bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress induced martensite transformation texture in AISI 304 austenitic stainless steel
Authors: de Abreu H F G , Gomes da Silva M J , Maia do Nascimento A , Freitas F N C
Published: October 2012

The phenomenological theory of martensitic transformation was applied to a tension induced martensitic transformation in an AISI 304 austenitic stainless steel in order to estimate the transformation texture. Input data were obtained from the published literature. Calculated pole figures were constructed assuming a variant selection process based on Patel and Cohen's theory, which emphasises that a mechanical component of free energy is the driving force for martensitic transformation at temperatures above martensite start Ms. The results showed a remarkably good match between the calculated and published measured data.
Microstructure and mechanical properties of Al/Al2O3 MMC produced by anodising and cold roll bonding
Authors: Jamaati R , Toroghinejad M R
Published: October 2012

In the present paper, Al–Al2O3 composite strips are produced by the cold roll bonding process of anodised aluminium strips. This technique has the flexibility to control the volume fraction of metal matrix composites by varying the oxide layer thickness on the anodised aluminium strip. Microhardness, tensile strength and elongation of composite strips are investigated as a function of quantity of alumina and the applied production method. It is found that higher quantities of alumina improve microhardness and tensile strength, while the elongation value decreases negligibly. Furthermore, prerolling annealing is found to be the best method of producing this composite via the cold roll bonding process. Finally, it is found that both monolithic aluminium and aluminium/alumina composite exhibited a ductile fracture, having dimples and shear zones.
Effect of austenite grain size on isothermal bainite transformation in low carbon microalloyed steel
Authors: Lan L Y , Qiu C L , Zhao D W , Gao X H , Du L X
Published: October 2012

The effect of austenite grain size on isothermal bainite transformation in a low carbon microalloyed steel was studied by means of optical microscopy, SEM and TEM. Two widely varying austenite grain sizes, a fine average grain size (∼20 μm) and a coarse average grain size (∼260 μm), were obtained by different maximum heating temperatures. The results showed that the morphology of isothermal microstructure changes from bainite without carbide precipitation to bainitic ferrite with a decrease in holding temperature. Coarse austenite grain can retard the kinetics of bainite transformation and increase the incubation time of bainite transformation by reducing the number of nucleation site, but it does not influence the nose temperature of the C curve of bainite start transformation, which is ∼534°C.
Microstructure and friction performance of copper film fabricated by ion implantation assisted electroless plating on PTFE
Authors: Sui Y W , Sun Z , Wang X H , Ren Y J
Published: October 2012

The polytetrafluoroethylene (PTFE), which was implanted with Ni ion to different energy and doses, fabricated metallic structures by selective electroless copper plating. The characteristic and microstructure of the copper film were studied using SEM and X-ray diffraction. Friction performance of the interface between copper film and basal body of PTFE was tested with a CETR UMT-2 (CETR Co., Campbell, CA, USA) multifunction micromechanics instrument. The test loads were 10, 20 and 40 N, while the line velocity was 8 mm s−1, and the frequency of data acquisition was 1 Hz. The Ni ion implantation replaces the complicated electroless plating surface pretreatment, and it is an assisted technique of electroless plating of copper on the surface of PTFE and plate Cu directly on its surface. Continuous, prepressing and uniformity plating was obtained with proper technique parameters and the dosage of Ni+. The frictional performance comprehensive property of copper film was remarkably influenced by different plating methods, annealing treatment and testing loads under unlubricated condition. The friction coefficients and wear rates changed with the varied load. Annealing treatment improves the tightness and uniformity of the copper film, while it decreases its cavity. Friction performance of copper film was thus increased. The mechanisms of friction and wear of copper film under different test conditions are also discussed.
Forming and fracture limits of aluminium alloy
Authors: Korhonen A S , Heikinheimo E
Published: October 2012

Forming and fracture limits of an AA 3104-H19 aluminium alloy sheet were studied by hydraulic bulging and Marciniak type deep drawing and tensile tests. The alloy appeared to be highly anisotropic, exhibiting distinctly different fracture patterns in the rolling and transverse directions. The preferred fracture direction was transverse to the rolling direction. In the tensile test, samples loaded in the rolling direction failed transverse to the rolling direction, but in the transverse direction, the fracture was inclined at ∼55° to the tensile axis. In some cases, two such competing fractures in the characteristic directions could be observed. Scanning electron microscopy studies revealed a typical ductile fracture pattern. The fracture occurred by shearing in the through thickness direction, and typical alternating shear lips in a direction inclined at ∼45° to the through thickness direction could be observed. Forming limit diagrams for both rolling and transverse directions were determined from the experiments. The measured limit strains in uniaxial tension were predicted well by the modified Rice–Tracey theory, but in equibiaxial tension, the theory overestimated the fracture limit strains.
Effects of package geometry on thermal fatigue life and microstructure of Sn–Ag–Cu solder joint
Authors: Zeng Z , Li X B , Li L , Wang Z H
Published: October 2012

Soldering experiments of chip scale package devices were carried out by means of diode laser soldering system with Sn–Ag–Cu solders. In addition, pull tests and a scanning electron microscope were used to analyse the effect of processing parameters on mechanical strength of solder joints. Viscoplastic finite element simulation was utilised to predict solder joint reliability for different package geometry under accelerated temperature cycling conditions. The results indicate that under the conditions of laser continuous scanning mode as well as the fixed soldering time, an optimal power and package geometry exists, while the optimal mechanical properties of microjoints are gained.
High strength low carbon hot rolled δ-ferritic steel: microstructure and mechanical properties
Authors: Bhowmik N , Ghosh S K , Haldar A , Chattopadhyay P P
Published: October 2012

The present study concerns the development of high strength low carbon hot rolled bainitic and martensitic δ transformation induced plasticity steels. Equilibrium and para-equilibrium phase evolution have been examined by carrying out thermodynamic calculation using MT-DATA software. Microanalysis demonstrates that both manganese and aluminium partition between liquid and solid phases. Isothermal treatment and tempering at 350°C for bainitic and martensitic microstructures respectively have yielded the best combination of strength and ductility. All the steels have exhibited the continuous yielding behaviour and favourable ratio of yield and tensile strength, which are desirable for formability. The annealed steel has yielded a high level of tensile strength with the static toughness value in between the conventional transformation induced plasticity assisted and dual phase steels.
De novo sequencing and analysis of the Ulva linza transcriptome to discover putative mechanisms associated with its successful colonization of coastal ecosystems
Authors: Zhang Xiaowen , Ye Naihao , Liang Chengwei , Mou Shanli , Fan Xiao , Xu Jianfang , Xu Dong , Zhuang Zhimeng
Published: October 2012

Background

The green algal genus Ulva Linnaeus (Ulvaceae, Ulvales, Chlorophyta) is well known for its wide distribution in marine, freshwater, and brackish environments throughout the world. The Ulva species are also highly tolerant of variations in salinity, temperature, and irradiance and are the main cause of green tides, which can have deleterious ecological effects. However, limited genomic information is currently available in this non-model and ecologically important species. Ulva linza is a species that inhabits bedrock in the mid to low intertidal zone, and it is a major contributor to biofouling. Here, we presented the global characterization of the U. linza transcriptome using the Roche GS FLX Titanium platform, with the aim of uncovering the genomic mechanisms underlying rapid and successful colonization of the coastal ecosystems.

Results

De novo assembly of 382,884 reads generated 13,426 contigs with an average length of 1,000 bases. Contiguous sequences were further assembled into 10,784 isotigs with an average length of 1,515 bases. A total of 304,101 reads were nominally identified by BLAST; 4,368 isotigs were functionally annotated with 13,550 GO terms, and 2,404 isotigs having enzyme commission (EC) numbers were assigned to 262 KEGG pathways. When compared with four other full sequenced green algae, 3,457 unique isotigs were found in U. linza and 18 conserved in land plants. In addition, a specific photoprotective mechanism based on both Lhc SR and Psb S proteins and a C4-like carbon-concentrating mechanism were found, which may help U. linza survive stress conditions. At least 19 transporters for essential inorganic nutrients (i.e., nitrogen, phosphorus, and sulphur) were responsible for its ability to take up inorganic nutrients, and at least 25 eukaryotic cytochrome P450s, which is a higher number than that found in other algae, may be related to their strong allelopathy. Multi-origination of the stress related proteins, such as glutamate dehydrogenase, superoxide dismutases, ascorbate peroxidase, catalase and heat-shock proteins, may also contribute to colonization of U. linza under stress conditions.

Conclusions

The transcriptome of U. linza uncovers some potential genomic mechanisms that might explain its ability to rapidly and successfully colonize coastal ecosystems, including the land-specific genes; special photoprotective mechanism based on both Lhc SR and Psb S; development of C4-like carbon-concentrating mechanisms; muti-origin transporters for essential inorganic nutrients; multiple and complex P450s; and glutamate dehydrogenase, superoxide dismutases, ascorbate peroxidase, catalase, and heat-shock proteins that are related to stress resistance.
Nitrilases in nitrile biocatalysis: recent progress and forthcoming research
Authors: Gong Jin-Song , Lu Zhen-Ming , Li Heng , Shi Jin-Song , Zhou Zhe-Min , Xu Zheng-Hong
Published: October 2012

Over the past decades, nitrilases have drawn considerable attention because of their application in nitrile degradation as prominent biocatalysts. Nitrilases are derived from bacteria, filamentous fungi, yeasts, and plants. In-depth investigations on their natural sources function mechanisms, enzyme structure, screening pathways, and biocatalytic properties have been conducted. Moreover, the immobilization, purification, gene cloning and modifications of nitrilase have been dwelt upon. Some nitrilases are used commercially as biofactories for carboxylic acids production, waste treatment, and surface modification. This critical review summarizes the current status of nitrilase research, and discusses a number of challenges and significant attempts in its further development. Nitrilase is a significant and promising biocatalyst for catalytic applications.
Control of lipid metabolism by adipocyte FGFR1-mediated adipohepatic communication during hepatic stress
Authors: Yang Chaofeng , Wang Cong , Ye Min , Jin Chengliu , He Weimin , Wang Fen , McKeehan Wallace L , Luo Yongde
Published: October 2012

Background

Endocrine FGF19 and FGF21 exert their effects on metabolic homeostasis through fibroblast growth factor receptor (FGFR) and co-factor betaKlotho (KLB). Ileal FGF19 regulates bile acid metabolism through specifically FGFR4-KLB in hepatocytes where FGFR1 is not significant. Both FGF19 and FGF21 activate FGFR1-KLB whose function predominates in adipocytes. Recent studies using administration of FGF19 and FGF21 and genetic ablation of KLB or adipocyte FGFR1 indicate that FGFR1-KLB mediates the response of adipocytes to both FGF21 and FGF19. Here we show that adipose FGFR1 regulates lipid metabolism through direct effect on adipose tissue and indirect effects on liver under starvation conditions that cause hepatic stress.

Methods

We employed adipocyte-specific ablations of FGFR1 and FGFR2 genes in mice, and analyzed metabolic consequences in adipose tissue, liver and systemic parameters under normal, fasting and starvation conditions.

Results

Under normal conditions, the ablation of adipose FGFR1 had little effect on adipocytes, but caused shifts in expression of hepatic genes involved in lipid metabolism. Starvation conditions precipitated a concurrent elevation of serum triglycerides and non-esterified fatty acids, and increased hepatic steatosis and adipose lipolysis in the FGFR1-deficient mice. Little effect on glucose or ketone bodies due to the FGFR1 deficiency was observed.

Conclusions

Our results suggest an adipocyte-hepatocyte communication network mediated by adipocyte FGFR1 that concurrently dampens hepatic lipogenesis and adipocyte lipolysis. We propose that this serves overall to mete out and extend lipid reserves for neural fuels (glucose and ketone bodies), while at the same time governing extent of hepatosteatosis during metabolic extremes and other conditions causing hepatic stress.
Leukocytes regulate retinal capillary degeneration in the diabetic mouse via generation of leukotrienes
Authors: Talahalli Ramaprasad , Zarini Simona , Tang Jie , Li Guangyuan , Murphy Robert , Kern Timothy S , Gubitosi-Klug Rose A
Published: October 2012

Critical involvement of the leukocyte and 5-lipoxygenase metabolites in retinal capillary degeneration using a chimeric mouse model of diabetic retinopathy.

Understanding the early pathogenesis of DR may uncover new therapeutic targets to prevent or slow the progression of this sight-threatening disorder. We investigated the role of leukocyte-mediated generation of LTs in regulation of retinal capillary degeneration and inflammation in the diabetic mouse. We generated (1) chimeric mice that lacked the ability to generate LTs by transplanting 5LO−/− bone marrow cells into ND.WT mice and into SD.WT mice and (2) “control” chimeric mice by transplanting WT bone marrow cells into 5LO−/− mice or into WT mice. Retinas from diabetic chimeric mice with WT marrow demonstrated capillary degeneration to the same extent as retinas from diabetic, nonchimeric WT mice. In contrast, retinas from diabetic chimeric mice with 5LO−/− marrow developed significantly less capillary degeneration and pericyte loss (P<0.05). In the retinas from chimeric mice with WT marrow, diabetes induced a rise in leukocyte adherence to the microvasculature, expression of the NF-κB p65 subunit, and ICAM1, superoxide generation, and retinal microvascular permeability, yet these characteristic responses were blunted by >50% in diabetic chimeras containing 5LO−/− leukocytes (P<0.05). Our data suggest the critical involvement of leukocytes and LTs in the regulation of inflammation and capillary degeneration in DR.
Selective inhibition of the gliadin-specific, cell-mediated immune response by transamidation with microbial transglutaminase
Authors: Lombardi Emanuela , Bergamo Paolo , Maurano Francesco , Bozzella Giuseppina , Luongo Diomira , Mazzarella Giuseppe , Rotondi Aufiero Vera , Iaquinto Gaetano , Rossi Mauro
Published: October 2012

mTGase-mediated transamidation of wheat flour reverses the T cell mediated inflammatory response in models of gliadin sensitivity.

CD is an immune-mediated enteropathy caused by the ingestion of wheat gluten. The modification of gluten by intestinal tTGase plays a crucial role in CD pathogenesis. In this study, we observed that extensive transamidation of wheat flour with K-C2H5 by mTGase yielded spf and K-gliadins fractions. By Western blot, we found that these modifications were associated with strongly reduced immune cross-reactivity. With the use of DQ8 tg mice as a model of gluten sensitivity, we observed a dramatic reduction in IFNγ production in gliadin-specific spleen cells challenged with spf and K-gliadins in vitro (n=12; median values: 813 vs. 29 and 99; control vs. spf and K-gliadins, P=0.012 for spf, and P=0.003 for K-gliadins). For spf, we also observed an increase in the IL-10/IFNγ protein ratio (n=12; median values: 0.3 vs. 4.7; control vs. spf, P=0.005). In intestinal biopsies from CD patients challenged in vitro with gliadins (n=10), we demonstrated further that K-gliadins dramatically reduced the levels of antigen-specific IFNγ mRNA in all specimens responsive to native gliadins (four of 10; P<0.05). As cytotoxic effects have been described for gliadins, we also studied GST and caspase-3 activities using the enterocytic Caco-2 cell line. We found that neither activities were modified by flour transamidation. Our results indicate that K-C2H5 cross-linking via mTGase specifically affects gliadin immunogenicity, reversing the inducible inflammatory response in models of gluten sensitivity without affecting other aspects of the biological activity of gliadins.
Influenza-induced, helper-independent CD8+ T cell responses use CD40 costimulation at the late phase of the primary response
Authors: Seah Shirley G K , Brady Jamie L , Carrington Emma M , Ng Wy Ching , Sutherland Robyn M , Hancock Manuela S , La Gruta Nicole L , Brown Lorena E , Turner Stephen J , Lew Andrew M , Zhan Yifan
Published: October 2012

Direct costimulation of CD8+ T cells is more important than the canonical licensing of DCs by CD4 help, in influenza.

The helper-dependent pathway of priming CD8+ T cells involves “licensing” of DCs by CD40L on CD4+ T cells. The helper-independent (“helpless”) pathways elicited by many viruses, including influenza, are less widely understood. We have postulated that CD40L can be up-regulated on DCs by such viruses, and this promotes priming of CD8+ T cells via CD40. Most studies on costimulation have been performed in the presence of CD4+ T cells, and so the role of CD40L costimulation under helpless circumstances has not been fully elucidated. Here, we investigated such a role for CD40L using CD40L KO mice. Although the number of influenza-specific CD8+ T cells was unaffected by the absence of CD4+ T cells, it was markedly decreased in the absence of CD40L. Proliferation (the number of CD44+BrdU+ influenza-specific CD8+ T cells) in the primary response was diminished in CD40L KO mice at Day 8 but not at Day 5 after infection. MLR studies indicated that CD40L expression on DCs was critical for CD8+ T cell activation. Adoptive transfer of CD40 KO CD8+ T cells compared with WT cells confirmed that CD40 on such cells was critical for the generation of primary anti-influenza CD8+ T cell responses. The late effect also corresponded with the late expression of CD40 by influenza-specific CD8+ T cells. We suggest that costimulation via CD40L on DCs and CD40 on CD8+ T cells is important in optimizing primary CD8+ T cell responses during influenza infection.
Acupuncture for Cancer-Related Fatigue in Patients With Breast Cancer: A Pragmatic Randomized Controlled Trial
Authors: Molassiotis Alexander , Bardy Joy , Finnegan-John Jennifer , Mackereth Peter , Ryder David W. , Filshie Jacqueline , Ream Emma , Richardson Alison
Published: October 2012

Purpose

We aimed to assess the effectiveness of acupuncture for cancer-related fatigue (CRF) in patients with breast cancer.

Patients and Methods

We conducted a pragmatic, randomized controlled trial comparing acupuncture with enhanced usual care. Three hundred two outpatients with breast cancer participated. We randomly assigned 75 patients to usual care and 227 patients to acupuncture plus usual care (random assignment of 1:3 respectively) with minimization controlling for baseline general fatigue and maintenance treatment. Treatment was delivered by acupuncturists once a week for 6 weeks through needling three pairs of acupoints. The usual care group received a booklet with information about fatigue and its management. Primary outcome was general fatigue at 6 weeks, measured with the Multidimensional Fatigue Inventory (MFI). Other measurements included the Hospital Anxiety and Depression Scale, Functional Assessment of Cancer Therapy–General quality-of-life scale, and expectation of acupuncture effect. Analyses were by intention to treat.

Results

Two hundred forty-six of 302 patients randomly assigned provided complete data at 6 weeks. The difference in the mean General Fatigue score, between those who received the intervention and those who did not, was −3.11 (95% CI, −3.97 to −2.25; P < .001). The intervention also improved all other fatigue aspects measured by MFI, including Physical Fatigue and Mental Fatigue (acupuncture effect, −2.36 and −1.94, respectively; both at P < .001), anxiety and depression (acupuncture effect, −1.83 and −2.13, respectively; both at P < .001), and quality of life (Physical Well-Being effect, 3.30; Functional Well-Being effect, 3.57; both at P < .001; Emotional Well-Being effect, 1.93; P = .001; and Social Functioning Well-Being effect, 1.05; P < .05).

Conclusion

Acupuncture is an effective intervention for managing the symptom of CRF and improving patients' quality of life.
A Role for Common Genomic Variants in the Assessment of Familial Breast Cancer
Authors: Sawyer Sarah , Mitchell Gillian , McKinley Joanne , Chenevix-Trench Georgia , Beesley Jonathan , Chen Xiao Qing , Bowtell David , Trainer Alison H. , Harris Marion , Lindeman Geoffrey J. , James Paul A.
Published: October 2012

Purpose

Genome-wide association studies have identified common genomic variants associated with increased susceptibility to breast cancer. In the general population, the risk associated with these known variants seems insufficient to inform clinical management. Their contribution to the development of familial breast cancer is less clear.

Patients and Methods

We studied 1,143 women with breast cancer who had completed BRCA1 and BRCA2 mutation screening as a result of a high risk for hereditary breast cancer. Genotyping of 22 breast cancer–associated genomic variants was performed. A polygenic risk score (PRS), calculated as the sum of the log odds ratios for each allele, was compared with the same metric in 892 controls from the Australian Ovarian Cancer Study. The clinical features associated with the high and low ends of the polygenic risk distribution were compared.

Results

Women affected by familial breast cancer had a highly significant excess of risk alleles compared with controls (P = 1.0 × 10−16). Polygenic risk (measured by the PRS) was greater in women who tested negative for a BRCA1 or BRCA2 mutation compared with mutation carriers (P = 2.3 × 10−6). Non-BRCA1/2 women in the top quartile of the polygenic risk distribution were more likely to have had early-onset breast cancer (< 30 years of age, odds ratio [OR]= 3.37, P = .03) and had a higher rate of second breast cancer (OR 1.96, P = .02) compared with women with low polygenic risk.

Conclusion

Genetic testing for common risk variants in women undergoing assessment for familial breast cancer may identify a distinct group of high-risk women in whom the role of risk-reducing interventions should be explored.
Opioid Prescribing for Cancer Pain During the Last 3 Months of Life: Associated Factors and 9-Year Trends in a Nationwide United Kingdom Cohort Study
Authors: Higginson Irene J. , Gao Wei
Published: October 2012

Purpose

To determine time trends and characteristics associated with opioid analgesic prescribing to patients with cancer who are approaching the end of life.

Patients and Methods

This population-based cohort study used data on 29,825 patients diagnosed with five common cancers—lung (34.2%), colorectal (19.9%), female breast (21.6%), prostate (19.1%), and head and neck (5.2%)—in the United Kingdom General Practice Research Database (GPRD) who died between 2000 and 2008. Opioid prescription rates in the last 3 months of life were described. Characteristics associated with opioid prescribing were investigated by using generalized estimation equation models.

Results

In the last 3 months of life, 43.6% (95% CI, 43.0% to 44.2%) of patients received at least one prescription of opioids: morphine (33.4%; 95% CI, 32.8% to 33.9%), diamorphine (11.6%; 95% CI, 11.2% to 11.9%), and fentanyl family (10.2%; 95% CI, 9.8% to 10.5%). Over time, prescription rates increased for opioids predominant during specific time periods, especially oxycodone. Older patients (age > 60 years) had significantly lower chances of receiving opioids than their younger (age < 50 years) peers (prevalence ratio [PR] range, 0.14 to 0.78), even adjusted for comorbidity. Women were slightly more likely than men to receive any type of opioid (PR,1.07; 95% CI, 1.04 to 1.11). Morphine and diamorphine (PR range, 1.14 to 1.56) were more commonly prescribed for lung and colorectal cancers and fentanyl family for head and neck cancers (PR, 1.39; 95% CI, 1.19 to 1.62) compared with for prostate cancers.

Conclusion

Morphine and diamorphine remain the stronghold for treating cancer pain in the United Kingdom. Opioid prescription rates are increasing over time. Prescription rates are lower for older people for all opioids, suggesting that this group needs attention.
Pemetrexed Versus Pemetrexed and Carboplatin As Second-Line Chemotherapy in Advanced Non–Small-Cell Lung Cancer: Results of the GOIRC 02-2006 Randomized Phase II Study and Pooled Analysis With the NVALT7 Trial
Authors: Ardizzoni Andrea , Tiseo Marcello , Boni Luca , Vincent Andrew D. , Passalacqua Rodolfo , Buti Sebastiano , Amoroso Domenico , Camerini Andrea , Labianca Roberto , Genestreti Giovenzio , Boni Corrado , Ciuffreda Libero , Di Costanzo Francesco , de Marinis Filippo , Crinò Lucio , Santo Antonio , Pazzola Antonio , Barbieri Fausto , Zilembo Nicoletta , Colantonio Ida , Tibaldi Carmelo , Mattioli Rodolfo , Cafferata Mara A. , Camisa Roberta , Smit Egbert F.
Published: October 2012

Purpose

To compare efficacy of pemetrexed versus pemetrexed plus carboplatin in pretreated patients with advanced non–small-cell lung cancer (NSCLC).

Patients and Methods

Patients with advanced NSCLC, in progression during or after first-line platinum-based chemotherapy, were randomly assigned to receive pemetrexed (arm A) or pemetrexed plus carboplatin (arm B). Primary end point was progression-free survival (PFS). A preplanned pooled analysis of the results of this study with those of the NVALT7 study was carried out to assess the impact of carboplatin added to pemetrexed in terms of overall survival (OS).

Results

From July 2007 to October 2009, 239 patients (arm A, n = 120; arm B, n = 119) were enrolled. Median PFS was 3.6 months for arm A versus 3.5 months for arm B (hazard ratio [HR], 1.05; 95% CI, 0.81 to 1.36; P = .706). No statistically significant differences in response rate, OS, or toxicity were observed. A total of 479 patients were included in the pooled analysis. OS was not improved by the addition of carboplatin to pemetrexed (HR, 90; 95% CI, 0.74 to 1.10; P = .316; P heterogeneity = .495). In the subgroup analyses, the addition of carboplatin to pemetrexed in patients with squamous tumors led to a statistically significant improvement in OS from 5.4 to 9 months (adjusted HR, 0.58; 95% CI, 0.37 to 0.91; P interaction test = .039).

Conclusion

Second-line treatment of advanced NSCLC with pemetrexed plus carboplatin does not improve survival outcomes as compared with single-agent pemetrexed. The benefit observed with carboplatin addition in squamous tumors may warrant further investigation.
Retinoic acid signaling in Sertoli cells regulates organization of the blood-testis barrier through cyclical changes in gene expression
Authors: Hasegawa Kazuteru , Saga Yumiko
Published: October 2012

Mammalian spermatogenesis contributes a constant production of large numbers of spermatozoa, which is achieved by a cyclically regulated program known as the seminiferous epithelial cycle. Sertoli cells, functionally unique somatic cells, create a microenvironment to support the continuous differentiation of germ cells especially through the formation of a blood-testis barrier (BTB). The BTB is essential for maintaining homeostasis in seminiferous tubules and opens transiently at stages VII-VIII to ensure constant differentiation of spermatogenic cells. However, it is poorly understood how the dynamic organization of BTB is regulated. In our current study, we find that the overexpression of a dominant-negative form of RARα (dnRARα) in Sertoli cells disrupts the BTB at stages VII-XII and causes the large-scale apoptosis of differentiating germ cells. These abnormal events are found to be associated with cyclical gene expression changes in Sertoli cells, which can be represented by abnormal activation and repression of genes showing peaks of expression during stages I-VI and VII-XII, respectively. We find that one such gene, Ocln, encoding a tight junction component, partly contributes to the BTB disruption caused by dnRARα. Taken together, our data suggest that the cyclical activation of RA signaling in Sertoli cells during stages VII-XII contributes to a periodic organization of the BTB through changes in stage-dependent gene expression.
Autotaxin/Lpar3 signaling regulates Kupffer's vesicle formation and left-right asymmetry in zebrafish
Authors: Lai Shih-Lei , Yao Wan-Ling , Tsao Ku-Chi , Houben Anna J. S. , Albers Harald M. H. G. , Ovaa Huib , Moolenaar Wouter H. , Lee Shyh-Jye
Published: October 2012

Left-right (L-R) patterning is essential for proper organ morphogenesis and function. Calcium fluxes in dorsal forerunner cells (DFCs) are known to regulate the formation of Kupffer's vesicle (KV), a central organ for establishing L-R asymmetry in zebrafish. Here, we identify the lipid mediator lysophosphatidic acid (LPA) as a regulator of L-R asymmetry in zebrafish embryos. LPA is produced by Autotaxin (Atx), a secreted lysophospholipase D, and triggers various cellular responses through activation of specific G protein-coupled receptors (Lpar1-6). Knockdown of Atx or LPA receptor 3 (Lpar3) by morpholino oligonucleotides perturbed asymmetric gene expression in lateral plate mesoderm and disrupted organ L-R asymmetries, whereas overexpression of lpar3 partially rescued those defects in both atx and lpar3 morphants. Similar defects were observed in embryos treated with the Atx inhibitor HA130 and the Lpar1-3 inhibitor Ki16425. Knockdown of either Atx or Lpar3 impaired calcium fluxes in DFCs during mid-epiboly stage and compromised DFC cohesive migration, KV formation and ciliogenesis. Application of LPA to DFCs rescued the calcium signal and laterality defects in atx morphants. This LPA-dependent L-R asymmetry is mediated via Wnt signaling, as shown by the accumulation of β-catenin in nuclei at the dorsal side of both atx and lpar3 morphants. Our results suggest a major role for the Atx/Lpar3 signaling axis in regulating KV formation, ciliogenesis and L-R asymmetry via a Wnt-dependent pathway.
A conserved function for Strabismus in establishing planar cell polarity in the ciliated ectoderm during cnidarian larval development
Authors: Momose Tsuyoshi , Kraus Yulia , Houliston Evelyn
Published: October 2012

Functional and morphological planar cell polarity (PCP) oriented along the oral-aboral body axis is clearly evident in the ectoderm of torpedo-shaped planula larvae of hydrozoan cnidarians such as Clytia hemisphaerica. Ectodermal epithelial cells bear a single motile cilium the beating of which is coordinated between cells, causing directional swimming towards the blunt, aboral pole. We have characterised PCP during Clytia larval development and addressed its molecular basis. PCP is first detectable in ectodermal cells during gastrulation as coordinated basal body positioning, the ciliary root becoming consistently positioned on the oral side of the apical surface of the cell. At later stages, more pronounced structural polarity develops around the base of each cilium in relation to the cilia beating direction, including a characteristic asymmetric cortical actin organisation. Morpholino antisense oligonucleotide and mRNA injection studies showed that PCP development requires the Clytia orthologues of the core Fz-PCP pathway components Strabismus (CheStbm), Frizzled (CheFz1) and Dishevelled (CheDsh). Morpholinos targeting any of these components prevented ectodermal PCP, disrupted ciliogenesis and inhibited embryo elongation during gastrulation, which involves cell intercalation. We show that YFP-tagged CheStbm adopts a polarised intracellular distribution, localising preferentially to the aboral boundary of each cell, as has been demonstrated in Drosophila and some vertebrate PCP studies. Our findings in a cnidarian strongly suggest that the Fz-PCP pathway is a highly conserved and evolutionary ancient metazoan feature that is probably widely responsible for oriented swimming and/or feeding in relation to body axis in the many ciliated larval types found throughout the animal kingdom.
Antibodies binding the ADAM10 substrate recognition domain inhibit Eph function
Authors: Atapattu Lakmali , Saha Nayanendu , Llerena Carmen , Vail Mary E. , Scott Andrew M. , Nikolov Dimitar B. , Lackmann Martin , Janes Peter W.
Published: October 2012

The ADAM10 transmembrane metalloprotease cleaves a variety of cell surface proteins that are important in disease, including ligands for receptor tyrosine kinases of the erbB and Eph families. ADAM10-mediated cleavage of ephrins, the ligands for Eph receptors, is suggested to control Eph/ephrin-mediated cell-cell adhesion and segregation, important during normal developmental processes, and implicated in tumour neo-angiogenesis and metastasis. We previously identified a substrate-binding pocket in the ADAM10 C domain that binds the EphA/ephrin-A complex thereby regulating ephrin cleavage. We have now generated monoclonal antibodies specifically recognising this region of ADAM10, which inhibit ephrin cleavage and Eph/ephrin-mediated cell function, including ephrin-induced Eph receptor internalisation, phosphorylation and Eph-mediated cell segregation. Our studies confirm the important role of ADAM10 in cell-cell interactions mediated by both A- and B-type Eph receptors, and suggest antibodies against the ADAM10 substrate-recognition pocket as promising therapeutic agents, acting by inhibiting cleavage of ephrins and potentially other ADAM10 substrates.
Sirtuin-3 modulates Bak- and Bax-dependent apoptosis
Authors: Verma Manish , Shulga Nataly , Pastorino John G.
Published: October 2012

Sirtuin-3 exhibits properties of a tumor suppressor partly emanating from its ability to control the state of mitochondrial metabolism, with depletion of sirt-3 increasing tumor cell survival. In the present study we demonstrate that depletion of sirtuin-3 brings about an anti-apoptotic phenotype via stimulating cyclophilin-D activity, which promotes the binding of hexokinase II to the mitochondria, thereby preventing Bak/Bax dependent mitochondrial injury and cell death. By contrast, increased expression of sirtuin-3 decreases cyclophilin-D activity, resulting in detachment of hexokinase II from the mitochondria and potentiation of Bak- and Bax-induced mitochondrial injury and loss of cell viability.
Lysosomes shape Ins(1,4,5)P3-evoked Ca2+ signals by selectively sequestering Ca2+ released from the endoplasmic reticulum
Authors: López-Sanjurjo Cristina I. , Tovey Stephen C. , Prole David L. , Taylor Colin W.
Published: October 2012

Most intracellular Ca2+ signals result from opening of Ca2+ channels in the plasma membrane or endoplasmic reticulum (ER), and they are reversed by active transport across these membranes or by shuttling Ca2+ into mitochondria. Ca2+ channels in lysosomes contribute to endo-lysosomal trafficking and Ca2+ signalling, but the role of lysosomal Ca2+ uptake in Ca2+ signalling is unexplored. Inhibition of lysosomal Ca2+ uptake by dissipating the H+ gradient (using bafilomycin A1), perforating lysosomal membranes (using glycyl-L-phenylalanine 2-naphthylamide) or lysosome fusion (using vacuolin) increased the Ca2+ signals evoked by receptors that stimulate inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] formation. Bafilomycin A1 amplified the Ca2+ signals evoked by photolysis of caged Ins(1,4,5)P3 or by inhibition of ER Ca2+ pumps, and it slowed recovery from them. Ca2+ signals evoked by store-operated Ca2+ entry were unaffected by bafilomycin A1. Video-imaging with total internal reflection fluorescence microscopy revealed that lysosomes were motile and remained intimately associated with the ER. Close association of lysosomes with the ER allows them selectively to accumulate Ca2+ released by Ins(1,4,5)P3 receptors.
Iron autointoxication in a 16-year-old girl: a protective role for hepcidin?
Authors: Simonse1 E , Valk-Swinkels C G H , Van 't Veer N E , Ermens A A M , Veldkamp E J M
Published: October 2012

Intentional iron overdose appears to be an increasingly common form of attempted suicide. We present a case of iron overdose in a 16-year-old girl who was found unconscious in her bed and brought to our emergency department. The most remarkable diagnostic findings were the patient's comatose condition, divergent eye position and positive Babinski foot pad reflexes. Laboratory tests showed hyperglycaemia and mild metabolic acidosis. A computed tomography scan of the cerebrum showed no signs of intracerebral haemorrhage or elevated intracerebral pressure. Toxicology screening showed no use of acetaminophen, ethanol or drugs of abuse. The patient was stabilized and monitored on the intensive care ward. When she woke up, she confessed to having taken Fero-Gradumet®®. Retrospectively analysed, the serum iron concentration in the first blood sample (seven hours after ingestion) was 62 μmol/L which corresponds with moderate iron intoxication. The patient received whole bowel irrigation with 2 L polyethyleneglycol solution and de-ironing treatment with intravenous deferoxamine 20 mg/kg in eight hours. She was discharged from the hospital after three days in a good clinical condition. Retrospectively, serum hepcidin concentrations were determined and evaluated in conjunction with serum iron concentrations and the installed treatment. Before medical de-ironing interventions were started, we saw that the serum iron concentration in our patient was already declining. At the same time, we observed a sharp increase in the serum hepcidin concentration. After normalization of serum iron concentrations, hepcidin normalized as well.
Temporal artery biopsy for giant cell arteritis: retrospective audit
Authors: Saedon Habiba , Saedon Mahmud , Goodyear Steve , Papettas Trifonas , Marshall Colette
Published: October 2012

Objectives

Temporal artery biopsy (TAB) is performed in suspected cases of sight-threatening giant cell arteritis (GCA). We aimed to determine the feasibility of TAB in patients who are suspected of having GCA.

Design, setting and participants

A retrospective audit of all patients undergoing TAB at a single teaching hospital between 2005 and 2011, identified from the histopathology database.

Main outcome measures

(1) Clinical profile and biochemical criteria associated with positive histology. (2) Proportion of negative histology patients who were commenced on steroid therapy.

Results

One hundred and fifty-three TAB were performed (mean age 70.8 years, men:women = 3:2, 110 Caucasian: 43 Asian). Thirty-two biopsies were positive for GCA and 121 were negative. In total, 68 (61%) of 112 negative TAB patients were clinically diagnosed with GCA despite histological findings ( P < 0.001). Nine out of 153 biopsies were non-arterial. Histologically positive TAB patients were of higher mean age (77.1 [95% CI 74.5–79.7] versus 69.1 [95% CI 66.7–71.6]; P < 0.001) and had a higher erythrocyte sedimentation rate (ESR) (60 [95% CI 46.1–73.9] versus 39.8 [95% CI 34.2–45.3]; P < 0.01)] than those with negative histology.

Conclusions

Raised ESR and higher age may be the most useful indicators of GCA. Many histologically negative individuals were nevertheless clinically diagnosed and managed as GCA.
Socioeconomic determinants of non-communicable-diseases among the Cypriot population: questionnaire study
Authors: Kiliari Nitsa , Theodosopoulou Eleni , Papanastasiou Elena , Charalambous Andreas
Published: October 2012

Objective

To investigate the extent to which the socioeconomic status of Cypriots is associated with the lifetime prevalence of self-reported non-communicable disease (NCDs), with emphasis on those accounting for most Death and Disability-adjusted Life Years (DALYs) among the population, including cardiovascular disease (CVD), metabolic risks and neuropsychiatric disorders.

Design

A nationally based survey conducted through personal interviews, using a structured questionnaire design.

Setting

Cyprus rural and urban areas (excluding Turkish-occupied areas).

Participants

Four hundred and sixty-five Cypriot adults of an average age of 53 years.

Main outcome measures

Lifetime prevalence of self-reported NCDs.

Results

Most self-reported NCDs were shown to have significant associations with socioeconomic status, defined for this study by level of education and family income. Education was significantly inversely associated with CVD (18.1% at elementary education level (EE); 2.7% at high school education level (HE); and 1.7% at University/College education level (UE)), hypertension (23.4% at EE; 8.6% at HE; and 2.6% at UE), hypercholesterolaemia (12.8% at EE; 7.1% at HE; and 5.2% at UE), obesity (10.7% at EE; 4.7% at HE; and 3.5% at UE), diabetes (13.8% at EE; 2.4% at HE; and 0.9% at UE), and drug addiction (7.6% at EE; 1.6% at HE; and 0.0% at UE). Depression was more frequent amongst middle level graduates (3.2% at EE; 5.1% at HE; and 2.6% at UE). Income was significantly negatively associated with CVD ( r = –0.130, p = 0.005), stress ( r = –0.103, p = 0.028) and drug addiction ( r = –0.117, p = 0.012), and significantly positively associated with the ‘no problems'statement ( r = 0.201, p = 0.000) which was reported by almost two fifths of the population. Worth noting is stress which, demonstrating no socioeconomic discrimination, was reported by high percentages of the population (17.2% of the sample).

Conclusions

Although with some limitations, this study has provided initial evidence for the existence of socioeconomically determined health inequalities, which may have potentially important implications for understanding the deeper aetiology of common NCDs and for informing public policies. More research in this area is required to reveal the magnitude of NCDS–socioeconomic relation.
Islamic Manuscript Collections on the Web: An Evaluation of the User Interfaces
Authors: Sen F.
Published: October 2012

This paper presents a survey conducted to provide an overview of the functions and features of digital library user interfaces within the Islamic manuscript context. Based on Internet and bibliographical keyword search, the survey identifies 49 digital libraries that contain Islamic manuscript collections. The findings illustrate varying patterns for browsing, searching, navigation, and page-viewing systems as well as uncommon yet relevant tools and features offered by the interfaces for digital libraries.
Digital Archive Systems Using CMS and Gallery Tools
Authors: Kawano H.
Published: October 2012

Recently, we have good opportunities to integrate various digital collections and archive systems using loosely coupled and meaningfully connected hyperlinks from various view points of cultural, social and technical aspects. In this paper, from technical view points, we present our implementation of digital anthropological museum using CMSs (Contents Management System) and gallery tools. Firstly, we have a brief comparison of digital archive software including popular CMSs. Recent years, Museums, Libraries and Archives (MLA) are making efforts to provide various digital collections and born-digital information by using digital archive systems. For example, major national libraries and long-term preserving organisations, such as IIPC (International Internet Preservation Consortium), gather and preserve huge amount of web pages, and curate them using web curator tools. Secondary, we propose a metadata schema for digital collections in “ the Anthropological Museum of Nanzan University”, which is based on the guideline of museum objects. Our proposed schema based on XML metadata formats like URI/RDF/MODS. Finally, we show the system architecture of digital anthropological museum and implementation of three different prototype systems based on different CMSs add-on modules and other related software. From 2005 to 2012, we have 1776 digital collections with 74 metadata attributes and 40,000 ethnographic photographs without metadata, at present we store 277 digital contents having detail values into our prototype of digital museum system. Using interfaces of prototype systems, we also introduce workflows of museum collections including content rights management.
A Dynamic Online Interface Representing a Polyvalent Cultural Identity: The Case of Crete
Authors: Parthenios P. , Patsavos N.
Published: October 2012

Conceptual models offer the ability to capture several concepts, and more importantly their often complicated relationships, in one single view. When applying this method in order to represent a geographical region's past, this would mean an emphasis on the dynamic structure of the cultural phenomena represented and not on a formalistic evolutionary catalogue of data and de-contextualized information. Especially when dealing with complex and deep hierarchies or intangible notions, a conceptual model can offer an additional level of perceptual understanding. We use the Conceptual Modeling Language (ConML) in our proposed application for the presentation of the main monuments of Crete as a tool for organizing, manipulating, and communicating the large amounts of data such a project entails. Conceptualization and abstraction of information through different levels of detail allows the application to be light and easy to use. Moreover, the ability to switch between different historical periods offers a comparative study of the monuments evolution in time. Thus, we aim at a dynamic representation from the user of Crete's, an island characterized by the Mediterranean's rich and polyvalent historical development, culture.