The goal of this work is to report the main dermatological alterations occurring during pregnancy and actual cosmetic protocols available and recommended for safe use. Throughout pregnancy, woman's body undergoes many transformations such as hormonal changes and weight gain. These alterations can result in undesirable skin aspects that end up affecting the future mother's life. The main complaints of pregnant women involve melasma advent, varicose veins, edema, and natural skin aging. Even if most of the time is recommended to wait for the birth to use cosmetics, there are some alternatives to prevent and to treat these alterations during pregnancy. For all these cases, there is a need to update information about safety and efficacy of new actives and technologies in cosmetic products. The purpose of this study was to conduct a literature review about the main skin alterations during pregnancy and actual recommended treatments, according to the current legislation. Keywords—Pregnancy, cosmetic, treatment, physiological changes.


This study was undertaken to investigate the effect of alcohol on the activity of jejunal disaccharidases (DS). The activity of DS in a preparation of purified brush border membrane of hamster jejunum was measured in the absence and in the presence (0.8 to 6.4% wt/vol) of ethanol. To compare the effect of alcohol on DS with its action on a brush border enzyme of a different group, we also measured the activity of alkaline phosphatase (AP) under similar conditions. Ethanol depressed the activity of sucrase, maltase, and lactase in a dose-dependent and time-dependent manner, but it stimulated the activity of AP. The ethanol-induced inhibition of DS was completely reversible. Kinetic studies indicate that ethanol depressed the Vmax and increased the Km of sucrase and lactase. The Vmax of maltase also decreased, but the Km of this hydrolase was not affected by ethanol. From the results of this study it would appear that acute exposure of the jejunal brush border to ethanol depresses the DS activity of the membrane and that (because the AP was not depressed) the ethanol-induced inhibition of DS is not the result of a general inhibition of all enzymes of the brush border.


Despite many decades of experimentation with supplier-led approaches to credit in many developing countries, limited success has been achieved in terms of improving access to credit for smallholder farmers. In the case of Mozambique, previous attempts by government to improve access to credit for farmers were not successful and the government is looking for more effective strategies. The purpose of this study is to examine experiences in other developing countries in Africa and Asia. The study is a multiple case studies selected from Zimbabwe, Thailand and Indonesia. The data collection method comprised a combination of primary collected through in-depth interviews with key informants and secondary sources. The data analysis techniques consisted of searching for themes regarding successful strategies in terms of dealing with costs and risks of lending to agriculture. Lessons from these cases were drawn to shed light on what the most effective intervention strategy for the Government of Mozambique could entail if it is to succeed to improve access to credit for smallholder farmers. The study concludes that an alternative strategy by the government to improve access to credit for smallholder farmers includes the re-establishment of a public rural bank. The study recommends that rural financial institutions should adopt a demand-driven approach, and the fundos do fomento (special development funds) need to be reformed.


We propose a novel semi-autonomous haptic teleoperation control architecture for multiple unmanned aerial vehicles (UAVs), consisting of three control layers: 1) UAV control layer, where each UAV is abstracted by, and is controlled to follow the trajectory of, its own kinematic Cartesian virtual point (VP); 2) VP control layer, which modulates each VP's motion according to the teleoperation commands and local artificial potentials (for VP-VP/VP-obstacle collision avoidance and VP-VP connectivity preservation); and 3) teleoperation layer, through which a single remote human user can command all (or some) of the VPs' velocity while haptically perceiving the state of all (or some) of the UAVs and obstacles. Master-passivity/slave-stability and some asymptotic performance measures are proved. Experimental results using four custom-built quadrotor-type UAVs are also presented to illustrate the theory.


The changing needs of society informed by rapid technological, social and ecological changes have disturbed the foundation of permanence on which much of architecture was built. Traditional Western architecture is too solid, hard, and slow—presenting difficulties for it to adequately adapt to change and uncertainty. A reconceptualization of architecture is necessary, one not focused on the certainty of solutions or forms, but one patterned by the dynamic feedback of human agency and environmental forces. For architecture to adapt, and to adapt to unpredictable circumstances, requires that architecture accept uncertainty in its formulation and materialization. Embracing systems-based thinking, a conceptual model based on the complex systems of granular matter provides a unique approach to architecture's material and immaterial structures. Architecture will then be critically poised at the edge of chaos, ready to reorganize and evolve towards a new fluid paradigm.


It is well known that the variability and complexity of projection proportionality factors of Dual Projective Synchronization (DPS) can effectively enhance signal confidentiality. However, in most literatures, the proportionality factors are some simple fixed constants, which can't ensure high security of information. For two pairs of fractional-order hyperchaotic systems (FOHS), how to expand the projection proportionality factors to increase its complexity? Then, our work will propose a new synchronization type, i.e., Dual Function Matrix Projective Synchronization (DFMPS) and realize the DFMPS for FOHS for the first time. Firstly, based on the traditional DPS, we generalize the proportionality factors to a general function matrix depending on time t, present the error functions and define the DFMPS. Then, for FOHS, the active controller and synchronization condition are designed and proved. At the same time, when the system is affected by parameter disturbance, the proposed active controller can eliminate the influence of parameter disturbance to the system's DFMPS, which indicates that the proposed control strategy has strong robustness. Finally, the DFMPS of two pairs of fractional-order hyperchaotic Chen and Rabinovich systems are realized, and synchronizing analysis and system robustness analysis are verified by numerical simulation. Particularly, the DFMPS can be degenerated to dual anti-synchronization, dual complete synchronization, DPS, modified DPS and dual matrix projective synchronization. This work extends the synchronization types for FOHS and offers a useful method to explore DFMPS for other fractional-order systems.


The authors report data from a longitudinal study of the reading development of children who were assessed in the years of their 8th, 11th, 14th, and 16th birthdays. They examine the evidence for Matthew effects in reading and vocabulary between ages 8 and 11 in groups of children identified with good and poor reading comprehension at 8 years. They also investigate evidence for Matthew effects in reading and vocabulary between 8 and 16 years, in the larger sample. The poor comprehenders showed reduced growth in vocabulary compared to the good comprehenders, but not in word reading or reading comprehension ability. They also obtained lower scores on measures of out-of-school literacy. Analyses of the whole sample revealed that initial levels of reading experience and reading comprehension predicted vocabulary at ages 11, 14, and 16 after controlling for general ability and vocabulary skills when aged 8. The authors discuss these findings in relation to the influence of reading on vocabulary development.


In Pomak (Greece), we attest to the loss of a morphologically overt expression of mediate information, passing through a stage of variation (determined by syntactic, semantic, and discursive criteria). This change takes place in a trilingual setting where the main contact language (Greek) has no grammaticalized form to express mediate information, while the second contact language (Turkish), has a verbal past paradigm specialized for evidentiality. This phenomenon is analyzed within a multiple causation approach in which language contact acts as a catalyst.


The general purpose of the present study was to examine the
current status of full-time school counselors in the country. More
specifically, this investigation attempted to study the relationships
between school counselors' perceptions of supervision needs, job
performance and job involvement. In the testing of the conceptual
framework of perceptions of supervision needs, demographic variables
were included. In addition, the study also sought to examine school
counselors' preferences of supervisory emphasis and its relation to
experience.
A total of 268 of the randomly selected subjects responded, yielding a 67% response rate. A correlational design was used and the
theoretical framework of the study was based on the developmental
models of supervision. The perceptions of supervision needs was
measured by the Perceptions of Supervision Needs Scale developed by
the researcher; whereas job performance and job involvement were
measured by the Counselor Rating Form-Short and the Job involvement
Scale respectively. The three instruments showed reliability coefficients
of .89, .88 and .91 respectively. For school counselors' preferences of
supervisory emphasis areas, they were measured by the Supervisor
Emphasis Rating Form-Revised which showed the reliability coefficients
of the four scales ranging from .94 to .96.


In the last three decades of rapid economic growth since the reform and opening-up, the traditional manufacturing mode of "high investment, high consumption, high pollution" along with unilateral pursuit of fast-growth of GDP makes resources and environmental problems emerged. Via high-tech, remanufacturing industry which is based on circular economy revitalizes waste products, dramatically improves the efficiency of resources utilization and reduces pollution in the manufacturing process, leading the transformation of economic development pattern. It is a kind of promising strategical industry in the sustainable development of regional economy. With the guidance of industrial cluster theory, it will create a new growth pole for regional economic development through vigorously developing remanufacturing industry, forming industrial clusters and remanufacturing industrial zones with regional and industrial characteristics and perfecting relevant laws and regulations and strengthening the industrial chain.


Mycobacterium tuberculosis (Mtb) is the leading infectious disease killer worldwide. We discovered that intracellular Mtb fails to grow in macrophages in which fatty acid β-oxidation (FAO) is blocked. Macrophages treated with FAO inhibitors rapidly generate a burst of mitochondria-derived reactive oxygen species, which promotes NADPH oxidase recruitment and autophagy to limit the growth of Mtb. Furthermore, we demonstrate the ability of trimetazidine to reduce pathogen burden in mice infected with Mtb. These studies will add to the knowledge of how host metabolism modulates Mtb infection outcomes. ABSTRACT Macrophage activation involves metabolic reprogramming to support antimicrobial cellular functions. How these metabolic shifts influence the outcome of infection by intracellular pathogens remains incompletely understood. Mycobacterium tuberculosis (Mtb) modulates host metabolic pathways and utilizes host nutrients, including cholesterol and fatty acids, to survive within macrophages. We found that intracellular growth of Mtb depends on host fatty acid catabolism: when host fatty acid β-oxidation (FAO) was blocked chemically with trimetazidine, a compound in clinical use, or genetically by deletion of the mitochondrial fatty acid transporter carnitine palmitoyltransferase 2 (CPT2), Mtb failed to grow in macrophages, and its growth was attenuated in mice. Mechanistic studies support a model in which inhibition of FAO generates mitochondrial reactive oxygen species, which enhance macrophage NADPH oxidase and xenophagy activity to better control Mtb infection. Thus, FAO inhibition promotes key antimicrobial functions of macrophages and overcomes immune evasion mechanisms of Mtb. IMPORTANCE Mycobacterium tuberculosis (Mtb) is the leading infectious disease killer worldwide. We discovered that intracellular Mtb fails to grow in macrophages in which fatty acid β-oxidation (FAO) is blocked. Macrophages treated with FAO inhibitors rapidly generate a burst of mitochondria-derived reactive oxygen species, which promotes NADPH oxidase recruitment and autophagy to limit the growth of Mtb. Furthermore, we demonstrate the ability of trimetazidine to reduce pathogen burden in mice infected with Mtb. These studies will add to the knowledge of how host metabolism modulates Mtb infection outcomes.


In the 21st century, the demands of digital presence and the distractions of the internet simultaneously challenge writers wishing to represent contemporary life and threaten the attention readers are willing to give to literature. In this paper I argue that the short story cycle is a literary form that is capable of representing digital life and does so in a way that extends and expands the way that we read. I take Elizabeth Tan's 2017 book Rubik as my case study and my analysis focuses on the way Tan uses two key features of the short story cycle form to represent and simulate life in the digital age. I begin with a discussion of how Tan uses the multiplicity of the cycle form to demonstrate the polymediation of life in the developed world and that the use of discrete, separate stories in the cycle allows for switches in voice and style which not only simulates the polyphony of digital life but also encourages us to contrast the different ways individuals use mobile technology to manage their lives. Following this, I demonstrate how Tan uses the connectedness of the cycle form to create hyperreal nested narratives in Rubik, highlighting the blurring of the boundaries between online and offline, between reality and simulation, and in doing so encourages active participation from the reader.


For nearly a decade, Brazil has surpassed Thailand as the world's premier sex tourism destination. As the first full-length ethnography of sex tourism in Brazil, this pioneering study treats sex tourism as a complex and multidimensional phenomenon that involves a range of activities and erotic connections, from sex work to romantic transnational relationships. Erica Lorraine Williams explores sex tourism in the Brazilian state of Bahia from the perspectives of foreign tourists, tourism industry workers, sex workers who engage in liaisons with foreigners, and Afro-Brazilian men and women who contend with foreigners' stereotypical assumptions about their licentiousness. She shows how the Bahian state strategically exploits the touristic desire for exotic culture by appropriating an eroticized blackness and commodifying the Afro-Brazilian culture in order to sell Bahia to foreign travelers.


Einstein's famous equation, , revolutionized the theory of physics and introduced new perspectives to the study of energy and mass. However, a close consideration of its principles raises essential concerns on the equitability of mass and energy as well as other phenomena like the speed of light. The unavoidable scientific claim of this paper is that the total energy of matter depends on its internal and external energies, which are accounted for by kinetic and potential energies. In the current work, thought experiments reveal important additions to this idea regarding the apparent effects of external energy on the nature of matter and particles. This paper employs detailed thought experiments and theoretical discussions to identify and address several notable inconsistencies related to the energy and mass equation based on previous works in physics. The relative external energy of an object will be influenced by the position of the observer. The outcomes of the experiments presented herein also provide key insights into the constancy of the internal energy of all matter and particles. Generally, this paper provides an important basis for analyzing the theory underlying the physics of energy and mass, addressing questionable ideas that are common but poorly substantiated and providing a new understanding of the nature of mass and energy that lays the foundations for further research in this area by projecting the difference between them.


The extraction of the succinate dianion from a neutral aqueous solution into dichloromethane is obtained using a lipophilic cage-like dicopper(II) complex as the extractant. The quantitative extraction exploits the high affinity of the succinate anion for the cavity of the azacryptate. The anion is effectively transferred from the aqueous phase, buffered at pH 7 with HEPES, into dichloromethane. A 1:1 extractant:anion adduct is obtained. Extraction can be easily monitored by following changes in the UV-visible spectrum of the dicopper complex in dichloromethane, and by measuring the residual concentration of succinate in the aqueous phase by HPLC−UV. Considering i) the relevance of polycarboxylates in biochemistry, as e.g. normal intermediates of the TCA cycle, ii) the relevance of dicarboxylates in the environmental field, as e.g. waste products of industrial processes, and iii) the recently discovered role of succinate and other dicarboxylates in pathophysiological processes including cancer, our results open new perspectives for research in all contexts where selective recognition, trapping and extraction of polycarboxylates is required.


: Content analysis is a research technique used to organise large amounts of textual data into standardised formats which allows arriving at suggestions/conclusions. Content analysis can be carried out quantitatively by counting the words or qualitatively by coding. The former approach refers to counting the frequency of the keywords and the later refers to identifying similar themes or concepts from the data set. This paper discusses the use of conceptual content analysis by using computerised software to analyse data gathered from semi-structured interviews. The context of the research within which content analysis is used is to identify the influence of performance measurement towards construction research activities. The paper first explains the research methodology pertaining to this study by reasoning out the selection of case study research approach coupled with semi-structured interviews. The paper then discusses how the information gathered from semi-structured interviews is fed into the computerised software to identify and generate main concepts of the study .


Although mesenchymal stromal (stem) cell (MSC) administration attenuates sepsis-induced lung injury in pre-clinical models, the mechanism(s) of action and host immune system contributions to its therapeutic effects remain elusive. We show that treatment with MSCs decreased expression of host-derived microRNA (miR)-193b-5p and increased expression of its target gene, the tight junctional protein occludin (Ocln), in lungs from septic mice. Mutating the Ocln 3′ untranslated region miR-193b-5p binding sequence impaired binding to Ocln mRNA. Inhibition of miR-193b-5p in human primary pulmonary microvascular endothelial cells prevents tumour necrosis factor (TNF)-induced decrease in Ocln gene and protein expression and loss of barrier function. MSC-conditioned media mitigated TNF-induced miR-193b-5p upregulation and Ocln downregulation in vitro. When administered in vivo, MSC-conditioned media recapitulated the effects of MSC administration on pulmonary miR-193b-5p and Ocln expression. MiR-193b-deficient mice were resistant to pulmonary inflammation and injury induced by lipopolysaccharide (LPS) instillation. Silencing of Ocln in miR-193b-deficient mice partially recovered the susceptibility to LPS-induced lung injury. In vivo inhibition of miR-193b-5p protected mice from endotoxin-induced lung injury. Finally, the clinical significance of these results was supported by the finding of increased miR-193b-5p expression levels in lung autopsy samples from acute respiratory distress syndrome patients who died with diffuse alveolar damage. The therapeutic effects of MSCs on polymicrobial sepsis-induced acute lung injury is mediated in part by regulation of recipient-derived miR-193b. This is important in human acute respiratory distress syndrome and may represent a new target for therapy. https://bit.ly/3ibZCOQ


Silicon photomultipliers (SiPMs) have remarkable advantages for use in photo-detection. Compared with PMT, SiPM shows advantages of high gain, excellent time resolution, insensitivity to magnetic fields and a lower operating voltage. SiPMs from Hamamatsu are used in the electromagnetic calorimeter (ECAL) sub-detector in the Positron Electron Balloon Spectrometer (PEBS) experiment, a balloon-borne spectrometer experiment aiming at the precise measurement of the cosmic-ray positron fraction. This paper introduces the evaluation and test results of several SiPM detector types, the dedicated front-end application specific integrated circuit (ASIC) electronics and the design of the data acquisition system (DAQ) system.


In a recent paper, [1], Sasa, Hiura, Nakagawa, and Yoshida showed that a natural extension of the minimum work principle to small systems uniquely determines the factor N ! that arrises in relations connecting statistical mechanical functions (such as the partition function) and thermodynamic functions (such as the free energy). We believe that this provides us with the clearest answer to the "puzzle" in classical statistical mechanics that goes back to Gibbs. Here we attempt at explaining the theory of Sasa, Hiura, Nakagawa, and Yoshida [1] by using a process discussed by Horowitz and Parrondo [2] in a different context. Although the content of the present note should be obvious to anybody familiar with both [1] and [2], we believe it is useful to have a commentary that presents the same theory from a slightly different perspective. The present note is written in a self-contained manner. We only assume basic knowledge of classical statistical mechanics and thermodynamics. We nevertheless invite the reader to refer to the original paper [1] for background, references, and related discussions, as well as the original thoughts.


Spawning time, total fecundity, fertilization, and hatching rates of turbot (Psetta maxima) were investigated in 10 wild female broodstock (mean wt: 3809.7 ± 1238.4 g). Spawning lasted 37 days, from April 17 to May 23. Mean total fecundity was 2329 ± 1260 x 103 eggs per female. Fertilization and hatching rates were 30.6 ± 25.4% and 17.9 ± 16.1%, respectively. A significant positive correlation was observed between body weight and total fecundity (r = 0.637, P < 0.05). The timing and frequency of hand stripping, fecundity, fertilization, and hatching rates in turbot are presented.


As Robert Veatch observes, bioethics as a field is fundamentally oriented towards being "applied to real problems of the real world." That is, although theories of ethics do play a role in the field, these theories must be "integrate[d]…with detailed knowledge of the relevant facts and customs of a particular sphere of life." One way of making this progression is to follow the two-tiered system of standard and operational test such as that used by Allen Buchanan and Dan Brock in their discussion of their balancing model of competence. In this paper I will argue in favor of a representative (although not naive) empirical operational test for the reasonable person standard. In each of the three sections that comprise the first chapter, I will identify the normative goals of a bioethical context and compare the reasonable person standard to its main competitors in light of those goals. Then, in the second half of the paper, I will defend both the reasonable person standard itself and the use of empirical data as an operational test for it. This defense will only be a partial one, however, as there are certain limits to the empirical approach. The goal of this paper is to show how empirical data can be used, albeit with some limitations, to help bring some clarity and precision to a standard that is often criticized for lacking precisely those qualities.


: Investigations of morphology and morphometry of the breathing organs (trachea, bronchi and lungs) and immunogenesis of mice subject to a combined sequential exposure to fractionated external γ-irradiation by the total dose of 350 cGy and a mix of acetone, ethanol and acetaldehyde in MPCs for piloted spacecrafts simulating the estimated levels in crewed exploration missions were conducted. Morphologic changes in the breathing organs of animals after space missions point to immunogenesis activation and appearance of a "structural trace" as a chronic inflammation with the growth of fibrous connective tissue in tracheal, bronchial and lung walls, increase in volume fractions of glands and vessels and reduction in loose fibrous connective tissue. Formation of the fibrous connective tissue was particularly noticeable in respiratory parts of the breathing organs suggesting a high risk of long-term adverse effects.


Abstract does not appear. First page follows.
 The experiments reported in this paper consist of a series of five trials in which
 it was attempted to combat artificially-produced coccidial infection in chicks by
 feeding them with sufficient lactose or dry skim milk to change the hydrogen ion concentration
 of the ceca from the normal range of 6.0-7.4 to a range of 4.4-5.6. It was thought
 that, by this means, an environment unfavorable or destructive to the tissue-invading
 stages of the parasite, viz., the sporozoites and merozoites, might be created.
 The first three trials were carried out under laboratory conditions, the chicks being
 confined in cages with grilled bottoms and fed in cups suspended on the cage doors.
 In the last two trials, the chicks were reared in brooder pens under normal field
 conditions, except that no outside runs were provided.
 After the feeding of lactose or dry skim milk was begun, the chicks were inoculated
 by introducing into their crops with a pipette a large number of sporulated ooeysts
 of Eimeria aoium. A control group of chicks that was fed neither lactose nor dry skim milk was included
 in each trial. An estimate of the number of cysts administered to each chick was obtained
 by making a direct microscopic count of the cysts in 1/100 c.c. of the inoculum. Material
 for inoculation was provided by cultures of the cecal contents of chicks affected
 with coccidiosis prepared as follows: A thin layer of cecal contents containing large
 numbers of oocysts was spread over the surface of salt solution agar plates,1 Salt solution to keep the surface of the plates moist was added as required. The
 cultures were incubated at room temperature until microscopic examination showed that
 sporulation of the ooeysts had occurred.


Aiming at questions of accurate detection of experimental installation's angle is difficulty like rotating platform, which designs the angle inspection control system adopting incremental photoelectric encoder and PLC. Using gear mechanism and magnified angle pulse of electrical fourfold frequency circuit, switching in biphasic high-speed interfaces of PLC and being displayed on panel calculated by PLC, or achieving to correct the output pulse of motor driving with setting angle value. With experiments testing, the system of inspection and control has advantages of simple construction and angle inspected accuracy of 0.0225°, which satisfying the demands of angle accurate inspection and control of experimental installation.


This chapter is based on a doctoral thesis on the development of a destination image (DI) recovery model for enhancing the performance of the tourism sector in Zimbabwe. The study was prompted by the failure of African destinations to develop DI image recovery models. A pragmatist paradigm, a convergent parallel mixed methodology research approach and a cross sectional survey were adopted. A sample of three hundred and nineteen comprising international tourists, service providers and key informants was used. A structured, semi-structured questionnaire and semi-structured interview guide were used respectively. Quantitative data was analyzed using the Statistical Package for Social Sciences (SPSS) and AMOS version 25 while qualitative data was analyzed using NVivo version 12. Tests were conducted using descriptive statistics, exploratory factor analysis, and confirmatory factor analysis. Structural Equation Modeling (SEM) was used to analyze the multiple independent variables. The major findings were that price, ancillary services and amenities significantly influenced affective image while ancillary services significantly influenced destination performance. The study recommended that the Ministry of Environment, Climate, Tourism and Hospitality Industry trains tourism stakeholders including the host community in order to achieve sustainable destination image recovery.


The transfer of matter between a circumbinary disk and a young binary system remains poorly understood, obscuring the interpretation of accretion indicators. To explore the behavior of these indicators in multiple systems, we have performed the first systematic time-domain study of young binaries in the ultraviolet. We obtained far- and near-ultraviolet HST/COS spectra of the young spectroscopic binaries DQ Tau and UZ Tau E. Here we focus on the continuum from 2800 to 3200 Å and on the C iv doublet (λλ1548.19, 1550.77 Å) as accretion diagnostics. Each system was observed over three or four consecutive binary orbits, at phases ∼0, 0.2, 0.5, and 0.7. Those observations are complemented by ground-based U-band measurements. Contrary to model predictions, we do not detect any clear correlation between accretion luminosity and phase. Further, we do not detect any correlation between C iv flux and phase. For both stars the appearance of the C iv line is similar to that of single Classical T Tauri Stars (CTTSs), despite the lack of stable long-lived circumstellar disks. However, unlike the case in single CTTSs, the narrow and broad components of the C iv lines are uncorrelated, and we argue that the narrow component is powered by processes other than accretion, such as flares in the stellar magnetospheres and/or enhanced activity in the upper atmosphere. We find that both stars contribute equally to the narrow component C iv flux in DQ Tau, but the primary dominates the narrow component C iv emission in UZ Tau E. The C iv broad component flux is correlated with other accretion indicators, suggesting an accretion origin. However, the line is blueshifted, which is inconsistent with its origin in an infall flow close to the star. It is possible that the complicated geometry of the region, as well as turbulence in the shock region, are responsible for the blueshifted line profiles.


Background We present the disease course and long-term follow-up of two patients who were phenotypically diagnosed with atypical Leber Hereditary Optic Neuropathy (LHON) 14 and 12 years ago, respectively, whereby whole exome sequencing revealed recently described recessive DNAJC30:c.152G>A 152 A>G (p.Tyr51Cys) homozygous pathogenic variant with significant spontaneous visual acuity recovery in one. Case presentation Two presented unrelated males with atypical LHON with sequential visual acuity (VA) loss were followed for many years. Both patients had negative family history. At the presentation at ages 17 (Case 1) and 18 years (Case 2), both had reduced visual acuity (Snellen): (Case 1) right eye (RE):CF 3m, left eye (LE):0.6, (Case 2) RE:0.2, LE:0.15; and color vision (Ishihara): (Case 1) 1/15 and 13/15; (Case 2) 2/15 and 3/15. Both had hyperemic optic disks (PNO) and central scotoma in their visual fields. Electrophysiology in the acute phase showed reduced and delayed visually evoked potentials (VEP) P100 in both patients, with reduced N95 amplitude in Case 2, and initially normal N95 amplitude in Case 1. Fluorescein angiography showed no early leakage with some late pooling at optic disks. Extensive clinical workout, including brain magnetic resonance imaging (MRI), aquaporin 4 (Aq4), and anti-myelin oligodendrocyte protein (anti-MOG) antibodies, was negative. Intravenous corticosteroids did not improve vision. Both experienced further deterioration several months after the onset accompanied by thinning of the peripapillary retinal nerve fiber layer (RNFL). Genetic testing for typical LHON pathogenic variants and whole mitochondrial DNA (mtDNA) sequencing was negative. 1 year after the onset, modest VA improvement began in Case 2 and continued over the next 3 years. VA improved bilaterally to 0.7, color vision 15/15, and islands of vision appeared within the visual field scotoma. VEP P100 peak time shortened, and amplitude increased, despite further RNFL thinning on optical coherent tomography (OCT). The patient's visual function remained stable during the entire 12-year follow-up period. Case 1 experienced modest VA improvement to 0.1 with some improvement in the visual field seven years after the disease onset, remaining stable during the entire 14-year follow-up period. VEP P100 wave remained undetectable. Conclusions Presented are two autosomal recessive LHON (arLHON, OMIM:619382) cases with the same DNAJC30:c.152G>A pathogenic variant and different degrees of spontaneous visual recovery despite progressive RNFL thinning during a long-term follow-up. This mutation should be screened in every atypical LHON patient.


Pre-TCR and IL-7R signals regulate β-selection of thymocytes and then must be down-regulated for further development. However, the molecular events that control down-regulation remain unknown. We and others have previously shown that β-catenin in cooperation with TCF regulates β-selection. In this paper, we demonstrate that β-catenin expression is stringently regulated by intrathymic signals, it is expressed at the highest levels in the pre-TCR signaled thymocytes, and is down-regulated in post-β-selection thymocytes. Pre-TCR-induced β-catenin regulates initial stages of pre-TCR signaling including expression of early growth response (Egr) genes but must be down-regulated to express RORγt, which is essential for maturation to the CD4+CD8+ double positive (DP) stage. Sustained expression of β-catenin results in the generation of IL-7R-, Egr-, and TGFβ-expressing pre-DP thymocytes that are blocked in development. These data are consistent with a model in which post-β-selection, pre-TCR-induced β-catenin expression must return to background levels for efficient transition to the DP stage.


Aminoglycoside phosphotransferase was isolated from the mycelium of Act. fradiae, the neomycin-producing organism, with paromomycin, neomycin and to a less extent ribostamycin being substrates of aminoglycoside-phosphotransferase. It was purified to homogenous state. The maximum activity of the enzyme preparations was observed at pH 7.7--7.8;KM for neomycin and paromomycin was about 20 micron and KM for ATP was 150 micron. Mg2+ ions were necessary for the enzyme activity. None of the divalent cations tested could replace the magnesium ions in the reaction of phosphorylation catalyzed by the enzyme. High sensitivity to the ionic strength of the buffer was characteristic of the enzyme. It lost about 80 per cent of the initial activity at a concentration of KC1 equal to 1.0 M. The molecular mass of the enzyme from the mycelium of Act. fradiae was determined by the method of gel-filtration through sefadex G-100. It was about 22,000. High stability was characteristic of the enzyme. The fingings indicate that aminoglycoside phosphotransferase from Act. fradiae differs from the described aminoglycoside-3'-phosphotransferases isolated from antibiotic resistant bacteria.


This paper presents results on the modelling, simulation and experimental tests of a cable-based parallel manipulator to be used as an aiding or guiding system for people with motion disabilities. There is a high level of motivation for people with a motion disability or the elderly to perform basic daily-living activities independently. Therefore, it is of great interest to design and implement safe and reliable motion assisting and guiding devices that are able to help end-users. In general, a robot for a medical application should be able to interact with a patient in safety conditions, i.e. it must not damage people or surroundings; it must be designed to guarantee high accuracy and low acceleration during the operation. Furthermore, it should not be too bulky and it should exert limited wrenches after close interaction with people. It can be advisable to have a portable system which can be easily brought into and assembled in a hospital or a domestic environment. Cable-based robotic structures can fulfil those requirements because of their main characteristics that make them light and intrinsically safe. In this paper, a reconfigurable four-cable-based parallel manipulator has been proposed as a motion assisting and guiding device to help people to accomplish a number of tasks, such as an aiding or guiding system to move the upper and lower limbs or the whole body. Modelling and simulation are presented in the ADAMS environment. Moreover, experimental tests are reported as based on an available laboratory prototype.


This paper analyses the effectiveness of depositor discipline in the East Asian banking system during the time surrounding the 1997 crisis period. Firstly, the paper investigates the 'wake-up call' hypothesis, to find out whether depositor responses are higher during the post-crisis period. Secondly, the paper analyses the possible non-linear relationship between price elasticity and bank quality by separately analysing depositors' reaction to the price offered by both weak and healthy banks. Thirdly, this paper analyses the weakening effect of the depositor protection scheme. Analyses were carried out on a total of 193 banks in the East Asian banking system during the period from 1995 to 2005. The findings confirm that depositors do discipline banks and provide support for the 'wake-up call' hypotheses. The analysis, which was done by subdividing the sample of banks based on their quality, shows that depositors did not discipline weaker banks by demanding higher premiums. The findings also confirm the weakening effect of the depositor protection schemes.


Recently, copper (Cu) in its metallic form has regained interest for its antimicrobial properties. Use of metallic Cu surfaces in worldwide hospital trials resulted in remarkable reductions in surface contaminations. Yet, our understanding of why microbes are killed upon contact to the metal is still limited and different modes of action have been proposed. This knowledge, however, is crucial for sustained use of such surfaces in hospitals and other hygiene-sensitive areas. Here, we report on the molecular mechanisms by which the Gram-positive Staphylococcus haemolyticus is inactivated by metallic Cu. Staphylococcus haemolyticus was killed within minutes on Cu but not on stainless steel demonstrating the antimicrobial efficacy of metallic Cu. Inductively coupled plasma mass spectroscopy (ICP-MS) analysis and in vivo staining with Coppersensor-1 indicated that cells accumulated large amounts of Cu ions from metallic Cu surfaces contributing to lethal damage. Mutation rates of Cu- or steel-exposed cells were similarly low. Instead, live/dead staining indicated cell membrane damage in Cu- but not steel-exposed cells. These findings support a model of the cellular targets of metallic Cu toxicity in bacteria, which suggests that metallic Cu is not genotoxic and does not kill via DNA damage. In contrast, membranes constitute the likely Achilles' heel of Cu surface-exposed cells.


In this work, surface modification of silk fibroin was conducted by grafting dimethylaminoethyl methacrylate (DMAEMA) via ATRP to produce well controlled grafting silk. First, the amino groups and hydroxyl groups on the side chains of the silk fibroin reacted with 2-bromoisobutyryl bromide (BriB-Br) to obtain efficient initiator for ATRP. Subsequently, the functional silk fibroin was used as macroinitiator of DMAEMA in 1,2-dichlorobenzene in conjunction with CuBr/N,N,N',N",N" -pentamethyldiethylenetriamine (PMDETA) as a catalyst system. FT-IR characterization of the modified silk substrate showed a peak corresponding to DMAEMA indicating that the polymer had been formed on the silk surface. Following the polymerization, the tertiary amino groups on the grafted silk fibroin were quaternized to produce a large concentration of quaternary ammonium groups, which endowed the silk substrate with potential antibacterial surface. The graft chains were cleaved by acid hydrolysis and analyzed by gel permeation chromatography (GPC). The GPC results indicated that the graft layer were well-controlled.


Hitherto, the historiography of Jamaican slavery has ignored the period of Apprenticeship which lasted from 1834 until 1838 when Jamaica changed from a forced labour to a free labour economy. The purpose of this article is to show that the period deserves studying as it was 'slavery by another name'. It does this by examining the experiences of apprenticed women in the island's workhouses. The disciplinary regime that the women faced was similar to that exercised on the estates prior to 1834 and was enforced by a similar set of officers. It is shown that the disciplinary regime served above all the needs of the local planters. It not only safeguarded their economic enterprises but also enabled them to regain some of the arbitrary and proprietary power they had lost after 1834. The planters therefore fiercely combated attempts by the colonial governor and the Colonial Office to change the disciplinary regime. They only lost their fight in March 1838 when the British parliament issued an Act in Aid which allowed the colonial governor to legislate against abuses in the workhouses. It is argued that the planters were able to stay in control of the workhouse for such a long time because the Apprenticeship System depended upon existing administrative, judicial and legal systems.


Maximising the durability of crop disease resistance genes in the face of pathogen evolution is a major challenge in modern agricultural epidemiology. Spatial diversification in the deployment of resistance genes, where susceptible and resistant fields are more closely intermixed, is predicted to drive lower epidemic intensities over evolutionary timescales. This is due to an increase in the strength of dilution effects, caused by pathogen inoculum challenging host tissue to which it is not well-specialised. The factors that interact with and determine the magnitude of this spatial effect are not currently well understood however, leading to uncertainty over the pathosystems where such a strategy is most likely to be cost-effective. We model the effect on landscape scale disease dynamics of spatial heterogeneity in the arrangement of fields planted with either susceptible or resistant cultivars, and the way in which this effect depends on the parameters governing the pathosystem of interest. Our multi-season semi-discrete epidemiological model tracks spatial spread of wild-type and resistance breaking pathogen strains, and incorporates a localised reservoir of inoculum, as well as the effects of within and between field transmission. The pathogen dispersal characteristics, any fitness cost(s) of the resistance breaking trait, the efficacy of host resistance, and the length of the timeframe of interest, all influence the strength of the spatial diversification effect. These interactions, which are often complex and non-linear in nature, produce substantial variation in the predicted yield gain from the use of a spatial diversification strategy. This in turn allows us to make general predictions of the types of system for which spatial diversification is most likely to be cost-effective, paving the way for potential economic modelling and pathosystem specific evaluation. These results highlight the importance of studying the effect of genetics on landscape scale spatial dynamics within host-pathogen disease systems.


A 42-year-old man was referred to our department for the evaluation of multiple polypoid masses with ulcers and hyperemia in the terminal ileum (TI), which was incidentally detected on screening colonoscopy (Fig. 1A, B). The patient had no relevant medical, surgical, or family history. He had no abdominal symptoms, such as nausea, vomiting, diarrhea, or abdominal pain. Physical examination results were unremarkable. Initial laboratory test results, including routine blood tests, liver function tests, carcinoembryonic antigens, and inflammatory markers, were within normal ranges. Both tuberculosis-stimulating specific antigen (interferon-γ) and tuberculin skin tests were negative. Stool studies were negative for ova, parasites, Gram staining, and culture. Examination of the ileocolonoscopic biopsy specimen revealed noncaseating granulomatous inflammation. Contrast-enhanced abdominal computed tomography revealed a polypoid mass in the TI with marked enhancement (Fig. 1C). Regional lymph node enlargement was also observed (Fig. 1D). Positron emission tomography revealed increased fluorodeoxyglucose uptake in the TI and regional lymph nodes (Fig. 1E). Increased fluorodeoxyglucose uptake was also observed in the right upper lobe and mediastinal lymph nodes (Fig. 1F). Based on this information, what is the most likely diagnosis?


The aim of this study is to analyse the influence of differently fabricated HA-scaffolds on bone marrow stromal cells. Therefore, three methods were used (a polyurethane (PU)-replica technique, the dispense-plotting and a negative mould technique) to produce porous hydroxyapatite (HA) ceramics. The different HA-scaffolds were then cultivated with an osteoblastic precursor cell line. In our study, highest cell proliferation and differentiation was achieved by using (PU)-replica technique. However, this study shows also that all three types of scaffolds are suitable for tissue engineering applications and as bone substitute material. The knowledge about the influence of pore size and geometry on the cell behaviour will help to tailor scaffolds, by different 3D fabrication methods, for the needs of tissue engineering laboratories or patients.


We observed 82 healthy subjects, from both sexes, aged between 19 and 77 years. All subjects
performed two different tests: for being scientifically acknowledged, the first one was used as a
reference and it was a stress test (CPX). During the entire test, heart rate and gas exchange were
recorded continuously; the second, the actual object of this study, was a submaximal test (TOP).
Only heart rate was recorded continuously.
The main purpose was to determinate an index of physical fitness as result of TOP.
CPX test allowed us to individuate anaerobic threshold. We used an incremental protocol of 10/20
Watt/min, different by age.
For our TOP test we used an RHC400 UPRIGHT BIKE, by Air Machine. Each subject was
monitored for heart frequency. After 2 minutes of resting period there was a first step: 3 minutes of
pedalling at a constant rate of 60 RPM, (40 watts for elder subjects and 60 watts for the younger
ones). Then, the subject was allowed to rest for a recovery phase of 5 minutes. Third and last step
consisted of 3 minutes of pedalling again at 60 RPM but now set to 60 watts for elder subjects and
80 watts for the young subjects. Finally another five minutes of recovery.
A good correlation was found between TOP and CPX results especially between punctua l heart rate
reserve (HRR') and anaerobic threshold parameters such as Watt, VO2, VCO2 .
HRR' was obtained by subtracting maximal heart rate during TOP from maximal theoretic heart
rate (206,9-(0,67*age)).
Data were analyzed through cluster analysis in order to obtain 3 homogeneous groups. The first
group contains the least fit subjects (inactive, women, elderly). The other groups contain the
"average fit" and the fittest subjects (active, men, younger).
Concordance between test resulted in 83,23%.
Afterwards, a linear combinations of the most relevant variables gave us a formula to classify
people in the correct group.
The most relevant result is that this submaximal test is able to discriminate subjects with different
physical condition and to provide information (index) about physical fitness through HRR'.
Compared to a traditional incremental stress test, the very low load of TOP, short duration and
extended resting period, make this new method suitable to very different people.
To better define the TOP index, it is necessary to enlarge our subject sample especially by
diversifying the age range.


Environmental variation is a potent force affecting phenotypic expression. While freshwater fishes have provided a compelling example of the link between the environment and phenotypic diversity, few studies have been conducted with arid-zone fishes, particularly those that occur in geographically isolated regions where species typically inhabit intermittent and ephemeral creeks. We investigated morphological variation of a freshwater fish (the western rainbowfish, Melanotaenia australis) inhabiting creeks in the Pilbara region of northwest Australia to determine whether body shape variation correlated with local environmental characteristics, including water velocity, habitat complexity, predator presence, and food availability. We expected that the geographic isolation of creeks within this arid region would result in habitat-specific morphological specializations. We used landmark-based geometric morphometrics to quantify the level of morphological variability in fish captured from 14 locations within three distinct subcatchments of a major river system. Western rainbowfish exhibited a range of morphologies, with variation in body depth accounting for a significant proportion (>42%) of the total variance in shape. Sexual dimorphism was also apparent, with males displaying deeper bodies than females. While the measured local habitat characteristics explained little of the observed morphological variation, fish displayed significant morphological differentiation at the level of the subcatchment. Local adaptation may partly explain the geographic patterns of body shape variation, but fine-scale genetic studies are required to disentangle the effects of genetic differentiation from environmentally determined phenotypic plasticity in body shape. Developing a better understanding of environment–phenotype relationships in species from arid regions will provide important insights into ecological and evolutionary processes in these unique and understudied habitats.


The number of reported cases of syphilis, including primary, secondary and congenital syphilis, has been rapidly rising since 1987. The greatest increases have occurred in urban areas. An association between human immunodeficiency virus infection and syphilis has been established. Primary syphilis is manifested by a clean, painless ulcer called a chancre. Secondary disease often presents with constitutional symptoms and a maculopapular rash. Most infants with congenital syphilis are born without signs of infection. Serologic testing for both nontreponemal and treponemal antibodies is essential for diagnosis. Penicillin is the treatment of choice for all stages of syphilis. Case reporting and treatment of sexual contacts are two aspects of this disease that warrant greater attention from physicians.


This article reports the findings of a study conducted to evaluate a blog used in a dental terminology course. The blog was established using free online software to provide more learning exercises for students and to collect feedback about course proceedings. The instructor posted exercises such as multiple choice and true/false questions and invited students to publish answers. Students were also encouraged to post comments about difficult parts of the course that needed clarification. Students contributed 149 comments, mostly as answers in response to thirteen posts of exercises over three months. All users of the blog who responded to a questionnaire considered it useful, and most of them expressed the opinion that blogs should be used in other courses. The main reason that students reported for not using the blog was lack of time. Statistically significant differences in examination performance existed between students who used the blog and those who did not. Based on these findings, the blog achieved its purposes, which were to enhance instructor communication with students and provide students with practice exercises to improve their understanding of dental terminology. Further research about the application of blogging and its potential to enhance dental education is needed.


Background
Non-small-cell lung cancer (nsclc) is the most common cause of cancer deaths worldwide, with a 5-year survival of 17%. The low survival rate observed in patients with nsclc is primarily attributable to advanced stage of disease at diagnosis, with more than 50% of cases being stage iv at presentation. For patients with advanced disease, palliative systemic therapy can improve overall survival (os); however, a recent review at our institution of more than 500 consecutive cases of advanced nsclc demonstrated that only 55% of the patients received palliative systemic therapy. What is unknown to date is whether that observed low rate of systemic therapy in our previous study is uniform across oncologists.

Methods
With ethics approval, we performed a retrospective analysis of newly diagnosed patients with stage iv nsclc seen as outpatients at our institution between 2009 and 2012 by 4 different oncologists. Demographics, treatment, and survival data were collected and compared for the 4 oncologists.

Results
The 4 oncologists saw 528 patients overall, with D seeing 115; L, 158; R, 137; and M, 118. Significant variation was observed in the proportion receiving 1 line or more of chemotherapy: D, 60%; L, 65%; R, 43%; and M, 52%. Physician assignment was not associated with a difference in median os, with D's cohort having a median os of 6.8 months; L, 8.4 months; R, 7.0 months; and M, 7.0 months.

Conclusions
Practice size and proportion of patients treated varied between oncologists, but those differences did not translate into significantly different survival outcomes for patients.


A single-chip Bluetooth v2.1-compliant CMOS radio SoC that supports Enhanced Data Rates is implemented in standard 0.13 mum CMOS technology. All functions of a Bluetooth radio are integrated in the SoC, including RF, analog and digital parts. The RF transceiver features a polar transmitter, a two-point modulated fractional-N synthesizer, a 500 kHz IF receiver with first order low-pass analog filtering, and a DeltaSigma ADC with 74 dB dynamic range. The total SoC die area is 9.2 mm2 with only 3.0 mm2 for analog and RF circuits. The basic-rate radio power consumption is below 30 mA for both receive and transmit.


Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants in aqueous environments. They affect cardiovascular development and function in fishes. The 3‐ring PAH phenanthrene has recently been shown to impair cardiac excitation–contraction coupling by inhibiting Ca and K currents in marine warm‐water scombrid fishes. To see if similar events take place in a boreal freshwater fish, we studied whether the PAHs phenanthrene and retene (an alkylated phenanthrene) modify the action potential (AP) via effects on Na (INa), Ca 2+ (ICaL), or K + (IKr, IK1) currents in the ventricular myocytes of the rainbow trout (Oncorhynchus mykiss) heart. Electrophysiological characteristics of myocytes were measured using whole‐cell patch clamp. Micromolar concentrations of phenanthrene and retene modified the shape of the ventricular AP, and retene profoundly shortened the AP at low micromolar concentrations. Both PAHs increased INa and reduced ICaL and IKr, but retene was more potent. Neither of the PAHs had an effect on IK1. Our results show that phenanthrene and retene affect cardiac function in rainbow trout by a mechanism that involves multiple cardiac ion channels, and the final outcome of these changes (shortening of AP) is opposite to that observed in scombrid fishes (prolongation of AP). The results also show that retene and aryl hydrocarbon receptor (AhR) agonist have an additional mechanism of toxicity besides the previously known AhR‐mediated, transcription‐dependent one. Environ Toxicol Chem 2019;38:2145–2153. © 2019 SETAC


Near-shore deposits of Upper Jurassic age occur along the margin of the former Coahuila Peninsula of northern Mexico and along the site of the Sierra Madre Oriental in eastern Mexico. These deposits contain a mixed bivalve and ammonite fauna whose description will furnish a means of correlation between various facies in the Mexican Geosyncline. Studies of the ammonites, undertaken in the present paper, confirm the validity of most of Burckhardt's stratigraphic divisions for the off-shore deposits and show that they can be traced into the near-shore deposits. New information concerning the stratigraphic ranges of certain ammonite genera and the discovery of the presence of other genera have made necessary slight changes in Burckhardt's subdivisions and have shown that the succession of ammonite assemblages in the Upper Jurassic of Mexico agrees fairly well with that of the Mediterranean province.


ABSTRACT This article explores the practice of self-translation by two bilingual Russian-American poets, Andrey Gritsman and Katia Kapovich. A close reading of some of their self-translated texts elucidates the idiosyncratic nature of self-translation and its poetics of displacement. For both Gritsman and Kapovich, translating their own work becomes a means of exploring the mutation of the self through time, migration, and changing linguistic and cultural environments. A significant difference between the two authors concerns the way in which they present their poems. Gritsman invites a comparison between source and target text and the gaps between them in a bilingual en face edition, whereas Kapovich camouflages her self-translated poems as English originals. In spite of the different staging and performance of self-translation, both poets – by stressing difference rather than similarity in translation – turn their self-translated texts into a metacommentary on their own shifting transnational identities.


We assess the role played by fiscal policy in explaining the dynamics of asset markets. Using a panel of ten industrialized countries, we show that a positive fiscal shock has a negative impact in both stock and housing prices. However, while stock prices immediately adjust to the shock and the effect of fiscal policy is temporary, housing prices gradually and persistently fall. Consequently, the attempts of fiscal policy to mitigate stock price developments (e.g. via taxes on capital gains) may severely de-stabilize housing markets. The empirical findings also point to significant fiscal multiplier effects in the context of severe housing busts, which gives rise to the importance of the implementation of fiscal stimulus packages. In addition, our results suggest that when governments run a budget deficit, they place an upward pressure on real interest rates, which "crowds-out" private consumption and investment. In contrast, during bust periods, unexpected variation in the fiscal stance crowds-in private spending, which reflects the "direct" and "indirect" effects of policy actions impact arising from a downward movement in real interest rates and an upward revision in price level expectations.


To control Euler-Lagrange (EL) systems, we propose an adaptive control which is itself EL. Through a novel interconnection of these two passive systems, the closed-loop kinetic energy is modified by the potential energy of the EL controller, while a switched update law is used to update the dynamic model. It is proved that the control guarantees convergence to zero tracking error, while simulations show that it achieves faster convergence and better transient performance than an established adaptive control.


Background. Poor insight and impairment in Theory of Mind (ToM) reasoning are common in schizophrenia, predicting poorer clinical and functional outcomes. The present study aimed to explore the relationship between these phenomena. Methods. 61 individuals with a DSM-IV diagnosis of schizophrenia during a stable phase were included. ToM was assessed using a picture sequencing task developed by Langdon and Coltheart (1999), and insight with the Scale to Assess Unawareness of Mental Disorder (SUMD; Amador et al., 1993). Multivariate linear regression analysis was carried out to estimate the predictive value of insight on ToM, taking into account several possible confounders and interaction variables. Results. No direct significant associations were found between any of the insight dimensions and ToM using bivariate analysis. However, a significant linear regression model which explained 48% of the variance in ToM was revealed in the multivariate analysis. This included the 5 insight dimensions and 3 interaction variables. Misattribution of symptoms—in aware patients with age at onset >20 years—and unawareness of need for medication—in patients with GAF >60—were significantly predictive of better ToM. Conclusion. Insight and ToM are two complex and distinct phenomena in schizophrenia. Relationships between them are mediated by psychosocial, clinical, and neurocognitive variables. Intact ToM may be a prerequisite for aware patients to attribute their symptoms to causes other than mental illness, which could in turn be associated with denial of need for medication.


Cocktail parties pose a difficult yet solvable problem for the auditory system. Previous work has shown that the cocktail-party problem is considerably easier when all sounds in the target stream are spoken by the same talker (the voice-continuity benefit). The present study investigated the contributions of two of the most salient voice features — glottal-pulse rate (GPR) and vocal-tract length (VTL) — to the voice-continuity benefit. Twenty young, normal-hearing listeners participated in two experiments. On each trial, listeners heard concurrent sequences of spoken digits from three different spatial locations and reported the digits coming from a target location. Critically, across conditions, GPR and VTL either remained constant or varied across target digits. Additionally, across experiments, the target location either remained constant (Experiment 1) or varied (Experiment 2) within a trial. In Experiment 1, listeners benefited from continuity in either voice feature, but VTL continuity was more helpful than GPR continuity. In Experiment 2, spatial discontinuity greatly hindered listeners' abilities to exploit continuity in GPR and VTL. The present results suggest that selective attention benefits from continuity in target voice features, and that VTL and GPR play different roles for perceptual grouping and stream segregation in the cocktail party.


Zoledronic acid (ZOL), a nitrogen-containing compound, is effective in the treatment of skeletal disorders, but its long-term use in high doses gives rise to complications such as osteonecrosis. We aimed to investigate the effect of low-dose ZOL on the expression of the neural cell adhesion molecule (NCAM), which may be correlated with tumor growth and spinal cord metastasis in lung adenocarcinoma with neuroendocrine differentiation. First, we used the small hairpin RNA technique to directly knock down NCAM expression in cells of a murine lung adenocarcinoma line, line 1 cells, and found that the tumor cells generated showed lower invasive capacity, slower tumor growth, and lesser tendency for spinal cord metastasis than control cells. Further, ZOL decreased NCAM expression and invasiveness in line 1 tumor cells in vitro. Line 1/lacZ cells, a stable clone tagged with the lacZ gene, were introduced into mice, followed by ZOL treatment (1 &mgr;g/kg/weekly). Low-dose ZOL significantly reduced spinal cord metastasis probably through reduced NCAM expression in vivo. These findings indicated that NCAM is involved in tumor growth and spinal cord metastasis of lung adenocarcinoma with neuroendocrine differentiation. Treatment with low-dose ZOL can reduce NCAM expression that may contribute toward reduced spinal cord metastasis, suggesting that NCAM is an alternative therapeutic target and that the low-dose ZOL treatment protocol is a reasonable approach for its treatment.


INTRODUCTION: leishmaniosis has been regarded by the World Health Organization as one of the most important tropical diseases. It is very difficult to control such parasitosis because there are not vaccines, and therapy is generally toxic and unsatisfactory. It is of vital importance to set prompt diagnostic method along with identification of the parasite in order to select the suitable treatment and to design the most convenient control measures. Recently, the advances in molecular biology have made it possible to characterize Leishmania species by different methods. The random amplified polymorphic DNA technique is a simple method to detect the genetic polymorphic DNA. OBJECTIVE: to standardize the random amplified polymorphic DNA technique for its use in New World Leishmania species typing. METHODS: by using 5 pmol primer concentration, 75 ng of template DNA, 2 mM of magnesium chloride and 2 U of polymerase DNA Taq in 25μL reaction, two reproducible amplification patters were obtained. The optimized random amplified polymorphic DNA technique served to determine the genetic differences among ten reference strains of Leishmania, with 6 sets of randomly designed conventional primers. The UP GMA method-based grouping strategy determined the phylogenetic relation among the studied species. RESULTS: OPA primers -3, 4 and 8 allowed distinguishing the ten reference strains of Leishmania under study. Two well defined genetic groups including species of Leishmania and Viannia subgenres were obtained; these 2 subgenres showed genetic differences. CONCLUSIONS: in this way, our laboratory has the optimized random amplified polymorphic DNA for the identification of Leishmania species.


This article considers how women's life writing has offered a situated mode of resistance to dominant racial regimes in the US and South Africa. Based on a reading of diverse texts, it employs concepts such as entanglement, disentanglement, estrangement and dislocation as keys to understand the relationship between blackness and whiteness, not in abstract, theoretical terms but as a complex configuration of meanings arising from and within specific circumstances. It examines the technique of self-disclosure in life writing against racism as a means to illustrate the tentacles of power and privilege on many levels, and suggests a way of reading and interpreting self-narratives as a means to work through the psychological, material and symbolic processes entailed in the struggle for change. South African writer Antjie Krog work frames this enquiry since her life-project is both ontological, expressed as a search for a different kind of self, and epistemological, in the sense that this it explores the possibility of a different way of knowing. This task requires a deep reckoning with aspects of the past, her own as well as the catastrophic legacies of European colonial expansion and apartheid.


Genome-wide screens of genetic variation can reveal signatures of population-specific selection implicated in adaptation and speciation. Yet, unrelated processes such as linked selection arising as a consequence of genome architecture can generate comparable signatures across taxa. To investigate prevalence and phylogenetic stability of linked selection, we took a comparative approach utilizing population-level data from 444 re-sequenced genomes of three avian clades spanning 50 million years of evolution. Levels of nucleotide diversity (π),population-scaled recombination rate (ρ), genetic differentiation (FST, PBS) and sequence divergence (Dxy) were remarkably similar in syntenic genomic regions across clades. Elevated local genetic differentiation was associated with inferred centromere and sub-telomeric regions. Our results support a role of linked selection shaping genome-wide heterogeneity in genetic diversity within and between clades. The long-term conservation of diversity landscapes and stable association with genomic features make the outcome of this evolutionary process in part predictable.


Lung cancer is the main cause of mortalities among all types of cancer. Lots of efforts have been made to elucidate the pathogenesis of lung cancer, but the molecular mechanisms are still not well understood. To identify the candidate genes in the carcinogenesis and progression of lung cancer, we acquired three datasets (GSE19188, GSE33532 and GSE30219) from Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs), then function enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape. A total of 185 DEGs was identified, consisting of 32 upregulated genes and 153 down regulated genes. The enriched functions and pathways of the DEGs include angiogenesis, cell adhesion, G2/M transition of mitotic cell cycle, mitotic nuclear division, ECM-receptor interaction, PPAR signaling pathway, etc. we selected ten hub genes (UBE2C, RRM2, KIF11, CDKN3, KIAA0101, PRC1, ASPM, HMMR, TOP2A, and BIRC5) and further analyzed their biological functions. It was found that these genes play an active role in positive regulation of exit from mitosis, mitotic nuclear division, spindle organization, and cell division. Furthermore, Survival analysis showed that these 10 hub genes positively correlated with survival time of lung cancer patients. In conclusion, the discovery of the functions of DEGs and Hub genes can help us to understand the mechanism of the occurrence and development of lung cancer at the molecular level, and provide candidate targets for the diagnosis and treatment of lung cancer in the future.


Influence of polymerization of the d-amino-acid oxidase on the behaviour of the enzyme covalently immobilized on chitosan.

d-Amino-acid oxidase is a flavoprotein using FAD as cofactor. The enzyme has been immobilized in the presence of FAD on a non-porous matrix: chitosan. This support is covalently bound to the enzyme with glutaraldehyde as cross-linking reagent. It is characterized by a good mechanical resistance to mechanical stirring. The enzymatic assays have been performed in batch reactor with d-phenylglycine as substrate by a spectrophotometric method which is based on the variation of the absorbance at 252 or 280 nm.

The behaviour of the biocatalysts has been studied during repeated assays of 1 h at 25 °C in the absence of exogeneous FAD. The experimental results have been compared with those obtained with the soluble enzyme tested in the presence or in the absence of FAD. The dependence of d-amino-acid oxidase on FAD concentration has been studied. Immobilized enzyme on chitosan appears to be less sensitive to the association-dissociation equilibrium of FAD. This property and the capacity of the enzyme to polymerize spontaneously in solution according to the experimental conditions have been established. The fact that the enzyme can exist in various oligomeric forms is of major importance because its catalytic expression is dependent of this phenomenon. The polymerization is known to be responsible for a decrease of the maximal rate V of the enzyme. It has also been shown that in the same way this decrease was accompanied by an improvement of the affinity of enzyme for substrates. Furthermore, the value of the dissociation constant of the apoenzyme-FAD complex is significantly smaller as the degree of polymerization is high. The conclusion is that the dissociation of the cofactor can be avoided if the immobilization step is carried out at high concentration of enzyme which is favourable to its polymerization.


China's anti-ship ballistic missile (ASBM), the DF-21D, has reached the equivalent of Initial Operational Capability. Although it probably has been deployed in small numbers, additional challenges and tests remain. This study examines the ASBM's capability and history, showing how the DF-21D meets multiple priorities in Chinese defense modernization and in the national security bureaucracy, as well its implications for the United States. The ASBM's physical threat to U.S. Navy ships will be determined by the development of associated systems and organizations, which currently limit data fusion and coordination in the complex task of identifying a U.S. aircraft carrier in the open ocean. Still, the ASBM poses a direct threat to the foundations of U.S. power project in Asia and will undermine the U.S. position, unless efforts to counter its political-military effects are taken.


Cloud computing has received a great deal of attention during the past few years. However, processing data remotely in unknown systems creates a number of challenges related to data privacy and security, which may hinder the adoption of cloud technology in, for example, the health care domain. This paper presents results from the ongoing EU FP7 research project, which aims to provide mechanism and tools to enable organisations involved in cloud service delivery chains to act as responsible stewards for the personal data that they process. We outline a number of accountability obligations that will arise in a health care scenario and explain how the project results can be used to meet these challenges.


When pulsed photothermal radiometry (PPTR) is used for depth profiling of hypervascular lesions in human skin, melanin absorption also heats the most superficial skin layer (epidermis). Determination of lesion depth may be difficult when it lies close to the epidermal dermal junction, due to PPTR's limited spatial resolution. To overcome this problem, we have developed an approximation technique, which uses two excitation wavelengths (585 and 600 nm) to separate the vascular and epidermal components of the PPTR signal. This technique permits a noninvasive determination of lesion depth and epidermal thickness in vivo, even when the two layers are in close physical proximity to each other. Such information provides the physician with guidance in selecting the optimal parameters for laser therapy on an individual patient basis.


Electricity theft is a major concern for the utilities. Many times power theft has been major impact on the economy as well as the development of the country. At present to monitor the various parameters like power consumption, the amount of load and to prevent electricity siphoning, an intelligent device would come handy to solve the problem for the power company and the clients. Application of techniques of power monitoring allows to power monitoring systems to receive the information remotely and in relation to the coordinates and time. In this project we are using smart power meter which are fitted on both at the transmission and load side. These meters are capable of measuring power sent over the load sand power consumed by the load over the time respectively. Both the parameters are sent to the base station wirelessly. Whenever there is a mismatch above the tolerance level parameters, then power theft is detected. The system will trigger the alarm to intimate to the concern authority so that they take necessary legal action and prevent power theft in the future.


INTRODUCTION
Asthma and atopy are complex traits, the phenotypes being influenced by the interaction of both genetic and environmental factors. In view of the growing evidence for inter-ethnic differences in genetic susceptibility to complex diseases such as asthma and atopy, we have assessed genetic factors for these diseases in the local population.

METHODS
The genetic analysis of asthma and atopy is being approached by candidate gene analysis as well as linkage studies for mapping of susceptibility loci. We reviewed published studies, which include data from our population on some candidate genes, as well as our preliminary data on susceptibility locus mapping for linkage to chromosome 5q31-33.

RESULTS
In local studies of the interleukin-4 receptor and tumour necrosis factor polymorphisms, we failed to find associations with genetic variants previously implicated to be associated with asthma and atopy. Evaluation of markers on chromosome 5q31-32 identified novel loci for susceptibility to asthma and atopy in addition to loci already described by others.

CONCLUSION
Both the published literature and our own findings indicate that there are inter-ethnic differences in genetic susceptibility to asthma and atopy.


The positive impact for young people in alternative care of attachment relationships with adults is well documented. The potential role of peers in fulfilling attachment needs in this population warrants further investigation. This paper presents a systematic review of existing quantitative evidence exploring how positive peer relationships influence psychological variables related to coping and resilience in young people in alternative care The review targeted literature relating to adolescents aged 10-18 living in alternative care. A systematic search of the literature for studies of psychological resilience-based variables and peer relationships led to the inclusion of 10 papers. An assessment of the studies using methodological quality ratings was conducted. Four key themes emerged: (1) Perceived satisfaction with peer relationships; (2) The impact of peer group networks; (3) Positive attachments in adolescence and; (4) The role of social skills. The findings highlight the need to investigate more positive outcomes using standardized measures for variables of resilience and peer attachment directly in this population. It summarizes the current evidence and lays the foundation for future robust longitudinal studies exploring peer relationships and resilience variables directly. It puts forward the need for a positive developmental rhetoric, drawn directly from the strengths of this group.


Abstract Canine parvovirus type 2 (CPV‐2) emerged as dog pathogen in the late 1970s, causing severe and often fatal epizootics of gastroenteritis in the canine population worldwide. Although to date CPV‐2 is circulating in all continents, most of the current studies have analysed the amino acid changes accounted in the VP2 gene sequence, with limited information on virus introductions from other countries. The aim of this study was to analyse the genetic features of CPV‐2c strains currently spreading in Italy. Swabs and tissue samples were collected from dogs suspected of CPV infection. The nearly complete genome sequence from the CPV‐positive samples was obtained. The co‐circulation of two different but related CPV‐2c strains, with amino acid changes characteristic of CPV strains of Asian origin (NS1: 60V, 544F, 545F, 630P – NS2: 60V, 151N, 152V ‐ VP2: 5A/G, 267Y, 297A, 324I, 370R), were observed. The phylogenetic analyses inferred from the NS1 and VP2 gene sequences confirmed the relationship with Asian CPV‐2c strains. This study reports the spread of novel CPV‐2c mutants in Italy and supports further studies to evaluate the coexistence of genetically divergent CPV strains in the same geographical environment.


Large-scale corporate restructures are a commonly used business strategy performed to streamline structure and systems, and hence, improve efficiency and competitive advantage. Reconfiguring a workforce is not an easy task, however, especially if it involves the amalgamation of previously distinct workgroups. The personal and work-related consequences of merger-related change have been well-researched and documented, as have the support mechanisms that change managers can use to support the change. Following the proposition that sociocultural adjustment may also contribute to merger outcomes, the current study used structural equation modelling to assess the experiences of two previously distinct employee groups as they interacted during an internal merger. The two employee samples were sourced from a multi-national communications organisation (N = 295; males = 45%, females = 55%). Data was collected through questionnaires at three points in time (baseline, 6 months and 12 months). Structural equation results indicated that sociocultural adjustment was an important factor that contributed to employees' personal (i.e. psychological distress) and work-related (i.e. role ambiguity, job satisfaction, and organisational commitment) outcomes of change over. Sociocultural adjustment played a role above antecedent mechanisms used by the employee (i.e. openness to change) and the organisation (communication, social support, and employee participation). A multiple-group model showed that sociocultural adjustment affected psychological distress, but not work-related outcomes, differently for the host and acculturated groups. Specifically, sociocultural adjustment contributed to the acculturated group's psychological distress significantly more than to the host group's. Overall, the findings of the current research highlight the importance of managing the sociocultural aspects of merger-related change.


This paper explores how two organizations have changed their software development practices by implementing Open Source technology. Our aim is to understand the institutional changes needed in and emerging from this process. The paper develops a conceptualization building on the insights of entrepreneurial institutionalism and concentrating on the changing relationships of organizational groups in the areas of reward and communication. We identify the links between the 1) emerging yet embedded technology and 2) the underlying institutional reward and communication structures. In terms of contribution, we propose to move the Open Source 2.0 research agenda forward by concentrating empirical work on the nuances of institutional change that open source brings forward in large hierarchical organisations.


The Adaptive Optics (AO) Group in I Division develops and tests a broad range of advanced wavefront control technologies. Current applications focus on: Remote sensing, High power lasers, Astronomy, and Human vision. In the area of remote sensing, the AO Group leads a collaborative effort with LLNL's Nonproliferation, Arms Control & International Security (NAI) Directorate on Enhanced Surveillance Imaging. The ability to detect and identify individual people or vehicles from long-range is an important requirement for proliferation detection and homeland security. High-resolution imaging along horizontal paths through the atmosphere is limited by turbulence, which blurs and distorts the image. For ranges over {approx}one km, visible image resolution can be reduced by over an order of magnitude. We have developed an approach based on speckle imaging that can correct the turbulence-induced blurring and provide high resolution imagery. The system records a series of short exposure images which freeze the atmospheric effects. We can then estimate the image magnitude and phase using a bispectral estimation algorithm which cancels the atmospheric effects while maintaining object information at the diffraction limit of the imaging system.


ABSTRACT Lee, H.S.; Kim, I.H., and Kim, H.G., 2016. Application of terrestrial 3D laser scanning to monitor changes of beach landforms. In: Vila-Concejo, A.; Bruce, E.; Kennedy, D.M., and McCarroll, R.J. (eds.), Proceedings of the 14th International Coastal Symposium (Sydney, Australia). Journal of Coastal Research, Special Issue, No. 75, pp. 173–177. Coconut Creek (Florida), ISSN 0749-0208. Monitoring changes in the beach morphology of coastal landforms is important when considering coastal management measures. In this paper, to create a changing beach surface, point cloud data of the beach are obtained using three-dimensional (3D) terrestrial laser scanning (TLS), and a beach surface model is analysed based on 3D point data. The 3D point cloud is generated from the scanned beach, including breakwaters, and these points are registered and merged through a reference point (scan origin and ball target) surveyed by RTK-GPS. Noise elements and unnecessary points are eliminated to yield better surface modelling results. Mesh data of the scan point features are created from the integrated points and represent the beach surface of the triangulated irregular network (TIN) model. The 3D modelling of the mesh data enables the user to determine the width, length, and height of breakwater structures through outline extraction and analyse the beach profile. These dimensions of the structure are designed as a 2D plan. It is recommended that the point measurement interval must be dense to create a complete beach surface over a wide area. The approach to TLS appears to provide an efficient means of accurately measuring the beach surface.


The coming years may see the advent of distributed implantable devices to support bioelectronic medicinal treatments. Communication between implantable components and between deep implants and the outside world can be challenging. Percutaneous wired connectivity is undesirable and both radiofrequency and optical methods are limited by tissue absorption and power safety limits. As such, there is a significant potential niche for ultrasound communications in this domain. In this paper, we present the design and testing of a reliable and efficient ultrasonic communication telemetry scheme using piezoelectric transducers that operate at 320 kHz frequency. A key challenge results from the multi-propagation path effect. Therefore, we present a method, using short pulse sequences with relaxation intervals. To counter an increasing bit, and thus packet, error rate with distance, we have incorporated an error correction encoding scheme. We then demonstrate how the communication scheme can scale to a network of implantable devices. We demonstrate that we can achieve an effective, error-free, data rate of 0.6 kbps, which is sufficient for low data rate bioelectronic medicine applications. Transmission can be achieved at an energy cost of 642 nJ per bit data packet using on/off power cycling in the electronics.


This article discusses the role of refusal in the analysis and communication of qualitative data, that is, the role of refusal in the work of making claims. Refusal is not just a no, but a generative stance, situated in a critical understanding of settler colonialism and its regimes of representation. Refusals are needed to counter narratives and images arising (becoming-claims) in social science research that diminish personhood or sovereignty, or rehumiliate when circulated. Refusal, in this article, refers to a stance or an approach to analyzing data within a matrix of commitments, histories, allegiances, and resonances that inform what can be known within settler colonial research frames, and what must be kept out of reach.


The endocannabinoid system is a crucial regulator of hepatic fibrogenesis. We have previously shown that the endocannabinoid anandamide (AEA) is a lipid mediator that blocks proliferation and induces death in hepatic stellate cells (HSCs), the main fibrogenic cell type in the liver, but not in hepatocytes. However, the effects of other endocannabinoids such as N-arachidonoyl dopamine (NADA) have not yet been investigated. The NADA-synthesizing enzyme tyrosine hydroxylase was mainly expressed in sympathetic neurons in portal tracts. Its expression pattern stayed unchanged in normal or fibrotic liver. NADA dose dependently induced cell death in culture-activated primary murine or human HSCs after 2-4 h, starting from 5 μM. Despite caspase 3 cleavage, NADA-mediated cell death showed typical features of necrosis, including ATP depletion. Although the cannabinoid receptors CB1, CB2, or transient receptor potential cation channel subfamily V, member 1 were expressed in HSCs, their pharmacological or genetic blockade failed to inhibit NADA-mediated death, indicating a cannabinoid-receptor-independent mechanism. Interestingly, membrane cholesterol depletion with methyl-β-cyclodextrin inhibited AEA- but not NADA-induced death. NADA significantly induced reactive oxygen species formation in HSCs. The antioxidant glutathione (GSH) significantly decreased NADA-induced cell death. Similar to AEA, primary hepatocytes were highly resistant against NADA-induced death. Resistance to NADA in hepatocytes was due to high levels of GSH, since GSH depletion significantly increased NADA-induced death. Moreover, high expression of the AEA-degrading enzyme fatty acid amide hydrolase (FAAH) in hepatocytes also conferred resistance towards NADA-induced death, since pharmacological or genetic FAAH inhibition significantly augmented hepatocyte death. Thus the selective induction of cell death in HSCs proposes NADA as a novel antifibrogenic mediator.


This report documents the main findings of vulnerable group profiling work in Nepal. It identifies the characteristics and investigates the vulnerability for seven particular livelihood groups, notably marginal farm households in the Terai, in the hills and in the mountains, agricultural labour households in the Terai, porters in the hills and mountains, rural service castes, and poor urban workers in the informal economy in the Kathmandu Valley. Based on this analysis, it considers how these people cope during times of insufficient food production and/or earnings, and proposes actions that could be taken to reduce their vulnerability to becoming food insecure in the future. Most of the research on poverty in Nepal during the past decades has focused exclusively on determining the poverty line and calculating the proportion of people living under this line, rather than unmasking the characteristics, particularly the locational aspects, of poverty other than the rural and urban distribution (Sadeque, 1998). This report therefore contributes to new knowledge by identifying and characterising particular vulnerable groups of people in broad geographic areas based on their livelihoods. The knowledge and insights gained through this process is intended to complement existing assessments at the household/community and national level, and to help bridge the gap between local knowledge and national level decision-making. It is hoped that this study will draw attention to the need for greater policy and programme support to food security in Nepal. In this context, the findings could inform the design of a food security policy (as recommended in the UN progress report on implementation of the Millennium Development Goals in Nepal), as well as the development and strengthening of other policies and programmes that reduce vulnerability and increase food security for a larger share of the population in the country. In particular, it could be useful in supporting implementation of the Government's recently formulated Poverty Reduction Strategy Paper (PRSP) which received cabinet endorsement in May 2003.


For several decades, the countries in Central and Eastern Europe pursued an energyintensive strategy of economic development based on distorted relative prices of energy. This typical feature of central planning created the illusion of a virtually unlimited supply of energy. The illusion came to an end in the 1980s, when the widening gap between energy supply and energy demand faced by the region led to a severe energy crisis. 9 Bulgaria is one of the countries most affected by the energy crisis in Central and Eastern Europe. Poorly endowed with energy resources, Bulgaria relies largely on international trade to satisfy its demand for energy. During Bulgaria's membership in the CMEA, energy-intensive growth resulted in a strong dependency on only one energy exporter, the former Soviet Union. With the CMEA's dissolution, Bulgaria was left to design and implement a new energy policy as a part of its own efforts to transform its economy into a market economy. • In spite of the far-reaching liberalization of prices experienced by Bulgaria in 1991, economic transition has been rather slow and energy reform has been neglected. Domestic energy prices have remained under government control, and energy prices have been falling in real terms due to the high overall inflation. Domestically produced primary energy is not priced at international levels, and consumer prices for final energy do not reflect domestic production costs. Moreover, current energy pricing favours small-scale users (households) and discriminates against large-scale users (industry). The continuing high level of energy consumption and the prevailing fuel mix (oil products and lignite) have a particularly adverse effect on the environment in terms of SO2 and CO2 emissions. • In the short run, energy policy should concentrate on the liberalization of domestic energy prices. Primary energy should be priced at world market prices and final energy at marginal costs. A realistic valuation of energy products will support the structural change component of the transformation process and increase energy efficiency in Bulgaria. A policy of fuel diversification complemented by one of regional diversification of energy imports will constitute the best long-run hedge against the risk of supply disruptions. Energy utilities should be privatized, and foreign companies should be allowed to play a leading role in the modernization of the energy sector. The Bulgarian government should create optimal conditions for cooperating closely with EC member countries in the field of energy, as already delineated in the European Energy Charter and in Bulgaria's Association Treaty with the EC. As long as sophisticated emission fees can be neither implemented nor enforced, energy-related environmental pollution should be dealt with by taxing energy use at the consumer level with a simple uniform ad valorem rate applied to all fuels.


Since the end of the last dictatorship in 1983, Argentina's visual artists and art-activists have been central to campaigns to demand the criminal prosecution of those initially granted amnesty and to a variety of commemorative projects. In The Art of Post-Dictatorship: Ethics and Aesthetics in Transitional Argentina Vikki Bell examines this involvement and intervention. She argues that the problematics that arise within the aesthetic realm cannot be understood solely through an art-historical approach; instead, they must be understood as a constitutive part of a broader collective endeavour. In this sense, the 'art' of post-dictatorship is not something that belongs to art or the artists themselves, but is about how the subjectivities and imaginations of new generations are constituted and entwined with questions of response, ethics and justice. It concerns how people align themselves between the past and the future.


Expression of the paired-box 7 (PAX7) transcription factor is regulated during both myoblast proliferation and differentiation: high levels of PAX7 compromise myogenic differentiation because of excess and prolonged proliferation, whereas low levels of PAX7 result in precocious differentiation. We showed that myogenin repressed Pax7 transcription in differentiating myoblasts by binding to specific recognition sites in the Pax7 promoter, and that high-mobility group box 1 (HMGB1)–receptor for advanced glycation end-products (RAGE) signaling was required for myogenin induction and myogenin-dependent repression of Pax7 transcription. In addition, PAX7 negatively and myogenin positively regulated RAGE expression. RAGE, a multiligand receptor of the immunoglobulin superfamily, was not expressed in adult skeletal muscles, and was transiently expressed in activated, proliferating and differentiating satellite cells (SCs) in injured muscles. Compared with wild-type muscles, Rage−/− muscles exhibited increased numbers of basal SCs that were further increased in injured Rage−/− muscles following elevated myoblast asymmetric division; complete regeneration of injured Rage−/− muscles was found to be delayed by ~1 week. Thus, RAGE signaling physiologically repressed Pax7 transcription in SCs by upregulating myogenin, thereby accelerating muscle regeneration and limiting SC self-renewal.


Chatbots are reactive applications with a conversational interface. They are usually implemented as compositions of client-side components and cloud-hosted services, including artificial-intelligence technology. Unfortunately, programming such reactive multi-tier applications with traditional programming languages is cumbersome. This paper introduces wcs-ocaml, a new multi-tier chatbot generator library designed for use with the reactive language ReactiveML. The paper explains our library with small didactic examples throughout, and closes with a larger case-study of a chatbot for authoring event-processing rules.


The terminal alkyne is one of the most widely used chemical moieties in chemical biology. Thanks to the relative absence of this functional group in biology, it has become a widespread functional handle for a plethora of biorthogonal chemistries. Our group has extended the scope of this functionality by developing a biological variant of the Glaser-Hay coupling, which brings together two terminal alkynes to form a diyne linkage. However, our initial findings revealed that the chemistry is plagued by protein degradation due to a deleterious copper(II) hydroxyl intermediate. Herein we extend the scope of the terimanl alkyne be developing a biological variant of the Cadiot-Chodkiewicz coupling, which brings together a bromoalkyne and a terminal alkyne to form a diyne linkage. Unlike the Glaser-Hay, the Cadiot-Chodkiewicz is thought to be net redox neutral. We found that this chemistry is biologically compatible and does indeed reduce copper(II)-mediated cytotoxicity while increasing rates of diyne formation. Finally, we extend our findings on diyne-forming chemistries by applying this conjugation to a variety of projects, ranging from undergraduate teaching labs, bioconjugate preparation, and protein function, thereby expanding the scope of this conjugation strategy.