the exhibitionAnti-Illusion: Procedures/Materials, Richard Serra, Sol LeWitt, and movements such as process art and conceptualism. I suggest that, rather than revealing Reich's prior compositional philosophy, his 1968 treatise ‘Music as a Gradual Process’ demonstrated aesthetic cohesion with the stance of a particular milieu, mirroring a broader linguistic turn in contemporaneous art and revealing a certain discrepancy between theory and praxis. Drawing on newspaper reception, I explore Reich's compositions fromMelodica(1966) toPendulum Music(1968), arguing that these pieces gained both aesthetic value and institutional credibility through being understood in relation to concurrent artwork and ideas, affording productive horizons of expectation.
Beware the Lamb: Staging Bach's Passions
Authors: VARWIG BETTINA
Published: July 2014

This article considers the twentieth- and twenty-first-century practice of presenting Johann Sebastian Bach's Passion compositions on stage, in light of recent debates about performativity, presence and liveness. By tracing the history of such stagings from Ferruccio Busoni's plans in the 1920s to contemporary versions by Peter Sellars, Alain Platel, and others, I explore the increasing tendency to turn these canonical works into politically or aesthetically relevant events. Through a close reading of the critical reception of each production, I show how stagings have the capacity to challenge productively our easy familiarity with these pieces outside their initial liturgical setting. Unlike a standard concert presentation, staged performances tend to confront audiences more immediately with the violent imagery and spiritual demands of the Passions, thereby continually renewing the dialogue between Bach's works and later audiences. The article thus offers a contribution to an anthropological enquiry into the present-day cult of Bach and the particular forms of aesthetic pleasure that classical music affords its twenty-first-century devotees.
A NATO perspective on applicability and application of IHL to multinational forces
Authors: Olson Peter M.
Published: July 2014

Questions of the applicability and application of international humanitarian law (IHL) to multinational forces are of central interest to the North Atlantic Treaty Organisation (NATO, also referred to as ‘the Alliance’ or ‘the Organisation’). Far from being incidental, multinational military coordination is the Organisation's raison d’être and the driving concept behind its methods, history and operations. Since the end of the Cold War, it has conducted a series of major multinational military operations – in and around the Balkans, Afghanistan, Libya and elsewhere – in which questions of the application of IHL have inevitably arisen.
Psychosoziale Aspekte bei der Behandlung der HIV-Infektion
Authors: Battegay Manuel , Haerry David Hans-U. , Fehr Jan , Staehelin Cornelia , Wandeler Gilles , Elzi Luigia
Published: July 2014

Psychosoziale Faktoren spielen eine zentrale Rolle in der Behandlung der HIV-Infektion. Sie beeinflussen die Bereitschaft der Patienten, die antiretrovirale Therapie zu beginnen und langfristig erfolgreich einzunehmen. Angst begleitet in unterschiedlichem Ausmaß den ganzen Verlauf der HIV-Infektion, vom „Diagnoseschock“ bis zum Entscheid, eine Therapie zu beginnen. Dies stellt insbesondere eine Herausforderung bei Patienten mit psychiatrischen Komorbiditäten wie Depression oder Suchtkrankheiten und ihren behandelnden Ärzten dar. Stigmatisierung und Diskriminierung im sozialen Umfeld, vom engen familiären Kreis bis hin zum Arbeitsplatz und im Alltag, betreffen die meisten HIV-infizierten Menschen, vor allem Drogenkonsumenten und Migranten. Die Erkennung und Berücksichtigung von psychosozialen Aspekten ist eine der Voraussetzungen für eine erfolgreiche, langfristige HIV-Behandlung.
Is Watching Others Self-Disclose Enjoyable?
Authors: Tsay-Vogel Mina , Beth Oliver Mary
Published: July 2014

Self-disclosure is a means through which closeness, familiarity, and satisfaction are produced between partners. The present study integrated interpersonal and mass communication literature to theoretically inform the outcomes of mediated forms of self-disclosure between a viewer and character on television. Empirically testing the effects of two dimensions of disclosure – depth (low intimacy versus high intimacy) and mode (character-to-viewer versus character-to-character versus narrator-to-viewer) of information delivery – this research supported the prediction that a viewer’s overall enjoyment of witnessing a character self-disclose personal information would be mediated by identification and transportation. The results suggest the meaningful role of “character address” in heightening audience engagement with both the character and narrative. Implications for the similarity of interpersonal and mediated relationships, effective entertainment formats, social reality perceptions, and online self-disclosure are discussed.
Moved to Think
Authors: Bartsch Anne , Kalch Anja , Beth Oliver Mary
Published: July 2014

Recent conceptualizations of eudaimonic entertainment and aesthetic experience highlight the role of emotions in stimulating rewarding experiences of insight, meaning, and reflectiveness among entertainment audiences. The current evidence is mainly correlational, however. This study used an experimental approach to examine the assumed causal influence of being moved, on reflective thoughts. Participants were randomly assigned to see one of two versions of a short film that elicited different levels of feeling moved, while keeping the cognitive, propositional content constant. Feeling moved was conceptualized and operationalized as an affective state characterized by negative valence, moderate arousal, mixed affect, and by the labeling of the experience in terms of feeling moved. As expected, the more moving film version elicited more reflective thoughts, which in turn predicted individuals’ overall positive experience of the film. The effect of the film stimulus on reflective thoughts was fully mediated by individuals’ affective state.
Theory of rapid force spectroscopy
Authors: Bullerjahn Jakob T. , Sturm Sebastian , Kroy Klaus
Published: July 2014

In dynamic force spectroscopy, single (bio-)molecular bonds are actively broken to assess their range and strength. At low loading rates, the experimentally measured statistical distributions of rupture forces can be analysed using Kramers’ theory of spontaneous unbinding. The essentially deterministic unbinding events induced by the extreme forces employed to speed up full-scale molecular simulations have been interpreted in mechanical terms, instead. Here we start from a rigorous probabilistic model of bond dynamics to develop a unified systematic theory that provides exact closed-form expressions for the rupture force distributions and mean unbinding forces, for slow and fast loading protocols. Comparing them with Brownian dynamics simulations, we find them to work well also at intermediate pulling forces. This renders them an ideal companion to Bayesian methods of data analysis, yielding an accurate tool for analysing and comparing force spectroscopy data from a wide range of experiments and simulations.
A tool kit for rapid cloning and expression of recombinant antibodies
Authors: Dodev Tihomir S. , Karagiannis Panagiotis , Gilbert Amy E. , Josephs Debra H. , Bowen Holly , James Louisa K. , Bax Heather J. , Beavil Rebecca , Pang Marie O. , Gould Hannah J. , Karagiannis Sophia N. , Beavil Andrew J.
Published: July 2014

Over the last four decades, molecular cloning has evolved tremendously. Efficient products allowing assembly of multiple DNA fragments have become available. However, cost-effective tools for engineering antibodies of different specificities, isotypes and species are still needed for many research and clinical applications in academia. Here, we report a method for one-step assembly of antibody heavy- and light-chain DNAs into a single mammalian expression vector, starting from DNAs encoding the desired variable and constant regions, which allows antibodies of different isotypes and specificity to be rapidly generated. As a proof of principle we have cloned, expressed and characterized functional recombinant tumor-associated antigen-specific chimeric IgE/κ and IgG1/κ, as well as recombinant grass pollen allergen Phl p 7 specific fully human IgE/λ and IgG4/λ antibodies. This method utilizing the antibody expression vectors, available at Addgene, has many applications, including the potential to support simultaneous processing of antibody panels, to facilitate mechanistic studies of antigen-antibody interactions and to conduct early evaluations of antibody functions.
Carbohydrate-Based Ice Recrystallization Inhibitors Increase Infectivity and Thermostability of Viral Vectors
Authors: Ghobadloo Shahrokh M. , Balcerzak Anna K. , Gargaun Ana , Muharemagic Darija , Mironov Gleb G. , Capicciotti Chantelle J. , Briard Jennie G. , Ben Robert N. , Berezovski Maxim V.
Published: July 2014

The inability of vaccines to retain sufficient thermostability has been an obstacle to global vaccination programs. To address this major limitation, we utilized carbohydrate-based ice recrystallization inhibitors (IRIs) to eliminate the cold chain and stabilize the potency of Vaccinia virus (VV), Vesicular Stomatitis virus (VSV) and Herpes virus-1 (HSV-1). The impact of these IRIs was tested on the potency of the viral vectors using a plaque forming unit assay following room temperature storage, cryopreservation with successive freeze-thaw cycles and lyophilization. Viral potency after storage with all three conditions demonstrated that N-octyl-gluconamide (NOGlc) recovered the infectivity of shelf stored VV, 5.6 Log10 PFU mL−1 during 40 days and HSV-1, 2.7 Log10 PFU mL−1 during 9 days. Carbon-linked antifreeze glycoprotein analogue ornithine-glycine-glycine-galactose (OGG-Gal) increases the recovery of VV and VSV more than 1 Log10 PFU mL−1 after 10 freeze-thaw cycles. In VSV, cryostorage with OGG-Gal maintains high infectivity and reduces temperature-induced aggregation of viral particles by 2 times that of the control. In total, OGG-Gal and NOGlc preserve virus potency during cryostorage. Remarkably, NOGlc has potential to eliminate the cold chain and permit room temperature storage of viral vectors.
Soliris (Eculizumab): Discovery and Development
Authors: Lambert Matthew A. , Finlay William J. J.
Published: July 2014

Eculizumab, marketed as ‘Soliris’ by Alexion Pharmaceuticals Inc., is a humanised, Fc-engineered (low effector function), IgG2/4 hybrid monoclonal antibody that blocks the activity of human complement factor C5. This activity enables eculizumab to potently suppress the pro-inflammatory and cytolytic effects of the terminal complement system, which are key factors in the pathology of the rare haemolytic disease paroxysmal nocturnal haemoglobinuria (PNH). This antibody therapeutic has become an important example of a potential therapeutic molecule that was originally developed for a series of common inflammatory diseases (rheumatoid arthritis, lupus, etc.), but was repurposed with great success to become a first-in-class complement inhibitor in the rare disease space.
Possible Solutions to Accelerate Access to Rare Disease Treatments
Authors: Dunoyer Marc
Published: July 2014

The introduction of legislative incentives to promote rare disease research, along with changes to regulatory policy, has resulted in increases in the number or orphan drug designations. Despite this, the number of drugs reaching marketing approval across OECD countries remains frustratingly flat. Research into rare diseases faces inherent challenges throughout clinical drug development and regulatory approval. Tailor-made regulatory and access solutions are needed to overcome these problems. Here I suggest areas for consideration that could have an immediate impact in facilitating regulatory approval and access to treatments for rare diseases.
Development of a gas chromatography-mass spectrometry method for the determination of ultraviolet filters in beach sand samples
Authors: Tarazona Isuha , Chisvert Alberto , Salvador Amparo
Published: July 2014

An analytical method for the determination of eight fat-soluble ultraviolet (UV) filters in beach sand samples is presented for the first time.
A DFT study on the reaction mechanism of dimerization of methyl methacrylate catalyzed by N-heterocyclic carbene
Authors: Li Yunxia , Zhu Yanyan , Zhang Wenjing , Wei Donghui , Ran Yingying , Zhao Qilin , Tang Mingsheng
Published: July 2014

The novel proton transfers assisted by methyl methacrylate lower the energy barrier of the dimerization.
Identification of TiO2 nanoparticles using La and Ce as labels: application to the evaluation of surface contamination during the handling of nanosized matter
Authors: Gomez Virginia , Clemente Alberto , Irusta Silvia , Balas Francisco , Santamaria Jesus
Published: July 2014

Rare earth elements as high sensitive labels to identify and monitor nanomaterials fate following manipulation.
Quercetin reduces pluripotency, migration and adhesion of human teratocarcinoma cell line NT2/D1 by inhibiting Wnt/β-catenin signaling
Authors: Mojsin Marija , Vicentic Jelena Marjanovic , Schwirtlich Marija , Topalovic Vladanka , Stevanovic Milena
Published: July 2014

In human teratocarcinoma cell line NT2/D1 quercetin exerts its anticancer effect through the inhibition of Wnt signaling.
Detection of Kaposi's sarcoma associated herpesvirus nucleic acids using a smartphone accessory
Authors: Mancuso Matthew , Cesarman Ethel , Erickson David
Published: July 2014

A smartphone accessory is created to read out a gold nanoparticle aggregation assay targeted at Kaposi's sarcoma associated herpesvirus DNA.
Microbubble array diffusion assay for the detection of cell secreted factors
Authors: Bobo Bryan , Phelan Dana , Rebhahn Jonathan , Piepenbrink Michael S. , Zheng Bo , Mosmann Tim R. , Kobie James J. , DeLouise Lisa A.
Published: July 2014

To address concerns with suboptimal methods for screening cells, we have developed a cell-sorting array composed of nanoliter spherical cell culture compartments termed microbubble (MB) wells. We demonstrate a proof-of-concept system for the detection of cell secreted factors from both immortalized cell lines and primary B cell samples.
Influence of the synthesis route on the formation of 12R/10H-polytypes and their magnetic properties within the Ba(Ce,Mn)O3family
Authors: Macías Mario A. , Mentré Olivier , Pirovano Caroline , Roussel Pascal , Colis Silviu , Gauthier Gilles H.
Published: July 2014

A selective synthesis of 12R/10Hpolytypes within the Ba–Ce–Mn–O family can be induced by a Mn precursor.
A reversible supramolecular assembly containing ionic interactions and disulfide linkages
Authors: Lin Xinrong , Godeau Guilhem , Grinstaff Mark W.
Published: July 2014

A reversible ionic supramolecular assembly is described which can be disrupted and reformed by application of either a heating–cooling cycle or a mild redox reaction.
Facile fabrication and enhanced gas sensing properties of In2O3 nanoparticles
Authors: Wang Shuangming , Wang Pan , Li Zhifang , Xiao Chuanhai , Xiao Bingxin , Zhao Rui , Yang Tianye , Zhang Mingzhe
Published: July 2014

The sensor based on In2O3 nanoparticles exhibits excellent acetone gas sensing performance.
Hybrid periodic mesoporous organosilica designed to improve the properties of immobilized enzymes
Authors: Gascón V. , Díaz I. , Blanco R. M. , Márquez-Álvarez C.
Published: July 2014

Hybrid organosilica supports synthesized with pore size adjusted to enzyme dimensions provide high stability in organic solvent systems and prevent leaching.
Strong anodic electrochemiluminescence from dissolved oxygen with 2-(dibutylamino) ethanol for glucose oxidase assay
Authors: Kargbo Osman , Zheng Chun-Lan , Ding Shou-Nian
Published: July 2014

A strong anodic electrochemiluminescence of dissolved oxygen with 2-(dibutylamino) ethanol is developed to detect glucose oxidase.
Fast switching of liquid crystals on transferred reactive mesogens film via soft imprinting method
Authors: Park Hong-Gyu , Lee Hak Moo , Jeong Hae-Chang , Seo Dae-Shik
Published: July 2014

Unidirectional alignment of liquid crystal (LC) molecules is a prerequisite for advanced LC devices.
A catalytic asymmetric total synthesis of (−)-perophoramidine
Authors: Trost B. M. , Osipov M. , Krüger S. , Zhang Y.
Published: July 2014

We describe a catalytic asymmetric total synthesis of the ascidian alkaloid (−)-perophoramidine employing a Mo-catalyzed asymmetric allylic alkylation and unprecedented imino ether allylation as key steps.
“Nano to nano” electrodeposition of WO3 crystalline nanoparticles for electrochromic coatings
Authors: Liu Liang , Layani Michael , Yellinek Shai , Kamyshny Alexander , Ling Han , Lee Pooi See , Magdassi Shlomo , Mandler Daniel
Published: July 2014

Nanoparticles in the dispersion are electrodeposited onto conductive substrates forming crystalline nano-structured films. The deposition process can be well manipulated, and the films prepared have excellent electrochromic performance.
Lacritin-mediated regeneration of the corneal epithelia by protein polymer nanoparticles
Authors: Wang Wan , Despanie Jordan , Shi Pu , Edman Maria C. , Lin Yi-An , Cui Honggang , Heur Martin , Fini M. Elizabeth , Hamm-Alvarez Sarah F. , MacKay J. Andrew
Published: July 2014

Protein polymer nanoparticles decorated with the mitogenic human tear protein, lacritin, heal a defect in the corneal epithelium faster than a soluble control peptide.
CXCR4 dysfunction in non-alcoholic steatohepatitis in mice and patients
Authors: Boujedidi Hédia , Robert Olivier , Bignon Alexandre , Cassard-Doulcier Anne-Marie , Renoud Marie-Laure , Gary-Gouy Hélène , Hemon Patrice , Tharinger Hugo , Prévot Sophie , Bachelerie Françoise , Naveau Sylvie , Emilie Dominique , Balabanian Karl , Perlemuter Gabriel
Published: July 2014

Homing of inflammatory cells to the liver is key in the progression of non-alcoholic steatohepatitis (NASH). An abnormal response of CD4+ T-cells from obese mice to the chemotactic effect of CXCL12 has been reported but the mechanism involved in this process and relevance in patients are unknown. We aimed to explore the mechanism involved in the abnormal chemotaxis of CXC chemokine ligand 12 (CXCL12) in several mouse models of NASH and the relevance in the context of human non-alcoholic fatty liver disease (NAFLD). We assessed chemotactic responsiveness of CD4+ T-cells to CXCL12, the effect of AMD3100, a CXC chemokine receptor 4 (CXCR4) antagonist, in mice and lymphocytes from patients with NAFLD, and the affinity of CXCL12 for CXCR4. CXCL12-promoted migration of CD4+ T-cells from three different mouse models of NASH was increased and dependent of CXCR4. CD4+ T-cells from patients with NASH, but not from patients with pure steatosis, responded more strongly to the chemotactic effect of CXCL12, and this response was inhibited by AMD3100. Treatment with AMD3100 decreased the number of CD4+ T-cells to the liver in ob/ob mice. CXCL12 expression in the liver, CXCR4 and CXCR7 expression in CD4+ T-cells were not increased in three different mouse models of NASH. However, the affinity of CXCL12 for CXCR4 was increased in CD4+ T-cells of ob/ob mice. In conclusion, the CXCL12/CXCR4 pathway contributes in both mice and patients to the enhanced recruitment of CD4+ T-cells in NASH. An increased affinity of CXCL12 to CXCR4 rather than a higher expression of the chemokine or its receptors is involved in this process.
Phonetic Imitation by Young Children and Its Developmental Changes
Authors: Nielsen Kuniko
Published: July 2014

Purpose

In the current study, the author investigated the developmental course of phonetic imitation in childhood, and further evaluated existing accounts of phonetic imitation.

Method

Sixteen preschoolers, 15 third graders, and 18 college students participated in the current study. An experiment with a modified imitation paradigm with a picture-naming task was conducted, in which participants' voice-onset time (VOT) was compared before and after they were exposed to target speech with artificially increased VOT.

Results

Extended VOT in the target speech was imitated by preschoolers and 3rd graders as well as adults, confirming previous findings in phonetic imitation. Furthermore, an age effect of phonetic imitation was observed; namely, children showed greater imitation than adults, whereas the degree of imitation was comparable between preschoolers and 3rd graders. No significant effect of gender or word specificity was observed.

Conclusions

Young children imitated fine phonetic details of the target speech, and greater degree of phonetic imitation was observed in children compared to adults. These findings suggest that the degree of phonetic imitation negatively correlates with phonological development.
Ultra‐low‐noise 1 µm optical frequency comb
Authors: Kundermann S. , Portuondo‐Campa E. , Lecomte S.
Published: July 2014

A robust optical frequency comb is realised with an Origami‐10 mode‐locked femtosecond laser from Onefive GmbH generating a 100 MHz pulse train at a centre wavelength of 1047 nm. The carrier‐envelope offset frequency has been stabilised to a record level contributing to relative fluctuations of the optical carrier frequency of 1.1 × 10−18 at 1 s and averaging down to the 10−22 level at 10 000 s. Cycle‐slip free carrier‐envelope offset frequency stabilisation has been routinely achieved over 10 h. Ultra‐low relative intensity noise has been measured as well and makes such a system very attractive for demanding applications where low noise and high reliability are requested.
Magnetic circuit model and finite‐element analysis of a modular switched reluctance machine with E‐core stators and multi‐layer common rotors
Authors: Ding Wen , Yin Zhonggang , Liu Ling , Lou Jianyong , Hu Yanfang , Liu Yunpeng
Published: July 2014

This study presents a novel switched reluctance machine (SRM) with modular E‐core stators and multi‐layer common rotors for high reliability applications. The stator is composed of six independent modular E‐cores with the windings wound around the yoke of the E‐cores. The rotor consists of three magnetically independent common rotors which are place in the same shaft without any angular shift. The equivalent magnetic circuit (EMC) models of this new SRM at the aligned and unaligned positions are described. To evaluate the motor performance, two types of analysis, namely, approximate simplified two‐dimensional (2D) model and 3D model finite‐element analysis (FEA) have been utilised. The 2D FEA static and dynamic results are compared with 3D FEA results. Furthermore, comparisons between the novel modular SRM and a conventional 6/4 SRM are made. Finally, a prototype of this modular SRM has been fabricated and tested in the laboratory. Comparison between FEA and EMC analysis for flux linkage are made and compared with measured characteristics. The simulated and measured phase currents and average torque are also presented and compared to verify the analytical and simulation results.
Electronic structure and x-ray magnetic circular dichroism in the Mn3CuN perovskite
Authors: Antonov V. N. , Bekenov L. V.
Published: July 2014

The electronic and magnetic structures of Mn3CuN are investigated theoretically from first principles using the fully relativistic Dirac LMTO band structure method. Mn3CuN possesses a magnetic phase transition at TC = 143 K from a high temperature paramagnetic phase to a low temperature ferromagnetic one with a noncollinear magnetic structure. The transition is accompanied by a structural change from the cubic to the tetragonal lattice. In low temperature phase two Cu moments and two Mn moments (Mn2 and Mn3) ferromagnetically align along the c axis while other four Mn1 magnetic moments are canted from the c axis to [111] direction by angle Θ = ±76.2. The x-ray absorption spectra and x-ray magnetic circular dichroism (XMCD) spectra of Mn3CuN are investigated theoretically from first principles. The origin of the XMCD spectra in the Mn3CuN compound is examined. The calculated results are compared with the experimental data.
Characterization of spatially resolved high resolution x-ray spectrometers for high energy density physics and light source experiments
Authors: Hill K. W. , Bitter M. , Delgado-Aparacio L. , Efthimion P. , Pablant N. A. , Lu J. , Beiersdorfer P. , Chen H. , Magee E.
Published: July 2014

A high resolution 1D imaging x-ray spectrometer concept comprising a spherically bent crystal and a 2D pixelated detector is being optimized for diagnostics of small sources such as high energy density physics (HEDP) and synchrotron radiation or x-ray free electron laser experiments. This instrument is used on tokamak experiments for Doppler measurements of ion temperature and plasma flow velocity profiles. Laboratory measurements demonstrate a resolving power, E/ΔE of order 10 000 and spatial resolution better than 10 μm. Initial tests of the high resolution instrument on HEDP plasmas are being performed.