bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Treatment and Transfusion of Normal Blood Components Following Tolerance Induction in Patients with Anti-IgA Anaphylactic Reactions
Authors: Salama Abdulgabar , Kardashi Romina , Arbach Olga
Published: September 2014

Background: In general, patients with significant anti-Ig-A do not tolerate intravenous (i.v.) administration of normal blood products. Here, we present our experiences in the induction of immune tolerance (IIT) and long-term treatment in a series of such patients affected in such a way. The question whether blood components from IgA-deficient donors are required will be discussed. Methods: Ten adult patients (4 females and 6 males; age ranging from 36 to 75 years) with anti-IgA were included in this study. All patients required long-term treatment with blood components. One patient had IgA deficiency and paroxysmal nocturnal hemoglobinuria (PNH), and all other patients had common variable immunodeficiency (CVID). The particle gel immunoassay was used for the detection of anti-IgA. Immune tolerance to IgA was induced by controlled subcutaneous (s.c.) and/or i.v. infusions of IgG preparations. Results: Prior to IIT, anti-IgA was detectable in plasma samples of all patients and significantly diminished or abolished by controlled s.c. and/or i.v. infusions of IgG. Multiple transfusions with normal blood components could be repeatedly performed with the patient suffering from PNH without any complications. As long as i.v. IgG (IVIgG) infusions were consequently administered as individually required (intervals 2-8 weeks), none of the patients developed reactions during observation (up to 10 years). However, interruption of treatment and re-exposure to IVIgG resulted in adverse reactions. Conclusion: Patients with significant anti-IgA can be safely desensitized and tolerate long-term IgG substitutions independent of the IgA concentration of the used blood component.
The Effect of Erythropoiesis-Stimulating Agents in Patients with Therapy-Refractory Autoimmune Hemolytic Anemia
Authors: Salama Abdulgabar , Hartnack Dirk , Lindemann Hans-Walter , Lange Hans-Joachim , Rummel Mathias , Loew Andreas
Published: September 2014

Background: Many patients with autoimmune hemolytic anemia (AIHA) do not respond to standard therapy and/or may develop severe complications which can be of fatal outcome. There is some evidence that erythropoiesis-stimulating agents (ESAs) may be helpful in the management of such patients. Methods: We describe the effect of ESAs in 12 new patients with therapy-refractory AIHA (7 of warm type and 5 of cold type) and review 5 previously reported cases. Serological testing was performed using standard methods. Results: All patients responded well to treatment with ESAs. At least 5 of the 17 patients demonstrated complete recovery, and none of the patients developed significant adverse reactions due to treatment with ESAs. Conclusion: The mechanism by which ESAs improves hemolysis in AIHA is not completely clear. In addition to increased production and prolonged RBC survival, it may inhibit eryptosis (programmed cell death). ESAs represent a new option in the treatment of decompensated and/or refractory AIHA of warm and cold type. However, more information is required to assess which patients can be treated with ESAs.
Hypophysiotropic Gonadotropin-Releasing Hormone Projections Are Exposed to Dense Plexuses of Kisspeptin, Neurokinin B and Substance P Immunoreactive Fibers in the Human: A Study on Tissues from Postmenopausal Women
Authors: Borsay Beáta Á. , Skrapits Katalin , Herczeg László , Ciofi Philippe , Bloom Stephen R. , Ghatei Mohammad A. , Dhillo Waljit S. , Liposits Zsolt , Hrabovszky Erik
Published: September 2014

Neuronal populations that synthesize kisspeptin (KP), neurokinin B (NKB) and substance P (SP) in the hypothalamic infundibular nucleus of humans are partly overlapping. These cells are important upstream regulators of gonadotropin-releasing hormone (GnRH) neurosecretion. Homologous neurons in laboratory animals are thought to modulate episodic GnRH secretion primarily via influencing KP receptors on the hypophysiotropic fiber projections of GnRH neurons. To explore the structural basis of this putative axo-axonal communication in humans, we analyzed the anatomical relationship of KP-immunoreactive (IR), NKB-IR and SP-IR axon plexuses with hypophysiotropic GnRH fiber projections. Immunohistochemical studies were carried out on histological samples from postmenopausal women. The neuropeptide-IR axons innervated densely the portal capillary network in the postinfundibular eminence. Subsets of the fibers formed descending tracts in the infundibular stalk, some reaching the neurohypophysis. KP-IR, NKB-IR and SP-IR plexuses intermingled, and established occasional contacts, with hypophysiotropic GnRH fibers in the postinfundibular eminence and through their lengthy course while descending within the infundibular stalk. Triple-immunofluorescent studies also revealed considerable overlap between the KP, NKB and SP signals in individual fibers, providing evidence that these peptidergic projections arise from neurons of the mediobasal hypothalamus. These neuroanatomical observations indicate that the hypophysiotropic projections of human GnRH neurons in the postinfundibular eminence and the descending GnRH tract coursing through the infundibular stalk to the neurohypophysis are exposed to neurotransmitters/neuropeptides released by dense KP-IR, NKB-IR and SP-IR fiber plexuses. Localization and characterization of axonal neuropeptide receptors will be required to clarify the putative autocrine and paracrine interactions in these anatomical regions.
Modulation of Alpha Activity in the Parieto-occipital Area by Distractors during a Visuospatial Working Memory Task: A Magnetoencephalographic Study
Authors: Ichihara-Takeda Satoe , Yazawa Shogo , Murahara Takashi , Toyoshima Takanobu , Shinozaki Jun , Ishiguro Masanori , Shiraishi Hideaki , Ikeda Nozomu , Matsuyama Kiyoji , Funahashi Shintaro , Nagamine Takashi
Published: September 2014

Oscillatory brain activity is known to play an essential role in information processing in working memory. Recent studies have indicated that alpha activity (8–13 Hz) in the parieto-occipital area is strongly modulated in working memory tasks. However, the function of alpha activity in working memory is open to several interpretations, such that alpha activity may be a direct neural correlate of information processing in working memory or may reflect disengagement from information processing in other brain areas. To examine the functional contribution of alpha activity to visuospatial working memory, we introduced visuospatial distractors during a delay period and examined neural activity from the whole brain using magnetoencephalography. The strength of event-related alpha activity was estimated using the temporal spectral evolution (TSE) method. The results were as follows: (1) an increase of alpha activity during the delay period as indicated by elevated TSE curves was observed in parieto-occipital sensors in both the working memory task and a control task that did not require working memory; and (2) an increase of alpha activity during the delay period was not observed when distractors were presented, although TSE curves were constructed only from correct trials. These results indicate that the increase of alpha activity is not directly related to information processing in working memory but rather reflects the disengagement of attention from the visuospatial input.
Size Precedes View: Developmental Emergence of Invariant Object Representations in Lateral Occipital Complex
Authors: Nishimura Mayu , Scherf K. Suzanne , Zachariou Valentinos , Tarr Michael J. , Behrmann Marlene
Published: September 2014

Although object perception involves encoding a wide variety of object properties (e.g., size, color, viewpoint), some properties are irrelevant for identifying the object. The key to successful object recognition is having an internal representation of the object identity that is insensitive to these properties while accurately representing important diagnostic features. Behavioral evidence indicates that the formation of these kinds of invariant object representations takes many years to develop. However, little research has investigated the developmental emergence of invariant object representations in the ventral visual processing stream, particularly in the lateral occipital complex (LOC) that is implicated in object processing in adults. Here, we used an fMR adaptation paradigm to evaluate age-related changes in the neural representation of objects within LOC across variations in size and viewpoint from childhood through early adulthood. We found a dissociation between the neural encoding of object size and object viewpoint within LOC: by age of 5–10 years, area LOC demonstrates adaptation across changes in size, but not viewpoint, suggesting that LOC responses are invariant to size variations, but that adaptation across changes in view is observed in LOC much later in development. Furthermore, activation in LOC was correlated with behavioral indicators of view invariance across the entire sample, such that greater adaptation was correlated with better recognition of objects across changes in viewpoint. We did not observe similar developmental differences within early visual cortex. These results indicate that LOC acquires the capacity to compute invariance specific to different sources of information at different time points over the course of development.
“Me & My Brain”: Exposing Neuroscience's Closet Dualism
Authors: Mudrik Liad , Maoz Uri
Published: September 2014

Our intuitive concept of the relations between brain and mind is increasingly challenged by the scientific world view. Yet, although few neuroscientists openly endorse Cartesian dualism, careful reading reveals dualistic intuitions in prominent neuroscientific texts. Here, we present the “double-subject fallacy”: treating the brain and the entire person as two independent subjects who can simultaneously occupy divergent psychological states and even have complex interactions with each other—as in “my brain knew before I did.” Although at first, such writing may appear like harmless, or even cute, shorthand, a closer look suggests that it can be seriously misleading. Surprisingly, this confused writing appears in various cognitive-neuroscience texts, from prominent peer-reviewed articles to books intended for lay audience. Far from being merely metaphorical or figurative, this type of writing demonstrates that dualistic intuitions are still deeply rooted in contemporary thought, affecting even the most rigorous practitioners of the neuroscientific method. We discuss the origins of such writing and its effects on the scientific arena as well as demonstrate its relevance to the debate on legal and moral responsibility.
DRD4 Long Allele Carriers Show Heightened Attention to High-priority Items Relative to Low-priority Items
Authors: Gorlick Marissa A. , Worthy Darrell A. , Knopik Valerie S. , McGeary John E. , Beevers Christopher G. , Maddox W. Todd
Published: September 2014

Humans with seven or more repeats in exon III of the DRD4 gene (long DRD4 carriers) sometimes demonstrate impaired attention, as seen in attention-deficit hyperactivity disorder, and at other times demonstrate heightened attention, as seen in addictive behavior. Although the clinical effects of DRD4 are the focus of much work, this gene may not necessarily serve as a “risk” gene for attentional deficits, but as a plasticity gene where attention is heightened for priority items in the environment and impaired for minor items. Here we examine the role of DRD4 in two tasks that benefit from selective attention to high-priority information. We examine a category learning task where performance is supported by focusing on features and updating verbal rules. Here, selective attention to the most salient features is associated with good performance. In addition, we examine the Operation Span (OSPAN) task, a working memory capacity task that relies on selective attention to update and maintain items in memory while also performing a secondary task. Long DRD4 carriers show superior performance relative to short DRD4 homozygotes (six or less tandem repeats) in both the category learning and OSPAN tasks. These results suggest that DRD4 may serve as a “plasticity” gene where individuals with the long allele show heightened selective attention to high-priority items in the environment, which can be beneficial in the appropriate context.
Zadbimyia, a new genus of asynaptine Porricondylinae (Diptera: Cecidomyiidae) with twenty-two new species from the cloud forest of Costa Rica
Authors: JASCHHOF MATHIAS , JASCHHOF CATRIN
Published: September 2014

Twenty-two new species of Zadbimyia, a new genus of the tribe Asynaptini, are described from Costa Rica, the first new descriptions of Neotropical Porricondylinae (Cecidomyiidae) in modern times. The new species are: Zadbimyia aberrans, Z. anniae, Z. artborkenti, Z. browni, Z. carolinae, Z. costaricensis, Z. dubia, Z. elenae, Z. elviae, Z. holdenae, Z. inornata, Z. lasalturas, Z. marcoi, Z. membranacea, Z. minima, Z. spinapiscis, Z. talamanca, Z. tapanti, Z. viquezi, Z. wendyae, Z. zumbadoi, and Z. zurqui. All species were found during the Zurquí All-Diptera Biodiversity Inventory, in mid-elevation (1600 m) cloud forest in the central highlands of Costa Rica. A maximum of 19 species occurred at a single site. Pseudocamptomyia Parnell, a genus known from one species in northeastern United States and possibly two species in Somalia, was identified as the closest relative of Zadbimyia. Ultraviolet light traps proved to be the most effective device to collect adults of Zadbimyia. As a peculiarity in Porricondylinae, the circumfila of Zadbimyia males are multi-looped and not substantively different from the circumfila known from male Cecidomyiidi (subfamily Cecidomyiinae).
Discovery of new populations and DNA barcoding of the Arapahoe snowfly Arsapnia arapahoe (Plecoptera: Capniidae)
Authors: HEINOLD BRIAN D. , GILL BRIAN A. , BELCHER THOMAS P. , VERDONE CHRIS J.
Published: September 2014

The Arapahoe Snowfly, Arsapnia arapahoe (Nelson & Kondratieff)was recently discovered in six different first-order streams outside of the Cache la Poudre River Basin where it was previously considered endemic. Specimens of A. arapahoe were always collected in much lower relative abundance, 1.09% (±2.3SD), than other sympatric adult capniids. The first mitochondrial deoxyribonucleic acid (DNA) barcodes for A. arapahoe and A. coyote (Nelson & Baumann) are presented and compared with those of A. decepta. DNA barcoding was not able to differentiate between A. arapahoe and A. decepta Banks but it was able to indicate that A. coyote is specifically distinct.
Drepanosticta machadoi spec. nov. from New Guinea (Odonata: Platystictidae)
Authors: THEISCHINGER G. , RICHARDS S. J.
Published: September 2014

Drepanosticta machadoi sp. nov. (Holotype ♂: Dablin Creek, Hindenburg Range) from Papua New Guinea is described. The new species is a predominantly black damselfly, the male with four pale/bright pattern elements on each side of the synthorax, dorsum of segments 9 and 10 largely bright blue, and a uniquely shaped posterior lobe of the pronotum which is a wide-angled fork with rather straight, narrow finger-like prongs. It is referred to the Drepanosticta conica group of species and a key to the males of the D. conica group is provided.
Characterization of Low-Level Winds of Southern and Coastal Delaware
Authors: Hughes Christopher P. , Veron Dana E.
Published: September 2014

Winds across the Delaware Peninsula transport pollutants, modify the temperature, and play a critical role within the state’s agricultural and tourism industries. The low-level winds inland and near Delaware’s coastline are characterized using observations from eight meteorological stations operated by the Delaware Environmental Observing System and the National Data Buoy Center from 2005 through 2012. The low-level winds have pronounced dominant directions during the summer (southwest/southeast) and winter (northwest) seasons, with the greatest spatial and temporal variability occurring in the summer. This inhomogeneity was further investigated with a set of simulations of the low-level winds over the Delaware Bay and surrounding landmass using the Weather Research and Forecasting Model for a subset of days from 2006 through 2012. The model was run with three nests, with the inner nest having a 2-km horizontal resolution. The randomly selected days were organized by synoptic type and season. Mesoscale wind events such as the sea-breeze circulation introduce significant variability in the local wind field of coastal Delaware—an effect that is seen in both observed and modeled data. Southerly winds off Delaware’s coast frequently shift counterclockwise up the Delaware Bay in alignment with the bay coastline. Long-term data from station B44009 (1984–2012) indicate a May decrease (0.03 m s−1 yr−1; significance p = 0.026) and an October increase (0.04 m s−1 yr−1; p = 0.006) of the mean wind speed. Results suggest that the local wind regime is multifaceted and contains significant seasonal, diurnal, and spatial variations.
The Relationship between Hurricane Potential Intensity and CAPE
Authors: Garner Stephen
Published: September 2014

The theoretical minimum eyewall pressure of tropical cyclones can be computed from convective available potential energy (CAPE) if the buoyancy in the CAPE is allowed to feed back on the surface pressure via hydrostatic balance. The relationship between this so-called hurricane CAPE and the surface pressure is exploited by a widely used algorithm for hurricane potential intensity (PI). For the observed atmosphere, the algorithm is shown to yield significantly weaker pressure intensity (20%–25%) and velocity intensity (5%–10%) than the most familiar analytical formulas. This discrepancy is found to come mostly from thermodynamic approximations in the formulas.

The CAPE–PI algorithm makes a significant adjustment to the hurricane CAPE by subtracting the environmental CAPE. Most of the environmental profile becomes irrelevant as a result. Other steady-state theories retain the influence of the full environmental column. The impact of this choice on the pressure and velocity PI is analyzed. Another important choice—whether to allow the eyewall kinetic energy to contribute to the surface pressure perturbation—is also analyzed and quantified. The analytical formula for the velocity is updated with full moist thermodynamics and compared to the algorithm. The latter emerges as an excellent overall diagnostic of the underlying model. An exact algorithm for the velocity is also derived, based on its relationship to the radial derivative of hurricane CAPE. The thermodynamic efficiency often invoked to interpret velocity PI is identified as a marginal efficiency measured at the point of maximum energy dissipation rate and is contrasted with the global efficiency, which has a direct connection with the pressure intensity.
Timing Uncertainty of the Lightning Imaging Sensor
Authors: Bitzer Phillip M. , Christian Hugh J.
Published: September 2014

The timing uncertainty of the Lightning Imaging Sensor (LIS), on orbit, is not currently accurately known. This is due to an imprecise value of the frame rate in the literature; the conceptual design value of 500 frames per second (fps) is often quoted. As researchers explore more ways to apply LIS data—in particular, the utility of group-level data, which correspond to strokes—a more precise value of the frame rate and timing uncertainty is important for proper understanding and use of the data. In this study, the average on-orbit frame rate was documented. From this, the timing uncertainty for LIS data was determined. Using on-orbit LIS data, the average frame rate of LIS is 558.58 fps and the timing uncertainty for LIS groups and events is 250 μs. It is shown that this uncertainty is associated with the quantization of the time of each frame. Further, the source time of optical pulses from lightning can have a bias that is not currently accounted for in the LIS data. This study shows how this correction can be on the order of the timing uncertainty, and a method in which this correction can be determined is outlined.
Characteristics of Low Pressure Systems Associated with Intraseasonal Oscillation of Rainfall over Bangladesh during Boreal Summer
Authors: Hatsuzuka Daisuke , Yasunari Tetsuzo , Fujinami Hatsuki
Published: September 2014

Characteristics of low pressure systems (LPSs) responsible for submonthly-scale (7–25 days) intraseasonal oscillation (ISO) in rainfall over Bangladesh and their impact on the amplitude of active peaks are investigated for 29 summer monsoon seasons. Extreme and moderate active peaks are obtained based on the amplitude of 7–25-day-filtered rainfall series. By detecting the LPSs that formed over the Indian monsoon region, it was found that about 59% (62%) of extreme (moderate) active peaks of rainfall are related to LPSs. These LPSs have horizontal scale of about 600 km and vertical scale of about 9 km. For the extreme active peak, the locations of the LPS centers are clustered significantly over and around Bangladesh, accompanied by the maximum convergence in the southeast sector of the LPSs. After their formation, they tend to remain almost stationary over and around Bangladesh. In contrast, for the moderate active peak, the LPS centers are located over the Ganges Plain around 85°E, and the maximum convergence of the LPSs occurs around their centers. This difference in the convergence fields is closely associated with the geographical features to the north and east of Bangladesh and the horizontal scale of the LPSs. These features suggest that the amplitude of the active peaks in the submonthly-scale ISO is modulated by small differences in the locations of the LPS centers. These findings suggest that improved predictions of both genesis location and the tracks of the LPSs are crucial to forecasting seasonal rainfall over Bangladesh.
The Editor’s Note
Authors: Richardson Joan
Published: September 2014

The author contemplates the writings of W.E.B. Dubois and Haim Ginott and calls for schools and teachers to recognize that they exert an extraordinary amount of power and control over children, and for them to use that capacity to positively shape their interactions with black male children as well as all students.
HIGHLIGHTED & UNDERLINED
Authors: Richardson Joan
Published: September 2014

News and information from the education world. Suburban poverty grows; American kids are sleepier in class than others around the world; major foundations in education have simultaneously shifted away from funding traditional educational institutions toward support for organizations that could create competition for the public sector; the Vergara v. California strategy lays out a roadmap for battling teacher tenure.
Social-emotional learning is essential to classroom management
Authors: Jones Stephanie M. , Bailey Rebecca , Jacob Robin
Published: September 2014

Research tells us that children’s social-emotional development can propel learning. A new program, SECURe, embeds that research into classroom management strategies that improve teaching and learning. Across all classrooms and grade levels, four principles of effective management are constant: Effective classroom management is based in planning and preparation; is an extension of the quality of relationships in the room; is embedded in the school environment; and includes ongoing processes of observation and documentation.
Boys from the ‘hood — often misunderstood
Authors: Patterson Gregory A.
Published: September 2014

An undeniable issue of classroom management is the mix of white, middle-class teachers and administrators serving schools and classrooms with significant populations of male students of color. In some ways this is a widely researched and reported topic but rarely do we stop to consider the basic racial dynamic. A panel of African-American (mostly male) educators give their views on such classrooms primarily from the perspective of the boys.
Lessons learned the hard way but learned well
Authors: Dirksen Debra J.
Published: September 2014

The author spins a tale of how she learned classroom management largely by trial and error and by making a commitment to never give up on her students.
Uncovering “The Deal” in classroom management
Authors: McDonald Joseph P. , Hudder Daniel
Published: September 2014

A teacher educator and a former student, now a classroom teacher, have a 14-year conversation about the deep dynamics of classroom management, which is more complicated than it first appears. The teacher educator introduces the classroom teacher to The Deal, an idea that can guide early-career teachers as well as veteran teachers. The Deal is, in part, about projecting confidence when confidence is thin but also about believing resolutely in the possibility of development for both students and teachers even when that possibility seems most dubious.
Improve assessment literacy outside of schools too
Authors: Stiggins Rick
Published: September 2014

Educators need to become more assessment literate. When they do, they will be able to use assessments better to guide their teaching and communicate their expectations and results with students and the broader education stakeholders and audiences.
PDK CONNECTION
Authors: Patterson Gregory A.
Published: September 2014

News and information about PDK. PDK membership approves bylaws changes. Kappan strikes professional partnership with the International Journal of Education Policy and Leadership (IJEPL). Two Emerging Leaders respond to Kappan’s question about teacher tenure.
A transformative social scientist: Karl Deutsch and the discipline of International Relations
Authors: Ruzicka Jan
Published: September 2014

This introduction to this Special Issue of International Relations dedicated to Karl Deutsch makes the case that his scholarship was transformative in more ways than is typically recognized in the discipline. Besides being a theoretical and methodological innovator, Deutsch also envisaged that research must have transformative qualities for the future of human relations. The latter in particular deserves attention of International Relations (IR) students because it opens up possibilities for novel empirical and theoretical research of international politics. Deutsch clearly believed that social scientific research must be normatively grounded and serve normative purposes.
Working with Karl W. Deutsch: A life-changing experience on the professional and personal level
Authors: Markovits Andrei S
Published: September 2014

In tracing his 15-year relationship with Karl W. Deutsch, Andrei S. Markovits portrays the key intellectual agendas and major scholarly contributions that formed the core of Deutsch’s academic life. The article highlights how Deutsch’s personal life as well as his singularly impressive qualities shaped the originality and greatness of his intellectual contributions but also the profound humaneness of his quotidian life.
In the footsteps of Karl Deutsch: On nationalism, self-determination and international relations
Authors: Stullerova Kamila
Published: September 2014

The article argues that Karl Deutsch’s work on nationalism is not only a precursor to his ‘security communities’ but that it is central to his international relations (IR). Nationalism impacts what people expect from the state and influences the state’s international behaviour. While these processes are mostly automatic and cannot be controlled, their trajectories are not fully determined. Deutsch is interested in theorising moments when automatic processes do not suffice or become harmful and intervention is needed. The article first introduces Deutsch as a theorist of nationalism, examining his contribution in the context of the field of nationalism studies and the reasons for his equivocal reception in this field. In its second part, the article makes sense of the legacy of Deutsch’s work on nationalism for contemporary IR by focusing on his use of the notion of self-determination with which Deutsch transcends the normative imperatives of the narrower concept of national self-determination.
The richness of the liberal tradition in international relations: Karl Deutsch on political community and the European integration
Authors: Drulák Petr , Druláková Radka
Published: September 2014

Karl Deutsch focused in his work on many social, political and technical aspects of building political community which can enrich our understanding of international cooperation and European integration. It is especially his concept of the political community that helps us to explain current problems of the European integration: namely, the current pre-occupation with the market and institutions leads to the neglect of the common redistribution and of the horizontal ties among the state institutions and among the peoples. This article also points to the tension between Deutsch’s awareness that the study of political communities requires the examination of values, love and spirituality, and his positivist, quantitative methods which do not allow for such an examination. This tension invites to a re-reading of Deutsch, which can enrich the liberal tradition of international relations (IR).
Security community: A future for a troubled concept?
Authors: Ditrych Ondrej
Published: September 2014

This article offers first a brief commentary on Karl Deutsch and his collaborators’ development of the concept of security community, before moving to a critical review of constructivist attempts by Adler, Barnett and their colleagues at resurrecting it. The article makes the case that while the serious effort to give security community a new life is laudable, the appropriation also renders the concept at once theoretically complex and methodologically superficial. Drawing constructive lessons from the previous research, it seeks to demonstrate the potential of the security communities research provided that it (1) restores the Deutschian ethos of rigorous, transparent, collective and transdisciplinary research; (2) takes seriously the challenge to the realist paradigm by zooming in and out of the modern state when thinking about security community; and (3) in addition to processes of integration investigates more thoroughly also the processes of disintegration.
A fetish for measurement? Karl Deutsch in the second debate
Authors: Ruzicka Jan
Published: September 2014

This article begins by asking why Karl Deutsch never directly intervened in what has come to be known in the field as the second debate. This point of departure is used to outline Deutsch’s views on the purpose of knowledge. It is apparent that Deutsch was unwilling to make the distinction between the traditional and scientific approaches, which stood at the heart of the debate started by Hedley Bull. Deutsch’s position tried to embrace both approaches, because they were necessary in order to answer the big and important questions he asked. Deutsch also rejected the notion that the scientific approach could be devoid of normative concerns. Finally, the article argues that Deutsch keenly adopted methods connected with the scientific approach because he believed they made it possible to spot new patterns which might hold novel answers to the profoundly normative question of humankind’s survival.
Mobile language in mobile places
Authors: Jaworski Adam
Published: September 2014

Common methodological and conceptual threads are discussed with reference to the approaches adopted in the four papers of this special issue: Goffman’s frame analysis, Bakhtin’s chronotopes, Blommaert’s spatialization of language, and the Scollons’ nexus analysis. The commentary concludes with brief reflections on ‘mobile’ places.
RETRACTED ARTICLE: Jacarelhyperol A induced apoptosis in leukaemia cancer cell through inhibition the activity of Bcl-2 proteins
Authors: Zhang Shoude , Yin Jun , Li Xia , Zhang Jigang , Yue Rongcai , Diao Yanyan , Li Honglin , Wang Hui , Shan Lei , Zhang Weidong
Published: September 2014

Background

Hypericum japonicum Thunb. ex Murray is widely used as an herbal medicine for the treatment of hepatitis and tumours in China. However, the molecular mechanisms of its effects are unclear. Our previous research showed that extracts of H. japonicum can induce apoptosis in leukaemia cells. We also previously systematically analysed and isolated the chemical composition of H. japonicum.

Methods

The fluorescence polarisation experiment was used to screen for inhibitors of Bcl-2 proteins which are proved as key proteins in apoptosis. The binding mode was modelled by molecular docking. We investigated the proliferation attenuating and apoptosis inducing effects of active compound on cancer cells by MTT assay and flow cytometry analysis. Activation of caspases were tested by Western blot. A broad-spectrum caspase inhibitor Z-VAD-FMK was used to investigate the caspases-dependence. In addition, co-immunoprecipitation was performed to analyse the inhibition of heterodimerization between anti-apoptotic Bcl-2 proteins with pro-apoptotic proteins. Moreover, in vivo activity was tested in a mouse xenograph tumour model.

Result

Jacarelhyperol A (Jac-A), a characteristic constituent of H. japonicum, was identified as a potential Bcl-2 inhibitor. Jac-A showed binding affinities to Bcl-xL, Bcl-2, and Mcl-1 with Ki values of 0.46 μM, 0.43 μM, and 1.69 μM, respectively. This is consistent with computational modelling results, which show that Jac-A presents a favorable binding mode with Bcl-xL in the BH3-binding pocket. In addition, Jac-A showed potential growth inhibitory activity in leukaemia cells with IC50 values from 1.52 to 6.92 μM and significantly induced apoptosis of K562 cells by promoting release of cytochrome c and activating the caspases. Jac-A also been proved that its effect is partly caspases-dependent and can disrupt the heterodimerization between anti-apoptotic Bcl-2 proteins with pro-apoptotic proteins. Moreover, Jac-A dose-dependently inhibited human K562 cell growth in a mouse xenograph tumour model with low toxicity.

Conclusion

In this study, a characteristic constituent of H. japonicum, Jac-A, was shown to induce apoptosis in leukaemia cells by mediating the Bcl-2 proteins. Therefore, we propose a new lead compound for cancer therapy with a low toxicity, and have provided evidence for using H. japonicum as an anti-cancer herb.
CheS-Mapper 2.0 for visual validation of (Q)SAR models
Authors: Gütlein Martin , Karwath Andreas , Kramer Stefan
Published: September 2014

Background

Sound statistical validation is important to evaluate and compare the overall performance of (Q)SAR models. However, classical validation does not support the user in better understanding the properties of the model or the underlying data. Even though, a number of visualization tools for analyzing (Q)SAR information in small molecule datasets exist, integrated visualization methods that allow the investigation of model validation results are still lacking.

Results

We propose visual validation, as an approach for the graphical inspection of (Q)SAR model validation results. The approach applies the 3D viewer CheS-Mapper, an open-source application for the exploration of small molecules in virtual 3D space. The present work describes the new functionalities in CheS-Mapper 2.0, that facilitate the analysis of (Q)SAR information and allows the visual validation of (Q)SAR models. The tool enables the comparison of model predictions to the actual activity in feature space. The approach is generic: It is model-independent and can handle physico-chemical and structural input features as well as quantitative and qualitative endpoints.

Conclusions

Visual validation with CheS-Mapper enables analyzing (Q)SAR information in the data and indicates how this information is employed by the (Q)SAR model. It reveals, if the endpoint is modeled too specific or too generic and highlights common properties of misclassified compounds. Moreover, the researcher can use CheS-Mapper to inspect how the (Q)SAR model predicts activity cliffs. The CheS-Mapper software is freely available at http://ches-mapper.org.

Graphical abstract

Comparing actual and predicted activity values with CheS-Mapper.
Identification of positron emission tomography (PET) tracer candidates by prediction of the target-bound fraction in the brain
Authors: Fridén Markus , Wennerberg Marie , Antonsson Madeleine , Sandberg-Ställ Maria , Farde Lars , Schou Magnus
Published: September 2014

Background

Development of tracers for imaging with positron emission tomography (PET) is often a time-consuming process associated with considerable attrition. In an effort to simplify this process, we herein propose a mechanistically integrated approach for the selection of tracer candidates based on in vitro measurements of ligand affinity (Kd), non-specific binding in brain tissue (Vu,brain), and target protein expression (Bmax).

Methods

A dataset of 35 functional and 12 non-functional central nervous system (CNS) PET tracers was compiled. Data was identified in literature for Kd and Bmax, whereas a brain slice methodology was used to determine values for Vu,brain. A mathematical prediction model for the target-bound fraction of tracer in the brain (ftb) was derived and evaluated with respect to how well it predicts tracer functionality compared to traditional PET tracer candidate selection criteria.

Results

The methodology correctly classified 31/35 functioning and 12/12 non-functioning tracers. This predictivity was superior to traditional classification criteria or combinations thereof.

Conclusions

The presented CNS PET tracer identification approach is rapid and accurate and is expected to facilitate the development of novel PET tracers for the molecular imaging community.
Flow of generalized Burgers fluid between parallel walls induced by rectified sine pulses stress
Authors: Sultan Qamar , Nazar Mudassar , Imran Muhammad , Ali Usman
Published: September 2014

This paper presents the unsteady magnetohydrodynamic (MHD) flow of a generalized Burgers’ fluid between two parallel side walls perpendicular to a plate. The plate applies a shear stress induced by rectified sine pulses to the fluid. The obtained solutions by means of the Laplace and Fourier cosine and sine transforms are presented as a sum of the corresponding Newtonian and non-Newtonian contributions. The effects of the magnetic field, permeability, and the period of the oscillation have been observed on the fluid motion. Moreover, the influence of the side walls on the fluid motion and the distance between the walls for which the velocity of the fluid in the middle of the channel is negligible are presented by graphical illustrations.

MSC: 76A05, 76A10.
Transcriptional factor snail controls tumor neovascularization, growth and metastasis in mouse model of human ovarian carcinoma
Authors: Abdulkhalek Samar , Geen Olivia D , Brodhagen Lacey , Haxho Fiona , Alghamdi Farah , Allison Stephanie , Simmons Duncan J , O'Shea Leah K , Neufeld Ronald J , Szewczuk Myron R
Published: September 2014

Background

Snail, a transcriptional factor and repressor of E‐cadherin is well known for its role in cellular invasion. It can regulate epithelial to mesenchymal transition (EMT) during embryonic development and in epithelial cells. Snail also mediates tumor progression and metastases. Silencing of Snail and its associate member Slug in human A2780 ovarian epithelial carcinoma cell line was investigated to identify its role in tumor neovascularization.

Methods

Live cell sialidase, WST‐1 cell viability and immunohistochemistry assays were used to evaluate sialidase activity, cell survival and the expression levels of tumor E‐cadherin, N‐cadherin, VE‐cadherin, and host endothelial CD31+(PECAM‐1) cells in archived paraffin‐embedded ovarian A2780, A2780 Snail shRNA GIPZ lentiviral knockdown (KD) and A2780 Slug shRNA GIPZ lentiviral KD tumors grown in RAGxCγ double mutant mice.

Results

Oseltamivir phosphate (OP), anti‐Neu1 antibodies and MMP‐9 specific inhibitor blocked Neu1 activity associated with epidermal growth factor (EGF) stimulated A2780 ovarian epithelial carcinoma cells. Silencing Snail in A2780 cells abrogated the Neu1 activity following EGF stimulation of the cells compared to A2780 and A2780 Slug KD cells. OP treatment of A2780 and cisplatin‐resistant A2780cis cells reproducibly and dose‐dependently abated the cell viability with a LD50 of 7 and 4 μm, respectively, after 48 h of incubation. Heterotopic xenografts of A2780 and A2780 Slug KD tumors developed robust and bloody tumor vascularization in RAG2xCγ double mutant mice. OP treatment at 50 mg/kg daily intraperitoneally did not significantly impede A2780 tumor growth rate but did cause a significant reduction of lung metastases compared with the untreated and OP 30mg/kg cohorts. Silencing Snail in A2780 tumor cells completely abrogated tumor vascularization, tumor growth and spread to the lungs in RAGxCγ double mutant mice. A2780 and A2780 Slug KD tumors expressed high levels of human N‐ and VE‐cadherins, and host CD31+ endothelial cells, while A2780 Snail KD tumors expressed E‐cadherin and reduced host CD31+ cells. OP 50mg/kg cohort tumors had reduced numbers of host CD31+ cells compared to a higher expression levels of CD31+ cells in tumors from the untreated control and OP 30mg/kg cohorts.

Conclusion

Snail transcriptional factor is an important intermediate player in human ovarian tumor neovascularization.
Lung flute improves symptoms and health status in COPD with chronic bronchitis: A 26 week randomized controlled trial
Authors: Sethi Sanjay , Yin Jingjing , Anderson Pamela K
Published: September 2014

Background

Chronic obstructive pulmonary disease (COPD) is characterized by mucus hypersecretion that contributes to disease related morbidity and is associated with increased mortality. The Lung Flute® is a new respiratory device that produces a low frequency acoustic wave with moderately vigorous exhalation to increase mucus clearance. We hypothesized that the Lung Flute, used on a twice daily basis will provide clinical benefit to patients with COPD with chronic bronchitis.

Methods

We performed a 26 week randomized, non‐intervention controlled, single center, open label trial in 69 patients with COPD and Chronic Bronchitis. The primary endpoint was change in respiratory symptoms measured with the Chronic COPD Questionnaire (CCQ). Secondary endpoints included health status, assessed by the St. George Respiratory questionnaire (SGRQ), BODE (Body‐Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity)

index score and exacerbation frequency.

Results

While the control patients did not demonstrate any significant changes in the primary endpoint (CCQ change at 26 weeks of +0.01, p = 0.8), a trend (p = 0.08) to decrease (improvement) in the CCQ (‐0.23 at 26 weeks) was seen with the Lung Flute. Furthermore, a significant improvement in the symptom domain of the CCQ was seen only with the lung flute (‐0.42, p = 0.004). Health status (SGRQ) improvement, was also only seen with the Lung Flute (‐3.23, p = 0.03). The BODE score increased in the control group (3.31 at baseline, 4.14 at 26 weeks), however it remained stable in the Lung Flute arm (3.16 at baseline and 26 weeks), with the changes from baseline being significantly different between the 2 arms (p = 0.01). There was a trend for less exacerbations in the Lung Flute group (p = 0.07). Adverse effects were minor, with only 1 patient discontinuing treatment because of lack of efficacy. Serious adverse effects seen were all determined to be unrelated to the device use.

Conclusions

The Lung Flute is a safe and effective treatment in COPD with chronic bronchitis, providing a wide array of benefits.

ClinicalTrials.gov Identifier

NCT01186822
Influence of Early Zoledronic Acid Administration on Bone Marrow Fat in Ovariectomized Rats
Authors: Li Guan-Wu , Xu Zheng , Chang Shi-Xin , Zhou Lei , Wang Xiao-Yan , Nian Hua , Shi Xiao
Published: September 2014

Although the primary target cell of bisphosphonates is the osteoclast, increasing attention is being given to other effector cells influenced by bisphosphonates, such as osteoblasts and marrow adipocytes. Early zoledronic acid (ZA) treatment to ovariectomized (OVX) rats has been found to fully preserve bone microarchitecture over time. However, little is known regarding the influence of ZA on marrow adipogenesis. The purpose of this study was to monitor the ability of early administration of ZA in restoring marrow adiposity in an estrogen-deficient rat model. Thirty female Sprague-Dawley rats were randomly divided into sham-operated (SHAM), OVX + vehicle, and OVX + ZA groups (n=10/group). Dual-energy x-ray absorptiometry and water/fat magnetic resonance imaging were performed at baseline, 6 weeks, and 12 weeks after treatment to assess bone mineral density and marrow fat fraction. Serum biochemical markers, bone remodeling, and marrow adipocyte parameters were analyzed using biochemistry, histomorphometry, and histopathology, respectively. The expression levels of osteoblast, adipocyte, and osteoclast-related genes in bone marrow were assessed using RT-PCR. The OVX rats showed marked bone loss, first detected at 12 weeks, but estrogen deficiency resulted in a remarked increase in marrow fat fraction, first detected at 6 weeks compared with the SHAM rats (all P < .001). Similarly, the OVX rats had a substantially larger percent adipocyte area (+163.0%), mean diameter (+29.5%), and higher density (+57.3%) relative to the SHAM rats. Bone histomorphometry, levels of osteoclast-related gene expression, and a serum resorption marker confirmed that ZA significantly suppressed bone resorption activities. Furthermore, ZA treatment returned adipocyte-related gene expression and marrow adipocyte parameters toward SHAM levels. These data suggest that a single dose of early ZA treatment acts to reverse marrow adipogenesis occurring during estrogen deficiency, which may contribute to its capacity to reduce bone loss.
Untangling Searchable and Experiential Quality Responses to Counterfeits
Authors: Qian Yi , Gong Qiang , Chen Yuxin
Published: September 2014

In this paper, we untangle the searchable and experiential dimensions of quality responses to entry by counterfeiters in emerging markets with weak intellectual property rights. Our theoretical framework analyzes market equilibria under competition from counterfeiting as well as under monopoly branding. A key theoretical prediction is that emerging markets can be self-corrective with respect to counterfeiting issues in the following sense: First, counterfeiters can earn positive profits by pooling with authentic brands only when consumers have good faith in the market (i.e., they believe there is low probability that any product is a counterfeit). When the proportion of counterfeits in the market exceeds a cutoff value, brands invest in self-differentiation from the competitive-fringe counterfeiters. Second, to attain a separating equilibrium with counterfeiters, branded incumbents upgrade the searchable quality (e.g., appearance) of their products more and improve the experiential quality (e.g., functionality) less compared with monopoly equilibrium. However, in the pooling equilibrium with sporadic counterfeits, authentic firms instead may invest in experiential quality to attract more of the expert consumers who are well versed in quality. This prediction uncovers the nature of product differentiation in the searchable dimension and helps with analyzing real-world innovation strategies employed by authentic firms in response to entries by counterfeit entities. In addition, welfare analysis hints at a nonlinear relationship between social welfare and intellectual property enforcement.