bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesoscopic and Macroscopic Optoacoustic Imaging of Cancer
Authors: Taruttis Adrian , van Dam Gooitzen M. , Ntziachristos Vasilis
Published: April 2015

Optoacoustic imaging combines the rich contrast of optical methods with the resolution of ultrasound imaging. It can therefore deliver optical visualization of cancer far deeper in tissue than optical microscopy and other conventional optical imaging methods. Technological progress and novel contrast media have resulted in optoacoustic imaging being propagated to basic cancer research and in clinical translation projects. We briefly review recent technological advances, showcase the ability to resolve unique cancer biomarkers based on spectral features at different imaging scales, and highlight the imaging performance achieved in preclinical and clinical imaging applications. Cancer Res; 75(8); 1548–59. ©2015 AACR.
MAP17 (PDZKIP1) Expression Determines Sensitivity to the Proteasomal Inhibitor Bortezomib by Preventing Cytoprotective Autophagy and NFκB Activation in Breast Cancer
Authors: Muñoz-Galván Sandra , Gutierrez Gabriel , Perez Marco , Carnero Amancio
Published: April 2015

MAP17 is a small nonglycosylated membrane protein that is overexpressed in a high percentage of carcinomas. High levels of MAP17 enhance the tumorigenic properties of tumor cells by increasing oxidative stress, which is dependent on Na+-coupled cotransport. Here, we show that MAP17 is associated with proteins involved in protein degradation and that proteasome inhibition induces autophagy. To analyze whether MAP17 could also alter this process, we used the proteasome inhibitor bortezomib (Velcade, PS-341), which is approved for the treatment of multiple myeloma and mantle cell lymphoma, although it has a high rate of resistance emergence and poor efficacy in solid tumors. We provide evidence that bortezomib induces a cytoprotective effect by activating autophagy and NFκB nuclear translocation, responses that are repressed in the presence of high levels of MAP17 both in vitro and in vivo. Indeed, patients with multiple myeloma treated with bortezomib showed higher response rates and a longer time to progression associated with increased levels of MAP17 expression. The MAP17-induced sensitivity to bortezomib is dependent on the oxidative status of the cells and the activity of Na+-coupled transporters because treatment with antioxidants or the inhibitor furosemide restores the cytoprotective activity induced by bortezomib. Therefore, bortezomib induces a prosurvival response through cytoprotective autophagy and NFκB nuclear translocation, which is repressed by high levels of MAP17. We propose that the levels of MAP17 could be used as a prognostic marker to predict the response to bortezomib in hematologic malignancies and in other tissues that are not commonly responsive to the drug. Mol Cancer Ther; 14(6); 1454–65. ©2015 AACR.
Identification of Pathogenic Cardiac CD11c
+
Macrophages in Nod1-Mediated Acute Coronary Arteritis
Authors: Motomura Yoshitomo , Kanno Shunsuke , Asano Kenichi , Tanaka Masato , Hasegawa Yutaka , Katagiri Hideki , Saito Takashi , Hara Hiromitsu , Nishio Hisanori , Hara Toshiro , Yamasaki Sho
Published: April 2015

Objective—

Nod1 is an intracellular pattern recognition receptor for bacterial peptidoglycan fragments. We previously reported that a synthetic Nod1 ligand, FK565, induced acute coronary arteritis in mice similar to that of Kawasaki disease. However, the molecular mechanisms underlying this characteristic inflammation have remained elusive.

Approach and Results—

We found that CD11c
+
MHC class II
+
cells accumulated in the heart of FK565-treated mice before arteritis development. Morphological features and gene expression signatures of the cardiac CD11c
+
MHC class II
+
cells suggested that this population is closely related to macrophages, and thus, we designated them cardiac CD11c
+
macrophages. Nod1 in nonhematopoietic cells, rather than hematopoietic cells, was required for the increase of cardiac CD11c
+
macrophages and arteritis development. Among nonhematopoietic cells, cardiac endothelial cells produced a large amount of chemokines in response to FK565. Endothelial cell–specific blockade of Nod1 signaling suppressed FK565-induced expression of these chemokines, accumulation of cardiac CD11c
+
macrophages, and subsequent coronary arteritis development. We also found that CCR2
+
Ly6C
hi
inflammatory monocytes in peripheral blood supplied precursors of cardiac CD11c
+
macrophages. CCR2-deficient mice or pertussis toxin–treated mice exhibited decreased numbers of cardiac CD11c
+
macrophages and reduced arteritis.

Conclusions—

These results suggest that Ly6C
hi
monocytes are recruited to FK565-activated endothelial cells to generate cardiac CD11c
+
macrophages, which play a pivotal role in the pathogenesis of acute coronary arteritis.
Loss of Interleukin-21 Receptor Activation in Hypoxic Endothelial Cells Impairs Perfusion Recovery After Hindlimb Ischemia
Authors: Wang Tao , Cunningham Alexis , Dokun Ayotunde O. , Hazarika Surovi , Houston Kevin , Chen Lingdan , Lye R. John , Spolski Rosanne , Leonard Warren J. , Annex Brian H.
Published: April 2015

Objective—

Surgical hindlimb ischemia (HLI) in mice has become a valuable preclinical model to study peripheral arterial disease. We previously identified that the different phenotypic outcomes after HLI across inbred mouse strains is related to a region on the short arm of mouse chromosome 7. The gene coding the interleukin-21 receptor (IL-21R) lies at the peak of association in this region.

Approach and Results—

With quantitative real-time polymerase chain reaction, we found that a mouse strain with a greater ability to upregulate IL-21R after HLI had better perfusion recovery than a strain with no upregulation after HLI. Immunofluorescent staining of ischemic hindlimb tissue showed IL-21R expression on endothelial cells (ECs) from C57BL/6 mice. An EC-enriched fraction isolated from ischemic hindlimb muscle showed higher Il-21R levels than an EC-enriched fraction from nonischemic limbs. In vitro, human umbilical vein ECs showed elevated IL-21R expression after hypoxia and serum starvation. Under these conditions, IL-21 treatment increased cell viability, decreased cell apoptosis, and augmented tube formation. In vivo, either knockout
Il21r
or blocking IL-21 signaling by treating with IL-21R-Fc (fusion protein that blocks IL-21 binding to its receptor) in C57BL/6 mice resulted in less perfusion recovery after HLI. Both in vitro and in vivo modulation of the IL-21/IL-21R axis under hypoxic conditions resulted in increased signal transducer and activator of transcription 3 phosphorylation and a subsequent increase in the B-cell lymphoma leukemia-2/BCL-2–associated X protein ratio.

Conclusion—

Our data indicate that IL-21R upregulation and ligand activation in hypoxic ECs may help perfusion recovery by limiting/preventing apoptosis and favoring cell survival and angiogenesis through the signal transducer and activator of transcription 3 pathway.
Liver X Receptor Activation Promotes Polyunsaturated Fatty Acid Synthesis in Macrophages
Authors: Varin Alexis , Thomas Charles , Ishibashi Minako , Ménégaut Louise , Gautier Thomas , Trousson Amalia , Bergas Victoria , de Barros Jean Paul Pais , Narce Michel , Lobaccaro Jean Marc A. , Lagrost Laurent , Masson David
Published: April 2015

Objective—

Liver X receptors (LXRs) modulate cholesterol and fatty acid homeostasis as well as inflammation. This study aims to decipher the role of LXRs in the regulation of polyunsaturated fatty acid (PUFA) synthesis in macrophages in the context of atherosclerosis.

Approach and Results—

Transcriptomic analysis in human monocytes and macrophages was used to identify putative LXR target genes among enzymes involved in PUFA biosynthesis. In parallel, the consequences of LXR activation or LXR invalidation on PUFA synthesis and distribution were determined. Finally, we investigated the impact of LXR activation on PUFA metabolism in vivo in apolipoprotein E–deficient mice. mRNA levels of acyl-CoA synthase long-chain family member 3, fatty acid desaturases 1 and 2, and fatty acid elongase 5 were significantly increased in human macrophages after LXR agonist treatment, involving both direct and sterol responsive element binding protein-1–dependent mechanisms. Subsequently, pharmacological LXR agonist increased long chain PUFA synthesis and enhanced arachidonic acid content in the phospholipids of human macrophages. Increased fatty acid desaturases 1 and 2 and acyl-CoA synthase long-chain family member 3 mRNA levels as well as increased arachidonic acid to linoleic acid and docosahexaenoic acid to eicosapentaenoic acid ratios were also found in atheroma plaque and peritoneal foam cells from LXR agonist–treated mice. By contrast, murine LXR-deficient macrophages displayed reduced expression of fatty acid elongase 5, acyl-CoA synthase long-chain family member 3 and fatty acid desaturases 1, as well as decreased cellular levels of docosahexaenoic acid and arachidonic acid.

Conclusions—

Our results indicate that LXR activation triggers PUFA synthesis in macrophages, which results in significant alterations in the macrophage lipid composition. Moreover, we demonstrate here that LXR agonist treatment modulates PUFA metabolism in atherosclerotic arteries.
Insular Cortex Lesions, Cardiac Troponin, and Detection of Previously Unknown Atrial Fibrillation in Acute Ischemic Stroke
Authors: Scheitz Jan F. , Erdur Hebun , Haeusler Karl Georg , Audebert Heinrich J. , Roser Mattias , Laufs Ulrich , Endres Matthias , Nolte Christian H.
Published: April 2015

Background and Purpose—

Detection rates of paroxysmal atrial fibrillation (AF) after acute ischemic stroke increase with duration of ECG monitoring. To date, it is unknown which patient group may benefit most from intensive monitoring strategies. Therefore, we aimed to identify predictors of previously unknown AF during in-hospital ECG monitoring.

Methods—

All consecutive patients with imaging-confirmed ischemic stroke admitted to our tertiary care hospital from February 2011 to December 2013 were registered prospectively. Patients received continuous bedside ECG monitoring for at least 24 hours. Detection of previously unknown AF during in-hospital ECG monitoring was obtained from medical records. Patients with AF on admission ECG or known history of AF were excluded from analysis.

Results—

Among 1228 patients (median age, 73 years; median National Institutes of Health Stroke Scale, 4; 43.4% women), previously unknown AF was detected in 114 (9.3%) during a median time of continuous ECG monitoring of 3 days (interquartile range, 2–4 days). Duration of monitoring (
P
<0.01), older age (
P
<0.01), history of hypertension (
P
=0.03), insular cortex involvement (
P
<0.01), and higher high-sensitivity cardiac troponin T (
P
=0.04) on admission were independently associated with subsequent detection of AF in a multiple regression analysis. Addition of high-sensitivity cardiac troponin T, insular cortex stroke, or both to the CHADS2 score (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke [2P]) significantly improved
c
-statistics from 0.63 to 0.68 (
P
=0.01), 0.70 (
P
<0.01), and 0.72 (
P
<0.001), respectively.

Conclusions—

Insular cortex involvement, higher admission high-sensitivity cardiac troponin T, older age, hypertension, and longer monitoring are associated with new detection of AF during in-hospital ECG monitoring. Patients with higher high-sensitivity cardiac troponin T or insular cortex involvement may be candidates for prolonged ECG monitoring.
Negative Affect as a Mechanism of Exemplification Effects
Authors: Dixon Graham N.
Published: April 2015

This study explores the effect of negative exemplars on two-sided message recall and risk perception, as mediated by negative affect. In an experiment, participants were randomly assigned to an article presenting conflicting risk arguments about vaccination that included a photograph exemplifying one argument side (receiving a vaccine is risky), a photograph exemplifying the other argument side ( not receiving a vaccine is risky), or no photograph (control condition). Exemplifying the risks associated with vaccination influenced uneven recall and risk perception. Negative affect, rather than perceived argument strength, mediated these effects and was a stronger predictor of risk perception than risk argument recall, lending support to the affect heuristic. However, exemplifying the risk of not vaccinating produced null effects on affect, risk perception, and recall, despite using the same photograph. A follow-up study suggests that motivated reasoning played a role in this null finding, providing direction for future research.
Liver Disease, Systemic Inflammation, and Growth Using a Mixed Parenteral Lipid Emulsion, Containing Soybean Oil, Fish Oil, and Medium Chain Triglycerides, Compared With Soybean Oil in Parenteral Nutrition–Fed Neonatal Piglets
Authors: Turner Justine M. , Josephson Jessica , Field Catherine J. , Wizzard Pamela R. , Ball Ronald O. , Pencharz Paul B. , Wales Paul W.
Published: April 2015

Background: The optimal parenteral lipid emulsion for neonates should reduce the risk of intestinal failure–associated liver disease and inflammation, while supporting growth and development. This could be best achieved by balanced content of ω‐6 and ω‐3 polyunsaturated fatty acids (PUFAs). Using a neonatal piglet model of parenteral nutrition (PN), we compared a 100% soy oil–based emulsion (ω‐6:ω‐3 PUFA: 7:1) with a mixed lipid emulsion comprising 30% soy oil, 30% medium‐chain triglycerides, 25% olive oil, and 15% fish oil (ω‐6:ω‐3 PUFA: approximately 2.5:1) with regard to liver disease, inflammation, and fatty acid content in plasma and brain. Method: Neonatal piglets, 3–6 days old, underwent jugular catheter insertion for isonitrogenous, isocaloric PN delivery over 14 days. The IL group (n = 8) was treated with Intralipid; the ML group (n = 10) was treated with the mixed lipid (SMOFlipid). Bile flow, liver chemistry, C‐reactive protein (CRP), and PUFA content in plasma phospholipids and brain were compared. Results: Compared with the IL group, ML‐treated piglets had increased bile flow (P = .008) and lower total bilirubin (P = .001) and CRP (P = .023) concentrations. The ω‐6 long‐chain PUFA content was lower in plasma and brain for the ML group. The key ω‐3 long‐chain PUFA for neonatal development, docosahexaenoic acid (DHA), was not different between groups. Conclusion: The mixed lipid, having less ω‐6 PUFA and more ω‐3 PUFA, was able to prevent liver disease and reduce systemic inflammation in PN‐fed neonatal piglets. However, this lipid did not increase plasma or brain DHA status, which would be desirable for neonatal developmental outcomes.
Pulmonary vein isolation for persistent atrial fibrillation. Long-term results
Authors: Garcia-Villarreal Ovidio A
Published: April 2015

Background

Pulmonary vein isolation has been employed to eliminate paroxysmal atrial fibrillation. However, the long-term outcome in terms of long-standing persistent atrial fibrillation is unclear.

Methods

One hundred patients with rheumatic mitral valve disease and long-standing (>1 year) persistent atrial fibrillation were operated on between July 1998 and June 2007. Mitral valve surgery and surgical isolation (cut-and-sew) of the pulmonary veins were performed in all cases. Transthoracic echocardiography and 24-h Holter monitoring were obtained after 3 and 6 months and yearly thereafter.

Results

Early and late follow-up was 99% and 92% complete, respectively. The endpoint was freedom from atrial fibrillation. There was one (1%) hospital death. Atrial fibrillation was present in 39%, 47%, 63% and 68% of patients at 3 months, 1 year, 3 years, and 5 years after surgery, respectively. The odds ratios for recurrence of atrial fibrillation postoperatively were 1.41 (95% confidence interval 1.14–1.74), 2.17 (95% confidence interval 1.63–2.90), and 3.62 (95% confidence interval 2.44–5.38) at 1 week, 3 years, and 5 years, respectively. Actuarial freedom from atrial fibrillation was 35% at 3 years, and 30% at 5 years. A direct relationship was observed between preoperative left atrial size >6 cm and atrial fibrillation recurrence at 5 years ( p < 0.05 odds ratio = 2.5, 95% confidence interval 1.15 – 5.4).

Conclusions

No beneficial effects of simple pulmonary vein isolation for long-standing persistent atrial fibrillation concomitant with rheumatic mitral valve disease were observed. Atrial fibrillation cannot be fully treated using only pulmonary vein isolation.
Uterine cervical cancer volumetry using T2- and diffusion-weighted MR images in patients treated by primary surgery and neoadjuvant chemotherapy
Authors: Tanaka Yumiko Oishi , Okada Satoshi , Satoh Toyomi , Matsumoto Koji , Saida Tsukasa , Minami Manabu , Yoshikawa Hiroyuki
Published: April 2015

Background

Tumor volumetry with magnetic resonance imaging (MRI) is very common; however, the accuracy of such measures remains unclear, especially after treatment.

Purpose

To determine the accuracy of preoperative volume measurements of uterine cervical carcinomas resected with and without neoadjuvant chemotherapy (NAC) on T2-weighted (T2W) and diffusion-weighted (DWI) MRI.

Material and Methods

Twenty-nine consecutive patients with surgically confirmed uterine cervical carcinoma were included in this study. MRI scans were performed before preoperative treatment in 17 patients and after two courses of NAC in 12 patients. In all patients, T2W images and DWI were obtained to measure the tumor diameters. The maximum diameter of the surgical specimens was macroscopically measured. The correlation coefficients between the measured tumor size using T2W imaging and DWI and the size measured on the surgical specimens were calculated for all specimens.

Results

The correlation coefficient of the three-dimensional (3D) tumor volume measurement using T2W imaging and DWI was 0.97 in the primary surgery group and was 0.96 in the NAC group. The 3D tumor volume measurement using MRI and the measurement of the actual surgical specimen was 0.55 for T2WI and 0.48 for DWI in the primary surgery group and 0.88 for T2WI and 0.95 for DWI in the NAC group.

Conclusion

T2WI and DWI can provide accurate 3D tumor volume measurements of uterine cervical carcinomas in patients with and without preoperative chemotherapy, suggesting that tumor volumetry using 3 T MRI after uterus-preserving treatment is feasible.
Technology as movement
Authors: Dahlberg-Grundberg Michael
Published: April 2015

New communication technologies bring about new ways for political groups and movements to mobilize and organize. A consequence of this might be that established interpretations of and attitudes towards social movements may have to be revisited, for example, when it comes to their internal constitution and their modes of working. This interview case study looks at the digital activist cluster Telecomix and its interventions during the Arab Spring. The study addresses how the network used technological and communicational infrastructures and platforms and how it was organizationally affected by these. By using concepts such as ‘one media bias’, ‘media ecology’, ‘hybridity’ and ‘cognitive praxis’, the article aims to conceptualize how the identity of a movement and its technological infrastructure mutually constitute each other.
Frontline therapy of multiple myeloma
Authors: Moreau Philippe , Attal Michel , Facon Thierry
Published: April 2015

In the past decade, one of the major advances in the management of patients with symptomatic newly diagnosed multiple myeloma has been the introduction of novel agents, thalidomide, bortezomib, and lenalidomide, as part of frontline treatment in both transplant and nontransplant candidates. These drugs have markedly improved the rate of complete remission, and time to progression, progression-free survival, and overall survival have significantly increased. This article focuses on more recent frontline therapeutic approaches both in older patients, not eligible for high-dose therapy and autologous stem cell transplantation (ASCT), and in younger patients eligible for early ASCT.
Turkey at a Turning Point
Authors: Belge Murat
Published: April 2015

Turkey, like many Westernizing/modernizing societies, was for a long time ruled by an “enlightened” minority, composed of the urban intelligentsia and the bureaucracy. The military formed the backbone of this elite. From the end of the Second World War, a multiparty parliamentary system was introduced, but the regime was interrupted by military takeovers in 1960, 1971, 1980, and finally in 1997.

This pattern began to change after the elections of 2002, which saw the victory of the AKP (Justice and Development Party). The AKP emerged from the Islamist political movements of the 1970s, but came to represent a more moderate and democratic form of political Islam under the leadership of Recep Tayyip Erdoğan. This party, in power for the last twelve years, is beginning to show strong signs of establishing a majoritarian-authoritarian regime, a gain lacking in democracy. This is the new turning point Turkey faces at the moment.
Collective Disindividuation and/or Barbarism: Technics and Proletarianization
Authors: Vesco Shawna
Published: April 2015

This essay serves as an overview of Bernard Stiegler’s project by offering a critical examination of “(de)proletarianization” and the pharmakon as refracted through his writings on technics (tekhnē), and his commitment to associations such as Ars Industrialis.

I argue that in approaching the relation between society and the technical system as the very question of the pharmakon (that which is both poisonous and curative), Stiegler’s work allows ethical questions to eschew sites of transcendental judgment as well as ethical absolutes in order to instead become questions of art—of ars and of tekhnē. I then proceed with the assertion that Stiegler recognizes in our postglobal society what he calls a state of generalized proletarianization, a state in which there is a loss of knowledge on the part of individuals and collectives in terms of both savoir-faire (know-how) and savoir-vivre (knowing how to live). I then establish that his work gestures toward a “system of care” intended to cultivate new modes of individual and collective existence through what he calls “nootechnologies,” or technologies of the spirit and mind. These technologies, however, bear within them the question of the pharmakon insofar as they are made manifest through hypomnemata, or pharmacological artificial memory supports. In order to better situate the political and ethical stakes of Stiegler’s thought of (de)proletarianization, the remainder of the essay reads several of Stiegler’s models (individuation, citizenship, memory, disorientation) alongside the work of his interlocuters including Derrida, Plato, Marx, Heidegger, and Blanchot.
Comparison, Allegory, and the Address of “Global” Realism (The Part about Bolaño)
Authors: Kurnick David
Published: April 2015

Roberto Bolaño’s work repeatedly asks readers to compare various entities (continents, national literatures, ethnicities, the realms of culture and politics). The essay reads this obsessive comparativism as the first step in a totalizing aesthetic project, one tied to Bolaño’s preoccupation with the twentieth century’s supreme comparand of state crime, National Socialism. Bolaño’s seeming promotion of Nazism to mythical status in fact serves the more urgent geopolitical project of mapping a continental American history with US political power firmly at its center.

The essays reads Bolaño’s fascist preoccupation—visible from early works like the coauthored Consejos de un discípulo de Morrison a un fanático de Joyce (Advice from a Morrison disciple to a Joyce fan) and The Third Reich—in terms of Erich Auerbach’s elaboration of figura, the mode of medieval exegesis according to which Old Testament events lose none of their historical validity once they are interpreted as figures for New Testament events to come. Bolaño’s employment of this arcane hermeneutic device records the insistent geopolitical closure that has been registered across a variety of cultural realms under the name of globalization. This obscurely but palpably unified world is Bolaño’s subject in 2666, which locates an Auerbachian interpretive provocation on the geopolitical ground of the US-Mexico border (one of the most spectacularly visible dividing lines between global North and South). Bolaño’s spatializing of Auerbachian figura offers a potent model for a contemporary comparative practice, one that recognizes the necessity of mapping totality precisely in recording the geopolitical obstacles to doing so.
Muslims, Jews, and Christians: How the Bible Was Translated into Arabic
Authors: Fishbein Michael
Published: April 2015

Sidney H. Griffith’s recent book, The Bible in Arabic: The Scriptures of the “People of the Book” in the Language of Islam, discusses how the Bible was translated into Arabic, the language of Islam, but increasingly the vernacular of Jewish and Christian communities in the Middle East: When, where, and by whom was the Bible translated partially or fully into Arabic? Were such translations made from the original Hebrew and Greek, or from the Septuagint or the Syriac versions? Why did Christians, Jews, and Muslims make translations? For what purposes did they use them? How did these translations reflect the religious and intellectual life of their communities? Griffith draws carefully supported conclusions on these subjects based on his expertise as a historian of Middle Eastern Christian communities before and after the spread of Islam.
From Roots and Routes to Returns: Is There a History of Consciousness Here?
Authors: Chun Allen
Published: April 2015

This is a review essay of James Clifford’s recent book, Returns: Becoming Indigenous in the Twenty-First Century, viewed in the context of his entire trilogy. The thematic transition from roots and routes to returns is the evolution of an approach to cultural relocations and indigenous histories that parallels Clifford’s subjective shift from that of discursive observer to cultural-historical interlocutor.
Can There Be a Plausible Ethics Developed from Poststructuralist Ontology?
Authors: Altieri Charles
Published: April 2015

This essay argues that an ethics based on the demand of the other simply flees from the typical issues of traditional ethical thinking, which have to concern the self as the primary locus of response and responsibility but also have to justify what can be a demand on that self and with what degree of importance. The ethics of the other seems dangerously close to existentialist versions of authenticity. The test case is Simon Critchley’s elegantly argued Infinitely Demanding: Ethics of Commitment, Politics of Resistance. This book seems trapped into having to convert the negatives of poststructural ontology into a positive force for shaping ethical responsibility, with no positive term. Seeing Critchley’s problems sets off, by contrast, the importance of William V. Spanos’s work because he retained in his postmodernist thinking the importance of Martin Heidegger’s sense of event that provides a significant positive term for determining values.
Xrn1/Pacman affects apoptosis and regulates expression of hid and reaper
Authors: Waldron Joseph A. , Jones Christopher I. , Towler Benjamin P. , Pashler Amy L. , Grima Dominic P. , Hebbes Stephen , Crossman Samuel H. , Zabolotskaya Maria V. , Newbury Sarah F.
Published: April 2015

Programmed cell death, or apoptosis, is a highly conserved cellular process that is crucial for tissue homeostasis under normal development as well as environmental stress. Misregulation of apoptosis is linked to many developmental defects and diseases such as tumour formation, autoimmune diseases and neurological disorders. In this paper, we show a novel role for the exoribonuclease Pacman/Xrn1 in regulating apoptosis. Using Drosophila wing imaginal discs as a model system, we demonstrate that a null mutation in pacman results in small imaginal discs as well as lethality during pupation. Mutant wing discs show an increase in the number of cells undergoing apoptosis, especially in the wing pouch area. Compensatory proliferation also occurs in these mutant discs, but this is insufficient to compensate for the concurrent increase in apoptosis. The phenotypic effects of the pacman null mutation are rescued by a deletion that removes one copy of each of the pro-apoptotic genes reaper, hid and grim, demonstrating that pacman acts through this pathway. The null pacman mutation also results in a significant increase in the expression of the pro-apoptotic mRNAs, hid and reaper, with this increase mostly occurring at the post-transcriptional level, suggesting that Pacman normally targets these mRNAs for degradation. Our results uncover a novel function for the conserved exoribonuclease Pacman and suggest that this exoribonuclease is important in the regulation of apoptosis in other organisms.
Apolipoprotein CIII regulates lipoprotein-associated phospholipase A2 expression via the MAPK and NFκB pathways
Authors: Han Xiaolei , Wang Tiedong , Zhang Jifeng , Liu Xingxing , Li Zhuang , Wang Gangqi , Song Qi , Pang Daxin , Ouyang Hongsheng , Tang Xiaochun
Published: April 2015

Apolipoprotein CIII (apo CIII), a small glycoprotein that binds to the surfaces of certain lipoproteins, is associated with inflammatory and atherogenic responses in vascular cells. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been proposed as an inflammatory biomarker and potential therapeutic target for cardiovascular disease (CVD). Here, we report that apo CIII increases Lp-PLA2 mRNA and protein levels in dose- and time- dependent manner in human monocytic THP-1 cells, and the increase can be abolished by MAPK and NFκB pathway inhibitors. Lp-PLA2 inhibitor, 1-linoleoyl glycerol attenuates the inflammation induced by apo CIII. In turn, exogenous Lp-PLA2 expression upregulates apo CIII and the upregulation can be inhibited by 1-linoleoyl glycerol in HepG2 cells. Moreover, plasma Lp-PLA2 level is correlated with apo CIII expression in pig liver. In vivo, Lp-PLA2 expression in monocytes and its activity in serum were significantly increased in human apo CIII transgenic porcine models compared with wild-type pigs. Our results suggest that Lp-PLA2 and apo CIII expression level is correlated with each other in vitro and in vivo.
Optical Resolution of C2-Symmetric Racemic 1,4-Diols with o-Xylylene Structure by Chiral Resolving Agent (S)-ALBO-V
Authors: Asami Masatoshi , Zhong Lvling , Sekiguchi Naoki , Yamada Kumiko , Hiwatashi Yuya , Taniguchi Toshiro , Hosoda Naoya , Ito Suguru
Published: April 2015

Optical resolution of C2-symmetric racemic 1,4-diols, 1,2-bis(1-hydroxyalkyl)benzene, was examined using (S)-5-allyl-2-oxabicyclo[3.3.0]octene ((S)-ALBO-V) as chiral resolving agent. Diastereomeric acetals obtained from the 1,4-diols with (S)-ALBO-V were easily separated by silica-gel column chromatography. After removal of the resolving agent, both enantiomers of the 1,4-diols were obtained with high enantiomeric excesses.
A Disposable and Flexible Graphene Electrode Fabricated by Inkjet Printing of an Aqueous Surfactant-free Graphene Oxide Dispersion
Authors: Pothipor Chamari , Kungwan Nawee , Jakmunee Jaroon , Ounnunkad Kontad
Published: April 2015

Herein, the fabrication of a simple, low-cost, disposable, and flexible graphene (GP) electrochemical electrode by inkjet printing of the aqueous graphene oxide (GPO) dispersion ink was investigated. In terms of conductivity enhancement, the inkjet-printed GPO chip was chemically reduced, and exhibited high electrochemical response, reactivity, and stability. The electrode is a promising candidate for electrochemical applications.
Highly Efficient Acetalization of Carbonyl Compounds Catalyzed by Aniline–Aldehyde Resin Salts
Authors: Tanemura Kiyoshi , Suzuki Tsuneo
Published: April 2015

A mild procedures for the syntheses of ethylene acetals and dimethyl acetals from the corresponding aldehydes and ketones catalyzed by 1 mol % of aniline–aldehyde resin salts are described. This method is also useful for the synthesis of dimethyl acetals of diaryl ketones.
Interactions of Hydrophobically Random-modified and End-capped Polysulfonates with Surfactants Studied by Fluorescence Technique
Authors: Mizusaki Masanobu
Published: April 2015

The interactions of hydrophobically random-modified and end-capped poly(2-(acrylamido)-2-methylpropanesulfonate)s (PAMPSs) with the nonionic surfactant dodecyl hexa(oxyethylene) glycol monoether (C12E6) were investigated by fluorescence spectroscopic technique of labeled pyrene. The results revealed that the random-modified PAMPS interacts with C12E6 and that the intrapolymer micelle formed from the polymer gets disrupted. In contrast, the end-capped PAMPS interacts without disruption of the multipolymer aggregate formed from the polymer at a comparably low concentration range of C12E6. The conformation of the polymer–surfactant complex depends on the position of the hydrophobic group in the polymer chains.
USG Uses Stochastic Optimization to Lower Distribution Costs
Authors: David Amy , Farr David , Januszyk Ross , Diwekar Urmila
Published: April 2015

We present a case study of a large-scale stochastic optimization problem for USG, a building supply manufacturer with plants and customers throughout North America. USG seeks to minimize total delivered cost (including production and freight costs) of products in its Durock® product line, subject to capacity constraints and uncertainties in both demand and production costs. We first demonstrate that demand uncertainty, rather than production-cost uncertainty, is the main cause of month-to-month variations in total cost. We then use the chance constraint method to optimize the network, and propagate uncertainty through the cost models, applying a penalty cost for unfulfilled constraints. We show that we can reduce theoretical costs by approximately 4.8 percent by optimizing the network for the 50th percentile of demand, as compared to the base case that uses demand and cost data for a single month. We implemented the new network plan via sourcing rules in both USG’s order fulfillment system and Oracle’s advanced supply-chain planning module. Several practical delivery concerns limit the benefits realized to an amount less than the theoretical cost reductions, but savings are still considered to be substantial.
Digital publishing as the great leveller
Authors: Kats Pavel
Published: April 2015

Proverbs are a fascinating genre of cultural expression that is studied by folklorists, linguists, philologists, anthropologists, literary scholars, philosophers, logicians, and cognitive psychologists (at least). This multitude of perspectives created in turn a multitude of approaches to how proverbial collections should be organized, classified, and used. These approaches may involve criteria based on alphabetical, chronological, ethnic, geographical, functional, lexicographical, metaphorical, thematic, or stylistic (a partial list) characteristics of proverbial performances. Consequences of this variety of approaches to the classification of subject matter ranged from inconvenience caused by heterogeneous resources to personal discrepancies between scholars.

It is exactly here that digital humanities have another edge on traditional humanities. Contemporary information technologies increasingly allow to store data without commiting in advance to how it is structured when used. If in traditional publishing the order of lexicographical entries and their content is predefined, digital publishers can use such technologies as relational databases, data warehouses, semantic ontologies, or faceted search, in order to implement flexible access to data that can satisfy even most exotic research demands.

In the proposed contribution I overview traditional challenges, suggest their domain-independent analysis in the perspective of ‘the big data challenge’, and describe some present achievements and future directions.
The Shahnama Project: A digital index of illustrated manuscripts
Authors: Melville Charles
Published: April 2015

This article documents the progress of the Cambridge Shahnama Project, initiated in 1999, and some of the issues that had to be addressed in implementing its ambitious aim to provide an open access, online corpus of illustrations of scenes from the Persian Book of Kings. This epic poem, Firdausi’s Shahnama, completed in ad 1010, was copied in thousands of manuscripts that are now dispersed in collections throughout the world, many of them lavishly illustrated: together, they provide a rich base of material for studying the arts of the book in Persian culture over several centuries, and the reception of Firdausi’s poem. The focus is on the development of the database and its transformation into a website, and the experience of applying appropriate technology to research in the humanities. The article identifies several phases of the project, up to its recent success in attracting a substantial endowment that will permit the work to continue for the foreseeable future.
The Language Archive and its solutions for sustainable endangered languages corpora
Authors: Drude Sebastian , Broeder Daan , Trilsbeek Paul
Published: April 2015

Since the late 1990s, the technical group at the Max-Planck-Institute for Psycholinguistics has worked on solutions for important challenges in building sustainable data archives, in particular, how to guarantee long-time-availability of digital research data for future research.

The support for the well-known DOBES (Documentation of Endangered Languages) programme has greatly inspired and advanced this work, and lead to the ongoing development of a whole suite of tools for annotating, cataloguing and archiving multi-media data. At the core of the LAT (Language Archiving Technology) tools is the IMDI metadata schema, now being integrated into a larger network of digital resources in the European CLARIN project. The multi-media annotator ELAN (with its web-based cousin ANNEX) is now well known not only among documentary linguists.

We aim at presenting an overview of the solutions, both achieved and in development, for creating and exploiting sustainable digital data, in particular in the area of documenting languages and cultures, and their interfaces with related other developments.
A medical panorama: The Casebooks Project
Authors: Hawkins Michael , Ralley Robert , Young John
Published: April 2015

The casebooks of the fellow astrologer-physicians Simon Forman and Richard Napier, covering the period 1596–1634, are among the largest and richest medical archives in history. The Casebooks Project is making them accessible online to both specialist and non-specialist users in a way that would be completely impossible in a print edition. This paper describes the nature and significance of the archive, the challenges involved in interpreting and encoding it, and the strategies we have developed to meet those challenges. In particular, it focuses on the task of making the material comprehensible to a modern audience while remaining true to the structure and terminology of the original documents.
Fragments of an Eleventh-Century Beneventan Gradual
Authors: Planchart Alejandro Enrique
Published: April 2015

This article describes and analyzes two leaves from a mid-eleventh-century Gradual that survive today in the Franciscan Library repository in Dublin’s Trinity College Library and in the Archivo Histórico Nacional in Madrid. The fragments contain parts of the masses for St. Lawrence and for St. Martin, including introit tropes, a number of prosulas for the alleluia, and the beginnings of the prose for each mass, in Beneventan script. Despite the small amount of music and text that survives, a collation with manuscripts from Benevento and Montecassino allows us to posit that the Gradual was copied probably at but not for Montecassino, that the context of some of the pieces as cited in the extended tonary in MC 318 points to the cathedral of Capua as the place for which the Gradual was copied, and that these two leaves are virtually the only surviving monument of the Capua liturgy in the eleventh century. A number of the prosulas are apparently unica, which adds considerably to our knowledge of the repertory of prosulas south of Rome. Moreover, the notation of the proses was clearly modeled on an exemplar written in a manner used virtually nowhere else in Europe outside St. Gall and Reichenau, indicating that in some cases the Notkerian canon reached southern Italy in versions unmediated by north Italian transmission. The concordance pattern of one of the proses also indicates apparently unmediated transmission of parts of the Beneventan repertory to southern France, confirming direct contacts between Aquitaine and Benevento that have hitherto been observed only in the transmission of Aquitanian material to Italy.
Review of robot-assisted partial nephrectomy in modern practice
Authors: Potretzke Aaron M. , Weaver John , Benway Brian M.
Published: April 2015

Partial nephrectomy (PN) is currently the standard treatment for T1 renal tumors. Minimally invasive PN offers decreased blood loss, shorter length of stay, rapid convalescence, and improved cosmesis. Due to the challenges inherent in laparoscopic partial nephrectomy, its dissemination has been stifled. Robot-assisted partial nephrectomy (RAPN) offers an intuitive platform to perform minimally invasive PN. It is one of the fastest growing robotic procedures among all surgical subspecialties. RAPN continues to improve upon the oncological and functional outcomes of renal tumor extirpative therapy. Herein, we describe the surgical technique, outcomes, and complications of RAPN.
Renal functional outcomes after surgery for renal cortical tumors
Authors: Lascano Danny , Finkelstein Julia B. , DeCastro G. Joel , McKiernan James M.
Published: April 2015

Historically, radical nephrectomy represented the gold standard for the treatment of small (≤ 4cm) as well as larger renal masses.  Recently, for small renal masses, the risk of ensuing chronic kidney disease and end stage renal disease has largely favored nephron-sparing surgical techniques, mainly partial nephrectomy. In this review, we surveyed the literature on renal functional outcomes after partial nephrectomy for renal tumors. The largest randomized control trial comparing radical and partial nephrectomy failed to show a survival benefit for partial nephrectomy. With regards to overall survival, surgically induced chronic kidney disease (GFR < 60 ml/min/ 1.73m2) caused by nephrectomy might not be as deleterious as medically induced chronic kidney disease. In evaluating patients who underwent donor nephrectomy, transplant literature further validates that surgically induced reductions in GFR may not affect patient survival, unlike medically induced GFR declines.  Yet, because patients who present with a renal mass tend to be elderly with multiple comorbidities, many develop a mixed picture of medically, and surgically-induced renal disease after extirpative renal surgery.  In this population, we believe that nephron sparing surgery optimizes oncological control while protecting renal function.
Short-term low-protein diet during pregnancy alters islet area and protein content of phosphatidylinositol 3-kinase pathway in rats
Authors: SALVATIERRA CRISTIANA S.B. , REIS SÍLVIA R.L. , PESSOA ANA F.M. , SOUZA LETÍCIA M.I. DE , STOPPIGLIA LUIZ F. , VELOSO ROBERTO V. , REIS MARISE A.B. , CARNEIRO EVERARDO M. , BOSCHERO ANTONIO C. , COLODEL EDSON M. , ARANTES VANESSA C. , LATORRACA MÁRCIA Q.
Published: April 2015

The phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways mediate β cell growth, proliferation, survival and death. We investigated whether protein restriction during pregnancy alters islet morphometry or the expression and phosphorylation of several proteins involved in the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways. As controls, adult pregnant and non-pregnant rats were fed a normal-protein diet (17%). Pregnant and non-pregnant rats in the experimental groups were fed a low-protein diet (6%) for 15 days. Low protein diet during pregnancy increased serum prolactin level, reduced serum corticosterone concentration and the expression of both protein kinase B/AKT1 (AKT1) and p70 ribosomal protein S6 kinase (p70S6K), as well as the islets area, but did not alter the insulin content of pancreatic islets. Pregnancy increased the expression of the Src homology/collagen (SHC) protein and the extracellular signal-regulated kinases 1/2 (ERK1/2) independent of diet. ERK1/2 phosphorylation (pERK1/2) was similar in islets from pregnant and non-pregnant rats fed a low-protein diet, and was higher in islets from pregnant rats than in islets from non-pregnant rats fed a normal-protein diet. Thus, a short-term, low-protein diet during pregnancy was sufficient to reduce the levels of proteins in the phosphatidylinositol 3-kinase pathway and affect islet morphometry.
Antioxidant, hemolytic, antimicrobial, and cytotoxic activities of the tropical Atlantic marine zoanthid Palythoa caribaeorum
Authors: ALENCAR DANIEL B. , MELO ARTHUR A. , SILVA GISELLE C. , LIMA REBECA L. , PIRES-CAVALCANTE KELMA M.S. , CARNEIRO RÔMULO F. , RABELO ADRIANA S. , SOUSA OSCARINA V. , VIEIRA REGINE H.S.F. , VIANA FRANCISCO A. , SAMPAIO ALEXANDRE H. , SAKER-SAMPAIO SILVANA
Published: April 2015

Marine invertebrates are capable of synthesizing bioactive compounds, which may be beneficial to human health. The aim of this study was to evaluate the antioxidant, hemolytic, antimicrobial and cytotoxic activities of crude extract (70% EtOH), and dichloromethane (DCM), ethyl acetate (EtOAc), and aqueous (Aq) fractions of the marine zoanthid Palythoa caribaeorum. The phenolic compound contents of the crude extract, DCM, EtOAc and Aq fractions were 12.33, 18.17, 10.53, and 3.18 mg GAE per gram, respectively. DPPH radical scavenging activity showed slight variation. IC50 of crude extract, DCM, EtOAc and Aq fractions were 11.13, 11.25, 11.74, and 11.28 µg mL-1, respectively. Among the sample, ferrous ion chelating was the highest in crude extract (IC50 302.90 µg mL-1), followed by EtOAc, Aq, and DCM fractions with 457.77, 547.91, and 641.82 µg mL-1, respectively. Ferric-reducing antioxidant power showed optical density at about 0.5. The samples tested exhibited low hemolytic activity under 10% up to a concentration of 50 μg mL-1. No antimicrobial activity was observed against any of the tested bacterial strains. For the cytotoxic activity, LC50 of DCM, crude extract, EtOAc, and Aq were 52.10, 83.06, 86.34, and 117.45 μg mL-1, showing high toxicity.
Avaliação de genótipos de Panicum maximum Jacq. à cárie do sino e à mancha foliar
Authors: Santos Évellyn da Cunha Macêdo dos , Fernandes Celso Dornelas , Verzignassi Jaqueline Rosemeire , Jank Liana , Mallmann Guilherme , Queiróz Carolina de Arruda
Published: April 2015

Cultivares de Panicum maximumvêm apresentando danos elevados com doenças, como a cárie do sino e a mancha foliar, causadas por Tilletia ayresiie Bipolaris maydis,respectivamente. Objetivou-se, neste trabalho, avaliar a reação de genótipos desta gramínea forrageira a essas doenças. Os experimentos foram conduzidos na Embrapa Gado de Corte, em Campo Grande (MS), no período de fevereiro a julho de 2012. Avaliaram-se, semanalmente, as intensidades das doenças em 26 genótipos de P. maximum.Dentre os genótipos avaliados, houve variação de graus de resistência para a cárie do sino e para a mancha foliar. As condições ambientais de temperatura e umidade relativa favoráveis à cárie do sino foram 16ºC a 27ºC e 62% a 88% e à mancha foliar 22ºC a 27°C e 62% a 83%. A resistência à cárie do sino mostrou ser caráter herdável e o genótipo PM40 comportou-se como a testemunha suscetível, Tanzânia-1, em relação à mancha foliar. O manejo de P. maximumcom corte de uniformização mostrou-se promissor na composição das estratégias de controle para redução da intensidade da mancha foliar.