bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of compression ratio and injection timing on the performance characteristics of a diesel engine running on palm oil methyl ester
Authors: Debnath Biplab K , Saha Ujjwal K , Sahoo Niranjan
Published: March 2013

Diesel fuel has a limited resource, and concerns over environmental pollution are leading to the use of ‘bio-origin fuels’ as they are renewable and environmentally benign. Palm oil methyl ester, an esterified biofuel, has an excellent cetane number and a reasonable calorific value. Besides, palm oil methyl ester (C18.07H34.93O2) has around 11.25% of oxygen bonded in its molecular structure which increases its burning intensely. Thus, it closely resembles the behavior of diesel. However, being a fuel of different origin, the standard design limits of a diesel engine is not suitable for palm oil methyl ester. Therefore, in this work, a set of design and operational parameters are studied to find out the optimum performance of a palm oil methyl ester run diesel engine. The parameters varied are the compression ratio (CR) and injection timing (IT) along with load in a variable compression ratio diesel engine. The palm oil methyl ester run engine is investigated for its performance, combustion and emission characteristics. The combination of CR = 18 and IT = 20°BTDC improves the efficiency by 8% and cuts the exhaust gas temperature by 5%. Moreover, the palm oil methyl ester run engine lowers the ignition delay which further gets reduced by 7% and 12% with CR augmentation and IT retardation, respectively. The increase in CR trims down carbon monoxide by 40%, nitrogen oxides by 46% and hydrocarbon by 40%; however, it increases carbon dioxide emission by 19%. The IT retardation reduces the carbon dioxide emission by 16%.
Relevance or ‘relevate’? How university business schools can add value through reflexively learning from strategic partnerships with business
Authors: Paton Steve , Chia Robert , Burt George
Published: March 2013

Much has been debated about the perceived relevance/irrelevance of business schools in addressing business needs with some suggesting that academic research is not applicable to practice. We contribute by claiming the debate is itself somewhat misplaced and the real task of business schools is to instil the art of ‘relevating’ the seemingly irrelevant in order to prepare managers for the challenges they face. Paradoxically, we contend that in relentlessly pursuing scholarship, academics can make a valuable contribution to practice by offering counterintuitive viewpoints that challenge business mindsets. Ironically, value-adding contributions to practice are best made when academia resists the seductive tendency to capitulate to the immediate demands of the client. For it is only by challenging conventional wisdom and expectations and thereby creating dissonance in the minds of managers, that new and unthought avenues of action may be opened up for consideration. We illustrate this by examining the experiences of a partnership between a multinational corporation and a university in the United Kingdom where the executive education programme was carried out using action learning techniques while encouraging reflexivity in practice.
Personal attitudes, perceived social norms, and health-risk behavior among female adolescents with chronic medical conditions
Authors: Kunz Jennifer H , Greenley Rachel N , Mussatto Kathleen A , Roth-Wojcicki Betsy , Miller Tami , Freeman Mary E , Lerand Sarah
Published: March 2013

To examine whether perceived peer/parent norms or personal beliefs about adolescent substance use influence substance use among female adolescents with chronic medical conditions. Sixty-eight females reported on substance use, personal beliefs, and perceived peer/parent norms. Personal beliefs and perceived peer/parent norms were associated with adolescent’s current and future substance use. Although perceived peer norms accounted for variance in current substance use, only personal beliefs accounted for variance in future alcohol use. Targeting perceived peer norms may be effective for intervention efforts among adolescents endorsing current substance use, whereas alcohol use prevention efforts should target personal beliefs.
Metadiscourse in English and Chinese research article introductions
Authors: Kim Loi Chek , Lim Jason Miin-Hwa
Published: March 2013

The present study examines the use of metadiscourse in English and Chinese research article introductions in the field of educational psychology. The corpus for this study comprises 40 introductions of research articles – 20 Chinese and 20 English – in the field of educational psychology. Hyland’s (2004) model of metadiscourse has been employed as the analytical framework for the present study. The similarities and differences in the use of metadiscourse (i.e. the interactive and interactional resources) between the two sets of texts are looked at from a socio-cultural point of view. The findings of the present study provide some insights into the teaching and learning of academic English writing for Chinese ESL (English as a Second Language) students.
Rationalism and tradition: The Popper–Oakeshott conversation
Authors: Jacobs Struan , Tregenza Ian
Published: March 2013

In 1948 Karl Popper sent a copy of his paper, ‘Utopia and Violence’, to Michael Oakeshott. Popper had recently read Oakeshott’s essay ‘Rationalism in Politics’, appreciating its relevance to views he had expressed in The Open Society. Oakeshott wrote to Popper at some length, explaining his thoughts about reason, tradition and kindred matters, to which Popper responded. This paper reproduces these letters and discusses them with reference to pertinent writings of Popper and Oakeshott. While showing there was much common ground between the two men and that they significantly influenced each other, the writings reveal important differences over the role of reason and tradition in social and political life.
Serum soluble receptor for advanced glycation end products (sRAGE) is independently associated with cigarette smoking in non-diabetic healthy subjects
Authors: Biswas Subrata K , Mudi Sonchita R , Mollah Forhadul H , Bierhaus Angelika , Arslan M Iqbal
Published: March 2013

This study was designed to explore the relationship between serum levels of soluble receptor for advanced glycation end products (sRAGE) and cigarette smoking in non-diabetic healthy subjects. A total of 98 non-diabetic, otherwise healthy male subjects were recruited. A fasting blood sample and medical history including detail history of cigarette smoking was collected. The serum sRAGE levels were found significantly higher ( p=0.002) in cigarette smokers (1475±422 pg/ml, n=45) compared with non-smokers (1165±350 pg/ml, n=53). Moreover, among the cigarette smokers, serum sRAGE levels were found significantly correlated with number of cigarettes smoked per day (r=0.60, p<0.001). In bivariate analysis in the total population, sRAGE positively correlated with smoking habit (r=0.37, p=0.002) and negatively correlated with systolic (r=−0.32, p=0.01) and diastolic blood pressure (r=−0.36, p=0.003). However, in stepwise multivariate linear regression model, sRAGE showed a significant independent association with smoking habit (b=0.32, p=0.007, R2=0.23). In conclusion, this study for the first time shows a significant elevation of serum sRAGE in cigarette smokers compared with non-smokers, a strong correlation between sRAGE and number of cigarettes smoked per day and an independent association of sRAGE with smoking habit in non-diabetic healthy subjects.
Failed back surgery syndrome – definition, epidemiology and demographics
Authors: Thomson Simon
Published: March 2013

Failed back surgery syndrome is an unhelpful term that hides the true issues concerning the mechanism of pain and subsequent therapies that patients with chronic radicular neuropathic pain are exposed to. Patients with chronic radicular neuropathic pain who have had previous spinal surgery are numerous and comparable in prevalence and incidence to other pain associated diseases such as rheumatoid arthritis but with higher annual costs. Better recognition of this patient group with the effective recognition and multi-disciplinary care aimed at achieving best patient and societal outcomes is required.
An Exploration of Cultural Sensitivity
Authors: Jones Laura , Brookes Michael , Shuker Richard
Published: March 2013

In seeking to provide a custodial therapeutic environment able to meet the diverse needs of every prisoner, an understanding of the background and cultural heritage of each individual is an essential component of a comprehensive assessment, case formulation, and therapeutic engagement. It is especially important for prisoners whose historical, systemic, social, and familial backgrounds deviate from those of the White British majority. This study, through qualitative interviews, explored the experiences of eight randomly selected Black or Minority Ethnic (BME) prisoners (within this study this refers to prisoners who did not identify themselves as being White British1) who had been engaged in therapy for a minimum of 12 months, to determine how culturally sensitive HMP Grendon, as a therapeutic community prison, was to their culture and backgrounds. Transcripts were analyzed using thematic analysis. The results indicated that Grendon’s BME prisoners experienced a lack of cultural sensitivity when engaging with the therapeutic process. Five main themes emerged: therapy and cultural values; relating to others; cultural competency; cultural understanding/awareness; and responses to experiences. Ways identified to improve this include increased staff awareness and providing increased opportunities for BME prisoners to share their experiences.
Recovery in Scotland
Authors: Smith-Merry Jennifer , Sturdy Steve
Published: March 2013

“Recovery” has become a key element in Scottish mental health policy and practice, despite continuing uncertainty over just what is meant by the term. This article draws on social movement theory to explore the processes underlying the growth of recovery in Scotland. Based on documentary analysis and semi-structured interviews with key actors, it looks at the emergence of a “recovery movement” in Scotland and in particular at how that movement articulated a “recovery frame” that subsequently came to inform policy and practice. It then reflects on the dilemmas posed by this success, as the recovery movement expanded to intersect with state agencies and the recovery frame was adapted to accommodate the needs of government policy. It concludes that the future of the recovery movement in Scotland will depend on its ability to maintain a sufficiently broad and inclusive framing of recovery even as it becomes associated with specific policies and practice.
Phenomenological Pedagogy in Higher Education of Mental Health Workers
Authors: Bongaardt Rob , Frøyen Gro , Tangvald-Pedersen Olav
Published: March 2013

This article describes the use of phenomenological pedagogy in the higher education of mental health workers. The mental health field is an immensely complex professional field. To create access, the conventional education of mental health professionals compartmentalizes the field according to traditional professional boundaries. Personal–professional expertise and user preference are thereby lost. Such personal experience is privileged in a pedagogy based on Giorgi’s descriptive phenomenological method. Students learn systematically to describe a mental health phenomenon of their interest and reflect on this using each other’s professional insights as well as relevant research literature. Phenomenological description and reflection are repeated several times in the curriculum. Kegan’s subject–object theory of adult development explains how this repetition may support transformation of insight in rather than an accumulation of information about mental health work. The complexity of the mental health field thus emerges as a source of knowledge to exploit rather than merely a rugged landscape to navigate.
Inactivation of TP53 correlates with disease progression and low miR-34a expression in previously treated chronic lymphocytic leukemia patients
Authors: Dufour Annika , Palermo Giuseppe , Zellmeier Evelyn , Mellert Gudrun , Duchateau-Nguyen Guillemette , Schneider Stephanie , Benthaus Tobias , Kakadia Purvi M. , Spiekermann Karsten , Hiddemann Wolfgang , Braess Jan , Truong Sim , Patten Nancy , Wu Lin , Lohmann Sabine , Dornan David , GuhaThakurta Debraj , Yeh Ru-Fang , Salogub Galina , Solal-Celigny Philippe , Dmoszynska Anna , Robak Tadeusz , Montillo Marco , Catalano John , Geisler Christian H. , Weisser Martin , Bohlander Stefan K.
Published: March 2013

Key Points

Only a complete disruption of TP53 function increases the risk for disease progression in previously treated CLL patients. MiR-34a expression significantly correlates with the predicted TP53 activity in previously treated CLL patients with TP53 abnormalities.
SDM-Assist software to design site-directed mutagenesis primers introducing “silent” restriction sites
Authors: Karnik Abhijit , Karnik Rucha , Grefen Christopher
Published: March 2013

Background

Over the past decades site-directed mutagenesis (SDM) has become an indispensable tool for biological structure-function studies. In principle, SDM uses modified primer pairs in a PCR reaction to introduce a mutation in a cDNA insert. DpnI digestion of the reaction mixture is used to eliminate template copies before amplification in E. coli; however, this process is inefficient resulting in un-mutated clones which can only be distinguished from mutant clones by sequencing.

Results

We have developed a program - ‘SDM-Assist’ which creates SDM primers adding a specific identifier: through additional silent mutations a restriction site is included or a previous one removed which allows for highly efficient identification of ‘mutated clones’ by a simple restriction digest.

Conclusions

The direct identification of SDM clones will save time and money for researchers. SDM-Assist also scores the primers based on factors such as Tm, GC content and secondary structure allowing for simplified selection of optimal primer pairs.
Exome profiling of primary, metastatic and recurrent ovarian carcinomas in a BRCA1-positive patient
Authors: Zhang Jian , Shi Yuhao , Lalonde Emilie , Li Lili , Cavallone Luca , Ferenczy Alex , Gotlieb Walter H , Foulkes William D , Majewski Jacek
Published: March 2013

Background

Ovarian carcinoma is a common, and often deadly, gynecological cancer. Mutations in BRCA1 and BRCA2 genes are present in at least a fifth of patients. Uncovering other genes that become mutated subsequent to BRCA1/BRCA2 inactivation during cancer development will be helpful for more effective treatments.

Methods

We performed exome sequencing on the blood, primary tumor, omental metastasis and recurrence following therapy with carboplatin and paclitaxel, from a patient carrying a BRCA1 S1841R mutation.

Results

We observed loss of heterozygosity in the BRCA1 mutation in the primary and subsequent tumors, and somatic mutations in the TP53 and NF1 genes were identified, suggesting their role along with BRCA1 driving the tumor development. Notably, we show that exome sequencing is effective in detecting large chromosomal rearrangements such as deletions and amplifications in cancer. We found that a large deletion was present in the three tumors in the regions containing BRCA1, TP53, and NF1 mutations, and an amplification in the regions containing MYC. We did not observe the emergence of any new mutations among tumors from diagnosis to relapse after chemotherapy, suggesting that mutations already present in the primary tumor contributed to metastases and chemotherapy resistance.

Conclusions

Our findings suggest that exome sequencing of matched samples from one patient is a powerful method of detecting somatic mutations and prioritizing their potential role in the development of the disease.
Resveratrol abrogates the Temozolomide-induced G2 arrest leading to mitotic catastrophe and reinforces the Temozolomide-induced senescence in glioma cells
Authors: Filippi-Chiela Eduardo C , Thomé Marcos Paulo , Bueno e Silva Mardja Manssur , Pelegrini Alessandra Luíza , Ledur Pitia Flores , Garicochea Bernardo , Zamin Lauren L , Lenz Guido
Published: March 2013

Background

Temozolomide (TMZ) is the most widely used drug to treat glioblastoma (GBM), which is the most common and aggressive primary tumor of the Central Nervous System and one of the hardest challenges in oncotherapy. TMZ is an alkylating agent that induces autophagy, apoptosis and senescence in GBM cells. However, therapy with TMZ increases survival after diagnosis only from 12 to 14.4 months, making the development of combined therapies to treat GBM fundamental. One candidate for GBM therapy is Resveratrol (Rsv), which has additive toxicity with TMZ in several glioma cells in vitro and in vivo. However, the mechanism of Rsv and TMZ additive toxicity, which is the aim of the present work, is not clear, especially concerning cell cycle dynamics and long term effects.

Methods

Glioma cell lines were treated with Rsv and TMZ, alone or in combinations, and the induction and the role of autophagy, apoptosis, cell cycle dynamics, protein expression and phosphorylation status were measured. We further evaluated the long term senescence induction and clonogenic capacity.

Results

As expected, temozolomide caused a G2 cell cycle arrest and extensive DNA damage response. Rsv did not reduced this response, even increasing pATM, pChk2 and gammaH2Ax levels, but abrogated the temozolomide-induced G2 arrest, increasing levels of cyclin B and pRb(S807/811) and reducing levels of pWee1(S642) and pCdk1(Y15). This suggests a cellular state of forced passage through G2 checkpoint despite large DNA damage, a scenario that may produce mitotic catastrophe. Indeed, the proportion of cells with high nuclear irregularity increased from 6 to 26% in 48 h after cotreatment. At a long term, a reduction in clonogenic capacity was observed, accompanied by a large induction of senescence.

Conclusion

The presence of Rsv forces cells treated with TMZ through mitosis leading to mitotic catastrophe and senescence, reducing the clonogenic capacity of glioma cells and increasing the chronic effects of temozolomide.
The effect of Lycium barbarum on spinal cord injury, particularly its relationship with M1 and M2 macrophage in rats
Authors: Zhang Yu-Kai , Wang Jian , Liu Ling , Chang Raymond Chuen-Chung , So Kwok-Fai , Ju Gong
Published: March 2013

Background

Our past researches suggested thatL. barbarumexhibits direct neuroprotective and immune regulatory effects on the central nervous system, which are highly related to the events involved in the spinal cord injury, but not yet been investigated. Immune responses play an important role in the development of the pathology after secondary injury, particularly the M1 and M2 types of macrophage, on which special emphasis was laid in this study.

Methods

In our previous studiesL. barbarumwas administrated orally from 7 days before the injury to ensure a stabilized concentration in the blood. For clinical application,L. barbarumcan only be administered after the injury. Therefore, both pre-injury and post-injury administration protocols were compared.In vivoandin vitrostudies were conducted and analyzed immunohistochemically, including Western blotting.

Results

The lesion size in the pre-treated group was much larger than that in the post-treated group. To explain this difference, we first studied the effect ofL. barbarumon astrocytes, which forms the glial scar encircling the lesion.L. barbarumdid not significantly affect the astrocytes. Then we studied the effect ofL. barbarumon microglia/macrophages, particularly the M1 and M2 polarization. After spinal cord injury, the deleterious M1 cells dominant the early period, whereas the beneficial M2 cells dominate later. We found that in the pre-treated groupL. barbarumsignificantly enhanced the expression of M1 cells and suppressed that of M2 cells, while in the post-treated group LBP markedly promoted the activity of M2 cells. This explained the difference between the pre- and post-treated groups.

Conclusions

Lycium barbarumhas been wildly accepted to have beneficial effects in various central nervous system diseases. Our finding of deleterious effect of LBP administered at early period of spinal cord injury, indicates that its application should be avoided. The substantial beneficial effect of LBP when administered at later stage has an important impact for clinical application.
Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events
Authors: Shahabi Vafa , Berman David , Chasalow Scott D , Wang Lisu , Tsuchihashi Zenta , Hu Beihong , Panting Lisa , Jure-Kunkel Maria , Ji Rui-Ru
Published: March 2013

Background

Treatment with ipilimumab, a fully human anti-CTLA-4 antibody approved for the treatment of advanced melanoma, is associated with some immune-related adverse events (irAEs) such as colitis (gastrointestinal irAE, or GI irAE) and skin rash, which are managed by treatment guidelines. Nevertheless, predictive biomarkers that can help identify patients more likely to develop these irAEs could enhance the management of these toxicities.

Methods

To identify candidate predictive biomarkers associated with GI irAEs, gene expression profiling was performed on whole blood samples from 162 advanced melanoma patients at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and CA184007). Overall, 49 patients developed Grade 2 or higher (grade 2+) GI irAEs during the course of treatment. A repeated measures analysis of variance (ANOVA) was used to evaluate the differences in mean expression levels between the GI irAE and No-GI irAE groups of patients at the three time points.

Results

In baseline samples, 27 probe sets showed differential mean expression (≥ 1.5 fold, P ≤ 0.05) between the GI irAE and No-GI irAE groups. Most of these probe sets belonged to three functional categories: immune system, cell cycle, and intracellular trafficking. Changes in gene expression over time were also characterized. In the GI irAE group, 58 and 247 probe sets had a ≥ 1.5 fold change in expression from baseline to 3 and 11 weeks after first ipilimumab dose, respectively. In particular, on-treatment expression increases of CD177 and CEACAM1, two neutrophil-activation markers, were closely associated with GI irAEs, suggesting a possible role of neutrophils in ipilimumab-associated GI irAEs. In addition, the expression of several immunoglobulin genes increased over time, with greater increases in patients with grade 2+ GI irAEs.

Conclusions

Gene expression profiling of peripheral blood, sampled before or early in the course of treatment with ipilimumab, resulted in the identification of a set of potential biomarkers that were associated with occurrence of GI irAEs. However, because of the low sensitivity of these biomarkers, they cannot be used alone to predict which patients will develop GI irAEs. Further investigation of these biomarkers in a larger patient cohort is warranted.
Development of a robust flow cytometry-based pharmacodynamic assay to detect phospho-protein signals for phosphatidylinositol 3-kinase inhibitors in multiple myeloma
Authors: Li Congfen , Takahashi Chikara , Zhang Liangxuan , Huseni Mahrukh , Stankovich Basha , Mashhedi Haider , Lee Joanna , French Dorothy , Anderson Jeff Eastham , Kim Doris , Howell Kathy , Brauer Matthew J , Kowanetz Marcin , Yan Yibing , Humke Eric , Ebens Allen , Hampton Garret , Lackner Mark R , Hegde Priti , Jia Shidong
Published: March 2013

Background

The phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in multiple myeloma (MM), a blood cancer associated with uncontrolled proliferation of bone marrow plasma cells. This study aimed to develop a robust clinical pharmacodynamic (PD) assay to measure the on-target PD effects of the selective PI3K inhibitor GDC-0941 in MM patients.

Methods

We conducted an in vitro drug wash-out study to evaluate the feasibility of biochemical approaches in measuring the phosphorylation of S6 ribosomal protein (S6), one of the commonly used PD markers for PI3K pathway inhibition. We then developed a 7-color phospho-specific flow cytometry assay, or phospho flow assay, to measure the phosphorylation state of intracellular S6 in bone marrow aspirate (BMA) and peripheral blood (PB). Integrated mean fluorescence intensity (iMFI) was used to calculate fold changes of phosphorylation. Assay sensitivity was evaluated by comparing phospho flow with Meso Scale Discovery (MSD) and immunohistochemistry (IHC) assays. Finally, a sample handling method was developed to maintain the integrity of phospho signal during sample shipping and storage to ensure clinical application.

Results

The phospho flow assay provided single-cell PD monitoring of S6 phosphorylation in tumor and surrogate cells using fixed BMA and PB, assessing pathway modulation in response to GDC-0941 with sensitivity similar to that of MSD assay. The one-shot sample fixation and handling protocol herein demonstrated exceptional preservation of protein phosphorylation. In contrast, the IHC assay was less sensitive in terms of signal quantification while the biochemical approach (MSD) was less suitable to assess PD activities due to the undesirable impact associated with cell isolation on the protein phosphorylation in tumor cells.

Conclusions

We developed a robust PD biomarker assay for the clinical evaluation of PI3K inhibitors in MM, allowing one to decipher the PD response in a relevant cell population. To our knowledge, this is the first report of an easily implemented clinical PD assay that incorporates an unbiased one-shot sample handling protocol, all (staining)-in-one (tube) phospho flow staining protocol, and an integrated modified data analysis for PD monitoring of kinase inhibitors in relevant cell populations in BMA and PB. The methods described here ensure a real-time, reliable and reproducible PD readout, which can provide information for dose selection as well as help to identify optimal combinations of targeted agents in early clinical trials.
Occurrence of congenital disorders in Swiss sheep
Authors: Greber Deborah , Doherr Marcus , Drögemüller Cord , Steiner Adrian
Published: March 2013

Background

The rates of congenital disorders in Swiss sheep were determined by a questionnaire which was sent to 3,183 members of the Swiss Sheep Breeders’ Association.

Findings

A total of 993 questionnaires were returned, giving a response rate of 31.2%. Of these, 862 questionnaires originated from farms keeping one of the predominant Swiss sheep breeds: Swiss White Alpine sheep, Brown-Headed Meat sheep, Swiss Black Brown Mountain sheep and Valais Blacknose sheep. During a 10-year-period, entropion was reported in 33.6% of the farms, brachygnathia inferior in 29.5%, abdominal/umbilical hernia in 15.9%, cryptorchidism in 10.5% and torticollis in 10.5%. The most significant difference between the four breeds (P < 0.001) occurred for entropion in Swiss White Alpine sheep and Brown-Headed Meat sheep, brachygnathia inferior in Swiss Black Brown Mountain sheep, and scrotal/inguinal hernia in Valais Blacknose sheep. The Swiss White Alpine breed showed a significantly higher animal prevalence of entropion (6.2% in 2011 and 5.5% in 2012) than other breeds (P < 0.001).

Conclusions

These findings indicate a breed-specific necessity for action, particularly regarding Swiss animal welfare legislation, especially entropion in Swiss White Alpine sheep is concerned. In general, careful selection of breeding stock is to be recommended.
THRAP3 Interacts with HELZ2 and Plays a Novel Role in Adipocyte Differentiation
Authors: Katano-Toki Akiko , Satoh Tetsurou , Tomaru Takuya , Yoshino Satoshi , Ishizuka Takahiro , Ishii Sumiyasu , Ozawa Atsushi , Shibusawa Nobuyuki , Tsuchiya Takafumi , Saito Tsugumichi , Shimizu Hiroyuki , Hashimoto Koshi , Okada Shuichi , Yamada Masanobu , Mori Masatomo
Published: March 2013

Using yeast two-hybrid screen, we previously isolated HELZ2 (helicase with zinc finger 2, transcriptional coactivator) that functions as a coregulator of peroxisome proliferator-activated receptorγ (PPARγ). To further delineate its molecular function, we here identified thyroid hormone receptor-associated protein3 (THRAP3), a putative component of the Mediator complex, as a protein stably associating with HELZ2 using immunoprecipitation coupled with mass spectrometry analyses. In immunoprecipitation assays, Thrap3 could associate with endogenous Helz2 as well as Pparg in differentiated 3T3-L1 cells. HELZ2 interacts with the serine/arginine-rich domain and Bcl2 associated transcription factor1-homologous region in THRAP3, whereas THRAP3 directly binds 2 helicase motifs in HELZ2. HELZ2 and THRAP3 synergistically augment transcriptional activation mediated by PPARγ, whereas knockdown of endogenous THRAP3 abolished the enhancement by HELZ2 in reporter assays. Thrap3, similar to Helz2, is evenly expressed in the process of adipogenic differentiation in 3T3-L1 cells. Knockdown of Thrap3 in 3T3-L1 preadipocytes using short-interfering RNA did not influence the expression of Krox20, Klf5, Cebpb, or Cebpd during early stages of adipocyte differentiation, but significantly attenuated the expression of Pparg, Cebpa, and Fabp4/aP2 and accumulation of lipid droplets. Pharmacologic activation of Pparg by troglitazone could not fully restore the differentiation of Thrap3-knockdown adipocytes. In chromatin immunoprecipitation assays, endogenous Helz2 and Thrap3 could be co-recruited, in a ligand-dependent manner, to the PPARγ-response elements in Fabp4/aP2 and Adipoq gene enhancers in differentiated 3T3-L1 cells. These findings collectively suggest that Thrap3 could play indispensable roles in terminal differentiation of adipocytes by enhancing PPARγ-mediated gene activation cooperatively with Helz2.
Minireview: Obesity and Breast Cancer: A Tale of Inflammation and Dysregulated Metabolism
Authors: Simpson Evan R. , Brown Kristy A.
Published: March 2013

In addition to the spectrum of conditions known collectively as the Metabolic Syndrome, obesity is now recognized to be associated with increased risk of several cancers including colon, endometrial, and breast cancer. Obesity and carcinogenesis share 2 characteristics in common. On the one hand, they involve inflammatory pathways, and on the other hand, they involve dysregulated metabolism. In this review we focus on postmenopausal breast cancer and discuss the metabolic and cellular mechanisms whereby obesity and breast cancer are related. Because a majority of postmenopausal breast tumors are estrogen responsive, we include a discussion of the action of obesity-related factors on estrogen formation within the breast.
Reversible thiol oxidation in the H2O2-dependent activation of the transcription factor Pap1
Authors: Calvo Isabel A. , Ayté José , Hidalgo Elena
Published: March 2013

Reversible thiol oxidation is both a mark of H2O2 toxicity and an initiator of signalling events. H2O2 sensors contain exposed and reactive cysteine residues, which become transiently oxidized as an activation mechanism. In fission yeast, the Pap1 (pombe AP-1) transcription factor has cytosolic localization, and upon H2O2 stress it undergoes post-translational modifications impairing its nuclear export; genetic evidences suggested the formation of a disulfide bond in Pap1 as a triggering activation event. Nuclear Pap1 is then recruited to about 50–80 promoters and induces an adaptation response. We have now dissected the role of all seven cysteine residues in Pap1 using genetic and proteomic techniques, and we show that four of them are required for Pap1 to be activated by H2O2 stress. Thus, mutants lacking each one of these cysteine residues display sensitivity to peroxides. Furthermore, these mutant proteins do not become oxidized by H2O2 and cannot bind to promoters or trigger the Pap1-dependent gene expression program. We also demonstrate by proteomic analysis of reduced and oxidized Pap1 that these four cysteine residues are reversibly oxidized upon H2O2 stress. Our study suggests that not only one but probably two disulfide bonds are required to promote the important conformational changes that promote Pap1 activation and nuclear accumulation.
Identification of Hydrogen-Bonded Oligomers in Associating Liquid by 1H NMR: 1-Phenyl-1-cyclohexanol
Authors: Nagatomo Shigenori , Nobuhira Megumi , Yamamura Yasuhisa , Sumita Masato , Saito Kazuya
Published: March 2013

Nonmonotonous temperature dependence, which suggests formation of closed oligomer(s) via hydrogen-bonds, is detected in heat capacity and dielectric constant of the title compound in the liquid state. The 1H NMR signal of hydroxy protons showed a temperature-dependent fine structure. Quantum-chemical calculations on oligomers of several types revealed that the fine structure is plausibly interpreted as a temperature-dependent formation/destruction of oligomers. A coherent analysis of calorimetric, FT-IR, dielectric, and 1H NMR results shows that the neat liquid of the title compound consists mostly of closed (square) tetramers via H-bonds at lower temperatures, and oligomers with open (or straight) H-bonding and non-H-bonding (monomer) at higher temperature.
Syntheses, Crystal Structures, and Photophysical Properties of Platinum(II) Complexes Containing a Disulfanenitrile Ligand
Authors: Honda Hiroya , Fujii Takayoshi , Kuwabara Junpei , Kanbara Takaki
Published: March 2013

New PtII complexes of bidendate Ph2S(=N(Ph2)S≡N)2 (ndsdsd) ligand were prepared, including the homoleptic complex, i.e., [Pt(ndsdsd)2](hfac)2 (1) (hfac: 1,1,1,5,5,5-hexafluoro-2,4-pentanedionato), and the heteroleptic complexes, [Pt(N^N)(ndsdsd)]X2 [N^N = 1,10-phenanthroline (phen) (2), 4,7-diphenylphenanthroline (bathophen) (3); X = PF6 (a) and ClO4 (b)] and [Pt(C^N)(ndsdsd)]X [C^N = 2-phenylpyridine (ppy) (4) and benzo[h]quinoline (bzq) (5); X = PF6 (a) and ClO4 (b)]. The complexes were characterized by IR, NMR spectroscopy, and elemental analysis. The molecular structures of complexes 1, 2a, and 4b have been elucidated by X-ray crystallographic analysis. The photophysical properties of all complexes were examined. Complexes 2 and 3a are very weakly luminescent in solution, whereas they show highly emissive in the solid state (Φem = 0.11–0.27).
Structural Transition of Lipopolysaccharide and Reduction in the Biological Activity by Amphiphilic Lipid with Cationic Amino Acid
Authors: Li Wenjing , Mochizuki Shinichi , Sakurai Kazuo
Published: March 2013

Lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria, is a strong elicitor in the immune system by interacting with lipopolysaccharide-binding protein and CD14 with high specificity. The removal of LPS contamination in protein drug products expressed by bacteria is essential in pharmaceutical products for human use. Although polymyxin B (PMB)-immobilized columns are mainly used for removal of LPS, there are some problems, such as high production cost, and the toxicity of ligands. We synthesized aromatic lipids bearing lysine or arginine at the headgroup. These lipids form a complex with LPS through electrostatic interaction between cationic amino acids and phosphate groups in the lipid A backbone. The resultant complexes induce the structural transition of LPS from a cylindrical structure to a vesicle. Addition of amino-lipid/LPS complexes to RAW264.7 cells, a macrophage-like cell line, decrease the LPS activity. The efficiencies are higher than commonly used cationic compounds, such as dioleoyltrimethylammoniumpropane (DOTAP) and PMB. These results show that amphiphilic lipids with cationic amino acids can be used for deactivation of LPS.
Improved performance of sequence search algorithms in remote homology detection
Authors: Joshi Adwait Govind , Raghavender Upadhyayula Surya , Sowdhamini Ramanathan
Published: March 2013

The protein sequence space is vast and diverse, spanning across different families. Biologically meaningful relationships exist between proteins at superfamily level. However, it is highly challenging to establish convincing relationships at the superfamily level by means of simple sequence searches. It is necessary to design a rigorous sequence search strategy to establish remote homology relationships and achieve high coverage. We have used iterative profile-based methods, along with constraints of sequence motifs, to specify search directions. We address the importance of multiple start points (queries) to achieve high coverage at protein superfamily level. We have devised strategies to employ a structural regime to search sequence space with good specificity and sensitivity. We employ two well-known sequence search methods, PSI-BLAST and PHI-BLAST, with multiple queries and multiple patterns to enhance homologue identification at the structural superfamily level. The study suggests that multiple queries improve sensitivity, while a pattern-constrained iterative sequence search becomes stringent at the initial stages, thereby driving the search in a specific direction and also achieves high coverage. This data mining approach has been applied to the entire structural superfamily database.
The Persistent Effect of Geographic Distance in Acquisition Target Selection
Authors: Chakrabarti Abhirup , Mitchell Will
Published: March 2013

Valuable resources often exist at distant points from a firm’s current locations, with the result that strategic decisions such as growth have a spatial dimension in which firms seek information and choose between geographically distributed alternatives. Studies show that geographic proximity facilitates the flow of resources, but there is limited understanding of factors that exacerbate or ease the impact of geographic distance when firms seek new resources. This paper argues that the difficulty of search increases with distance, particularly when search involves greater information processing, but that firms can partially overcome the constraints of distance with direct, contextual, and vicarious learning. We study 2,070 domestic acquisition announcements by U.S. chemical manufacturers founded after 1979. The results demonstrate the persistent effect of spatial geography on organizational search processes.
Entrepreneurial Action, Unique Assets, and Appropriation Risk: Firms as a Means of Appropriating Profit from Capability Creation
Authors: Kaul Aseem
Published: March 2013

This paper examines organizational boundary choice from an entrepreneurial perspective. Entrepreneurs create new profit opportunities by recombining existing assets into novel combinations based on their subjective judgment under conditions of uncertainty. In doing so, they become vulnerable to ex post appropriation by owners of uniquely complementary assets, especially where ex ante uncertainty translates into ex post causal ambiguity. Firms are a means by which entrepreneurs overcome this problem, maximizing the appropriation of pure profits from their actions. The paper formalizes this insight in an integrative model of entrepreneurial governance choice, highlighting the trade-off between the risk of appropriation and the incremental cost of asset ownership. Comparative statics from this model provide predictions about the conditions under which hierarchical governance will be preferred. In particular, they suggest that firms are preferred where entrepreneurial action results in the creation of combinations of assets that are rare, valuable, and difficult to imitate (i.e., the creation of strategic capabilities). The paper thus contributes to work on the dynamics of capabilities and transaction costs, highlighting the structurally uncertain nature of capability creation and its implications for the theory of the firm.
Decreased Expression of Intercellular Adhesion Molecules in Acantholytic Squamous Cell Carcinoma Compared With Invasive Well-Differentiated Squamous Cell Carcinoma of the Skin
Authors: Griffin John R. , Wriston Cooper C. , Peters Margot S. , Lehman Julia S.
Published: March 2013

Intercellular adhesion proteins are poorly characterized in acantholytic squamous cell carcinoma (ASCC), a more aggressive tumor than nonacantholytic invasive well-differentiated squamous cell carcinoma (SCC) of the skin. In this study we compared expression of Dsg3, E-cadherin, and syndecan-1 in ASCC and SCC. Immunohistochemical detection of Dsg3, E-cadherin, and syndecan-1 in 22 ASCCs and 22 SCCs was graded on a semiquantitative scale for intensity of staining (SI) and degree of circumferential staining (CS) about the cell membrane. Results were assessed by means of conditional logistic regression and χ2 analysis. Dsg3 and E-cadherin expression (SI, CS) was significantly decreased (P < .05) in ASCC compared with SCC, whereas staining for syndecan-1 was similar in the 2 tumor types. Differences in expression of adhesion markers between ASCC and SCC may contribute to the development of acantholysis in ASCC and its more aggressive biologic behavior.
Effect of UV and UV–Ozone Treatment of Polyolefin Fibers on Toughness of Fiber Concrete Composite
Authors: Payrow Pouria , Nokken Michelle R. , Banu Dorina , Schmidt Rolf , DeWolf Christine E. , Feldman Dorel
Published: March 2013

Ultraviolet (UV) irradiation and a combination of UV irradiation and ozone treatment of polyolefin fibers were investigated for possible improvement of mechanical properties in concrete composites. In both treatment methods, various fiber exposure durations were used, and surface modification was monitored by measuring the water contact angle. Untreated and treated fibers were added to concrete at 0.32 % by volume, and the specimens were tested for flexural strength according to ASTM International specifications. Fiber surface treatment by UV alone was found to be an unattractive technique based on the results of flexural tests and contact angle measurements. Ten minutes of UV and ozone surface treatment of fibers was found to improve the composite peak stress by 11 % and the toughness by 4 %; longer periods of exposure led to lower flexural strength results, perhaps as a result of fiber deformation or degradation.
Workability and Setting Time of Alkali Activated Blast Furnace Slag Paste
Authors: Qureshi Mohd. Nadeem , Ghosh Somnath
Published: March 2013

This paper reports the results of an experimental investigation of blast furnace slag paste activated by potassium hydroxide and sodium silicate. Reasonable workability and setting times were maintained. The workability was measured in terms of flow diameter. The loss of flow with time was also studied. The major parameters studied were water/binder ratio, alkali content, silicate content, slag/activator ratio, silicate modulus, and sodium silicate/potassium hydroxide ratio, and their effects on workability and setting time are presented. It was found that the workability and setting time of alkali activated ground granulated blast furnace slag paste are dependent basically on the alkali content, silicate content, and silicate modulus. Locally available blast furnace slag has been utilized, and its potential as source material has been verified. This information will be useful to manufacturers and researchers.
Wind Tunnel and Field Evaluation of Drift from Aerial Spray Applications with Multiple Spray Formulations
Authors: Fritz Bradley K. , Hoffmann W. Clint , Wolf Robert E. , Bretthauer Scott , Bagley W. E.
Published: March 2013

The impact of tank mix adjuvants and a formulated fungicide on spray atomization and in-field movement under aerial application conditions was examined. High speed wind tunnel testing was conducted to determine droplet size resulting from treatments selected for evaluation in the field. These treatments included a “blank” (water plus a non-ionic surfactant) as well as five additional solutions with a formulated fungicide, four of which have an additional adjuvant. The wind tunnel testing measured droplet size using the flat fan nozzles and operational parameters (spray pressure, nozzle orientation, and airspeed) selected for field trials. These treatments were then evaluated in the field for both in-swath and downwind deposition, with a mass balance on the measured results used to compare each of the formulated product treatments to a reference treatment. Wind tunnel results showed the formulated product tank mixes resulted in significantly different droplet sizes than the water and non-ionic surfactant “blank” reference sprays. Additional adjuvants resulted in minimal changes in droplet size as compared to the formulated product mixture. However the polymer tested broadened the droplet size distribution. Drift modeling of the wind tunnel droplet size results demonstrated little difference between the formulated product and spray adjuvant spray mixtures. However, all treatment solutions significantly reduced modeled drift as compared to the reference treatment. While the field study results did highlight significant differences between treatments solutions, it also showed a great degree in data variability as a result of meteorological and sampling issues. These results have led the authors to conclude that field testing of potential drift reduction technologies under aerial application conditions will be cost prohibitive and likely would give highly variable results. Wind tunnel evaluations at certified laboratories offer a much quicker and inexpensive method for evaluating large numbers of nozzle and spray formulation treatments.
Histology and immunohistochemistry of the parathyroid glands in renal secondary hyperparathyroidism refractory to vitamin D or cinacalcet therapy
Authors: Vulpio Carlo , Bossola Maurizio , Di Stasio Enrico , Tazza Luigi , Silvestri Patrizia , Fadda Guido
Published: March 2013

Background

Cinacalcet is a new effective treatment of secondary hyperparathyroidism (SHPT) in hemodialysis patients (HP), but the alterations of parathyroid gland (PTG) hyperplasia determined by cinacalcet and vitamin D have not been extensively investigated in humans.

Methods

We performed histological analyses of 94 PTGs removed from 25 HP who underwent parathyroidectomy (PTx) because of SHPT refractory to therapy with vitamin D alone (group A=13 HP and 46 PTGs) or associated with cinacalcet (group B=12 HP and 48 PTGs). The number, weight, the macroscopic cystic/hemorrhagic changes, and type of hyperplasia of PTG (nodular=NH, diffuse=DH) were assessed. In randomly selected HP of group A (4 HP and 14 PTGs) and group B (4 HP and 15 PTGs), the labeling index of cells positive to Ki-67 and TUNEL and the semiquantitative score of immunohistochemistry staining of vitamin D receptor, calcium-sensing receptor, and vascular endothelial growth factor-α (VEGF-α) were measured in the entire PTGs and in the areas with DH or NH.

Results

The number and weight of single and total PTG of each HP were similar in the two groups as well as the number of PTG with macroscopic cystic/hemorrhagic areas. TUNEL, Ki-67, and VEGF-α scores were higher in NH than in DH areas.

Conclusion

This observational study of a highly selected population of HP, submitted to PTx because SHPT refractory to therapy, shows that the macroscopic, microscopic, and immunochemistry characteristics of PTG in HP who received or did not receive cinacalcet before PTx did not differ significantly.