bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential psychophysiological effects of operant and cognitive behavioural treatments in women with fibromyalgia
Authors: Thieme K. , Turk D.C. , Gracely R.H. , Flor H.
Published: June 2016

Background

Determination of psychophysiological effects of operant behavioural (OBT) and cognitive behavioural treatment (CBT) for fibromyalgia patients.

Methods

One hundred and fifteen female patients randomized to OBT (N = 43), CBT (N = 42), or whole‐body infrared heat (IH) (N = 30) were compared before and after group treatment as well as at 6‐ and 12‐month follow‐ups using intent‐to‐treat analysis (12 drop‐outs). Thirty matched pain‐free controls (CON) served as reference group for the initial psychophysiological analysis. Surface electromyogram (EMG), blood pressure, heart rate (HR) and skin conductance levels (SCL) were continuously recorded during adaptation, baseline, social conflict, mental arithmetic and relaxation tasks.

Results

At baseline, fibromyalgia patients showed higher SCL and HR, lower diastolic blood pressure and EMG in comparison to controls. OBT and CBT compared to IH significantly reduced pain intensity [OBT: effect size (ES) = 1.21 CI: 0.71–1.71, CBT: ES = 1.23, CI: 0.72–1.74]. OBT increased diastolic blood pressure [ES = 1.13, CI: 0.63–1.63 and CBT reduced SCL (ES) = −0.66, CI: −1.14–0.18] 12 months after treatment. Both CBT and OBT significantly increased EMG levels (OBT: ES = 0.97, CI: 0.48–1.46, CBT: ES = 1.17, CI: 0.67–1.68). In contrast, the IH group did not show any significant changes in the psychophysiological parameters.

Conclusion

Increased diastolic blood pressure and decreased pain after OBT suggest a reactivation of baroreflex‐mechanisms in fibromyalgia and a normalization of the blood pressure and pain functional relationship. Reduced SCL following CBT may indicate reduced general arousal levels. Increased muscle tension after CBT and OBT suggest a normalization of physical parameters. The reduction in pain seems to be mediated by different psychophysiological processes, providing support for mechanism‐based treatments might be indicated for CBT and OBT.

What does this study add?

Differential physiological stress responses followed different psychological interventions.

While OBT influenced blood pressure by restoring blood pressure‐pain interaction, CBT reduced stress‐related sudomotor activity.

These results implicate specific mediating mechanisms in fibromyalgia suggesting a basis for matching based on specific patient psychophysiological features.
Functional interaction between orexin‐1 and CB1 receptors in the periaqueductal gray matter during antinociception induced by chemical stimulation of the lateral hypothalamus in rats
Authors: Esmaeili M.H. , Reisi Z. , Ezzatpanah S. , Haghparast A.
Published: June 2016

Background

Chemical stimulation of the lateral hypothalamus (LH) with carbachol induces antinociception which is antagonized by blockade of orexin receptors in some pain modulatory sites in the tail‐flick test. In this study, we evaluated the role of orexin‐1 and CB1 receptors in the periaqueductal gray matter (PAG), a critical pain modulatory site, in mediation of antinociceptive responses induced by LH stimulation in rats.

Methods

One hundred thirty‐two adult male albino Wistar rats weighing 180–250 g were unilaterally implanted with two separate cannulae into the LH and ventrolateral PAG (vlPAG). Intra‐vlPAG administration of SB334867, as a selective orexin‐1 receptor antagonist (0.5, 1.5, 5, 15 and 50 nM), or AM251, as a selective CB1 receptor antagonist (1, 3, 10, 30 and 100 nM), was performed just 5 min before carbachol (125 nM) microinjection into the LH.

Results

Our findings showed that SB334867 or AM251 administration dose dependently prevented the development of LH‐induced antinociception in rats. Treatment with two antagonists at the same time could not intensify their effects in comparison with separate administration of antagonists.

Conclusion

It seems that antinociceptive effect of intra‐LH administration of carbachol is mediated, at least partially, through the activation of orexin‐1 and CB1 receptors in the vlPAG.

Significance

This work demonstrates a pain modulatory role of the orexinergic system via the PAG in hypothalamic‐mediated analgesia suggesting that orexins can be advantageously targeted to achieve analgesia.

What does this study add?

OX1 receptor antagonist (SB334867) administration into the ventrolateral periaqueductal gray matter (vlPAG) dose dependently blocked the carbachol‐induced antinociception. CB1 receptor antagonist (AM251) microinjection in the vlPAG prevented carbachol‐induced antinociception in a dose‐dependent manner. Concurrent administration of SB334867 and AM251 into the vlPAG did not reinforce the antinociceptive responses.
Cleavage of SNAP‐25 ameliorates cancer pain in a mouse model of melanoma
Authors: Olbrich K. , Costard L. , Möser C.V. , Syhr K.M.J. , King‐Himmelreich T.S. , Wolters M.C. , Schmidtko A. , Geisslinger G. , Niederberger E.
Published: June 2016

Background

Cancer pain is associated with increased pain sensitivity to noxious (hyperalgesia) and normally innocuous (allodynia) stimuli due to activation of nociceptors by tumour‐derived mediators or tumour infiltration of nerves. The pain sensitization is accompanied by modifications in gene expression, but specifically regulated genes are largely unknown. The 25 kDa synaptosomal‐associated protein (SNAP‐25) is involved in chemical neurotransmission at the synaptic cleft. Its inhibition by Botulinum neurotoxin A (BoNT/A) has been associated with antinociceptive effects in migraine, inflammatory and neuropathic pain. However, its potential to reduce tumour‐associated pain remains to be clarified.

Methods

We applied a melanoma model of tumour pain in C57BL/6 mice and investigatedSNAP‐25 expression and regulation byqRT‐PCR, Western Blot and immunofluorescence as well as tumour‐associated mechanical allodynia with and without BoNT/A treatment.

Results

We found increasedSNAP‐25 expression in the dorsal root ganglia and the sciatic nerve. Intraplantar injection of BoNT/A induced the cleavage ofSNAP‐25 in these tissues and was associated with decreased mechanical allodynia after therapeutic treatment at early and late stages of tumour pain while the tumour size was not affected.

Conclusions

Our data indicate thatSNAP‐25 plays a role in tumour pain but has no influence on the initiation and progression of skin cancer. Its cleavage inhibits the development of allodynia in the mouse melanoma model and might be useful as new therapeutic approach for the treatment of cancer pain.

What does this study add?

SNAP‐25 is differentially regulated during melanoma‐induced tumour pain. Its cleavage by BoNT/A might be a suitable therapeutic option for tumour pain patients since tumour‐associated pain can be strongly and significantly reduced after preventive and therapeutic BoNT/A treatment, respectively.
Determination of Local Anesthetics of Amide Group in Pharmaceutical Preparations by Cyclic Voltammetry
Authors: Plotycya Serhij , Dubenska Liliya , Blazheyevskiy Mykola , Pysarevska Solomiya , Sarahman Olha
Published: June 2016

A novel voltammetric method of local anesthetics such as lidocaine, trimecaine and mepivacaine determination has been developed. The proposed method was based on the obtaining of anesthetic N‐oxides in oxidation reaction with futher reduction of reaction product. Experimental conditions affecting quantitative yield of anesthetic N‐oxides such as oxidation time, oxidant concentration and temperature were studied. This assay was found to be linear (R=0.999) over a concentration range n⋅10−6–5 ⋅ 10−5 mol L−1. Calculated LOD and LOQ were found to be 0.38 and 1.14 μg mL−1 respectively. Sensitivity of presented method is comparable with that of chromatographic method. Overall, the developed method exhibited good selectivity towards components of pharmaceuticals and biological fluids. The proposed method was successfully applied to the analysis of studied anesthetics in different pharmaceutical samples.
Carbon Aerogel as Electrode Material for Improved Direct Electron Transfer in Biosensors Incorporating Cellobiose Dehydrogenase
Authors: Fort Carmen Ioana , Ortiz Roberto , Cotet Liviu Cosmin , Danciu Virginia , Popescu Ionel Catalin , Gorton Lo
Published: June 2016

High mesoporous carbon aerogels (CA) were prepared by a sol‐gel method, followed by supercritical drying with liquid CO2and pyrolysis under inert atmosphere. The morphological and structural characteristics (surface area, pore size distribution and pore volume) of CA were examined by using N2adsorption/desorption isotherms, TEM, SEM and AFM measurements. CA, dispersed in a chitosan (Chi) solution, was immobilized on the surface of a glassy carbon (GC) electrode aiming to prepare an amperometric transducer able to improve the direct electron transfer (DET) betweenPhanerochaete chrysosporiumcellobiose dehydrogenase (PcCDH) and the electrode. The resulting GC/CA‐Chi/PcCDH biosensor was optimized with regards to the loading of CA andPcCDH, as well as pH of the buffer solution. The electroanalytical parameters of the optimized biosensor (maximum current responses (Imax), apparent Michaelis‐Menten constants (KM)) were estimated from amperometric calibration curves for lactose. The remarkably high sensitivity towards lactose (133.7±0.2 µA cm−2 mM−1) at the GC/CA‐Chi/PcCDH electrode recommends the GC/CA‐Chi electrode as an efficient transducer forPcCDH based biosensors, exploiting DET.
Evaluation of a passive gap damper to control displacements in a shaking test of a seismically isolated three‐story frame
Authors: Zargar Hamed , Ryan Keri L. , Rawlinson Taylor A. , Marshall Justin D.
Published: June 2016

Recent studies have indicated uncertainty about the performance limit states of seismically isolated buildings in very large earthquakes, especially if the isolator displacement demands exceed the seismic gap and induce pounding. Previous research has shown the benefit of providing phased supplemental damping that does not affect the isolation system response in a design event. A phased passive control device, or gap damper, was designed, fabricated, and experimentally evaluated during shake table testing of a quarter scale base‐isolated three‐story steel frame building. Identical input motions were applied to system configurations without a gap damper and with a gap damper, to directly assess the influence of the gap damper on displacement and acceleration demands. The gap damper was observed to reduce displacement demands by up to 15% relative to the isolated system without the gap damper. Superstructure floor accelerations increased substantially because of damper activation, but were limited to a peak of about 1.18 g. The gap damper reduces displacement most effectively if the ground motion contains one or more of the following characteristics: the spectral displacement increases with increasing period near the effective period of the isolation system, the motion is dominated by a single large pulse rather than multiple cycles at a consistent intensity, and the motion has a dominant component aligned with a major axis of the structure. Copyright © 2016 John Wiley & Sons, Ltd.
Assessing Intercultural Competence in Higher Education: Existing Research and Future Directions
Authors: Griffith Richard L. , Wolfeld Leah , Armon Brigitte K. , Rios Joseph , Liu Ou Lydia
Published: June 2016

The modern wave of globalization has created a demand for increased intercultural competence (ICC) in college graduates who will soon enter the 21st‐century workforce. Despite the wide attention to the concepts and assessment of ICC, few assessments meet the standards for a next‐generation assessment in areas of construct clarity, innovative item types, response processes, and validity evidence. The objectives of this report are to identify current conceptualizations of ICC, review existing assessments and their validity evidence, propose a new framework for a next‐generation ICC assessment, and discuss key assessment considerations. To summarize, we found the current state of the literature to be murky in terms of the clarity of the ICC construct. Definitions of the construct vary considerably as to whether it is a trait, skill, or performance outcome. In addition, current measurements of ICC overly rely on self‐report methods, which have a number of flaws that result in less than optimal assessment. In this paper, we propose a new framework based on a model of the social thinking process developed by Grossman and colleagues that describes the knowledge, skills, and abilities that promote success in complex social situations. From this social process model, as well as Earley and Peterson's definition of ICC (a person's capability to gather, interpret, and act upon these radically different cues to function effectively across cultural settings or in a multicultural situation), three stages are developed: approach, analyze, and act. Guided by this framework, we discuss assessment considerations such as innovative task types and multiple response formats to help translate the framework to an assessment of ICC.
Safety of micronized palmitoylethanolamide (microPEA): lack of toxicity and genotoxic potential
Authors: Nestmann Earle R.
Published: June 2016

Palmitoylethanolamide (PEA) is a natural fatty acid amide found in a variety of foods, which was initially identified in egg yolk. MicroPEA of defined particle size (0.5–10 μm) was evaluated for mutagenicity in Salmonella typhimurium, for clastogenicity/aneuploidy in cultured human lymphocytes, and for acute and subchronic rodent toxicity in the rat, following standard OECD test protocols, in accordance with Good Laboratory Practice (GLP). PEA did not induce mutations in the bacterial assay using strains TA1535, TA97a, TA98, TA100, and TA102, with or without metabolic activation, in either the plate incorporation or liquid preincubation methods. Similarly, PEA did not induce genotoxic effects in human cells treated for 3 or 24 h without metabolic activation, or for 3 h with metabolic activation. PEA was found to have an LD50 greater than the limit dose of 2000 mg/kg body weight (bw), using the OECD Acute Oral Up and Down Procedure. Doses for the 90‐day rat oral toxicity study were based on results from the preliminary 14‐day study, that is, 250, 500, and 1000 mg/kg bw/day. The No Effect Level (NOEL) in both subchronic studies was the highest dose tested.
Archaeological Evidence for Modern Coastal Uplift at Diu, Saurashtra Peninsula, India
Authors: Kázmér Miklós , Bhatt Nilesh , Ukey Vishal , Prizomwala Siddharth , Taboroši Danko , Székely Balázs
Published: June 2016

There is a tank hewn into coastal Pleistocene limestone near Diu city on the Saurashtra Peninsula of western India. Site survey and a review of similar structures worldwide provide evidence that this tank could have been used for holding fish orMurexsnails. The approximately 5 × 5 m tank is connected to the sea by a 1‐m‐deep canal; today it would be impossible to use the tank, given that not even the high spring tides can fill it. It is suggested that the Diu coast was uplifted by ∼0.5 m after the tank was hewn in the coastal platform. Since that time, the carved surfaces have been modified by coastal karst dissolution and have developed deep gouge marks. Uplift of the Diu coast raises the possibility of a major seismic event in Diu during the latter part of the last millennium.
Backfill of segmental lining – State of the art, redistribution behaviour of pea gravel, possible improvements / Tübbingbettung – Stand der Technik, Umlagerungsverhalten von Perlkies, Verbesserungspotenzial
Authors: Henzinger Michael R. , Radončić Nedim , Moritz Bernd A. , Schubert Wulf
Published: June 2016

With mechanized shield tunnelling the quality of the backfill is of significant importance for the stability of the lining. The used material affects the interaction between support and rock mass. Therefore, the choice of a proper backfilling material is of great importance for the system behaviour. Scaled model tests have been carried out investigating the relocation behaviour of pea gravel within the annular gap. The tests have shown that especially with Double shielded TBMs a distinct relocation mechanism is triggered by the regripping process. This leads to an unfavourable bedding situation immediately behind the TBM shield.

Within a numerical study the influence of an incomplete bedding situation on the section forces within the lining segments has been carried out. The simulations have shown that crack propagation is more likely in unfavourable bedding situations. Nevertheless, numerical simulations have proven that cracks within the segments denote a higher utilization level but do not directly imply an acute danger to the load‐bearing capacity. As observed in reality, the state of incomplete bedding represents the relevant load case.

A design improvement has been introduced overcoming the temporary state of a partially bedded segmental lining. Furthermore, this approach prevents a large‐scale relocation process of pea gravel within the annular gap.

Bei Schildvortrieben hat die Qualität der Ringspaltverfüllung einen wesentlichen Einfluss auf die Qualität des Tübbingausbaus. Das verwendete Bettungsmaterial beeinflusst die Interaktion Gebirge‐Tübbingausbau. Deshalb ist die Wahl eines geeigneten Materials für die Ringraumverfüllung von hoher Bedeutung für das Systemverhalten. Zur Untersuchung des Umlagerungsverhaltens von Perlkies innerhalb des Ringspalts wurden Laborversuche durchgeführt. Die Versuche zeigten, dass vor allem bei Doppelschildmaschinen eine ausgeprägte Tendenz zur Umlagerung des Perlkieses in Längsrichtung während des Umsetzvorgangs gegeben ist. In Folge dessen sind die Tübbingringe unmittelbar hinter dem Schildschwanz nur teilgebettet.

Mittels numerischer Simulationen wurde der Einfluss der unvollständigen Bettung auf die Schnittkräfte der Tübbingsegmente untersucht. Die Simulationen haben gezeigt, dass die Rissentwicklung vor allem bei ungünstigen Bettungsszenarien bevorzugt auftritt. Weiters wurde festgestellt, dass Betonrisse lediglich auf einen erhöhten Ausnutzungsgrad innerhalb der Stahlbetonfertigteile, jedoch nicht auf eine Gefährdung der Ausbautragfähigkeit hinweisen. Wie in der Realität beobachtet, repräsentiert der Zustand der unvollständigen Bettung den maßgebenden Lastfall.

Abschließend wird eine Maßnahme vorgestellt, die die temporäre Bettung gezielt verbessern soll. Zudem verhindert diese eine großräumige Umlagerung von Perlkies innerhalb des Ringspalts.
3D images for digital tunnel face documentation at TBM headings – Application at Koralmtunnel lot KAT2 / 3D‐Bilder zur digitalen Ortsbrustdokumentation bei TBM‐ Vortrieben – Anwendung beim Koralmtunnel Baulos KAT2
Authors: Gaich Andreas , Pötsch Markus
Published: June 2016

Within the scope of a research activity of ÖBB‐Infrastruktur AG (Austrian Federal Railways) improvements for tunnel face documentation during TBM tunnelling are investigated. This contribution presents an autonomous imaging unit for taking videos of the tunnel face. The unit is installed during maintenance shift in the cutter head of a hard rock TBM. While turning the cutter head, a video is taken. Simultaneously a smartphone that also controls the camera tracks the orientation of the imaging system. From the video a consistent three‐dimensional image is generated using latest algorithms from photogrammetry. The resulting 3D images are used for determining single block detachments from the tunnel face as well as quantifying the planarity in general. They serve for enhancing geological mapping including the determination of discontinuities and provide comprehensive and objective documentation information. First successful applications at Koralmtunnel lot KAT2 showed the value of this new way of documentation and measurements.

Im Rahmen einer Forschungsaktivität der ÖBB Infrastruktur AG werden Verbesserungen zur Dokumentation der Ortsbrust bei TBM‐Vortrieben untersucht. Dieser Beitrag zeigt eine autonome Aufnahmeeinheit, die Videos der Ortsbrust erfasst. Die Aufnahmeeinheit wird während der Wartungsschicht im Bohrkopf einer Hartgesteins‐Tunnelvortriebsmaschine installiert, und während einer Drehung des Bohrkopfs wird ein Video aufgenommen. Gleichzeitig zeichnet ein Smartphone, das auch die Kamera steuert, Orientierungsinformationen auf. Aus dem Video wird unter Anwendung aktueller Algorithmen der Photogrammetrie ein konsistentes dreidimensionales Bild erzeugt. Die resultierenden 3D‐Bilder werden dazu benutzt, um einzelne Ausbrüche aus der Ortsbrust sowie die Ebenheit der aufgenommenen Bereiche zu quantifizieren. Sie dienen außerdem für eine verbesserte geologische Kartierung inklusive der Bestimmung von Trennflächenorientierungen und stellen eine umfassende und objektive Dokumentation dar. Erste erfolgreiche Anwendungen beim Baulos KAT2 des Koralmtunnels zeigen den Wert dieser neuartigen Art der Dokumentation und messtechnischen Bewertung.
Increased fibrinogen levels at diagnosis are associated with adverse outcome in patients with acute myeloid leukemia
Authors: Berger Martin D. , Heini Alexander D. , Seipel Katja , Mueller Beatrice , Angelillo‐Scherrer Anne , Pabst Thomas
Published: June 2016

Increased plasma fibrinogen levels are associated with shortened overall survival (OS) in some solid tumor types. In contrast, the prognostic significance of varying fibrinogen levels in acute myeloid leukemia (AML) at diagnosis is unknown. In this study, we assessed the prognostic significance of fibrinogen levels in AML patients. In a comprehensive retrospective single‐center study, we determined the survival rates of 375 consecutive AML patients undergoing at least one cycle of intensive chemotherapy induction treatment. Patients were dichotomized between low (<4.1 g/L) and high fibrinogen levels (≥4.1 g/L) at diagnosis of AML before initiation of treatment. Subsequently, quartile ranges were applied to analyze the association of varying fibrinogen levels on survival. We observed that the rates of complete remission, early death, and admission to intensive care unit were equal in the low versus high fibrinogen group. However, OS was significantly better in the low fibrinogen group (27.3 vs 13.5 months; p = 0.0009) as well as progression‐free survival (12.3 vs 7.8 months; p = 0.0076). This survival difference remained significant in the multivariate analysis (p = 0.003). Assessing quartiles of fibrinogen values, we further confirmed this observation. Our data suggest that high fibrinogen levels at diagnosis of AML are associated with unfavorable OS and progression‐free survival but not with increased mortality during induction treatment. Copyright © 2016 John Wiley & Sons, Ltd.
The impact of additional malignancies in patients diagnosed with gastrointestinal stromal tumors
Authors: Smith Myles J. , Smith Henry G. , Mahar Alyson L. , Law Calvin , Ko Yoo‐Joung
Published: June 2016

A higher incidence of additional malignancies has been described in patients diagnosed with gastrointestinal stromal tumors (GIST). This study aimed to identify risk factors for developing additional malignancies in patients diagnosed with GIST and evaluate the impact on survival. Individuals diagnosed with GIST from 2001 to2009 were identified from the SEER database. Logistic regression was used to identify predictors of additional malignancies and Cox‐proportional hazards regression used to identify predictors of survival. In the study period, 1705 cases of GIST were identified, with 181 (10.6%) patients developing additional malignancies. Colorectal cancer was the most common cancer developing within 6 months of GIST diagnosis (30%). The median time to diagnosis of a malignancy after 6 months of GIST diagnosis was 21.9 months. Older age (p < 0.0001) and extraoesophagogastric GIST (p = 0.0027) were significant prognostic factors associated with additional malignancies. The overall 5‐year survival was 65%, with the presence of additional malignancies within 6 months of GIST diagnosis associated with poor overall survival (54%, HR 1.55 1.05–2.3 95% CI, p = 0.04). Predictive factors of additional malignancies in patients diagnosed with GIST are increasing age and the primary disease site. Developing additional malignancies within 6 months of GIST diagnosis is associated with poorer overall survival. Targeted surveillance may be warranted in patients diagnosed with GIST that are at high risk of developing additional malignancies.
Myeloid‐derived suppressor cells as effectors of immune suppression in cancer
Authors: Pyzer Athalia Rachel , Cole Leandra , Rosenblatt Jacalyn , Avigan David E
Published: June 2016

The tumor microenvironment consists of an immunosuppressive niche created by the complex interactions between cancer cells and surrounding stromal cells. A critical component of this environment are myeloid‐derived suppressor cells (MDSCs), a heterogeneous group of immature myeloid cells arrested at different stages of differentiation and expanded in response to a variety of tumor factors. MDSCs exert diverse effects in modulating the interactions between immune effector cells and the malignant cells. An increased presence of MDSCs is associated with tumor progression, poorer outcomes, and decreased effectiveness of immunotherapeutic strategies. In this article, we will review our current understanding of the mechanisms that underlie MDSC expansion and their immune‐suppressive function. Finally, we review the preclinical studies and clinical trials that have attempted to target MDSCs, in order to improve responses to cancer therapies.
The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels
Authors: Alsina‐Sanchis Elisenda , Figueras Agnès , Lahiguera Álvaro , Vidal August , Casanovas Oriol , Graupera Mariona , Villanueva Alberto , Viñals Francesc
Published: June 2016

In a search for new therapeutic targets for treating epithelial ovarian cancer, we analyzed the Transforming Growth Factor Beta (TGFβ) signaling pathway in these tumors. Using a TMA with patient samples we found high Smad2 phosphorylation in ovarian cancer tumoral cells, independently of tumor subtype (high‐grade serous or endometrioid). To evaluate the impact of TGFβ receptor inhibition on tumoral growth, we used different models of human ovarian cancer orthotopically grown in nude mice (OVAs). Treatment with a TGFβRI&II dual inhibitor, LY2109761, caused a significant reduction in tumor size in all these models, affecting cell proliferation rate. We identified Insulin Growth Factor (IGF)1 receptor as the signal positively regulated by TGFβ implicated in ovarian tumor cell proliferation. Inhibition of IGF1R activity by treatment with a blocker antibody (IMC‐A12) or with a tyrosine kinase inhibitor (linsitinib) inhibited ovarian tumoral growth in vivo. When IGF1R levels were decreased by shRNA treatment, LY2109761 lost its capacity to block tumoral ovarian cell proliferation. At the molecular level TGFβ induced mRNA IGF1R levels. Overall, our results suggest an important role for the TGFβ signaling pathway in ovarian tumor cell growth through the control of IGF1R signaling pathway. Moreover, it identifies anti‐TGFβ inhibitors as being of potential use in new therapies for ovarian cancer patients as an alternative to IGF1R inhibition.
Targeting atypical protein kinase C iota reduces viability in glioblastoma stem‐like cells via a notch signaling mechanism
Authors: Phillips Emma , Lang Verena , Bohlen Jonathan , Bethke Frederic , Puccio Laura , Tichy Diana , Herold‐Mende Christel , Hielscher Thomas , Lichter Peter , Goidts Violaine
Published: June 2016

In a previous study, Protein Kinase C iota (PRKCI) emerged as an important candidate gene for glioblastoma (GBM) stem‐like cell (GSC) survival. Here, we show that PKCι is overexpressed and activated in patient derived GSCs compared with normal neural stem cells and normal brain lysate, and that silencing of PRKCI in GSCs causes apoptosis, along with loss of clonogenicity and reduced proliferation. Notably, PRKCI silencing reduces tumor growth in vivo in a xenograft mouse model. PKCι has been intensively studied as a therapeutic target in non‐small cell lung cancer, resulting in the identification of an inhibitor, aurothiomalate (ATM), which disrupts the PKCι/ERK signaling axis. However, we show that, although sensitive to pharmacological inhibition via a pseudosubstrate peptide inhibitor, GSCs are much less sensitive to ATM, suggesting that PKCι acts along a different signaling axis in GSCs. Gene expression profiling of PRKCI‐silenced GSCs revealed a novel role of the Notch signaling pathway in PKCι mediated GSC survival. A proximity ligation assay showed that Notch1 and PKCι are in close proximity in GSCs. Targeting PKCι in the context of Notch signaling could be an effective way of attacking the GSC population in GBM.
Seeking a Balance: Discussion Strategies That Foster Reading With Authorial Empathy
Authors: Brett Aidan T.
Published: June 2016

This study investigates the extent to which students' use of different discussion strategies fosters a balance between attending to the technical elements of authored texts and responding empathetically. Because small‐group discussion is a common approach to literary study, the analysis focuses on two small‐group discussions of “Charlie Howard's Descent,” Mark Doty's poem about the murder of a young gay man by other young men in his community. The two discussions were parsed into episodes that were scored according to the extent that they displayed balance. Then, each student turn was analyzed in terms of the discussion strategies employed. The analysis suggests that the strategies of searching for meaning, contextualizing, and interpreting contribute to the most balanced readings. Noting author's craft can lead to overly technical readings, although it has the potential to be paired with other strategies to facilitate a more balanced discussion.
At the Intersection of Creativity and Civic Engagement: Adolescents' Literacies in Action
Authors: Bean Thomas W. , Dunkerly‐Bean Judith
Published: June 2016

The purpose of this commentary is to explore the intersection of creativity, civic engagement, and literacy instruction that takes into consideration real‐world concerns. The authors define and consider recent work on creativity and utilize Westheimer's model of citizenship to frame an example of adolescents engaged in both purposeful literacies and civic engagement in a project in which the authors are currently involved. They advocate for providing students with the opportunity to investigate global issues that matter to them while engaging in literacies to address those issues.
Constructions for Circulant and Group‐Developed Generalized Weighing Matrices
Authors: Craigen Robert , de Launey Warwick
Published: June 2016

An elementary construction yields a new class of circulant (so‐called “Butson‐type”) generalized weighing matrices, which have order and weight n2, all of whose entries are nth roots of unity, for all positive integers , where . The idea is extended to a wider class of constructions giving various group‐developed generalized weighing matrices.
The Performance of the Abbott i2000 for Measuring Serum Markers of Infectious Diseases
Authors: Wang Linchuan , Chen Wei , Yu Yan
Published: June 2016

Background

To date, there is a trend that the chemiluminescent microparticle immunoassays (CMIA) and electrochemiluminescence immunoassays (ECIA) technology gradually replacing the enzyme‐linked immunosorbent assay (ELISA). But the performance such as the limit of quantitation (LOQ), precision, linear range of CMIA, or ECIA for serum markers of infectious diseases has rarely been reported.

Methods

Using proficiency testing samples and standard materials, we confirmed the LOQ of the ELISA and the precision, linear range, LOQ, and instrument biases of the Abbott i2000 for eight serum markers. We used the Abbott i2000 and ELISAs to assess five HIV samples; the researchers were blinded to the true status of the samples.

Results

For the Abbott i2000, the coefficients of variation (CV) for the low, medium, and high concentration samples ranged from 1.06 to 12.74%, which were less than the allowable error; the linear ranges of HBsAg and HBsAb were 0.66–304.11 IU/ml and 8.16–1205.9 mIU/ml, respectively. For the Abbott i2000, the LOQs of HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, anti‐HCV, anti‐TP, and anti‐HIV were 0.026 IU/ml, 4 mIU/ml, 0.14 NCU/ml, 0.56 NCU/ml, 0.99 NCU/ml, 0.5 NCU/ml, 8.8 mIU/ml, and 1.92 NCU/ml, respectively, and these values were 0.16 IU/ml, 6.97 mIU/ml, 1.16 NCU/ml, 1.63 NCU/ml, 1.79 NCU/ml, 1.03 NCU/ml, 8.33 mIU/ml, and 1.3 NCU/ml, respectively, for the ELISA. When five HIV samples were blindly assessed, two cases were missed by the Abbott i2000 and the ELISA results were consistent with the expected results.

Conclusions

The Abbott i2000 performed significantly better than the ELISA on HBV and HCV screening; however, for anti‐TP and anti‐HIV, the ELISA remained the preferred method.
Selective hydrogenation of fatty acids and methyl esters of fatty acids to obtain fatty alcohols–a review
Authors: Sánchez María A , Torres Gerardo C , Mazzieri Vanina A , Pieck Carlos L
Published: June 2016

In this paper, a review is presented of the evolution of different catalytic systems and operating conditions used in the selective hydrogenation of acids and esters of fatty acids to obtain fatty alcohols, which have broad industrial applications in the oleochemical industry. In addition, the current status of the different technologies used industrially (Lurgi, Davy and Henkel) for obtaining fatty alcohols, as well as major global sources of raw materials for the oleochemical industry are put forward. Finally, the reaction mechanisms of the selective hydrogenation process of oleic acid and methyl oleate to obtain the corresponding unsaturated alcohol as well as the new catalysts proposed by researchers are described. © 2016 Society of Chemical Industry
Partitioning Perfect Graphs into Stars
Authors: van Bevern René , Bredereck Robert , Bulteau Laurent , Chen Jiehua , Froese Vincent , Niedermeier Rolf , Woeginger Gerhard J.
Published: June 2016

The partition of graphs into “nice” subgraphs is a central algorithmic problem with strong ties to matching theory. We study the partitioning of undirected graphs into same‐size stars, a problem known to be NP‐complete even for the case of stars on three vertices. We perform a thorough computational complexity study of the problem on subclasses of perfect graphs and identify several polynomial‐time solvable cases, for example, on interval graphs and bipartite permutation graphs, and also NP‐complete cases, for example, on grid graphs and chordal graphs.
Higher‐resolution MR elastography reveals early mechanical signatures of neuroinflammation in patients with clinically isolated syndrome
Authors: Fehlner Andreas , Behrens Janina Ruth , Streitberger Kaspar‐Josche , Papazoglou Sebastian , Braun Jürgen , Bellmann‐Strobl Judith , Ruprecht Klemens , Paul Friedemann , Würfel Jens , Sack Ingolf
Published: June 2016

Purpose

To assess if higher‐resolution magnetic resonance elastography (MRE) is a technique that can measure the in vivo mechanical properties of brain tissue and is sensitive to early signatures of brain tissue degradation in patients with clinically isolated syndrome (CIS).

Materials and Methods

Seventeen patients with CIS and 33 controls were investigated by MRE with a 3T MRI scanner. Full‐wave field data were acquired at seven drive frequencies from 30 to 60 Hz. The spatially resolved higher‐resolution maps of magnitude |G*| and phase angle φ of the complex‐valued shear modulus were obtained in addition to springpot model parameters. These parameters were spatially averaged in white matter (WM) and whole‐brain regions and correlated with clinical and radiological parameters.

Results

Spatially resolved MRE revealed that CIS reduced WM viscoelasticity, independent of imaging markers of multiple sclerosis and clinical scores. |G*| was reduced by 14% in CIS (1.4 ± 0.2 kPa vs. 1.7 ± 0.2 kPa, P < 0.001, 95% confidence interval [CI] [–0.4, –0.1] kPa), while φ (0.66 ± 0.04 vs. 0.67 ± 0.04, P = 0.65, 95% CI [–0.04, 0.02]) remained unaltered. Springpot‐based shear elasticity showed only a trend of CIS‐related reduction (3.4 ± 0.5 kPa vs. 3.7 ± 0.5 kPa, P = 0.06, 95% CI [–0.6, 0.02] kPa) in the whole brain.

Conclusion

We demonstrate that CIS leads to significantly reduced elasticity of brain parenchyma, raising the prospect of using MRE as an imaging marker for subtle and diffuse tissue damage in neuroinflammatory diseases. J. Magn. Reson. Imaging 2016;44:51–58.
Type inactivated bivalent hantavirus vaccines using dual fluorescence quantitative real‐time PCR: Establishment and evaluation
Authors: Jiang Wei , Ma Ning , Hui Qi , Chen Bo , Qiu Ye , Sun Hongliang , Li Yuhua
Published: June 2016

To establish a dual fluorescence quantitative real‐time polymerase chain reaction (DFqRT‐PCR) method for typing inactivated bivalent vaccines of Hantaan virus (HTNV, type I) and Seoul virus (SEOV, type II) found in China. Primers and probes were designed based on S segment of the Hantavirus. FAM and HEX were added to the probes for the type I and type II vaccines, respectively. The S fragments were cloned into the pMD18‐T vector to create pMD18‐T/HTNV and pMD18‐T/SEOV plasmids, respectively. The DFqRT‐PCR reaction conditions were optimized. The specificity, sensitivity, accuracy, and reproducibility of the DFqRT‐PCR method within and among batches of the samples and labs were evaluated. The sensitivity of the DFqRT‐PCR method for detecting type I and II vaccines was 4.68 × 101 copies/µL and 5 × 101 copies/µL of pMD18‐T/HTNV and pMD18‐T/SEOV, respectively. This method distinguished the hantavirus vaccines from several other virus genus and distinguished the type I and II vaccines from each other with coefficients of variation (CVs) of the intra‐ and inter‐batch assay of 0.19–0.66% and 0.09–0.69%, respectively. For bivalent inactivated vaccine, the CVs of the intra‐ and inter‐batch assays, and the intra‐ and inter‐laboratory assays were 0.06–1.82% for the samples from the same batches and different batches from the same manufacturer or the samples from the different manufacturers. The DFqRT‐PCR method was simple, fast, and sensitive for identifying and determining the inactivated hantavirus vaccine with high accuracy and reproducibility. Therefore, it can be used for quality control of hantavirus vaccines. J. Med. Virol. 89:10–16, 2017. © 2016 Wiley Periodicals, Inc.
Enterovirus but not Parvovirus B19 is associated with idiopathic dilated cardiomyopathy and endomyocardial CD3, CD68, or HLA‐DR expression
Authors: N'Guyen Yohan , Lesaffre François , Metz Damien , Tassan Sophie , Saade Yves , Boulagnon Camille , Fornes Paul , Renois Fanny , Andreoletti Laurent
Published: June 2016

We assessed Enterovirus (EV) &Parvovirus B19 (PVB19) genomes and CD3, CD68&HLA‐DR detection in dilated cardiomyopathies (DCM). EV&PVB19 genomes and CD3, CD68&HLA‐DR were detected by PCR and immunohistochemistry assays in 115 endomyocardial biopsies obtained in 13 idiopathic DCM (iDCM) and 10 explained DCM (eDCM) patients. Results were compared with those of 47 atrial surgical samples (47 surgery controls) and 22 autoptic cardiac samples (11 healthy heart controls) (2008–2014, Reims, France). EV was detected in 23.1% of iDCM patients but not in eDCM and controls (P = 0.003) (viral load 803 copies/μg). PVB19 was detected in 76.9%, 80.0%, 63.6% and 78.2% of iDCM, eDCM, healthy heart and surgery controls (P = 0.99) with a mean viral load of 413, 346, 1,428, and 71 copies/μg. CD3, CD68 or HLA‐DR were detected in 100 and 50% of EV and PVB19 “mono‐infected” iDCM patients. EV was exclusively detected in iDCM cases in association with CD3, CD68, or HLA‐DR indicating that EV could be an etiological cause in a subset of iDCM cases. By contrast the equal frequent detection of PVB19 in iDCM cases and controls without association with CD3, CD68, or HLA‐DR suggested that PVB19 could be a bystander in many DCM cases. J. Med. Virol. 89:55–63, 2017. © 2016 Wiley Periodicals, Inc.
A novel Na+‐Independent alanine‐serine‐cysteine transporter 1 inhibitor inhibits both influx and efflux of D‐Serine
Authors: Sakimura Katsuya , Nakao Kenji , Yoshikawa Masato , Suzuki Motohisa , Kimura Haruhide
Published: June 2016

NMDA receptor dysfunctions are hypothesized to underlie the pathophysiology of schizophrenia, and treatment with D‐serine (D‐Ser), an NMDA receptor coagonist, may improve the clinical symptoms of schizophrenia. Thus, upregulating the synaptic D‐Ser level is a novel strategy for schizophrenia treatment. Na+‐independent alanine‐serine‐cysteine transporter 1 (asc‐1) is a transporter responsible for regulating the extracellular D‐Ser levels in the brain. In this study, we discovered a novel asc‐1 inhibitor, (+)‐amino(1‐(3,5‐dichlorophenyl)‐3,5‐dimethyl‐1H‐pyrazol‐4‐yl)acetic acid (ACPP), and assessed its pharmacological profile. ACPP inhibited the D‐[3H]Ser uptake in human asc‐1‐expressing CHO cells and rat primary neurons with IC50 values of 0.72 ± 0.13 and 0.89 ± 0.30 μM, respectively. In accordance with the lower asc‐1 expression levels in astrocytes, ACPP did not inhibit D‐Ser uptake in rat primary astrocytes. In a microdialysis study, ACPP dose dependently decreased the extracellular D‐Ser levels in the rat hippocampus under the same conditions in which the asc‐1 inhibitor S‐methyl‐L‐cysteine (SMLC) increased it. To obtain insights into this difference, we conducted a D‐[3H]Ser efflux assay using asc‐1‐expressing CHO cells. ACPP inhibited D‐[3H]Ser efflux, whereas SMLC increased it. These results suggest that ACPP is a novel inhibitor of asc‐1. © 2016 Wiley Periodicals, Inc.
Multi‐decadal variability of soil moisture–temperature coupling over the contiguous United States modulated by Pacific and Atlantic sea surface temperatures
Authors: Ford Trent W. , Quiring Steven M. , Frauenfeld Oliver W.
Published: June 2016

Regions of strong land–atmosphere coupling are often depicted as static in time. However, the mechanisms through which the land surface impacts atmospheric conditions vary on sub‐daily to multi‐decadal timescales. Therefore, characterizing the long‐term variability of land–atmosphere interactions may provide a means of predicting when surface‐induced extreme temperature events will be more or less likely to occur. We evaluate the coupling strength between soil moisture, as represented by in situ observations and 1‐month Standardized Precipitation Index (SPI), and subsequent monthly maximum temperature (TMAX) over the contiguous United States. We find that the utility of SPI as a proxy for soil moisture anomalies is limited to the summer, as the correlations between SPI and TMAX are not significantly related in the other seasons. We examine the variability in summer SPI–TMAX coupling in four regions of the United States. In general, we find the strongest relationships between SPI and TMAX in the Southern Great Plains. However, our results demonstrate that the coupling strength varies considerably over time in most regions of the United States. The long‐term variability in SPI–TMAX coupling strength is strongly related to the Pacific Decadal Oscillation in the northwest and midwest United States, and the Atlantic Multidecadal Oscillation in the southeast United States The results of this study suggest that land–atmosphere coupling in the contiguous United States is modulated by multi‐decadal oscillations in Pacific and Atlantic sea surface temperatures.
Can significant trends be detected in surface air temperature and precipitation over South America in recent decades?
Authors: de Barros Soares Daniel , Lee Huikyo , Loikith Paul C. , Barkhordarian Armineh , Mechoso Carlos R.
Published: June 2016

Trends in near‐surface air temperature and precipitation over South America are examined for the periods 1975–2004 and 1955–2004, respectively, using multiple observational and climate model data sets. The results for observed near‐surface air temperature show an overall warming trend over much of the continent, with the largest magnitudes over central Brazil. These observed trends are found to be statistically significant using pre‐industrial control simulations from the fifth phase of the Coupled Model Intercomparison Project (CMIP5) as the baseline to estimate natural climate variability. The observed trends are compared with those obtained in natural‐only CMIP5 simulations, in which only natural forcings (i.e. volcanoes and solar variability) are included, and in historical CMIP5 simulations, in which anthropogenic forcings (i.e. changes in the atmospheric composition) are further incorporated. The historical CMIP5 simulations are more successful in capturing the observed temperature trends than the simulations with natural forcings only. It is suggested that anthropogenic warming is already evident over much of South America. Unlike the warming trends, observed precipitation trends over South America are less spatially coherent with both negative and positive values across the continent. Significant positive trends are found over South America in only one of the data sets used, and over a region that roughly encompasses the southern part of La Plata Basin (southern Brazil, Uruguay, and northeastern Argentina) in all data sets used. The historical CMIP5 simulations do not capture this feature. No firm conclusions are reached, therefore, for anthropogenic influences on precipitation changes in the period selected for study.
Virtual stress testing of fracture stability in soldiers with severely comminuted tibial fractures
Authors: Petfield Joseph L. , Hayeck Garry T. , Kopperdahl David L. , Nesti Leon J. , Keaveny Tony M. , Hsu Joseph R. ,   on Behalf of the Skeletal Trauma Research Consortium (STReC)
Published: June 2016

Virtual stress testing (VST) provides a non‐invasive estimate of the strength of a healing bone through a biomechanical analysis of a patient's computed tomography (CT) scan. We asked whether VST could improve management of patients who had a tibia fracture treated with external fixation. In a retrospective case‐control study of 65 soldier‐patients who had tibia fractures treated with an external fixator, we performed VST utilizing CT scans acquired prior to fixator removal. The strength of the healing bone and the amount of tissue damage after application of an overload were computed for various virtual loading cases. Logistic regression identified computed outcomes with the strongest association to clinical events related to nonunion within 2 months after fixator removal. Clinical events (n = 9) were associated with a low tibial strength for compression loading (p < 0.05, AUC = 0.74) or a low proportion of failed cortical bone tissue for torsional loading (p < 0.005, AUC = 0.84). Using post‐hoc thresholds of a compressive strength of four times body‐weight and a proportional of failed cortical bone tissue of 5%, the test identified all nine patients who failed clinically (100% sensitivity; 40.9% positive predictive value) and over three fourths of those (43 of 56) who progressed to successful healing (76.8% specificity; 100% negative predictive value). In this study, VST identified all patients who progressed to full, uneventful union after fixator removal; thus, we conclude that this new test has the potential to provide a quantitative, objective means of identifying tibia‐fracture patients who can safely resume weight bearing. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:805–811, 2017.