bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond the ICF: Italian network strategies for job placement of persons with disabilities
Authors: Corbisiero Fabio
Published: June 2014

The Second National Conference on Disability, held in Bari in 2003, took the World Health Organization's International Classification of Functioning, Disability and Health (ICF), adopted by all WHO member states in 2001, as its frame of reference for future action and policies on disability. The ICF broke decisively with the medical model by seeing disability as an interaction between a biological and psychological condition and environmental and attitudinal barriers. Although existing Italian legislation on access to work for persons with disabilities, particularly Law 68/1999 on ‘collocamento mirato’ (targeted placement), anticipated some of the principles and definitions of the ICF, its implementation in practice was often snared in complex bureaucratic procedures and compromised by narrowly medical assessments of impairment and by considerable variations in standard from region to region. In 2009–2011 a pilot project, Progetto ICF4, was launched in 11 regions of Italy. It applied ICF principles, using Social Network Analysis (SNA) to assess the suitability of a work environment in terms of the networks of relations between the different actors involved in it. The way this has functioned in practice is illustrated by a case study of Teramo, one of the provinces in the pilot.
The American War for Independence as a Revolutionary War
Authors: McDonnell Michael A.
Published: June 2014

The American War for Independence lasted eight years. It was one of the longest and bloodiest wars in America’s history, and yet it was not such a protracted conflict merely because the might of the British armed forces was brought to bear on the hapless colonials. The many divisions among Americans themselves over whether to fight, what to fight for, and who would do the fighting often had tragic and violent consequences. The Revolutionary War was by any measure the first American civil war. Yet national narratives of the Revolution and even much of the scholarship on the era focus more on simple stories of a contest between the Patriots and the British. Loyalists and other opponents of the Patriots are routinely left out of these narratives, or given short shrift. So, too, are the tens of thousands of ordinary colonists—perhaps a majority of the population—who were disaffected or alienated from either side or who tried to tack between the two main antagonists to make the best of a bad situation. Historians now estimate that as many as three-fifths of the colonial population were neither active Loyalists nor Patriots.

When we take the war seriously and begin to think about narratives that capture the experience of the many, rather than the few, an illuminating picture emerges. The remarkably wide scope of the activities of the disaffected during the war—ranging from nonpayment of taxes to draft dodging and even to armed resistance to protect their neutrality—has to be integrated with older stories of militant Patriots and timid Loyalists. Only then can we understand the profound consequences of disaffection—particularly in creating divisions within the states, increasing levels of violence, prolonging the war, and changing the nature of the political settlements in each state. Indeed, the very divisions among diverse Americans that made the War for Independence so long, bitter, and bloody also explains much of the Revolutionary energy of the period. Though it is not as seamless as traditional narratives of the Revolution would suggest, a more complicated story also helps better explain the many problems the new states and eventually the new nation would face. In making this argument, we may finally suggest ways we can overcome what John Shy long ago noted as the tendency of scholars to separate the ‘destructive’ War for Independence from the ‘constructive’ political Revolution.
Race, Gender, and the Making of New Netherland
Authors: Romney Susanah Shaw
Published: June 2014

On the mid-Atlantic coast between 1624 and 1664, the Dutch developed a successful and expansive colony, one that depended on particular interactions among women and men from American, European, and African backgrounds. Unlike some other colonial efforts, such as Jamestown, New Netherland had white women colonists from its inception. In contrast to Plymouth and other English settler colonies, a population of African men and women did the crucial work of establishing the colony’s initial infrastructure in its first years. What is more, a thriving cross-cultural trade between Netherlanders and Munsee, Mahican, and Mohawk residents of the region nurtured the development of the infant colony. Looking at the colony’s establishment and growth reveals that complex interactions among ethnically distinct families gave New Netherland its particular form and character. As European and African populations took root, many households engaged in the frontier trading economy, creating a web of connections reaching into multiple indigenous villages. Women and men cooperated to sustain this trade over long distances by relying on marriage and the economic unit of the household to organize production and exchange. In addition, the colonial government used these households to stake claims to the ground and to define Dutch jurisdiction, just as they recognized that residence by Indian or English households determined where Dutch power ended. Thus ethnic and gender relations shaped not only the colony’s internal hierarchies, but also its economy and its very boundaries.
Liberalism from the Fair Deal to the Great Society
Authors: Bell Jonathan
Published: June 2014

In 1944 President Franklin D. Roosevelt’s State of the Union address set out what he termed an “economic Bill of Rights” that would act as a manifesto of liberal policies after World War Two. Politically, however, the United States was a different place than the country that had faced the ravages of the Great Depression of the 1930s and ushered in Roosevelt’s New Deal to transform the relationship between government and the people. Key legacies of the New Deal, such as Social Security, remained and were gradually expanded, but opponents of governmental regulation of the economy launched a bitter campaign after the war to roll back labor union rights and dismantle the New Deal state.

Liberal heirs to FDR in the 1950s, represented by figures like two-time presidential candidate Adlai Stevenson, struggled to rework liberalism to tackle the realities of a more prosperous age. The long shadow of the U.S. Cold War with the Soviet Union also set up new challenges for liberal politicians trying to juggle domestic and international priorities in an era of superpower rivalry and American global dominance. The election of John F. Kennedy as president in November 1960 seemed to represent a narrow victory for Cold War liberalism, and his election coincided with the intensification of the struggle for racial equality in the United States that would do much to shape liberal politics in the 1960s. After his assassination in 1963, President Lyndon Johnson launched his “Great Society,” a commitment to eradicate poverty and to provide greater economic security for Americans through policies such as Medicare. But his administration’s deepening involvement in the Vietnam War and its mixed record on alleviating poverty did much to taint the positive connotations of “liberalism” that had dominated politics during the New Deal era.
Public Authorities
Authors: Radford Gail
Published: June 2014

Public authorities are agencies created by governments to engage directly in the economy for public purposes. They differ from standard agencies in that they operate outside the administrative framework of democratically accountable government. Since they generate their own operating income by charging users for goods and services and borrow for capital expenses based on projections of future revenues, they can avoid the input from voters and the regulations that control public agencies funded by tax revenues.

Institutions built on the public authority model exist at all levels of government and in every state. A few of these enterprises, such as the Tennessee Valley Authority and the Port Authority of New York and New Jersey, are well known. Thousands more toil in relative obscurity, operating toll roads and bridges, airports, transit systems, cargo ports, entertainment venues, sewer and water systems, and even parking garages. Despite their ubiquity, these agencies are not well understood. Many release little information about their internal operations. It is not even possible to say conclusively how many exist, since experts disagree about how to define them, and states do not systematically track them.

One thing we do know about public authorities is that, over the course of the 20th century, these institutions have become a major component of American governance. Immediately following the Second World War, they played a minor role in public finance. But by the early 21st century, borrowing by authorities constituted well over half of all public borrowing at the sub-federal level. This change means that increasingly the leaders of these entities, rather than elected officials, make key decisions about where and how to build public infrastructure and steer economic development in the United States
The Peace Movement since 1945
Authors: Danielson Leilah
Published: June 2014

Peace activism in the United States between 1945 and the 2010s focused mostly on opposition to U.S. foreign policy, efforts to strengthen and foster international cooperation, and support for nuclear nonproliferation and arms control. The onset of the Cold War between the United States and the Soviet Union marginalized a reviving postwar American peace movement emerging from concerns about atomic and nuclear power and worldwide nationalist politics that everywhere seemed to foster conflict, not peace. Still, peace activism continued to evolve in dynamic ways and to influence domestic politics and international relations.

Most significantly, peace activists pioneered the use of Gandhian nonviolence in the United States and provided critical assistance to the African American civil rights movement, led the postwar antinuclear campaign, played a major role in the movement against the war in Vietnam, helped to move the liberal establishment (briefly) toward a more dovish foreign policy in the early 1970s, and helped to shape the political culture of American radicalism. Despite these achievements, the peace movement never regained the political legitimacy and prestige it held in the years before World War II, and it struggled with internal divisions about ideology, priorities, and tactics.

Peace activist histories in the 20th century tended to emphasize organizational or biographical approaches that sometimes carried hagiographic overtones. More recently, historians have applied the methods of cultural history, examining the role of religion, gender, and race in structuring peace activism. The transnational and global turn in the historical discipline has also begun to make inroads in peace scholarship. These are promising new directions because they situate peace activism within larger historical and cultural developments and relate peace history to broader historiographical debates and trends.
Cinema
Authors: Plate S. Brent
Published: June 2014

This is an advance summary of a forthcoming article in the Oxford Research Encyclopedia of Religion. Please check back later for the full article.

Cinema and religion both participate in processes of world construction, utilizing the raw materials of time, space, and objects. Cinema works with what film theorists call “afilmic reality” to create “profilmic reality”: reordering time, space, and objects through cinematography, editing, sound, mise-en-scene, and other elements of film production. Analogously, religious traditions work with what we might call “areligious reality” to create “proreligious reality”: reordering time, space, and objects through myths, rituals, symbols, doctrines, and other elements of religious life and experience. Other studies have examined “religion in film” or “film as religion,” but the analogous model allows insights into the ways religious tradition operates by learning about cinema and vice versa.

Space is reconstructed through the cinematographic framing of a shot, seeing space through a rectangular lens that provides extreme close-ups or long shots, enlarging or shrinking bodies or setting them in relation to natural and built environments to heightened affect. Religions orient space around varying centers (Mecca, Jerusalem, the confluence of Yamuna and Ganges), creating pilgrimages and prayers to heighten the power of the place. Time is chopped up and reset through cinematic editing, placing various shots in juxtaposition to others, thus speeding up or slowing down the affects of time to enhance the audiovisual impact. In religion, myths and rituals aim to transport participants to past times, compressing history and reactualizing the past, meanwhile creating a chronological continuum or situating participants within a cyclical orientation. And objects, set on a stage or altar, in the hands of actors or adherents, demonstrate connections with the physical environment and with larger communities. In the end, many of the differences between afilmic and profilmic, areligious and proreligious realities dissolve as the sensual experiences of cinema and religion reorient the perceptual apparatus of the human body.
God and Chance: Christian Perspectives
Authors: Bartholomew David J.
Published: June 2014

In many quarters God and chance are still seen as mutually exclusive alternatives. It is common to hear that ascribing anything to “chance” rules out God’s action.

Recent scientific developments have tended to reinforce that distinction. Quantum theory introduced an irreducible uncertainty at the atomic level by requiring that certain microscopic physical events were unpredictable in principle. This was followed by the biologists’ claim that mutations, on which evolution depends, were effectively random and hence that evolutionary development was undirected. The problem this posed to Christian apologists was put most forcibly by Jacques Monod when he asserted “Pure chance,… at the root of the stupendous edifice of evolution alone is the source of every innovation.”

Several attempts have been made to include chance within a theistic account. One, advocated by the intelligent design movement, is to contend that some biological structures are too complex to have originated in the way that evolutionary theory supposes and therefore that they must be attributed to God. Another is to suppose that God acts in an undetectable way at the quantum level without destroying the random appearance of what goes on there.

A third approach is to contend that chance is real and hence is a means by which God works. A key step in this argument is the recognition that chance and order are not mutually exclusive. Reality operates at a number of different levels of aggregation so that what is attributable to chance at one level emerges as near certainty at a higher level.

Further arguments, based on what is known as the anthropic principle, are also used to judge whether or not chance is sufficient to account for existence. These are critically evaluated.
Religion and Book Cultures in America
Authors: Hedstrom Matthew S.
Published: June 2014

This is an advance summary of a forthcoming article in the Oxford Research Encyclopedia of Religion. Please check back later for the full article.

At the center of the long, intertwined history of religion and books in America from the early seventeenth century to the early twenty-first century is the dynamic interplay of Protestantism and print in American culture. The Protestant doctrine of sola scriptura energized the publication of Bibles in vernacular languages. The first large-scale publishing project in North America was John Eliot’s Algonquin Bible of 1663. From these beginnings, though the nineteenth-century Bible and tract societies, to the Christian Booksellers Association of the early twenty-first century, the story of Protestant community life and evangelism in America has been inseparable from the Protestant drive to control and disseminate print.

Protestantism shaped both American religious history and the history of American reading, as the drive for mass literacy in New England and the early public school movement were largely driven by the religious imperative to access the Word. Yet all along, print has also served as a site of religious conflict and a tool of religious innovation. These conflicts can be tracked through the writings of Thomas Paine, Joseph Smith, Elizabeth Cady Stanton, and other religious dissenters and innovators, structured around four large themes: the relationship between scriptural and nonscriptural forms of print; the role of print in bolstering institutional authority on one hand and in undermining authority on the other; the gendered dimensions of reading, literacy, and authorship; and print as commodity and therefore as a site where market dynamics shape religion with particular potency.
Potosí Mines
Authors: Lane Kris
Published: June 2014

This article examines the long history of Potosí, Bolivia, home of the world’s most productive silver mines. The mines, discovered in 1545 and still active today, are discussed in terms of their geology, discovery, productivity, labor history, and technological development. The article also treats the social and environmental consequences of nearly five hundred years of continuous mining and refining.
Does Organic Command a Premium When the Food is Already Local?
Authors: Connolly Cristina , Klaiber H. Allen
Published: June 2014

The emergence of community supported agriculture (CSA) farms has been recognized as a new way for small farms to remain competitive while engaging in their local community through direct marketing. In this study, we report on first revealed preference valuation of CSA attributes using data on share prices and CSA characteristics for the summer 2012 growing season. Using data covering 453 CSA farms in Michigan, New York, Ohio, and Pennsylvania, we develop a hedonic model based on firm‐level prices to reveal consumer valuations of CSA attributes, including various types of organic certification. We also test for competition in the CSA market using a model of firm entry to evaluate whether firms appear perfectly competitive, which is a requirement when using firm‐level prices in our hedonic analysis. Our results reveal a price premium of approximately 7% for USDA organic certification, although this value is heterogeneous across states. We find no premium associated with competing certified naturally grown programs. Finally, we find that CSA farms exhibit little market power and appear to act competitively even with few market entrants.
Network-guided regression for detecting associations between DNA methylation and gene expression
Authors: Wang Zi , Curry Edward , Montana Giovanni
Published: June 2014

Motivation: High-throughput profiling in biological research has resulted in the availability of a wealth of data cataloguing the genetic, epigenetic and transcriptional states of cells. These data could yield discoveries that may lead to breakthroughs in the diagnosis and treatment of human disease, but require statistical methods designed to find the most relevant patterns from millions of potential interactions. Aberrant DNA methylation is often a feature of cancer, and has been proposed as a therapeutic target. However, the relationship between DNA methylation and gene expression remains poorly understood.

Results: We propose Network-sparse Reduced-Rank Regression (NsRRR), a multivariate regression framework capable of using prior biological knowledge expressed as gene interaction networks to guide the search for associations between gene expression and DNA methylation signatures. We use simulations to show the advantage of our proposed model in terms of variable selection accuracy over alternative models that do not use prior network information. We discuss an application of NsRRR to The Cancer Genome Atlas datasets on primary ovarian tumours.

Availability and implementation: R code implementing the NsRRR model is available at http://www2.imperial.ac.uk/∼gmontana

Contact:  giovanni.montana@kcl.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Blue: correcting sequencing errors using consensus and context
Authors: Greenfield Paul , Duesing Konsta , Papanicolaou Alexie , Bauer Denis C.
Published: June 2014

Motivation: Bioinformatics tools, such as assemblers and aligners, are expected to produce more accurate results when given better quality sequence data as their starting point. This expectation has led to the development of stand-alone tools whose sole purpose is to detect and remove sequencing errors. A good error-correcting tool would be a transparent component in a bioinformatics pipeline, simply taking sequence data in any of the standard formats and producing a higher quality version of the same data containing far fewer errors. It should not only be able to correct all of the types of errors found in real sequence data (substitutions, insertions, deletions and uncalled bases), but it has to be both fast enough and scalable enough to be usable on the large datasets being produced by current sequencing technologies, and work on data derived from both haploid and diploid organisms.

Results: This article presents Blue, an error-correction algorithm based on k-mer consensus and context. Blue can correct substitution, deletion and insertion errors, as well as uncalled bases. It accepts both FASTQ and FASTA formats, and corrects quality scores for corrected bases. Blue also maintains the pairing of reads, both within a file and between pairs of files, making it compatible with downstream tools that depend on read pairing. Blue is memory efficient, scalable and faster than other published tools, and usable on large sequencing datasets. On the tests undertaken, Blue also proved to be generally more accurate than other published algorithms, resulting in more accurately aligned reads and the assembly of longer contigs containing fewer errors. One significant feature of Blue is that its k-mer consensus table does not have to be derived from the set of reads being corrected. This decoupling makes it possible to correct one dataset, such as small set of 454 mate-pair reads, with the consensus derived from another dataset, such as Illumina reads derived from the same DNA sample. Such cross-correction can greatly improve the quality of small (and expensive) sets of long reads, leading to even better assemblies and higher quality finished genomes.

Availability and implementation: The code for Blue and its related tools are available from http://www.bioinformatics.csiro.au/Blue . These programs are written in C# and run natively under Windows and under Mono on Linux.

Contact:  paul.greenfield@csiro.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
Outcome of Transplant-fallout Patients With Unresectable Cholangiocarcinoma
Authors: Sio Terence T. , Martenson James A. , Haddock Michael G. , Novotny Paul J. , Gores Gregory J. , Alberts Steven R. , Miller Robert C. , Heimbach Julie K. , Rosen Charles B.
Published: June 2014

Objectives:

The aim of this was to determine survival after starting neoadjuvant therapy for patients who became ineligible for orthotopic liver transplantation (OLT).

Methods and Materials:

Since January 1993, 215 patients with unresectable cholangiocarcinoma began treatment with planned OLT. Treatment included external-beam radiation therapy (EBRT) with fluorouracil, bile duct brachytherapy, and postradiotherapy fluorouracil or capecitabine before OLT. Adverse findings at the staging operation, death, and other factors precluded OLT in 63 patients (29%), of whom 61 completed neoadjuvant chemoradiation.

Results:

By October 2012, 56 (89%) of the 63 patients unable to undergo OLT had died. Twenty-two patients (35%) became ineligible for OLT before the staging operation, 38 (60%) at the staging operation, and 3 (5%) after staging. From the date of diagnosis, median overall survival was 12.3 months. Survival was 17% at 18 months and 7% at 24 months. Median survival after fallout was 6.8 months. Median survival after the staging operation was 6 months. Two patients lived for 3.7 and 8.7 years before dying of cancer or liver failure caused by persistent biliary stricture at the site of the original cancer, respectively. Univariate analysis showed that time from diagnosis to fallout correlated with overall survival (P=0.04).

Conclusions:

In highly selected patients initially suitable for OLT, the mortality rate for cholangiocarcinoma was high in patients who became ineligible for OLT. Their survival, however, was comparable to expected survival for patients with locally advanced or metastatic disease treated with nontransplant therapies. The most common reason for patient fallout was adverse findings at the staging operation.
Meiotic long non-coding meiRNA accumulates as a dot at its genetic locus facilitated by Mmi1 and plays as a decoy to lure Mmi1
Authors: Shichino Yuichi , Yamashita Akira , Yamamoto Masayuki
Published: June 2014

Long non-coding RNAs (lncRNAs) play key roles in the formation of nuclear bodies. In the fission yeast
Schizosaccharomyces pombe
, a lncRNA species termed meiRNA forms a nuclear dot structure at its own genetic locus, the
sme2
locus, with its protein-binding partner Mei2. This dot structure, called Mei2 dot, promotes the progression of meiosis by suppressing Mmi1, a crucial factor involved in the selective elimination of meiosis-specific transcripts. The meiRNA itself is a target of Mmi1-mediated elimination and is supposed to function as a decoy to lure Mmi1. However, detailed mechanisms underlying the formation of Mei2 dot and inactivation of Mmi1 remain ambiguous. Here, we show that the localization of meiRNA, at its genetic locus
sme2
, depends on its association with Mmi1. We also demonstrate that one of the multiple Mmi1 foci in mitotic cells localizes to the
sme2
locus. Furthermore, the overexpression of meiRNA promotes the accumulation of Mmi1 to the
sme2
locus even in the absence of Mei2 and reduces the activity of Mmi1. These findings indicate that the retention of meiRNA at its genetic locus is facilitated by Mmi1, which then attracts scattered Mmi1 to inhibit its function.
Effect of erythropoietin on primed leucocyte expression profile
Authors: Pesce Mirko , Felaco Paolo , Franceschelli Sara , Speranza Lorenza , Grilli Alfredo , Anna De Lutiis Maria , Ferrone Alessio , Sirolli Vittorio , Bonomini Mario , Felaco Mario , Patruno Antonia
Published: June 2014

Resistance to erythropoietin (EPO) affects a significant number of anaemic patients with end-stage renal disease. Previous reports suggest that inflammation is one of the major independent predictors of EPO resistance, and the effects of EPO treatment on inflammatory mediators are not well established. The aim of this study was to investigate EPO-induced modification to gene expression in primary cultured leucocytes. Microarray experiments were performed on primedex vivoperipheral blood mononuclear cells (PBMCs) and treated with human EPO-α. Data suggested that EPO-α modulated genes involved in cell movement and interaction in primed PBMCs. Of note, EPO-α exerts anti-inflammatory effects inhibiting the expression of pro-inflammatory cytokine IL-8 and its receptor CXCR2; by contrast, EPO-α increases expression of genes relating to promotion of inflammation encoding for IL-1β and CCL8, and inducesde novosynthesis of IL-1α, CXCL1 and CXCL5 in primed cells. The reduction in MAPK p38-α activity is involved in modulating both IL-1β and IL-8 expression. Unlike the induction of MAPK, Erk1/2 activity leads to upregulation of IL-1β, but does not affect IL-8 expression and release. Furthermore, EPO-α treatment of primed cells induces the activation of caspase-1 upstream higher secretion of IL-1β, and this process is not dependent on caspase-8 activation. In conclusion, our findings highlight new potential molecules involved in EPO resistance and confirm the anti-inflammatory role for EPO, but also suggest a plausiblein vivoscenario in which the positive correlation found between EPO resistance and elevated levels of some pro-inflammatory mediators is due to treatment with EPO itself.
Evidence for immune activation in patients with residual hepatitis C virus RNA long after successful treatment with IFN and ribavirin
Authors: Radkowski Marek , Opoka-Kegler Jolanta , Cortes Kamila Caraballo , Bukowska-Ośko Iwona , Perlejewski Karol , Pawełczyk Agnieszka , Laskus Tomasz
Published: June 2014

Low-level hepatitis C virus (HCV) RNA may persist in PBMCs after successful treatment of chronic hepatitis C, but the consequences of this phenomenon are unclear. Forty-nine patients who achieved a sustained virological response (SVR) after pegylated IFN and ribavirin therapy were analysed 52–66 months after the SVR. HCV RNA was detected in PBMCs from 18 patients (47.4 %), and PBMCs in two patients stained positive for non-structural protein 3 (NS3). Quantification of various cytokine and chemokine transcripts in PBMCs revealed that levels of IL-6, IL-8, IL-12, TNF-α and macrophage inflammatory protein 1β were significantly higher in HCV-positive patients than in HCV-negative individuals. In conclusion, persistence of HCV RNA in PBMCs of patients with a SVR appears to be associated with immune activation.
Genome-wide Identification of Zero Nucleotide Recursive Splicing inDrosophila
Authors: Duff Michael , Olson Sara , Wei Xintao , Osman Ahmad , Plocik Alex , Bolisetty Mohan , Celniker Susan , Graveley Brenton R.
Published: June 2014

Recursive splicing is a process in which large introns are removed in multiple steps by resplicing at ratchet points - 5’ splice sites recreated after splicing1. Recursive splicing was first identified in theDrosophila Ultrabithorax(Ubx) gene1and only three additionalDrosophilagenes have since been experimentally shown to undergo recursive splicing2,3. Here, we identify 196 zero nucleotide exon ratchet points in 130 introns of 115Drosophilagenes from total RNA sequencing data generated from developmental time points, dissected tissues, and cultured cells. Recursive splicing events were identified by splice junctions that map to annotated 5’ splice sites and unannotated intronic 3’ splice sites, the presence of the sequence AG/GT at the 3’ splice site, and a 5’ to 3’ gradient of decreasing RNA-Seq read density indicative of co-transcriptional splicing. The sequential nature of recursive splicing was confirmed by identification of lariat introns generated by splicing to and from the ratchet points. We also show that recursive splicing is a constitutive process, and that the sequence and function of ratchet points are evolutionarily conserved. Together these results indicate that recursive splicing is commonly used inDrosophilaand provides insight into the mechanisms by which some introns are removed.
The rugged adaptive landscape of an emerging plant RNA virus
Authors: Lalić Jasna , Elena Santiago F.
Published: June 2014

RNA viruses are the main source of emerging infectious diseases owed to the evolutionary potential bestowed by their fast replication, large population sizes and high mutation and recombination rates. However, an equally important parameter, which is usually neglected, is the topography of the fitness landscape, that is, how many fitness maxima exist and how well connected they are, which determines the number of accessible evolutionary pathways. To address this question, we have reconstructed the fitness landscape describing the adaptation ofTobacco etch potyvirusto its new host,Arabidopsis thaliana. Fitness was measured for most of the genotypes in the landscape, showing the existence of peaks and holes. We found prevailing epistatic effects between mutations, with cases of reciprocal sign epistasis being common at latter stages. Therefore, results suggest that the landscape was rugged and holey, with several local fitness peaks and a very limited number of potential neutral paths. The viral genotype fixed at the end of the evolutionary process was not on the global fitness optima but stuck into a suboptimal peak.
Polycomb-Group Proteins andFLOWERING LOCUS TMaintain Commitment to Flowering inArabidopsis thaliana
Authors: Müller-Xing Ralf , Clarenz Oliver , Pokorny Lena , Goodrich Justin , Schubert Daniel
Published: June 2014

The switch from vegetative to reproductive growth is extremely stable even if plants are only transiently exposed to environmental stimuli that trigger flowering. In the photoperiodic pathway, a mobile signal, florigen, encoded by FLOWERING LOCUS T (FT) in Arabidopsis thaliana, induces flowering. Because FT activity in leaves is not maintained after transient photoperiodic induction, the molecular basis for stable floral commitment is unclear. Here, we show that Polycomb-group (Pc-G) proteins, which mediate epigenetic gene regulation, maintain the identity of inflorescence and floral meristems after floral induction. Thus, plants with reduced Pc-G activity show a remarkable increase of cauline leaves under noninductive conditions and floral reversion when shifted from inductive to noninductive conditions. These phenotypes are almost completely suppressed by loss of FLOWERING LOCUS C (FLC) and SHORT VEGETATIVE PHASE, which both delay flowering and promote vegetative shoot identity. Upregulation of FLC in Pc-G mutants leads to a strong decrease of FT expression in inflorescences. We find that this activity of FT is needed to prevent floral reversion. Collectively, our results reveal that floral meristem identity is at least partially maintained by a daylength-independent role of FT whose expression is indirectly sustained by Pc-G activity.
Spatial and temporal distribution of γH2AX fluorescence in human cell cultures following synchrotron-generated X-ray microbeams: lack of correlation between persistent γH2AX foci and apoptosis
Authors: Anderson Danielle L. , Mirzayans Razmik , Andrais Bonnie , Siegbahn E. Albert , Fallone B. Gino , Warkentin Brad
Published: June 2014

Formation of γH2AX foci (a marker of DNA double-strand breaks), rates of foci clearance and apoptosis were investigated in cultured normal human fibroblasts and p53 wild-type malignant glioma cells after exposure to high-dose synchrotron-generated microbeams. Doses up to 283 Gy were delivered using beam geometries that included a microbeam array (50 µm wide, 400 µm spacing), single microbeams (60–570 µm wide) and a broad beam (32 mm wide). The two cell types exhibited similar trends with respect to the initial formation and time-dependent clearance of γH2AX foci after irradiation. High levels of γH2AX foci persisted as late as 72 h post-irradiation in the majority of cells within cultures of both cell types. Levels of persistent foci after irradiationviathe 570 µm microbeam or broad beam were higher when compared with those observed after exposure to the 60 µm microbeam or microbeam array. Despite persistence of γH2AX foci, these irradiation conditions triggered apoptosis in only a small proportion (<5%) of cells within cultures of both cell types. These results contribute to the understanding of the fundamental biological consequences of high-dose microbeam irradiations, and implicate the importance of non-apoptotic responses such as p53-mediated growth arrest (premature senescence).
A comparative study of two polymorphs ofL-aspartic acid hydrochloride
Authors: Benali-Cherif Rim , Takouachet Radhwane , Bendeif El-Eulmi , Benali-Cherif Nourredine
Published: June 2014

Two polymorphs of L-aspartic acid hydrochloride, C4H8NO4+·Cl−, were obtained from the same aqueous solution. Their crystal structures have been determined from single-crystal data collected at 100 K. The crystal structures revealed three- and two-dimensional hydrogen-bonding networks for the triclinic and orthorhombic polymorphs, respectively. The cations and anions are connected to one anotherviaN—H...Cl and O—H...Cl interactions and form alternating cation–anion layer-like structures. The two polymorphs share common structural features; however, the conformations of the L-aspartate cations and the crystal packings are different. Furthermore, the molecular packing of the orthorhombic polymorph contains more interesting interactions which seems to be a favourable factor for more efficient charge transfer within the crystal.
Poly[(μ5-3-carboxybenzene-1,2-dicarboxylato)lead(II)]: a helical lead(II) coordination polymer
Authors: Cheng Shao-Min , Wang Xian-Fei , Yang Fang , Chen Hang , Liu Wen-Long
Published: June 2014

In the title polymer, [Pb(C9H4O6)]n, the asymmetric unit contains a monomer of a PbIIcation with a doubly deprotonated 3-carboxybenzene-1,2-dicarboxylate dianion (1,2,3-Hbtc2−). Each PbIIcentre is seven-coordinated by seven O atoms of bridging carboxy/carboxylate groups from five 1,2,3-Hbtc2−ligands, forming a distorted pentagonal bipyramid. The PbIIcations are bridged by 1,2,3-Hbtc2−anions, yielding two-dimensional chiral layers. The layers are stacked above each other to generate a three-dimensional supramolecular architectureviaa combination of C—H...O interactions. The thermogravimetric and optical properties are also reported.
A multiple-common-lines method to determine the orientation of snapshot diffraction patterns from single particles
Authors: Zhou Liang , Zhang Tian-Yi , Liu Zhong-Chuan , Liu Peng , Dong Yu-Hui
Published: June 2014

With the development of X-ray free-electron lasers (XFELs), it is possible to determine the three-dimensional structures of noncrystalline objects with coherent X-ray diffraction imaging. In this diffract-and-destroy mode, many snapshot diffraction patterns are obtained from the identical objects which are presented one by one in random orientations to the XFEL beam. Determination of the orientation of an individual object is essential for reconstruction of a three-dimensional structure. Here a new method, called the multiple-common-lines method, has been proposed to determine the orientations of high- and low-signal snapshot diffraction patterns. The mean errors of recovered orientations (α, β, γ) of high- and low-signal patterns are about 0.14, 0.06, 0.12 and 0.77, 0.31, 0.60°, respectively; both sets of errors can meet the requirements of the reconstruction of a three-dimensional structure.
Speech and language therapists’ approaches to communication intervention with children and adults with profound and multiple learning disability
Authors: Goldbart Juliet , Chadwick Darren , Buell Susan
Published: June 2014

Background

People with profound intellectual and multiple disabilities (PMLD) have communication impairments as one defining characteristic.

Aims

To explore speech and language therapists' (SLTs) decision making in communication interventions for people with PMLD, in terms of the intervention approaches used, the factors informing the decisions to use specific interventions and the extent to which the rationales underpinning these decisions related to the components of evidence based practice (EBP), namely empirical evidence, clinical experience and client/carer views and values.

Methods & Procedures

A questionnaire on communication assessment and intervention for people with PMLD was sent to SLTs in the UK to elicit information on: the communication intervention approaches they used; their rationales for their intervention choices; their use of published evidence to inform decision making.

Outcomes & Results

Intensive interaction and objects of reference were the communication interventions most often used with people with PMLD, with some differences between children and adults evident. Rationales provided conformed somewhat to the EBP framework though extension of the existing framework and addition of practical and organizational considerations led to a revised typology of rationale for decision making. Rationales most frequently related to the empowerment, development and behavioural preferences of the person with PMLD.

Conclusions & Implications

Empirical research evidence was seldom mentioned by SLTs as informing intervention decision making leading to very diverse practice. There is a need for further research on the effectiveness of commonly used but under‐evaluated interventions. There is also a need to alert SLTs to the evidence base supporting other approaches, particularly switch‐based, cause and effect approaches.
Are we (mis)guided by current guidelines on intrapartum fetal heart rate monitoring? Case for a more physiological approach to interpretation
Authors: Ugwumadu A
Published: June 2014

Original interpretations of fetal heart rate (FHR) patterns equated FHR decelerations with ‘fetal distress’, requiring expeditious delivery. This simplistic interpretation is still implied in our clinical guidelines despite 40 years of increasing understanding of the behaviour and regulation of the fetal cardiovascular system during labour. The physiological basis of FHR responses and adaptations to oxygen deprivation is de‐emphasised, whilst generations of obstetricians and midwives are trained to focus on, and classify, the morphological appearances of decelerations into descriptive categories, with no attempt to understand how the fetus defends itself and compensates for intrapartum hypoxic ischaemic insults, or the patterns that suggest progressive loss of compensation. Consequently, there is a lack of confidence, marked variation in FHR interpretation, defensive practices, unnecessary operative interventions, and a failure to recognise abnormal FHR patterns, resulting in adverse outcomes and expensive litigation.
Small‐colony variants and phenotype switching of intracellular Staphylococcus aureus in chronic rhinosinusitis
Authors: Tan N. C.‐W. , Cooksley C. M. , Roscioli E. , Drilling A. J. , Douglas R. , Wormald P.‐J. , Vreugde S.
Published: June 2014

Background

Chronic rhinosinusitis (CRS) has been linked to the gram‐positive bacteria Staphylococcus aureus (S. aureus) in its biofilm or intracellular forms. Recent evidence suggests that S. aureus also exists in a small‐colony variant (SCV) form as a mechanism of altering its virulence capabilities. The aim of this study was to investigate the presence of SCVs in sinonasal mucosa of CRS patients and whether the phenomenon of phenotype switching can be applied to intracellular epithelial infections.

Methods

Sinonasal specimens were examined for the presence of intramucosal S. aureus and characterized to the strain level. An airway epithelial cell culture infection model was utilized to investigate whether bacteria were capable of alterations in virulence phenotype.

Results

Intramucosal organisms harvested from sinonasal biopsies demonstrate phenotypic growth patterns and lack of coagulase activity consistent with SCVs. Intracellular infection of airway epithelial cell cultures with S. aureus led to decreased secretion of enterotoxins and phenotypic growth alterations consistent with SCVs.

Conclusions

Regulation of S. aureus virulence factors is a dynamic process, and exposure to the intracellular environment appears to provide the necessary conditions to enable these alterations in an attempt for the bacterium to survive and persist within host tissues. Further work is required to ascertain whether SCVs in CRS hold a clinically relevant pathogenic role in recalcitrant disease.
Meta‐analysis of handsewn versus stapled reversal of loop ileostomy
Authors: Markides Georgios A. , Wijetunga Imeshi U. , Brown Steve R. , Anwar Suhail
Published: June 2014

Background

The morbidity associated with closure of loop ileostomy (LI) may be attributed to the various surgical techniques employed for the closure. The purpose of this review was to review the hand‐sutured (HS) versus the stapled anastomosis (SA) techniques, used in the reversal of LI.

Methods

The MEDLINE, PubMed, CINHAL, Cochrane library and Web of Knowledge databases were searched for randomized controlled trials (RCTs) and case‐control trials (CCTs), evaluating HS and SA in reversal of LI. Data extraction with risk of bias assessment was followed by subgroup and pooled data meta‐analysis where applicable per outcome.

Results

Four RCTs (HS: 321, SA: 328) and 10 CCTs (HS: 2808, SA: 1044) were identified, with a total of 4508 patients. Regardless of subgroup analysis, no difference was seen between the two techniques with regard to anastomotic leaks (P = 0.24, odds ratio (OR): 1.37, 95% confidence interval (CI): 0.81–2.29) or re‐operation. The stapled group showed a significantly lower rate of conservatively managed small bowel obstruction (SBO)/ ileus at 30 days (P < 0.001, OR: 2.27, 95% CI: 1.59–2.96) (P < 0.001) and SBO during combined short‐ and long‐term follow‐up (P < 0.001). The SA also showed significant shorter operative time (P = 0.02; WMD 11.52 min), time to first bowel opening (P < 0.001; WMD 0.52 days) and length of hospital stay (P = 0.03; WMD 0.70 days).

Conclusion

The stapled technique offers an advantage in terms of lower post‐operative subacute SBO rates, a faster operative technique and shorter hospitalization times. These perceived benefits make it potentially superior to HS for the reversal of LI.
The clinical characteristics and new classification of sticky eyelid syndrome in East Asian patients
Authors: Chang Minwook , Lee Hwa , Park Min Soo , Baek Sehyun
Published: June 2014

Purpose

The aim of this study was to demonstrate the characteristics of sticky eyelid syndrome (SES) and to suggest a modified definition and new classification of the disease in relation to the severity of the syndrome in East Asian patients.

Methods

Forty‐four eyes of 31 patients with sticky eyelid syndrome were included in this study. The medical records of patients who were diagnosed with sticky eyelid syndrome were retrospectively reviewed. Sticky eyelid syndrome was defined as an abnormal adhesion between the upper and lower eyelids during blinking. We divided the subjects into four grades according to the severity of the disease.

Results

Among 31 patients, there were 10 men and 21 women. The mean age of patients was 62.5 years. A total of 13 patients had SES bilaterally. All patients had meibomian gland dysfunction (MGD). Thirty‐three eyes had dermatochalasis, and 30 eyes had involutional ptosis. Horizontal lower lid laxity was observed in 23 eyes, and reverse ptosis found in 15 eyes. Patients were classified into four groups as follows: G1: 11 (25%), G2: 24 (54.5%), G3: 6 (13.6%) and G4: 3 eyes (6.8%). Patients in Grade 1 tended to improve only with medical treatment for MGD. However, surgical management was necessary for patients in Grades 3 and 4.

Conclusions

Meibomian gland dysfunction is a fundamental risk factor for developing sticky eyelid syndrome. Further, combined upper lid ptosis or lower lid laxity may be aggravating factors. According to the grading, medical or surgical management can be chosen.