bluuebunny/crossref_metadata_2025 huggingface dataset:
A blended design approach for pervasive healthcare: Bringing together users, experts and technology
Authors: van der Linden Janet , Waights Verina , Rogers Yvonne , Taylor Crissman
Published: September 2012

Pervasive healthcare is beginning to investigate how novel sensory technologies can be used to measure body movements and provide various forms of feedback. This position paper reflects on a blended design approach that uses a combination of technology inspiration, consultation with experts and user-centred design for the development of a personalized pervasive healthcare system to support stroke rehabilitation.
Wound Care in China
Authors: Fu Xiaobing
Published: September 2012

Wounds in China are severe problems, and China has a huge demand for tissue repair and regeneration. In the past decades, there has been significant development in genetics, auxology, stem cell biology, and tissue engineering, which have been further translated into and integrated with clinical treatment of tissue injury. In China, this synergy has contoured the discipline of tissue repair and regeneration to be one of the best and fastest performing disciplines with regard to bench-to-bed connection and translation.
Long-Term Functional Outcome of Bilateral Spontaneous and Simultaneous Achilles Tendon Ruptures
Authors: Ellanti Prasad , Davarinos Nikos , Burke Thomas E. , D’Souza Lester G.
Published: September 2012

Bilateral simultaneous ruptures are rare comprising less than 1% of all Achilles tendon ruptures. Risk factors for bilateral ruptures include chronic diseases and medications such as corticosteroids and fluoroquinolones. There is little in the literature on the long-term functional outcome of bilateral Achilles tendon ruptures. This article present a series of 3 cases of simultaneous and spontaneous bilateral Achilles tendon ruptures with a minimum of 5-year follow up suggesting a good functional outcome.

Level of Evidence: Therapeutic Level IV
Men in pain: masculinity, medicine and the Miracles of St. Artemios
Authors: Alwis Anne P.
Published: September 2012

The Miracles of St Artemios, which reveal a catalogue of men who are in severe pain and who express their anguish volubly, are analysed to provide two methodological frameworks (anthropological and medical), within which to investigate the masculinity of these ‘ordinary’ Byzantine men.
Mapping the symbol of the statue in Ritsos’ short poems
Authors: Giannakopoulou Liana
Published: September 2012

A first attempt is made here to map the presence of the symbol of the statue in Ritsos’ short poems. Starting from his early work and reaching the years of the military dictatorship, the main line of the argument is that references to sculpture become significant in Ritsos’ poetry after the 1960s and culminate in the period of the junta. This is attributed to Ritsos’ subtle reaction to the regime and its use and abuse of the cultural heritage of ancient Greece in a context of propaganda and oppression. This response makes Ritsos’ use of the symbol of the statue utterly distinctive.
Regulatory network operations in the Pathway Tools software
Authors: Paley Suzanne M , Latendresse Mario , Karp Peter D
Published: September 2012

Background

Biologists are elucidating complex collections of genetic regulatory data for multiple organisms. Software is needed for such regulatory network data.

Results

The Pathway Tools software supports storage and manipulation of regulatory information through a variety of strategies. The Pathway Tools regulation ontology captures transcriptional and translational regulation, substrate-level regulation of enzyme activity, post-translational modifications, and regulatory pathways. Regulatory visualizations include a novel diagram that summarizes all regulatory influences on a gene; a transcription-unit diagram, and an interactive visualization of a full transcriptional regulatory network that can be painted with gene expression data to probe correlations between gene expression and regulatory mechanisms. We introduce a novel type of enrichment analysis that asks whether a gene-expression dataset is over-represented for known regulators. We present algorithms for ranking the degree of regulatory influence of genes, and for computing the net positive and negative regulatory influences on a gene.

Conclusions

Pathway Tools provides a comprehensive environment for manipulating molecular regulatory interactions that integrates regulatory data with an organism’s genome and metabolic network. Curated collections of regulatory data authored using Pathway Tools are available for Escherichia coli, Bacillus subtilis, and Shewanella oneidensis.
ncRNAclassifier: a tool for detection and classification of transposable element sequences in RNA hairpins
Authors: Tempel Sébastien , Pollet Nicolas , Tahi Fariza
Published: September 2012

Background

Inverted repeat genes encode precursor RNAs characterized by hairpin structures. These RNA hairpins are then metabolized by biosynthetic pathways to produce functional small RNAs. In eukaryotic genomes, short non-autonomous transposable elements can have similar size and hairpin structures as non-coding precursor RNAs. This resemblance leads to problems annotating small RNAs.

Results

We mapped all microRNA precursors from miRBASE to several genomes and studied the repetition and dispersion of the corresponding loci. We then searched for repetitive elements overlapping these loci. We developed an automatic method called ncRNAclassifier to classify pre-ncRNAs according to their relationship with transposable elements (TEs). We showed that there is a correlation between the number of scattered occurrences of ncRNA precursor candidates and the presence of TEs. We applied ncRNAclassifier on six chordate genomes and report our findings. Among the 1,426 human and 721 mouse pre-miRNAs of miRBase, we identified 235 and 68 mis-annotated pre-miRNAs respectively corresponding completely to TEs.

Conclusions

We provide a tool enabling the identification of repetitive elements in precursor ncRNA sequences. ncRNAclassifier is available athttp://EvryRNA.ibisc.univ-evry.fr.
Comparative exome sequencing of metastatic lesions provides insights into the mutational progression of melanoma
Authors: Gartner Jared J , Davis Sean , Wei Xiaomu , Lin Jimmy C , Trivedi Niraj S , Teer Jamie K ,   NISC Comparative Sequencing Program, Meltzer Paul S , Rosenberg Steven A , Samuels Yardena
Published: September 2012

Background

Metastasis is characterized by spreading of neoplastic cells to an organ other than where they originated and is the predominant cause of death among cancer patients. This holds true for melanoma, whose incidence is increasing more rapidly than any other cancer and once disseminated has few therapeutic options. Here we performed whole exome sequencing of two sets of matched normal and metastatic tumor DNAs.

Results

Using stringent criteria, we evaluated the similarities and differences between the lesions. We find that in both cases, 96% of the single nucleotide variants are shared between the two metastases indicating that clonal populations gave rise to the distant metastases. Analysis of copy number variation patterns of both metastatic sets revealed a trend similar to that seen with our single nucleotide variants. Analysis of pathway enrichment on tumor sets shows commonly mutated pathways enriched between individual sets of metastases and all metastases combined.

Conclusions

These data provide a proof-of-concept suggesting that individual metastases may have sufficient similarity for successful targeting of driver mutations.
Expression analyses of the genes harbored by the type 2 diabetes and pediatric BMI associated locus on 10q23
Authors: Zhao Jianhua , Deliard Sandra , Aziz Ali Rahim , Grant Struan FA
Published: September 2012

Background

There is evidence that one of the key type 2 diabetes (T2D) loci identified by GWAS exerts its influence early on in life through its impact on pediatric BMI. This locus on 10q23 harbors three genes, encoding hematopoietically expressed homeobox (HHEX), insulin-degrading enzyme (IDE) and kinesin family member 11 (KIF11), respectively.

Methods

We analyzed the impact of adipogeneis on the mRNA and protein expression levels of these genes in the human adipocyte Simpson-Golabi-Behmel syndrome (SGBS) cell line in order to investigate which could be the culprit gene(s) in this region of linkage disequilibrium.

Results

Following activation of differentiation with a PPARγ ligand, we observed ~20% decrease in IDE, ~40% decrease in HHEX and in excess of 80% decrease in KIF11 mRNA levels when comparing the adipocyte and pre-adipocyte states. We also observed decreases in KIF11 and IDE protein levels, but conversely we observed a dramatic increase in HHEX protein levels. Subsequent time course experiments revealed some marked changes in expression as early as three hours after activation of differentiation.

Conclusion

Our data suggest that the expression of all three genes at this locus are impacted during SGBS adipogenesis and provides insights in to the possible mechanisms of how the genes at this 10q23 locus could influence both adipocyte differentiation and susceptibility to T2D through insulin resistance.
MHC2TA mRNA levels and human herpesvirus 6 in multiple sclerosis patients treated with interferon beta along two-year follow-up
Authors: Dominguez-Mozo Maria Inmaculada , Garcia-Montojo Marta , De Las Heras Virginia , Garcia-Martinez Angel , Arias-Leal Ana Maria , Casanova Ignacio , Arroyo Rafael , Alvarez-Lafuente Roberto
Published: September 2012

Background

In previous studies we found that MHC2TA +1614 genotype frequency was very different when MS patients with and without human herpesvirus 6 (HHV-6) in serum samples were compared; a different clinical behavior was also described. The purpose of the study was: 1. To evaluate if MHC2TA expression in MS patients was influenced by interferon beta (IFN-beta) treatment. 2. To study MHC2TA expression in MS patients with and without minor allele C. 3. To analyze the relation between MHC2TA mRNA levels and HHV-6 active infection in MS patients.

Methods

Blood and serum samples of 154 MS patients were collected in five programmed visits: basal (prior to beginning IFN-beta treatment), six, twelve, eighteen and twenty-four months later. HHV-6 in serum and MHC2TA mRNA levels were evaluated by PCR and RT-PCR, respectively. Neutralizing antibodies (NAbs) against IFN-beta were analyzed by the cytopathic effect assay.

Results

We found that MHC2TA mRNA levels were significantly lower among MS patients with HHV-6 active infection at the basal visit (without treatment) than in those MS patients without HHV-6 active infection at the basal visit (p = 0.012); in all the positive samples we only found variant A. Furthermore, 58/99 (58.6%) MS patients without HHV-6 along the five programmed visits and an increase of MHC2TA expression after two-years of IFN-beta treatment were clinical responders vs. 5/21 (23.8%) among those MS patients with HHV-6 and a decrease of MHC2TA mRNA levels along the two-years with IFN-beta treatment (p = 0.004); no differences were found between patients with and without NAbs.

Conclusions

MHC2TA mRNA levels could be decreased by the active replication of HHV-6; the absence of HHV-6 in serum and the increase of MHC2TA expression could be further studied as markers of good clinical response to IFN-beta treatment.
Hypoxic enhancement of exosome release by breast cancer cells
Authors: King Hamish W , Michael Michael Z , Gleadle Jonathan M
Published: September 2012

Background

Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour progression, angiogenesis and metastasis, potentially through exosome-mediated signalling.

Methods

Breast cancer cell lines were cultured under either moderate (1% O2) or severe (0.1% O2) hypoxia. Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA) and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by real-time reverse transcription polymerase chain reaction and normalised to exogenous and endogenous control genes. Statistical significance was determined using the Student T test with a P value of < 0.05 considered significant.

Results

Exposure of three different breast cancer cell lines to moderate (1% O2) and severe (0.1% O2) hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a hypoxia-inducible factor (HIF) hydroxylase inhibitor, resulted in significant increase in exosome release. Transfection of cells with HIF-1α siRNA prior to hypoxic exposure prevented the enhancement of exosome release by hypoxia. The hypoxically regulated miR-210 was identified to be present at elevated levels in hypoxic exosome fractions.

Conclusions

These data provide evidence that hypoxia promotes the release of exosomes by breast cancer cells, and that this hypoxic response may be mediated by HIF-1α. Given an emerging role for tumour cell-derived exosomes in tumour progression, this has significant implications for understanding the hypoxic tumour phenotype, whereby hypoxic cancer cells may release more exosomes into their microenvironment to promote their own survival and invasion.
Obstructive sleep apnea and multimorbidity
Authors: Robichaud-Hallé Laurence , Beaudry Michel , Fortin Martin
Published: September 2012

Background

Obstructive sleep apnea (OSA) is becoming increasingly prevalent in North America and has been described in association with specific chronic diseases, particularly cardiovascular diseases. In primary care, where the prevalence of co-occurring chronic conditions is very high, the potential association with OSA is unknown. The purpose of this study was to explore the association between OSA and 1) the presence and severity of multimorbidity (multiple co-occurring chronic conditions), and 2) subcategories of multimorbidity.

Methods

A cluster sampling technique was used to recruit 120 patients presenting with OSA of various severities from the records of a sleep laboratory in 2008. Severity of OSA was based on the results of the polysomnography. Patients invited to participate received a mail questionnaire including questions on sociodemographic characteristics and the Disease Burden Morbidity Assessment (DBMA). They also consented to give access to their medical records. The DBMA was used to provide an overall multimorbidity score and sub-score of diseases affecting various systems.

Results

Bivariate analysis did not demonstrate an association between OSA and multimorbidity (r = 0.117; p = 0.205). However, severe OSA was associated with multimorbidity (adjusted odds ratio = 7.33 [1.67-32.23], p = 0.05). OSA was moderately correlated with vascular (r = 0.26, p = 0.01) and metabolic syndrome (r = 0.26, p = 0.01) multimorbidity sub-scores.

Conclusions

This study showed that severe OSA is associated with severe multimorbidity and sub-scores of multimorbidity. These results do not allow any causal inference. More research is required to confirm these associations. However, primary care providers should be aware of these potential associations and investigate OSA when deemed appropriate.
Triple-negative breast cancer is associated with EGFR, CK5/6 and c-KIT expression in Malaysian women
Authors: Kanapathy Pillai Shant Kishen , Tay Annie , Nair Suseela , Leong Chee-Onn
Published: September 2012

Background

Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of breast cancer characterized by the lack of estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) expressions. This subgroup of refractory disease tends to have aggressive clinical behavior, high frequency of metastasis and lack of response to current hormonal or targeted therapies. Despite numerous studies reporting the clinicopathological features of TNBC and its association with the basal-like phenotype in the Western population, only limited data are available in the Asian population. Therefore, the aim of this study was to investigate the clinicopathological characteristics of TNBC and its association with epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6) and mast/stem cell growth factor receptor (c-KIT or CD117) expression in Malaysian women.

Methods

A total of 340 patients diagnosed with primary breast cancer between 2002 and 2006 in Malaysia were reviewed and analyzed.

Results

The incidence of TNBC was 12.4% (42/340). Bivariate analysis revealed that TNBC was strongly associated with a younger age, higher grade tumor and p53 expression. Further immunohistochemical analysis suggested that TNBC in Malaysian women was strongly associated with EGFR, CK5/6 and c-KIT expression with high a Ki-67 proliferation index.

Conclusion

In conclusion, our study confirms the association of TNBC with basal-like marker expression (EGFR, CK5/6 and c-KIT) in Malaysian women, consistent with studies in other populations.
Chromosomal structural analysis in carcinoma of the gallbladder
Authors: Dixit Ruhi , Kumar Prabhat , Tripathi Ratnakar , Basu Somprakash , Mishra Rajnikanth , Shukla VK
Published: September 2012

Background

The etiopathogenesis of gallbladder cancer is still unknown. Both environmental and patient factors have been incriminated in its cause. That it is found in pockets of epidemiological distribution raises an issue of genetic changes associated with it. The aim of this study was to find out the chromosomal changes in gallbladder cancer.

Methods

Lymphocyte cell culture was carried out on blood of gallbladder cancer patients to determine chromosomal banding abnormalities. Native PAGE was also evaluated to analyze lactate dehydrogenase (LDH), superoxide dismutase (SOD) and catalase enzyme activity from the same blood of gallbladder cancer patients.

Results

Out of 30 gallbladder cancer patients, 4 male showed breakage on the long arm of chromosome 1 while only one male patient showed the translocation from the long arm of chromosome 4 to the long arm of chromosome 6 in a male patient.

Conclusion

The aberrations found in our study may suggest underlying genetic predisposition for the development of gallbladder cancer. They can act as a marker for gallbladder cancer, which needs further study.
Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile women with endometriosis
Authors: Khan Meraj A , Sengupta Jayasree , Mittal Suneeta , Ghosh Debabrata
Published: September 2012

Background

In order to obtain a lead of the pathophysiology of endometriosis, genome-wide expressional analyses of eutopic and ectopic endometrium have earlier been reported, however, the effects of stages of severity and phases of menstrual cycle on expressional profiles have not been examined. The effect of genetic heterogeneity and fertility history on transcriptional activity was also not considered. In the present study, a genome-wide expression analysis of autologous, paired eutopic and ectopic endometrial samples obtained from fertile women (n = 18) suffering from moderate (stage 3; n = 8) or severe (stage 4; n = 10) ovarian endometriosis during proliferative (n = 13) and secretory (n = 5) phases of menstrual cycle was performed.

Methods

Individual pure RNA samples were subjected to Agilent’s Whole Human Genome 44K microarray experiments. Microarray data were validated (P < 0.01) by estimating transcript copy numbers by performing real time RT-PCR of seven (7) arbitrarily selected genes in all samples. The data obtained were subjected to differential expression (DE) and differential co-expression (DC) analyses followed by networks and enrichment analysis, and gene set enrichment analysis (GSEA). The reproducibility of prediction based on GSEA implementation of DC results was assessed by examining the relative expressions of twenty eight (28) selected genes in RNA samples obtained from fresh pool of eutopic and ectopic samples from confirmed ovarian endometriosis patients with stages 3 and 4 (n = 4/each) during proliferative and secretory (n = 4/each) phases.

Results

Higher clustering effect of pairing (cluster distance, cd = 0.1) in samples from same individuals on expressional arrays among eutopic and ectopic samples was observed as compared to that of clinical stages of severity (cd = 0.5) and phases of menstrual cycle (cd = 0.6). Post hoc analysis revealed anomaly in the expressional profiles of several genes associated with immunological, neuracrine and endocrine functions and gynecological cancers however with no overt oncogenic potential in endometriotic tissue. Dys-regulation of three (CLOCK, ESR1, and MYC) major transcription factors appeared to be significant causative factors in the pathogenesis of ovarian endometriosis. A novel cohort of twenty-eight (28) genes representing potential marker for ovarian endometriosis in fertile women was discovered.

Conclusions

Dysfunctional expression of immuno-neuro-endocrine behaviour in endometrium appeared critical to endometriosis. Although no overt oncogenic potential was evident, several genes associated with gynecological cancers were observed to be high in the expressional profiles in endometriotic tissue.
Overexpression of FoxM1 is associated with tumor progression in patients with clear cell renal cell carcinoma
Authors: Xue Yi-Jun , Xiao Ri-Hai , Long Da-Zhi , Zou Xiao-Feng , Wang Xiao-Ning , Zhang Guo-Xi , Yuan Yuan-Hu , Wu Geng-Qing , Yang Jun , Wu Yu-Ting , Xu Hui , Liu Fo-Lin , Liu Min
Published: September 2012

Background

Fork head box M1 (FoxM1) is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FoxM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. The present study was conducted to investigate the expression of FoxM1 and its prognostic significance in clear cell renal cell carcinoma (ccRCC). Meanwhile, the function of FoxM1 in human ccRCC was further investigated in cell culture models.

Methods

Real-time quantitative PCR, western blot and immunohistochemistry were used to explore FoxM1 expression in ccRCC cell lines and primary ccRCC clinical specimens. FoxM1 expression was knocked down by small interfering RNA (siRNA) in Caki-1 and 786-O cells; proliferation, colony formation, cell cycle, migration, invasion, and angiogenesis were assayed.

Results

FoxM1 expression was up-regulated in the majority of the ccRCC clinical tissue specimens at both mRNA and protein levels. Clinic pathological analysis showed that FoxM1 expression was significantly correlated with primary tumor stage (P <0.001), lymph node metastasis (P = 0.01), distant metastasis (P = 0.01), TNM stage (P < 0.001) and histological grade (P = 0.003). The Kaplan–Meier survival curves revealed that high FoxM1 expression was associated with poor prognosis in ccRCC patients (P < 0.001). FoxM1 expression was an independent prognostic marker of overall ccRCC patient survival in a multivariate analysis (P = 0.008). Experimentally, we found that down-regulation of FoxM1 inhibited cell proliferation and induced cell cycle arrest with reduced expression of cyclin B1, cyclin D1, and Cdk2, and increased expression of p21 and p27. Also, down-regulation of FoxM1 reduced expression and activity of matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF), resulting in the inhibition of migration, invasion, and angiogenesis.

Conclusions

These results suggest that FoxM1 expression is likely to play important roles in ccRCC development and progression, and that FoxM1 is a prognostic biomarker and a promising therapeutic target for ccRCC.
Epitope mapping by random peptide phage display reveals essential residues for vaccinia extracellular enveloped virion spread
Authors: He Yong , Wang Yonggang , Struble Evi B , Zhang Pei , Chowdhury Soma , Reed Jennifer L , Kennedy Michael , Scott Dorothy E , Fisher Robert W
Published: September 2012

Background

A33 is a type II integral membrane protein expressed on the extracellular enveloped form of vaccinia virus (VACV). Passive transfer of A33-directed monoclonal antibodies or vaccination with an A33 subunit vaccine confers protection against lethal poxvirus challenge in animal models. Homologs of A33 are highly conserved among members of theOrthopoxvirusgenus and are potential candidates for inclusion in vaccines or assays targeting extracellular enveloped virus activity. One monoclonal antibody directed against VACV A33, MAb-1G10, has been shown to target a conformation-dependent epitope. Interestingly, while it recognizes VACV A33 as well as the corresponding variola homolog, it does not bind to the monkeypox homolog. In this study, we utilized a random phage display library to investigate the epitope recognized by MAb-1G10 that is critical for facilitating cell-to-cell spread of the vaccinia virus.

Results

By screening with linear or conformational random phage libraries, we found that phages binding to MAb-1G10 display the consensus motif CEPLC, with a disulfide bond formed between two cysteine residues required for MAb-1G10 binding. Although the phage motif contained no linear sequences homologous to VACV A33, structure modeling and analysis suggested that residue D115 is important to form the minimal epitope core. A panel of point mutants expressing the ectodomain of A33 protein was generated and analyzed by either binding assays such as ELISA and immunoprecipitation or a functional assessment by blocking MAb-1G10 mediated comet inhibition in cell culture.

Conclusions

These results confirm L118 as a component of the MAb-1G10 binding epitope, and further identify D115 as an essential residue. By defining the minimum conformational structure, as well as the conformational arrangement of a short peptide sequence recognized by MAb-1G10, these results introduce the possibility of designing small molecule mimetics that may interfere with the function of A33in vivo. This information will also be useful for designing improved assays to evaluate the potency of monoclonal and polyclonal products that target A33 or A33-modulated EV dissemination.
The Cytochrome P450 Inhibitor, Ketoconazole, Inhibits Oxidized Linoleic Acid Metabolite-Mediated Peripheral Inflammatory Pain
Authors: Ruparel Shivani , Green Dustin , Chen Paul , Hargreaves Kenneth M
Published: September 2012

Background:

Oxidized linoleic acid metabolites (OLAMs) are a class of endogenous agonists to the transient receptor potential V1 (TRPV1) receptor. Although TRPV1 mediates inflammatory heat hyperalgesia, it is not known if the OLAMs contribute to the peripheral activation of this receptor during tissue inflammation. In the present study, we evaluated whether the OLAM system is activated during inflammation and whether cytochrome P450 enzymes mediate OLAM contributions to heat hyperalgesia using the complete Freund's adjuvant (CFA) model of inflammation.

Results:

Our results demonstrate that the intraplantar (ipl) injection of anti-OLAM antibodies significantly reversed CFA-induced heat hyperalgesia. Moreover, application of lipid extracts from inflamed rat skin to cultured sensory neurons triggered a significant release of iCGRP that is blocked by co-treatment with I-RTX, a TRPV1 antagonist. To determine the role of CYP enzymes in mediating OLAM effects, we used a broad spectrum CYP inhibitor, ketoconazole. Pretreatment with ketoconazole inhibited the release of TRPV1 agonists in lipid extracts from inflamed skin and significantly reversed CFA-induced heat hyperalgesia by a peripheral mechanism of action. Moreover, the ipl injection of linoleic acid to rats 24 hr after CFA evoked spontaneous nocifensive behaviors that were significantly reduced by capsazepine, by knockout of the TRPV1 gene, or by pretreatment with either anti-OLAM antibodies or ketoconazole.

Conclusions:

Taken together, our data suggests that OLAMs contribute to inflammatory nociception in the periphery and that cytochrome P450 enzymes play a crucial role in mediating OLAM contributions to inflammatory heat hyperalgesia.
Fire ignition during laser surgery in pet rodents
Authors: Collarile Tommaso , Di Girolamo Nicola , Nardini Giordano , Ciraci Ivano Antonio , Selleri Paolo
Published: September 2012

Background

Laser surgery is an attractive alternative to other means of section device in terms of tissue inflammation and interaction, which has been extensively used in human and veterinary medicine. Although accidental ignition during laser surgeries is sporadically reported in human medical literature, to the authors’ knowledge this is the first report regarding laser-dependent fire ignition during surgery in veterinary medicine.

Case presentation

Two rodents, a 13-month old, 27-gram, male pet mouse (Mus musculus) and a 1-year old, female Russian hamster (Phodopus sungorus), underwent surgical removal of masses with diode laser. During the surgical procedures fires ignited from the face masks. The mouse presented severe burns on the head and both forelimbs, it was hospitalized and approximately 2 months after surgery burns were resolved. The hamster presented severe burns on the face and the proximal regions of the body. At 72 hours from the accident the hamster was euthanized.

Conclusion

The present report suggests that fire ignition is a potential life-threatening complication of laser surgery in non-intubated rodents maintained under volatile anesthesia. High oxygen concentrations, the presence of combustible, and the narrowness of the surgical field with the face mask during laser surgery on rodents are risk factors for fire ignition.
Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise
Authors: Birtwistle Marc R , Rauch Jens , Kiyatkin Anatoly , Aksamitiene Edita , Dobrzyński Maciej , Hoek Jan B , Kolch Walter , Ogunnaike Babatunde A , Kholodenko Boris N
Published: September 2012

Background

Cell-to-cell variability in protein expression can be large, and its propagation through signaling networks affects biological outcomes. Here, we apply deterministic and probabilistic models and biochemical measurements to study how network topologies and cell-to-cell protein abundance variations interact to shape signaling responses.

Results

We observe bimodal distributions of extracellular signal-regulated kinase (ERK) responses to epidermal growth factor (EGF) stimulation, which are generally thought to indicate bistable or ultrasensitive signaling behavior in single cells. Surprisingly, we find that a simple MAPK/ERK-cascade model with negative feedback that displays graded, analog ERK responses at a single cell level can explain the experimentally observed bimodality at the cell population level. Model analysis suggests that a conversion of graded input–output responses in single cells to digital responses at the population level is caused by a broad distribution of ERK pathway activation thresholds brought about by cell-to-cell variability in protein expression.

Conclusions

Our results show that bimodal signaling response distributions do not necessarily imply digital (ultrasensitive or bistable) single cell signaling, and the interplay between protein expression noise and network topologies can bring about digital population responses from analog single cell dose responses. Thus, cells can retain the benefits of robustness arising from negative feedback, while simultaneously generating population-level on/off responses that are thought to be critical for regulating cell fate decisions.
Synthesis, structure and solvatochromic properties of some novel 5-arylazo-6-hydroxy-4-phenyl-3-cyano-2-pyridone dyes
Authors: Alimmari Adel , Mijin Dušan , Vukićević Radovan , Božić Bojan , Valentić Nataša , Vitnik Vesna , Vitnik Željko , Ušćumlić Gordana
Published: September 2012

Background

A series of some novel arylazo pyridone dyes was synthesized from the corresponding diazonium salt and 6-hydroxy-4-phenyl-3-cyano-2-pyridone using a classical reaction for the synthesis of the azo compounds.

Results

The structure of the dyes was confirmed by UV-vis, FT-IR, 1H NMR and 13C NMR spectroscopic techniques and elemental analysis. The solvatochromic behavior of the dyes was evaluated with respect to their visible absorption properties in various solvents.

Conclusions

The azo-hydrazone tautomeric equilibration was found to depend on the substituents as well as on the solvent. The geometry data of the investigated dyes were obtained using DFT quantum-chemical calculations. The obtained calculational results are in very good agreement with the experimental data.
Chloramine-induced anaphylaxis while showering: a case report
Authors: D’Alò Simona , De Pasquale Tiziana , Incorvaia Cristoforo , Illuminati Ilenia , Mistrello Gianni , Roncarolo Daniela , Pucci Stefano
Published: September 2012

Introduction

Sodium-N-chlorine-p-toluene sulfonamide, commonly known as chloramine-T, is a derivative of chlorine which is widely used as a disinfectant. For many years, chloramine-T has been described as a cause of immediate-type hypersensitivity, especially with regard to asthma and rhinitis, and as a cause of occupational dermatoses in cleaning personnel in hospitals, although no anaphylactic reaction has yet been reported. Hence, to the best of our knowledge we present the first case of anaphylaxis to chloramine-T with evidence of specific immunoglobulin E antibodies.

Case presentation

We describe the case of a 25-year-old Caucasian woman who was in good health and with a negative history for atopy, including no respiratory symptoms of rhinitis or asthma, and with no professional exposure to chloramine-T. She, while showering, applied a chloramine-T solution to a skin area with folliculitis on her leg, and within a few minutes developed generalized urticaria and angioedema, followed by vomiting and collapse with loss of consciousness. A skin prick test with a chloramine-T solution at 10mg/mL concentration was positive, and specific immunoglobulin E to chloramine-T was quantified at a value of 2.9 optical density as measured by the enzyme allergosorbent test technique.

Conclusion

The strict cause-effect relationship and the results of the skin test and the in vitro test make certain the causative role of chloramine-T in this case of anaphylaxis. This suggests that chloramine-T, based on its wide use as a disinfectant, should be considered a possible cause in anaphylaxis of unknown origin.
A role for low-abundance miRNAs in colon cancer: the miR-206/Krüppel-like factor 4 (KLF4) axis
Authors: Parasramka Mansi A , Dashwood W Mohaiza , Wang Rong , Saeed Hassaan H , Williams David E , Ho Emily , Dashwood Roderick H
Published: September 2012

Background

MicroRNAs (miRNAs or miRs) are short non-coding RNAs that affect the expression of genes involved in normal physiology, but that also become dysregulated in cancer development. In the latter context, studies to date have focused on high-abundance miRNAs and their targets. We hypothesized that among the pool of low-abundance miRNAs are some with the potential to impact crucial oncogenic signaling networks in colon cancer.

Results

Unbiased screening of over 650 miRNAs identified miR-206, a low-abundance miRNA, as the most significantly altered miRNA in carcinogen-induced rat colon tumors. Computational modeling highlighted the stem-cell marker Krüppel-like factor 4 (KLF4) as a potential target of miR-206. In a panel of primary human colon cancers, target validation at the mRNA and protein level confirmed a significant inverse relationship between miR-206 and KLF4, which was further supported by miR-206 knockdown and ectopic upregulation in human colon cancer cells. Forced expression of miR-206 resulted in significantly increased cell proliferation kinetics, as revealed by real-time monitoring using HCT116 cells.

Conclusions

Evolutionarily conserved high-abundance miRNAs are becoming established as key players in the etiology of human cancers. However, low-abundance miRNAs, such as miR-206, are often among the most significantly upregulated miRNAs relative to their expression in normal non-transformed tissues. Low-abundance miRNAs are worthy of further investigation, because their targets include KLF4 and other pluripotency and cancer stem-cell factors.
Measuring Direct Thrombin Inhibitors With Routine and Dedicated Coagulation Assays
Authors: Curvers Joyce , van de Kerkhof Daan , Stroobants An K. , van den Dool Erik-Jan , Scharnhorst Volkher
Published: September 2012

The use of direct thrombin inhibitors (DTIs) for prophylactic or therapeutic anticoagulation is increasing because of the predictable bioavailability and short half-life of these DTIs. However, in certain situations, indication of the concentration is warranted. We investigated the effects of 3 DTIs (lepirudin, argatroban, and bivalirudin) in 6 pooled plasma specimens on routine coagulation assays (activated partial thromboplastin time [aPTT], prothrombin time [PT], and thrombin time [TT]) and dedicated DTI assays (Hemoclot, HemosIL, the ecarin clotting time, and a chromogenic ecarin clotting time) on 2 coagulation analyzers. We found routine tests to be nondiscriminative between concentrations of different DTIs in the aPTT. Moreover, for PT and TT, the responses for different DTIs differed. This was similar for ecarin clotting assays. The Hemoclot and HemosIL assays showed identical linear increases for all 3 DTIs. We conclude that dedicated calibrated assays based on a diluted TT (Hemoclot and HemosIL) appear to be the most suitable for monitoring purposes.
Modonomics: Participation and competition in contention
Authors: Van der Graaf Shenja
Published: September 2012

This article considers user participation in 3D development practices, known as mod development, in the commercial setting of the 3D software industry. By drawing on two prominent developer firms, i.e. Valve Inc.® and Linden Lab®, this article is designed to learn more about
the increasing importance attributed to user participation in this context by exploring the ways in which these software developer firms facilitate or invite users to participate in development practices. The results of interviews conducted with employees of these firms, and an online survey
with their respective user base, are used as evidence. The article demonstrates that, to various extents, interdependencies develop between the firm, users and technologies, directing our attention to the boundaries of participation and competition. It extends our understanding of how certain
participatory designs provide a structure to how game development is informed and organized across firm boundaries based on the moderating role of product and user characteristics.
Impact of Globalization on Income Distribution Inequality in 60 Countries: Comments
Authors: Tsai Pan-Long , Huang Chao-Hsi , Yang Chih-Yuan
Published: September 2012

In a recent article in the Global Economy Journal, Lei Zhou, Basudeb Biswas, Tyler Bowles and Peter J. Saunders (2011) have shown that globalization does not contribute to income inequality in a sample of 60 countries. In this comments we have demonstrated that their conclusion is misleading for improperly pooling countries with extremely different economic systems in their regression analyses. Specifically, only countries with sufficiently high level of development could expect to benefit from globalization as far as income distribution is concerned.
DNA Pooling and Statistical Tests for the Detection of Single Nucleotide Polymorphisms
Authors: Ramsey David M. , Futschik Andreas
Published: September 2012

The development of next generation genome sequencers gives the opportunity of learning more about the genetic make-up of human and other populations. One important question involves the location of sites at which variation occurs within a population. Our focus will be on the detection of rare variants. Such variants will often not be present in smaller samples and are hard to distinguish from sequencing errors in larger samples. This is particularly true for pooled samples which are often used as part of a cost saving strategy. The focus of this article is on experiments that involve DNA pooling. We derive experimental designs that optimize the power of statistical tests for detecting single nucleotide polymorphisms (SNPs, sites at which there is variation within a population). We also present a new simple test that calls a SNP, if the maximum number of reads of a prospective variant across lanes exceeds a certain threshold. The value of this threshold is defined according to the number of available lanes, the parameters of the genome sequencer and a specified probability of accepting that there is variation at a site when no variation is present. On the basis of this test, we derive pool sizes which are optimal for the detection of rare variants. This test is compared with a likelihood ratio test, which takes into account the number of reads of a prospective variant from all the lanes. It is shown that the threshold based rule achieves a comparable power to this likelihood ratio test and may well be a useful tool in determining near optimal pool sizes for the detection of rare alleles in practical applications.
Hepatoprotective and in vivo antioxidant activities of ethanolic extract of whole fruit of Lagenaria breviflora
Authors: Saba Adebowale B. , Onakoya Omowumi M. , Oyagbemi Ademola A.
Published: September 2012

Background: This study was designed to investigate the hepatoprotective and in vivo antioxidant effects of the ethanol extract of whole fruit of Lagenaria breviflora (LB) in experimental animals.

Methods: Forty nine Wistar albino rats were divided into seven groups of seven. Group I served as the control group; rats in Group II were given i.p. carbon tetrachloride (CCL4) (1.5 mL/kg) alone; Groups III–VI received different concentrations of plant extract (100, 250 and 500 mg/kg) with CCL4 and Group VII received kolaviron (KV) at 200 mg/kg as a reference hepatoprotective agent.

Results: There was a significant (p<0.05) increase in malondialdehyde (MDA) and hydrogen peroxide (H202) generation in the serum of CCL4 treated rats (Group II) while the serum glutathione (GSH) level decreased significantly. Pretreatment with LB extract led to a significant (p<0.05) increase in serum GSH and a significant (p<0.05) reduction in MDA and H2O2generation. The activities of marker enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin, creatinine and blood urea nitrogen (BUN) increased (p<0.05) significantly in CCL4 treated rats (Group II).

Conclusions: The present study suggested that treatment with LB extract enhances the recovery from CCL4 induced hepatic damage and oxidative stress via its antioxidant and hepatoprotective properties.
Local fusion graphs for symmetric groups
Authors: Ballantyne John , Greer Nicholas , Rowley Peter
Published: September 2012

For a group
Implementation of Collaborative Software in Enterprises: A Thematic Analysis
Authors: Schubert Petra , Williams Susan P.
Published: September 2012

The article investigates 16 implementation projects (cases) of collaborative systems to identify structures, processes and activities associated with implementing change. Using an interpretive research process we apply thematic content analysis to the case documents to identify key themes in the introduction of collaborative technologies. The coding process yielded 184 individual codes which were grouped into 28 themes. These themes are discussed and the findings presented using the 8C Framework. The findings indicate a complex array of methods, processes and strategies for the management of change.
Vorhersage des Phasenrauschens in optischen Messsystemen mit strukturierter Beleuchtung
Authors: Fischer Marc , Petz Marcus , Tutsch Rainer
Published: September 2012

In dieser Arbeit wird eine Methode vorgestellt, mit der sich ein Schätzwert für das Phasenrauschen in optischen Messsystemen mit strukturierter Beleuchtung direkt aus den aufgezeichneten Grauwerten berechnen lässt. Das verwendete Rauschmodell basiert auf einer Richtlinie zur Charakterisierung von Bildsensoren (EMVA 1288), so dass die benötigten Parameter direkt einem konformen Datenblatt entnommen werden können. Alternativ wird in dieser Arbeit auch eine Methode beschrieben, mit der die Parameter ohne zusätzlichen Geräteaufwand experimentell ermittelt werden können.
Fundamental Investigation of the HER on a Pt(111) Surface at Temperatures down to 120K
Authors: Brülle Tine , Schneider Oliver , Stimming Ulrich
Published: September 2012

The hydrogen evolution reaction (HER) is of fundamental importance in electrochemistry, and despite the large number of theoretical and experimental investigations, it is still far from being completely understood. In the present work, the HER is studied on a Pt(111) surface in a wide range of temperatures down to 120 K. The overall reaction and the first reaction step, the Volmer reaction, were evaluated separately using potentiostatic pulses in order to obtain a detailed understanding of the different reaction steps. At room temperature, the Volmer reaction exhibits a Tafel slope of 120 mV/dec, which is the expected value for a single electron transfer. For the overall reaction a change in Tafel slope at -η ≈ 50 mV is found. While the Tafel slope is ≈ 30 mV/dec for small overpotentials, it is 120 mV/dec for larger overpotentials. For both the overall reaction and the Volmer reaction, a strong dependence of the apparent transfer coefficient on temperature is found. This temperature dependence cannot be explained using classical electron transfer theory.
No “Perfect Garden”: American Constructions of Hawaiian Landscapes and the Making of a Climatic Borderland
Authors: Kessler Lawrence
Published: September 2012

Based on earlier published descriptions by missionaries and others, the US Exploring Expedition of 1838-1842, under Charles Wilkes, expected to find Hawai‘i a fertile tropical garden. Instead, they found a significantly westernized climatic borderland between tropical and temperate zones. Wilkes’s report is a case of landscape creation. It represented Hawai‘i in terms of comparison to American readers’ experience and expectations. In presenting Hawaiian landscapes as distinct from the tropics, the expedition made the islands seem more inviting to American expansionism.
Aleitamento materno: conhecimento e prática
Authors: Fonseca-Machado Mariana de Oliveira , Haas Vanderlei José , Stefanello Juliana , Nakano Ana Márcia Spanó , Gomes-Sponholz Flávia
Published: September 2012

Objetivou-se caracterizar as práticas de promoção ao aleitamento materno desenvolvidas pelos profissionais de enfermagem da Estratégia de Saúde da Família e analisar a correlação entre seu conhecimento sobre aleitamento materno e a frequência com que realizavam orientações sobre o tema nesses momentos. Trata-se de estudo observacional, transversal, descritivo e exploratório desenvolvido nas unidades de saúde da família do município de Uberaba-MG, com 85 profissionais de enfermagem, por meio de dois questionários. Na análise, utilizaram-se distribuição de frequências e análise de correlação de Spearman. A maioria dos profissionais afirmou que, frequentemente, abordava o aleitamento materno nas atividades práticas investigadas. Entretanto, houve uma fraca correlação entre a frequência dessa abordagem e a média de acertos no teste de conhecimento. As declarações dos profissionais de enfermagem indicam que as orientações sobre aleitamento materno eram feitas independentemente do conhecimento que possuíam sobre o tema.