bluuebunny/crossref_metadata_2025 huggingface dataset:
Die Kölnische Maschinenbau‐Actien‐Gesellschaft und der frühe Eisenbau im Rheinland
Authors: Kierdorf Alexander
Published: May 2015

Kurz nach der Mitte des 19. Jahrhunderts entstehen auch in Köln die ersten Großbauten unter maßgeblicher Verwendung von Eisen. Historisch stehen sie an der Schwelle vom Gusseisen zum modernen Schmiede‐ und Walzeisen, das eine völlig neue, wissenschaftlich begründete Konstruktionsweise ermöglicht. In Köln treffen dabei französische, englische und deutsche Einflüsse aufeinander. Führende Architekten wie Zwirner und Stüler, aber auch die Ingenieure der Eisenbahn‐ und Wasserbauverwaltungen beschäftigen sich mit dem neuen Baumaterial, insbesondere für den Brückenbau. Eine zentrale Rolle spielt die 1856 von Gustav von Mevissen ins Leben gerufene, heute weitgehend vergessene Kölnische Maschinenbau‐Actien‐Gesellschaft (später BAMAG) in Köln‐Bayenthal. Sie ist unter anderem im Bau von Brücken für die expandierende Eisenbahn, von Gasanstalten und im Maschinenbau aktiv.

Der Beitrag eröffnet bisher unbekannte Perspektiven auf die industrielle und bautechnische Entwicklung in Köln und der Rheinprovinz und lässt Großbauten wie den Glaspalast der Flora und das Ensemble Dom − Hauptbahnhof sowie die ersten Eisenbrücken als regionale Pionierleistungen ihrer Zeit in neuem Licht erscheinen.

The Cologne Machine Building Joint‐stock Company and early construction in iron on the Rhine. Soon after the middle of the 19th century, also at Cologne first mayor constructions in iron were erected. Historically, they stand at the turn from cast to wrought iron: the latter of which made possible an absolutely new, scientifically based structural building practice. At Cologne, British, French and German influences meet and melt. Leading architects of the time like Zwirner and Stueler, but also engineers of the railway companies and waterways administration get interested in iron as a building material, especially for bridges. A leading role on the Rhine at that time played the Cologne Machine Building Company (later known as BAMAG) at Bayenthal near Cologne, founded by the region’s most important industrialist, Gustav Mevissen, and today almost forgotten. The company is active in bridgebuilding for the rapidly expanding railway systems, but also the production of engines and gas works equipment.

The study opens new perspectives on the development of industry and construction in Cologne and the Prussian Rhine province. The first iron constructions like the Flora glasshouse, parts of the first central railway station and Cologne cathedral roof and transept spire, as well as the first larger railway bridges of the region shed a new light on its time as regional pioneer achievements.
Gas‐phase Preparation of SO3‐Graphite: Host‐Exchange and Exfoliation
Authors: Feicht Patrick , Breu Josef
Published: May 2015

The reaction of sulfur trioxide with graphite via gas phase led to an intercalation of a double layer of sulfur trioxide with a basal spacing of 11.1 Å. The SO3‐graphite was obtained atom‐efficient as a single phase product without the need of purification. The increased basal space should facilitate an exfoliation by rendering the tactoids more shear labile. A further weakening of the attractive forces within a stack was done by the replacement of sulfur trioxide with the surfactant perfluorobutanesulfonic acid leading to a basal spacing of 16.8 Å. The large basal spacings were also preserved in suspension and no defects were created. The mechanical exfoliation with ultrasound predominantly broke the platelets. A rotor‐stator device offering high shear forces was found to exfoliate the platelets more gently but there was still a good number of very small particles.
Comorbidities and Risk of Complications After Surgery for Esophageal Cancer: A Nationwide Cohort Study in Sweden
Authors: Backemar Lovisa , Lagergren Pernilla , Djärv Therese , Johar Asif , Wikman Anna , Lagergren Jesper
Published: May 2015

Background

The selection for surgery is multifaceted for patients diagnosed with esophageal cancer. Since it is uncertain how comorbidity should influence the selection, this study addressed comorbidities in relation to risk of severe complications following esophageal cancer surgery.

Methods

This population‐based cohort study was based on prospectively included patients who underwent surgical resection for an esophageal or gastro‐esophageal junctional cancer in Sweden during 2001–2005. The participation rate was 90 %. Associations between pre‐defined comorbidities and pre‐defined post‐operative complications occurring within 30 days of surgery were analyzed using multivariable logistic regression. The resulting odds ratios (ORs) and 95 % confidence intervals (CIs) were adjusted for age, sex, tumor stage, tumor histology, neoadjuvant therapy, type of surgery, annual hospital volume, other comorbidities, and other complications.

Results

Among 609 included patients, those with cardiac disease (n = 92) experienced an increased risk of pre‐defined complications in general (adjusted OR 1.81, 95 % CI 1.13–2.90), while patients with hypertension (n = 137), pulmonary disorders (n = 79), diabetes (n = 67), and obesity (n = 66) did not. Patients with a Charlson comorbidity index score ≥2 had substantially increased risks of pre‐defined complications (adjusted OR 2.44, 95 % CI 1.60–3.72).

Conclusion

Cardiac disease and a Charlson comorbidity index score ≥2 seem to increase the risk of severe and early post‐operative complications in patients with esophageal cancer, while hypertension, pulmonary disorders, diabetes, and obesity do not. These findings should be considered in the clinical decision‐making for improved selection of patients for surgery.
Growth of Bacillus methanolicus in 2 M methanol at 50 °C: the effect of high methanol concentration on gene regulation of enzymes involved in formaldehyde detoxification by the ribulose monophosphate pathway
Authors: Bozdag Ahmet , Komives Claire , Flickinger Michael C
Published: May 2015

Bacillus methanolicus MGA3 is a Gram-positive aerobic methylotroph growing optimally at 50–53 °C. Methylotrophy in B. methanolicus is encoded on pBM19 and by two chromosomal copies of the methanol dehydrogenase (mdh), hexulose phosphate synthase (hps) and phosphohexuloisomerase (phi) genes. However, there are no published studies on the regulation of methylotrophy or the dominant mechanism of detoxification of intracellular formaldehyde in response to high methanol concentration. The µ  max of B. methanolicus MGA3 was assessed on methanol, mannitol and glucose. B. methanolicus achieved a µ  max at 25 mM initial methanol of 0.65 ± 0.007 h−1, which decreased to 0.231 ± 0.004 h−1 at 2 M initial methanol. Slow growth was also observed with initial methanol concentrations of >2 M. The µ  max on mannitol and glucose are 0.532 ± 0.002 and 0.336 ± 0.003 h−1, respectively. Spiking cultures with additional methanol (100 mM) did not disturb the growth rate of methanol-grown cells, whereas, a 50 mM methanol spike halted the growth in mannitol. Surprisingly, growth in methanol was inhibited by 1 mM formaldehyde, while mannitol-grown cells tolerated 2 mM. Moreover, mannitol-grown cells removed formaldehyde faster than methanol-grown cells. Further, we show that methanol oxidation in B. methanolicus MGA3 is mainly carried out by the pBM19-encoded mdh. Formaldehyde and formate addition down-regulate the mdh and hps genes in methanol-grown cells. Similarly, they down-regulate mdh genes in mannitol-grown cells, but up-regulate hps. Phosphofructokinase (pfk) is up-regulated in both methanol and mannitol-grown cells, which suggests that pfk may be a possible synthetic methylotrophy target to reduce formaldehyde growth toxicity at high methanol concentrations.
Enhanced production of l-sorbose in an industrial Gluconobacter oxydans strain by identification of a strong promoter based on proteomics analysis
Authors: Hu Yudong , Wan Hui , Li Jianghua , Zhou Jingwen
Published: May 2015

Gluconobacter oxydans is capable of rapidly incomplete oxidation of many sugars and alcohols, which means the strain has great potential for industrial purposes. Strong promoters are one of the essential factors that can improve strain performance by overexpression of specific genes. In this study, a pipeline for screening strong promoters by proteomics analysis was established. Based on the procedure, a new strong promoter designated as PB932_2000 was identified in G. oxydans WSH-003. The promoter region was characterized based on known genome sequence information using BPROM. The strength of PB932_2000 was further assessed by analysis of enhanced green fluorescent protein (egfp) expression and comparison with egfp expression by two commonly used strong promoters, PE. coli_tufB and PG. oxydans_tufB. Both quantitative real-time PCR and fluorescence intensities for egfp gene expression showed that PB932_2000 promoter is stronger than the other two. Overexpression of d-sorbitol dehydrogenase (sldh) by PB932_2000 in G. oxydans WSH-003 enhanced the titer and productivity of l-sorbose synthesis from d-sorbitol by 12.0 % and 33.3 %, respectively. These results showed that proteomics analysis is an efficient way to identify strong promoters. The isolated promoter PB932_2000 could further facilitate the metabolic engineering of G. oxydans.
Increasing succinic acid production using the PTS-independent glucose transport system in a Corynebacterium glutamicum PTS-defective mutant
Authors: Zhou Zhihui , Wang Chen , Xu Hongtao , Chen Zhongjun , Cai Heng
Published: May 2015

Succinic acid synthesized from glucose shows potential as a bio-based platform chemical. However, the need for a high glucose concentration, and the accompanying low yields, limit its industrial applications. Despite efficient glucose uptake by the phosphotransferase system (PTS), 1 mol of phosphoenolpyruvate is required for each mole of internalized glucose. Therefore, a PTS-defective Corynebacterium glutamicum mutant was constructed to increase phosphoenolpyruvate availability for succinic acid synthesis, resulting in a lower glucose utilization rate and slower growth. The transcriptional regulator iolR was also deleted to enable the PTS-defective mutant to utilize glucose via iolT-mediated glucose transport. Deletion of iolR and overexpression of iolT1 and ppgk (polyphosphate glucokinase) in the PTS-deficient C. glutamicum strain completely restored glucose utilization, increasing production by 11.6 % and yield by 32.4 % compared with the control. This study revealed for the first time that iolR represses the expression of the two glucokinase genes (glk and ppgk).
Aboveground carbon dynamics following strip clear‐cutting in the Peruvian Amazon
Authors: Rondon Xanic J. , Gorchov David L. , Noble Robert B. , Cornejo Fernando
Published: May 2015

Aboveground carbon dynamics were estimated in two strips (30 m × 150 m) clear‐cut in the Peruvian Amazon following 15 years after clearing. While strip 1 recovered 50 % (64 Mg C ha−1) of its pre‐clearing carbon stocks, the clear‐cut portion of strip 2 recovered 39 % (53 Mg C ha−1). During this period, there were high carbon sequestration rates (>6 Mg C ha−1 year−1) from tree growth and low carbon emission rates from tree mortality (up to 3 Mg C ha−1 year−1) in both strip 1 and the clear‐cut portion of strip 2. Recruits make up most of the tree composition in both strips, and therefore play an important role in carbon sequestration. However, there were high carbon emission rates from timber harvesting and processing (>20 Mg C ha−1 year−1). A thinning treatment, applied 7 years after clearing, did not affect carbon dynamics. In the 15‐year period total carbon emissions (+) were greater than sequestration (−). Net carbon fluxes for strip 1 and the clear‐cut portion of strip 2 were +26 and +68 Mg C ha−1. Comparable carbon dynamics were found in the deferment‐cut treatment, applied to the south half of strip 2. To conclude, the 15 year‐old clear‐cut strips are not carbon sinks yet, and will require >140 years to reach old‐growth carbon stocks.
Cervical fractures with associated spinal cord injury in children and adolescents: Epidemiology, costs, and in-hospital mortality rates in 4418 patients
Authors: Jain Amit , Brooks Jaysson T. , Rao Sandesh S. , Ain Michael C. , Sponseller Paul D.
Published: May 2015

Background

Cervical spine fractures with spinal cord injury (CFSCI) can be devastating. We describe the epidemiology of children and adolescents with CFSCI.

Methods

Using the Nationwide Inpatient Sample (NIS) database, we identified 4418 patients (≤18 years old) who had CFSCI from 2000 through 2010. Outcomes of interest were patient characteristics (age, sex), injury characteristics [fracture location, spinal cord injury (SCI) pattern], economic variables (duration of hospital stay, total hospital charges), and mortality.

Results

Upper cervical fractures (UCFs) occurred half as often (31.4 %) as lower cervical fractures (LCFs; 68.8 %). Among patients <8 years old, 73.6 % had UCFs; among patients ≥8 years old, 72.3 % had LCFs. Overall, 68.7 % had incomplete SCI, 22.4 % had complete SCI, 6.6 % had central cord syndrome, and 2.3 % had anterior cord syndrome. Patients with complete SCI had the longest hospital stays and highest hospital charges. The overall in-hospital mortality rate was 7.3 %, with a sixfold higher rate in patients <8 (30.6 %) vs. those ≥8 (5.1 %) years old ( p < 0.001). There was a threefold higher mortality rate in patients with upper (13.5 %) vs. lower (4.3 %) cervical fractures ( p < 0.001). Patients with complete SCI had a 1.85-fold higher mortality rate than patients with other cord syndromes ( p < 0.001).

Conclusions

Patients <8 years old were more likely than older patients to sustain UCFs. Patients with UCFs had a significantly higher mortality rate than those with LCFs. Patients with complete SCI had the longest duration of hospital stay and highest hospital charges and in-hospital mortality rate.
Candida albicans erythroascorbate peroxidase regulates intracellular methylglyoxal and reactive oxygen species independently of d‐erythroascorbic acid
Authors: Kwak Min-Kyu , Song Sung-Hyun , Ku MyungHee , Kang Sa-Ouk
Published: May 2015

Candida albicans d‐erythroascorbate peroxidase (EAPX1), which can catalyze the oxidation of d‐erythroascorbic acid (EASC) to water, was observed to be inducible in EAPX1‐deficient and EAPX1‐overexpressing cells via activity staining. EAPX1‐deficient cells have remarkably increased intracellular reactive oxygen species and methylglyoxal independent of the intracellular EASC content. The increased methylglyoxal caused EAPX1‐deficient cells to activate catalase‐peroxidase and cytochrome c peroxidase, which led to defects in cell growth, viability, mitochondrial respiration, filamentation and virulence. These findings indicate that EAPX1 mediates cell differentiation and virulence by regulating intracellular methylglyoxal along with oxidative stresses, regardless of endogenous EASC biosynthesis or alternative oxidase expression.
Cloning and characterization of the Escherichia coli Heptosyltransferase III: Exploring substrate specificity in lipopolysaccharide core biosynthesis
Authors: Mudapaka Jagadesh , Taylor Erika Anne
Published: May 2015

Bacterial lipopolysaccharide (LPS) molecules are an important cell surface component that enables adhesion to surfaces and cell motility, amongst other functions. In Escherichia coli, there are multiple Heptosyltransferase enzymes involved in the biosynthesis of the core region of LPS. Here we describe the first ever cloning, expression, purification and characterization of Heptosyltransferase III (HepIII) from E. coli, which catalyzes the addition of an l‐glycero‐
d‐manno‐heptose (Hep) residue to the growing LPS core via an α(1 → 7) bond. Inspired by results from our lab on the E. coli HepI, we assessed the catalytic efficiency with phospho‐Hep2‐Kdo2‐Lipid A (PH2K2LA) and two deacylated analogues.
Induction of heat shock protein HSPA6 (HSP70B′) upon HSP90 inhibition in cancer cell lines
Authors: Kuballa Petric , Baumann Anna-Lena , Mayer Klaus , Bär Ute , Burtscher Helmut , Brinkmann Ulrich
Published: May 2015

Genome‐wide transcript profiling to elucidate responses to HSP90 inhibition revealed strong induction of HSPA6 in MCF‐7 cells treated with 17‐AAG. Time‐ and dose dependent induction of HSPA6 (confirmed by qPCR and Western Blots) occurred also upon treatment with Radicicol, another HSP90 inhibitor. HSPA6 was not detectable in untreated cells or cells treated with toxins that do not inhibit HSP90, or upon applying oxidative stress. Thus, HSPA6 induction is not a general response to cytotoxic insults. Modulation of HSPA6 levels by siRNA‐mediated inhibition or recombinant expression did not influence 17‐AAG mediated cell death. HSPA6 induction as a consequence of HSP90 inhibition occurs in various (but not all) cell lines and may be a more specific marker for HSP90 inhibition than induction of other HSP70 proteins.
Chemical chronobiology: Toward drugs manipulating time
Authors: Wallach Thomas , Kramer Achim
Published: May 2015

Circadian clocks are endogenous timing systems orchestrating the daily regulation of a huge variety of physiological, metabolic and behavioral processes. These clocks are important for health – in mammals, their disruption leads to a diverse number of pathologies. While genetic and biochemical approaches largely uncovered the molecular bases of circadian rhythm generation, chemical biology strategies targeting the circadian oscillator by small chemical compounds are increasingly developed. Here, we review the recent progress in the identification of small molecules modulating circadian rhythms. We focus on high‐throughput screening approaches using circadian bioluminescence reporter cell lines as well as describe alternative mechanistic screens. Furthermore, we discuss the potential for chemical optimization of small molecule ligands with regard to the recent progress in structural chronobiology.
APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern
Authors: Risacher Shannon L. , Kim Sungeun , Nho Kwangsik , Foroud Tatiana , Shen Li , Petersen Ronald C. , Jack Clifford R. , Beckett Laurel A. , Aisen Paul S. , Koeppe Robert A. , Jagust William J. , Shaw Leslie M. , Trojanowski John Q. , Weiner Michael W. , Saykin Andrew J. ,   Alzheimer's Disease Neuroimaging Initiative (ADNI)
Published: May 2015

Introduction

This study assessed apolipoprotein E (APOE) ε4 carrier status effects on Alzheimer's disease imaging and cerebrospinal fluid (CSF) biomarkers in cognitively normal older adults with significant memory concerns (SMC).

Methods

Cognitively normal, SMC, and early mild cognitive impairment participants from Alzheimer's Disease Neuroimaging Initiative were divided by APOE ε4 carrier status. Diagnostic and APOE effects were evaluated with emphasis on SMC. Additional analyses in SMC evaluated the effect of the interaction between APOE and [18F]Florbetapir amyloid positivity on CSF biomarkers.

Results

SMC ε4+ showed greater amyloid deposition than SMC ε4−, but no hypometabolism or medial temporal lobe (MTL) atrophy. SMC ε4+ showed lower amyloid beta 1–42 and higher tau/p‐tau than ε4−, which was most abnormal in APOE ε4+ and cerebral amyloid positive SMC.

Discussion

SMC APOE ε4+ show abnormal changes in amyloid and tau biomarkers, but no hypometabolism or MTL neurodegeneration, reflecting the at‐risk nature of the SMC group and the importance of APOE in mediating this risk.
On the transport of heavy particles through an upward displacement-ventilated space
Authors: Mingotti Nicola , Woods Andrew W.
Published: May 2015

We explore the transport of heavy particles through an upward displacement-ventilated space. The space incorporates a localised source of buoyancy which generates a turbulent buoyant plume. The plume fluid is contaminated with a small concentration of particles, which are subject to gravitational settling. A constant flow of uncontaminated fluid is supplied at a low level into the space, while an equal amount of fluid is vented from the space at a high level. At steady state, a two-layer density stratification develops associated with the source of buoyancy. New laboratory experiments are conducted to explore how particles are transported by this flow. The experiments identify that the upper layer may either become well-mixed in particles or it may develop a vertical stratification in particle concentration, with the particle concentration decreasing with height. We develop a quantitative model which identifies that such stratification develops for larger particle setting speeds, or smaller ventilation rates. In accord with our experiments, the model predicts that the number of particles extracted from the space through the high-level vent is controlled by the magnitude of the particle stratification in the upper layer, and this in turn depends on the particle settling speed relative to the ventilation speed and also the cross-sectional area and height of the space. We compare the predictions of the model with measurements of the flux of particles vented from the space for a range of operating conditions. We explore the relevance of the model for the removal of airborne contaminants by displacement ventilation in hospital rooms, and we discuss how contamination is propagated in the room as a result of lateral mixing of pathogens in the upper layer.
On damping of two-dimensional piston-mode sloshing in a rectangular moonpool under forced heave motions
Authors: Faltinsen O. M. , Timokha A. N.
Published: May 2015

Based on a similarity between piston-mode sloshing in a two-dimensional rectangular moonpool and a small-amplitude oscillatory flow through a slot in a slatted screen, a pressure discharge in the moonpool opening is theoretically quantified. This makes it possible, by changing the dynamic free-surface condition inside the moonpool, to account for the vortex-induced damping and thereby to modify the inviscid potential flow statement. The present paper is an important addition to Faltinsenet al.(J. Fluid Mech., vol. 575, 2007, pp. 359–397), where a discrepancy between the potential flow theory and model tests was reported. New calculations are supported by the earlier model tests of the authors as well as numerical data obtained by means of viscous solvers.
Rebecca Jessen, 'Gap', Brisbane: University of Queensland Press, 2014, IBSN 9780 7022 5320 1, 232 pp., $22.95
Authors: Skeat Jean
Published: May 2015

Rebecca Jessen, Gap, Brisbane: University of Queensland Press, 2014, IBSN 9780 7022 5320 1, 232 pp., $22.95
'Something that makes us ponder'
Authors: Buckridge Patrick
Published: May 2015

When considering the question of reading provision in remote regions, Australian historians have tended to focus on the challenge of distributing books and other reading matter affordably across vast and sparsely populated areas. In the back-blocks of Western Queensland between the wars, however, the problem of distribution had been addressed with some success: by mail orders to metropolitan book retailers, subsidised postal rates, local Schools of Arts libraries, the Workers’ Educational Association and, above all, the efficient operations of the Queensland Bush Book Club, which performed extraordinary feats of remote distribution throughout the interwar period.
Nostalgia and belonging
Authors: Pocock Celmara
Published: May 2015

Henry George Lamond is no longer a household name, but he was once popular and widely known in Australia and overseas. An extremely prolific writer, he published fifteen books of fiction and non-fiction, and more than 900 essays and magazine articles in his lifetime. His essays and articles include writing in a wide range of subjects and genres, from romantic fiction to practical agricultural advice. This article concerns a small portion of Lamond’s lesser known writing, specifically his portrayals of the Whitsunday Islands and Great Barrier Reef tourism. Lamond is better known as a rural outback writer than an island writer, and this article explores how he maintained a strong outback pastoral identity even as he wrote from and about the tropical islands of the Whitsundays.
The business of myth-making
Authors: Pearce Sharyn
Published: May 2015

In just one of the many extraordinary moments during the spectacular Opening Ceremony of the 2012 London Olympic Games, thirty Mary Poppinses floated into the stadium on their umbrellas to battle a 40 foot-long inflatable Lord Voldemort. This multi-million pound extravaganza was telecast to a global audience of over one billion people, highlighting in an extremely effective manner the grandeur and eccentricities of the host nation, and featuring uniquely British icons such as Mr Bean, James Bond, The Beatles and Harry Potter, as well as those quintessential icons of Englishness, the Royal Family, double-decker red buses and the National Health Service.
PREFERENCES VS. DESIRES: DEBATING THE FUNDAMENTAL STRUCTURE OF CONATIVE STATES
Authors: Schulz Armin W.
Published: May 2015

I address an overlooked question about the structure of the cognitive/conative model of the mind that underlies much of the work in economics, psychology and philosophy: namely, whether conative states are fundamentally monistic (desire-like) or comparative (preference-like). I argue that two seemingly promising sets of theoretical considerations – namely, the structure of Rational Choice Theory, and considerations of computational efficiency – are unable to resolve this debate. Given this, I suggest that a consideration that speaks in favour of the preference-based view is the fact that it makes it easier to explain certain empirically observed patterns in decision making.
IAPT: Improving Access to Psychiatric Training. CBT delivery by junior psychiatrists in primary care is good for the service, good for training and good for patients
Authors: Moorhead Steve
Published: May 2015

The feasibility and effectiveness of trainee psychiatrists providing CBT in primary care was assessed by a triangulated procedure of service overview, trainee feedback and assessment of clinical measures. Hitherto trainees sought ‘suitable’ cases by individual request. In the primary-care setting: 82% of 11 trainees (50% previously) completed a ‘short case’ treatment within a 6-month attachment; 86% of trainees found the level of supervision ‘about right’; depression and anxiety scores for patients (n= 16) achieved statistically significant gains and showed moderate to large effect sizes. Although there was no comparator group, findings were just above the IAPT aim of a 50% recovery. Conclusions are that completion of their ‘short case’ experience within a 6-month attachment is feasible in a primary-care setting. Evidence that patients and the service also benefited demonstrates this to be good and ethical ‘business’ for the service provider. Integrating these skills into routine medical psychiatric practice may remain a later supervision need. Other training experiences including psychological treatments could initially be best met in less testing clinical encounters than those experienced in secondary care. Locally agreed formal arrangements would facilitate this and there is potential for the development of greater cross-service understanding in the longer term.
The use of CBT in dementia care: a rationale for Communication and Interaction Therapy (CAIT) and therapeutic lies
Authors: James Ian A.
Published: May 2015

At the very beginning of our lives we have similar needs, but as we get older the ways of maintaining our wellbeing will vary greatly. Quite simply, we get more different and complex as we age! Hence, attempts to both meet older people's needs and treat their psychological difficulties often require comprehensive assessments and biopsychosocial formulations. It is relevant to note that many of the latter formulations are informed by CBT theory, even when dealing with people presenting with dementia and challenging behaviour. Despite the conceptual complexities, there is increasing evidence to suggest that the most effective interventions for this ‘challenging’ population are basic communication strategies. This paper outlines the key principles of effective communication under the heading of Communication and Interaction Therapy (CAIT). The concepts underpinning CAIT are illustrated via a number of case studies of people living in 24-hour care. It will be argued that an implication of this approach is the judicious use of therapeutic lies, but only as a last resort.
Peptides derived from the dependence receptor ALK are proapoptotic for ALK-positive tumors
Authors: Aubry A , Galiacy S , Ceccato L , Marchand C , Tricoire C , Lopez F , Bremner R , Racaud-Sultan C , Monsarrat B , Malecaze F , Allouche M
Published: May 2015

ALK is a receptor tyrosine kinase with an oncogenic role in various types of human malignancies. Despite constitutive activation of the kinase through gene alterations, such as chromosomal translocation, gene amplification or mutation, treatments with kinase inhibitors invariably lead to the development of resistance. Aiming to develop new tools for ALK targeting, we took advantage of our previous demonstration identifying ALK as a dependence receptor, implying that in the absence of ligand the kinase-inactive ALK triggers or enhances apoptosis. Here, we synthesized peptides mimicking the proapoptotic domain of ALK and investigated their biological effects on tumor cells. We found that an ALK-derived peptide of 36 amino acids (P36) was cytotoxic for ALK-positive anaplastic large-cell lymphoma and neuroblastoma cell lines. In contrast, ALK-negative tumor cells and normal peripheral blood mononuclear cells were insensitive to P36. The cytotoxic effect was due to caspase-dependent apoptosis and required N-myristoylation of the peptide. Two P36-derived shorter peptides as well as a cyclic peptide also induced apoptosis. Surface plasmon resonance and mass spectrometry analysis of P36-interacting proteins from two responsive cell lines, Cost lymphoma and SH-SY5Y neuroblastoma, uncovered partners that could involve p53-dependent signaling and pre-mRNA splicing. Furthermore, siRNA-mediated knockdown of p53 rescued these cells from P36-induced apoptosis. Finally, we observed that a treatment combining P36 with the ALK-specific inhibitor crizotinib resulted in additive cytotoxicity. Therefore, ALK-derived peptides could represent a novel targeted therapy for ALK-positive tumors.
Uncoupling Neogenin association with lipid rafts promotes neuronal survival and functional recovery after stroke
Authors: Shabanzadeh A P , Tassew N G , Szydlowska K , Tymianski M , Banerjee P , Vigouroux R J , Eubanks J H , Huang L , Geraerts M , Koeberle P D , Mueller B K , Monnier P P
Published: May 2015

The dependence receptor Neogenin and its ligand, the repulsive guidance molecule a (RGMa), regulate apoptosis and axonal growth in the developing and the adult central nervous system (CNS). Here, we show that this pathway has also a critical role in neuronal death following stroke, and that providing RGMa to neurons blocks Neogenin-induced death. Interestingly, the Neogenin pro-death function following ischemic insult depends on Neogenin association with lipid rafts. Thus, a peptide that prevents Neogenin association with lipid rafts increased neuronal survival in several in vitro stroke models. In rats, a pro-survival effect was also observed in a model of ocular ischemia, as well as after middle cerebral artery occlusion (MCAO). Treatments that prevented Neogenin association with lipid rafts improved neuronal survival and the complexity of the neuronal network following occlusion of the middle artery. Toward the development of a treatment for stroke, we developed a human anti-RGMa antibody that also prevents Neogenin association with lipid rafts. We show that this antibody also protected CNS tissue from ischemic damage and that its application resulted in a significant functional improvement even when administrated 6 h after artery occlusion. Thus, our results draw attention to the role of Neogenin and lipid rafts as potential targets following stroke.
Arachidonic acid promotes skin wound healing through induction of human MSC migration by MT3-MMP-mediated fibronectin degradation
Authors: Oh S Y , Lee S-J , Jung Y H , Lee H J , Han H J
Published: May 2015

Arachidonic acid (AA) is largely released during injury, but it has not been fully studied yet how AA modulates wound repair with stem cells. Therefore, we investigated skin wound-healing effect of AA-stimulated human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in vivo and its molecular mechanism in vitro. We found that transplantation of hUCB-MSCs pre-treated with AA enhanced wound filling, re-epithelization, and angiogenesis in a mouse skin excisional wound model. AA significantly promoted hUCB-MSCs migration after a 24 h incubation, which was inhibited by the knockdown of G-protein-coupled receptor 40 (GPR40). AA activated mammalian target of rapamycin complex 2 (mTORC2) and Aktser473 through the GPR40/phosphoinositide 3-kinase (PI3K) signaling, which was responsible for the stimulation of an atypical protein kinase C (PKC) isoform, PKCζ. Subsequently, AA stimulated phosphorylation of p38 MAPK and transcription factor Sp1, and induced membrane type 3-matrix metalloproteinase (MT3-MMP)-dependent fibronectin degradation in promoting hUCB-MSCs motility. Finally, the silencing of MT3-MMP in AA-stimulated hUCB-MSCs failed to promote the repair of skin wounds owing to impaired cell motility. In conclusion, AA enhances skin wound healing through induction of hUCB-MSCs motility by MT3-MMP-mediated fibronectin degradation, which relies on GPR40-dependent mTORC2 signaling pathways.
Platelet-activating factor induces cell cycle arrest and disrupts the DNA damage response in mast cells
Authors: Puebla-Osorio N , Damiani E , Bover L , Ullrich S E
Published: May 2015

Platelet-activating factor (PAF) is a potent phospholipid modulator of inflammation that has diverse physiological and pathological functions. Previously, we demonstrated that PAF has an essential role in ultraviolet (UV)-induced immunosuppression and reduces the repair of damaged DNA, suggesting that UV-induced PAF is contributing to skin cancer initiation by inducing immune suppression and also affecting a proper DNA damage response. The exact role of PAF in modulating cell proliferation, differentiation or transformation is unclear. Here, we investigated the mechanism(s) by which PAF affects the cell cycle and impairs early DNA damage response. PAF arrests proliferation in transformed and nontransformed human mast cells by reducing the expression of cyclin-B1 and promoting the expression of p21. PAF-treated cells show a dose-dependent cell cycle arrest mainly at G2–M, and a decrease in the DNA damage response elements MCPH1/BRIT-1 and ataxia telangiectasia and rad related (ATR). In addition, PAF disrupts the localization of p-ataxia telangiectasia mutated (p-ATM), and phosphorylated-ataxia telangiectasia and rad related (p-ATR) at the site of DNA damage. Whereas the potent effect on cell cycle arrest may imply a tumor suppressor activity for PAF, the impairment of proper DNA damage response might implicate PAF as a tumor promoter. The outcome of these diverse effects may be dependent on specific cues in the microenvironment.
The p38α mitogen-activated protein kinase is a key regulator of myelination and remyelination in the CNS
Authors: Chung S-H , Biswas S , Selvaraj V , Liu X-B , Sohn J , Jiang P , Chen C , Chmilewsky F , Marzban H , Horiuchi M , Pleasure D E , Deng W
Published: May 2015

The p38α mitogen-activated protein kinase (MAPK) is one of the serine/threonine kinases regulating a variety of biological processes, including cell-type specification, differentiation and migration. Previous in vitro studies using pharmacological inhibitors suggested that p38 MAPK is essential for oligodendrocyte (OL) differentiation and myelination. To investigate the specific roles of p38α MAPK in OL development and myelination in vivo, we generated p38α conditional knockout (CKO) mice under the PLP and nerve/glial antigen 2 (NG2) gene promoters, as these genes are specifically expressed in OL progenitor cells (OPCs). Our data revealed that myelin synthesis was completely inhibited in OLs differentiated from primary OPC cultures derived from the NG2 Cre-p38α CKO mouse brains. Although an in vivo myelination defect was not obvious after gross examination of these mice, electron microscopic analysis showed that the ultrastructure of myelin bundles was severely impaired. Moreover, the onset of myelination in the corpus callosum was delayed in the knockout mice compared with p38α fl/fl control mice. A delay in OL differentiation in the central nervous system was observed with concomitant downregulation in the expression of OPC- and OL-specific genes such as Olig1 and Zfp488 during early postnatal development. OPC proliferation was not affected during this time. These data indicate that p38α is a positive regulator of OL differentiation and myelination. Unexpectedly, we observed an opposite effect of p38α on remyelination in the cuprizone-induced demyelination model. The p38α CKO mice exhibited better remyelination capability compared with p38α fl/fl mice following demyelination. The opposing roles of p38α in myelination and remyelination could be due to a strong anti-inflammatory effect of p38α or a dual reciprocal regulatory action of p38α on myelin formation during development and on remyelination after demyelination.
IPS-1 differentially induces TRAIL, BCL2, BIRC3 and PRKCE in type I interferons-dependent and -independent anticancer activity
Authors: Kumar S , Ingle H , Mishra S , Mahla R S , Kumar A , Kawai T , Akira S , Takaoka A , Raut A A , Kumar H
Published: May 2015

RIG-I-like receptors are the key cytosolic sensors for RNA viruses and induce the production of type I interferons (IFN) and pro-inflammatory cytokines through a sole adaptor IFN-β promoter stimulator-1 (IPS-1) (also known as Cardif, MAVS and VISA) in antiviral innate immunity. These sensors also have a pivotal role in anticancer activity through induction of apoptosis. However, the mechanism for their anticancer activity is poorly understood. Here, we show that anticancer vaccine adjuvant, PolyIC (primarily sensed by MDA5) and the oncolytic virus, Newcastle disease virus (NDV) (sensed by RIG-I), induce anticancer activity. The ectopic expression of IPS-1 into type I IFN-responsive and non-responsive cancer cells induces anticancer activity. PolyIC transfection and NDV infection upregulate pro-apoptotic gene TRAIL and downregulate the anti-apoptotic genes BCL2, BIRC3 and PRKCE. Furthermore, stable knockdown of IPS-1, IRF3 or IRF7 in IFN-non-responsive cancer cells show reduced anticancer activity by suppressing apoptosis via TRAIL and anti-apoptotic genes. Collectively, our study shows that IPS-1 induces anticancer activity through upregulation of pro-apoptotic gene TRAIL and downregulation of the anti-apoptotic genes BCL2, BIRC3 and PRKCE via IRF3 and IRF7 in type I IFN-dependent and -independent manners.
Inhibition of autophagy sensitizes malignant pleural mesothelioma cells to dual PI3K/mTOR inhibitors
Authors: Echeverry N , Ziltener G , Barbone D , Weder W , Stahel R A , Broaddus V C , Felley-Bosco E
Published: May 2015

Malignant pleural mesothelioma (MPM) originates in most of the cases from chronic inflammation of the mesothelium due to exposure to asbestos fibers. Given the limited effect of chemotherapy, a big effort is being made to find new treatment options. The PI3K/mTOR pathway was reported to be upregulated in MPM. We tested the cell growth inhibition properties of two dual PI3K/mTOR inhibitors NVP-BEZ235 and GDC-0980 on 19 MPM cell lines. We could identify resistant and sensitive lines; however, there was no correlation to the downregulation of PI3K/mTOR activity markers. As a result of mTOR inhibition, both drugs efficiently induced long-term autophagy but not cell death. Autophagy blockade by chloroquine in combination with the dual PI3K/mTOR inhibitors significantly induced caspase-independent cell death involving RIP1 in the sensitive cell line SPC212. Cell death in the resistant cell line Mero-82 was less pronounced, and it was not induced via RIP1-dependent mechanism, suggesting the involvement of RIP1 downstream effectors. Cell death induction was confirmed in 3D systems. Based on these results, we identify autophagy as one of the main mechanisms of cell death resistance against dual PI3K/mTOR inhibitors in MPM. As PI3K/mTOR inhibitors are under investigation in clinical trials, these results may help interpreting their outcome and suggest ways for intervention.
Myocardial MiR-30 downregulation triggered by doxorubicin drives alterations in β-adrenergic signaling and enhances apoptosis
Authors: Roca-Alonso L , Castellano L , Mills A , Dabrowska A F , Sikkel M B , Pellegrino L , Jacob J , Frampton A E , Krell J , Coombes R C , Harding S E , Lyon A R , Stebbing J
Published: May 2015

The use of anthracyclines such as doxorubicin (DOX) has improved outcome in cancer patients, yet associated risks of cardiomyopathy have limited their clinical application. DOX-associated cardiotoxicity is frequently irreversible and typically progresses to heart failure (HF) but our understanding of molecular mechanisms underlying this and essential for development of cardioprotective strategies remains largely obscure. As microRNAs (miRNAs) have been shown to play potent regulatory roles in both cardiovascular disease and cancer, we investigated miRNA changes in DOX-induced HF and the alteration of cellular processes downstream. Myocardial miRNA profiling was performed after DOX-induced injury, either via acute application to isolated cardiomyocytes or via chronic exposure in vivo, and compared with miRNA profiles from remodeled hearts following myocardial infarction. The miR-30 family was downregulated in all three models. We describe here that miR-30 act regulating the β-adrenergic pathway, where preferential β1- and β2-adrenoceptor (β1AR and β2AR) direct inhibition is combined with Giα-2 targeting for fine-tuning. Importantly, we show that miR-30 also target the pro-apoptotic gene BNIP3L/NIX. In aggregate, we demonstrate that high miR-30 levels are protective against DOX toxicity and correlate this in turn with lower reactive oxygen species generation. In addition, we identify GATA-6 as a mediator of DOX-associated reductions in miR-30 expression. In conclusion, we describe that DOX causes acute and sustained miR-30 downregulation in cardiomyocytes via GATA-6. miR-30 overexpression protects cardiac cells from DOX-induced apoptosis, and its maintenance represents a potential cardioprotective and anti-tumorigenic strategy for anthracyclines.
Mcl-1 is a key regulator of the ovarian reserve
Authors: Omari S , Waters M , Naranian T , Kim K , Perumalsamy A L , Chi M , Greenblatt E , Moley K H , Opferman J T , Jurisicova A
Published: May 2015

A majority of ovarian follicles are lost to natural death, but the disruption of factors involved in maintenance of the oocyte pool results in a further untimely follicular depletion known as premature ovarian failure. The anti-apoptotic B-cell lymphoma 2 (Bcl-2) family member myeloid cell leukemia-1 (MCL-1) has a pro-survival role in various cell types; however, its contribution to oocyte survival is unconfirmed. We present a phenotypic characterization of oocytes deficient in Mcl-1, and establish its role in maintenance of the primordial follicle (PMF) pool, growing oocyte survival and oocyte quality. Mcl-1 depletion resulted in the premature exhaustion of the ovarian reserve, characterized by early PMF loss because of activation of apoptosis. The increasingly diminished surviving cohort of growing oocytes displayed elevated markers of autophagy and mitochondrial dysfunction. Mcl-1-deficient ovulated oocytes demonstrated an increased susceptibility to cellular fragmentation with activation of the apoptotic cascade. Concomitant deletion of the pro-apoptotic Bcl-2 member Bcl-2-associated X protein (Bax) rescued the PMF phenotype and ovulated oocyte death, but did not prevent the mitochondrial dysfunction associated with Mcl-1 deficiency and could not rescue long-term breeding performance. We thus recognize MCL-1 as the essential survival factor required for conservation of the postnatal PMF pool, growing follicle survival and effective oocyte mitochondrial function.
Integrated digital inverters based on two-dimensional anisotropic ReS2 field-effect transistors
Authors: Liu Erfu , Fu Yajun , Wang Yaojia , Feng Yanqing , Liu Huimei , Wan Xiangang , Zhou Wei , Wang Baigeng , Shao Lubin , Ho Ching-Hwa , Huang Ying-Sheng , Cao Zhengyi , Wang Laiguo , Li Aidong , Zeng Junwen , Song Fengqi , Wang Xinran , Shi Yi , Yuan Hongtao , Hwang Harold Y. , Cui Yi , Miao Feng , Xing Dingyu
Published: May 2015

Semiconducting two-dimensional transition metal dichalcogenides are emerging as top candidates for post-silicon electronics. While most of them exhibit isotropic behaviour, lowering the lattice symmetry could induce anisotropic properties, which are both scientifically interesting and potentially useful. Here we present atomically thin rhenium disulfide (ReS2) flakes with unique distorted 1T structure, which exhibit in-plane anisotropic properties. We fabricated monolayer and few-layer ReS2 field-effect transistors, which exhibit competitive performance with large current on/off ratios (∼107) and low subthreshold swings (100 mV per decade). The observed anisotropic ratio along two principle axes reaches 3.1, which is the highest among all known two-dimensional semiconducting materials. Furthermore, we successfully demonstrated an integrated digital inverter with good performance by utilizing two ReS2 anisotropic field-effect transistors, suggesting the promising implementation of large-scale two-dimensional logic circuits. Our results underscore the unique properties of two-dimensional semiconducting materials with low crystal symmetry for future electronic applications.
Microwave spectroscopy of the low-filling-factor bilayer electron solid in a wide quantum well
Authors: Hatke A. T. , Liu Y. , Engel L. W. , Shayegan M. , Pfeiffer L. N. , West K. W. , Baldwin K. W.
Published: May 2015

At the low Landau filling factor termination of the fractional quantum Hall effect series, two-dimensional electron systems exhibit an insulating phase that is understood as a form of pinned Wigner solid. Here we use microwave spectroscopy to probe the transition to the insulator for a wide quantum well sample that can support single-layer or bilayer states depending on its overall carrier density. We find that the insulator exhibits a resonance which is characteristic of a bilayer solid. The resonance also reveals a pair of transitions within the solid, which are not accessible to dc transport measurements. As density is biased deeper into the bilayer solid regime, the resonance grows in specific intensity, and the transitions within the insulator disappear. These behaviours are suggestive of a picture of the insulating phase as an emulsion of liquid and solid components.
Surface lattice resonances and magneto-optical response in magnetic nanoparticle arrays
Authors: Kataja M. , Hakala T. K. , Julku A. , Huttunen M. J. , van Dijken S. , Törmä P.
Published: May 2015

Structuring metallic and magnetic materials on subwavelength scales allows for extreme confinement and a versatile design of electromagnetic field modes. This may be used, for example, to enhance magneto-optical responses, to control plasmonic systems using a magnetic field, or to tailor magneto-optical properties of individual nanostructures. Here we show that periodic rectangular arrays of magnetic nanoparticles display surface plasmon modes in which the two directions of the lattice are coupled by the magnetic field-controllable spin–orbit coupling in the nanoparticles. When breaking the symmetry of the lattice, we find that the optical response shows Fano-type surface lattice resonances whose frequency is determined by the periodicity orthogonal to the polarization of the incident field. In striking contrast, the magneto-optical Kerr response is controlled by the period in the parallel direction. The spectral separation of the response for longitudinal and orthogonal excitations provides versatile tuning of narrow and intense magneto-optical resonances.