bluuebunny/crossref_metadata_2025 huggingface dataset:
Droplet-based microfluidic washing module for magnetic particle-based assays
Authors: Lee Hun , Xu Linfeng , Oh Kwang W.
Published: August 2014

In this paper, we propose a continuous flow droplet-based microfluidic platform for magnetic particle-based assays by employing in-droplet washing. The droplet-based washing was implemented by traversing functionalized magnetic particles across a laterally merged droplet from one side (containing sample and reagent) to the other (containing buffer) by an external magnetic field. Consequently, the magnetic particles were extracted to a parallel-synchronized train of washing buffer droplets, and unbound reagents were left in an original train of sample droplets. To realize the droplet-based washing function, the following four procedures were sequentially carried in a droplet-based microfluidic device: parallel synchronization of two trains of droplets by using a ladder-like channel network; lateral electrocoalescence by an electric field; magnetic particle manipulation by a magnetic field; and asymmetrical splitting of merged droplets. For the stable droplet synchronization and electrocoalescence, we optimized droplet generation conditions by varying the flow rate ratio (or droplet size). Image analysis was carried out to determine the fluorescent intensity of reagents before and after the washing step. As a result, the unbound reagents in sample droplets were significantly removed by more than a factor of 25 in the single washing step, while the magnetic particles were successfully extracted into washing buffer droplets. As a proof-of-principle, we demonstrate a magnetic particle-based immunoassay with streptavidin-coated magnetic particles and fluorescently labelled biotin in the proposed continuous flow droplet-based microfluidic platform.
Attention Modulation of Stimulus Rivalry under Swapping Paradigm
Authors: Doualot Audrey , Simard Mathieu , Saint-Amour Dave
Published: August 2014

Stimulus rivalry refers to the sustained periods of perceptual dominance that occur when different visual stimuli are swapped at a regular rate between eyes. This phenomenon is thought to involve mainly eye-independent mechanisms. Although several studies have reported that attention can increase image predominance in conventional binocular rivalry, it is unknown whether attention can specifically modulate stimulus rivalry. We addressed this question and manipulated the spatial characteristic of the stimuli to assess whether such an attention modulation could depend on visual processing hierarchy. The results showed that selective attention of stimulus rivalry significantly increased the predominance of the attended stimulus, regardless of the stimulus' spatial characteristics. No effect was observed on the swapping percept. The findings are discussed in the context of recent models attempting to characterize stimulus rivalry between eye-dependent and eye-independent levels.
Nanoscale Order in Molecular Systems from Single Crystal Diffuse Scattering
Authors: Goossens Darren J. , Welberry T. Richard
Published: August 2014

Diffuse scattering – the coherently scattered intensity that is not localised on the reciprocal lattice – contains a wealth of information about the local order (order on the nanoscale) in crystalline materials. Since molecules and atoms will respond most strongly to their local chemical environments, it is a valuable tool in understanding how structure leads to properties. However, at present its collection and analysis are relatively specialised. Monte Carlo (MC) computer simulation of a model structure has become a powerful and well-accepted technique for aiding the interpretation and analysis of diffuse scattering patterns. Its great strength is its flexibility – as long as an MC energy can be defined, a model can be developed and tested. At one extreme a very simplified model may be useful in demonstrating particular qualitative effects, while at the other a quantitative and very detailed description of disordered structures can be obtained. Examples discussed include new results concerning p-chloro-N-(p-chloro-benzylidene)aniline, a molecule showing various degrees of molecular flexibility.
Vigour reduction in girdled peach trees is related to lower midday stem water potentials
Authors: Tombesi Sergio , Day Kevin R. , Johnson R. Scott , Phene Rebecca , DeJong Theodore M.
Published: August 2014

Stem or trunk girdling is a technique used in physiological studies and in horticultural practice for interrupting carbon flow through the phloem to other parts of the plant without influencing water flow in the xylem. Trunk girdling in peaches is practiced primarily to stimulate fruit growth but it also tends to decrease shoot vigour for a period of time after girdling. Water flow through the trunk or branches of peach trees is thought to be primarily dependent on the most recently formed ring of xylem and vegetative growth is closely related to stem water potential and stem hydraulic conductance. The aim of the present work was to determine whether vigour reduction due to girdling was correlated with a reduction in midday stem water potential during the period of time between girdling and the subsequent healing of stem tissue. ‘Springcrest’ peach trees were girdled on two different dates. Fruit yield and size, water sprout growth, proleptic shoot growth and stem water potential were measured. Early and late girdled trees yielded larger fruits and fewer and shorter water sprouts in comparison with control trees. Midday stem water potential declined significantly after girdling and gradually recovered until the time of fruit harvest. These results suggest that the vigour reduction of girdled trees is related to a decrease of midday stem water potential caused by girdling. Early tree girdling increased the reduction in midday stem water potential and shoot growth compared with the later girdling treatment. These results point out that even though girdling only removes bark and phloem tissue it can apparently affect water flow in xylem.
Post–flood nitrogen and basal phosphorus management affects survival, metabolic changes and anti-oxidant enzyme activities of submerged rice (Oryza sativa)
Authors: Gautam Priyanka , Lal Banwari , Raja Rajagounder , Baig Mirza Jaynul , Haldar Deepika , Rath Liza , Shahid Mohammad , Tripathi Rahul , Mohanty Sangita , Bhattacharyya Pratap , Nayak Amaresh Kumar
Published: August 2014

Flooding is one of the major harmful abiotic stresses in the low lying areas of Asia and crop losses due to submergence are considerably high. Along with plant breeding techniques, agronomic management options in general and nutrient management in particular should be taken into consideration. Response of Sub 1 and non-Sub1 cultivars of rice to post-flood nitrogen (N) management under variable flood water was compared at maximum tillering stage. Submergence tolerance on survival, leaf senescence, metabolic changes, and anti-oxidant enzymatic activities were evaluated. Sub1 cultivars proved their superiority over IR-20 in terms of significantly higher survival, anti-oxidant enzymes and lower metabolic changes. Turbid water resulted in lower survival because of poor light transmission, chlorophyll retention and silt deposition. Basal phosphorus reduced the elongation, senescence and ethylene accumulation. Post-flood foliar spray of urea substantially increased the chlorophyll, soluble sugars and extenuated ethylene accumulation resulting in significantly higher survival. These nutrient management options can provide opportunities for better survival and productivity even under turbid water, helping farmers to cope with the existing problems in flood-prone areas.
Modulation of a cytoskeletal calpain-like protein induces major transitions in trypanosome morphology
Authors: Hayes Polly , Varga Vladimir , Olego-Fernandez Sofia , Sunter Jack , Ginger Michael L. , Gull Keith
Published: August 2014

Individual eukaryotic microbes, such as the kinetoplastid parasite Trypanosoma brucei, have a defined size, shape, and form yet transition through life cycle stages, each having a distinct morphology. In questioning the structural processes involved in these transitions, we have identified a large calpain-like protein that contains numerous GM6 repeats (ClpGM6) involved in determining T. brucei cell shape, size, and form. ClpGM6 is a cytoskeletal protein located within the flagellum along the flagellar attachment zone (FAZ). Depletion of ClpGM6 in trypomastigote forms produces cells with long free flagella and a shorter FAZ, accompanied by repositioning of the basal body, the kinetoplast, Golgi, and flagellar pocket, reflecting an epimastigote-like morphology. Hence, major changes in microbial cell form can be achieved by simple modulation of one or a few proteins via coordinated association and positioning of membrane and cytoskeletal components.
PDK1-mediated activation of MRCKα regulates directional cell migration and lamellipodia retraction
Authors: Gagliardi Paolo Armando , di Blasio Laura , Puliafito Alberto , Seano Giorgio , Sessa Roberto , Chianale Federica , Leung Thomas , Bussolino Federico , Primo Luca
Published: August 2014

Directional cell migration is of paramount importance in both physiological and pathological processes, such as development, wound healing, immune response, and cancer invasion. Here, we report that 3-phosphoinositide-dependent kinase 1 (PDK1) regulates epithelial directional migration and invasion by binding and activating myotonic dystrophy kinase–related CDC42-binding kinase α (MRCKα). We show that the effect of PDK1 on cell migration does not involve its kinase activity but instead relies on its ability to bind membrane phosphatidylinositol (3,4,5)-trisphosphate. Upon epidermal growth factor (EGF) stimulation, PDK1 and MRCKα colocalize at the cell membrane in lamellipodia. We demonstrate that PDK1 positively modulates MRCKα activity and drives its localization within lamellipodia. Likewise, the retraction phase of lamellipodia is controlled by PDK1 through an MRCKα-dependent mechanism. In summary, we discovered a functional pathway involving PDK1-mediated activation of MRCKα, which links EGF signaling to myosin contraction and directional migration.
EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step
Authors: Ninagawa Satoshi , Okada Tetsuya , Sumitomo Yoshiki , Kamiya Yukiko , Kato Koichi , Horimoto Satoshi , Ishikawa Tokiro , Takeda Shunichi , Sakuma Tetsushi , Yamamoto Takashi , Mori Kazutoshi
Published: August 2014

Glycoproteins misfolded in the endoplasmic reticulum (ER) are subjected to ER-associated glycoprotein degradation (gpERAD) in which Htm1-mediated mannose trimming from the oligosaccharide Man8GlcNAc2 to Man7GlcNAc2 is the rate-limiting step in yeast. In contrast, the roles of the three Htm1 homologues (EDEM1/2/3) in mammalian gpERAD have remained elusive, with a key controversy being whether EDEMs function as mannosidases or as lectins. We therefore conducted transcription activator-like effector nuclease–mediated gene knockout analysis in human cell line and found that all endogenous EDEMs possess mannosidase activity. Mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 is performed mainly by EDEM3 and to a lesser extent by EDEM1. Most surprisingly, the upstream mannose trimming from Man9GlcNAc2 to Man8GlcNAc2 is conducted mainly by EDEM2, which was previously considered to lack enzymatic activity. Based on the presence of two rate-limiting steps in mammalian gpERAD, we propose that mammalian cells double check gpERAD substrates before destruction by evolving EDEM2, a novel-type Htm1 homologue that catalyzes the first mannose trimming step from Man9GlcNAc2.
El Greco
Authors: Bass Laura R. , Tiffany Tanya J.
Published: August 2014

Domenikos Theotokopoulos (c. 1541–1614), known as El Greco, was born on the Greek island of Crete, but he is most renowned for his long career in Spain. El Greco began his professional life as a successful icon painter and, in the first of many journeys, moved from Crete to Venice in 1567 or 1568. There, he remade his art on the examples of Renaissance masters, in particular Titian and Tintoretto. Several contemporaries described him as Titian’s disciple, but it is unclear whether he worked in the master’s studio or merely emulated his style. El Greco relocated to Rome in 1570; for a time he enjoyed the protection of the powerful Roman Cardinal Alessandro Farnese, although he apparently received few commissions in the city. Perhaps hoping to join the many Italian painters working for King Philip II, El Greco traveled to Spain in 1577 and shortly thereafter to Toledo, where he settled definitively in 1583. El Greco’s critical fortunes have changed dramatically over the centuries. His contemporaries differed in their appraisals of his art, recognizing his immense talent but often censuring his pictorial innovations. He won particular admiration as a portraitist and gained renown for his sacred works. At the same time, several of his religious paintings were criticized for contravening the strict standards of decorum that emerged in the wake of the Council of Trent. For much of the 17th and 18th centuries, writers disparaged what they perceived as the extravagance of his late painterly style. El Greco was discovered outside Spain in the 19th century, when Romantic writers characterized him as a rebellious genius, and painters such as Manet embraced his bold color and loose brushwork. Castilian scholars of the early 20th century associated El Greco with a quintessential “Spanishness” (despite his Greek origins) and argued that his painting embodied the mysticism of religious figures such as Teresa of Ávila and John of the Cross. Others claimed him as a forerunner of modern art. Overall, the view of the mystical artist endured for decades, even as some scholars proposed spurious theories that El Greco suffered from astigmatism and used madmen as models. In the 1980s, scholarly opinion was transformed following the publication of writings by the painter himself, which demonstrated that he was an intellectual fully schooled in Italian artistic theory. El Greco brought his humanistic learning to bear on sacred and secular imagery in ways that remain to be fully explored.
Giovanni Boccaccio
Authors: Houston Jason
Published: August 2014

Giovanni Boccaccio (b. 1313–d. 1375), along with the two other great Florentine writers, Dante Alighieri and Francesco Petrarch, is one of the Three Crowns of Italian literature. His vast body of poetic and prose works represents a great variety of classical and medieval literary genres. Boccaccio was acutely aware of his position as mediator between different cultures—classical and medieval; Italian, French, and Latin; and Christian and pagan—and thus he stands as an important figure in the development of a European humanist literary culture that defines the Renaissance and beyond. Although his Latin encyclopedic works were his most important and influential works for centuries, modern audiences, both scholarly and otherwise, have made the Decameron Boccaccio’s most read text. Italian, German, and French scholars made the first critical editions of Boccaccio in the late 19th century. Italian scholars, primarily Vittore Branca but also others, renewed efforts to create authoritative critical editions in the late 20th century. Italian criticism of Boccaccio remains mostly philological, with important exceptions. North American scholars of Boccaccio have focused on the Decameron. The late 20th century saw great interest in Boccaccio’s early vernacular works, primarily in North America. American critics have read Boccaccio in light of new critical categories, particularly feminism and Mediterranean studies, although more-recent critical attention has shifted back to Boccaccio’s Latin texts in order to illuminate his intellectual contributions to the late Middle Ages and Renaissance. The 700th centenary of his birth in 2013 saw a number of publications in which a range of scholars considered Boccaccio’s influence across genre and period. Besides his writings, Boccaccio was an important figure in the creation of an Italian literary tradition, promoting the poetic importance both of Dante and Petrarch.
Mary Astell
Authors: Broad Jacqueline
Published: August 2014

Mary Astell (b. 1666–d. 1731) is widely considered to be one of the earliest English feminists. She is best known for her prose works A Serious Proposal to the Ladies (Part 1, 1694; Part 2, 1697) and Some Reflections upon Marriage (1700). The first Proposal to the Ladies, subtitled “For the Advancement of their True and Greatest Interest. By a Lover of Her Sex,” is an eloquent appeal for the higher education of women in early modern England. The second part, “Wherein a Method is offered for the Improvement of their Minds,” extends a further plea to the ladies of quality, urging them to practice Cartesian rules for thinking in order to attain virtue and wisdom. In the Reflections, Astell provides a careful analysis of the most common causes of marital discontent in her time. To avoid such discontent, she suggests, women ought to be educated thoroughly so that they will choose their husbands wisely—or else not marry at all. In Astell’s heyday (c. 1694–1709), these works were greatly admired, and she was celebrated by leading literary figures, such as Daniel Defoe, John Evelyn, and Mary Chudleigh. Among 21st-century scholars, the consensus view is that Astell’s feminist ideas must be understood in the context of her wider political, philosophical, and religious principles. Recent commentators have interpreted Astell’s feminist writings in light of her support for the Tory political party, her Cartesian-Platonist philosophy, and her utter devotion to the Anglican religion. A substantial amount of work has been done on her political thought in relation to the radical Whig ideology of John Locke. More recently, scholars have delved deeper into Astell’s religio-philosophical writings, including her Letters Concerning the Love of God (with John Norris, 1695) and The Christian Religion, as Professed by a Daughter of the Church of England (1705). Scholars have also begun to appreciate Astell’s use of poetry, rhetoric, and figurative language more generally. Some have claimed her as a successor to John Milton, while others have credited her with influencing Samuel Richardson’s literary masterpiece, Clarissa. This article lists the principal overviews and biographies of Astell, as well as the standard editions of her works. It also covers five key areas of Astell scholarship: her feminist views (on education and marriage), her politics, her philosophy, her religion, and the literary aspects of her work.
Freedom of Expression
Authors: Richards Mark J.
Published: August 2014

Freedom of expression is a fundamental international human right. It is intrinsically valuable and necessary for the healthy functioning of democracy and civil society. Freedom of expression is necessary for the achievement of other human rights such as fair administration of justice, education, adequate standard of living, equality, human dignity, and the rights of women, peoples, and minorities. Although it is generally a negative liberty, freedom of expression places positive obligations on the state to provide access to information, Internet access, and to promote a child’s right to participate in education, work, and family life. Freedom of expression broadly understood encompasses a package of rights that are intimately intertwined, including freedom of opinion, speech, press, information, association, assembly, thought, conscience, belief, and religion. Although the rights can be conceptually organized into the four categories of expression, association, assembly, and thought, each with distinct meaning, actual cases commonly involve more than one of the rights. For example, a ban on wearing headscarves in a public educational setting raises issues of freedom of expression and religion. Freedom of expression is recognized by the Universal Declaration of Human Rights (UDHR), the International Covenant on Civil and Political Rights (ICCPR), the African Charter on Human and Peoples’ Rights (ACHPR), the American Convention on Human Rights (ACHR), the Arab Charter on Human Rights (Arab Charter), and the European Convention on Human Rights (ECHR). Although freedom of expression is fundamental, it is not absolute. Article 19 of the ICCPR allows for restrictions on freedom of expression that are necessary to protect the rights or reputations of others, national security, public order, public health, or public morals. Any such restriction must be provided for by law and be proportionate. The literature on freedom of expression as an international human right tends to focus on cases and jurisprudence, with some attention paid to the roles of international human rights institutions. Regional and international civil society groups actively highlight current threats to freedom of expression, often in cases of threats to individuals, journalists, or small groups, but also more systematically via annual, country, regional, and thematic reports. Many of the most prevalent issues of the past decade revolve around the Internet such as hate speech, regulation of social media, Internet access, disinformation, and surveillance. Of course, the Internet has transformed communications, but it has also enabled unprecedented state and international surveillance that threatens privacy and freedom of expression alike. Other contemporary free expression issues arising under international law include protection of journalists and human rights defenders, sexual orientation and gender identity (SOGI), genocide and atrocity crimes, the speech rights of the child, and religion.
Charles Kingsley
Authors: Conlin Jonathan
Published: August 2014

Polymath and Church of England priest, Charles Kingsley’s prolific literary output, sanitary crusades, and “muscular Christianity” seem to epitomize the bustling Victorian man of faith and letters. Kingsley packed a lot of activity into a short life (b. 1819–d. 1875), including a good deal of controversy (most famously with John Henry Newman) and anguished struggles with himself. A strong rather than subtle mind, Kingsley saw intellectual activity as a pendant to physical activity. In practice the latter could overshadow the former at times, notably in his justification of armed conflict and imperial expansion. This conflict and expansion formed part of a racialist, providentialist view of England’s mission to subdue the world. Kingsley’s definition of “English” included Scots and English settlers in Canada, Australia, and New Zealand, as well as citizens of the United States, who gave Kingsley a hero’s welcome when he toured their country in 1874. Within a few years of Kingsley’s death the following year, swashbuckling historical novels such as Westward Ho! (1855) merged with that public-school manliness more often associated with Kingsley’s fellow Christian Socialist, Thomas Hughes, author of Tom Brown’s School Days (1857). Such works remained popular among teenage readers until World War II, while Kingsley’s reputation as a thinker on social justice stood surprisingly high among Fabian Socialists. Kingsley’s posthumous influence on British identity has been largely overlooked, however. Kingsley’s historical fiction and his 1860 appointment as Regius Professor of History at Cambridge University have aroused considerable scholarly interest in Kingsley as an “amateur” excluded from the ranks of “professional” historians in the founding era of the historical discipline in Britain. All of Kingsley’s writing is strongly gendered. Although heteronormative, Kingsley’s enthusiastic embrace of the sexual body within companionate marriage was unusual for the times. With the revival of interest in Kingsley in the 1970s, scholars became fascinated with this aspect of his personal life. Psychobiographical approaches found a rich field for investigation in Kingsley’s evolutionary fairy tale, The Water-Babies (1863). Many set themselves the task of exposing, pathologizing, or apologizing for Kingsley’s formal infelicities and intellectual shallowness or inconsistency. As scholars have become more attentive to, and curious about, the ways in which literary genres and disciplines have been constructed in historical time and discursive space, however, so Kingsley’s own engagement (often ludic and satirical) with such boundaries and categories have grown in interest. The engagement of historians of science with Kingsley’s writings has been particularly fruitful in this regard. In a sense, Kingsley scholarship of the 2000s and 2010s begins where the earlier generation left off: identifying the paradoxes and tensions in his thought is not the end, but serves as prolegomenon to discussion of the many ways in which his texts shaped the Victorian mind.
North American Biomes
Authors: Peters Debra P.C. , Scroggs Stacey L.P. , Yao Jin
Published: August 2014

Biomes of North America are contained within the land area of Canada, the United States, Mexico, and countries in Central America. The area is bordered to the north by the Arctic Ocean, to the east by the Atlantic Ocean, to the west and south by the Pacific Ocean, and to the southeast by South America and the Caribbean Sea. This large area (over 24 x 106 km2) is characterized by a broad range of temperature and precipitation that result in nine biomes ranging from tropical rainforests and seasonal deciduous forests in the south near the equator to boreal forests and tundra at high latitudes near the North Pole. Temperate forests (deciduous, coniferous), grasslands, deserts, and Chaparral woodlands occur at mid-latitudes. Landscape-scale patterns in contemporary ecosystems within each biome reflect variability in climate and soil parent material combined with human activities that have increased in extent and intensity over the past several centuries. These patterns are often influenced by the redistribution of organisms, water and sediment, fire, and air chemistry. Connections with biome types on other continents on Earth can lead to invasion by exotic species including pests and pathogens, large climatic events such as hurricanes and drought, and changes in air quality through dust storms and volcanic eruptions. These tele-connections often occur infrequently, yet with large and surprising effects on ecosystem properties and dynamics. Directional changes in climate are expected to influence biome distributions and composition in novel ways. Increasing awareness of these broad-scale dynamics that connect biomes globally is leading to new avenues of research that intersect ecology with other disciplines.
Martin Buber
Authors: Mendes-Flohr Paul
Published: August 2014

Martin Buber (b. 1878–d. 1965) was among the most distinguished Jewish religious thinkers in the twentieth century. Although he published mostly in German and lived in Germany from his early twenties until his immigration to Palestine at the age of sixty, he regarded himself as a Polish Jew. Born in Vienna, after the divorce of his parents he was raised from the age of three by his paternal grandparents in the Austrian-Hungarian province of Eastern Galicia, which had a predominantly Polish and Ukrainian population as well as a large, overwhelmingly traditional Jewish minority. In the home of his observant grandparents, he received tuition in classical Jewish texts and secular subjects; he would later attend a Polish high school. He pursued his higher education in Berlin, Leipzig, Vienna, and Zurich, earning his doctorate in 1904 with a dissertation on medieval German mysticism. He continued to publish widely on mysticism as a freelance author and editor, eventually introducing to European audiences the hitherto unknown world of Jewish mysticism, especially as represented by Hasidism. He also issued works on art, folklore, literature, mysticism and myth, philosophy, and sociology. A veritable polymath, his interests ranged from art to theater, from Celtic to Chinese myths, from Finnish to Yiddish folklore. The full scope of his extraordinary erudition is documented by the thematic division of the twenty-one volume, critical edition of his works in German was recently completed. (See Martin Buber WerkausgabeMendes-Flohr, et al. 2001–2019, cited under Original German Texts: Collected Editions.) He was also active in promoting religious socialism and adult education; he made his mark in the public sphere, however, primarily as a Zionist intellectual who advocated the spiritual and cultural renewal of post-traditional Jewry; indeed, already in 1901 he spoke of a “Jewish Renaissance,” which inspired Zionists and non-Zionists alike. Toward this renaissance, he undertook, initially with Franz Rosenzweig (b. 1886–d. 1929), a non-Zionist, the translation of the Hebrew Bible, which would resonate the original dialogical and thus religious character of the Hebrew. He is best known, however, for I and Thou, published in German in 1923, in which he distinguished between I-Thou (Ich-Du) relations, characterized by dialogical mutuality, and I-It (Ich-Es) or instrumental relations. He further developed this doctrine as a philosophical anthropology in which he challenged the ontological presuppositions of Dilthey, Heidegger, Husserl, Kant, Kierkegaard, Marx, Nietzsche, Simmel, and later Levinas. Upon immigrating to Palestine in 1938, he taught social philosophy at the Hebrew University of Jerusalem and was prominently engaged in promoting a bi-national state as the basis for a just political solution to the Palestinian-Zionist conflict.
Survival of Cercospora sojina on Soybean Leaf Debris in Illinois
Authors: Zhang Guirong , Bradley Carl A.
Published: August 2014

Historically, frogeye leaf spot (FLS, caused by Cercospora sojina) of soybean has been observed more frequently in the southern United States than the north-central United States. However, in recent years, FLS field observations have increased in the north-central United States. To better understand the survival rate of C. sojina in Illinois, a field study was conducted at three locations: Monmouth (west-central Illinois), Urbana (east-central Illinois), and Dixon Springs (southeastern Illinois). At each location, soybean leaves affected by FLS were placed at depths of 0, 10, and 20 cm and retrieved at different durations up to 24 months. To determine the viability of C. sojina in the collected leaves, a greenhouse bioassay was used. Survival of C. sojina declined equally with time at all three locations through 19 months. After 24 months, C. sojina from leaves that had been placed at Monmouth and Urbana were no longer viable, whereas leaves that had been placed at Dixon Springs produced viable inoculum. Depth of leaf placement had no effect on survival of C. sojina at any of the locations. These results suggest that planting a nonhost crop for two years in central Illinois will reduce levels of C. sojina inoculum to a negligible amount; however, soybean farmers in southern Illinois may need a longer rotation for FLS management.

Accepted 10 May 2014. Published 23 July 2014.
Selective Internal Yttrium-90 Radioembolization Therapy (90Y-SIRT) Versus Best Supportive Care in Patients With Unresectable Metastatic Melanoma to the Liver Refractory to Systemic Therapy
Authors: Xing Minzhi , Prajapati Hasmukh J. , Dhanasekaran Renumathy , Lawson David H. , Kokabi Nima , Eaton Bree R. , Kim Hyun S.
Published: August 2014

Objectives:

To investigate survival, efficacy, and safety of selective internal yttrium-90 radioembolization therapy (90Y-SIRT) in patients with unresectable metastatic melanoma (MM) to liver refractory to systemic therapy.

Methods:

An IRB-approved retrospective review of 58 patients diagnosed with unresectable MM to the liver, refractory to systemic therapy, between February 2003 and March 2012 was conducted. Of these, 28 received resin-based 90Y-SIRT (group A), and 30 patients received best supportive care (group B). Survival was calculated using the Kaplan-Meier method and Cox proportional hazard models.

Results:

Groups A and B were similar for the Child-Pugh class, ECOG scores, age, sex, and race. Median overall survival (OS) from diagnosis of primary melanoma in groups A and B were 119.9 and 26.1 months, respectively (P<0.001). Median OS from hepatic metastasis in groups A and B were 19.9 and 4.8 months, respectively (P<0.0001). In group A, median OS from hepatic metastasis in the Child-Pugh A, B, and C patients was 37.7, 4.2, and 3.6 months, respectively (P<0.001). In group B, median OS from hepatic metastasis in the Child-Pugh A, B, and C patients was 7.8, 4.2, and 1.9 months, respectively (P=0.04). Within group A, median OS from first 90Y-SIRT was 10.1 months; median OS of the Child-Pugh A, B, and C patients from first 90Y-SIRT was 10.3, 1.2, and 0.9 months, respectively (P=0.04). Median OS from first 90Y-SIRT was significantly greater in the absence of diffuse (>10) liver metastases (15.1 vs. 4.7 mo, P=0.02), and in the absence of extrahepatic metastases (21.3 vs. 8.6 mo, P<0.001). Common clinical toxicities following 90Y-SIRT included abdominal pain (17.9%), fatigue (14.3%), and self-limiting grade III bilirubin toxicity (10.7%).

Conclusion:

For patients with unresectable MM to the liver refractory to systemic therapy, resin-based 90Y was associated with longer survival from liver metastases than best supportive care. Child-Pugh A patients with <10 metastatic lesions and absence of extrahepatic metastases demonstrated greatest survival following 90Y-SIRT.
Lymph Node Ratio-based Staging System Outperforms the Seventh AJCC System for Gastric Cancer
Authors: Lee Yueh-Chang , Yang Po-Jen , Zhong Yuxin , Clancy Thomas E. , Lin Ming-Tsan , Wang Jiping
Published: August 2014

Background:

On the basis of SEER data, in which most gastric cancer patients had limited lymph node dissection, node ratio–based staging system (TNrM) has been shown to have better accuracy than the AJCC TNM system. This study is to validate the result with patients from Taiwan, where D2 lymphadenectomy is routinely performed.

Patient and Method:

A total of 1405 consecutive gastric cancer patients treated at National Taiwan University Hospital between 1998 and 2010 were included. To evaluate the performance of the AJCC system, each TNM stage was stratified by TNrM stages. The homogeneity of patients’ survival across TNrM strata was evaluated using the log-rank test. The performance of the TNrM system was evaluated with the same approach.

Results:

Five of the 7 evaluable AJCC stages (IA, IIA, IIIA, IIIB, and IIIC) contained TNrM subgroups with statistically heterogenous survival (P=0.003, 0.04, 0.002, 0.04, and <0.001, respectively). Thirty-six percent of patients (506/1405) were misclassified by the AJCC TNM system. However, of the assessable 6 TNrM stages, none of the AJCC subgroups showed significantly heterogenous survivals (P>0.05). About 19% of patients (264/1405) were misclassified by using the TNrM system.

Conclusions:

Lymph node ratio significantly decreases the stage migration caused by inadequate examined lymph nodes. The advantage of TNrM was validated with a patient cohort from the Eastern medical center.
Etoposide, Methotrexate, and Dactinomycin Alternating With Cyclophosphamide and Vincristine (EMACO) for Male Patients With HCG-expressing, Chemoresistant Germ Cell Tumors
Authors: Raggi Daniele , Giannatempo Patrizia , Miceli Rosalba , Farè Elena , Piva Luigi , Biasoni Davide , Catanzaro Mario , Torelli Tullio , Stagni Silvia , Marongiu Manuela , Gianni Alessandro M. , Nicolai Nicola , Salvioni Roberto , Necchi Andrea
Published: August 2014

Objectives:

To retrospectively analyze the efficacy and safety results of the combination of methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMACO) regimen for patients with human chorionic gonadotropin (HCG)-producing germ cell tumors and who had failed multiple courses of chemotherapy.

Methods:

Patients who had failed at least 2 regimens received methotrexate 100 mg/m2, followed by methotrexate 200 mg/m2 over 12 hours day 1, etoposide 100 mg/m2 and dactinomycin 0.5 mg days 1 and 2, folinic acid 25 mg orally every 6 hours days 2 and 3, alternating with cyclophosphamide 600 mg/m2 plus vincristine 1 mg/m2 day 8, every 21 days. Treatment was continued until marker normalization and for additional 2 cycles. Response rate, progression-free (PFS), and overall survival (OS) were the efficacy endpoints. Cox regression analyses examined the prognostic impact of candidate factors on PFS and OS.

Results:

From February 92 to May 13, 41 patients were treated in third line (n=20, 49%) or beyond (n=21, 51%). Seventeen (41%) had received high-dose chemotherapy. Thirty-one patients (75.6%) had a response with marker reduction, including 4 complete (9.8%) and 5 (12.2%) partial responses with HCG normalization. Median PFS was 3 months (95% confidence interval [CI], 2-4) and median OS was 8 months (95% CI, 6-10). Most frequent grade 3-4 toxicity was hematologic (20 patients, 48.8%). One toxic death (cerebral hemorrhage) occurred. On multivariable analysis, the line of treatment (greater than third vs. third) was the only significant predictor of both PFS (hazard ratio: 2.50, 95% CI, 1.20-5.24, P=0.015) and OS (hazard ratio: 3.17, 95% CI: 1.46-6.89, P=0.004).

Conclusions:

EMACO is an attractive regimen with acceptable toxicity and could be considered an option for HCG-expressing germ cell tumors whenever multiple relapses occur.
Purification of Dorsal Root Ganglion Neurons from Rat by Immunopanning
Authors: Zuchero J. Bradley
Published: August 2014

Dorsal root ganglion neurons (DRGs) are sensory neurons that facilitate somatosensation and have been used to study neurite outgrowth, regeneration, and degeneration and PNS and CNS myelination. Studies of DRGs have relied on cell isolation strategies that generally involve extended culture in the presence of antimitotic agents or other cytotoxic treatments that target dividing cells. The surviving cells typically are dependent on serum for growth. Other methods, involving purification of DRGs based on their large size, produce low yield. In contrast, the immunopanning-based method described here for prospective isolation of DRGs from rodents allows for rapid purification in the absence of antimitotic agents and serum. These DRG cultures take place in a defined medium. They are free of Schwann cells and other glia and thus can be used to study the role of glia in the biology of DRG neurons.
Measuring Ca2+-Dependent Ca2+-Uptake Activity in the Mouse Heart
Authors: Holemans Tine , Vandecaetsbeek Ilse , Wuytack Frank , Vangheluwe Peter
Published: August 2014

The apparent Ca2+ affinity of the isoforms of the sarco/endoplasmic reticulum Ca2+ ATPase SERCA2 is controlled primarily by two proteins, phospholamban (PLB) and sarcolipin (SLN). The rate of ATP-driven Ca2+ uptake into sarcoplasmic reticulum (SR)-derived vesicles can be monitored by a technique in which the net uptake of 45Ca2+ in the form of an intravesicular calcium oxalate precipitate is recorded. Here, we present details of a modification of such a protocol for determining the apparent Ca2+ affinity of the Ca2+ pump, and its control by various regulators, in crude homogenates of mouse heart.
Preparation of Rough Microsomes from Rat Liver
Authors: Sabatini David D.
Published: August 2014

This protocol describes how to prepare rat liver rough microsomes that contain undegraded membrane-bound polysomes and can function very well in an in vitro translation system. It uses endogenous ribonuclease inhibitor in all steps, avoiding pelleting rough microsomes in all steps and sacrificing good recovery.
Analyses of Tumor-Suppressor Genes in Germline Mouse Models of Cancer
Authors: Wang Jingqiang , Abate-Shen Cory
Published: August 2014

Tumor-suppressor genes are critical regulators of growth and functioning of cells, whose loss of function contributes to tumorigenesis. Accordingly, analyses of the consequences of their loss of function in genetically engineered mouse models have provided important insights into mechanisms of human cancer, as well as resources for preclinical analyses and biomarker discovery. Nowadays, most investigations of genetically engineered mouse models of tumor-suppressor function use conditional or inducible alleles, which enable analyses in specific cancer (tissue) types and overcome the consequences of embryonic lethality of germline loss of function of essential tumor-suppressor genes. However, historically, analyses of genetically engineered mouse models based on germline loss of function of tumor-suppressor genes were very important as these early studies established the principle that loss of function could be studied in mouse cancer models and also enabled analyses of these essential genes in an organismal context. Although the cancer phenotypes of these early germline models did not always recapitulate the expected phenotypes in human cancer, these models provided the essential foundation for the more sophisticated conditional and inducible models that are currently in use. Here, we describe these “first-generation” germline models of loss of function models, focusing on the important lessons learned from their analyses, which helped in the design and analyses of “next-generation” genetically engineered mouse models.
Measuring Apoptosis: Caspase Inhibitors and Activity Assays
Authors: McStay Gavin P. , Green Douglas R.
Published: August 2014

Caspases are proteases that initiate and execute apoptotic cell death. These caspase-dependent events are caused by cleavage of specific substrates that propagate the proapoptotic signal. A number of techniques have been developed to follow caspase activity in vitro and from apoptotic cellular extracts. Many of these techniques use molecules that are based on optimal peptide motifs for each caspase and on our understanding of caspase cleavage events that occur during apoptosis. Although these approaches are useful, there are several drawbacks associated with them. The optimal peptide motifs are not unique recognition sites for each caspase, so techniques that use them may yield information about more than one caspase. Furthermore, caspase cleavage does not take into account the different caspase activation mechanisms. Recently, probes having greater specificity for individual caspases have been developed and are being used successfully. This introduction provides background on the various caspases and introduces a set of complementary techniques to examine the activity, substrate specificity, and activation status of caspases from in vitro or cell culture experiments.
Optogenetics: Opsins and Optical Interfaces in Neuroscience
Authors: Adamantidis Antoine R. , Zhang Feng , de Lecea Luis , Deisseroth Karl
Published: August 2014

Optogenetics is defined as the integration of optics and genetics to control well-defined events within specified cells of living tissue. In this introduction, we focus on the basic techniques necessary for employing microbial opsins as optogenetic tools in mammalian brains. We provide a guide for the fundamentals of optogenetic application—selecting an opsin, implementing expression of opsins based on the neuroscientific experimental requirements, and adapting the corresponding optical hardware for delivery of light into mammalian brains.
The Impacts of Elicitation Context on Stated Preferences for Agricultural Landscapes
Authors: Tinch Dugald , Colombo Sergio , Hanley Nick
Published: August 2014

Statements of willingness to pay (WTP) have been shown to be dependent upon the framing of the hypothetical market. In this paper we investigate the effects of variations in the timing and location of choice experiment questions concerned with conservation of a UK national park, as research involving measurement of psychological well‐being suggests potential differences for the same individual dependent upon when and where preferences are elicited. We apply the choice experiment technique to the valuation of changes in upland agricultural and semi‐natural landscapes in the Peak District National Park in the UK, to investigate whether timing and location of elicitation (context) affects the value associated with changes in ecosystem services under different management regimes. Four treatments are employed – using the same sample of individuals answering the same choice scenarios – to measure WTP ex‐ante (off site), in situ (on site), and ex‐post at two different time intervals (off site). We show that our on‐site (in situ) treatment generates very different estimates of preferences than any of the off‐site treatments. That stated preferences associated with environmental goods are so context dependent may have implications for the use of stated preferences in policy analysis in terms of identifying how environmental policy is funded and the divergence in value attributed to sampling different populations.
Anthropological Facial Approximation in Three Dimensions (AFA3D): Computer‐Assisted Estimation of the Facial Morphology Using Geometric Morphometrics
Authors: Guyomarc'h Pierre , Dutailly Bruno , Charton Jérôme , Santos Frédéric , Desbarats Pascal , Coqueugniot Hélène
Published: August 2014

This study presents Anthropological Facial Approximation in Three Dimensions (AFA3D), a new computerized method for estimating face shape based on computed tomography (CT) scans of 500 French individuals. Facial soft tissue depths are estimated based on age, sex, corpulence, and craniometrics, and projected using reference planes to obtain the global facial appearance. Position and shape of the eyes, nose, mouth, and ears are inferred from cranial landmarks through geometric morphometrics. The 100 estimated cutaneous landmarks are then used to warp a generic face to the target facial approximation. A validation by re‐sampling on a subsample demonstrated an average accuracy ofc. 4 mm for the overall face. The resulting approximation is an objective probable facial shape, but is also synthetic (i.e., without texture), and therefore needs to be enhanced artistically prior to its use in forensic cases.AFA3D, integrated in theTIVMIsoftware, is available freely for further testing.
Why Do People Hang Themselves on Trees? An Evaluation of Suicidal Hangings on Trees in Konya, Turkey, between 2001 and 2008
Authors: Dogan Kamil Hakan , Demirci Serafettin , Deniz Idris
Published: August 2014

Hanging is the most common method of suicide in the world, and many public places offer a means or opportunity to carry out the activity. Of 4,452 death examinations and autopsies, there were 378 (8.5%) suicides and suicide method was hanging in 185 (48.9%) cases. In 20 of these (10.8%), the suspension point was the branch of a tree. The incident location was the garden of the victim's house in nine cases, the woodlands in seven cases. The suicides were attributed to psychiatric disorders in nine cases, economic problems in six cases, and family problems in five cases. It is concluded that hanging on a tree as a suicide method is often committed by males and the underlying motive may be different in suicidal hangings on trees occurring at daytime and night. For preventional purposes, the reporting of such suicides in public places by the media may be restricted by local authorities.