PURPOSE
In computed tomographic colonography (CTC), a patient will be scanned twice-Once supine and once prone-to improve the sensitivity for polyp detection. To assist radiologists in CTC reading, in this paper we propose an automated method for colon registration from supine and prone CTC scans.

METHODS
We propose a new colon centerline registration method for prone and supine CTC scans using correlation optimized warping (COW) and canonical correlation analysis (CCA) based on the anatomical structure of the colon. Four anatomical salient points on the colon are first automatically distinguished. Then correlation optimized warping is applied to the segments defined by the anatomical landmarks to improve the global registration based on local correlation of segments. The COW method was modified by embedding canonical correlation analysis to allow multiple features along the colon centerline to be used in our implementation.

RESULTS
We tested the COW algorithm on a CTC data set of 39 patients with 39 polyps (19 training and 20 test cases) to verify the effectiveness of the proposed COW registration method. Experimental results on the test set show that the COW method significantly reduces the average estimation error in a polyp location between supine and prone scans by 67.6%, from 46.27 +/- 52.97 to 14.98 mm +/- 11.41 mm, compared to the normalized distance along the colon centerline algorithm (p < 0.01).

CONCLUSIONS
The proposed COW algorithm is more accurate for the colon centerline registration compared to the normalized distance along the colon centerline method and the dynamic time warping method. Comparison results showed that the feature combination of z-coordinate and curvature achieved lowest registration error compared to the other feature combinations used by COW. The proposed method is tolerant to centerline errors because anatomical landmarks help prevent the propagation of errors across the entire colon centerline.


This vision paper frames requirements engineering as a creative problem solving process. Its purpose is to enable requirements researchers and practitioners to recruit relevant theories, models, techniques and tools from creative problem solving to understand and support requirements processes more effectively. It uses 4 drivers to motivate the case for requirements engineering as a creative problem solving process. It then maps established requirements activities onto one of the longest-established creative problem solving processes, and uses these mappings to locate opportunities for the application of creative problem solving in requirements engineering. The second half of the paper describes selected creativity theories, techniques, software tools and training that can be adopted to improve requirements engineering research and practice. The focus is on support for problem and idea finding – two creative problem solving processes that our investigation revealed are poorly supported in requirements engineering. The paper ends with a research agenda to incorporate creative processes, techniques, training and tools in requirements projects.


We present a geometric construction of a lattice that emulates the action of a gauge field on a fermion. The construction consists of a square lattice made of polymeric sites, where all clustered atoms are identical and represented by potential wells or resonators supporting one bound state. The emulation covers both abelian and non-abelian gauge fields. In the former case, Hofstadter's butterfly is reproduced by means of a chain made of rotating dimers, subject to periodic boundary conditions parallel to the chain. A rigorous map between this model and Harper's Hamiltonian is derived. In the non-abelian case, band mixing and wave confinement are obtained by interband coupling using SU(2) as an internal group, \ie the effects are due to non-commutability of field components. A colored model with SU(3) made of trimers is also studied, finding thereby the appearance of flat bands in special configurations. This work constitutes the first all-geometric emulation of the Peierls substitution, and is valid for many types of waves.


The CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) is the standard treatment for younger and elderly patients with diffuse large-B-cell lymphoma, but it induces complete responses in only 40 to 50 percent of elderly patients. The benefit of adding Rituximab (R) – a chimeric anti-CD20 IgG1 monoclonal antibody, to CHOP was observed among patients with relatively low risk disease or high risk disease. In comparative studies of CHOP and R-CHOP, the rate of complete response was significantly higher in the group that received R-CHOP than in the group that received CHOP alone. In several EU countries there are cost-effectiveness studies regarding the treatment of aggressive NHL with CHOP vs. R-CHOP, but in Romania there is no such a study done. The authors used a cost-effectiveness model where they compared the costs of both type of treatments and the benefits expressed in gained years of life, in order to have the Romanian perspective for the economic evaluation of treatment of aggressive NHL with CHOP vs. R-CHOP. The Romanian cost-effectiveness analysis is based on a model developed by Best et al. which calculates the cost-effectiveness ratio of R-CHOP vs. CHOP over time horizon of 10 years for patients with diffuse large B-cell lymphoma DLCL. The analysis was done based on local Romanian costs and the clinical benefits from the GELA study. Rituximab administered together with CHOP gives patients an increased chance of cure, a significantly superior survival and represents a cost-effective therapy compared to standard treatment with CHOP. When costs and survival benefits are considered over 10 years, the additional cost per patient on R-CHOP is 12,929 Euro. Over a 10 years time frame, the estimated survival benefit of R-CHOP compared to standard CHOP treatment alone in this group of patients is on average 0.60 extra years of life gained per patient. The estimated additional cost per extra year of life gained for the combination therapy is 21,549 Euro. Using the same cost-effectiveness model we observed that using R-CHOP vs. CHOP we obtained in Romania the lowest cost per additional year of life gained compared with France or United Kingdom. Keywords: cost-effectiveness analysis, cost per life year gained, NHL non-Hodgkin lymphoma


Collecting midstream specimens of urine (MSU) is a common nursing activity. It is indicated for adults and children who are continent and can empty their bladder on request. The general principle is to collect the midstream or middle part of a void if a urinary tract infection (UTI) is suspected. Since this is one of the most frequently occurring infections, an MSU may be required in many areas of clinical practice. Yet despite being a regular nursing activity, the procedure is often undertaken incorrectly.


The concentration response for altered gene expression in primary lung epithelial cells was determined following two treatments with arsenicals: (1) a mixture of trivalent arsenic compounds representative of urinary arsenic concentrations in exposed human populations, and (2) arsenite (As2O3) a common form of inhaled arsenic dust that is frequently used in both in vivo and in vitro experimental exposures. Biochemical assays did not detect any evidence of cytotoxicity at the concentrations used, apart from a concentration‐related increase in cellular heme oxygenase that was also indicated by the genomic analysis. Cell signal pathway enrichment analysis indicated similar responses to both treatments, with concentration‐related responses in pathways related to cell adhesion, cytoskeleton remodeling, development (morphogenesis), cell cycle control, and to a lesser extent inflammatory responses. These cellular responses to arsenic were consistent with those observed in a previous study with primary uroepithelial cells. Benchmark dose analysis also demonstrated similar potency of the two treatments as well as comparable sensitivity of the two cell types. A number of genes showing similar concentration‐dependent expression across individuals in both bladder and lung cells were identified, including heme oxygenase 1, thioredoxin reductase, DNA damage binding protein 2, and thrombomodulin. The data on human primary lung cells from this study, together with the data from human primary uroepithelial cells, support a conclusion that biological responses to arsenic by human cells under study conditions are unlikely to occur at concentrations below 0.1 µM. Environ. Mol. Mutagen. 56:477–490, 2015. © 2015 Wiley Periodicals, Inc.


As there are conflicting reports regarding the association between obstructive sleep apnoea (OSA) and cancer incidence and mortality, a meta-analysis was performed to evaluate whether OSA is independently associated with cancer incidence and mortality. Pubmed, EMBASE and Web of Science were searched up until November 2014. Studies that assessed OSA and the future risk of cancer incidence or mortality were included. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) were calculated. Subgroup analysis was conducted based on the polysomnographic variable, apnoea-hypopnoea index. Six studies, which involved 114 105 participants, were pooled in this meta-analysis. Fixed-effects analysis showed the pooled adjusted HR of cancer incidence as 0.91 (95% CI, 0.74-1.13; P = 0.408) for mild OSA, 1.07 (95% CI, 0.86-1.33; P = 0.552) for moderate OSA and 1.03 (95% CI, 0.85-1.26; P = 0.743) for severe OSA. Random-effects analysis demonstrated neither mild OSA (adjusted HR, 0.79; 95% CI, 0.46-1.34; P = 0.381), moderate OSA (adjusted HR, 1.92; 95% CI, 0.63-5.88; P = 0.251) nor severe OSA (adjusted HR, 2.09; 95% CI, 0.45-9.81; P = 0.349) correlated with cancer mortality. This meta-analysis indicates that OSA is not independently associated with cancer incidence and mortality according to currently available data. Additional experimental and human research is required to determine the exact association between OSA and cancer.


Opposition to Hawaii's geothermal program, which is coming not only from the usual citizens' and environmental groups, but also from worshippers of a native god and, it has been alleged, growers of marijuana, is discussed. The clash occurs just as geothermal power sources have finally proven commercially viable. The most effective opposition to the project has been mounted by local residents and environmentalists with two main concerns: damage to the Wao Kele O Puna rain forest-one of a very few in the United States-in which some of the facilities would have to be built; and noise and gases, particularly hydrogen sulfide, emitted by the plant.<<ETX>>


In order to fully develop market economy, establish a modern system of company law and tally with WTO rules, the 18th meeting of the Standing Committee of the Tenth National People's Congress amended and adopted the new Company Law of the People's Republic of China on October 27, 2005. The Law, as amended, is hereby promulgated and comes into force on January 1, 2006. By comparing the differences between the company law of 1993 and the new version, the authors list the following four significant amendments of the new company law, ie requirements of formation a company are relaxed; the autonomy of company management is highlighted, the protection of shareholders is increased; the interest of company and its creditors is balanced. The following section illustrates in detail and analyzes objectively contents about one-person company and piercing the corporate veil. In the last section the authors point out some deficiencies that still exist in the new version of company law.


Twisted files (TFs) are rotary nickel-titanium (NiTi) instruments that are produced with a newly developed manufacturing process that is supposed to improve their properties, especially flexibility and resistance to cyclic flexural fatigue failure. The aim of this study was to study the cyclic flexural fatigue failure resistance of tip size International Standards Organization 25 TFs with two tapers 0.04 and 0.06 and to compare them with the Profile (PF) rotary NiTi files of similar tip size and taper. Four groups of fifteen files were used in this study. TF (25/0.04), TF (25/0.06), PF (25/0.04) and PF (25/0.06) were tested using the cyclic flexural fatigue testing device. The time to failure during cyclic flexural fatigue testing was recorded. The mean time required for the instrument to fail under cyclic flexural fatigue testing was 235.5 ± 68 s for 25/0.04 TF, 188.5 ± 75 s for 25/0.06 TF, 180.3 ± 102 s for 25/0.04 PF and 156.3 ± 17 s for 25/0.06 PF. The difference between the time to failure of 25/0.04 TF and 25/0.06 TF was not statistically significant. The difference between the time to failure of TF and PF of similar tip size and taper was not statistically significant. The findings of this study indicate that size 25/0.04 and 25/0.06 TFs had similar resistance to cyclic flexural fatigue failure. In addition, TFs were not superior, in terms of resistance to cyclic flexural fatigue failure, to PF of similar tip size and taper.


Temporal analysis of crop development in commercial fields requires tools for large area monitoring, such as remote sensing. This paper describes the temporal evolution of sugar cane biophysical parameters such as total biomass (BMT), yield (TSS), leaf area index (LAI), and number of plants per linear meter (NPM) correlated to Landsat data. During the 2000 and 2001 cropping seasons, a commercial sugarcane field in Araras, Sao Paulo state, Brazil, planted with the SP80-1842 sugarcane variety in the 4th and 5th cuts, was monitored using nine Landsat images. Spectral data were correlated with agronomic data, obtained simultaneously to the imagery acquisition. Two methodologies were used to collect spectral data from the images: four pixels (2 × 2) window and average of total pixels in the field. Linear and multiple regression analysis was used to study the spectral behavior of the plants and to correlate with agronomic variables (days after harvest-DAC, LAI, NPM, BMT and TSS). No difference was observed between the methodologies to collect spectral data. The best models to describe the spectral crop development in relation to DAC were the quadratic and cubic models. Ratio vegetation index and normalized difference vegetation index demonstrated correlation with DAC, band 3 (B3) was correlated with LAI, and NDVI was well correlated with TSS and BMT. The best fit curves to estimate TSS and BMT presented r2 between 0.68 and 0.97, suggesting good potential in using orbital spectral data to monitor sugarcane fields.


Vision processing for control of agile autonomous robots requires low-latency computation, within a limited power and space budget. This is challenging for conventional computing hardware. Parallel processor arrays (PPAs) are a new class of vision sensor devices that exploit advances in semiconductor technology, embedding a processor within each pixel of the image sensor array. Sensed pixel data are processed on the focal plane, and only a small amount of relevant information is transmitted out of the vision sensor. This tight integration of sensing, processing, and memory within a massively parallel computing architecture leads to an interesting trade-off between high performance, low latency, low power, low cost, and versatility in a machine vision system. Here, we review the history of image sensing and processing hardware from the perspective of in-pixel computing and outline the key features of a state-of-the-art smart camera system based on a PPA device, through the description of the SCAMP-5 system. We describe several robotic applications for agile ground and aerial vehicles, demonstrating PPA sensing functionalities including high-speed odometry, target tracking, obstacle detection, and avoidance. In the conclusions, we provide some insight and perspective on the future development of PPA devices, including their application and benefits within agile, robust, adaptable, and lightweight robotics.


Summary Human population growth has increased the demand for food crops, animal feed, biofuel and biomaterials, all the while climate change is impacting environmental growth conditions. There is an urgent need to develop crop varieties which tolerate adverse growth conditions while requiring fewer inputs. Plant breeding is critical to global food security and, while it has benefited from modern technologies, it remains constrained by a lack of valuable genetic diversity, linkage drag, and an effective way to combine multiple favourable alleles for complex traits. CRISPR/Cas technology has transformed genome editing across biological systems and promises to transform agriculture with its high precision, ease of design, multiplexing ability and low cost. We discuss the integration of CRISPR/Cas‐based gene editing into crop breeding to advance domestication and refine inbred crop varieties for various applications and growth environments. We highlight the use of CRISPR/Cas‐based gene editing to fix desirable allelic variants, generate novel alleles, break deleterious genetic linkages, support pre‐breeding and for introgression of favourable loci into elite lines.


Understanding sources of sustained competitive advantage has become a major area of research in strategic management. Building on the assumptions that strategic resources are heterogeneously distributed acrossfirms and that these differences are stable over time, this article examines the link betweenfirm resources and sustained competitive advantage. Four empirical indicators of the potential of firm resources to generate sustained competitive advantage-value, rareness, imitability, and substitutability-are discussed. The model is applied by analyzing the potential of severalfirm resourcesfor generating sustained competitive advantages. The article concludes by examining implications of this firm resource model of sustained competitive advantage for other business disciplines.


A 62-year-old man with uncontrolled diabetes mellitus under treatment in the department of internal medicine of our hospital presented with urinary retention. He was referred to our department, because it was impossible to conduct irrigation and catheter drainage after urethral catheterization. Computed tomographic scan showed abnormal air in his bladder and bladder wall. We diagnosed the patient with emphysematous cystitis, but we could not determine the reason for the failure of irrigation. By panendoscopy we found the inflammatory mucous flap in his urethra. This flap was thought to have caused the retention. Urinary catheter drainage is most important for the treatment of emphysematous cystitis. To our knowedge, this is the first report in Japan of a case in which catheter drainage was impossible.


This paper connects the biological function concept with adaptations in order to clarify the former. In this way, it is proposed that adaptations— defined in present and non-historical terms—are functional. Hence, the term function is equivalent to the concept of adaptation.


Linked data presents different social and ethical issues for different contexts and communities. The Statistics New Zealand Integrated Data Infrastructure (IDI) is a collection of de-identified whole-population administrative datasets that researchers are increasingly using to answer pressing social and policy research questions. Our work seeks to provide an overview of the IDI, associated issues for Māori (the Indigenous peoples of New Zealand), and steps to realise Māori data aspirations. In this paper, we first introduce the IDI including what it is and how it developed. We then move to an overview of Māori Data Sovereignty. Our paper then turns to examples of organisations, agreements, and frameworks which seek to make the IDI and data better for Māori communities. We then discuss the main issues with the IDI for Māori including technical issues, deficit-framed work, involvement from communities, consent, social license, further data linkage, and barriers to access for Māori. We finish with a set of recommendations around how to improve the IDI for Māori, making sure that Māori can get the most out of administrative data for our communities. These include the need to build data researcher capacity and capability for Māori, Māori data co-governance and accountability, reducing practical and skill barriers for access by Māori and Māori organisations, providing robust, consistent and transparent practice exemplars for best practice, and potentially even abolishing the IDI and starting again. These issues are being worked through via Indigenous engagement and co-governance processes that could provide useful exemplars for Indigenous and community engagement with linked data resources.


Administrative decisions, related to the selection of the priority of activities minimising acoustic e ects in the analysed areas, are determined by the index M values. This index is also known as the noise protection agents demand. A form of its function is determined by variables describing the number of residents and the level of exceeding the permissible noise in these inhabited regions. Uncertainty of decisions resulting from such assessments is conditioned by numerical measures: inaccurate measurements of exceeding permissible noise indicators as well as errors in the estimation of the number of residents exposed to them, formulated in probabilistic categories and interpreted in an interval way. Thus, the uncertainty assessment of index M , being the function determined by means of those variables, requires the determination of the density of probability distribution function of its occurrence. The method of its determination constitutes the contents of the presented hereby paper. The study concentrates on the derivation of the density of probability distribution function of index M , at the assumption that the distribution of variable errors is in a form of the normal cut distribution. The computational algorithm, allowing to perform necessary numerical calculations assigned to the uncertainty assessment process of indexM , is presented. The obtained results are illustrated by the example.


The first description of epileptic encephalopathies dates back to Dr. West who, in 1857, described the syndrome that took his name. In addition to West syndrome, in the last century other epileptic syndromes entered into the chapter of epileptic encephalopathies. Henry Gastaut has the virtue of having created the modern concept of epileptic encephalopathy and entering it into the official terminology of the International League Against Epilepsy (ILAE). After the first proposal, it was further defined and refined over time.


Secret knowledge, like remembering password or token based authentication systems are deemed inconvenience and difficult to use for users such as password may be forgotten or token may be lost. So burdens like remembering password and stolen or forged token based authentication have raised a current trend of biometric authentication system. Now in this current tech world, everyone needs security everywhere to protect our personal gadgets.  So to keep it secured, biometric based approach can be applied for better convenience and ease of use for the user. In this paper, a novel hybrid multimodal approach for ear recognition and finger print recognition has been presented for better robustness and efficiency which can be applied in various fields of applications like authentication in banking transactions. Biometric based human recognition is rapidly gaining popularity due to breached of traditional security systems and the lowering cost of sensors. This paper comprehensively reviews multimodal recognition using ear pattern and finger print data, it is concluded that further research should investigate fast and fully automatic ear-finger print multimodal systems robust to occlusions and deformations.


Two "targeted bidentate" photoaffinity cross-linking reagents, the monoanhydride of 8-N3ADP with N-(4-(benzoyl)phenylmethyl)phosphoramide ([gamma-32P]8-N3ATP gamma BP) and the monoanhydride of 8-N3GDP with N-(4-(benzoyl)phenylmethyl)-phosphoramide ([gamma-32P]8-N3GTP gamma BP), were developed for studying the inter- and intramolecular interactions of nucleotide-binding proteins. Experiments using these bidentate reagents with two photoactive groups led to specific cross-linking: [gamma-32P]8-N3GTP gamma BP and [gamma-32P]8-N3ATP gamma BP showed intersubunit cross-linking of glutamate dehydrogenase and [gamma-32P]8-N3GTP gamma BP appeared to cross-link the alpha- and beta-subunits of tubulin. The non-azido "monodentate" versions of these reagents, the monoanhydride of ADP with N-(4-(benzoyl)phenylmethyl)-phosphoramide ([gamma-32P]ATP gamma BP) and the monoanhydride of GDP with N-(4-(benzoyl)phenylmethyl)-phosphoramide ([gamma-32P]GTP gamma BP), were also synthesized and characterized. The ability of these monodentate reagents with one photoactive group to serve as photoaffinity probes was established by photolabeling specifically the exchangeable GTP-binding domain of tubulin with [gamma-32P]GTP gamma BP and the ATP-binding domain of purified adenylate kinase and several nucleotide-binding proteins in human brain homogenate with [gamma-32P]ATP gamma BP.


A systematic archaeoseismological study indicates that at least three earthquakes occurred between 400 B.C. and A.D. 600, causing destruction to numerous ancient monuments in Sicily. Evidence for these earthquakes comes from the collapse style of buildings (toppled walls, column drums in a domino‐style arrangement, directional collapses, etc.), and the exclusion of other likely causes for such effects. Dating of inferred earthquakes is based on coins (accurate to within 5–10 years), pottery (accurate to within 50–200 years), and other artifacts. The oldest documented earthquake occurred between 370 and 300 B.C. and caused the collapse of two Greek temples in Selinunte. This otherwise poorly documented event was probably also the cause of extensive destruction in northeastern Sicily in the first century A.D. Destruction of some sites may be assigned to an earthquake that occurred between 360 and 374 and correlates with the A.D. 365 seismic sequence known from historical sources. This study covers a wider region and provides a more precise dating of earthquakes than previous studies. Although it focuses on a certain period (4th–3rd centuries B.C., 4th–7th centuries A.D.), it indicates that the period before A.D. 1000 is not a period of seismic quiescence in Sicily as was previously believed, but to a period characterized by strong and destructive earthquakes. © 2009 Wiley Periodicals, Inc.


The advent of no-flow fluxing underfills for Flip Chip on Board application has required a new investigation of optimal processing for increased reliability. This research provides a systematic development of optimal process parameters for 3 currently available fluxing underfills. The impact of the dispensing pattern on void formation is determined. A DOE is utilized with dispense pattern at 3 levels, and speed at 2 levels. Metrics include material voiding, and fillet shape. Low temperature cure is used to isolate the effects of dispensing by avoiding any volatility of a standard reflow cure. The impact of the placement process is determined. A second DOE involves varying placement force, speed, and dwell time at 2 levels. Metrics include underfill voiding, solder voiding, and electrical yield. The results of these two experimental studies will be used to choose an optimal placement process for each material, to be used in further optimization of the reflow process.


Herein, we describe a simple and cost-effective design for the fabrication of a novel ternary RGO/BiOCl/TiO2 nanocomposites through a simple hydrothermal process. The prepared nanocomposites were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray diffraction (XRD), UV–vis diffuse reflectance spectroscopy (UV–vis DRS) and N2 adsorption–desorption analysis. Organic contaminants—such as methylene blue (MB), methyl orange (MO), rhodamine B (RhB) and amido black-10B (AB-10B)—were employed as the target pollutants to evaluate the adsorption capacity and photocatalytic activity of RGO/BiOCl/TiO2 nanocomposites. From experimental data, it was also found that the amount of TiO2 impressed the photocatalytic performance, and the nanocomposites with 10% of TiO2 showed the best photocatalytic activity. The improved photocatalytic performance may be mainly due to the narrow band gap, and the charge separation and migration of RGO. Moreover, good recyclability was obtained from RGO/BiOCl/TiO2 nanocomposites, and scavenger tests indicated that photogenerated holes were the main active species in the reaction system. Therefore, the prepared RGO/BiOCl/TiO2 nanocomposites have broad applications foreground in pollutants purification.


In the USA, in the last decade, standards have been adapted for each grade level. These standards are annually checked by state-wide tests. The results of these tests often determine the school's funding and even the school's future existence. Due to this importance, a large amount of time is spent on teaching to the tests. Most teachers believe that this testing approach is detrimental to student education. This belief seems to be empirically supported by the fact that so far, the testing approach has not led to spectacular improvements promised by its proponents. While this empirical evidence is reasonably convincing, the teacher community has not yet fully succeeded in clearly explaining their position to the general public - because the opposing argument of the need for accountability also seems to be reasonably convincing. In this paper, we show that the situation becomes much clearer if we take uncertainty into account - and that, hopefully, a proper use of uncertainty can help in resolving this situation.


This is the fourth issue in Harper's Annotated Bible Series. As the title indicated the author accepts the theory of Deuteroand Trito-Isaiah. After a brief introduction the chapters 40-55, he incorporates an outline. The Scripture text of these chapters in the King James Version is printed with a very helpful outline. Beneath this the author has included brief helpful commentary notes. After the treatment of "Second Isaiah," Prof. Bewer treats "Third Isaiah" in similar manner. The setting of Isaiah 56-66 is after the exile. He dates this section in the latter part of the sixth century and the earlier part of the fifth century and the earlier part of the fifth century. He indicates four authors for this section who are (1) A prophet of hope and consolation; (2) a warner and reprover; (3) a Torah teacher; (4) a praying saint. Furthermore, he indicates the notable insights of teaching. The latter half of this volume contains the outlined text of the King James Version with brief notes. J. J. Owens


The molecular geometry of gaseous cuprous chloride oligomers was determined by gas-phase electron diffraction at two different temperatures. Quantum chemical calculations were also performed for Cu(n)Cl(n) (n=1-4) molecules. A complex vapor composition was found in both experiments. Molecules of Cu(3)Cl(3) and Cu(4)Cl(4) were present at the lower temperature (689 K), while dimeric molecules (Cu(2)Cl(2)) were found in addition to the trimers and tetramers at the higher temperature (1333 K). All Cu(n)Cl(n) species were found to have planar rings by both experiment and computation. The bond lengths from electron diffraction (r(g)) at 689 K are 2.166+/-0.008 A and 2.141+/-0.008 A and the Cu-Cl-Cu bond angles are 73.9+/-0.6 degrees and 88.0+/-0.6 degrees for the trimer and the tetramer, respectively. At 1333 K the bond lengths are 2.254+/-0.011 A, 2.180+/-0.011 A, and 2.155+/-0.011 A, and the Cu-Cl-Cu bond angles 67.3+/-1.1 degrees, 74.4+/-1.1 degrees, and 83.6+/-1.1 degrees for the dimer, trimer, and tetramer, respectively.


This work presents experimental results on grafted polymer films. The aim was to understand transition processes in grafted polymer films regarding their structure and chain mechanics. For such purpose structural attributes of grafted polymer films were related to mechanical attributes. First the fundamental background, which is needed to analyze and understand experimental data, is pictured. This includes also new approaches for scattering data analysis. Experimental studies were focused on two different kinds of polymer film systems were investigated. Endgrafted poly-mehtyl-methacrylate (PMMA) brush films were investigated regarding their collapse - swelling transition on the solvent quality. It was observed that attractive interactions in the brush decreased for theta solvent conditions. For grafted to polystyrene (PS)/poly-vinyl-methyl-ether (PVME) blend films was concluded that the grafted polymer chains need an adequate degree of entropical freedom to undergo phase separations. Mechanical surface stress experiments made the understanding of the observed phase separation mechanisms possible.


The goal of the current investigation is to formulate Fluconazole loaded microemulsion (ME) with Lemongrass oil for deeper skin penetration and to obtain the dual benefit of drug and oil combination to improve antifungal efficacy of a drug with a reduced dose. We developed a Pseudo ternary phase diagram to identify the microemulsion zone by using the oil (clove oil), surfactant (Tween 20 and Tween 80), and co-surfactant (Propylene glycol) by water titration method. We formulated six different formulations (LM1 – LM6) by changing the oil/surfactant and cosurfactant ratio. The developed microemulsion formulation was characterized for various parameters % Transmittance, viscosity, pH, drug content, surface morphology, zeta potential, and in-vitro drug release study. The optimized microemulsion emulsion formulation is further converted into Microemulgel by dispersing the ME into 2% w/v Carbapol gel (LM-G) and further evaluated for various parameters. The antifungal efficacy was carried out for ME and Microemulgel by diffusion method against Candida albicans (MTCC no: 227) and compared with marketed gel which showed LM and LM-G have a better antifungal effect than marketed product, proved that the synergistic effect could be achieved by both clove oil and fluconazole drug by microemulsion formulation with deeper skin penetration effect.


Hyperthyroid syndromes can be approached in three different ways: medical, surgical and radiant. The medical therapy concerning the treatment of Basedow's disease is based on the extended use of thionamide drugs, which inhibits thyroid hormone biosynthesis and allows progressive recovery to normal glandular function. Agranulocytosis has been reported as the most serious side-effect. Inorganic iodide, lithium salts, beta-adrenergic receptor blocking agents and glucocorticoids have been employed as therapeutic alternatives, though of not common clinical use. Thyroidectomy is preferentially indicated in the treatment of toxic adenoma in fertile age groups and hyperfunctional bulky goiters. The postoperative complications connected with thyroidectomy are the main disadvantages. The use of radioactive iodine is currently the therapy chosen for toxic adenoma after forty years of age and particularly for hyperthyroid syndromes of elderly people, in whom scanty compliance with therapeutic suggestions and the increased postoperative risk make it preferable to other therapies, though incidental development of hypothyroidism after radioactive iodine treatment is not an unusual consequence.


Primary care physicians are in an excellent position to identify women most at risk for cancer precursors. They can use a variety of modalities, including colposcopy thus reducing patient anxiety and waiting time. This article describes a training program for such a service, which includes at least 100 colposcopy examinations under supervision. It is applicable outside a hospital clinic setting. Subsequent practice must have a referral base sufficient to maintain competence as well as economic viability. All GP colposcopists in the Perth area attend regular quality assurance meetings. An audit has shown that properly trained GPs can achieve a level of competence equivalent to that expected of their specialist colleagues (89% concordance between colposcopic impression and histology). The format of the audit was based on that of the Royal Australian College of Obstetricians and Gynaecologists (RACOG). Treatment must be performed by experts. General practice is the appropriate location for community screening studies using colposcopy.


RAF (Ras activating factor) kinases are important and attractive targets for cancer therapy. With the aim of discovering RAF inhibitors that bind to DFG-out inactive conformation created by the movement of Asp-Phe-Gly (DFG), we conducted structure-based drug design using the X-ray cocrystal structures of BRAF (v-raf murine sarcoma viral oncogene homolog B1), starting from bisarylurea derivative based on 1H-pyrazolo[3,4-d]pyrimidine scaffold 1a. Most of the synthesized compounds showed good to excellent inhibitory activities against BRAFV600E kinase, possessed moderate to potent anti-proliferative activities against four tumor cell lines (A375, HT-29, PC-3 and A549) and good selectivity towards cancer cells rather normal cells (Madin-Darby canine kidney, MDCK). The most promising compound, 1v, exhibited potent inhibitory activity against not only BRAFV600E (half maximal inhibitory concentration, IC50 = 23.6 nM) but also wild-type BRAF (IC50 = 51.5 nM) and C-RAF (IC50 = 8.5 nM), and effective cellular anti-proliferative activities against A375, HT-29, PC-3 and A549 cell lines as well as a very good selectivity profile. Moreover, compound 1v mainly arrested the A375 cell line in the G0/G1 stage, and showed significant suppression of MEK (mitogen-activated protein kinase kinase) phosphorylation in A375 and HT-29 cell lines. Taken together, the optimal compound 1v showed excellent in vitro potency as a pan-RAF inhibitor. In addition, the promise of compound 1v was further confirmed by molecular dynamics simulation and binding free energy calculations.


Some active pharmaceutical ingredients possess poor mechanical properties and are not suitable for tableting. Using fine sand (silicon dioxide), we show that a core/shell structure, where a core particle (sand) is coated with a thin layer of polyvinylpyrrolidone (PVP), can profoundly improve powder compaction properties. Sand coated with 5% PVP could be compressed into intact tablets. Under a given compaction pressure, tablet tensile strength increases dramatically with the amount of coating. This is in sharp contrast to poor compaction properties of physical mixtures, where intact tablets cannot be made when PVP content is 20% or less. The profoundly improved tabletability of core/shell particles is attributed to the formation of a continuous three-dimensional bonding network in the tablet.


The two-dimensional electromagnetic scattering by layered periodic arrays of circular cylinders embedded in a ferrite slab magnetized in the direction parallel to the cylinder axis are analyzed, using the lattice sums technique, the T-matrix of cylindrical objects, and the generalized reflection and transmission matrices for a layered system. It is shown that the reflection and transmission properties of the embedded arrays are accurately calculated by a simple matrix calculus based on the one-dimensional lattice sums and the T-matrix of the circular cylinder isolated in the magnetized ferrite slab. Numerical examples for the frequency response in the reflectance and transmittance are presented, and the switching properties of the embedded arrays controllable by the applied magnetic field are discussed.


Background The involvement of the enthesis in the patients with spondyloarthritis (SpA) can be a factor of disability. The efficacy of the TNF antagonists on the SpA activity is well established and is similar between all the drugs available at the moment. On the other hand, the efficacy of the anti-TNF treatment on the enthesitis is not as well-known and doesn't seem as strong as its effect on the overall disease activity. Objectives To analyze the effectiveness of anti-TNF drugs in the treatment of enthesitis in patients with SpA. Methods A retrospective analysis of all patients with SpA that started or switched treatment with TNF antagonists in a rheumatology department of a Portuguese University Hospital. The data were collected from the national database for rheumatic patients between July/2012 and December/2013. The demographic and clinic baseline data, disease activity (ASDAS and BASDAI) and functional impairment (determined with BASMI and BASFI) at baseline, 3 and 9 months of therapy were collected. The variations in the enthesitis scores (SPARCC and MASES) were then determined, as well as their difference according to the ASDAS response and according to the diagnosis (ankylosing spondylitis (AS) vs. psoriatic arthritis (PsA)). Results In December 2013, 26 patients met the inclusion criteria; 61.5% were women, and the median disease duration was 13.5 years. Of the 26 patients, only 10 have HLA B27 determination registered on the database, which was positive in 90% of them. 53.8% of the patients were receiving treatment with a classic DMARD; 50% of them were TNF naïve, and the remaining 50% have already been treated with at least 1 anti-TNF, without adequate improvement in the disease activity. 57.7% have started golimumab, 23.1% adalimumab and 19.2% etanercept. The median baseline BASDAI was 6.4, ASDAS 4.2, and BASMI 4.8. ASDAS and BASDAI had a significant reduction at 3 months of treatment (p<0.0001 and 0.001 respectively), but at 9 months only the ASDAS reduction was significant (p=0.002). At 3 and 9 months, despite a trend to reduction in the MASES score, none was statistically significant: MASES score showed a reduction of 3.5 points at 3 and 9 months; SPARCC didn't varied between all the evaluations. The MASES and SPARCC scores didn't differed significantly between the patients with and without ASDAS response, despite a tendency to a greater reduction on both scores on the patients with ASDAS response at 3 months of treatment (reduction of 4 points in MASES and 2 points in SPARCC vs. reduction of 2.5 points in MASES and 1.5 points in SPARCC on the patients with and without ASDAS response respectively). Between the patients with AS and PsA there weren't any significant differences between the MASES and SPARCC scores, despite an trend towards a greater reduction at 3 months in the ones with AS (reduction of 4 points in MASES and 2 points in SPARCC in AS vs. reduction of 2.5 points in MASES and -1.5 in SPARCC in PsA). Conclusions This analysis suggests an improvement in the both the enthesitis scores with the introduction of anti-TNF treatment, especially in MASES at 3 and 9 months, and this response occurs in both AS and PsA groups. It also shows that the reduction of the enthesitis scores seems to be independent of the response of the overall disease activity to the treatment. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4738


This paper propose a LEAN design and LEAN approach for project development of Mobile Production Facility (MPF). The Mobile Production Facility (MPF) is the well known facility developed in onshore oil and gas field for mature field which the field development plan has extended to remote areas which contain small marginal oil prospects. The LEAN design for Mobile Production Facility could improve the economics of onshore oil and gas projects development by reducing capital expenditure (CAPEX) and project development lead times and increasing flexibility for production planning through the mobilization design, and be a key factor in the economic exploitation of both marginal and mature fields. Insight gained through in-house design, international code & standard, and package design experts led to the development of the LEAN Mobile Production Facility proposed in this paper. Discussion include a characteristic of a reference oilfield, project background, application of Mobile Production Facility, the innovative design of package and equipment leading to lower CAPEX in detail, as well as the benefits and limitations of the LEAN Mobile Production Facility. Areas of future project development in support of LEAN Mobile Production Facility are identified, including the potential to unlock the further marginal reserves.


This paper examines a popular belief that managers of high valuation companies have a stronger incentive to manipulate future earnings than low valuation companies. Using U.S. data from 1988 to 2004 as our sample, we find the belief only half true. A positive relationship between valuation and future discretionary accruals only exists for companies receiving limited attention. For companies included in the Standard & Poor's 1500 index, there is no such a relationship. As for the motivation of manipulation, the evidence suggests that it is used to increase the proceeds received from seasoned equity offerings; it is not used to facilitate executives to sell their personal stocks. Also, we do not find any evidence to support the claim that high valuation companies with a stronger equity-based compensation will manipulate more. On the contrary, there is weak evidence that high valuation companies with good governance will be less aggressive in using accruals.


Abstract The everolimus–exemestane combination is indicated in advanced breast cancer treatment and usually well tolerated. The objective of the study was to determine the frequency of everolimus lung side effects and investigate their imaging characteristics on positron emission tomography with 18F-fluoro-deoxy-glucose combined with computerized tomography (18F-FDG PET/CT). Our single-center retrospective descriptive study systematically included all patients with metastatic breast cancer treated by this combination (n = 29 representing 57 18F-FDG PET/CT). Number of segments involved was quantified. Maximum standardized uptake value (SUVmax), average standardized uptake value (SUVmean), metabolic target volume (MTV), and total lesion glycolysis (TLG) were measured. Severe pneumopathy was studied by subgroup analysis. Pleuroparenchymal anomalies rate detected on 18F-FDG PET/CT was 62%. Alveolar-interstitial lesions were mainly observed (89%) and affected 2.8 segments (0.5–11.5) with a median of 2 segments. S7 and S10 were the most involved segments with SUVmax 3.9 (1.3–8.8) and SUVmean 2.2 (0.7–4.9). Statistically significant difference (P = .02) was found with number of segment involved to characterize severe pneumopathy (average of 6.3 segments [2.5–11.5] vs 1.9 segments [0.5–8] for interstitial lung disease) but not with SUVmax, SUVmean, MTV, TLG (P = .14, 0.22, 0.22, and 0.17, respectively). The 18F-FDG PET/CT could highlight pulmonary everolimus side effects, with a typical imaging pattern: alveolar-interstitial opacities associated with moderate uptake, more or less extensive, mainly affecting the lower lobes. Rarely, a pseudotumoral aspect may be detected, corresponding to a pitfall. MTV or TLG showed a tendency to differentiate severe pneumopathy vs interstitial lung disease but no statistically significant differences was observed contrarily to the number of segments involved. Further studies are necessary to determine if the 18F-FDG PET/CT could early predict adverse effects of mTOR inhibitors.


I show that firms headquartered geographically close to a top-university engage in more research and development and produce more valuable patents. To address the endogeneity of university and firm location, I use 19th century as-good-as-random allocation of land-grant colleges. I find that firms located close to these colleges are more innovative. Moving from the first to the fifth quintile of the distance distribution is associated with a 0.75 percentage point reduction in research and development expenditure and a 1.72 percentage point reduction in the value of patents, representing 15% and 21% of the mean, respectively. My findings suggest that universities help firms innovate by supplying local labor markets with high human capital and by generating ideas for local knowledge spillovers.


Antibody-drug conjugates (ADCs) consist of an antibody that is specific for a disease antigen linked to one or more drug molecules. The goal is to utilize the antibody as a means of specific delivery of the drug to diseased cells. Theoretically this should decrease systemic exposure to the drug and allow for use of a lower dose. In cancer, the approach employs an antibody targeted at a tumor-associated antigen and a cytotoxic or cytostatic drug. To date there have been three ADCs approved by the US FDA for cancer treatment, and many more are now in the development stage. The efficacy of any ADC is dependent on three factors: the antibody, the attached drug, and the linker used to connect them. While each of these factors is of import, with the growth of interest in ADCs for cancer therapy, the use of specific drugs and linkers has become more routine. Thus, the specificities of the antibody and target antigen are now perhaps the primary obstacles towards the development of novel ADCs. Human aspartyl (asparaginyl) β-hydroxylase (HAAH) is an embryonic/developmental protein, which is downregulated in normal cells after birth but overexpressed on the surface of many malignant cells. It has been demonstrated to be sufficient to induce cancer cell proliferation, motility, and invasiveness. The enzyme hydroxylates important residues in the NOTCH protein altering signal transduction pathways that lead to increased growth and metastatic potential. Increased levels of HAAH have been detected by immunohistochemistry in a diverse array of solid and hematologic cancers (n > 20), including liver, bile duct, brain, breast, colon, prostate, ovary, pancreas, and lung cancers as well as various leukemias. HAAH is not found in measurable quantities in normal tissue (n > 500), including normal adjacent tissue within cancer biopsy specimens or in benign proliferative disorders. We have developed a fully human antibody against HAAH, PAN-622,that displays exquisite specificity for cancer. Here we explore PAN-622 drug conjugates for ultimate use in treating both hematologic and solid tumors. PAN-622 was conjugated to three different drugs: a maytansinoid (DM1), monomethyl auristatin E (MMAE), and duocarmycin (DUO). DM1 was conjugated via a noncleavable thio-ether linker while MMAE and DUO were conjugated using valine-citruline containing linkers that are cleavable by cathepsin B in the endosomal compartment. Conjugation of drugs to the PAN-622 antibody had little effect on the affinity of the antibody for HAAH. Binding affinities were determined by immunoassay on fixed cancer cells (H460, human lung cancer line) and were ~0.1, 0.2, and 0.5nM for PAN-622-DM1, PAN-622-MMAE, and PAN-622-DUO, respectively. The affinity of PAN-622 for HAAH as expressed on live cells has previously been shown to be ~1nM. Efficacies of the three ADCs for killing of H460 cells were determined using an MTS assay. The PAN-622-DM1 had an EC50 of ~15nM. The EC50 for PAN-622-MMAE was ~60nM, and that for PAN-622-DUO was ~300nM. Importantly, both unconjugated PAN-622 and a nonrelevant antibody conjugated to MMAE did not display any killing of the H460 cell line. Efficacy was also measured on a representative hematologic cancer line, MOLM-14 (acute myelogenous leukemia) where EC50s were in the 20-50nM range for all three ADCs. This work serves as a proof of concept, laying the groundwork for further development of HAAH-targeted ADCs. Citation Format: Kanam Malhotra, Susan Walker, Chen Fang, Karamveer Birthare, Michael S. Lebowitz, Steven Fuller, Muctarr Sesay, Hossein A. Ghanbari. Antibody-drug conjugates targeted at human aspartyl (asparaginyl) β-hydroxylase [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B106.


Abstract This paper edits and studies four Arabic legal documents, written on two papyri, now housed in the Beinecke Rare Book and Manuscript Library at Yale University. The documents belong to a certain ʿAmmār b. Salama b. ʿAbd al-Wārith, a merchant from al-Bahnasā. Document 1 (P.CTYBR inv. 1720 verso) records a contract of sale of two inherited portions belonging to a Copt with double names, a Christian and a Muslim one. The contract touches on two significant socio-religious subjects: 1. name change after religious conversion, and 2. the loss of paternal filiation (nasab) of children born outside wedlock or in wedlock but their paternity was disavowed via the Islamic procedure of liʿān "oath of condemnation" or upon evidence of certain circumstances that prove impossibility of paternity. Documents 2.1, 2.2, and 2.3 (P.CTYBR inv. 1715 recto and verso) contains three debt acknowledgements recording payments in coin and in kind. All documents date to the year 297/909–910.


Background. Increase in visceral fat is associated to the development of fatty liver and liver fibrosis. Hepatic elastography is a novel noninvasive method for assessing liver fibrosis. Objective. To evaluate the relationship between visceral adipose tissue volume (VAT), subcutaneous adi- pose tissue volume (SAT) as measured by Magnetic Resonance Imaging (MRI) and transient elastography (TrE) values using ARFI (Acoustic Radiation Force Impulse) in type 2 Diabetic Mellitus patients (DM2). Methods. We included 20 DM2 patients (mean age: 62 years, range: 55-75, mean weight: 77.8 kg, range: 61.5-97). Patients underwent an MRI study in a Philips Intera 1.5T scanner. MR imaging protocol included a spectral excitation sequence centered on the fat peak. The sequence included 32 cross sections, 7mm thick, from the diaphragmatic cupula to the inferior border of the kidney. VAT was measured by using the semiautomatic Image J software. Each patient underwent a hepatic elastograpy (HE); 10 ARFI measure- ments were performed in the right hepatic lobe. Finally, a statistical analysis was performed by applying Pearson correlation between abdominal fat volumes and ARFI scores Results. Mean VAT was 2472 ± 861 cc, (1173-4020 cc), whilst the mean ARFI was 1.62 ± 0.8 m/s, (0.8- 3.4 m/s). Correlations obtained were r= 0.08 between VAT and ARFI (p=0 .72); 0.13 between SAT and ARFI (p=0.57), and -0.06 between (VAT+SAT) and ARFI (p=0.77). By subdividing the sample universe, we observed that the group with ARFI scores greater than 1.6 m/s (7 patients) had a correlation of 0.63 between VAT and ARFI (p=0.12); of 0.66 between SAT and ARFI (p=0.10), and of 0.94 between VAT+SAT and ARFI (p=0.001). In the subgroup with ARFI values inferior to 1.6 m/s (13 patients), the correlation was of 0.11 between VAT and ARFI (p=0.71); of 0.26 between SAT and ARFI (p=0.38), and of 0.32 between ( VAT+SAT) and ARFI (p=0.28). When adjusted for gender, ARFI scores greater than 1.6m/s (6 patients) in the subgroup of female patients revealed a correlation of 0.79 (p=0.05) between ARFI and VAT, and of 0.92 (p=0.009) for VAT+SAT. Conclusions. In DM2 patients, ARFI values greater than 1.6 m/s seem to be indicative of a good correlation between VAT and VAT+SAT, thus indicating that those with greater liver damage may present increased abdominal fat accumulation. Keywords: Acoustic radiation force impulse, Diabetes Mellitus type 2, Fat assessment, Intra-abdominal fat, Magnetic resonance imaging, Nonalcoholic fatty liver disease, Transient elastography, Visceral adipose tissue.


Unilateral emission reduction commitments raise concerns on international competitiveness and emission leakage that result in preferential regulatory treatment of domestic energy-intensive and trade-exposed industries. Our analysis illustrates the potential pitfalls of climate policy design which narrowly focuses on competitiveness concerns about energy-intensive and trade-exposed (EITE) branches. The sector-specific gains of preferential regulation in favour of these branches must be traded off against the additional burden imposed on other industries. Beyond burden shifting between industries, differential emission pricing bears the risk for substantial excess cost in emission reduction as policy concedes (too) low carbon prices to EITE industries and thereby foregoes relatively cheap abatement options in these sectors. From the perspective of global cost-effectiveness we find that differential emission pricing of EITE industries hardly reduces emission leakage since the latter is driven through robust international energy market responses to emission constraints. As a consequence the scope for efficiency compared to uniform pricing is very limited. Only towards stringent emission reduction targets will a moderate price differentiation achieve sufficient gains from leakage reduction to offset the losses of diverging marginal abatement cost.


This review deals with two overlapping issues, namely polymer chemistry and deep eutectic solvents (DESs). With regard to polymers, specific aspects of synthetic polymers, polymerization processes producing such polymers, and natural cellulose-based nanopolymers are evaluated. As for DESs, their compliance with green chemistry requirements, their basic properties and involvement in polymer chemistry are discussed. In addition to reviewing the state-of-the-art for selected kinds of polymers, the paper reveals further possibilities in the employment of DESs in polymer chemistry. As an example, the significance of DES polarity and polymer polarity to control polymerization processes, modify polymer properties, and synthesize polymers with a specific structure and behavior, is emphasized.


We report on the use of dielectric elastomer actuators (DEAs) to measure the traction force field of cells with subcellular resolution. The study of cellular electrochemical and mechanical response to deformation is an important area of research, as mechanotransduction has been shown to be linked with fundamental cell functions, or the progression of diseases such as cancer or atherosclerosis. Experimental cell mechanics is based on two fundamental concepts: the ability to measure cell stiffness, and to apply controlled strains to small clusters of cells. However, there is a lack of tools capable of applying precise deformation to a small cell population while being compatible with an inverted microscope (stable focal plane, transparency, compactness, etc.). Here, we use an anisotropically prestretched silicone-based DEA to deform a soft (7.6kPa) polyacrylamide gel on which the cells are cultured. An array of micro-dots of fluorescent fibronectin is transferred on the gel by micro-contact printing and serves as attachment points for the cells. In addition, the fluorescent dots (which have a diameter of 2 μm with a spacing of 6 μm) are used during the experiment to monitor the traction forces of a single cell (or small cluster of cells). The cell locally exerts traction on the gel, thus deforming the matrix of dots. The position of dots versus time is monitored live when the cells are submitted to a uniaxial strain step. Our deformable bioreactor enables the measurement of the local stiffness of cells submitted to mechanical strain, and is fully compatible with an inverted microscope set-up.


In this paper, we show the existence and multiplicity of positive solutions of the following fractional Kirchhoff system\\ \begin{equation} \left\{ \begin{array}{rllll} \mc L_M(u)&=\lambda f(x)|u|^{q-2}u+ \frac{2\alpha}{\alpha+\beta}\left|u\right|^{\alpha-2}u|v|^\beta&\text{in } \Omega,\\ \mc L_M(v)&=\mu g(x)|v|^{q-2}v+ \frac{2\beta}{\alpha+\beta}\left|u\right|^{\alpha}|v|^{\beta-2}v&\text{in } \Omega,\\ u&=v=0&\mbox{in } \mathbb{R}^{N}\setminus \Omega, \end{array} \right. \end{equation} where $\mc L_M(u)=M\left(\displaystyle \int_\Omega|(-\Delta)^{\frac{s}{2}}u|^2dx\right)(-\Delta)^{s} u $ is a double non-local operator due to Kirchhoff term $M(t)=a+b t$ with $a, b>0$ and fractional Laplacian $(-\Delta)^{s}, s\in(0, 1)$. We consider that $\Omega$ is a bounded domain in $\mathbb{R}^N$, {$2s<N\leq 4s$} with smooth boundary, $f, g$ are sign changing continuous functions, $\lambda, \mu>0$ are {real} parameters, $1<q<2$, $\alpha, \beta\ge 2$ {and} $\alpha+\beta=2_s^*={2N}/(N-2s)$ {is a fractional critical exponent}. Using the idea of Nehari manifold technique and a compactness result based on {classical idea of Brezis-Lieb Lemma}, we prove the existence of at least two positive solutions for $(\lambda, \mu)$ lying in a suitable subset of $\mathbb R^2_+$.


Background Maternal age, parity and fetal sex are each known to affect obstetric and birth outcomes. The objective of the present study was to investigate the influence of the combination of maternal age, parity and fetal sex on outcomes of pregnancies._The aim of the study was to analyze the influence of maternal age on perinatal outcomes in both primiparous and multiparous women with different fetal sex. Methods The cross-sectional study was performed on data from 11,780 women, who have given birth at the General University Hospital in Prague, Czech Republic between 2008-2012. Results Maternal age significantly (P<0.01) influenced pregnancy weight gain, duration of pregnancy, birth weight and birth length. Primiparous women with female newborns aged ≤19 had higher rates of preterm delivery than comparable women 20-39 (P=0.012). Similarly, women with male newborns aged ≥40 had higher rates of preterm delivery than comparable women 20-39 (P=0.003). Women aged ≤24 expressed higher rates of low birth weight than women aged >24 (P<0.001), regardless of parity and fetal sex. The older (≥35) primiparous women with male newborns expressed a higher incidence of macrosomia (P=0.021) compared to other groups of women. The probability of caesarean delivery increased with age (P<0.001) and it was significantly affected by the parity and sex of the newborn with higher rates of caesarean section in primiparous women as well as in mothers carrying male fetuses. Conclusions Our results indicate that "optimal" maternal age without obstetrics and birth complications is 25-34 years, older age is associated with increased complications with a male fetus, especially in primiparous women. Our data suggests that not just the age of women, but the combination of age, parity, and fetal sex should be taken into consideration during assessment of health risks of pregnancy.


We construct a model of decaying, TeV-scale scalar dark matter motivated by data from the PAMELA and Fermi-LAT experiments. By introducing an appropriate Abelian discrete symmetry and an intermediate scale of vector-like states that are responsible for generating lepton Yukawa couplings, we show that Planck-suppressed corrections may lead to decaying dark matter that is leptophilic and has the desired lifetime. The dark matter candidate decays primarily to lepton/anti-lepton pairs, and at a subleading rate to final states with a lepton, anti-lepton and standard model Higgs boson. We show that the model can reproduce the observed positron flux and positron fraction while remaining consistent with the bounds on the cosmic ray antiproton flux.


Relational queries, and in particular join queries, often generate large output results when executed over a huge dataset. In such cases, it is often infeasible to store the whole materialized output if we plan to reuse it further down a data processing pipeline. Motivated by this problem, we study the construction of space-efficient compressed representations of the output of conjunctive queries, with the goal of supporting the efficient access of the intermediate compressed result for a given access pattern. In particular, we initiate the study of an important tradeoff: minimizing the space necessary to store the compressed result, versus minimizing the answer time and delay for an access request over the result. Our main contribution is a novel parameterized data structure, which can be tuned to trade off space for answer time. The tradeoff allows us to control the space requirement of the data structure precisely, and depends both on the structure of the query and the access pattern. We show how we can use the data structure in conjunction with query decomposition techniques in order to efficiently represent the outputs for several classes of conjunctive queries.


Methotrexate (MTX) is used in the treatment of rheumatic diseases, psoriasis, and cancer. Since more than 90% of MTX is excreted via the kidneys, nephrotoxicity is one of the most important reasons restricting the use of this drug. In our study, we aimed to evaluate biochemical and histopathological properties to determine whether mirtazapine has a protective effect on MTX-related nephrotoxicity in rats. A group of rats were given a dose of 30 mg/kg of mirtazapine orally through a tube and 1 h after a dose of 5 mg/kg of MTX intraperitoneally. The rats in the control group received MTX alone intraperitoneally. A group of healthy rats was given orally distilled water in equal volume as dissolvent, then distilled water was administered intraperitoneally 1 h later. These procedures were repeated for 7 days. At the end of this period, all animals were sacrificed by giving a high dose of sodium thiopental. The results of biochemical analysis revealed that in the kidney tissues of rats given MTX, malondialdehyde, myeloperoxidase, glutathione, glutathione S-transferase, and nitric oxide levels were 42.3 2.4 µmol/g protein, 31.3 1.9 U/g, 6.5 1.0 nmol/g protein, 5.7 0.8 U/g, and 14.7 1.2 µmol/g, respectively; in the mirtazapine group, these values were found to be 24.2 1.9 µmol/g protein, 19.7 1.8 U/g, 11.5 1.3 nmol/g protein, 10.5 1.1 U/g, and 25.2 2.7 µmol/g, respectively. No biomarkers for protein nitrosylation, nitration, or DNA damage were measured. In this study mirtazapine was found to be efficacious to prevent nephrotoxicity due to MTX, suggesting that MTX can be used safely in higher doses and for a longer course in combination with mirtazapine in cancer chemotherapy.


OBJECTIVE
The purpose of this study was to compare the biliary enhancement dynamics of gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid (Gd-EOB-DTPA) and mangafodipir trisodium (Mn-DPDP) for contrast-enhanced MR cholangiography (MRC) in healthy subjects.

METHODS
15 healthy volunteers underwent MRI at 1.5 T with volumetric interpolated breath-hold examination sequence. Each volunteer was scanned once for each contrast agent. The signal-to-noise ratio (SNR) of the liver parenchyma and common hepatic duct (CHD) and the contrast-to-noise ratio (CNR) of CHD to liver parenchyma were evaluated and compared before and at several time points (5, 15, 30, 45, 60, 90, and 120 min) after injection of each agent.

RESULTS
SNR was significantly higher for Gd-EOB-DTPA than for Mn-DPDP in liver parenchyma after 5 min and in CHD after 15 min (p<0.05). CNR of CHD to liver parenchyma using Gd-EOB-DTPA showed an initial decrease at 5 min post-injection followed by a steep increase to a peak at 15 min post-injection. CNR using Mn-DPDP showed a steady increase to a peak at 15 min post-injection without an initial decrease. At 15 min, the value of CNR was significantly higher for Gd-EOB-DTPA than for Mn-DPDP (p<0.05).

CONCLUSION
For both contrast agents, CNR reached a peak at 15 min after contrast injection. At this time point, CNR of Gd-EOB-DTPA was significantly higher than that of Mn-DPDP. Therefore, Gd-EOB-DTPA may provide better contrast-enhanced MRC than Mn-DPDP at 15 min after contrast administration.


The temporal recruitment of leukocytes to a site of inflammation is dependent on a complex interplay of a number of soluble mediators. Recently, two families of chemotactic cytokines have been discovered. The -C-X-C-family, which includes IL-8, appears to recruit neutrophils and lymphocytes. In contrast, the -C-C-family, which includes monocyte chemotactic peptide-1 (MCP-1), appears to recruit predominantly monocytes. Monocytes, after their arrival at a site of inflammation, could further amplify the immune response by secreting IL-8 and MCP-1. We sought to define conditions under which human peripheral blood monocytes produce IL-8 and MCP-1. Using serum-free media, we found that PHA-stimulated monocytes expressed MCP-1 and IL-8 protein and mRNA in a dose-dependent manner. However, the onset of mRNA expression for MCP-1 occurred at least 3 h later than did the onset of IL-8 mRNA expression. IL-8 and MCP-1 gene expression by monocytes appeared to require de novo protein synthesis, in that cycloheximide blocked the expression of mRNA for both IL-8 and MCP-1 in PHA-stimulated cells. However, treatment of monocytes with cycloheximide resulted in the superinduction of IL-8 compared with control monocytes. Monocytes costimulated with PHA and LPS demonstrated enhanced amounts of IL-8 mRNA and protein, but sharply decreased amounts of MCP-1 mRNA and protein. The addition of serum to culture media increased both the constitutive and PHA-induced production of monocyte-derived MCP-1 and IL-8, but had no effect on the inhibition of PHA-stimulated MCP-1 production by LPS. These findings suggest that distinct pathways of activation exist for the production of monocyte-derived IL-8 and MCP-1. The differential expression of these different but related polypeptides may offer a means of control of the type of immune cells that are recruited to a site of inflammation.


OBJECTIVE
Multiple anatomical targets for deep brain stimulation (DBS) have been proposed for the treatment of severe Tourette's syndrome. In this open study, the authors evaluated the effectiveness of DBS of the anteromedial globus pallidus interna on tic severity and common comorbidities.

METHOD
Eleven patients (eight of them men, mean age=39 years) with severe and medically intractable Tourette's syndrome underwent implantation of Medtronic quadripolar electrodes in the globus pallidus interna bilaterally. The primary outcome measure was the Yale Global Tic Severity Scale. Secondary outcome measures included the Yale-Brown Obsessive Compulsive Scale, the Hamilton Depression Rating Scale, the Gilles de la Tourette Syndrome-Quality of Life Scale, and the Global Assessment of Functioning Scale. Follow-up occurred at 1 month and then at a mean of 14 months after surgery (range=4-30 months).

RESULTS
Ten patients (91%) reported improvement in tic severity soon after DBS. Overall, there was a 48% reduction in motor tics and a 56.5% reduction in phonic tics at final follow-up. Six patients (54.5%) had a more than 50% reduction, sustained for at least 3 months, in Yale Global Tic Severity Scale score. Only two patients required ongoing pharmacotherapy for tics after surgery, and patients improved significantly on all secondary measures. One patient did not tolerate DBS and discontinued treatment after 3 months. Greater anxiety in two patients and hardware malfunction in three patients were noteworthy adverse outcomes.

CONCLUSIONS
The results suggest anteromedial globus pallidus interna DBS for Tourette's syndrome is an effective and well-tolerated treatment for a subgroup of patients with severe Tourette's syndrome.


Epididymal maturation of sperm entails molecular changes to the sperm plasma membrane. These changes are reflected by changes in lectin binding. The wheat germ agglutinin (WGA) lectin was used, since it binds to acetylglucosamine and sialic acid, which are involved in sperm function. The objective was to study changes in WGA-lectin binding during epididymal passage and in the ejaculate of the Chacma baboon and vervet monkey. The intensity and location of lectin binding on sperm from the ejaculate and the caput, corpus, and cauda epididymidis of 5 adult males from each species were studied. In both baboon and monkey sperm, the acrosomal region had the highest intensity stain and the equatorial region had the lowest intensity. Significant differences in staining of the different regions of sperm were found for the different epididymal sites and the ejaculate of both species. It was concluded that changes in the molecular composition of the sperm membrane, taking place during epididymal maturation, can at least in part be monitored by studying WGA-lectin binding on sperm. The changes noted are probably important for the organization of a membrane of the correct molecular conformation and mandatory for complete sperm function.


Measurements of the asymmetry in the scattering of unpolarised electrons from optically pumped spin-polarised sodium atoms have been carried out at incident electron energies of 20, 54.4 and 70 eV and for a range of scattering angles between 20' and 140'. This asymmetry, which was first proposed by Farago (1974) as a means of measuring spin-orbit effects in the presence of a dominant spin-exchange interaction, is less than 1% at all energies and scattering angles studied.


Drought is a complex natural hazard with variable patterns and severity that has become a trending phenomenon in all countries across the globe, impacting all sectors negatively. Due tothe importance of drought monitoring and early warning in terms of enhancing drought resilience and preparedness, drought characterization and vulnerability have beeninvestigated repeatedly during the last decade, leading to the development of various drought indices. However, a single drought index may not provide a clear understanding of drought spatial and temporal patterns and the impacts on various sectors; thus, a combination of various indices could provide a key tobetter interpolationand forecasting. The present study explores and evaluates the potential of using a combined drought index (CDI) based onprecipitation (PDI), temperature (TDI), and vegetation (VDI) drought indices, to characterise drought variability and trends in Jordan based on 1-, 2-, 3-, 6-, and 12-month timescales. The CDI was computed as a weighted average of the PDI, TDI, and VDI indicators as derived from daily rainfall, air temperature, and NDVI data respectively for 21 meteorological stations for dates from 1980 to 2017. Although the CDI is simply a statistical index that measures how much present conditions deviate from the reference level, CDI applicability to monitoring and its correlation with sector impacts is much better than for any single drought indicator. Generated CDI maps also provide better interpolation for national and local drought characteristics in terms of severity, amplitude, and duration, and, as such,the CDI can clearly trace the footprints of droughts in Jordan. However, the relative weights of the PDI, TDI, and VDI may require further assessments through sensitivity analyses for improvedsector based responses (specific crop yields, groundwater recharge, etc.). The use of timescale CDI also enables the potential use of indicators for detailed short duration investigations for the development of an-early warning system or long term forecasting for adaptation planning and capacity building.


Herein, we demonstrate that the REDV peptide modified nanoparticles (NPs) can serve as a kind of active targeting gene carrier to condensate pZNF580 for specific promotion of the proliferation of endothelial cells (ECs). First, we synthesized a series of biodegradable amphiphilic copolymers by ring-opening polymerization reaction and graft modification with REDV peptide. Second, we prepared active targeting NPs via self-assembly of the amphiphilic copolymers using nanoprecipitation technology. After condensation with negatively charged pZNF580, the REDV peptide modified NPs/pZNF580 complexes were formed finally. Due to the binding affinity toward ECs of the specific peptide, these REDV peptide modified NPs/pZNF580 complexes could be recognized and adhered specifically by ECs in the coculture system of ECs and human artery smooth muscle cells (SMCs) in vitro. After expression of ZNF580, as the key protein to promote the proliferation of ECs, the relative ZNF580 protein level increased from 15.7% to 34.8%. The specificity in actively targeting ECs of the REDV peptide conjugated NPs/pZNF580 complexes was still retained in the coculture system. These findings in the present study could facilitate the development of actively targeting gene carriers for the endothelialization of artificial blood vessels.


ABSTRACT Bovine leukemia virus (BLV) is a deltaretrovirus that infects cattle worldwide. In agriculturally intensive regions, approximately 30% of dairy cows are BLV infected. Like the human T-cell leukemia virus (HTLV), there is a lengthy period of viral quiescence after initial infection with BLV. Unlike HTLV, BLV resides predominantly in B cells. Lymphoma is observed in less than 10% of BLV-infected adult cattle. Although viremia is undetectable in vivo, BLV-infected peripheral blood mononuclear cells readily become productive when cultured in vitro. Productivity is markedly diminished when cultures are supplemented with bovine plasma. This inhibitory activity of bovine plasma has been attributed to the "plasma blocking factor" (PBF). Here, we describe the purification of a PBF whose activity was resistant to heating to 65°C for 10 min and was attributable to a fibronectin-containing complex of approximately 320 kDa under nonreducing conditions. By use of two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization-time of flight (mass spectrometry), a protein with a size of 220 kDa and a pI of 5.4 was identified as a member of the fibronectin group of molecules. Both the purified protein and the commercially available bovine fibronectin inhibited BLV production in naturally infected peripheral blood mononuclear cells, although the fibronectin was less biologically active.


SUMMARY The study examines the global product and marketing strategies and their development when globalising ICT companies. Two major globalisation paths are distinguished: Born Globals and Globalising Internationals. The paper describes the characteristics of these two approaches, outlines a framework for understanding the product, brand and channel strategies in the globalisation process. It further elaborates on two important dimensions, namely standardisation across countries and co-operation in value networks. The study shows how the product and marketing strategies should be standardised along the globalisation process. A novel finding relates to the importance of examining co-operation possibilities in both vertical and horizontal value networks.


A research case focused on vented wooden façade system with bonded joints is presented in this paper. The potential of bonded joints is studied and described in more detail and verified through experimental measurements. For the purpose of tests spruce timber profiles were chosen for the load bearing substructure and Siberian larch façade sheeting for the cladding. Three types of industrial adhesives intended for structural bonding were selected. The article is focused on the preparation as well as on the subsequent experimental verification of substructure bonding retention to the cladding. The adhesive bonds were tested both in tension as well as in shear at a temperature of (293.15 ± 3) K and a relative humidity of (55 ± 10) %. The test results proved the fact that bonded joints are more than suitable equivalent to the mechanical joints. During the tests appeared some differences in stability and failure behaviour between the adhesive systems as well as within the sheeting material. Additionally, the suitability of selected group of adhesives in combination with Siberian larch cladding material as well as with the timber substructure was confirmed.


Laser cooling of mechanical degrees of freedom is one of the most significant achievements in the field of optomechanics. Here, we report, for the first time to the best of our knowledge, efficient passive optomechanical cooling of the motion of a freestanding waveguide coupled to a whispering-gallery-mode (WGM) resonator. The waveguide is an 8 mm long glass-fiber nanospike, which has a fundamental flexural resonance at Ω/2π=2.5  kHz and a Q-factor of 1.2×105. Upon launching ∼250  μW laser power at an optical frequency close to the WGM resonant frequency, we observed cooling of the nanospike resonance from room temperature down to 1.8 K. Simultaneous cooling of the first higher-order mechanical mode is also observed. The strong suppression of the overall Brownian motion of the nanospike, observed as an 11.6 dB reduction in its mean square displacement, indicates strong optomechanical stabilization of linear coupling between the nanospike and the cavity mode. The cooling is caused predominantly by a combination of photothermal effects and optical forces between nanospike and WGM resonator. The results are of direct relevance in the many applications of WGM resonators, including atom physics, optomechanics, and sensing.


Introduction: Breast Cancer (Ca Br) is one of the most common cancer amongst women globally as well in India. Amongst various available modalities of treatment, the most common treatment being advised in Ca Br is mastectomy which is commonly associated with a lot of emotion and mental challenges. For Ca Br patients, any decision in this regard forms an integral part in the diagnosis, confirmatory and treatment phase. The present study aims to explore the psychosocial determinants to undertake surgical decisions. Objective: To explore the psychosocial determinants and dilemma of undertaking decision for surgical intervention in Ca Br cases amongst pre and peri-menopausal women. Methods: The participants of pre and peri- menopausal women with Ca Br were selected purposively from a tertiary care hospital. The inclusion criteria included patients with Ca Br who underwent a therapeutic mastectomy and willing to be a part of the study were included. Qualitative Inquiry method was used for data collection and Content analysis was done using Atlas.ti. Results: Five themes emerged from the content analysis. It was observed that patriarchy dominates as decision-makers; surgical decision – is it a ' No –brainer' thing?, the big emotional burden on shoulder, motivators & demotivators, and inspiration. Women's passivity as decision-makers along with emotional distress conditions like fear of loss of feminity was always accompanied. Strong support system and will power were the major motivating factor for participants. Conclusion: The study gave a prominent and complex view on determinants of undertaking surgical decisions. Findings from the study would contribute to better strategizing the management of patients in a local context from all aspects and not just from the clinical lens.


In this letter we model the deviation of the nominal exchange rate from the long run equilibrium level predicted by monetary fundamentals in a nonlinear framework consistent with the presence of transaction costs. We consider a novel approach that allows for the joint testing of nonlinearity and nonstationarity. Within this approach, we employ nonlinear threshold autoregressive (TAR) unit root tests to investigate whether the deviation of the nominal exchange rate from the level predicted by monetary fundamentals for three major currencies vis-a-vis the US dollar is mean reverting. We are able to reject the null hypotheses of linearity and nonstationarity, detecting nonlinear mean reversion of the deviation series. Further, large deviations are found to imply faster speed of mean reversion than small deviations, uncovering evidence in favour of the monetary model of exchange rate determination.


The halide anions are essential for supporting life. Therefore, halide anion analyses are of paramount importance. For this reason, we have performed both qualitative and quantitative ana- lyses of halides (chloride, bromide, iodide) using the Tl(III) complex of azodye, 4-(2-pyridylazo)re- sorcinol (PAR), a potential new chemical reagent/sensor that utilizes the substitution reaction whereas the Tl(III)PAR complex reacts with a halide to yield a more stable thallium(III)-halide while releasing the PAR ligand in a process accompanied by color change of the solution. The experimental conditions (e.g., pH, ratio metal ion-to-ligand ratio, etc.) for the substitution reaction between the metal complex and a halide were optimized to achieve increased sensitivity and a lower limit of detection (chloride 7 mM, bromide 0.15 mM, iodide 0.05 mM). It is demonstrated that this single chemosensor can, due to release of colored PAR ligand and the associated analyte-specific changes in the UV/VIS spectra, be employed for a multicomponent analysis of mixtures of anions (chloride + bromide, chloride + iodide, bromide + iodide). The spectrophotometric data evaluated by artificial neural networks (ANNs) enable distinguishing among the halides and to determine halide species concentrations in a mixture. The Tl(III)-PAR complex was also used to construct sensor arrays utilizing a standard 96-well plate format where the output was recorded at several wavelengths (up to 7) using a conventional plate reader. It is shown that the data obtained using a digital scanner employing only three different input channels may also be successfully used for a subsequent ANN analysis. The results of all approaches utilized for data evaluation were similar. To increase the practical utility of the chemosensor, we have developed a test paper strip indicator useful for routine naked-eye visual determination of halides. This test can also be used for halide anion determination in solutions using densitometer. The methodology described in this paper can be used for a simple, inexpensive, and fast routine analysis both in a laboratory as well as in a field setting.


This Outlook calls attention to two seemingly disparate and emerging fields regarding viral genomics that may be correlated in a way previously overlooked. First, we describe identification of conserved potential G-quadruplex-forming sequences (PQSs) in viral genomes relevant to human health. Studies have demonstrated that PQSs are highly conserved and can fold to G-quadruplexes (G4s) to regulate viral processes. Key examples include G4s as a countermeasure to the host's immune system or G4-guided regulation of replication or transcription. Second, emerging data are discussed concerning the epitranscriptomic modification N6-methyladenosine (m6A) in viral RNA installed by host proteins in a consensus sequence favoring 5′-GG(m6A)C-3′. The proposed pathways by which m6A is written, read, and erased in viral RNA genomes and the impact this has on viral replication are described. The structural reason why certain sites are selected for modification while others are not is still mysterious. Finally, we discuss our new observations regarding these previous sequencing data that identify m6A installation within the loops of two-tetrad PQSs in the RNA genomes of the Zika, HIV, hepatitis B, and SV40 viruses. We hypothesize that conserved viral PQSs can provide a framework (sequence and/or structural) for m6A installation. We also discuss literature sources suggesting that PQSs as sites of RNA modification could be a general phenomenon. We anticipate our observations will provide ample opportunities for exciting discoveries regarding the interplay between G4 structures and epitranscriptomic modifications of RNA.


Mouse oocytes receive sister cell factors Mammalian mature oocytes, the largest cells in the body, are capable of programming and reprogramming embryogenesis. Only about 20% of developing mouse germ cells become oocytes. Lei and Spradling show that organelles and the cytoplasm move through intercellular connections between sister germ cells in mouse fetal ovaries to enrich oocyte cytoplasm just before oocytes arrest to form the ovarian reserve (see the Perspective by Pepling). Similar transfers occur during oogenesis in many invertebrate and lower vertebrate species, possibly providing oocytes their special properties for programming embryo development. Science, this issue p. 95; see also p. 35 Sister germ cells provide organelles and cytoplasm to oocytes to augment their developmental potential. [Also see Perspective by Pepling] Oocytes differentiate in diverse species by receiving organelles and cytoplasm from sister germ cells while joined in germline cysts or syncytia. Mouse primordial germ cells form germline cysts, but the role of cysts in oogenesis is unknown. We find that mouse germ cells receive organelles from neighboring cyst cells and build a Balbiani body to become oocytes, whereas nurselike germ cells die. Organelle movement, Balbiani body formation, and oocyte fate determination are selectively blocked by low levels of microtubule-dependent transport inhibitors. Membrane breakdown within the cyst and an apoptosis-like process are associated with organelle transfer into the oocyte, events reminiscent of nurse cell dumping in Drosophila. We propose that cytoplasmic and organelle transport plays an evolutionarily conserved and functionally important role in mammalian oocyte differentiation.


Traditionally, the working environment has been poor especially when it comes to steel reinforcement and concrete casting on construction sites. Industrialised construction methods such as self compacting concrete (SCC) casting and prefabricated steel reinforcement are creating a basis for an improved working environment. By using these methods, it is assumed that the cost for sick leaves due to ergonomic injuries and accidents are reduced as health and safety risks inherent to the traditional working methods are decreased. Observations along with video filming and informal interviews were performed. With a sequence-based activity method ErgoSAM, an ergonomic risk analysis was conducted. The analysis showed that industrialised methods reduced ergonomic workload on concrete workers. The industrialisation of the production process through the introduction of innovative construction methods has benefited the construction workplace environment as well as the customer value in terms of improved material handling, elimination of additional adverse affect on health of handling vibrating tools, reduced on site congestion and reduced over all material costs.


Objectives: Tumors in brain are currently treated with conventional radiation therapy techniques with poor tumor control but are associated with considerable side effects. Synchrotron generated micro-beam radiation therapy (SMBRT) has shown promising results in preserving brain architecture; however physical characteristics of SMBRT limit its use. We have successfully implemented a new clinical device for use on linear accelerator in clinical use, which produces fine beams of radiation called mini-beams (MBRT) of 1000 um size using 6 MV photons. The objective of this study was to test if MBRT can emulate the SMBRT biological effects using spontaneous brain tumors in dogs. Methods: Pet dogs with de-novo brain tumors were accrued for treatment across the country. Dogs were randomized between standard Stereotactic (9 Gy x 3 fractions) radiation treatment (SRT) Vs single fraction MBRT (26 Gy to mean dose). Dogs were followed for clinical assessment and MRI. Whenever dogs were euthanized, a veterinary pathologist assessed the radiation changes and tumor response. Results: Between 2013 and 2017, we accrued 16 dogs (8 on SRT and 8 on MBRT arm and range of follow up 1.5 50 months SRT group Vs 3 36 months with MBRT group). SRT treated dogs follow-up scans and postmortem evaluation showed residual tumor in all of them. In contrast, > 50% dogs have pathological complete response in MBRT treated dogs. All these dogs have shown lymphocyte infiltration in the target area which was not seen in control group. There were definite treatment-related changes seen in both arms of treatment, however changes were more pronounced in SRT group. Conclusions: Results show MBRT has a superior therapeutic ratio with excellent tumor control and fewer long term pathologically correlated toxicities. Post mortem evaluation shows the possibility of immune response as noted with lymphocyte infiltration. This might pave way for a new modality of radiation treatment, which would require a phase I human studies. 1 2 3 4 5 6 Open Access Abstract


The phase behavior was investigated in water/phytoglycogen/SDS and C12EO20 systems. It was found that phytoglycogen was precipitated in the presence of these surfactants. Phytoglycogen in the SDS system was dispersed more homogeneously than in the C12EO20 system, and a liquid-liquid phase separation region appeared in the SDS system. In the C12EO20 system, the transmittance of a stirred solution in the single-phase region was slightly lower than that of the phytoglycogen controls, whereas the transmittance of the stirred solution was higher than that of the controls in the SDS system. It thus seems that phytoglycogen formed a complex with SDS and that this complex affected the transmittance in the single-phase region. Viscosity measurements of the aqueous solution supported the existence of such a phytoglycogen-SDS complex. These results enabled us to propose a schematic representation of the complex structure. It was clarified that phytoglycogen forms a complex with SDS, and that the structure of the complex modifies the dispersion stability of phytoglycogen.


Transcriptional responses to estrogens are controlled by the cell- and gene-specific interactions of the nuclear estrogen receptor (ER) with cofactors and other transcription factors. The pituitary-specific PRL enhancer/promoter is regulated by estrogens only when it is bound by both ER and the pituitary-specific transcription factor, Pit-1. Cooperative ER/Pit-1 activation of the dormant PRL enhancer/promoter in pituitary progenitor cells requires the estrogen-dependent activation function-2 (AF-2) of ER, but is inhibited by one AF-2-interacting cofactor, RIP140. Here, the complex actions of RIP140 and other AF-2-interacting proteins at the PRL enhancer/promoter were shown to operate via ER itself. RIP140 inhibition of ER/Pit-1 activation in the absence of AF-1 and RIP140 inhibition of both ER alpha and ER beta cooperative activation with Pit-1 suggested a conserved ER site for RIP140 action, possibly AF-2. Coexpression of other AF-2-interacting proteins, including the p160 factors, steroid receptor coactivator-1a (SRC-1a) and glucocorticoid receptor interacting protein-1 (GRIP1), had negligible effects on ER alpha/Pit-1 cooperative activation, but partially relieved RIP140 inhibition. Relief of RIP140 inhibition required the AF-2-binding, LXXLL motifs in SRC-1a and GRIP1. An ER AF-2 mutant that selectively blocked ER interaction with p160s, but not RIP140, still cooperated with Pit-1 and was inhibited by RIP140, but was not relieved by SRC-1a or GRIP1 expression. Thus, SRC-1a and GRIP1 binding to AF-2 counteracted the inhibition of ER/Pit-1 activation by another AF-2-interacting protein, RIP140. Complex, sometimes antagonistic, actions of different classes of AF-2-interacting proteins may play an important role in the cell- and gene-specific estrogen regulation of PRL and other genes.


High pressure behavior of sodium titanate nanotubes (Na2Ti2O5) is investigated by Raman spectroscopy in a diamond anvil cell (DAC) at room temperature. The two pressure-induced irreversible phase transitions are observed under the given pressure. One occurs at about 4.2 GPa accompanied with a new Raman peak emerging at 834 cm−1 which results from the lattice distortion of the Ti-O network in titanate nanotubes. It can be can be assigned to Ti-O lattice vibrations within lepidocrocite-type (H0.7Ti1.825V0.175O 4·H2O)TiO6 octahedral host layers with V being vacancy. The structure of the nanotubes transforms to orthorhombic lepidocrocite structure. Another amorphous phase transition occurs at 16.7 GPa. This phase transition is induced by the collapse of titanate nanotubes. All the Raman bands shift toward higher wavenumbers with a pressure dependence ranging from 1.58–5.6 cm−1/GPa.


I aim to shed theoretical light on the meaning of judicial dialogue by comparing its practice in different jurisdictions. I first examine the practice of dialogic judicial review in Westminster democracies and constitutional departmentalism in American constitutional theory, showing the tendency toward judicial supremacy in both cases. Turning finally to continental Europe, I argue that the practice of constitutional dialogue there is reconciled with its postwar tradition of judicial supremacy through the deployment of proportionality analysis-framed judicial admonition. I conclude that constitutional dialogue may take place amid the judicialization of constitutional politics, albeit in the shadow of judicial supremacy.


In this paper, to realize the hybrid position/force control of a flexible manipulator, the macro-micro manipulator system is used. The macro manipulator can move widely, but can not realize fast and precise motion because of its flexibility. To compensate the position and force errors, a micro manipulator is attached at the tip of the macro manipulator. The kinematic equations of the macro-micro manipulator system are introduced. By utilizing the redundancy and flexibility of the system, the trajectory planning is discussed. A quasi-static hybrid position/force control algorithm and a dynamic hybrid position/force control algorithm are proposed. Lastly, experimental results are shown to verify the effectiveness of the proposed control algorithms.<<ETX>>