ROR1 is an oncoembryonic receptor tyrosine kinase expressed on chronic lymphocytic leukemia (CLL) B cells, but not on most normal post-partum tissues. It functions as a receptor for Wnt5a, which is present at high levels in the plasma of patients with CLL relative to that of age-matched controls. Wnt5a/ROR1 is known to activate pro-survival signals in CLL cells, but detailed mechanisms are not fully understood. We found that monocyte-derived Nurse-Like Cells (NLC) could induce CLL cells to activate STAT3 (pY705) and that this effect could be blocked by neutralizing antibodies to Wnt5a, which we found expressed at high levels by NLC. We observed that this effect also could be blocked by cirmtuzumab, a humanized mAb that can inhibit ROR1-signaling, indicating this effect of NLC on CLL cells was Wnt5a and ROR1 dependent. We performed a time-course study examining for pSTAT3 in isolated serum-starved CLL cells treated with exogenous Wnt5a. This revealed that Wnt5a induced delayed activation of STAT3, appearing first at 3 hours. As such, we hypothesized that the noted activation of STAT3 in CLL cells was indirect, being caused by a factor(s) made by isolated CLL cells in response to Wnt5a. We examined harvested supernatants of CLL cells cultured with or without Wnt5a using a human cytokine array assay. Multiple proinflammatory factors including IL-6, IL-8, CCL2, CCL3, CCL4, and CXCL1 were detected in the medium of CLL cells cultured for 24 hours with Wnt5a that were either not detected or found at lower levels in the medium of CLL cells cultured without Wnt5a. Moreover, the medium harvested from CLL cells cultured with Wnt5a, but not the medium of CLL cells cultured without, could induce pSTAT3 within 30 minutes in serum-starved CLL cells; this effect could be inhibited by the anti-IL-6-receptor mAb, tocilizumab, but not by cirmtuzumab, even when used at concentrations that could block the capacity of Wnt5a to induce latent activation of STAT3 and production of IL-6. Since the genes encoding these proinflammatory factors are targets of nuclear factor kappa B (NF-κB), we hypothesized that they were induced through Wnt5a/ROR1-dependent activation of NF-κB. Consistent with this notion, we found that BAY 11-7082 or BMS-345541, which can each inhibit activation of NF-κB, also could block Wnt5a-induced CLL-cell activation of STAT3 and production of IL-6. Furthermore, Wnt5a could induce phosphorylation of NF-κB p65 in CLL cells within 30 minutes, and this effect could be blocked by cirmtuzumab. Using real-time PCR array to evaluate for expression of NF-κB target genes, we found Wnt5s could induce up-regulation of NF-κB target genes in CLL cells, and that this effect could be blocked by cirmtuzumab. Moreover, these studies revealed that Wnt5a/ROR1/NF-κB signaling could induce expression of genes encoding the noted proinflammatory factors in CLL cells. To examine the in vivo significance of these findings, we collected plasma and CLL cells from patients treated with cirmtuzumab in a phase I clinical trial (Choi, MY, et al, Cell Stem Cell 22:951, 2018). RNAseq and ELISA respectively were used to examine the transcriptomes of negatively-selected CLL cells and the concentrations of IL-6 in plasma collected before and after treatment. Consistent with our in vitro findings, treatment with cirmtuzumab downregulated CLL-cell expression of NF-κB target genes in vivo by gene set enrichment analysis (n = 3, NES = 2.10, FDR q = 0.01). The levels of IL-6 in plasma also were significantly decreased in patients after therapy (p = 0.02, n = 5, Paired Student t test). Collectively, these studies indicate that Wnt5a/ROR1-dependent signaling induced by NLC may play a major role in the noted activation of NF-κB in CLL, leading to the production of factors, such as IL-6, which are posted to contribute to pathogenesis. Moreover, these data suggest that some of the noted clinical effects of therapy with cirmtuzumab may be due to suppression of Wnt5a-induced, ROR1-dependent activation of NF-κB in patients with CLL.

 Choi: Genentech: Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Gilead: Speakers Bureau; AbbVie, Inc: Consultancy, Speakers Bureau; Rigel: Consultancy. Kipps:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech Inc: Consultancy, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy, Research Funding.


A novel evolutionary algorithm based on the new model for multiobjective optimization problems (MOPs) is presented in this paper. Firstly, we defined two measures, one is the rank variance of population and the other is the U - measure variance of population. The rank variance of population is a measure of the quality of solutions and the U -measure variance of population is a measure of the uniformity of the distribution of solutions. Using these two measures as two objective functions, the MOPs is finally converted into a two objective optimization problem. For the transformed problem, a novel multiobjective evolutionary algorithm is proposed. The new approach is tested on two well-known benchmark multiobjective optimization functions taken from the standard literature. Compared with other eight state- of-the-art algorithms, our algorithm remarkably outperforms them in terms of the quality of the solutions and the uniformly distribution of the solutions. So our algorithm can be considered a viable alternative to solve MOPs.


In thymidylate synthase (TS), the invariant residue Asp-221 provides the only side chain that hydrogen bonds to the pterin ring of the cofactor, 5,10-methylene-5,6,7,8-tetrahydrofolate. All mutants of D221 except cysteine abolish activity. We have determined the crystal structures of two ternary complexes of the Escherichia coli mutant D221N. In a complex with dUMP and the antifolate 10-propargyl-5,8-dideazafolate (CB3717), dUMP is covalently bound to the active site cysteine, as usual. CB3717, which has no imidazolidine ring, is also bound in the usual productive orientation, but is less ordered than in wild-type complexes. The side chain of Asn-221 still hydrogen bonds to N3 of the quinazoline ring of CB3717, which must be in the enol form. In contrast, the structure of D221N with 5-fluoro-dUMP and 5,10-methylene-5,6,7, 8-tetrahydrofolate shows the cofactor bound in two partially occupied, nonproductive binding sites. In both binding modes, the cofactor has a closed imidazolidine ring and adopts the solution conformation of the unbound cofactor. In one of the binding sites, the pterin ring is turned around such that Asn-221 hydrogen bonds to the unprotonated N1 instead of the protonated N3 of the cofactor. This orientation blocks the conformational change required for forming covalent ternary complexes. Taken together, the two crystal structures suggest that the hydrogen bond between the side chain of Asp-221 and N3 of the cofactor is most critical during the early steps of cofactor binding, where it enforces the correct orientation of the pterin ring. Proper orientation of the cofactor appears to be a prerequisite for opening the imidazolidine ring prior to formation of the covalent steady-state intermediate in catalysis.


In this paper, a modified normal form approach is proposed for the analysis of high dimensional nonlinear systems. Using the modified approach, calculations of normal forms and, in particular, the related coefficients are carried out much more conveniently. Certain high dimensional systems, including systems with inner resonances, are investigated. These systems exist widely in engineering applications. To illustrate the approach, five examples are presented.


Governments in several countries such as Pakistan are adopting the latest information and communication technologies to increase the efficiency of organizations and services. One of the major reasons for this is to transfer and store a large amount of very important government records as eDatabases (G-eDbases) such as the database managed by the National Database Registration Authority in Pakistan. This type of data is highly confidential therefore needs to be protected from an unauthorized access. Presently, access to these databases is based on software based authentication technologies such as password based encryption schemes, which can protect from an unauthorized access to some extent. This mode of authentication access can however be compromised. It is therefore important to use more secured and reliable methods to access to the GeDbases, which is increasingly important in the current situation of security in the country. In this paper, the authors suggest a hypothetical model of securing sensitive eDatabases using multibiometric technology that will replace the traditional password based access scheme and prevent unauthorized access to GeDbases.


The present study evaluated the effects of cover crops (Pennisetum glaucum, Crotalaria spectabilis and Urochloa ruziziensis) associated with the application of herbicides {glyphosate; (glyphosate + haloxyfop-R); (glyphosate + fluazifop-p-butyl); (glyphosate + imazethapyr) and (glyphosate + imazaquin)} in soybean desiccation management for volunteer RR® corn control. The experiment was conducted under field conditions at Sinop-MT, during the 2013/2014 crop season, in a randomized complete blocks design with factorial scheme and four replications. The following parameter were evaluated: dry matter of cover crops and ground coverage rate, control of volunteer RR® corn present at the time of desiccation, dry matter, height and intoxication level on soybean plants caused by herbicides at 7, 14 and 28 days after emergence (DAE), control of volunteer RR® corn derived from emergence fluxes subsequent to desiccation management and soybean yield. The joint application of (glyphosate + haloxyfop-R) provided the best level of volunteer RR® corn control present at the time of desiccation. Satisfactory control (80%) of volunteer corn was obtained with the application of (glyphosate + imazethapyr). This treatment displayed an additional residual effect of imazethapyr, which efficiently controled volunteer RR® corn derived from fluxes subsequent to desiccation management, especially in treatments performed under U. ruziziensis straw. None of the herbicides used in desiccation management caused any significant effect on dry matter, height and phytotoxicity of soybean plants at 7, 14 and 28 DAE nor on grain yield.


The synthesis of new perfluoroalkyl-containing phosphines from the reactions of the perfluoroalkyl iodides n-C3F7I, i-C3F7I, n-C4F9I, sec-C4F9I, cyc-C6F11Br or cyc-C6F11I, n-C6F13I and n-C8F17I with R2PSiMe3 or R2PLi (R = Ph2, t-Bu2, Et2, MePh and EtPh was investigated. The new perfluoroalkyl-containing phosphines were characterised by multinuclear NMR spectroscopy. The reaction between i-Pr2P-Pi-Pr2 and i-C3F7I resulted in some i-Pr2PCF(CF3)2, 11, but an elimination process was dominant. Compound 11 was obtained using a reaction of i-Pr2PCl with i-C3F7I in the presence of MePh2P, dpph, dppm, dppe or dppp. This method was also applied successfully to other systems.The reaction of PhPLi2 with n-C3F7I has been investigated, but does not result in production of a bis-perfluoroalkyl-containing phosphine, instead the previously unknown compound, PhHP(CF2)2CF3, 21, was formed.The chemistry of the perfluoroalkyl-containing phosphines has been investigated; oxides of the perfluoroalkyl-containing phosphines were made by either aerial oxidation, or by adding hydrogen peroxide solution. Oxidation with XeF2 was also investigated, to give compounds of the type F2PPh2Rf. These were water sensitive and also generated phosphine oxides. The phosphorus(V) selenides have been synthesised, and their 1J(PSe) coupling constants measured.The coordination chemistry of the perfluoroalkyl-containing phosphines was investigated and complexes of rhodium, molybdenum, gold, platinum and palladium were prepared. The crystal structures of six of these complexes have been obtained, they are: RhCl(CO)[Ph2P(CF2)2CF3]2, RhCl(CO)[Ph2P(C6F11)]2, RhCl(CO)[Ph2PCF(CF3)2]2, trans-[PdCl2(Ph2P(CF2)2CF3)2], cis-[PtCl2(Ph2P(CF2)2CF3)2] and trans-[PtCl2(Ph2P(CF2)5CF3)2]. In all of these structures aggregation of the fluorinated alkyl groups occur with F?F distances of ca. 2.8 A, resulting in fluorous domains being observed.


We study the geometric scaling in the new combined data of the hadron-electron ring accelerator by using the Golec-Biernat—Wüsthoff model. It is found that the description of the data is improved once the high accurate data are used to determine the model parameters. The value of x0 extracted from the fit is larger than the one from the previous study, which indicates a larger saturation scale in the new combined data. This makes more data located in the saturation region, and our approach is more reliable. This study lets the saturation model confront such high precision new combined data, and tests geometric scaling with those data. We demonstrate that the data lie on the same curve, which shows the geometric scaling in the new combined data. This outcome seems to support that the gluon saturation would be a relevant mechanism to dominate the parton evolution process in deep inelastic scattering, due to the fact that the geometric scaling results from the gluon saturation mechanism.


Fire raised the ire of the Hindu fundamentalists in India after its nationwide release, and Water was watered down in the midst of its filming. Why is a constitutionally secular and historically tolerant country up in arms against its own less-than-sympathetic, yet arguably necessary, self-representations? Is the fire directed against the content of these films, or against its once homegrown and constrained, but now Canadian and "free", director? Are western pronouncements of a lack of freedom of expression in developing societies like India producing such poetics of disturbance in their waters that a much needed self-appraisal is turning into a chauvinistic brand of religious nationalism?

 Deepa Mehta, the director of a trilogy comprising Fire, Earth, and Water, is a Hindu woman whose films tackle patriarchy and fundamentalist religion. In an attack that is reminiscent of the religious and political vitriol targeted at Salman Rushdie's Satanic Verses, all three of Mehta's films, but particularly Fire and Water, have been the subjects of critiques of too much freedom inside the country, and these critiques have in turn led those outside the country to condemn the Indian body-politic for its lack of freedom.

 In the case of Fire, it may not be unreasonable to assume that the opposition to the film arose due its depiction of an unbridled version of female sexuality that challenged prevalent religious-patriarchal norms. Reading the local rebuttal of the movie in light of the struggle to define the role of women in a global context, Sujata Moorti argues, "local resistance to the global is manifested in a series of practices that invoke religion to regulate women; control over female bodies becomes a crucial strategy for rejecting the global" ("Inflamed Passions", 20 June 2006). However, considering that Water was subject to the wrath of violent mobs right in the midst of its shooting in the ancient Hindu city of Varanasi, despite its script obtaining the approval of the Federal Government in India, the question arises—is religion merely an excuse to garner support for political battles? More importantly, are the political battles being fought in the name of a national cohesion that can only be achieved through "freedom" from the West?

 As developing societies like India make their way along the complex path of economic liberalisation and socio-political fundamentalism, is it the responsibility of the "enlightened" West to guide them through their difficult journey to the epitome of freedom? Is the West, then, not only claiming to be "free", but also exercising hegemony over the very concept of freedom by deciding whether or not a country is free? Can a country ever be free if a pseudo-free Western collective judges its degree of freedom? Perhaps the writings of Jasmine Yuen-Carrucan, an Australian who worked as a camera assistant on the film Water, can assist us in sorting through these questions:

 There I was in India, sitting on the steps of this government office, clutching my piece of paper, fighting for the first time for the right for freedom of expression. I waved a little paper flag with all my heart but wondered whether it was the business of a foreigner such as myself to enter a country like India, steeped in religious traditions and strong political codes, and try to challenge them. I was, after all, only going to put my flag down and head home. Perhaps it was not my fight to pursue ("The Politics of Deepa Mehta's Water", 5 June 2006).

 If the fight for freedom of expression is not that of the foreign crewmember, is it that of the diasporic filmmaker?

 Reflecting on the protests by Sikhs in Britain against the play Behzti (Dishonour) by Gurpreet Kaur Bhatti, who is herself a Sikh, Salil Tripathi issues a warning to those of the diaspora who dare to be self-critical: "The defiant and deviant will inevitably face the community's shame and dishonour" (164). Is Mehta being subjected to a similar fate? In reference to the ire over Fire, Moorti observes, "Mehta's status as a Canadian resident and the film's disavowal of traditional norms were used to mark the product as western" ("Inflamed Passions", 20 June 2006). The doubts over Mehta's "Indianness" are reminiscent of the primitivist/nativist tendency towards authenticity that post-colonial discourse has been attempting to dismantle in favour of a hybrid existence. Significantly, in the wake of a lack of self-appraisal from the so-called authentic Others, is it not the responsibility of the diasporic intellectual, with his/her awareness of the permeability of boundaries, to point out the "unfreedom" of exerting political or religious control to prescribe a unitary definition of cultural identity? In an interview with Richard Phillips, Mehta comments on her constrained freedom:

 The situation in India at the moment is that if you produce films with song and dance routines or unserious films, you are fine. It doesn't matter how violent or vulgar they are. But if you want to make something even slightly introspective it is a no-no and you are accused of exploiting Indian culture. I keep on saying: Is Indian culture so weak that one film can destroy it? ("Deepa Mehta Speaks Out", 5 June 2006).

 It seems that with the non-availability of both films in India, and the diasporic status of this very critical piece, the arabesque statue rather than the living form that is "Indian culture" is far from being destroyed.

 Perhaps it is time that "Westerners", diasporic critics, and liberal "Easterners" tolerated the firing and subsequent watering down of democratic rights like the freedom of expression in non-Western countries. However, any defence of "unfreedom" would sound bizarre to our free-thinking Selves. If, in this age of post-modern uncertainties we are deconstructing our own freedom, and fragmenting our own identity, should we expect the same of the Others? Braidotti sums up the dilemma of feminist, black, and post-colonial subjects in a similar question: "how can we undo a subjectivity we have not even historically been entitled to yet?" (15). It appears, therefore, that before commenting on a particular society's freedom or lack thereof, historical differences need to be acknowledged. While the current crisis of freedom in the West may not be entirely applicable to the East, its demonstration of freedom as "becoming" rather than "being" is perhaps indicative of a future we can all open ourselves to.

References

Braidotti, Rosi. Metamorphoses: Towards a Materialist Theory of Becoming. Cambridge and Malden: Polity Press, 2002.
Moorti, Sujata. "Inflamed Passions: Fire, the Woman Question, and the Policing of Cultural Borders". Genders. 20 June 2006 http://www.genders.org/g32/g32_moorti.html>.
Phillips, Richard. "Deepa Mehta Speaks Out against Hindu Extremist Campaign to Stop Her Film." World Socialist Web Site. 5 June 2006 http://www.wsws.org/articles/2000/feb2000/meht-f15_prn.shtml>.
Tripathi, Salil. "Drawing a Line." Index on Censorship 2 (2005): 162-6.
Yuen-Carrucan, Jasmine. "The Politics of Deepa Mehta's Water". Bright Lights Film Journal. 5 June 2006 http://www.brightlightsfilm.com/28/water.html.>. Citation reference for this article

 MLA Style

 Khorana, Sukhmani. "Whose Fire on Freedom Holds More Water?." M/C Journal 9.4 (2006). echo date('d M. Y'); ?> .
APA Style
 Khorana, S. (Sep. 2006) "Whose Fire on Freedom Holds More Water?," M/C Journal, 9(4). Retrieved echo date('d M. Y'); ?> from .


This qualitative case study utilized hybridity theory, particularly the notion of third spaces, to investigate the ways Turkish immigrants (18 parents and 15 children) negotiate culture, identity, and schooling in the midwestern United States. Data were collected through in-depth interviews, observations, and artifacts, and analyzed using traditional qualitative analysis tools. The findings demonstrated that Turkish immigrants' identity negotiation in third spaces included five elements: (1) drawing from multiple discourses, (2) navigating geo-cultural spaces, (3) becoming agents of negotiation, (4) mediating conflicts, and (5) regenerating traditions. These findings have several implications. Educators should understand the importance of out-of-school experiences that highlight the agency of immigrant children and their families so they can better support the children's academic and social growth. Further, educators and policymakers should rethink the notion of "immigration" and the traditional role of schools in this process as these may not reflect the complexity of contemporary immigrant identities.


In this article, we consider the motion of a liquid surface between two parallel surfaces. Both surfaces are non-ideal, and hence, subject to contact angle hysteresis effect. Due to this effect, the angle of contact between a capillary surface and a solid surface takes values in a closed interval. Furthermore, the evolution of the contact angle as a function of the contact area exhibits hysteresis. We study the two-point boundary value problem in time whereby a liquid surface with one contact angle at t = 0 is deformed to another with a different contact angle at t = ∞ while the volume remains constant, with the goal of determining the energy loss due to viscosity. The fluid flow is modeled by the Navier-Stokes equations, while the Young-Laplace equation models the initial and final capillary surfaces. It is well-known even for ordinary differential equations that two-point boundary value problems may not have solutions. We show existence of classical solutions that are non-unique, develop an algorithm for their computation, and prove convergence for initial and final surfaces that lie in a certain set. Finally, we compute the energy lost due to viscous friction by the central solution of the two-point boundary value problem.


In numerous controlled studies the effectivity of the streptokinase therapy of the acute myocardial infarction is proved by a significant decrease of the early lethality. The main difference of the therapeutic methods lies in the duration of the application of streptokinase. Of the number of patients of an intensive therapy ward for internal diseases comparisons of the results of therapy of one year with short-term lysis (3 hours) are contrasted with one year with protracted lysis therapy (24-72 hours). The findings demonstrated plead for the fact that by means of the short-time lysis may also be achieved good, perhaps even better results. Issuing from the therapeutic mechanisms of the lysis therapy in the sense of a prevention of the formation of thrombi in disturbed microcirculation by the achieved hyperplasminaemia the short-term lysis is to be regarded as optimum introduction of an anticoagulant long-term therapy.


A 42-year-old white woman, who was a general practitioner referral to the medical team, presented with a 3-day history of left upper quadrant pain; an urgent private ultrasound scan had showed splenomegaly. She was initially admitted with sepsis without an obvious cause but with a differential diagnosis of a haematological malignancy. Her admission blood tests showed a mildly reduced white cell count and low platelets. Her symptoms progressed and she developed right upper quadrant pain. Her blood counts deteriorated showing a disseminated intravascular coagulation (DIC) picture and mildly deranged liver function tests. Blood films were non-diagnostic. A CT scan of the abdomen/pelvis showed splenomegaly and also hepatomegaly and ascites, not seen in her initial ultrasound scan. Multiple cultures of blood/urine/ascites and infective serology were unremarkable. She was transferred to a larger tertiary centre under the care of the surgeons with presumed abdominal sepsis and underwent an open laparotomy, which showed a big firm liver and spleen but no obvious cause for sepsis. The infectious disease team were unable to find a cause, and haematology became involved to investigate the possibility of a haematological malignancy. The patient underwent two bone marrow biopsies, a percutaneous liver biopsy and had flow cytometry of her ascitic fluid, which revealed the diagnosis of a natural killer cell leukaemia. After some slight improvement on steroids, the patient was given cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab (CHOP-R) chemotherapy. The patient had an initial response to chemotherapy, with reduction in ascitic volume and hepatosplenomegaly, and normalisation of her coagulation. This was accompanied by an overall improvement in her physical condition. She had a second cycle of CHOP-R, but unfortunately approximately 2 weeks after that, she deteriorated rapidly. She was too weak for salvage chemotherapy, so she was put on comfort care. She died peacefully.


This study examined conceptions of the right to literacy in children, adolescents, and young adults living in rural Zulu villages in the mountains of KwaZulu Natal, South Africa, as one instantiation of the development of conceptions of human rights in a developing world setting. Of human rights, literacy was chosen because of its familiarity to children and adolescents and because of its recognized importance to the promotion of well-being and equality in the developing world; the setting was chosen as representative of a traditional non-Western group living in relative geographical isolation. The participants (N = 72), in three groups, 10-11, 15-16, and 18-21 years old, equally divided by sex, were posed questions about the right to literacy, its properties in the abstract, and about hypothetical scenarios presenting conflicts between the right to literacy and cultural preservation, parental authority, and gender roles. Participants were asked to justify their responses to each question. Findings showed that participants endorsed the right to literacy in the abstract assessments (93% - 100%) and conflict assessments (61% - 100%), using, in the majority of instances, rationales of agency - capacities and resources promoting self-determination and well-being - and morality. This understanding of human rights, as it was isomorphic with `Western' conceptions of human rights as determined by previous North American studies and by philosophical treatments of human rights, provided evidence for commonalities in moral development processes between Western and traditional `non-Western' settings. The conflict assessments provided evidence for how children coordinate this right in the context of their families and communities and their evaluations of the relative importance of rights in comparison to other social values.


On the 4th of January 2013, the National Energy Authority in Iceland issued two licenses for the exploration and production of hydrocarbons in the Dreki Area, there is also a third license being considered at the moment. There are plenty of hazards and risks of a possible oil spill related to the exploration and production of hydrocarbons, this paper looks to address the oceanographic conditions at the Dreki and Jan Mayen Ridge region. It also looks into the use of comparisons, historic events, effects on the ecosystem and then mainly at what area is most likely to be affected should an oil spill occur and what can be done in the event of a spill. This paper found that conditions at the same latitude, but different longitudes (i.e. East Greenland vs. West Norway) are very different. The complexity of the dynamics between Atlantic and Arctic waters in the Nordic Seas cause these differences and a characteristic of these seas are anti-clockwise eddies. These will factor heavily in the distribution of a potential oil spill and will most likely prevent a spill from flowing to shore in Iceland, Norway or Greenland. Exploration and production has been conducted at sites that endure similar or more extreme conditions and the use of a floating platform will be integral for any large operations. Health and safety management will have to be held to high standards and frequently reviewed. The main factor that will be problematic for the planned exploration and potential production in the area is its remoteness. Facilities for production and for a disaster response team, equipment and vessels will either have to be established in Iceland or co-ordinated with and on Norway.


This bachelor's degree will examine the Swedish translation of the publication Awake! a religious monthly periodical published by the Jehovah's witnesses as a way to complement their primary magazine The Watchtower. The purpose of this examination is to do a rhetorical analysis on how Awake! Magazine takes part in spreading the witnesses' message and to examine what is being communicated towards its readers and what sort of language and arguments is used. One of my primary goals during this paper will be to also examine what sort of messages the periodical is sending towards its younger readers. The gathered empirical material will be examined through Berger and Luckmanns theories about social constructs and institutionalizations and Bourdieu's Doxa theory. This study will show that the language that the periodical uses is constantly laden with religious meaning, every aspect of the everyday goings on that Awake! Magazine writes about is combined with excerpts from the Bible or other material published by Jehovah's Witness. There is also a clear distinction in the way the magazine communicates with its readers. The language used to older readers is often aimed at their sense of logic, reason and at times meant to evoke the reader's feelings towards different subject matters. The language and arguments aimed at the younger readers is instead focused on warnings and the importance of keeping chaste and obedient. The final summation shows that the periodical mostly uses a language and argument that is meant to bolster the readers pride and loyalty towards Jehovah's and to underline the importance of innocent and obedience in teenagers and the seductive and corrosive nature of society outside of the confines of their faith.


A study designed to investigate how the cellular laterality in rosto-caudal direction changes due to age and sex was presented. It is a well-known fact that asymmetry is an important issue in understanding brain functions. Frontal sections of 5 µm thickness with 200 µm intervals were taken from both dorsal hippocampi of 4- and 20-week-old male and female rats. Sections were stained with hematoxylin-eosin and the levels of sections were determined according to a stereotaxic atlas. In each level, numerical density of pyramidal cells of the right and left area CA1, CA3 and CA4 of dorsal hippocampi were estimated by means of counting pyramidal cells under 10 × 40 magnification. Numerical cell density obtained from the right and left dorsal hippocampi of male and female rats were compared. Results are as follows: 1) Numerical cell density in the left and right dorsal hippocampi of 20-week female rats was not high than 4-week female dorsal hippocampi (p>0.05). 2) Difference between 4-week old female and male dorsal hippocampi of right and left CA1, CA3 and CA4 areas were not raised a significant level (p>0.05). Differences between 20-week-old group of male and female rats with the exception of female CA4 area were not also significant. 3) Right and left dorsal hippocampi CA4 areas of the 20-week-old group showed a higher numerical density than the same area of the 4-week-old group (p<0.007). This difference may show a postnatal neurogenesis in area CA4. The results, which are summarized above, may be helpful in understanding the mechanisms of human brains.


To apply real-time polymerase chain reaction (PCR) to detect and quantify the gastrointestinal microbiota modulated by dietary feed additives was the objective of this study. Sixty-four three-crossbred weaning piglets at 24 days were used and randomly assigned to be fed one of the experimental diets supplemented with different feed additives (0.2% inulin, 0.1% fructooligosaccharide and sub-therapeutic antibiotics), and compared with the non-supplemented group. Comparison of microbiota enumeration by conventional culture and real-time PCR methods in response to feed additives was investigated. The microbiota enumeration by conventional culture and real-time PCR methods showed corresponding responses of selected bacterial counts (Lactobacilli, Bifidobacteria, Escherichia coli) in feces and digesta from caecum and colon to different feed additives. The inulin-treated group tended to have the highest Lactobacilli number, while the sub-therapeutic antibiotics-treated group had significantly lower number of Lactobacilli and Bifidobacteria in the fecal and digesta samples (p < 0.05) and tended to have a reduction in the population of Escherichia coli in the digesta. However, higher numbers were detected by real-time PCR due to the count of DNA copies from both non-viable and viable bacteria. The sensitivity of real-time PCR of this study could detect as low as 102 copies of specific bacteria 16S rRNA gene. Besides, the optimized real-time PCR had the advantage of being less time-consuming and less labor-intensive, and allowing samples to be stored until analysis compared to the culture method. Therefore, real-time PCR could be used as an effective method to detect microbiota changing in the GI tract. Moreover, this technique can be applied in the future for evaluation of feed quality, which affects microbiota balance.


Factual background By its decision No. 2012/DZ/R/2/030, the Council of the Antimonopoly Office of the Slovak Republic (the "Council"), acting in its capacity as the appellate body of the…


Background
There are abbreviations that are used daily such as BP for blood pressure and ECG for electrocardiogram, but many of the abbreviations found in medical documents are unclear.

Aim
The purpose of this study was to assess the frequency, type and comprehension of abbreviations in admission notes and discharge letters composed by orthopedic surgery and medical residents.

Methods
Abbreviations were extracted from discharge letters and admission notes composed by residents from orthopedic surgery and medical wards. The frequency of use of the abbreviations was determined. Additionally, the fifty commonest abbreviations from each specialty were graded by three medical and three orthopedic surgery senior physicians as 1. understandable or 2. Ambiguous or unknown.

Results
The number of abbreviations found in the documents composed by medical and orthopedic surgery residents was 1525 with 80 different abbreviations and 493 with 51 different abbreviations respectively (9.3% and 4.9% of the total word number respectively). Analysis revealed that 14% of the abbreviations from medical ward documents were graded as ambiguous or unknown by medical senior physicians compared with 25% by senior orthopedic surgeons. When abbreviations from orthopedic surgery documents were presented to both groups, senior orthopedic surgeons graded 8% as ambiguous or unknown compared with 21% by the medical senior physicians.

Conclusion
In order to prevent impairment of patient care, only standard abbreviations should be used in medical documents. Measures should be taken to decrease the use of non standard abbreviations such as the incorporation of authorized abbreviations to the electronic medical record.


We reported the existence of high and low responders to the streptococcal cell wall antigen (SCW) in the human population. To analyze the mechanism of the low responsiveness to SCW at the cellular level, we established SCW‐specific CD4+ T cell lines. During the course of generation of a SCW‐specific CD4+ T cell line restricted by HLA‐DQ from a low responder, we obtained autoreactive CD8+ cytotoxic T lymphocytes as a cell line (HYCD8). They proliferated in the presence of autologous monocytes and IL‐2, without SCW. HYCD8 lysed autologous monocytes and Epstein‐Barr virus‐transformed B lymphoblastoid cell line (BLCL). This cytotoxic activity was specifically inhibited by an anti‐HLA class I framework monoclonal antibody and restricted by HLA‐B52 or B54 specificity, as judged by killing activity against panel cells and HLA class I‐transfected BLCL. It was unique to HYCD8 that the HLA class I‐restricted cytotoxicity was observed only in the presence of soluble factor with low molecular mass (< 104 Da) produced mainly by B cells, which could not be replaced by known cytokines and their mixtures. We thus describe novel HLA class I‐restricted cytotoxic CD8+ T cells that kill antigen‐presenting cells in a soluble factor‐dependent manner.


This work aims to present a ray tracing analysis to determine the numerical aperture of step-index fibers with conical tips. A multi-mode fiber optics is modeled and a ray tracing study is performed in order to obtain an equation for the numerical aperture in terms of the cone angle.


Iron silicate minerals are a significant component of sedimentary systems but their modes of formation remain controversial. Our analysis of published data identifies end‐member compositions and mixtures and allows us to recognize controls of formation of different mineral species. The compositional fields of glaucony, Fe‐illite, Fe–Al smectites are determined in the M+/4Si vs. Fe/Sum of octahedral cations (M+ = interlayer charge). Solid solutions could exist between these phases. The Fe–Al and Fe‐rich clay minerals form two distinct solid solutions. The earliest phases to be formed are Fe–Al smectites or berthierine depending on the sedimentation rate. Reductive microsystems appear in the vicinity of organic debris in unconsolidated sediments. The Fe is incorporated first in pyrite and then in silicates after oxidation. Potassium ions diffuse from the sea‐water–sediment interface. If not interrupted, the diffusion process is active until reaction completion is reached, i.e. formation of Fe‐illite or glauconite or a mineral assemblage (berthierine–nontronite) according to the available Al ion amounts in the microsystem. Mixed‐layer minerals are formed when the diffusion process is interrupted because of sedimentation, compaction or cementation. Despite the common belief of their value as palaeoenvironment indicators, these minerals can form in a variety of environments and over a period of millions of years during sediment burial.


Incorporating ubiquitous wireless sensor networks (WSNs) and powerful cloud computing (CC), Sensor-Cloud (SC) is attracting growing attention from both academia and industry. However, pricing for SC is barely explored. In this paper, filling this gap, five SC pricing models (i.e., SCPM1, SCPM2, SCPM3, SCPM4 and SCPM5) are proposed first. Particularly, they charge a SC user, based on 1) the lease period of the user, 2) the required working time of SC, 3) the SC resources utilized by the user, 4) the volume of sensory data obtained by the user, 5) the SC path that transmits sensory data from the WSN to the user, respectively. Further, analysis is also presented to study and demonstrate the performance of the proposed SCPMs. We believe that the pricing designs and analysis performed in this work could be a very valuable guidance for future researches regarding pricing in SC.


This paper presents a new approach for solving network routing optimization problems. In particular, the goal is to optimize the traffic in the network structured event-driven systems as well as to provide means for efficient adaptation of the system to changes in the environment - i.e. when some nodes and/or links fail. Many network routing optimization problems belong to the class of NP hard problems, which can only be solved by using some heuristic approach. This Paper provides a path to an incoming packet much faster than existing routing algorithms. This is basically an AI Concept, which is useful to get from the source to the destination. DFS (depth first search) and BFS (breath first search) searching techniques. A routing algorithm. DB Routing is based on a general-purpose metaheuristic named Ant Colony Optimization, which is a framework for building ant-inspired algorithms. DB is applied as the routing algorithm in a simulated packet-switched point-to-point network. It is investigated whether DB is able to obtain an increase in speed of transmission when packets are sent between two distinct nodes. To this end, it is investigated how prioritizing different heuristics effect the quality of the routing performed. It is concluded that DB behaves differently depending on the relative priority of positive feedback negative feedback and local heuristics, and that it is possible to adjust the parameters to achieve distribution of traffic over several paths when the network is heavily loaded


Metabolic and respiratory acid-base disorders occur as single and mixed entities. When induced perturbations in PCO2, HCO3(-), pH, and serum electrolytes are interpreted in the light of sound physiologic principles, even the most complicated mixed disorders may be easily diagnosed. The pathophysiology underlying the simple disturbances is defined and used as a framework for discussion of the mixed metabolic, respiratory acid-base derangements. Formulae are presented which allow one to predict what the appropriate degree of metabolic compensation should be for any primary respiratory disorder, or what the PCO2 should be for any given degree of primary metabolic acidosis or alkalosis. The various clinical settings in which mixed acid-base disorders occur most commonly are discussed.


Recently, it has been activated the software education or coding education for the improvement of the Computational Thinking (CT) ability at home and abroad. Also the CT has influence on courses of Computer Science in the college levels. It has been introduced and the number of cases of using it to general K12 education has increased. However, the research on the software education's influence on the CT was still lacking. So In this paper, we proposed this study has been conducted on how Scratch education in the elementary school level influenced the ability of the CT. And we proposed software education can improve the ability of CT. First, we provided the theoretical base of the software education and evaluation process through analysis of computational thinking ability. A core analysis content of the CT is broader than algorithmic thinking and can be achieved without using computer. It includes abstract, algorithmic, logical, and measurable thinking. Second, we made efforts to improve the characteristics of the software education with categorization. Finally, we have managed the software education using Picoboard with Scratch and flowchart within 15 weeks based on these theocratical research. An examination of the effectiveness was committed to understand, analyze, and develop strategies of problem solving. It is designed as a strategy of problem solving before and after the software lesson. The result of the software education has improved authentically in all areas without the need to design a strategy for problem solving. ▸Keyword : Software Education, Computational Thinking


The capacity to achieve and retain control over one's own life—to make decisions about and exert power over one's situation—is strongly correlated with being healthy. For older persons, there is a real danger that professionals with good intentions will encroach on this control in the name of providing service. We examine the issues of power, control, decision making, and healthy aging from the perspective of educating health care providers. Particular attention is paid to how health care providers see their role in defining older adults as being at risk when they refuse service or take risks that providers define as unacceptable. We raise this issue of appropriate professional control and cite the literature on successful coping to argue for policies and practices that enhance personal autonomy and interdependence as effective vehicles for healthy aging. Lessons from primary health care are applied to healthy aging even in the face of diminished capacities.


Alzheimer's disease (AD) is a chronic and incurable condition that results in progressive cognitive decline and increasing dependence for the affected individual. However, its impact is not limited to the individual but extends to the family who usually have a fundamental role in providing support. Traditionally research and policy on Alzheimer's family care has been largely focused on dyadic relationships and the experience of burden and stress, providing little understanding of the complexity and reciprocity of the caring dynamic within the family unit as it unfolds over time.

Adopting a family systems approach and a constructivist grounded theory methodology this study explored the experiences of living with AD for native Spanish families. Data were collected from a series of 26 interviews with seven family units living with early stage AD and three focus groups with 14 caregivers of people with mid-advanced AD. Data were analysed to capture the main processes involved and charted how these evolved over time.

Three main temporal stages to the early AD experience were identified termed 'what's going on here', 'our life is changing' and 'keeping things together. These developed in an iterative rather than linear fashion. This model and the processes that shape the experience ('noticing', 'watching', redefining' and 'balancing') reinforce the evolutionary and dynamic nature of living with early AD. The data strongly suggested that the nature and quality of existing family relationships and interactions are significant factors influencing the experience of AD for all members. The findings highlighted the impact that AD has on family dynamics and how these shape family responses to living with this condition. Some family dynamics were and remained close, others had always been and remained conflicting, some dynamics remained constant whilst others changed. A major
finding of the study was the lack of professional support that all families experienced leaving them 'feeling abandoned'.

The study provides valuable new insights into the nature of family relationships when living with AD, the impact the condition has on family dynamics and the ways in which family works to keep things in balance in the face of uncertain and constantly evolving challenges. Implications for policy, practice, education and further research are considered.


Training in the field of crisis management is complex and costly, requiring a combination of approaches and techniques to acquire not only technical skills, but also to develop the capability to cooperate and coordinate individual activities towards a collective effort (soft skills). In this paper we focus on serious games for increasing participants' skills in a playful manner. In the paper we identify general issues characterizing crises management and we analyze the state of the art of serious games for crisis management in order to understand strengths and weaknesses of these environments.


The aim of this study was to evaluate the effects of the driving performance and workload according to changing driving environment and types of steering wheel. Twelve drivers who participated in this study consisted of two groups; six Japanese as the left-lane drivers who was accustomed to driving on left-hand side of the road, and six Europeans, Americans, and Korean as the right-lane drivers who was accustomed to driving on right-hand side of the road. They were asked to operate a driving simulator while using two different types of steering wheel (for the left-hand side driving and the right-hand side driving). During the experiment, a range of data were measured including driving performance, mental workload, and eye movements which were recorded in order to identify the amount of time looking towards the in-vehicle route guidance. Results indicated that the use of the steering wheel by parallel moving led to increase high attentional demand and worse glance behavior to traffic signs for the left-lane drivers. In the case of the right-lane drivers, the effects by changing driving direction were more effective than the types of steering wheel due to their habit or traits.


When freshwater planarians are exposed to a low-percentage (0.5%–1%) alcohol solution, they display a characteristic 'drunken' phenotype. Here we show that this drunken phenotype is a mixture of cilia-mediated gliding and scrunching, a muscular-based planarian gait which we recently demonstrated to be triggered by adverse environmental stimuli. At exogenous ethanol concentrations ≥2% (v/v), planarians become gradually immobilized and ultimately die. Using RNA interference (RNAi) for targeted gene knockdown, we elucidate the molecular basis for ethanol sensing and show that the big potassium ion channel SLO1 is necessary for ethanol sensitivity in planarians. Because slo1(RNAi) animals maintain their ability to scrunch in response to other adverse triggers, these results suggest that slo1 specifically regulates ethanol sensitivity and not the scrunching gait per se. Furthermore, this study demonstrates the ease of performing pharmacological studies in planarians. Combined with the worms' amenability to quantitative behavioral assays and targeted gene knockdown, planarians are a valuable model organism for studying the effect of neuroactive compounds on brain function and behavior.


This paper describes the development of notch filters and dichroic beam-splitters, the latter to be a visible 2-channel WDM Multiplexer/Demultiplexer (MUX/DEMUX). Both discrete devices are intended to be used on very short-haul links based on Poly-Methyl-Methacrylate (PMMA) Polymer Optical Fibres (POFs). The filters were built from commercially available multilayer dielectric stack and also from engineered Cholesteric Liquid Crystals (CLCs). The latter was manufactured by using nematic LC doped with appropriate chiral dopant. In order to have the reflection of above 80% for the desired wavelength and also for non-polarised light we used approximately 20 layers of CLC with both helicities in a planar Grandjean texture. The CLC with left handed helix will reflect left circularly polarised light, while the right handed helix will reflect the right handed circularly polarised light.


The interactions between different genotypes of Hepatitis B virus (HBV) in co-infected patients remain largely unknown, especially in acute infection. Here, the evolution of HBV strains was studied in an acute, self-limited hepatitis B patient co-infected with genotypes Ba (B2) and C. Virological analyses were performed at four time points after admission: T1 (5 days), T2 (11 days), T3 (22 days) and T4 (260 days). A dominant-genotype change from genotype C to Ba was found after anti-HBV e antigen (anti-HBe) seroconversion. Further clonal and phylogenetic analyses of the pre-S and pre-core/core regions of HBV were carried out to clarify the interactions between genotypes Ba and C. All clones propagated from T1 and T2 were of genotype C. In contrast, clones propagated from T3 (after anti-HBe seroconversion) were of genotype Ba, C and/or recombinant within the pre-S region. At T4, all clones were of genotype Ba with a 123 bp (from nt 3147 of the pre-S1 region to nt 54 of the pre-S2 region) in-frame pre-S deletion and had lost the start codon of the middle envelope protein and the nucleocapsid-binding site. Phylogenetic analysis showed that genetic distance was greater at T3 after seroconversion to anti-HBe. By using SimPlot, the breakpoint of one pre-S recombinant was located at nt 3069-3100 and the other two at nt 49-87. In conclusion, HBV genotype Ba may overtake genotype C as the predominant strain after anti-HBe seroconversion in acute hepatitis B. Recombination within the pre-S region emerged transiently and the pre-S deletion mutant was finally cleared.


The fossil renamed here was first described in 1959 as Aeolisaccus kotori RADOIČIĆ, a new species of a problematic fossil worm, Aeolisaccus ELLIOTT. In 1975 DE CASTRO recognized the true relationships of this microbial fossil: a cyanobacterium related closely to the modern genus Scytonema. The fossil is common in the sediments of the Mesozoic carbonate platforms of southern Europe. This contribution confirmed DE CASTRO's interpretation, determined, using the high resolution of the SEM, the extent to which these fossils have preserved their original architecture, and investigated their presumed modern counterparts among the abundant mat-forming species of Scytonema on the intertidal flats of Andros Island, a part of the Bahama carbonate platform. The systematic affinities of the fossil and the environments it inhabited were reconstructed by comparing the morphology of the fossils to that of their modern counterparts, along with their respective sedimentary contexts. Based on these comparisons, we conclude that the organism lived in a peritidal environment and was buried and fossilized in the shallow waters of an ancient carbonate platform. A formal transfer of the fossil to a new genus of fossil cyanobacteria thereby designated as Decastronema gen. nov. is proposed, honoring the contribution of Prof. Piero DE CASTRO to paleontology.


Pancreas divisum occurs when the embryological ventral and dorsal parts of the pancreas fail to fuse, so that pancreatic drainage is mainly through the accessory papilla. In 169 patients with primary biliary tract disease who underwent pancreatography incidental to endoscopic cholangiography, the incidence of pancreas divisum was 3.6%. Among 78 patients with unexplained recurrent pancreatitis, the incidence was 25.6%. The hypothesis that the duct anomaly can cause obstructive pain and pancreatitis is presented, and supported by a detailed analysis of 47 patients with the condition.


This study is an attempt to identify factors that cause divorce in the Syariah Court of Mukah Division from 2000 to 2010. A total of 356 cases are studied involving various types of divorce as enacted in the Ordinance of Islamic Family Law of Sarawak, also cases that are rejected and withdrawn, namely 44 cases. The study uses the method of data analysis from case files and complaint information forms. Divorce factors based on several demographic plaintiffs and defendants. The aspects studied are period of marriage, age of husband and wife, income, number of children, educational background and reasons of divorce. Data are analyzed quantitatively and presented in the types of frequency and percentage. The result shows that the neglect of responsibility between spouses is the fundamental internal factor of divorce in Mukah, Sarawak, besides external factors, namely marriage at young age and household income.


We introduce and formulate the Sport Event Filming (SEF) problem. We are interested in controlling the movement of a set of camera drones that are filming the event by moving over the field where the event takes place. The objective of the problem is to maximize the satisfaction of event viewers while minimizing the distance traveled by the camera-drones. We model the static version of the SEF problem as a Vehicle Routing Problem with Soft Time Window (VRP-STW), where the whole sequence of actions in the event are known a priori. Since this assumption is unrealistic for real sport events, we propose two families of heuristics to solve the dynamic version of the problem, where the camera-drones do not have any knowledge of the input sequence and move in reaction to the movements of the protagonists of the event. The first family (Nearest Neighbor) is based on a technique used in robotic systems, whereas the second family (Ball Movement Interception) is designed based on specific characteristics of the SEF problem. We present extensive simulation results for both families in terms of average viewer satisfaction and traveled distance for the camera-drones, when several parameters vary.


Extracellular vesicles (EVs) mediate cell-to-cell communication via the transfer of biomolecules locally and systemically between organs. It has been elucidated that the specific EV cargo load is fundamental for cellular response upon EV delivery. Therefore, revealing the specific molecular machinery that functionally regulates the precise EV cargo intracellularly is of importance in understanding the role of EVs in physiology and pathophysiology and conveying therapeutic use. The purpose of this review is to summarize recent findings on the general rules, as well as specific modulator motifs governing EV cargo loading. Finally, we address available information on potential therapeutic strategies to alter cargo loading.


For any information: email@example.com The study of air pollutants SO2, NO2 and PM10 in lower Onitsha basin, a densely populated city was performed using GPS and Matlab modeling. The pollutants were studied in nine specific locations for 3 months of rains over 3 consecutive years with each georeferenced. The Matlab pollution model was generated by integrating the spatial database and measured pollution attributes database using a polynomial expression. SO2 highest concentration (141 μg/m3) peaked in Upper Iweka at sampling point 1 before dispersing to lower concentrated regions in Awada and Resthouse. NO2 peaked at 207 μg/m3 in Upper Iweka at sampling point 3 and driven by wind towards Borromeo area to very low concentration of 38 ug/m3. The PM10 peaked in Upper Iweka (180 μg/m3) and driven by rains towards Borromeo before increasing again in concentration levels at Awada. The AQI showed that SO2 pollutants had acceptable air quality at all sampling points while NO2 and PM10 air quality affected sensitive groups. SO2 concentration levels exceeded the National air quality standard in Nigeria (NAQS) while NO2 and PM10 were below the NAQS standard. The GIS plot showed that 3 metrological forces were driving pollutants from Upper Iweka and Awada to other sampling areas in the order of SO2> NO2> PM10. The Matlab wind speed plot showed that there was an upward wind in upper Iweka driving the pollutants towards dispersal at some other region. Thus, Upper Iweka is an active point source pollution area and dispersed to Borromeo and Awada by scavenging rains under prevailing wind speed, wind direction and humidity. Hence calls for improved monitoring and regulation to address pollution.


Abstract The objective of this work was to formulate and characterize non-ionic surfactant vesicles (niosomes) as an ocular carrier of dorzolamide hydrochloride (Dorzo); one of the antiglaucoma drugs. Niosomes were prepared of Cholesterol (Chol) with sorbitan monoesters (Span 20, 40, 60) or sorbitan trioleate (Span 85) in a molar ratio of 40:150. Those prepared from Span 40 were selected for further investigation on the effect of addition of dicetylphosphate (DCP) and polyoxyethylene fatty acid esters (either Tween 20, 40 or 80). All The batches were prepared using mechanical shaking technique, followed by sonication and then characterized using Zetasizer, transmission electron microscopy (TEM), calculating percent drug entrapment efficiency and cumulative percent released. Z-average sizes of the niosomes were between 25.9 and 165.5 nm. All niosomal formulations showed negative zeta potential charge. Dorzo was successfully entrapped in all of the formulations with entrapment efficiencies ranging between 34.81% and 97.66%. With reference to release profiles, Dorzo-loaded niosomal formulations showed significant reduction in cumulative percent drug released than Dorzo solution. High entrapment efficiencies, biphasic prolonged release rate and small particles size highlight Dorzo-loaded niosomal preparations as a promising ophthalmic carrier to prolong the drug lowering effect on the intraocular pressure.


Early modern heraldry was far from a nostalgic remnant from a feudal past. From the Reformation to the French Revolution, aspiring men seized on these signs to position themselves in a changing society, imbuing heraldic tradition with fresh meaning. Whereas post-medieval developments are all too often described in terms of decadence and stifling formality, recent studies rightly stress the dynamic capacity of bearing arms. Heraldic Hierarchies aims to correct former misconceptions. Contributing authors rethink the influence of shifting notions of nobility on armorial display and expand this topic to heraldry's share in shaping and contesting status. Moreover, addressing a common thread, the volume explores how emerging states turned the heraldic experience into an instrument of power and policy. Contributing to debates on social and noble identity, Heraldic Hierarchies uncovers a vital and surprising aspect of the pre-modern hierarchical world.


beta-Lactam antibiotics rapidly kill bacteria during logarithmic growth but fail to kill nongrowing cells. This trait is the most universal example of phenotypic tolerance (the ability of bacteria to evade the bactericidal activity of antibiotics). Both nongrowing and slowly growing bacteria are found very frequently during infection in vivo, and phenotypic tolerance to the bactericidal activity of antibiotics as a consequence of reduced growth rate can be detected in vivo. With the use of an in vitro model system of nongrowing bacteria, a select group of beta-lactam antibiotics has been found that demonstrates a striking and unusual ability to kill nongrowing bacteria despite phenotypic tolerance to conventional beta-lactam antibiotics. These same compounds also effectively kill phenotypically tolerant cells in cerebrospinal fluid and serum. The extension of bactericidal activity to nongrowing and slowly growing bacteria may be a major advance in efforts to improve the chemotherapy for infectious diseases.


This paper discusses a method for optimizing production and operation for onshore/offshore wells. Optimizing the production of oil and gas fields necessitates the use of accurate predication techniques to minimize uncertainties associated with day-to-day operational challenges related to serious operational problems caused by asphaltene deposition. It involves the use of a dynamic flow simulator for modeling oil and gas production systems and reservoir management to determine the feasibility of its economic development. Many studies have focused on relating asphaltene precipitation flocculation and deposition in oil reservoirs and flow assurance in the wellbores. Experimental techniques and theoretical models have been developed trying to understand and predict asphaltene behavior. Nevertheless, some ambiguities still remain with regard to the characterization asphaltene in crude oil and its stability during the primary, secondary, and tertiary recovery stages within the near-wellbore regions.
 A synthetic onshore full-field scale that is based on a heterogeneous three-dimensional Cartesian single-well model is considered in this paper. Two wells (a producer and an injector) and one reservoirs are considered to evaluate the dynamic properties under the influence of asphaltene. The size of the reservoir is 25 ft × 25ft × 20 ft and is represented by grid numbers of 50 columns × 50 rows × 5 layers with 12 hydrocarbon components constituting the constant crude composition of this model. The model comprised a total of 12,500 grid blocks. The three-dimensional simulation employed 5-layers, incorporating all relevant production and reservoir data. Different production scenarios were investigated to define the most appropriate and efficient production strategy. This paper provides a method to assess the effect of asphaltene precipitation, flocculation, and deposition in the well productivity and the economic impacts related to it and investigating prevention techniques and other related in-situ pore level flow assurance parameters.
 The results will include a comparison of production rates with and without asphaltene precipitation, flocculation, and deposition. In addition, it provides a comparison of asphaltene precipitation, flocculation, and deposition at different times using varying bottomhole and production rate constraints. Several cases (i.e., WAG cycles, completion, target layers of injection, etc.) are tested to help in selection of the optimum completion and operating strategy in the presences asphaltene. The paper will provide insight into factors affecting the flow assurance of oil and gas reservoirs.


Main-group halide perovskites have generated much excitement of late because of their remarkable optoelectronic properties, ease of preparation, and abundant constituent elements, but these curious and promising materials differ in important respects from traditional semiconductors. The distinguishing chemical, structural, and electronic features of these materials present the key to understanding the origins of the optoelectronic performance of the well-studied hybrid organic-inorganic lead halides and provide a starting point for the design and preparation of new functional materials. Here we review and discuss these distinguishing features, among them a defect-tolerant electronic structure, proximal lattice instabilities, labile defect migration, and, in the case of hybrid perovskites, disordered molecular cations. Additionally, we discuss the preparation and characterization of some alternatives to the lead halide perovskites, including lead-free bismuth halides and hybrid materials with optically and electronically active organic constituents.


Local differential privacy (LDP) is a variant of differential privacy (DP) that avoids the necessity of a trusted central curator, at the expense of a worse trade-off between privacy and utility. The shuffle model has emerged as a way to provide greater anonymity to users by randomly permuting their messages, so that the direct link between users and their reported values is lost to the data collector. By combining an LDP mechanism with a shuffler, privacy can be improved at no cost for the accuracy of operations insensitive to permutations, thereby improving utility in many analytic tasks. However, the privacy implications of shuffling are not always immediately evident, and derivations of privacy bounds are made on a case-by-case basis. In this paper, we analyze the combination of LDP with shuffling in the rigorous framework of quantitative information flow (QIF), and reason about the resulting resilience to inference attacks. QIF naturally captures (combinations of) randomization mechanisms as information-theoretic channels, thus allowing for precise modeling of a variety of inference attacks in a natural way and for measuring the leakage of private information under these attacks. We exploit symmetries of k-RR mechanisms with the shuffle model to achieve closed formulas that express leakage exactly. We provide formulas that show how shuffling improves protection against leaks in the local model, and study how leakage behaves for various values of the privacy parameter of the LDP mechanism. In contrast to the strong adversary from differential privacy, who knows everyone's record in a dataset but the target's, we focus on an uninformed adversary, who does not know the value of any individual in the dataset. This adversary is often more realistic as a consumer of statistical datasets, and indeed we show that in some situations, mechanisms that are equivalent under the strong adversary can provide different privacy guarantees under the uninformed one. Finally, we also illustrate the application of our model to the typical strong adversary from DP.


Quantificational determiners have meanings that are "conservative" in the following sense: in sentences, repeating a determiner's internal argument within its external argument is logically insignificant. Using a verification task to probe which sets (or properties) of entities are represented when participants evaluate sentences, we test the predictions of three potential explanations for the cross-linguistic yet substantive conservativity constraint. According to "lexical restriction" views, words like every express relations that are exhibited by pairs of sets, but only some of these relations can be expressed with determiners. An "interface filtering" view retains the relational conception of determiner meanings, while replacing appeal to lexical filters (on relations of the relevant type) with special rules for interpreting the combination of a quantificational expression (Det NP) with its syntactic context and a ban on meanings that lead to triviality. The contrasting idea of "ordered predication" is that determiners don't express genuine relations. Instead, the second argument provides the scope of a monadic quantifier, while the first argument selects the domain for that quantifier: the sequences with respect to which it is evaluated. On this view, a determiner's two arguments each have a different logical status, suggesting that they might have a different psychological status as well. We find evidence that this is the case: When evaluating sentences like every big circle is blue , participants mentally group the things specified by the determiner's first argument (e.g., the big circles) but not the things specified by the second argument (e.g., the blue things) or the intersection of both (e.g., the big blue circles). These results suggest that the phenomenon of conservativity is due to ordered predication.


In urban India version of transportation, the traffic planners mostly give stress on motorized mode of movement .All kinds of steps are taken for development of roads in terms of safety, speed or time interval at intersections in case of motorized vehicle. But in present traffic condition, the non-motorized mode of traffic is also increasing. The pedestrians and bicyclists are occupying the track of motorized vehicle as no separate grades are provided for them. It leads to traffic congestion as well as the safety factor of pedestrian is at stake. According to HCM 2010, for this heterogeneous traffic, we can't just increase the level of service by developing the quality of roads for vehicles Steps have been taken to reclaim pavement for pedestrians by removing the encroachment on footpath. A study was carried out on Bhubaneswar market complex at Unit -2 where about 260 meters of footpath surrounding it and separated from road by divider along road side. The users were asked to answer the questions the quality of service provided by the system in terms of questionnaire formed .The format of questionnaire was based on the factors that user perceive. From the ratings, an analysis was carried out to find the level of service based on perception of the interviewers .The analysis consisted of five factors as safety, Comfort level vendors encroachment ,accessibility and side walk performance, climate condition. The analysis was done on SPSS and the area was categorized to a specific level of service out of 6 degrees of level of service (LOS). It is difficult to have LOS value for an area based on perception as it varies from person to person. So the trail is made to its best possible value of LOS depending on majority of the majority of user's perception.


MicroRNAs (miRNAs) are endogenous noncoding RNAs that negatively regulate gene expression by binding the 3′ noncoding region of the messenger RNA targets inducing their cleavage or blocking the protein translation. They play important roles in multiple biological and metabolic processes, including developmental timing, signal transduction, and cell maintenance and differentiation. Their deregulation can predispose to diseases and cancer. miRNA expression has been demonstrated to be deregulated in many types of human tumors, including thyroid cancers, and could be responsible for tumor initiation and progression. In this paper we reviewed the available data on miRNA deregulation in different thyroid tumors and describe the putative role of miRNA in thyroid cancer development.


Analytical methods are required by trading standards and regulatory authorities to confirm the authenticity of Scotch whisky brands. The characteristics of Scotch whisky are strongly influenced by the cereals used in fermentation and by distillation, maturation and blending regimes. This leads to characteristic analytical profiles for various congeners, which can be used as reference points in authenticity analysis. Scotch whisky higher-alcohol profiles for specific brands were shown to be very consistent over many production batches and so their gas-chromatographic determination, together with the presence of other specific congeners, offered an effective approach to authenticity analysis. Pyrolysis–mass spectrometry followed by multivariate analysis of the resulting mass spectra enabled non-authentic samples to be discriminated from the authentic product. Hence, an increasingly sophisticated portfolio of analytical strategies are available in order to confirm brand authenticity.


Abstract Employees' failures to follow information security policy can be costly to organizations, causing organizations to implement security controls to motivate secure behavior. Information security research has explored many control-related motivations (e.g., self-efficacy, response efficacy, and behavioral control) in the context of ISP compliance; however, the behavioral effects of perceptions of autonomous functioning are not well understood in security contexts. This paper examines employee autonomy as a control-related motivation from the lens of self-determination theory and psychological reactance theory. Self-determination theory is widely used in other disciplines to explain intrinsically driven behavior, but has not been applied to security research. Psychological reactance theory is also widely used, but is only beginning to receive attention in security research. Self-determination and psychological reactance offer complementary yet opposite conceptualizations of trait-based autonomy. This paper posits that perceptions of trait-based autonomy influence self-efficacy and response efficacy. Through a survey of government employees, we provide support for several hypotheses. We also discuss important directions for the use of self-determination theory and psychological reactance theory in future research.


The sequence of biosynthetic steps from phosphatidylserine to phosphatidylethanolamine (via decarboxylation) and then phosphatidylcholine (via methylation) is linked to the intracellular transport of these aminoglycerophospholipids. Using a [3H]serine precursor and permeabilized yeast cells, it is possible to follow the synthesis of each of the aminoglycerophospholipids and examine the requirements for their interorganelle transport. This experimental approach reveals that in permeabilized cells newly synthesized phosphatidylserine is readily translocated to the locus of phosphatidylserine decarboxylase 1 in the mitochondria but not to the locus of phosphatidylserine decarboxylase 2 in the Golgi and vacuoles. Phosphatidylserine transport to the mitochondria is ATP independent and exhibits no requirements for cytosolic factors. The phosphatidylethanolamine formed in the mitochondria is exported to the locus of the methyltransferases (principally the endoplasmic reticulum) and converted to phosphatidylcholine. The export of phosphatidylethanolamine requires ATP but not any other cytosolic factors and is not obligately coupled to methyltransferase activity. The above described lipid transport reactions also occur in permeabilized cells that have been disrupted by homogenization, indicating that the processes are extremely efficient and may be dependent upon stable structural elements between organelles.


The possibilities of morphometry in the study of normal and pathologically altered kidney at the macroscopical, light optical and ultrastructural levels are considered. Morphometrical approaches to the examination of the glomeruli, nephron canaliculi and collecting tubules, blood and lymph vessels, juxtaglomerular apparatus, interstitial medulla cells, intraorgan nerves are analysed. Some practical recommendations for quantitative analysis of the renal structure are given, the causes of possible errors are indicated.


A big issue in the paradigm of Service Oriented Architectures (SOA) is service discovery. Organizations publish their services via the Internet. These published services can then be automatically found and accessed by other services, meaning, the services are composed. A fundamental property of a service composition is weak termination, which guarantees the absence of deadlocks and livelocks. In principle, weak termination can be verified by inspecting the state space of the composition of (public views of) the involved services. We propose a methodology to build that state space from precomputed fragments, which are computed upon publishing a service. That way, we shift computation effort from the resource critical "find" phase to the less critical "publish" phase. Interestingly, our setting enables state space reduction methods that are intrinsically different from traditional state space reductions. We further show the positive impact of our approach to the computational effort of service discovery.


Serum can be used to investigate changes in cytokine concentration following burn injury in children, however for children receiving treatment in an outpatient setting, blood is not routinely collected and therefore cannot be used for monitoring. The aim of this study was to investigate the use of saliva as a non-invasive tool for predicting burn outcomes by measuring the concentration of salivary cytokines in children with small area burns. A multiplex cytokine assay was used to measure 17 cytokines in the saliva of paediatric patients with burns (n = 20) and healthy controls (n = 20). After the removal of cytokines that had >30% of samples below the assay lower detection limit, six cytokines including IL-1β, IL-4, IL-7, IL-8, MCP-1 and TNFα were analysed for association with burns. IL-1β and IL-4 were found to be significantly elevated in the paediatric burn patients compared to healthy controls. Interestingly, IL-1β was also significantly elevated in scald burns, compared to contact burns. In addition, biologically meaningful differences in cytokine concentration were identified in patients with different burn characteristics, which warrant further investigation. This exploratory study provides evidence that cytokines can be detected in the saliva of children and that salivary cytokine profiles differ between healthy controls and children with burns. Overall, this study demonstrates the value of saliva for the investigation of cytokines and its potential application in paediatric diagnostics, specifically in situations where blood collection is not appropriate.


Isolation of bacterial chromosomes under "mild" conditions enable us to purify a bacterial deoxyribonucleoprotein (DNP). This DNP is enriched in small basic proteins which are complexed with DNA throughout all the purification steps. The basic proteins are shown to be similar to some heat-resistant proteins of cellular extract and can interact with DNA in vitro. Extensive nuclease digestion of purified DNP of E. coli produced the smallest DNA fragments of 100--120 base pairs in length. The proteins of the DNP and the possible mode of arrangement of basic proteins along the DNA are discussed.


Dependent types are a powerful tool for maintaining program invariants. To take advantage of this aspect in real-world programming, efforts have been put into enriching dependently typed languages with missing constructs, most notably, effects. This paper presents a language that has two practically interesting ingredients: dependent inductive types, and the delimited control constructs shift and reset. When integrating delimited control into a dependently typed language, however, two challenges arise. First, the dynamic nature of control operators, which is the source of their expressiveness, can break fundamental language properties such as logical consistency and subject reduction. Second, CPS translations, which we often use to define the semantics of control operators, do not scale straightforwardly to dependently typed languages. We solve the former issue by restricting dependency of types, and the latter using answer-type polymorphism of pure terms. The main contribution of this paper is to give a sound type system of our language, as well as a type-preserving CPS translation. We also discuss various extensions, which would make our language more like a full-spectrum proof assistant but pose non-trivial issues.


Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC

Compared to the conventional monolayers or suspension cultures, 3D culture models have drawn attention as a vivo-mimic model which can produce clinically relevant data. Among the several types of 3D culture models, multicellular spheroid (MCS) is a appropriate model for study of penetration and efficacy of anticancer agents. Purpose of this study was to establish MCS of human pancreatic cancer cell (Panc-1) and evaluate its usefulness as anticancer efficacy test. Panc-1 MCS was produced successfully by using poly-dimethylsiloxane(PDMS) microwell instead of agarose-coated 96-well system. MCS with average diameter of 375 μm was prepared in 700 μm microwells after 4 days of culture. Spherical morphology with rather rough surface and junctional structures in outer cell layers were observed with no notable necrotic area. Extracellular matrix proteins such as collagen I, fibronectin, and laminin were detected in the interstitial space of MCS. Stem cell population with CD44+/CD24+/ESA+ expression increased from 0.1% to 2.1% when cultured as MCS. miRNA expression profiling showed a difference between monolayers and MCS, i.e., 36 and 85 genes were up- and down-regulated in MCS, respectively. Imaging of drug penetration and viability indicators including MitoSOX, Edu incorporation, and Ki-67 expression were optimized for microwell format. Colorimetric assays of MTS and APH were performed after transferring MCS to 96-well plates. Overall, we demonstrated that PDMS microwell is an appropriate platform for preparation of MCS of Panc-1 cells and MCS showed different biological features from monolayers, suggesting that Panc-1 MCS prepared using PDMS microwell may be a useful 3D model for anticancer efficacy test.

Citation Format: Sang-Eun Yeon, Sang-Hoon Lee, Hyo-Jeong Kuh. Characteristics of pancreatic cancer spheroids as a model for anticancer efficacy test. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2722. doi:10.1158/1538-7445.AM2013-2722

Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.


Cell growth and retamycin production in Streptomyces olindensis So20 were studied at different dissolved oxygen levels during fermentation. The profiles for cell growth and retamycin production in an experiment with dissolved oxygen control at 5% air saturation during production were similar to those in an experiment without dissolved oxygen control. However, despite slower cell growth, a twofold increase in the final retamycin concentration was achieved when dissolved oxygen was controlled at 100% during the growth phase, compared to a base experiment (no DO control). Therefore, the results revealed that retamycin production was dependent on dissolved oxygen concentration during the growth phase, even with sufficient oxygen. On the other hand, a large oxygen supply during the production phase did not contribute to an improvement in retamycin production.


Purpose of Study In both FOLFOX and FOLFIRI regimens used for colorectal cancer, the 5-FU is infused over 46 hours every 14 days. Given the 10–20% risk of neutropenic fever, these regimens may be given with pegfilgrastim support. There is evidence to support its use for 21 day cycles, but no phase III trials demonstrating its efficacy and safety for regimens given every 14 days, a potential concern, given the hypothesis that the hematopoietic stem cells mobilized by pegfilgrastim into the peripheral blood may undergo cell cycle arrest, apoptosis and death while under effect of chemotherapy. Pegfilgrastim regulates the proliferation, differentiation, and survival of the myeloid lineage. It mobilizes hematopoietic progenitor cells in the peripheral circulation, has a long half-life, and is given on day 4 of 14-day infusional 5-FU based regimens. Given the fact that cytotoxic chemotherapy is administered on day 11 after pegfilgrastim, we performed a retrospective study evaluating the correlation between decrease in complete blood count and chemotherapy administered at 11 day intervals after pegfilgrastim. Methods Used The medical records of colorectal cancer patients were reviewed from 2003–2013. Data collected included age, stage, ethnicity, complete blood count, chemotherapy, and use of pegfilgrastim. Summary of Results Data from 50 eligible charts was collected. Twenty one patients were treated with chemotherapy and pegfilgrastim, 29 patients had chemotherapy alone. Prior to chemotherapy, both groups had a mean leukocyte count of 6.6×109/L and 6.8×109/L and a mean platelet count of 313,000/mm3 and 255,000/mm3 respectively. At 9 months mean leukocyte counts were 6.3×109/L and 5.4×109/L and the mean platelet counts were 186,000/mm3 and 170,000/mm3 respectively. At 24 months, the mean leukocyte counts were 6.7×109/L and 5.7×109/L and the mean platelet counts were 220,000/mm3 and 196,000 mm3 respectively. Conclusions When given on day 4 of a 14 day cycle, there was no effect of pegfilgrastim on complete blood counts in this small retrospective cohort study; finding a more subtle effect would require a larger sample size.


From its very inception to the present day the French Resistance has been represented and commemorated in the epic mode. While Laurent Douzou's book, La Résistance française: Une histoire périlleuse, reaffirms this heroic vision, Pascal Convert's sculpture honoring executed Resistance fighters on Mont Valérien and his documentary film Mont Valérien, aux noms des fusillés propose a more human, even anti-heroic approach which nevertheless aims to unite a community in memory by celebrating the courage and sacrifice, but also the specific persons, of previously forgotten résistants. The poetics of memory implicit in Convert's works are emblematic of a more general evolution of sensibilities, since contemporary disinterest in the virtues of the warrior and a concomitant preference for recovering the humanity of war's victims can be best understood in reference to the successive trauma of World War I and the Holocaust.


Advice is a common but potentially problematic way to respond to someone who is distressed. Politeness theory (Brown & Levinson, 1987) suggests advice threatens a hearer's face and predicts that the speaker-hearer relationship and the use of politeness strategies can mitigate face threat and enhance the effectiveness of advice messages. Students (N=384) read 1 of 16 hypothetical situations that varied in speaker power and closeness of the speaker-hearer relationship. Students then read 1 of 48 advice messages representing different politeness strategies and rated the message for regard shown for face and for effectiveness. However, neither speaker-hearer relationship nor politeness strategies was consistently associated with perceived threat to face or perceived advice effectiveness. We suggest revisions to politeness theory and additional factors that may affect judgments of face sensitivity and advice effectiveness.


Many regions of Sub-Saharan Africa (SSA) are experiencing fast increases in human population pressure and urbanization. By 2050, feeding a planet of 9 billion people will require an estimated 50 percent increase in agricultural production. Farmers in in the Sahel are exposed to a highly variable weather over time, and to their limited adaptive capacity, therefore often use livestock as income generator, export earnings, and as insurance against weather risk. There is an increasing demand for livestock products, which increase pressure on crop residues use on the land. In this study, I use panel socio-economic data combined with village rainfall level from Niger to investigate how different types of weather shocks including drought and wet conditions influence farmer's inputs adaption. Using cluster and year fixed effects estimations, I find that exposure to drought results in a strong and deep decrease in use of crop residues on the soil, which is particularly concerning because crop residue is crucial for soil protection, and fertility. I also find that one of the reasons poor Nigerien farmers remove crop residues on their land, is for livestock feeding purposes. This results in a bad synergy because removing crop residues could decrease long-term food production, and might keep households in poverty trap. Other determinants affecting inputs adoption on the land including temperature increase, income, farm size, and rainfall level of the previous year. I discuss policy recommendations.


A linear elastic study is performed, as a first-order approximation, to investigate the geometry of the resin-rich region observed around fiber-optic sensors embedded in laminated 'adaptive' composites. The Rayleigh-Ritz method is employed with beam-bending functions as assumed trial functions. The total potential energy is minimized with respect to unknown force distributions in each layer and the unknown length of the resin pocket. The resulting system of coupled nonlinear equations is solved by the Levenberg-Marquardt algorithm to compute the shape and size of the resin pocket. Results of this analysis show the effect of laminate stacking sequence, lamination pressure, and optical fiber diameter on the geometry of the resin pocket; and are found to agree well with experimental observations. The computed geometry is automatically discretized for finite-element analysis in order to obtain stress information in the vicinity of the resin pocket.


Power system major transmission requirements and their associated costs are considerably influenced by the location of the future generating capacity. The object of major transmission planning is to select the most desirable transmission network for each of the generation expansion patterns under consideration. Both economics and reliability considerations are considered in the appraisal of the most desirable transmission network. The application of a digital computer to automated transmission planning allows the system planner to investigate many alternatives with much less effort than by manual means. The ultimate selection of the generation expansion plan is then made by considering the transmission as an integral part of the total cost.


Abstract The Global Registry of Acute Coronary Events (GRACE) risk score independently predicts major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS). This study aims to evaluate whether the level of plasma homocysteine in addition to the GRACE score enhances the predictive value for MACEs in patients with acute coronary syndrome. A total of 361 patients with ACS evaluated at our hospital were included in the study and tested for blood homocysteine levels. We recorded 40 (11.1%) instances of MACE during a median follow-up of 43.3 months (quartile 40.6–44.4 months), including 29 cases (8.0%) of all-cause death and 11 cases (3.1%) of nonfatal myocardial infarction. The GRACE score was significantly associated with homocysteine levels, and multivariate Cox regression analysis showed that both the GRACE risk score and homocysteine content were independent predictors of MACEs (HR 2.63; 95% confidence interval (CI) 1.54 to 4.49; P < .001 and 2.27; 1.06 to 4.86; P = .035, respectively). Moreover, meta-analysis showed that as the homocysteine level increased, the incidence of MACEs also increased (log-rank 8.41; P = .015). GRACE scores adjusted by homocysteine level increased the area under the curve (AUC) from 0.78 to 0.83 (P = 0.006). Blood homocysteine levels are significantly associated with the GRACE risk score, and using both parameters can further improve risk stratification in patients with acute coronary syndrome.


Vast ferromanganese nodule fields have been found on the deep-sea floor of all oceans worldwide. They have received attention because they potentially provide high-grade metal resources to develop future high- and green-technology. However, how these vast nodule fields were formed and developed owing to their widespread nature or tendency to be denser with an increasing number of nodules has not yet been established. In this study, the fine-scale inner structure of nodules of various sizes was analyzed on the basis of chemical mapping using microfocus X-ray fluorescence. We found that nodules distributed in the vast field around Minamitorishima (Marcus) Island have several types of innermost layers, which correspond to different chemostratigraphic layers of nodules that have been previously reported by us in this region. As nodules grow in order from the center to the outside, the different types in the innermost layer indicate a difference in the timing of the beginning of their growth. Moreover, because the differences in the chemical features of each layer reflect differences in the composition of the original deep-sea water, our results imply that the beginning of nodule formation occurred intermittently at each time of a water mass replacement due to new deep-sea currents flowing into this region. We recognized that the northern part of the study area was dominated by large nodules that started to grow in relatively earlier times, while the southern part tended to have many nodules that grew in relatively later times. Based on these observations, we hypothesize that the intermittent beginning of nodule formation is governed by the northward inflow of the deep-sea current that originated from the Lower Circumpolar Deep Water for an extended time to form the vast nodule field. Because patterns in the timing of nodule formation were different in the eastern and western regions, we thus further propose that the topographic framework, i.e., the arrangement of individual large seamounts and the cluster of small knolls and petit-spot volcanoes, strongly regulates the flow path of the deep-sea current, even if the position of the entire seamount changes owing to plate motion. The deep-sea current might supply some materials to be nuclei, resulting in the nodule formation at the beginning of the process.


In the literature, the effects of switching with average dwell time (ADT), Markovian switching, and intermittent coupling on stability and synchronization of dynamic systems have been extensively investigated. However, all of them are considered separately because it seems that the three kinds of switching are different from each other. This article proposes a new concept to unify these switchings and considers global exponential synchronization almost surely (GES a.s.) in an array of neural networks (NNs) with mixed delays (including time-varying delay and unbounded distributed delay), switching topology, and stochastic perturbations. A general switching mechanism with transition probability (TP) and mode-dependent ADT (MDADT) (i.e., TP-based MDADT switching in this article) is introduced. By designing a multiple Lyapunov–Krasovskii functional and developing a set of new analytical techniques, sufficient conditions are obtained to ensure that the coupled NNs with the general switching topology achieve GES a.s., even in the case that there are both synchronizing and nonsynchronizing modes. Our results have removed the restrictive condition that the increment coefficients of the multiple Lyapunov–Krasovskii functional at switching instants are larger than one. As applications, the coupled NNs with Markovian switching topology and intermittent coupling are employed. Numerical examples are provided to demonstrate the effectiveness and the merits of the theoretical analysis.


Experimental studies of a simple unipolar electrophoretic flow have revealed that, typically, between 10% and 25% of the electrical energy supplied was usefully converted into flow work. Certain experimental uncertainties prevent firm conclusions, but two mechanisms have been proposed to explain low mass transfer efficiency; (i) space charge effects at the collector which reduces the intensity of the 'useful' electric field in the region of the bulk flow and (ii) microscopic shear dissipation arising from the disperse nature of the electrophoretic point forces. The single streamer flows were generated in n-hexane by the localised injection of charge from discs of ion-exchange resin in a parallel plate electrode system. The mass transfer data were collected using a frequency shifted, purpose built laser Doppler anemometer employing specially developed polymethylmethacrylate light-scattering seed particles. Measured velocity profiles within the flow structure provided estimates of mass transfer efficiency at applied field strengths up to 3.75*104 V m-1.