bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of Breast Cancer in Europe and Africa
Authors: Abdulrahman Ganiy Opeyemi , Rahman Ganiyu Adebisi
Published: May 2012

Breast cancer continues to remain the most lethal malignancy in women across the world. This study reviews some of the epidemiological similarities and differences in breast cancer between white European women and black African women with the aim of optimising care for women with breast malignancy across the world. The incidence of breast cancer is lower among African women than their European counterparts. Majority of women in Europe are postmenopausal when they present with breast cancer; however, the peak incidence among African women is in the premenopausal period. Ductal carcinoma is the commonest type of breast cancer among women in Africa and Europe. However, medullary and mucinous carcinomas are more common in Africa than in Europe. While European women usually present at an early stage especially with the advent of screening, African women generally present late for treatment resulting in lower survival rates. There should be more research at the molecular level among African women to identify genetic factors that may contribute to the risk of developing breast cancer. There should also be improvement in the health care system in Africa in order to optimise care for women with breast cancer.
Towards a Molecular Understanding of the Fanconi Anemia Core Complex
Authors: Hodson Charlotte , Walden Helen
Published: May 2012

Fanconi Anemia (FA) is a genetic disorder characterized by the inability of patient cells to repair DNA damage caused by interstrand crosslinking agents. There are currently 14 verified FA genes, where mutation of any single gene prevents repair of DNA interstrand crosslinks (ICLs). The accumulation of ICL damage results in genome instability and patients having a high predisposition to cancers. The key event of the FA pathway is dependent on an eight-protein core complex (CC), required for the monoubiquitination of each member of the FANCD2-FANCI complex. Interestingly, the majority of patient mutations reside in the CC. The molecular mechanisms underlying the requirement for such a large complex to carry out a monoubiquitination event remain a mystery. This paper documents the extensive efforts of researchers so far to understand the molecular roles of the CC proteins with regard to its main function in the FA pathway, the monoubiquitination of FANCD2 and FANCI.
Polycyclic Aromatic Hydrocarbons in Electrocautery Smoke during Peritonectomy Procedures
Authors: Näslund Andréasson Sara , Mahteme Haile , Sahlberg Bo , Anundi Helena
Published: May 2012

Objective. This study identified and quantified polycyclic aromatic hydrocarbons (PAHs) in electrocautery smoke during 40 peritonectomy procedures and investigated any correlations and/or differences between levels of PAHs and perioperative variables.Methods. PAHs were measured in personal and stationary sampling by 40 mm Millipore cassettes, for adsorption of both gaseous and particle-bound PAHs.Results. All 16 USEPA priority pollutant PAHs were detected during peritonectomy procedures, naphthalene being the most abundant. For the only two PAHs with Swedish occupational exposure limits (OELs), benzo[a]pyrene and naphthalene, limits were never exceeded. Amount of bleeding was the only perioperative variable that correlated with levels of PAHs.Conclusions. Low levels of PAHs were detected in electrocautery smoke during peritonectomy procedures, and an increased amount of bleeding correlated with higher levels of PAHs. For evaluation of long-term health effects, more studies are needed.
The Intuitionistic Fuzzy Normed Space of Coefficients
Authors: Bilalov B. T. , Farahani S. M. , Guliyeva F. A.
Published: May 2012

Intuitionistic fuzzy normed space is defined using concepts of t‐norm and t‐conorm. The concepts of fuzzy completeness, fuzzy minimality, fuzzy biorthogonality, fuzzy basicity, and fuzzy space of coefficients are introduced. Strong completeness of fuzzy space of coefficients with regard to fuzzy norm and strong basicity of canonical system in this space are proved. Strong basicity criterion in fuzzy Banach space is presented in terms of coefficient operator.
Solar Photocatalytic Removal of Chemical and Bacterial Pollutants from Water Using Pt/TiO2-Coated Ceramic Tiles
Authors: Devipriya S. P. , Yesodharan Suguna , Yesodharan E. P.
Published: May 2012

Semiconductor photocatalysis has become an increasingly promising technology in environmental wastewater treatment. The present work reports a simple technique for the preparation of platinum-deposited TiO2catalysts and its immobilization on ordinary ceramic tiles. The Pt/TiO2is characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDAX), and diffuse reflectance spectroscopy (DRS). Deposition of Pt on TiO2extends the optical absorption of the latter to the visible region which makes it attractive for solar energy application. Optimum loading of Pt on TiO2was found to be 0.5%. The Pt/TiO2is coated on ceramic tiles and immobilized. This catalyst was found effective for the solar photocatalytic removal of chemical and bacterial pollutants from water. Once the parameters are optimized, the Pt/TiO2/tile can find application in swimming pools, hospitals, water theme parks, and even industries for the decontamination of water.
Selected Extracts of Chinese Herbal Medicines: Their Effect on NF-κB, PPARαand PPARγand the Respective Bioactive Compounds
Authors: Rozema E. , Atanasov A. G. , Fakhrudin N. , Singhuber J. , Namduang U. , Heiss E. H. , Reznicek G. , Huck C. W. , Bonn G. K. , Dirsch V. M. , Kopp B.
Published: May 2012

Chinese herbal medicinal (CHM) extracts from fourteen plants were investigated in cell-basedin vitroassays for their effect on nuclear factorκB (NF-κB), a key regulator of inflammation, as well as on peroxisome proliferator-activated receptors (PPARs) being key regulators of genes involved in lipid and glucose metabolism. 43% of the investigated CHMs showed NF-κB inhibitory and 50% PPARαand PPARγactivating effects. Apolar extracts from cortex and flos ofAlbizia julibrissinDurazz. and processed rhizomes ofArisaemasp. andPinellia ternata(Thunb.) Breit. that effectively inhibited TNF-α-induced NF-κB activation and dose-dependently activated PPARαand PPARγwere further investigated. Bioassay-guided fractionation and analysis by GC-MS led to the identification of fatty acids as PPAR agonists, including linoleic and palmitic acid.
Effect of Deoxycholic Acid on the Performance of Liquid Electrolyte Dye-Sensitized Solar Cells Using a Perylene Monoimide Derivative
Authors: Sharma Ganesh D. , Kurchania Rajnish , Ball Richard J. , Roy Mahesh S. , Mikroyannidis John A.
Published: May 2012

The effect of coadsorption with deoxycholic acid (DCA) on the performance of dye-sensitized solar cell based on perylene monoimide derivative (PCA) as sensitizer and liquid electrolyte had been investigated. The current-voltage characteristics under illumination and incident photon to current efficiency (IPCE) spectra of the DSSCs showed that the coadsorption of DCA with the PCA dye results in a significant improvement in short circuit photocurrent and slight increase in the open circuit photovoltage, which lead to an overall power conversion efficiency. The enhancement of short circuit current was attributed to the increased electron injection efficiency from the excited state of PCA into the conduction band of TiO2and charge collection efficiency. The current-voltage characteristics in dark indicates a positive shift in the conduction which also supports the enhancement in the photocurrent. The coadsorption with DCA suppressed charge recombination as indicated from the electrochemical impedance spectra and thus improved the open circuit photovoltage.
Ectopic Fat and Insulin Resistance: Pathophysiology and Effect of Diet and Lifestyle Interventions
Authors: Snel M. , Jonker J. T. , Schoones J. , Lamb H. , de Roos A. , Pijl H. , Smit J. W. A. , Meinders A. E. , Jazet I. M.
Published: May 2012

The storage of triglyceride (TG) droplets in nonadipose tissues is called ectopic fat storage. Ectopic fat is associated with insulin resistance and type 2 diabetes mellitus (T2DM). Not the triglycerides per se but the accumulation of intermediates of lipid metabolism in organs, such as the liver, skeletal muscle, and heart seem to disrupt metabolic processes and impair organ function. We describe the mechanisms of ectopic fat depositions in the liver, skeletal muscle, and in and around the heart and the consequences for each organs function. In addition, we systematically reviewed the literature for the effects of diet-induced weight loss and exercise on ectopic fat depositions.
The Neural Basis of Vivid Memory Is Patterned on Perception
Authors: Buchsbaum Bradley R. , Lemire-Rodger Sabrina , Fang Candice , Abdi Hervé
Published: May 2012

When we have a rich and vivid memory for a past experience, it often feels like we are transported back in time to witness once again this event. Indeed, a perfect memory would exactly mimic the experiential quality of direct sensory perception. We used fMRI and multivoxel pattern analysis to map and quantify the similarity between patterns of activation evoked by direct perception of a diverse set of short video clips and the vivid remembering, with closed eyes, of these clips. We found that the patterns of distributed brain activation during vivid memory mimicked the patterns evoked during sensory perception. Using whole-brain patterns of activation evoked by perception of the videos, we were able to accurately classify brain patterns that were elicited when participants tried to vividly recall those same videos. A discriminant analysis of the activation patterns associated with each video revealed a high degree (explaining over 80% of the variance) of shared representational similarity between perception and memory. These results show that complex, multifeatured memory involves a partial reinstatement of the whole pattern of brain activity that is evoked during initial perception of the stimulus.
FM-selective Networks in Human Auditory Cortex Revealed Using fMRI and Multivariate Pattern Classification
Authors: Hsieh I-Hui , Fillmore Paul , Rong Feng , Hickok Gregory , Saberi Kourosh
Published: May 2012

Frequency modulation (FM) is an acoustic feature of nearly all complex sounds. Directional FM sweeps are especially pervasive in speech, music, animal vocalizations, and other natural sounds. Although the existence of FM-selective cells in the auditory cortex of animals has been documented, evidence in humans remains equivocal. Here we used multivariate pattern analysis to identify cortical selectivity for direction of a multitone FM sweep. This method distinguishes one pattern of neural activity from another within the same ROI, even when overall level of activity is similar, allowing for direct identification of FM-specialized networks. Standard contrast analysis showed that despite robust activity in auditory cortex, no clusters of activity were associated with up versus down sweeps. Multivariate pattern analysis classification, however, identified two brain regions as selective for FM direction, the right primary auditory cortex on the supratemporal plane and the left anterior region of the superior temporal gyrus. These findings are the first to directly demonstrate existence of FM direction selectivity in the human auditory cortex.
Pride and prejudice, or class and character: Room at the Top revisited
Authors: Cardullo Robert J.
Published: May 2012

Room at the Top was unique among British social-realist films, not only in its depiction of upward mobility as opposed to social immobilization, but also in its choice of genre – high tragedy over popular melodrama. Paradoxically, Joe Lampton’s working-class pride drove him to educate himself out of the working class, then compelled him to try to get a piece of the upper class. Tragically, the pride that enabled him to endure years of poverty and social humiliation is the same pride that undoes him spiritually in the end. In a sense, the class of his origin finally has its revenge on him for leaving it, while he proves that class is no barrier to someone with strength, ability and determination. But Joe pays a great price in order to prove his point – he ‘wastes’ the outsider Alice Aisgill for marriage to the moneyed Susan Brown. Alice may be the ‘tragic waste’ of this story, but one could argue that in killing herself she has also ‘killed’ Joe and thus had her revenge on him too. In short, far from cheapening its action by resolving it through melodrama, Room at the Top enriches that action throughout by consistently suggesting its tragic underpinnings. There are no black-and-white characters in the film, no heroes or villains, no defeat of the guilty and reward of the innocent: each of the central characters wins, and each one loses.
Salvation, theology and organizational practices across the centuries
Authors: Dyck Bruno , Wiebe Elden
Published: May 2012

Humankind has a long history of seeking to be saved from suffering, although the understanding of just how to achieve this salvation has changed over time. Regardless of how it has been understood, throughout history the dominant understanding of salvation has been associated with how social structures and systems are organized. This article provides an historical review of the relationship between salvation and organizational practices, paying particular attention to various views of salvation within the Western Christian tradition over the past two millennia. Using a three dimensional analytical framework—the modality of salvation, the instantiation of salvation and the locus of ethical activity—we describe key changes in the meaning of salvation over time, and describe hallmark organizational practices associated with each meaning. We conclude by discussing implications of our analysis for examining relationships between organizational practices and salvation in other religious traditions, for developing a more nuanced understanding of emancipation, for developing counter-cultural approaches to management and for strengthening a ‘theological turn’ in organization and management theory.
‘Who are “we”?’, asks one of us
Authors: Cockburn Cynthia
Published: May 2012

The article seeks to strengthen the proposition of John Holloway’s Crack Capitalism, that we are capable of creatively breaking and transforming the system in which we live, by considering in greater depth the nature of the ‘we’ that are his actor for change. I suggest that Holloway’s representation of ‘difference’, such as that between women and men, or people of conflictual ethnicities, as a matter of theatrical ‘masks’ that may be discarded at will seriously understates the significance of division and mutual oppression among the ‘we’. I argue that gender, ethnic, racialized and other oppressions cannot be reduced to effects of capitalism. Rather, they manifest distinct, though intersected, dimensions of power, positioning us in objectively antagonistic relations. If a coherent ‘we’ is to be forged, capable of undoing capitalism and redesigning the mode of production, it can only be through simultaneous active struggle, for example by women and by oppressed ethnic groups, concerning institutional power and control of material resources (including bodies). Such struggles cannot be reduced to and dismissed as diversionary ‘identity politics’.
Refusing the terms of non-existence, breaking their constraints: John Holloway, cracking capitalism and the meaning of revolution today
Authors: Garland Christian
Published: May 2012

This essay seeks to contribute to theorizing the (anti) politics of refusal of the material and abstract limitations imposed by the non-existence of life under capitalism, with special reference to the work of John Holloway, and his recent concept of ‘the crack’, the radical confluence of resistant subjectivity and a radically different mode-of-doing. The essay seeks to conceptualize a negative ontology, the standpoint of critique and resistant subjectivity, negativity toward the given, the existent and ‘that which is’. The essay attempts to show that in this active ‘doing’ – what Marx identified as ‘species-being’ ( Gattungswesen) or creative human essence – human beings choose to do other than what is demanded by money and power, which is itself the re-appropriation of doing. The essay seeks to be one such contribution in that direction.
Predictive value of early molecular response in patients with chronic myeloid leukemia treated with first-line dasatinib
Authors: Marin David , Hedgley Corinne , Clark Richard E. , Apperley Jane , Foroni Letizia , Milojkovic Dragana , Pocock Christopher , Goldman John M. , O'Brien Stephen
Published: May 2012

Dasatinib is effective therapy for newly diagnosed patients with chronic myeloid leukemia, but not all patients respond well. We analyzed the outcome of patients treated with dasatinib as first-line therapy to identify patients who are more likely to fare poorly. The 8.6% of patients who at 3 months had a BCR-ABL1/ABL1 ratio > 10% had a significantly worse 2-year cumulative incidence of complete cytogenetic response (58.8% vs 96.6%, P < .001) and molecular responses than the remaining patients with a lower transcript levels. The predictive value of the 3-month transcript level could be improved using the dasatinib-specific transcript level cut-offs, namely, 2.2%, 0.92%, and 0.57% for complete cytogenetic response, 3 log and 4.5 log reductions in the transcript level, respectively. The study was registered at www.clinicaltrials.gov as #NCT01460693.
Modeling gene regulatory network motifs using statecharts
Authors: Fioravanti Fabio , Helmer-Citterich Manuela , Nardelli Enrico
Published: May 2012

Background

Gene regulatory networks are widely used by biologists to describe the interactions among genes, proteins and other components at the intra-cellular level. Recently, a great effort has been devoted to give gene regulatory networks a formal semantics based on existing computational frameworks.

For this purpose, we consider Statecharts, which are a modular, hierarchical and executable formal model widely used to represent software systems. We use Statecharts for modeling small and recurring patterns of interactions in gene regulatory networks, called motifs.

Results

We present an improved method for modeling gene regulatory network motifs using Statecharts and we describe the successful modeling of several motifs, including those which could not be modeled or whose models could not be distinguished using the method of a previous proposal.

We model motifs in an easy and intuitive way by taking advantage of the visual features of Statecharts. Our modeling approach is able to simulate some interesting temporal properties of gene regulatory network motifs: the delay in the activation and the deactivation of the "output" gene in the coherent type-1 feedforward loop, the pulse in the incoherent type-1 feedforward loop, the bistability nature of double positive and double negative feedback loops, the oscillatory behavior of the negative feedback loop, and the "lock-in" effect of positive autoregulation.

Conclusions

We present a Statecharts-based approach for the modeling of gene regulatory network motifs in biological systems. The basic motifs used to build more complex networks (that is, simple regulation, reciprocal regulation, feedback loop, feedforward loop, and autoregulation) can be faithfully described and their temporal dynamics can be analyzed.
Undetectable Sensitive Serum Thyroglobulin (<0.1 ng/ml) in 163 Patients with Follicular Cell-Derived Thyroid Cancer: Results of rhTSH Stimulation and Neck Ultrasonography and Long-Term Biochemical and Clinical Follow-Up
Authors: Chindris A. M. , Diehl N. N. , Crook J. E. , Fatourechi V. , Smallridge R. C.
Published: May 2012

Context:

Surveillance of patients with differentiated thyroid cancer (DTC) is achieved using serum thyroglobulin (Tg), neck ultrasonography (US), and recombinant human TSH (rhTSH)-stimulated Tg (Tg-stim).

Objective:

Our primary aim was to assess the utility of rhTSH Tg-stim in patients with suppressed Tg (Tg-supp) below 0.1 ng/ml using a sensitive assay. Our secondary aims were to assess the utility of US and to summarize the profile of subsequent Tg-supp measures.

Design:

This is a retrospective study conducted at two sites of an academic institution.

Patients:

A total of 163 patients status after thyroidectomy and radioactive iodine treatment who had Tg-supp below 0.1 ng/ml and rhTSH Tg-stim within 60 d of each other were included.

Results:

After rhTSH stimulation, Tg remained below 0.1 ng/ml in 94 (58%) and increased to 0.1–0.5 in 56 (34%), more than 0.5–2.0 in nine (6%), and above 2.0 ng/ml in four (2%) patients. Serial Tg-supp levels were obtained in 138 patients followed over a median of 3.6 yr. Neck US were performed on 153 patients; suspicious exams had fine-needle aspiration (FNA). All positive FNA were identified around the time of the initial rhTSH test. Six of seven recurrences were detected by US (Tg-stim >2.0 ng/ml in one, 0.8 in one and ≤0.5 in four). One stage IV patient had undetectable Tg-stim.

Conclusion:

In patients with DTC whose T4-suppressed serum Tg is below 0.1 ng/ml, long-term monitoring with annual Tg-supp and periodic neck US are adequate to detect recurrences. In our experience, rhTSH testing does not change management and is not needed in this group of patients.
Pediatric Pulmonary Arterial Hypertension and Hyperthyroidism: A Potentially Fatal Combination
Authors: Trapp Christine M. , Elder Robert W. , Gerken Adrienne T. , Sopher Aviva B. , Lerner Shulamit , Aranoff Gaya S. , Rosenzweig Erika B.
Published: May 2012

Context:

Patients with pulmonary arterial hypertension (PAH) who develop hyperthyroidism are at risk for acute cardiopulmonary decompensation and death.

Cases and Setting:

We present a series of eight idiopathic PAH/heritable PAH pediatric patients who developed hyperthyroidism between 1999 and 2011. Institutional Review Board approval was obtained; informed consent was waived due to the retrospective nature of the series. All eight patients were receiving iv epoprostenol; five of the eight patients presented with acute cardiopulmonary decompensation in the setting of hyperthyroidism. In the remaining three patients, hyperthyroidism was detected during routine screening of thyroid function tests. The one patient who underwent emergency thyroidectomy was the only survivor of those who presented in cardiopulmonary decline.

Evidence Synthesis:

Aggressive treatment of the hyperthyroid state, including emergency total thyroidectomy and escalation of targeted PAH therapy and β-blockade when warranted, may prove lifesaving in these patients. Prompt thyroidectomy or radioactive iodine ablation should be considered for clinically stable PAH patients with early and/or mild hyperthyroidism to avoid potentially life-threatening cardiopulmonary decompensation.

Conclusions:

Although the association between hyperthyroidism and PAH remains poorly understood, the potential impact of hyperthyroidism on the cardiopulmonary status of PAH patients must not be ignored. Hyperthyroidism must be identified early in this patient population to optimize intervention before acute decompensation. Thyroid function tests should be checked routinely in patients with PAH, particularly those on iv epoprostenol, and urgently in patients with acute decompensation or symptoms of hyperthyroidism.
A Novel Point Mutation in the KCNJ5 Gene Causing Primary Hyperaldosteronism and Early-Onset Autosomal Dominant Hypertension
Authors: Charmandari Evangelia , Sertedaki Amalia , Kino Tomoshige , Merakou Christina , Hoffman Dax A. , Hatch Michael M. , Hurt Darrell E. , Lin Lin , Xekouki Paraskevi , Stratakis Constantine A. , Chrousos George P.
Published: May 2012

Context:

Aldosterone production in the adrenal zona glomerulosa is mainly regulated by angiotensin II, [K+], and ACTH. Genetic deletion of subunits of K+-selective leak (KCNK) channels TWIK-related acid sensitive K+-1 and/or TWIK-related acid sensitive K+-3 in mice results in primary hyperaldosteronism, whereas mutations in the KCNJ5 (potassium inwardly rectifying channel, subfamily J, member 5) gene are implicated in primary hyperaldosteronism and, in certain cases, in autonomous glomerulosa cell proliferation in humans.

Objective:

The objective of the study was to investigate the role of KCNK3, KCNK5, KCNK9, and KCNJ5 genes in a family with primary hyperaldosteronism and early-onset hypertension.

Patients and Methods:

Two patients, a mother and a daughter, presented with severe primary hyperaldosteronism, bilateral massive adrenal hyperplasia, and early-onset hypertension refractory to medical treatment. Genomic DNA was isolated and the exons of the entire coding regions of the above genes were amplified and sequenced. Electrophysiological studies were performed to determine the effect of identified mutation(s) on the membrane reversal potentials.

Results:

Sequencing of the KCNJ5 gene revealed a single, heterozygous guanine to thymine (G → T) substitution at nucleotide position 470 (n.G470T), resulting in isoleucine (I) to serine (S) substitution at amino acid 157 (p.I157S). This mutation results in loss of ion selectivity, cell membrane depolarization, increased Ca2+ entry in adrenal glomerulosa cells, and increased aldosterone synthesis. Sequencing of the KCNK3, KCNK5, and KCNK9 genes revealed no mutations in our patients.

Conclusions:

These findings explain the pathogenesis in a subset of patients with severe hypertension and implicate loss of K+ channel selectivity in constitutive aldosterone production.
Suspicious Cervical Lymph Nodes Detected after Thyroidectomy for Papillary Thyroid Cancer Usually Remain Stable Over Years in Properly Selected Patients
Authors: Robenshtok E. , Fish S. , Bach A. , Domínguez Jose M. , Shaha A. , Tuttle R. M.
Published: May 2012

Context:

The risk of loco-regional recurrence in papillary thyroid cancer (PTC) patients ranges from 15–30%. However, the clinical significance of small-volume loco-regional recurrence detected by highly sensitive ultrasonography is unclear.

Objective:

Our objective was to describe the natural history of abnormal cervical lymph nodes (LN) diagnosed after initial treatment.

Design:

We conducted a retrospective cohort study.

Patients:

166 PTC with patients who had at least one abnormal LN outside the thyroid be on ultrasound and selected for active surveillance were included.

Main Outcome Measure:

LN growth during a period of active surveillance was the primary outcome.

Results:

Most patients had classical PTC (85%) and an intermediate risk of recurrence (77%). The median LN size at the start of the observation period was 1.3 cm (range, 0.5–2.7 cm) in largest diameter, with all nodes having at least one abnormal sonographic characteristic (70% of patients had LN with at least two abnormal features). In almost all patients, the LN were in the lateral neck, primarily in levels 3 (43%) and 4 (58%). After a median follow-up of 3.5 yr, only 20% (33 of 166) grew at least 3 mm, 9% (15 of 166) grew at least 5 mm, and 14% (23 of 166) resolved. None of the clinical or sonographic features were predictive of LN growth (positive predictive value range = 0.21–0.57). There were no local complications (nerve damage or local invasion) related to the abnormal nodes and no disease-related mortality.

Conclusions:

Suspicious cervical LN in the lateral neck usually remain stable for long periods of time in properly selected PTC patients and can be safely followed with serial ultrasounds
Strategies of Visual Intervention: Langston Hughes and Uncle Tom's Cabin
Authors: Peabody Rebecca
Published: May 2012

In 1952 publisher Dodd, Mead and Company invited African American writer and intellectual Langston Hughes to create an introduction, select illustrations, and prepare discursive captions for a new edition of Harriet Beecher Stowe's Uncle Tom's Cabin. The mid-twentieth century was a complex moment in the cultural reception of the novel, characterized both by public demand for new incarnations of the story and by protests against the book and the performances it inspired. Hughes, who had a long-standing relationship with the story, accepted the invitation and produced an unusual project that reflects the story's ambivalent cultural status, celebrating the novel even while unraveling its narrative threads. While Hughes's introduction to the 1952 edition is often cited by scholars, there has been little sustained consideration of the multiple layers of critical interpretation evident throughout the rest of the book. In fact, while Hughes takes Stowe's novel as a point of departure, the work done by his choice of images, their captions, and their placement in the text is the real story. This essay elucidates some of the deeply complex strategies Hughes employed in order to elicit multiple, sometimes contradictory, stories from Stowe's text and analyzes the effects they create for readers. The essay argues that Hughes used critical and creative tools in ways unique to this project to strategically disrupt readers' suspension of disbelief and thereby provoke a more critical, more culturally and historically inflected understanding of the story.
The lysosomal polypeptide transporter TAPL is stabilized by the interaction with LAMP-1 and LAMP-2
Authors: Demirel Özlem , Jan Irina , Wolters Dirk , Blanz Judith , Saftig Paul , Tampé Robert , Abele Rupert
Published: May 2012

TAPL (ABCB9) is a homodimeric polypeptide translocation machinery which transports cytosolic peptides into the lumen of lysosomes for degradation. Since the function of proteins is strongly dependent on the interaction network involved, we investigated the interactome of TAPL. A proteomic approach allowed to identify with lower frequency major histocompatibility complex II subunits and as most abundant interaction partners the lysosome-associated membrane proteins LAMP-1 and LAMP-2B. The interaction site of LAMP was mapped to TMD0 which is a four transmembrane helices comprising N-terminal domain of TAPL. The LAMP proteins bind independently from one another to TAPL. This interaction has neither influence on subcellular localization nor on peptide transport activity. However, in LAMP deficient cells the half-life of TAPL is decreased by a factor of five whereas LIMP-2 as another lysosomal membrane protein is not affected. Reduced stability of TAPL is caused by increased lysosomal degradation indicating that LAMP proteins retain TAPL on the limiting membrane of endosomes and prevent its sorting to intraluminal vesicles.
Confluence switch signaling regulates ECM composition and plasmin proteolytic cascade in keratinocytes
Authors: Botta Adrien , Delteil Frédéric , Mettouchi Amel , Viera Andhira , Estrach Soline , Négroni Luc , Stefani Caroline , Lemichez Emmanuel , Meneguzzi Guerrino , Laurent Gagnoux-Palacios
Published: May 2012

In culture, cell confluence generates signals that commit actively growing keratinocytes to exit the cell cycle and differentiate to form a stratified epithelium. Using a comparative proteomic approach, we studied this ‘confluence switch’ and identified a new pathway triggered by cell confluence that regulates basement membrane (BM) protein composition by suppressing the uPA/uPAR/plasmin pathway. Indeed, confluence triggers adherens junction maturation and enhances TGF-β/activin A activity, resulting in increased deposition of PAI-1 and perlecan in the BM. Extracellular matrix (ECM)-accumulated PAI-1 suppresses uPA/uPAR/plasmin pathway and further enhances perlecan deposition by inhibiting its plasmin-dependent proteolysis. We show that perlecan deposition in the ECM strengthens cell adhesion, inhibits keratinocyte motility and promotes additional accumulation of PAI-1 in the ECM at confluence. In agreement, during wound-healing, perlecan concentrates at the wound-margin, where BM matures to stabilize keratinocyte adhesion. Our results demonstrate that confluence dependent-signaling orchestrates not only growth-inhibition and differentiation but also controls ECM-proteolysis and BM formation. These data suggest that uncontrolled integration of confluence-dependent signaling, may favor skin disorders, including tumorigenesis, not only by promoting cell hyperproliferation but also by altering protease activity and deposition of ECM components.
Bone morphogenetic proteins differentially regulate pigmentation in human skin cells
Authors: Singh Suman K. , Abbas Waqas A. , Tobin Desmond J.
Published: May 2012

Bone morphogenetic proteins (BMPs) represent a large family of multi-functional secreted signaling molecules. Previously BMP2/4 were shown to inhibit skin pigmentation by down-regulating tyrosinase expression and activity in epidermal melanocytes (MC). However, a possible role for other BMP family members and their antagonists in melanogenesis has not yet been explored. In this study we show that BMP4 and BMP6, from two different BMP subclasses, and their antagonists noggin and sclerostin were variably expressed in MC and keratinocytes (KC) in human skin. We further examined their involvement in melanogenesis and melanin transfer using fully-matched primary cultures of adult human MC and keratinocyte (KC). BMP6 markedly stimulated melanogenesis by up-regulating tyrosinase expression and activity, and also stimulated the formation of filopodia and Myosin-X expression in MC, which was associated with increased melanosome transfer from MC to KC. BMP4, by contrast, inhibited melanin synthesis and transfer to below baseline levels. These findings were confirmed using siRNA knockdown of BMP receptors BMPR1A/1B or of Myosin-X, as well as by incubating cells with the antagonists noggin and sclerostin. While BMP6 was found to use the p38MAPK pathway to regulate melanogenesis in human MC independently of the Smad pathway, p38MAPK, PI-3K and Smad pathways were all involved in BMP6-mediated melanin transfer. This suggests that pigment formation may be regulated independently of pigment transfer. These data reveal a complex involvement of regulation of different members of the BMP family, their antagonists and inhibitory Smads, in MC behaviour.
Sonic hedgehog regulates presynaptic terminal size, ultrastructure and function in hippocampal neurons
Authors: Mitchell Nicholas , Petralia Ronald S , Yao Pamela J. , Currier Duane G. , Wang Ya-Xian , Kim Alvin , Mattson Mark P.
Published: May 2012

Sonic hedgehog (Shh) signaling is essential to the patterning of the embryonic neural tube, but its presence and function in the postmitotic differentiated neurons in the brain remain largely uncharacterized. We recently showed that Shh and its signaling components, Patched and Smoothened, are expressed in postnatal and adult hippocampal neurons. Here, we ask whether Shh signaling has a function in these neurons. Using cultured hippocampal neurons as a model system, we find that presynaptic terminals become significantly larger in response to the application of Shh. Ultrastructural examination confirms the enlarged presynaptic profiles and also reveals variable increases in the size of synaptic vesicles, with a resulting loss of uniformity.

Furthermore, electrophysiological analyses show significant increases in the frequency, but not the amplitude, of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in response to Shh, providing functional evidence of Shh's selective role in presynaptic terminals. Thus, we conclude that Shh signaling regulates the structure and functional properties of presynaptic terminals of hippocampal neurons.
Transformation Through Health Teaching for Adults with Intellectual and Developmental Disabilities: A Qualitative Study
Authors: Focht-New Ginny
Published: May 2012

Adults with intellectual and developmental disabilities have medical conditions similar to those among the general population but with more complex presentation, a extended life expectancy, and increased risk of morbidity and mortality. These adults' health education has been inadequate. In this qualitative study, the author describes the experiences of 23 registered nurses who provide health teaching to adults with intellectual and developmental disabilities, selection of and health topics taught, and teaching activities put into practice. The author used a rigorous descriptive, naturalistic inquiry design with purposive (n  =  22) and snowball (n  =  1) sampling. Data were gathered through individual interviews, focus groups, and nonparticipant observations, and analyzed with a constant comparative method. Findings concerned the educators' developmental process, use of a social context to teach, and health-teaching activities. Registered nurses s described their transformation from insecure, novice health educators to confident and passionate educators of adults with intellectual and developmental disabilities. Findings apply to multiple disciplines.
Rapid elimination kinetics of free PSA or human kallikrein-related peptidase 2 after initiation of gonadotropin-releasing hormone-antagonist treatment of prostate cancer: potential for rapid monitoring of treatment responses
Authors: Ulmert David , Vickers Andrew J. , Scher Howard I. , Becker Charlotte , Iversen Peter , Frankel David , Jensen Jens-Kristian , Olesen Tine Kold , Lilja Hans
Published: May 2012

Background: The utility of conventional prostate-specific antigen (PSA) measurements in blood for monitoring rapid responses to treatment for prostate cancer is limited because of its slow elimination rate. Prior studies have shown that free PSA (fPSA), intact PSA (iPSA) and human kallikrein-related peptidase 2 (hK2) are eliminated more rapidly after radical prostatectomy. In contrast, all three markers have similarly slow elimination rates after castration induced by gonadotropin-releasing hormone (GnRH) agonists, possibly due to the slow onset of castration. Therefore, we assessed elimination rates of tPSA, fPSA, iPSA and hK2 after rapid induction of castration with degarelix (Firmagon®), a novel GnRH antagonist.

Methods: This study included 24 patients treated with degarelix. Blood was taken at 1, 3, 7, 14, 21 and 28 days after injection of degarelix. Free and total PSA were measured with a commercial dual-label assay, and with inhouse research assays of intact PSA and hK2.

Results: Median (interquartile range, IQR) tPSA at baseline was 23.4 (15.8, 59.8). Twenty-two patients (92%) reached castrate levels of testosterone within 24 h of degarelix initiation, and all patients did so within 72 h. All kallikrein forms declined in an exponential fashion after degarelix administration. The median time to 50% reduction in biomarker level was 8–9 days for tPSA or complexed PSA vs. 2–4 days for hK2, iPSA and fPSA. The percentage eliminated at day 3 and day 7 was significantly higher for hK2, iPSA and fPSA than for tPSA (all p<0.02), while tPSA and complexed PSA were similar.

Conclusions: The rapid decline of fPSA, iPSA and hK2 after fast induction of castration with degarelix is similar to that reported after prostatectomy and offers a novel, informative method to monitor rapid onset of therapeutic action targeting signaling of the androgen receptor.
Degrees, class sizes and divisors of character values
Authors: Gallagher Patrick X.
Published: May 2012

In the character table of a finite group there is a tendency either for the character degree to divide the conjugacy class size or the character value to vanish. There is also a partial divisibility where the determinant of the character is not 1. There are versions of these depending on a subgroup, based on an arithmetic property of spherical functions which generalizes the integrality of the values of the characters and the central characters.
Delayed interval delivery in twin and triplet pregnancies: 6 years of experience in one perinatal center
Authors: Reinhard Joscha , Reichenbach Lena , Ernst Tina , Reitter Anke , Antwerpen Isabelle , Herrmann Eva , Schlösser Rolf , Louwen Frank
Published: May 2012

Objective: This study aimed to know the outcome of delayed-interval delivery for twin and triplet pregnancies at 22+0 to 25+0 weeks of gestation.

Study design: A retrospective cohort of twin and triplet deliveries at the 23rd to 26th weeks of gestation were managed with delayed interval delivery from 2005 to 2011.

Results: From 2005 until 2011, delayed delivery in five twin pregnancies and two triplet pregnancies were performed. The interval between delivery of the first fetus and the remaining twin/triplets was 1–18 days (mean, 9.7 days). In all cases, the first fetus was born vaginally. Survival of the first twin/triplet was 14.3%, whereas 57.1% of the second born twin/triplets survived. Birth weight gained due to delayed delivery was 131 g on average. No severe maternal complications were observed. When compared with a gestation age-matched group, where the delay was not possible, the delayed twin/triplet had a higher survival rate (57.1% vs. 0%, P=0.05).

Conclusion: In multiple pregnancies with preterm delivery between completed 22 and completed 25 weeks of gestational age, delayed delivery seems to be a useful therapeutic option to achieve a better outcome of the remaining fetus or fetuses.
EPR/PTFE Dosimetry for Test Reactor Environments
Authors: Vehar D. W. , Griffin P. J. , Quirk T. J.
Published: May 2012

In 1992 the Radiation Metrology Laboratory (RML) at Sandia National Laboratories implemented EPR/Alanine capabilities for use in routine and calibration activities at its Co-60 and pulsed-power facilities. At that time it also investigated the usefulness of the system for measurement of absorbed dose in the mixed neutron/photon environments of reactors such as the Sandia Pulsed Reactor and the Annular Core Research Reactor used for hardness testing of electronics. The RML concluded that the neutron response of alanine was a sufficiently high fraction of the overall dosimeter response that the resulting uncertainties in the photon dose would be unacceptably large for silicon-device testing. However, it also suggested that non-hydrogenous materials such as polytetrafluoroethylene (PTFE) would exhibit smaller neutron response and might be useful in mixed environments. Preliminary research with PTFE in photon environments indicated considerable promise, but further development was not pursued at that time. Because of renewed interest in absorbed dose measurements that could better define the individual contributions of photon and neutron components to the overall dose delivered to a test object, the RML has re-initiated the development of an EPR/PTFE dosimetry system. This paper presents a summary of the research, a description of the EPR/PTFE dosimetry system, and recommendations for preparation and fielding of the dosimetry in photon and mixed neutron/photon environments.
A Broad-Group Cross-Section Library Based on ENDF/B-VII.0 for Fast Neutron Dosimetry Using the CPXSD Methodology
Authors: Alpan F. A.
Published: May 2012

A new ENDF/B-VII.0-based coupled 44-neutron, 20-gamma-ray-group cross-section library was developed to investigate the latest evaluated nuclear data file (ENDF) ,in comparison to ENDF/B-VI.3 used in BUGLE-96, as well as to generate an objective-specific library. The objectives selected for this work consisted of dosimetry calculations for in-vessel and ex-vessel reactor locations, iron atom displacement calculations for reactor internals and pressure vessel, and 58Ni(n,γ) calculation that is important for gas generation in the baffle plate. The new library was generated based on the contributon and point-wise cross-section-driven (CPXSD) methodology and was applied to one of the most widely used benchmarks, the Oak Ridge National Laboratory Pool Critical Assembly benchmark problem. In addition to the new library, BUGLE-96 and an ENDF/B-VII.0-based coupled 47-neutron, 20-gamma-ray-group cross-section library was generated and used with both SNLRML and IRDF dosimetry cross sections to compute reaction rates. All reaction rates computed by the multigroup libraries are within ± 20 % of measurement data and meet the U. S. Nuclear Regulatory Commission acceptance criterion for reactor vessel neutron exposure evaluations specified in Regulatory Guide 1.190.
A Systematic Approach to the Study of Accelerated Weathering of Building Joint Sealants
Authors: White Christopher C. , Hunston Donald L. , Tan Kar Tean , Filliben James J. , Pintar Adam L. , Schueneman Greg
Published: May 2012

An accurate service life prediction model is needed for building joint sealants in order to greatly reduce the time to market of a new product and reduce the risk of introducing a poorly performing product into the marketplace. A stepping stone to the success of this effort is the precise control of environmental variables in a laboratory accelerated test apparatus in order to produce reliable weathering data that can be used to generate a predictive model. This contribution reports a systematic study, using a novel laboratory test apparatus, investigating the individual and synergistic impacts of four environmental factors (cyclic movement, temperature, relative humidity, and ultraviolet radiation) on the durability of a sealant system. The apparatus used is unique because it not only allows the precise control of environmental factors but also permits in situ characterization tests so that the specimens need not be removed from the apparatus chamber. Graphical and quantitative statistical approaches have been used to analyze the data. The study shows that the critical role of each individual factor, as well as synergism among the different factors, can be readily quantified, and modes of degradation possibly can be identified.
Development and Testing of the VITAMIN-B7/BUGLE-B7 Coupled Neutron-Gamma Multigroup Cross-Section Libraries
Authors: Risner J. M. , Wiarda D. , Miller T. M. , Peplow D. E. , Patton B. W. , Dunn M. E. , Parks B. T.
Published: May 2012

The U.S. Nuclear Regulatory Commission’s Regulatory Guide 1.190 states that calculational methods used to estimate reactor pressure vessel (RPV) fluence should use the latest version of the evaluated nuclear data file (ENDF). The VITAMIN-B6 fine-group library and BUGLE-96 broad-group library, which are widely used for RPV fluence calculations, were generated using ENDF/B-VI.3 data, which was the most current data when Regulatory Guide 1.190 was issued. We have developed new fine-group (VITAMIN-B7) and broad-group (BUGLE-B7) libraries based on ENDF/B-VII.0. These new libraries, which were processed using the AMPX code system, maintain the same group structures as the VITAMIN-B6 and BUGLE-96 libraries. Verification and validation of the new libraries were accomplished using diagnostic checks in AMPX, “unit tests” for each element in VITAMIN-B7, and a diverse set of benchmark experiments including critical evaluations for fast and thermal systems, a set of experimental benchmarks that are used for SCALE regression tests, and three RPV fluence benchmarks. The benchmark evaluation results demonstrate that VITAMIN-B7 and BUGLE-B7 are appropriate for use in RPV fluence calculations and meet the calculational uncertainty criterion in Regulatory Guide 1.190.
A Review of the Behavior of Structural Silicone Glazing Systems Subjected to a Mega-Earthquake
Authors: Bull Errol , Cholaky Jorge
Published: May 2012

Structural silicone glazed (SSG) curtain wall systems have offered architects and owners the ability to design a facade with unique aesthetic features since the 1970s. While their ability to durably withstanding natural weathering and even high wind locations across the globe has been well established, their performance under seismic events is less well recorded. This paper presents a review of the performance of SSG systems following the 8.8 magnitude earthquake that shocked Chile in Feb 2010, which registered within the top five recorded in past history. Field reviews of existing low-, medium-, and high-rise buildings were inspected in the aftermath of the event to evaluate the performance of the different SSG variations of this system type (two-sided, four-sided, stick, unitized, among other variations) combined with other facade components such as: type of glazing, glass sizes, interstory drift, width of structural grid, slab/beam rigidity, etc.