bluuebunny/crossref_metadata_2025 huggingface dataset:
Peer-Disagreement about Restaurant Bills and Abortion
Authors: Sticker Martin
Published: March 2017

The author defends Conciliationism as a response to peer-disagreement in ethics against a prominent objection: if in cases of peer-disagreement we have to move our credences towards those of our dissenting peers, then we have to adopt scepticism in fields where disagreement between peers abounds. For this objection, the case of ethics is particularly worrisome. The author argues that the objection from scepticism is based on a highly idealised notion of an epistemic peer. In cases of disagreement about ethical issues, it is often unknown to us what another person counts as her evidence, since one’s notions of what counts as evidence and what weight to attach to different forms of evidence are impacted by one’s global outlook. Being aware of what an agent considers as evidence requires familiarity with that agent’s global outlook. This introduces two constraints on epistemic peerhood in cases of disagreement about ethics: an epistemic constraint (I might not be sufficiently aware of what someone counts as evidence, and hence not consider that person a peer), and a factual constraint (we might disregard each other’s evidence, and hence not consider each other peers).
How it is Again
Authors: Katz Daniel
Published: March 2017

This essay examines How It Is in the context of Beckett’s personal creative crisis of the late fifties from which it arose, and also that of his psychoanalysis with Bion, 20 years earlier. Looking at How It Is as a work that tends to collapse the opposition between regression and renewal, the essay also examines the role of unpleasure in the text, as a complication of the oft noted sadism. Finally, the work’s parodic pedagogic episodes of “training” are compared to similar motifs in Murphy and Molloy, in light of Laplanche’s theory of seduction.
Beckett’s Mental Cartography in Le Dépeupleur and Company
Authors: Inoue Yoshiyuki
Published: March 2017

In this essay, I explore Beckett’s later fiction in terms of his figurative mind. First, I survey Beckett’s interest in anatomical tables in his later prose. Second, I reconsider the importance of Jung’s “Tavistock Lectures” in terms of the configuration of the mind, and compare his view of the dark centre of the unconscious with the central arena of Le Dépeupleur. Finally, I address the cylinder in Le Dépeupleur and the dark in Company in connection with the (im)possibility of a mental tabulation based on the art of geodesy.
Cognition Enactment
Authors: Van Hulle Dirk
Published: March 2017

This essay investigates to what extent it is possible with hindsight, on the basis of manuscripts, to reconstruct the cognitive process underlying the textual genesis of a literary work. The case study is Beckett’s novel Molloy and the characterization of Molloy and Moran against the background of Beckett’s reading of André Gide’s Dostoïevsky and Pierre Gustave Brunet’s Curiosités théologiques. The seemingly programmatic Molloy/Moran dichotomy, possibly modelled after Gide’s contrast between Dostoevsky and Balzac, turns out to be the result of an écriture à processus rather than à programme. This case study serves to illustrate how consciousness enactment, combined with an enactivist approach to cognition, can be of help in defining the role of the reader in genetic criticism.
The Crime of ‘Making Real’ in All That Fall
Authors: Chiang Michelle
Published: March 2017

Examining the potential crime in All That Fall as a crime of reification, this essay seeks to expose two ontological levels within the radio play that are governed by opposing temporalities. It concludes with an assertion that attempting to ‘make real’ distorts an intuitive experience of reality.
Two new species of Amphinemura (Plecoptera: Nemouridae) from Tibet
Authors: LI WEIHAI , WANG YING , YANG DING
Published: March 2017

Two new species of the nemourid genus Amphinemura are described based on recent material collected from the Tibet Autonomous Region of China. The new taxa include A. chayuensis sp. nov. and A. hexalobata sp. nov., the latter species is respresented by both sexes. The new species are compared to related taxa.
Internal-Wave-Driven Mixing: Global Geography and Budgets
Authors: Kunze Eric
Published: March 2017

Internal-wave-driven dissipation rates ε and diapycnal diffusivities K are inferred globally using a finescale parameterization based on vertical strain applied to ~30 000 hydrographic casts. Global dissipations are 2.0 ± 0.6 TW, consistent with internal wave power sources of 2.1 ± 0.7 TW from tides and wind. Vertically integrated dissipation rates vary by three to four orders of magnitude with elevated values over abrupt topography in the western Indian and Pacific as well as midocean slow spreading ridges, consistent with internal tide sources. But dependence on bottom forcing is much weaker than linear wave generation theory, pointing to horizontal dispersion by internal waves and relatively little local dissipation when forcing is strong. Stratified turbulent bottom boundary layer thickness variability is not consistent with OGCM parameterizations of tidal mixing. Average diffusivities K = (0.3–0.4) × 10−4 m2 s−1 depend only weakly on depth, indicating that ε = KN2/γ scales as N2 such that the bulk of the dissipation is in the pycnocline and less than 0.08-TW dissipation below 2000-m depth. Average diffusivities K approach 10−4 m2 s−1 in the bottom 500 meters above bottom (mab) in height above bottom coordinates with a 2000-m e-folding scale. Average dissipation rates ε are 10−9 W kg−1 within 500 mab then diminish to background deep values of 0.15 × 10−9 W kg−1 by 1000 mab. No incontrovertible support is found for high dissipation rates in Antarctic Circumpolar Currents or parametric subharmonic instability being a significant pathway to elevated dissipation rates for semidiurnal or diurnal internal tides equatorward of 28° and 14° latitudes, respectively, although elevated K is found about 30° latitude in the North and South Pacific.
Observation System Experiments with the Hourly Updating Rapid Refresh Model Using GSI Hybrid Ensemble–Variational Data Assimilation
Authors: James Eric P. , Benjamin Stanley G.
Published: March 2017

A set of observation system experiments (OSEs) over three seasons using the hourly updated Rapid Refresh (RAP) numerical weather prediction (NWP) assimilation–forecast system identifies the importance of the various components of the North American observing system for 3–12-h RAP forecasts. Aircraft observations emerge as the strongest-impact observation type for wind, relative humidity (RH), and temperature forecasts, permitting a 15%–30% reduction in 6-h forecast error in the troposphere and lower stratosphere. Major positive impacts are also seen from rawinsondes, GOES satellite cloud observations, and surface observations, with lesser but still significant impacts from GPS precipitable water (PW) observations, satellite atmospheric motion vectors (AMVs), and radar reflectivity observations. A separate experiment revealed that the aircraft-related RH forecast improvement was augmented by 50% due specifically to the addition of aircraft moisture observations. Additionally, observations from en route aircraft and those from ascending or descending aircraft contribute approximately equally to the overall forecast skill, with the strongest impacts in the respective layers of the observations. Initial results from these OSEs supported implementation of an improved assimilation configuration of boundary layer pseudoinnovations from surface observations, as well as allowing the assimilation of satellite AMVs over land. The breadth of these experiments over the three seasons suggests that observation impact results are applicable to general forecasting skill, not just classes of phenomena during limited time periods.
Youth self-harm in low- and middle-income countries: Systematic review of the risk and protective factors
Authors: Aggarwal Shilpa , Patton George , Reavley Nicola , Sreenivasan Shreenivas A , Berk Michael
Published: March 2017

Background:

Self-harm (defined here as an act of intentionally causing harm to own self, irrespective of the type, motive or suicidal intent) is one of the strongest antecedents of suicide in youth. While there have been a number of studies of youth self-harm in low- and middle-income countries (LMICs), there is currently no systematic review of studies of prevalence rates and risk and protective factors.

Aim:

To systematically review the evidence relating to the prevalence rates and forms of self-harm in youth in LMICs and its relationship to family economic status, family functioning, relationship with the peer group, social relationships and academic performance.

Methods:

Electronic searches of three databases, MEDLINE, PsycINFO and Scopus, were performed. In total, 27 school-, community- and hospital-based studies evaluating self-harm in LMICs with youth focus (with participants between 12 and 25 years) were included.

Results:

The self-harm was divided into suicidal and non-suicidal depending on the nature of self-harm. The 12-month prevalence rates of non-suicidal self-harm varied from 15.5% to 31.3%, and the range of suicidal behaviour rates was from 3.2% to 4.7%. Banging and hitting were the most common in the community-based studies, followed by cutting, scratching and wound picking. Self-poisoning with pesticides was most commonly reported in hospital-based studies. Risk factors for self-harm were family conflict, peer groups with members indulging in self-harm, truancy and school absenteeism. Protective factors were having an understanding family, having friends and higher school competence. Risk factors for suicidal thoughts and attempts were lack of close friends and history of suicide by a friend.

Conclusion:

The 12-month prevalence rates of youth self-harm in LMICs are comparable to high-income countries (HICs). The profile of risk and protective factors suggests that family-based interventions could be useful in treatment and prevention. Future studies should aim for greater consistency in assessment methods and the constructs under evaluation.
The synergy of the refugee crisis and the financial crisis in Greece: Impact on mental health
Authors: Anagnostopoulos Dimitris C , Giannakopoulos George , Christodoulou Nikos G
Published: March 2017

Background:

The current global financial crisis that started in 2008 resulted in a significant decline in global trade, slowing/reversing economic growth worldwide, and a dramatic increase in public sector debt. At the same time, the global migrant/refugee crisis has reached extreme rates, with millions of people being forced to abandon their homes and communities because of war, political violence or related threats. There is a broad consensus about the deleterious consequences of these crises on psychological well-being, depression, anxiety disorders, insomnia, alcohol abuse and suicidal behavior. Although the separate consequences of economic recession and immigration are extensively discussed in previous research, we know very little about the processes through which the intersection of economic crisis and migrant crisis contributes to the vulnerabilities of natives and migrants during these crises. Of particular concern is the status of children, adolescents and their families, who constitute one of the most vulnerable groups in society.

Aim:

To discuss the contexts that economic and migrant crises shape and suggest possible effects of this intersection on mental health risks, especially among children, adolescents and their families, through reflecting on the recent experience in Greece.

Method:

Review of the literature and critical analysis of the effects of the confluent crises.

Conclusion:

The interactive effects of these two crises need further exploration. Novel and diverse models of psychological understanding need to be developed in order to manage the effects of the confluent crises. The role of mental health professionals is crucial in this respect, offering culturally flexible, accommodating and empathetic approaches, allowing healing and acceptance in the face of adversity.
Heparanase overexpression down-regulates syndecan-1 expression in a gallbladder carcinoma cell line
Authors: Jin Hao , Zhou Shaobo , Yang Song , Cao Hai-ming
Published: March 2017

Objective

To discuss the relevance of heparanase and syndecan-1 and regulation of the heparanase-syndecan1 axis in the invasiveness of gallbladder carcinoma cells.

Methods

1. Generation of a gallbladder cancer cell line overexpressing a heparanase (GBD-SD) transgene. 2. Western blot analysis of syndecan-1 levels of GBD-SD and control gallbladder carcinoma (GBC-SD) cells. 3. RT-PCR analysis of syndecan-1 mRNA levels of GBD-SD and GBC-SD. 4. Evaluation of invasion and migration of GBD-SD and GBC-SD cells.

Results

1. Heparanase expression in GBD-SD cells was significantly increased. 2. The syndecan-1 mRNA level of GBD-SD cells was significantly lower compared with that of GBC-SD cells. 3. The syndecan-1 DNA copy number in GBD-SD cells was significantly lower compared with that of GBC-SD. 4. The invasiveness and migration of GBD-SD cells were significantly higher compared with GBC-SD cells.

Conclusions

1. The expression of heparanase negatively correlated with that of syndecan-1 in a gallbladder carcinoma cell line. 2. The expression of heparanase and syndecan-1 in gallbladder carcinomas negatively correlated, similar to other tumours. 3. The heparanase/syndecan1 axis in gallbladder carcinoma plays an important role in the invasion and metastasis, thus providing a new therapeutic target. 4. Further research is required to identify the detailed mechanisms.
Presence of Bacteria in Spontaneous Achilles Tendon Ruptures
Authors: Rolf Christer G. , Fu Sai-Chuen , Hopkins Chelsea , Luan Ju , Ip Margaret , Yung Shu-Hang , Friman Göran , Qin Ling , Chan Kai-Ming
Published: March 2017

Background:

The structural pathology of Achilles tendon (AT) ruptures resembles tendinopathy, but the causes remain unknown. Recently, a number of diseases were found to be attributed to bacterial infections, resulting in low-grade inflammation and progressive matrix disturbance. The authors speculate that spontaneous AT ruptures may also be influenced by the presence of bacteria.

Hypothesis:

Bacteria are present in ruptured ATs but not in healthy tendons.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

Patients with spontaneous AT ruptures and patients undergoing anterior cruciate ligament (ACL) reconstruction were recruited for this study. During AT surgical repair, excised tendinopathic tissue was collected, and healthy tendon samples were obtained as controls from hamstring tendon grafts used in ACL reconstruction. Half of every sample was reserved for DNA extraction and the other half for histology. Polymerase chain reaction (PCR) was conducted using 16S rRNA gene universal primers, and the PCR products were sequenced for the identification of bacterial species. A histological examination was performed to compare tendinopathic changes in the case and control samples.

Results:

Five of 20 AT rupture samples were positive for the presence of bacterial DNA, while none of the 23 hamstring tendon samples were positive. Sterile operating and experimental conditions and tests on samples, controlling for harvesting and processing procedures, ruled out the chance of postoperative bacterial contamination. The species identified predominantly belonged to the Staphylococcus genus. AT rupture samples exhibited histopathological features characteristic of tendinopathy, and most healthy hamstring tendon samples displayed normal tendon features. There were no apparent differences in histopathology between the bacterial DNA–positive and bacterial DNA–negative AT rupture samples.

Conclusion:

The authors have demonstrated the presence of bacterial DNA in ruptured AT samples. It may suggest the potential involvement of bacteria in spontaneous AT ruptures.
Perils and positives of science journalism in Australia
Authors: McKinnon Merryn , Howes Johanna , Leach Andrew , Prokop Natasha
Published: March 2017

Scientists, science communicators and science journalists interact to deliver science news to the public. Yet the value of interactions between the groups in delivering high-quality science stories is poorly understood within Australia. A recent study in New Zealand on the perspectives of the three groups on the challenges facing science journalism is replicated here in the context of New South Wales and the Australian Capital Territory. While all three groups perceived the quality of science journalism as generally high, the limitations of non-specialists and public relation materials were causes for concern. The results indicate that science communicators are considered to play a valuable role as facilitators of information flow to journalists and support for scientists. Future studies on the influence and implications of interactions between these three groups are required.
SIRT1 promotes the proliferation and metastasis of human pancreatic cancer cells
Authors: Jin Jianguang , Chu Zhijie , Ma Pengfei , Meng Yuanpu , Yang Yanhui
Published: March 2017

SIRT1 plays an important role in human malignant progression, inducing cancer cell proliferation and metastasis by regulating downstream gene expressions. However, little is known about the underlying mechanisms in which SIRT1 promotes pancreatic cancer tumorigenesis. The aim of this study is to investigate the SIRT1 expression levels and biological functions in promoting pancreatic cancer progression. We first investigated the expression of SIRT1 in a series of pancreatic cancer tissues as well as in a panel of pancreatic cancer cell lines. The effect of SIRT1 on cell activity was explored by knockdown experiments. Cell growth was measured using the MTT assay and colony-formation assay. Migration and invasion were tested using transwell assay. Our results showed that the expression of SIRT1 was significantly up-regulated both in pancreatic cancer tissues and cell lines. Knockdown of SIRT1 suppressed cell proliferation and migration of pancreatic cancer cells. This is the first report to disclose the role of SIRT1 in regulation of pancreatic cancer cell proliferation and migration, which may provide a potential therapeutic target for pancreatic cancer patients.
Nigericin decreases the viability of multidrug-resistant cancer cells and lung tumorspheres and potentiates the effects of cardiac glycosides
Authors: Yakisich Juan Sebastian , Azad Neelam , Kaushik Vivek , O’Doherty George A , Iyer Anand Krishnan V
Published: March 2017

Multiple factors including tumor heterogeneity and intrinsic or acquired resistance have been associated with drug resistance in lung cancer. Increased stemness and the plasticity of cancer cells have been identified as important mechanisms of resistance; therefore, treatments targeting cancer cells independent of stemness phenotype would be much more effective in treating lung cancer. In this article, we have characterized the anticancer effects of the antibiotic Nigericin in cells displaying varying degrees of stemness and resistance to anticancer drugs, arising from (1) routine culture conditions, (2) prolonged periods of serum starvation. These cells are highly resistant to conventional anticancer drugs such as Paclitaxel, Hydroxyurea, Colchicine, Obatoclax, Wortmannin, and LY294002, and the multidrug-resistant phenotype of cells growing under prolonged periods of serum starvation is likely the result of extensive rewiring of signaling pathways, and (3) lung tumorspheres that are enriched for cancer stem-like cells. We found that Nigericin potently inhibited the viability of cells growing under routine culture conditions, prolonged periods of serum starvation, and lung tumorspheres. In addition, we found that Nigericin downregulated the expression of key proteins in the Wnt canonical signaling pathway such as LRP6, Wnt5a/b, and β-catenin, but promotes β-catenin translocation into the nucleus. The antitumor effects of Nigericin were potentiated by the Wnt activator HLY78 and by therapeutic levels of the US Food and Drug Administration–approved drug Digitoxin and its novel synthetic analog MonoD. We believe that Nigericin may be used in a co-therapy model in combination with other novel chemotherapeutic agents in order to achieve potent inhibition of cancers that display varying degrees of stemness, potentially leading to sustained anticancer effects.
Upregulation of SENP3/SMT3IP1 promotes epithelial ovarian cancer progression and forecasts poor prognosis
Authors: Cheng Jialin , Su Min , Jin Yunfeng , Xi Qinghua , Deng Yan , Chen Jie , Wang Wei , Chen Yannan , Chen Lingling , Shi Nannan , Mao Guoxin
Published: March 2017

As a crucial member of the small ubiquitin-like modifier system, SUMO-specific protease 3, was identified to be essential for cell proliferation and ribosomal RNA processing. Recent studies showed that SUMO-specific protease 3 was elevated in ovarian cancer compared to normal tissue samples. However, the connection between SUMO-specific protease 3-specific expression and clinicopathological parameters of epithelial ovarian cancer, as well as the physiologically potential role of SUMO-specific protease 3 in epithelial ovarian cancer remained unclear. In this study, an analysis of 124 paraffin-embedded slices by immunohistochemistry indicated that SUMO-specific protease 3 expression was positively correlated with the International Federation of Gynecology and Obstetrics stages (p = 0.025), tumor grade (p = 0.004), and lymph node metastasis (p = 0.001) and was also a critical prognostic factor for the overall survival of epithelial ovarian cancer patients, as revealed by Kaplan–Meier curve analysis. Knockdown of SUMO-specific protease 3 weakened the proliferation, migration, and invasion capability of ovarian cancer cells, down-regulated the expression of Proliferating Cell Nuclear Antigen, Forkhead Box C2, and N-cadherin, and resulted in upregulation of p21 and E-cadherin. Consistent with our results, SUMO-specific protease 3 had been verified to promote cell proliferation, metastasis, and tumorigenesis in multiple malignant cancers, which was a redox-sensitive molecule mediating the epithelial–mesenchymal transition. Collectively, our findings for the first time specifically supported that SUMO-specific protease 3 might play an important role in the regulation of epithelial ovarian cancer progression and could serve as a potential biomarker for prognosis as well as provide a promising therapeutic target against epithelial ovarian cancer.
Suppression of p53-inducible gene 3 is significant for glioblastoma progression and predicts poor patient prognosis
Authors: Quan Jishu , Li Yong , Jin Meihua , Chen Dunfu , Yin Xuezhe , Jin Ming
Published: March 2017

Glioblastoma is the most malignant and invasive brain tumor with extremely poor prognosis. p53-inducible gene 3, a downstream molecule of the tumor suppressor p53, has been found involved in apoptosis and oxidative stress response. However, the functions of p53-inducible gene 3(PIG3) in cancer are far from clear including glioblastoma. In this study, we found that p53-inducible gene 3 expression was suppressed in glioblastoma tissues compared with normal tissues. And the expression of p53-inducible gene 3 was significantly associated with the World Health Organization grade. Patients with high p53-inducible gene 3 expression have a significantly longer median survival time (15 months) than those with low p53-inducible gene 3 expression (8 months). According to Cox regression analysis, p53-inducible gene 3 was an independent prognostic factor with multivariate hazard ratio of 0.578 (95% confidence interval, 0.352–0.947; p = 0.030) for overall survival. Additionally, gain and loss of function experiments showed that knockdown of p53-inducible gene 3 significantly increased the proliferation and invasion ability of glioblastoma cells while overexpression of p53-inducible gene 3 inhibited the proliferation and invasion ability. The results of in vivo glioblastoma models further confirmed that p53-inducible gene 3 suppression promoted glioblastoma progression. Altogether, our data suggest that high expression of p53-inducible gene 3 is significant for glioblastoma inhibition and p53-inducible gene 3 independently indicates good prognosis in patients, which might be a novel prognostic biomarker or potential therapeutic target in glioblastoma.
Inactivation of parkin by promoter methylation correlated with lymph node metastasis and genomic instability in nasopharyngeal carcinoma
Authors: Ni Haifeng , Zhou Zhen , Jiang Bo , Yuan Xiaoyang , Cao Xiaolin , Huang Guangwu , Li Yong
Published: March 2017

This study aimed to investigate the inactivation of the parkin gene by promoter methylation and its relationship with genome instability in nasopharyngeal carcinoma. Parkin was considered as a tumor suppressor gene in various types of cancers. However, its role in nasopharyngeal carcinoma is unexplored. Genomic instabilities were detected in nasopharyngeal carcinoma tissues by the random amplified polymorphic DNA. The methylation-specific polymerase chain reaction, semi-quantitative reverse transcription polymerase chain reaction, and immunohistochemical analysis were used to detect methylation and mRNA and protein expression of parkin in 54 cases of nasopharyngeal carcinoma tissues and 16 cases of normal nasopharyngeal epithelia tissues, and in 5 nasopharyngeal carcinoma cell lines (CNE1, CNE2, TWO3, C666, and HONE1) and 1 normal nasopharyngeal epithelia cell line (NP69). mRNA expression of parkin in CNE1 and CNE2 was analyzed before and after methyltransferase inhibitor 5-aza-2-deoxycytidine treatment. The relationship between promoter methylation and mRNA expression, demethylation and mRNA expression, and mRNA and protein expression of the gene and clinical factors and genomic instabilities were analyzed. The mRNA and protein expression levels were significantly reduced in 54 cases of human nasopharyngeal carcinoma compared with 16 cases of normal nasopharyngeal epithelia. Parkin-methylated cases showed significantly lower mRNA and protein expression levels compared with unmethylated cases. After 5-aza-2-deoxycytidine treatment, parkin mRNA expression was restored in CNE1 and CNE2; 92.59% (50/54) of nasopharyngeal carcinoma demonstrated genomic instability. Parkin is frequently inactivated by promoter methylation, and its mRNA and protein expression correlate with lymph node metastasis and genomic instability. Parkin deficiency probably promotes tumorigenesis in nasopharyngeal carcinoma.
gamma-H2AX: Can it be established as a classical cancer prognostic factor?
Authors: Palla Viktoria-Varvara , Karaolanis Georgios , Katafigiotis Ioannis , Anastasiou Ioannis , Patapis Paul , Dimitroulis Dimitrios , Perrea Despoina
Published: March 2017

Double-strand breaks are among the first procedures taking place in cancer formation and progression as a result of endogenic and exogenic factors. The histone variant H2AX undergoes phosphorylation at serine 139 due to double-strand breaks, and the gamma-H2AX is formatted as a result of genomic instability. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. gamma-H2AX has already been investigated in a variety of cancer types, including breast, lung, colon, cervix, and ovary cancers. The prognostic value of gamma-H2AX is indicated in certain cancer types, such as breast or endometrial cancer, but further investigation is needed to establish gamma-H2AX as a prognostic marker. This review outlines the role of gamma-H2AX in cell cycle, and its formation as a result of DNA damage. We investigate the role of gamma-H2AX formation in several cancer types and its correlation with other prognostic factors, and we try to find out whether it fulfills the requirements for its establishment as a classical cancer prognostic factor.
Impact of epidermal growth factor receptor gene expression level on clinical outcomes in epidermal growth factor receptor mutant lung adenocarcinoma patients taking first-line epidermal growth factor receptor–tyrosine kinase inhibitors
Authors: Chang Huang-Chih , Chen Yu-Mu , Tseng Chia-Cheng , Huang Kuo-Tung , Wang Chin-Chou , Chen Yung-Che , Lai Chien-Hao , Fang Wen-Feng , Kao Hsu-Ching , Lin Meng-Chih
Published: March 2017

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are first-choice treatments for advanced non-small-cell lung cancer patients harboring EGFR mutations. Although EGFR mutations are strongly predictive of patients’ outcomes and their response to treatment with EGFR-TKIs, early failure of first-line therapy with EGFR-TKIs in patients with EGFR mutations is not rare. Besides several clinical factors influencing EGFR-TKI efficacies studied earlier such as the Eastern Cooperative Oncology Group performance status or uncommon mutation, we would like to see whether semi-quantify EGFR mutation gene expression calculated by 2−ΔΔct was a prognostic factor in EGFR-mutant non-small cell lung cancer patients receiving first-line EGFR-TKIs. This retrospective study reviews 926 lung cancer patients diagnosed from January 2011 to October 2013 at the Kaohsiung Chang Gung Memorial Hospital in Taiwan. Of 224 EGFR-mutant adenocarcinoma patients, 148 patients who had 2−ΔΔct data were included. The best cutoff values of 2−ΔΔct for in-frame deletions in exon 19 (19 deletion) and a position 858 substituted from leucine (L) to an arginine (R) in exon 21 (L858R) were determined using receiver operating characteristic curves. Patients were divided into high and low 2−ΔΔct expression based on the above cutoff level. The best cutoff point of 2−ΔΔct value of 19 deletion and L858R was 31.1 and 104.7, respectively. In all, 92 (62.1%) patients showed high 2−ΔΔct expression and 56 patients (37.9%) low 2−ΔΔct expression. The mean age was 65.6 years. Progression-free survival of 19 deletion mutant patients with low versus high expression level was 17.07 versus 12.04 months (P = 0.004), respectively. Progression-free survival of L858 mutant patients was 13.75 and 7.96 months (P = 0.008), respectively. EGFR-mutant lung adenocarcinoma patients with lower EGFR gene expression had longer progression-free survival duration without interfering overall survival.
Stability of ovine serum protein fractions under different storage conditions
Authors: Nagyová Veronika , Arfuso Francesca , Rizzo Maria , Nagy Oskar , Piccione Giuseppe
Published: March 2017

We evaluated the effect of different storage conditions on the concentration of serum total proteins and their electrophoretic fractions in sheep. Blood samples were collected from 12 female Comisana sheep, and each serum obtained was divided into 4 aliquots. The first aliquot was analyzed immediately after separation (T0); the second was refrigerated at 4°C and analyzed after 24 h (T1), 48 h (T2), and 72 h (T3); the third was stored at −20°C immediately after centrifugation and analyzed after 2 days (T4); and the last aliquot was stored at −20°C after 24-h refrigeration and analyzed after 1 wk (T5). The concentrations of serum total proteins and their electrophoretic fractions (albumin, α-, β1-, β2-, and γ-globulins) was determined. A statistically significant ( p < 0.05) effect of storage conditions on all serum electrophoretic protein fractions and on the albumin-to-globulin (A/G) ratio was found. The values of albumin, α-globulins, and A/G ratio increased at T4 with respect to T0. The levels of α-globulins were higher at T1 than T0; the β1-globulins levels changed at T3, whereas the β2- and γ-globulins values as well as the A/G ratio changed at T2 and T3. At T4, we found an increase in the serum concentrations of albumin, α1-globulins, and on the A/G ratio, and a decrease of γ fraction. At T5, the concentration of α-globulins was higher than at T0. Hence, we recommend electrophoretic analysis of fresh ovine serum samples or of samples refrigerated for no more than 24 h to obtain accurate data.
Talimogene Laherparepvec: An Oncolytic Virus Therapy for Melanoma
Authors: Corrigan Patricia A. , Beaulieu Caroline , Patel Rashmi B. , Lowe Denise K.
Published: March 2017

Objective: To review the efficacy and safety of talimogene laherparepvec (T-VEC) as well as its pharmacology, pharmacokinetics, drug-drug interactions, handling procedures, cost considerations, and place in therapy. Data Sources: Searches of PubMed (1966 to February 2017) and Cochrane Library (1999 to February 2017) were conducted using the terms talimogene laherparepvec, T-VEC, OncoVEX, immunotherapy, melanoma, and oncolytic virus. Additional information was determined from bibliographies, manufacturer product labeling and website, meeting abstracts, Food and Drug Administration website, and clinicaltrials.gov. Study Selection and Data Extraction: A total of 79 English-language publications were identified. Articles that assessed T-VEC’s pharmacokinetics, pharmacodynamics, mechanism, dosing, safety, and efficacy were included as well as narrative reviews that provided practical information. Data Synthesis: Clinical trials have confirmed the safety and efficacy of T-VEC as monotherapy for the treatment of advanced melanoma, with an overall response rate (ORR) of 26%. Relative to granulocyte-macrophage colony-stimulating factor, T-VEC significantly increased durable response rate (DRR; 16.3% vs 2.1%, P < 0.001); however, median overall survival was not improved (23.3 vs 18.9 months, P = 0.051). Phase 1b trials have combined T-VEC and immunotherapies with promising results. T-VEC’s adverse effects are generally considered mild to moderate in severity. Conclusion: T-VEC is the first approved oncolytic virus for local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in melanoma recurrent after initial surgery. T-VEC improves ORR and DRR as a single agent, shows promise in combination therapy, and is well tolerated. Ongoing trials will determine if T-VEC has a role in early treatment or in combination therapy for melanoma or other malignancies.
Experimental assessment of multiple contact wear using airborne noise under dry and lubricated conditions
Authors: Khan MA , Basit Kanza , Khan SZ , Khan KA , Starr AG
Published: March 2017

The generation of wear and airborne noise is inevitable in the mechanical contacts of the machine components. This paper addresses the effectiveness of the airborne noise data in estimating the wear on a disc under multi-contact conditions. A pin-on-disc rig was employed to study the role of noise parameters on the evolution of the wear area. When a pin slides on the disc, the airborne noise is generated and subsequently a sound signal is obtained. These signals, for various sets of experiments, were recorded using a digital microphone. A Matlab code was developed and employed to estimate the noise parameters from the recorded sound. Noise parameters including values of voltage RMS, noise counts and amplitudes of dominant frequencies were used to analyse the variation in the disc wear at different time intervals. These parameters were found to be effective in the determination of the wear damage evaluation under different loads without lubrication.
Non-Newtonian mixed thermo-elastohydrodynamics of hypoid gear pairs
Authors: Mohammadpour M , Theodossiades S , Rahnejat H , Dowson D
Published: March 2017

Transmission efficiency is the main objective in the development of vehicular differential systems, comprising hypoid gear pairs. The overall aim is to contribute to improved vehicle fuel efficiency and thus levels of harmful emissions for modern desired eco-drive axles. Detailed predictive analysis plays an important role in this quest, particularly under realistic operating conditions, comprising high contact loads and shear rates. Under these conditions, the hypoid gear pairs are subject to mixed non-Newtonian thermo-elastohydrodynamic conditions, which is the approach undertaken in this paper. Such an approach for hypoid gear pair has not hitherto been reported in the literature.
Barriers to formal police–community corrections partnerships
Authors: Kim Bitna , Matz Adam K , Gerber Jurg
Published: March 2017

Although there has been continuing and increasingly intensive interest in police–community corrections partnerships over the past two decades, recent studies have found that the majority of partnerships remain informal endeavors. Little is known about the reasons why police and community corrections agencies do not formalize partnerships. To address this gap in knowledge, we collected state-wide survey data from police chiefs and chief probation/parole officers in Pennsylvania regarding barriers to partnerships as well as interest in new partnership opportunities. The results revealed that for both police and probation/parole agencies, the most common reason for nonparticipation was that they have not been approached by the respective agencies. A lack of funding resources was the second most common barrier for both agencies. The so-called stalking horse concern was another significant barrier for probation/parole agencies, but it was not significant for police agencies. Regarding favorability to future partnerships, most respondents were interested in formal partnerships, but only a few agency representatives noted that they were actively seeking out opportunities to partner. The implications for policies, training, and future research are discussed.
Multiple-step fault estimation for interval type-II T-S fuzzy system of hypersonic vehicle with time-varying elevator faults
Authors: Wang Jin , Hu Longze , Chen Fuyang , Wen Changyun
Published: March 2017

This article proposes a multiple-step fault estimation algorithm for hypersonic flight vehicles that uses an interval type-II Takagi–Sugeno fuzzy model. An interval type-II Takagi–Sugeno fuzzy model is developed to approximate the nonlinear dynamic system and handle the parameter uncertainties of hypersonic firstly. Then, a multiple-step time-varying additive fault estimation algorithm is designed to estimate time-varying additive elevator fault of hypersonic flight vehicles. Finally, the simulation is conducted in both aspects of modeling and fault estimation; the validity and availability of such method are verified by a series of the comparison of numerical simulation results.
Weathering evolution in lutites of the K/Pg transition red beds of the Tremp Group (Tremp-Isona Basin, south Pyrenees)
Authors: Bastida J. , Linares R. , López Buendía A.M. , Osácar M.C. , Rosell J. , Zarroca M.
Published: March 2017

The Tremp–Isona basin (south-central Pyrenees, Lleida, Spain) shows maximum development of the Tremp Group (early Maastrichtian to late Paleocene) covering a wide geological record across the Cretaceous–Paleogene (K/Pg) boundary in continental facies. The mineralogy and geochemistry of lutites were used to assess the evolution of weathering from the Maastrichtian to the Eocene, and particularly for the red beds of the Lower Red and Upper Red Units (pre- and post-K/Pg, respectively). Chemical weathering decreased initially in the Maastrichtian (Gray Unit to Lower Red Unit), increasing subsequently from the Paleocene (Upper Red Unit) to Eocene units. ANOVA analysis of mineralogical compositions and cluster hierarchical analysis have been useful tools to select convenient lutites for assessment of weathering evolution by the chemical alteration index and by broadening of the 001 X-ray diffraction line of illite after ethylene glycol solvation. The lesser chemical weathering found in the Upper Red Unit (Danian) is interpreted in the context of relative warming and aridification, in climates of contrasting seasons and pronounced dry seasons.
Tracking intruder ship in wireless environment
Authors: Rao Madhuri , Kamila Narendra Kumar
Published: March 2017

It is a challenging task for all Harbors or Naval Administration to restrict and monitor the movement of defense or commercial ships. Most commonly used techniques of monitoring are radars and satellite images. These techniques are not reliable as radars can be turned off voluntarily and receptions of images are affected by adverse climatic conditions. This paper proposes a reliable ship intruder detection algorithm that classifies different types of objects approaching the model system in and out of phase with the ocean waves. The proposed technique also takes care of superimposition of temporal and spatial values of nodes that are presumably deployed in the sea surface up to a certain distance. Simulation results prove that the proposed algorithm detects and classifies objects efficiently even when 50% of the nodes reporting the tracking phenomenon are tampered.
Can floseal™ be applied safely during otologic surgery? Assessment of ototoxicity in a chinchilla animal model
Authors: Nhan Carol , Bezdjian Aren , Alarfaj Abdullah , Daniel Sam J.
Published: March 2017

Background

In otologic surgery good visualization is paramount, and patients with bleeding diatheses or who need to be anti-coagulated can present a significant challenge. Here, we determine whether Floseal™, a hemostatic matrix, is ototoxic in a validated animal model.

Methods

Nine chinchillas housed in the animal care facilities of the Montreal Children's Hospital Research Institute were used for the study. After a myringotomy incision was made in each tympanic membrane, baseline auditory brainstem response measurements were performed at 8, 20, and 25 kHz. In each animal one ear was randomized to receive Floseal™ to the middle ear cavity, whereas the other ear served as the control and received 0.9% sodium chloride. Outcome measures included early (day 7) and late (day 30) auditory brainstem response, clinical evidence of facial nerve or vestibular disturbance and histological evidence of ototoxity.

Results

There was no significant hearing threshold shift on auditory brainstem response across all tested frequencies for both experimental and control ear. No animals receiving Floseal™ developed facial or vestibular nerve dysfunction and there was no histological evidence of ototoxicity.

Conclusion

Based on the preliminary ototoxicity assessment on nine chinchillas, transtympanic Floseal™ does not appear to be ototoxic. More studies are warranted to assess the safety and applicability of the product in humans.
Efficient 3D seismic data acquisition in deep water
Authors: Blanch Joakim , Hapney Jessica , Ishak Margaret , Rodriguez Aurora , Laake Andreas , Moldoveanu Nick
Published: March 2017

Traditionally, large areas have been imaged with 2D seismic data, and 3D imaging has been employed over smaller targeted areas. In many areas, however, 3D seismic imaging is required to provide useful images of the subsurface and accurate velocity models. Still, 3D can be cost prohibitive in some instances. To alleviate cost and time requirements, the authors employed a dual-source vessel acquisition configuration, which doubles the acquisition rate and significantly reduces cost. The acquisition configuration is somewhat unconventional and at first look may seem incapable of producing high-quality data. However, it is shown that, with the help of modern processing techniques, this efficient configuration produces images with the same quality as a conventional configuration.
Analysis of reduced traveltime creates nonlinear delay-time solution
Authors: Bridle Ralph
Published: March 2017

This case study utilizes time-arrival picks and a two-layer depth/velocity model to enhance the refraction solution using nonlinear refractor velocities. The near surface has rapidly changing topography and thickness of the low-velocity layer. The refractor velocity is varying due to outcropping limestone horizons. The acquisition of the 3D survey is hampered due to inaccessible terrain with cliffs up to 150 m in height. There are two large areas with source omissions due to irrigated cultivations. For this 3D seismic survey, multiple tests applying tomographic modeling fail to resolve the near-surface anomaly. The starting model for this analysis is a linear reciprocal-path delay-time model. The proposed method redetermines the delay time, taking into account the nonlinear refractor velocity. The enhancement produced near-surface static corrections that improved the imaging of the 3D seismic volume and created an analytical tool of the solutions uncertainty.
A comparison of popular neural network facies-classification schemes
Authors: Ross Christopher P. , Cole David M.
Published: March 2017

Two learning networks are commonly used for seismic facies classification: unsupervised and supervised neural networks. While unsupervised neural networks have proven to be effective processes for macro- and mesoscale depositional facies characterizations, published results from supervised neural networks have more often demonstrated effective reservoir-scale characterization studies by using neural network mapping rather than neural network classification methods. Neural networks are sophisticated techniques that reduce data dimensionality and assist in seismic interpretation for exploration, exploitation, and production projects. In essence, neural networks for seismic interpretation map multiple seismic attributes to an output attribute or attributes that incorporate combined facets of the input data sets that yield a more accurate subsurface interpretation. Selecting an appropriate neural network is crucial to maximize interpretation benefits, yielding an accurate representation of the subsurface such that it can be used meaningfully to effectively support exploration and production efforts. These two classification techniques are compared using Oligocene Catahoula oil-bearing sands overlying a shallow salt structure along the Gulf Coast, where well control is abundant and used to ground-truth the seismic classifications of shale, brine sands, and oil-sand extent and thickness. Extraction of the seismic facies traces at various wells within the 3D volume allows direct comparison of the two techniques with known geology, permitting an unbiased evaluation and demonstrating the advantages of supervised neural networks for the classification of pertinent geologies. The advantages of the supervised network are demonstrated further by horizon and stratal slices that properly identify productive fault blocks while minimizing false positives of single seismic attributes.