bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial-Specific Notch Blockade Inhibits Vascular Function and Tumor Growth through an eNOS-Dependent Mechanism
Authors: Patenaude Alexandre , Fuller Megan , Chang Linda , Wong Fred , Paliouras Grigorios , Shaw Rebecca , Kyle Alastair H. , Umlandt Patricia , Baker Jennifer H.E. , Diaz Erika , Tong Jade , Minchinton Andrew I. , Karsan Aly
Published: March 2014

Notch signaling is important for tumor angiogenesis induced by vascular endothelial growth factor A. Blockade of the Notch ligand Dll4 inhibits tumor growth in a paradoxical way. Dll4 inhibition increases endothelial cell sprouting, but vessels show reduced perfusion. The reason for this lack of perfusion is not currently understood. Here we report that inhibition of Notch signaling in endothelial cell using an inducible binary transgenic system limits VEGFA-driven tumor growth and causes endothelial dysfunction. Neither excessive endothelial cell sprouting nor defects of pericyte abundance accompanied the inhibition of tumor growth and functional vasculature. However, biochemical and functional analysis revealed that endothelial nitric oxide production is decreased by Notch inhibition. Treatment with the soluble guanylate cyclase activator BAY41-2272, a vasorelaxing agent that acts downstream of endothelial nitric oxide synthase (eNOS) by directly activating its soluble guanylyl cyclase receptor, rescued blood vessel function and tumor growth. We show that reduction in nitric oxide signaling is an early alteration induced by Notch inhibition and suggest that lack of functional vessels observed with Notch inhibition is secondary to inhibition of nitric oxide signaling. Coculture and tumor growth assays reveal that Notch-mediated nitric oxide production in endothelial cell requires VEGFA signaling. Together, our data support that eNOS inhibition is responsible for the tumor growth and vascular function defects induced by endothelial Notch inhibition. This study uncovers a novel mechanism of nitric oxide production in endothelial cells in tumors, with implications for understanding the peculiar character of tumor blood vessels. Cancer Res; 74(9); 2402–11. ©2014 AACR.
Auranofin Induces Lethal Oxidative and Endoplasmic Reticulum Stress and Exerts Potent Preclinical Activity against Chronic Lymphocytic Leukemia
Authors: Fiskus Warren , Saba Nakhle , Shen Min , Ghias Mondana , Liu Jinyun , Gupta Soumyasri Das , Chauhan Lata , Rao Rekha , Gunewardena Sumedha , Schorno Kevin , Austin Christopher P. , Maddocks Kami , Byrd John , Melnick Ari , Huang Peng , Wiestner Adrian , Bhalla Kapil N.
Published: March 2014

Chronic lymphocytic leukemia (CLL) exhibits high remission rates after initial chemoimmunotherapy, but with relapses with treatment, refractory disease is the most common outcome, especially in CLL with the deletion of chromosome 11q or 17p. In addressing the need of treatments for relapsed disease, we report the identification of an existing U.S. Food and Drug Administration-approved small-molecule drug to repurpose for CLL treatment. Auranofin (Ridaura) is approved for use in treating rheumatoid arthritis, but it exhibited preclinical efficacy in CLL cells. By inhibiting thioredoxin reductase activity and increasing intracellular reactive oxygen species levels, auranofin induced a lethal endoplasmic reticulum stress response in cultured and primary CLL cells. In addition, auranofin displayed synergistic lethality with heme oxygenase-1 and glutamate-cysteine ligase inhibitors against CLL cells. Auranofin overcame apoptosis resistance mediated by protective stromal cells, and it also killed primary CLL cells with deletion of chromosome 11q or 17p. In TCL-1 transgenic mice, an in vivo model of CLL, auranofin treatment markedly reduced tumor cell burden and improved mouse survival. Our results provide a rationale to reposition the approved drug auranofin for clinical evaluation in the therapy of CLL. Cancer Res; 74(9); 2520–32. ©2014 AACR.
Accelerating Translation of Physical Activity and Cancer Survivorship Research into Practice: Recommendations for a More Integrated and Collaborative Approach
Authors: Phillips Siobhan M. , Alfano Catherine M. , Perna Frank M. , Glasgow Russell E.
Published: March 2014

Physical activity has been deemed safe and effective in reducing many negative side effects of treatment for cancer survivors and promoting better overall health. However, most of this research has focused on highly controlled randomized trials and little of this research has been translated into care or policy for survivors. The purpose of the present article is to present a research agenda for the field to accelerate the dissemination and implementation of empirically supported physical activity interventions into care. We provide rationale for the role of basic, behavioral, clinical implementation, and population scientists in moving this science forward and call for a more coordinated effort across different phases of research. In addition, we provide key strategies and examples for ongoing and future studies using the RE-AIM (reach, efficacy/effectiveness, adoption, implementation, and maintenance) framework and pose recommendations for collaborations between researchers and stakeholders to enhance the integration of this research into policy and practice. Overall, we recommend that physical activity and cancer survivorship research use additional study designs, include relevant stakeholders, and be more collaborative, integrated, contextual, and representative in terms of both setting and participants. Cancer Epidemiol Biomarkers Prev; 23(5); 687–99. ©2014 AACR.
Replication of Genetic Polymorphisms Reported to Be Associated with Taxane-Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel
Authors: Abraham Jean E. , Guo Qi , Dorling Leila , Tyrer Jonathan , Ingle Susan , Hardy Richard , Vallier Anne-Laure , Hiller Louise , Burns Russell , Jones Linda , Bowden Sarah J. , Dunn Janet A. , Poole Christopher J. , Caldas Carlos , Pharoah Paul P.D. , Earl Helena M.
Published: March 2014

Purpose: Associations between taxane-related sensory neuropathy (TRSN) and single-nucleotide polymorphisms (SNP) have previously been reported, but few have been replicated in large, independent validation studies. This study evaluates the association between previously investigated SNPs and TRSN, using genotype data from a study of chemotherapy-related toxicity in patients with breast cancer.

Experimental Design: We investigated 73 SNPs in 50 genes for their contribution to TRSN risk, using genotype data from 1,303 European patients. TRSN was assessed using National Cancer Institute common toxicity criteria for adverse events classification. Unconditional logistic regression evaluated the association between each SNP and TRSN risk (primary analysis). Cox regression analysis assessed the association between each SNP and cumulative taxane dose causing the first reported moderate/severe TRSN (secondary analysis). The admixture likelihood (AML) test, which considers all SNPs with a prior probability of association with TRSN together, tested the hypothesis that certain SNPs are truly associated.

Results: The AML test provided strong evidence for the association of some SNPs with TRSN (P = 0.023). The two most significantly associated SNPs were rs3213619(ABCB1) [OR = 0.47; 95% confidence interval (CI), 0.28–0.79; P = 0.004] and rs9501929(TUBB2A) (OR = 1.80; 95% CI, 1.20–2.72; P = 0.005). A further 9 SNPs were significant at P-value ≤ 0.05.

Conclusion: This is currently the largest study investigating SNPs associated with TRSN. We found strong evidence that SNPs within genes in taxane pharmacokinetic and pharmacodynamic pathways contribute to TRSN risk. However, a large proportion of the inter-individual variability in TRSN remains unexplained. Further validated results from GWAS will help to identify new pathways, genes, and SNPs involved in TRSN susceptibility. Clin Cancer Res; 20(9); 2466–75. ©2014 AACR.
Disturbed Balance between Serum Levels of Receptor Tyrosine Kinases Tie-1, Tie-2 and Angiopoietins in Systemic Sclerosis
Authors: Gerlicz Zofia , Dziankowska-Bartkowiak Bozena , Dziankowska-Zaborszczyk Elzbieta , Sysa-Jedrzejowska Anna
Published: March 2014

Objective: The aim of this study was to determine the characteristic factors for vascular development and maintenance levels as well as correlation between Tie-1 receptors, Tie-2 receptors and the corresponding ligands - angiopoietins - in systemic sclerosis (SSc) patients. Materials and Methods: Serum levels of Tie-1, Tie-2, Ang-1 and Ang-2 were measured in 25 SSc patients and healthy controls. Results: There was a statistically significant difference in serum Tie-1 (p = 0.009) and Ang-2 (p = 0.001) levels in SSc patients compared with healthy controls. Significant correlations between Tie-1 and Tie-2 (ρ = 0.70, p = 0.0001) and between Tie-1 and Ang-2 (ρ = -0.92, p = 0.002) were found in the SSc group. Serum levels of Tie-2 were positively associated with esophagus changes (U = 2.03, p = 0.041) and Ang-1 was negatively correlated with duration of Raynaud's phenomenon (ρ = -0.75, p = 0.00008). Conclusion: The increase in serum concentration of Tie-1 and Ang-2 in patients with SSc may confirm a molecular imbalance between receptor tyrosine kinases Tie and their ligands.
Rapamycin Slows IgA Nephropathy Progression in the Rat
Authors: Tian Jihua , Wang Yanhong , Zhou Xiaoshuang , Li Yanjiao , Wang Chen , Li Jiaming , Li Rongshan
Published: March 2014

Background: IgA nephropathy (IgAN) is the most frequent glomerulonephritis worldwide. Different therapeutic approaches have been tested against IgAN. The present study was designed to explore the renoprotective potential of low-dose mammalian target of rapamycin (mTOR) inhibitor rapamycin in an IgAN rat model and the possible mechanism of action. Methods: After establishing an IgAN model, the rats were randomly divided into four groups: control, control with rapamycin treatment, IgAN model, and IgAN model with rapamycin treatment. Coomassie Brilliant Blue was utilized to measure 24-hour urinary protein levels. Hepatic and renal function was determined with an autoanalyzer. Proliferation was assayed via 5-bromo-2′-deoxyuridine incorporation. Real-time PCR and immunohistochemistry were utilized to detect the expression of α-SMA, collagen I, collagen III, TGF-β1 and platelet-derived growth factor. Western blotting and immunohistochemistry were performed to determine p-S6 protein levels. Results: Low-dose mTOR inhibitor rapamycin prevented an additional increase in proteinuria and protected kidney function in a model of IgAN. Rapamycin directly or indirectly interfered with multiple key pathways in the progression of IgAN to end-stage renal disease: (1) reduced the deposition of IgA and inhibited cell proliferation; (2) decreased the expression of fibrosis markers α-SMA and type III collagen, and (3) downregulated the expression of the profibrotic growth factors platelet-derived growth factor and TGF-β1. The expression of p-S6 was signiﬁcantly elevated in IgAN rats. Conclusions: The mTOR pathway was activated in IgAN rats and the early application of low-dose mTOR inhibitor rapamycin may slow the renal injury of IgAN in rats.
The Public Diplomacy of Federated Entities: Examining the Quebec Model
Authors: Huijgh Ellen
Published: March 2014

Calls to involve a wide range of actors in public diplomacy are coming thick and fast. Federated entities are waiting in line, hoping to advance their international influence and search for distinctiveness and self-affirmation. Despite the increasing interest the development of most federated entities’ public diplomacy has not yet moved out of the early phases: a borderline activity of ‘nation-branding’ and ‘paradiplomacy’. This is true not only in practice but also in the current research, a situation that this article aims to amend.

To this end, it is not necessary to start anew but to expand upon more advanced cases in the field. Particular interest is given to Quebec, which is busy creating a distinct profile for public diplomacy and alluding to a more normatively inspired network model. This article examines the public diplomacy model of Quebec’s ministry of international relations, and interprets the findings for federated entities in light of new evolutions in the field. The article concludes that despite significant discourse on public diplomacy development, major reforms remain in the realm of theory.
Periclimenaeus colemani sp. nov. (Crustacea; Palaemonidae; Pontoniinae) from Heron island, Queensland
Authors: BRUCE A. J.
Published: March 2014

A further new species of Periclimenaeus (Crustacea: Pontoniinae) from Heron Island, Queensland, Australia, is described and illustrated. Periclimenaeus colemani sp. nov., an ascidian associate, was collected from coral reef spur and groove zone and increases to 30 the numbers of Periclimenaeus known from Australia and to 17 the number of species known from Heron Island.
Two new species of the family Niphatidae van Soest, 1980 from Northeastern Brazil (Haplosclerida: Demospongiae: Porifera)
Authors: SANTOS GEORGE GARCIA , DOCIO LOYANA , PINHEIRO ULISSES
Published: March 2014

This paper deals with niphatid sponges from the coast of the Bahia State, northeastern coast of the Brazilian shelf (southwestern Atlantic). Two new species are described, Amphimedon estelae sp. nov. and Niphates luizae sp. nov. A taxonomic study of those samples is given, including description and illustrations. Both species were compared with their congeners present in the Atlantic Ocean.
New genus and species of Neotropical robber flies (Diptera, Asilidae, Asilinae)
Authors: ARTIGAS JORGE N. , VIEIRA RODRIGO
Published: March 2014

A new genus and species of Papaverellus aureocingulatus from Brazil, belonging to the asilid subfamily, is described and illustrated. Photographs of the habitus of the male and female in lateral view, and male terminalia in ventral view are provided. The systematic position of Papaverellus gen. nov. is suggested and will be addressed in a future paper.
The Exercise of Jesus' Royal Power: Lent through Trinity Sunday
Authors: Sheeley Steven
Published: March 2014

This article traces the theme of royal power through the lectionary readings in Matthew during the seasons of Lent and Easter, culminating in Trinity Sunday. An examination of major turning points in Matthew's story of Jesus—temptation, transfiguration, triumphal entry, passion, resurrection, and farewell—demonstrates Jesus' re-definition of kingship as obedience and service. Matthew characterizes Jesus as the perfect example of true righteousness, consistently obedient to the Father's will. As a result, Jesus possesses absolute and eternal power, and he commands his disciples to draw on that power and his presence as they make other disciples throughout the earth.
Political Theology in the Book of Daniel: An Internal Debate
Authors: Newsom Carol
Published: March 2014

Because the book of Daniel developed over a period of nearly four hundred years, it is not surprising that it contains some divergent perspectives. Historical and redaction criticism have allowed scholars to identify different layers of the text and their historical contexts. This critical work, however, has exposed theological differences in the book and presented readers with hermeneutical challenges. In particular, the theological perspectives on the nature of gentile kingship vary significantly. In several narratives in the book of Daniel, the king humbly confesses the sovereignty of the God of the Jews, acknowledging that he rules by the will of God. Other parts of the book depict the gentile king as being part of God's plan, but a part that will ultimately be destroyed as incompatible with divine sovereignty. The final chapters of the book contain the most negative view of gentile kingship, finding it to be monstrous and utterly evil. Although one can understand the different perspectives based on particular historical circumstances, a more fruitful hermeneutical approach is to read the different perspectives in Daniel as a never-fully-resolved conversation about the good or evil nature of political power, a conversation that continues to this day.
Learning to Preach Intentionally towards the Mission of the Local Church
Authors: Oliver Michael
Published: March 2014

This article summarizes a visioning process for a local church in which preaching parables was the primary element. The visioning process began with a series of readiness exercises including study, prayer triplet groups, formation of a vision team, sharing of the church's heritage, and creating urgency for seeking God's vision. Results of the visioning process were statements of mission, core values, vision story, and vision paths for the church. The role of preaching the parables is examined as a pivotal component to the visioning process. The article concludes with thoughts on the impact of preaching for vision.
Scorpion venoms as a potential source of novel cancer therapeutic compounds
Authors: Ding Jian , Chua Pei-Jou , Bay Boon-Huat , Gopalakrishnakone P
Published: March 2014

Scorpions and their venoms have been used in traditional medicine for thousands of years in China, India and Africa. The scorpion venom is a highly complex mixture of salts, nucleotides, biogenic amines, enzymes, mucoproteins, as well as peptides and proteins (e.g. neurotoxins). One of the recently observed biological properties of animal venoms and toxins is that they possess anticancer potential. An increasing number of studies have shown that scorpion venoms and toxins can decrease cancer growth, induce apoptosis and inhibit cancer progression and metastasis in vitro and in vivo. Several active molecules with anticancer activities, ranging from inhibition of proliferation and cell cycle arrest to induction of apoptosis and decreasing cell migration and invasion, have been isolated from scorpion venoms. These observations have shed light on the application of scorpion venoms and toxins as potential novel cancer therapeutics. This mini-review focuses on the anticancer potential of scorpion venoms and toxins and the possible mechanisms for their antitumor activities.
Autocrine inhibition of the c-fms proto-oncogene reduces breast cancer bone metastasis assessed with in vivo dual-modality imaging
Authors: Jeffery Justin J , Lux Katie , Vogel John S , Herrera Wynetta D , Greco Stephen , Woo Ho-Hyung , AbuShahin Nisreen , Pagel Mark D , Chambers Setsuko K
Published: March 2014

Breast cancer cells preferentially home to the bone microenvironment, which provides a unique niche with a network of multiple bidirectional communications between host and tumor, promoting survival and growth of bone metastases. In the bone microenvironment, the c-fms proto-oncogene that encodes for the CSF-1 receptor, along with CSF-1, serves as one critical cytokine/receptor pair, functioning in paracrine and autocrine fashion. Previous studies concentrated on the effect of inhibition of host (mouse) c-fms on bone metastasis, with resulting decrease in osteolysis and bone metastases as a paracrine effect. In this report, we assessed the role of c-fms inhibition within the tumor cells (autocrine effect) in the early establishment of breast cancer cells in bone and the effects of this early c-fms inhibition on subsequent bone metastases and destruction. This study exploited a multidisciplinary approach by employing two non-invasive, in vivo imaging methods to assess the progression of bone metastases and bone destruction, in addition to ex vivo analyses using RT-PCR and histopathology. Using a mouse model of bone homing human breast cancer cells, we showed that an early one-time application of anti-human c-fms antibody delayed growth of bone metastases and bone destruction for at least 31 days as quantitatively measured by bioluminescence imaging and computed tomography, compared to controls. Thus, neutralizing human c-fms in the breast cancer cell alone decreases extent of subsequent bone metastasis formation and osteolysis. Furthermore, we are the first to show that anti-c-fms antibodies can impact early establishment of breast cancer cells in bone.
Expression of phosphoenolpyruvate carboxykinase linked to chemoradiation susceptibility of human colon cancer cells
Authors: Park Ji-Won , Kim Seung Cheol , Kim Won Ki , Hong Jun Pyu , Kim Kyung-Hee , Yeo Hyun Yang , Lee Jae Yong , Kim M Sun , Kim Jong Heon , Yang Se Young , Kim Dae Yong , Oh Jae Hwan , Cho Jae Youl , Yoo Byong Chul
Published: March 2014

Background

Resistance to 5-fluorouracil (5-FU) in patients with colorectal cancer prevents effective treatment and leads to unnecessary and burdensome chemotherapy. Therefore, prediction of 5-FU resistance is imperative.

Methods

To identify the proteins linked to 5-FU resistance, two-dimensional gel electrophoresis-based proteomics was performed using the human colon cancer cell line SNU-C4R with induced 5-FU resistance. Proteins showing altered expression in SNU-C4R were identified by matrix-associated laser desorption/ionization–time-of-flight analysis, and their roles in susceptibility to 5-FU or radiation were evaluated in various cell lines by transfection of specific siRNA or creation of overexpression constructs. Changes in cellular signaling and expression of mitochondrial apoptotic factors were investigated by Western Blot analysis. A mitochondrial membrane potential probe (JC-1 dye) and a flow cytometry system were employed to determine the mitochondrial membrane potential. Finally, protein levels were determined by Western Blot analysis in tissues from 122 patients with rectal cancer to clarify whether each identified protein is a useful predictor of a chemoradiation response.

Results

We identified mitochondrial phosphoenolpyruvate carboxykinase (mPEPCK) as a candidate predictor of 5-FU resistance. PEPCK was downregulated in SNU-C4R compared with its parent cell line SNU-C4. Overexpression of mPEPCK did not significantly alter the susceptibility to either 5-FU or radiation. Suppression of mPEPCK led to a decrease in both the cellular level of phosphoenolpyruvate and the susceptibility to 5-FU and radiation. Furthermore, the cellular levels of phosphoenolpyruvate (an end product of PEPCK and a substrate of pyruvate kinase), phosphorylated AKT, and phosphorylated 4EBP1 were decreased significantly secondary to the mPEPCK suppression in SNU-C4. However, mPEPCK siRNA transfection induced changes in neither the mitochondrial membrane potential nor the expression levels of mitochondrial apoptotic factors such as Bax, Bcl-2, and Bad. Downregulation of total PEPCK was observed in tissues from patients with rectal cancer who displayed poor responses to preoperative 5-FU-based radiation therapy.

Conclusion

Our overall results demonstrate that mPEPCK is a useful predictor of a response to chemoradiotherapy in patients with rectal cancer.
Speech pathologists’ experiences with stroke clinical practice guidelines and the barriers and facilitators influencing their use: a national descriptive study
Authors: Hadely Kathleen A , Power Emma , O’Halloran Robyn
Published: March 2014

Background

Communication and swallowing disorders are a common consequence of stroke. Clinical practice guidelines (CPGs) have been created to assist health professionals to put research evidence into clinical practice and can improve stroke care outcomes. However, CPGs are often not successfully implemented in clinical practice and research is needed to explore the factors that influence speech pathologists’ implementation of stroke CPGs. This study aimed to describe speech pathologists’ experiences and current use of guidelines, and to identify what factors influence speech pathologists’ implementation of stroke CPGs.

Methods

Speech pathologists working in stroke rehabilitation who had used a stroke CPG were invited to complete a 39-item online survey. Content analysis and descriptive and inferential statistics were used to analyse the data.

Results

320 participants from all states and territories of Australia were surveyed. Almost all speech pathologists had used a stroke CPG and had found the guideline “somewhat useful” or “very useful”. Factors that speech pathologists perceived influenced CPG implementation included the: (a) guideline itself, (b) work environment, (c) aspects related to the speech pathologist themselves, (d) patient characteristics, and (e) types of implementation strategies provided.

Conclusions

There are many different factors that can influence speech pathologists’ implementation of CPGs. The factors that influenced the implementation of CPGs can be understood in terms of knowledge creation and implementation frameworks. Speech pathologists should continue to adapt the stroke CPG to their local work environment and evaluate their use. To enhance guideline implementation, they may benefit from a combination of educational meetings and resources, outreach visits, support from senior colleagues, and audit and feedback strategies.
Findings on ranking evaluation functions for feature weighting in image retrieval
Authors: da Silva Sergio F , Avalhais Letricia PS , Batista Marcos A , Barcelos Celia AZ , Traina Agma JM
Published: March 2014

Background

There are substantial benefits to be gained from ranking optimization in several information retrieval and recommendation systems. However, the analysis of ranking evaluation functions (REFs), which play a major role in many ranking optimization models, needs to be further investigated. An analysis of previous studies that investigated REFs was performed, and evidence was found which indicated that the choice of a proper REF is context sensitive.

Methods

In this study, we analyze a broad set of REFs for feature weighting aimed at increasing the image retrieval effectiveness. The REFs analyzed sums ten and includes the most successful and representative REFs from the literature. The REFs were embedded into a genetic algorithm (GA)-based relevance feedback (RF) model, called WLSP-C ±, aimed at improving image retrieval results through the use of learning weights for image descriptors and image regions.

Results

Analyses of precision-recall curves in five real-world image data sets showed that one non-parameterized REF named F5, not analyzed in previous studies, overcame recommended ones, which require parameter adjustment. We also provided a computational analysis of the GA-based RF model investigated, and it was shown that it is linear in regard to the image data set cardinality.

Conclusions

We conclude that REF F5 should be investigated in other contexts and problem scenarios centered on ranking optimization, as ranking optimization techniques rely heavily on the ranking quality measure.
Association of Zinc, Copper and Magnesium with bone mineral density in Iranian postmenopausal women – a case control study
Authors: Razmandeh Rezvan , Nasli-Esfahani Ensieh , Heydarpour Reza , Faridbod Farnoush , Ganjali Mohammad Reza , Norouzi Parviz , Larijani Bagher , Khoda-amorzideh Davood
Published: March 2014

Background

The risk of inadequate nutrition such as trace elements and vitamin deficiencies is considerable in postmenopausal women. The aim of this study was to compare trace elements (Zinc, Copper and Magnesium) concentration in nail, urine and serum among osteoporotic postmenopausal women with control group in Iran.

Methods

Forty eight postmenopausal women aged 36–60 years, were recruited, consisting 30 osteoporotic patients and 18 healthy controls. Blood, nail and urine concentration of Zinc (Zn), copper (Cu) and magnesium (Mg) were determined using Inductively Coupled Plasma -Atomic Emission Spectrometry (ICP-AES) method. Their Bone Mineral Density was measured by Dual X-ray Absorption (DEXA) method.

Results

The urine level of trace elements had significant difference between osteoporotic groups and controls (p < 0.001). Moreover Mg level significantly differed in serum between two groups (p < 0.04). There was no statistically significant difference in trace minerals in nail beyond groups.

Conclusion

Our findings indicate that Urine Zn level could be considerable an appropriate marker for bone absorption, usage of Zn supplements in postmenopausal women may result a beneficial reduction in osteoporotic risk.
A comparative study of finite element and spectral element methods in seismic wavefield modeling
Authors: Liu Youshan , Teng Jiwen , Lan Haiqiang , Si Xiang , Ma Xueying
Published: March 2014

The computational accuracy and efficiency of finite element method and spectral element method (SEM) are investigated thoroughly in time-domain elastic wavefield modeling. The diagonal mass matrices of the FEM and SEM free from matrix inversion are compared comprehensively by making full use of the mass-lumped technique and quadrature rules. We investigate the FEM and SEM based, respectively, on quadrilateral with the polynomials of degrees one and two, and on triangular grids with the polynomials of degrees one and three. Generally, the numerical solutions based on quadrilateral grids have a higher precision than those computed on triangular grids when the same order of polynomials is used. The FEM has a comparable accuracy to the SEM with the same number of interpolant points. In view of the triangular and quadrilateral SEMs, the former suffers from larger computational costs and relatively lower accuracy compared with the latter. Furthermore, the convergence study proves that the triangular SEM produces consistently larger errors than the quadrilateral SEM for any order and element sizes. However, the triangular SEM can adapt to arbitrary complex geometries effectively. In terms of efficiency, the FEM has an efficiency comparable with the SEM on condition that the order of interpolation polynomials is identical. In addition, a perfectly matched layer (PML) boundary condition in variational form is deduced. By introducing four intermediate variables in frequency domain, the PML avoids convolution calculation and obtains an exact solution through inverse Fourier transform in time domain. The numerical examples verify the validity and effectiveness of the PML.
Osr1 acts downstream of and interacts synergistically with Six2 to maintain nephron progenitor cells during kidney organogenesis
Authors: Xu Jingyue , Liu Han , Park Joo-Seop , Lan Yu , Jiang Rulang
Published: March 2014

Mammalian kidney organogenesis involves reciprocal epithelial-mesenchymal interactions that drive iterative cycles of nephron formation. Recent studies have demonstrated that the Six2 transcription factor acts cell autonomously to maintain nephron progenitor cells, whereas canonical Wnt signaling induces nephron differentiation. How Six2 maintains the nephron progenitor cells against Wnt-directed commitment is not well understood, however. We report here that Six2 is required to maintain expression of Osr1, a homolog of the Drosophila odd-skipped zinc-finger transcription factor, in the undifferentiated cap mesenchyme. Tissue-specific inactivation of Osr1 in the cap mesenchyme caused premature depletion of nephron progenitor cells and severe renal hypoplasia. We show that Osr1 and Six2 act synergistically to prevent premature differentiation of the cap mesenchyme. Furthermore, although both Six2 and Osr1 could form protein interaction complexes with TCF proteins, Osr1, but not Six2, enhances TCF interaction with the Groucho family transcriptional co-repressors. Moreover, we demonstrate that loss of Osr1 results in β-catenin/TCF-mediated ectopic activation of Wnt4 enhancer-driven reporter gene expression in the undifferentiated nephron progenitor cells in vivo. Together, these data indicate that Osr1 plays crucial roles in Six2-dependent maintenance of nephron progenitors during mammalian nephrogenesis by stabilizing TCF-Groucho transcriptional repressor complexes to antagonize Wnt-directed nephrogenic differentiation.
Glycoprotein folding and quality-control mechanisms in protein-folding diseases
Authors: Ferris Sean P. , Kodali Vamsi K. , Kaufman Randal J.
Published: March 2014

Biosynthesis of proteins – from translation to folding to export – encompasses a complex set of events that are exquisitely regulated and scrutinized to ensure the functional quality of the end products. Cells have evolved to capitalize on multiple post-translational modifications in addition to primary structure to indicate the folding status of nascent polypeptides to the chaperones and other proteins that assist in their folding and export. These modifications can also, in the case of irreversibly misfolded candidates, signal the need for dislocation and degradation. The current Review focuses on the glycoprotein quality-control (GQC) system that utilizes protein N-glycosylation and N-glycan trimming to direct nascent glycopolypeptides through the folding, export and dislocation pathways in the endoplasmic reticulum (ER). A diverse set of pathological conditions rooted in defective as well as over-vigilant ER quality-control systems have been identified, underlining its importance in human health and disease. We describe the GQC pathways and highlight disease and animal models that have been instrumental in clarifying our current understanding of these processes.
Effect on therapeutic ratio of planning a boosted radiotherapy dose to the dominant intraprostatic tumour lesion within the prostate based on multifunctional MR parameters
Authors: Riches S F , Payne G S , deSouza N M , Dearnaley D , Morgan V A , Morgan S C , Partridge M
Published: March 2014

Objective:

To demonstrate the feasibility of an 8-Gy focal radiation boost to a dominant intraprostatic lesion (DIL), identified using multiparametric MRI (mpMRI), and to assess the potential outcome compared with a uniform 74-Gy prostate dose.

Methods:

The DIL location was predicted in 23 patients using a histopathologically verified model combining diffusion-weighted imaging, dynamic contrast-enhanced imaging, T  2 maps and three-dimensional MR spectroscopic imaging. The DIL defined prior to neoadjuvant hormone downregulation was firstly registered to MRI-acquired post-hormone therapy and subsequently to CT radiotherapy scans. Intensity-modulated radiotherapy (IMRT) treatment was planned for an 8-Gy focal boost with 74-Gy dose to the remaining prostate. Areas under the dose–volume histograms (DVHs) for prostate, bladder and rectum, the tumour control probability (TCP) and normal tissue complication probabilities (NTCPs) were compared with those of the uniform 74-Gy IMRT plan.

Results:

Deliverable IMRT plans were feasible for all patients with identifiable DILs (20/23). Areas under the DVHs were increased for the prostate (75.1 ± 0.6 vs 72.7 ± 0.3 Gy; p < 0.001) and decreased for the rectum (38.2 ± 2.5 vs 43.5 ± 2.5 Gy; p < 0.001) and the bladder (29.1 ± 9.0 vs 36.9 ± 9.3 Gy; p < 0.001) for the boosted plan. The prostate TCP was increased (80.1 ± 1.3 vs 75.3 ± 0.9 Gy; p < 0.001) and rectal NTCP lowered (3.84 ± 3.65 vs 9.70 ± 5.68 Gy; p = 0.04) in the boosted plan. The bladder NTCP was negligible for both plans.

Conclusion:

Delivery of a focal boost to an mpMRI-defined DIL is feasible, and significant increases in TCP and therapeutic ratio were found.

Advances in knowledge:

The delivery of a focal boost to an mpMRI-defined DIL demonstrates statistically significant increases in TCP and therapeutic ratio.
Association Rules for Recommendations with Multiple Items
Authors: Ghoshal Abhijeet , Sarkar Sumit
Published: March 2014

In Web-based environments, a site has the ability to recommend multiple items to a customer in each interaction. Traditionally, rules used to make recommendations either have single items in their consequents or have conjunctions of items in their consequents. Such rules may be of limited use when the site wishes to maximize the likelihood of the customer being interested in at least one of the items recommended in each interaction (with a session comprising multiple interactions). Rules with disjunctions of items in their consequents and conjunctions of items in their antecedents are more appropriate for such environments. We refer to such rules as disjunctive consequent rules. We have developed a novel mining algorithm to obtain such rules. We identify several properties of disjunctive consequent rules that can be used to prune the search space when mining such rules. We demonstrate that the pruning techniques drastically reduce the proportion of disjunctive rules explored, with the pruning effectiveness increasing rapidly with an increase in the number of items to be recommended. We conduct experiments to compare the use of disjunctive rules with that of traditional (conjunctive) association rules on several real-world data sets and show that the accuracies of recommendations made using disjunctive consequent rules are significantly higher than those made using traditional association rules. We also compare the disjunctive consequent rules approach with two other state-of-the-art recommendation approaches—collaborative filtering and matrix factorization. Its performance is generally superior to both these techniques on two transactional data sets. The relative performance on a very sparse click-stream data set is mixed. Its performance is inferior to that of collaborative filtering and superior to that of matrix factorization for that data set.
Foreword
Authors: Bull James R.
Published: March 2014

The past 25 years have witnessed some quite extraordinary advances in the development and synthetic application of organometallic reagents and catalysts. This is reflected in the history of the conference series Organometallic Chemistry Directed Towards Organic Synthesis (OMCOS), which has established itself as a popular and enduring international forum for presentation and discussion of mainstream developments and opportunities in this field.

The series was inaugurated in Fort Collins, Colorado, USA in 1981. Proceedings of the plenary program of that event were published in Pure and Applied Chemistry (PAC)
53(12), 1981, and the topic has since become a regular feature in the Journal, with the distinction of having recorded some of the seminal advances of the period. Indeed, as the OMCOS series has grown in support and stature over the years, it has played a leading role in a trend toward more in-depth coverage of the scientific proceedings of selected IUPAC-sponsored conferences. There is encouraging evidence that this practice has the benefit of extending publication opportunities to the rising younger generation of scientists, thereby broadening and enriching the more traditional coverage of plenary proceedings, and adding value to the published record.

It is perhaps unsurprising that OMCOS has emerged as one of the leading series in the calendar of regular, IUPAC-sponsored conferences. How do we know that? Obviously, the committed participation of a succession of enthusiastic organizers and contributors, and consistently high attendance figures over the years, support this contention. More convincingly, the series generates what is regularly the most highly cited feature of PAC. For example, data collected on 30 April 2005 reveal that the OMCOS-9 collection with 239 citations averaging 14.9 citations per paper, and the OMCOS-10 collection with 408 citations averaging 21.5 citations per paper, head the citation rates for the Journal in those years. Early indications are that OMCOS-11 and OMCOS-12 head the comparable ratings of regular features for 2002 and 2004, respectively, although these more recent data are obviously in flux and still provisional.

Publication policy is responsive to these indicators of successful conference series, in the confident expectation that they will continue to serve the Journal readership with topical and sought-after content. These expectations have been handsomely fulfilled by OMCOS-13, held in Geneva, Switzerland on 17-21 July 2005, and this Special Topic issue is devoted to exclusive coverage of the event. No less than 37 papers drawn from invitations to all invited presenters on the main lecture program and a selection of meritorious contributed works feature, and constitute a salute to the centrality of this theme in modern organic synthesis. It is also a tribute to the exceptional efforts of the organizers and authors, whose energy and cooperation have ensured an expeditious passage to publication of this representative record of an outstanding event.

James R. Bull

Scientific Editor
Preface
Authors: Alexakis Alexandre
Published: March 2014

The 13th IUPAC International Symposium on Organometallic Chemistry Directed Towards Organic Synthesis (OMCOS-13) was held in Geneva, Switzerland, from 17-21 July 2005.

The aim of this series of symposia is to bring together chemists from academia and industry to define and discuss the most recent developments in the areas of catalysis, new organometallic reagents and reactions, and new materials chemistry. In 2001, Sharpless, Noyori, and Knowles received the Nobel Prize for their work in this area of chemistry; and the high profile has been maintained by the award of the 2005 Nobel Prize in Chemistry to Chauvin, Grubbs, and Schrock for the development of the metathesis method in organic synthesis.

OMCOS-13 had a record number of nearly 1200 participants from 41 countries, and there was an encouragingly high proportion of young scientists in attendance. Very strong Asian participation at this conference reflected the outstanding level of research and leadership in this field from countries such as Japan, China, South Korea, and Taiwan.

Prof. Shengming Ma, from the Shanghai Institute of Organic Chemistry of the Chinese Academy of Science and the Department of Chemistry, Zhejiang University, China received the OMCOS-13 Award (sponsored by the Yen Chuang Foundation and Springer Verlag). The prize was awarded for his creative research contributions in the field of transition-metal-catalyzed reactions of allenes.

Apart from the OMCOS-13 Award lecture, there were 23 plenary lectures and 20 oral communications that dealt with aspects of reactivity and chemoselectivity of main group and transition-metal organometallics. Stereoselectivity issues also figured prominently with a particular emphasis on asymmetric synthesis and catalysis. Mechanistic insights, new reagents for synthesis, new catalyst and ligand design, and ligand effects were other important topics.

The quality of the 620 posters that were on display during the entire conference was also outstanding. This extraordinary poster session was highlighted with the Monday evening "poster party" and culminated in the awarding of 37 poster prizes.

OMCOS-13 was held as a single session conference in an impressive lecture theater and a large exhibition area in the center of Geneva at a superb lakefront location. It was a fitting venue for the firstclass science that was presented.

Thirty-seven lecturers of OMCOS-13 present their chemistry in this issue of Pure and Applied Chemistry and provide a fine recollection of last summer's conference. The 14th edition of OMCOS will be held in Nara, Japan (2-6 August 2007) under the chairmanship of Prof. Koichiro Oshima.

Alexandre Alexakis

OMCOS-13 Co-chair

E. Peter Kündig

OMCOS-13 Co-chair
Preface
Authors: Sydnes Leiv K.
Published: March 2014

For IUPAC, the global, scientific organization that cares about chemistry and the chemical sciences in all senses of the word, it is a duty, but also a pleasure to follow the development in chemical research closely with the aim of spotting pioneering work and new trends as early as possible. In doing so, it became abundantly clear that the young chemists were about to become more important for the future of our science than they were just a decade or so ago. For chemistry, it is therefore important to encourage our young colleagues in their work, and IUPAC does so through the IUPAC Prize for Young Chemists. This prestigious annual prize honors 4-5 chemists with a fresh Ph.D. for exceptional work during their Ph.D. studies. The work is mainly judged on the basis of a 1000-word essay which is supported by recommendations from the senior scientist(s) with whom the candidate collaborated.

As immediate Past President of IUPAC, I had the pleasure of chairing an international prize selection committee of eminent chemists with a wide range of expertise in chemistry that adjudicated essays from 49 applicants from 19 countries. To pick the winners was not an easy task, because there were many outstanding candidates, but at the end the committee arrived at a unanimous decision and awarded the 2006 IUPAC Prize to the following young chemists:

Michelle Nena Chrétien, University of Ottawa, Ontario, Canada, with a thesis entitled "Photochemical, photophysical, and photobiological studies of zeolite guest–host complexes"

Valentina Domenici, University of Pisa, Italy, with a thesis entitled "Structure, orientational order and dynamics of rod-like and banana-shaped liquid crystals by means of 2H NMR: New developments"

Matt Law, University of California, Berkeley, CA, USA, with a thesis entitled "Oxide nanowires for sensing, photonics and photovoltaics"

Emilio M. Pérez, University of Edinburgh, UK, with a thesis entitled "Hydrogen-bonded synthetic molecular machines"

Dunwei Wang, Stanford University, CA, USA, with a thesis entitled "Synthesis and properties of germanium nanowires"

Each of the winners will receive both a cash prize of USD 1000 and a free trip to the 41st IUPAC World Chemistry Congress, which will take place in Turin, Italy, 5-11 August 2007. Here the winners will have the opportunity to present their work, which is an important stage of any research project. But to reach an even wider audience, the prizewinners have been invited to submit manuscripts on aspects of their research for publication in Pure and Applied Chemistry. It is therefore a pleasure to see that four refereed papers, containing critical reviews of high quality, appear in this issue of PAC.

It is a great pleasure to congratulate each of the winners (and their supervisors) with the 2006 IUPAC Prize. It is IUPAC's hope that each winner is encouraged to continue to do exciting research that will contribute to a bright future for the molecular-based sciences, which are so important for our common future.

Leiv K. Sydnes

IUPAC Immediate Past President and Chairman of the IUPAC Prize Selection Committee
Preface
Authors: Pyne Stephen
Published: March 2014

This issue of Pure and Applied Chemistry comprises 12 papers from some of the speakers at the 21st International Congress for Heterocyclic Chemistry, which was held at the University of New South Wales, Sydney, Australia from 15-20 July 2007. The topics of these papers cover some of the major themes of the conference, including natural products synthesis (as highlighted by the presentation of K. C. Nicolaou during his ISHC Senior Award in Heterocyclic Chemistry lecture on the synthesis of complex natural products and further demonstrated by contributions by Profs. Banwell, Bates, Sodeoka, Naito, Vogel, and Pyne); new methods for the synthesis of heterocycles based on metal-catalyzed reactions (Profs. Ma and Mase); and new catalysts for asymmetric synthesis based on chiral heterocyclic ligands (Prof. Nishiyama). Papers on the synthesis of heterocyclic compounds using the borono-Mannich reaction (Prof. Hutton) and green chemistry methods (Prof. Varma) are also included.

I would like to thank all contributors for their timely efforts and the editorial staff for their help.

Stephen Pyne

Conference Editor