Background: Pituitary adenoma (PA) is one of the most common intracranial neoplasms. Tissue inhibitors of metalloproteinases (TIMPs) are prognostic biological markers, but their biological roles remains largely unclear in invasive PA.
Methods: The promoter methylation status of TIMP2 and TIMP3 genes in invasive PA tissues and cells was measured by methylation-specific polymerase chain reaction (MSP). The expression of TIMP1-3 was validated by quantitative real time PCR and western blot analysis. Overexpression and knockdown of TIMP2 and TIMP3 in GH3 cells were created by transfection of pcDNA3.0 and siRNA against TIMP2 and TIMP3, respectively. Functional experiments in GH3 cells were performed with CCK-8 assay, wound healing assay and transwell assay. Effects of 5-Azacytidene (5-AzaC) on the methylation of TIMP2 and TIMP3 gene, and DNA methyltransferase 1 (DNMT1), DNMT3a and DNMT3b were determined by western blot analysis.
Results: We found the expression of TIMP1, TIMP2 and TIMP3 was down-regulated in invasive PA tissues and cells. Moreover, decreased TIMP2 and TIMP3 expression was closely associated with their promoter methylation. The in vitro experiments showed that overexpression of TIMP2 and TIMP3 exerted suppressive effects, while knockdown of TIMP2 and TIMP3 presented enhanced effects on cell proliferation, migration and invasion in PA cells. Furthermore, 5-AzaC treatment concomitantly up-regulated the protein levels of TIMP2, TIMP3, DNMT1, DNMT3a and DNMT3b.
Conclusions: In conclusion, our results support that DNA methylation at least partly accounts for TIMP2 or TIMP3 silencing in invasive PA, which will provide new insights into the mechanisms underlying the function of TIMPs in PA.
Key words: Invasive pituitary adenoma, TIMPs, DNA methylation, 5-AzaC, GH3


This paper presents a prototype of millimeter-wave multiple-beam phased array for limited scan on geosynchronous communication satellites. Major design considerations are put on the reduction of system weight, volume and power consumption, while maintaining the electric performance. Measurement results are provided for validation of the design.


We calibrate a stochastic computer simulation model of "moderate" computational expense. The simulator is an imperfect representation of reality, and we recognize this discrepancy to ensure a reliable calibration. The calibration model combines a Gaussian process emulator of the likelihood surface with importance sampling. Changing the discrepancy specification changes only the importance weights, which lets us investigate sensitivity to different discrepancy specifications at little computational cost. We present a case study of a natural history model that has been used to characterize UK bowel cancer incidence. Datasets and computer code are provided as supplementary material.


Ankyloglossia or tongue tie refers to restricted tongue movements, diagnosed in early childhood and adolescence that may cause changes in bone growth and other orofacial tissues results in altered oral functions of the child. It also affects speech, mastication and oral hygiene as well as social environment. Patients with oligodontia and tongue tie may have psychological, aesthetic, phonetic and functional problems. A rare case of female child patient with congenital partial anodontia and associated ankyloglossia with its comprehensive step wise multidisciplinary management is presented. The patient was advised for frenectomy to relieve tongue tie and functional fixed aesthetic space maintainer at an early age and was followed-up to be treated with definitive implant prosthesis with respect to the missing teeth. Early treatment and follow-up is the key to successful rehabilitation of young patients with congenitally missing teeth and ankyloglossia. It is imperative that oral rehabilitation be started as early as possible to maintain and correct the oral functions. This clinical report describes a successful aesthetic, functional, and psychological rehabilitation of a young adolescent girl with partial anodontia in mandibular anterior region and associated extensive tongue tie with step by step surgical and prosthetic management in accordance with the physical growth pattern of patient. It also offers guidelines for comprehensive management which can be used by the treating pedodontist and oral surgeon for diagnosis and treatment of ankyloglossia and partial anodontia.


Studies of information seeking and workplace collaboration often find that social relationships are a strong factor in determining who collaborates with whom. Social networks provide one means of visualizing existing and potential interaction in organizational settings. Groupware designers are using social networks to make systems more sensitive to social situations and guide users toward effective collaborations. Yet, the implications of embedding social networks in systems have not been systematically studied. This paper details an evaluation of two different social networks used in a system to recommend individuals for possible collaboration. The system matches people looking for expertise with individuals likely to have expertise. The effectiveness of social networks for matching individuals is evaluated and compared. One finding is that social networks embedded into systems do not match individuals' perceptions of their personal social network. This finding and others raise issues for the use of social networks in groupware. Based on the evaluation results, several design considerations are discussed.


This article explores the impact of deportation, a state practice increasingly applied by European and North American governments, on notions of sociality in transnational social fields. In particular, it concentrates on the dynamics between formal citizenship on the one hand and the moral economies of belonging and membership on the other. Drawing on anthropological fieldwork in Cape Verde, where deportation is producing a new social minority, this article examines the confluence of social and formal legal practices of exercising membership in transnational fields. After summarising the constitutive features of Cape Verdean transnational social formation, the trajectories and perspectives of deportees are highlighted in relation to their family networks, as well as in their encounters with the wider society and state structures. It is argued that understandings of social inclusion and perceptions of membership are embedded in moral discourses on 'law' and 'justice' as they circulate within transnational social fields. In the context of forced return migration, citizenship emerges as an arena for claiming legitimacy and integration and likewise becomes a key mode of the formulation of conditionalities for integration and social exclusion.


A new approach to the dating of uranium minerals using the spontaneous fission of uranium is proposed. The method involves thermal neutron irradiation of samples followed by mass spectrometric analysis of the xenon fractions released from them during stepwise heating. The potential advantages of the technique are the following: no separate explicit measurement of uranium is required, the error in age measurement due to inhomogeneous uranium distribution in samples is eliminated, and any diffusive loss of spontaneous fission xenon from less retentive sites is allowed for.


A 74 year old man developed progressive dyspnea under treatment with the tetracyclic antidepressant maprotiline for three months. A chest x-ray revealed extended pulmonary infiltrates. Marked eosinophilia of the periperal blood was found (up to 2300/microliter). Rapid clinical and radiological improvement was observed solely by withholding the drug. The eosinophil count retourned to normal within a few weeks. The possible pathogenesis is discussed and the literature reviewed.


Efforts to elucidate the nature of the bimolecular interaction of parathyroid hormone (PTH) with its cognate receptor, the PTH receptor type 1 (PTHR1), have relied heavily on benzoylphenylalanine- (Bpa-) based photoaffinity cross-linking. However, given the flexibility, size, and shape of Bpa, the resolution at the PTH-PTHR1 interface appears to be reaching the limit of this technique. Here we employ a disulfide-trapping approach developed by others primarily for use in screening compound libraries to identify novel ligands. In this method, cysteine substitutions are introduced into a specific site within the ligand and a region in the receptor predicted to interact with each other. Upon ligand binding, if these cysteines are in close proximity, they form a disulfide bond. Since the geometry governing disulfide bond formation is more constrained than Bpa cross-linking, this novel approach can be employed to generate a more refined molecular model of the PTH-PTHR1 complex. Using a PTH analogue containing a cysteine at position 1, we probed 24 sites and identified 4 in PTHR1 to which cross-linking occurred. Importantly, previous photoaffinity cross-linking studies using a PTH analogue with Bpa at position 1 only identified a single interaction site. The new sites identified by the disulfide-trapping procedure were used as constraints in molecular dynamics simulations to generate an updated model of the PTH-PTHR1 complex. Mapping by disulfide trapping extends and complements photoaffinity cross-linking. It is applicable to other peptide-receptor interfaces and should yield insights about yet unknown sites of ligand-receptor interactions, allowing for generation of more refined models.


Research infrastructures are large facilities primarily aimed at basic or fundamental research, built and made available to a wider community of researchers, and characterized by an Open Access policy based on the free competition among proposals/experiments that are ranked only by looking at their scientific content at an international level. These facilities have the extraordinary capability not only to stimulate and support the research of the host country, for which they have been funded and built, but may attract dozens of researchers from abroad, generating wealth in the territory where they are located. What is the situation in China, what research infrastructures are operating and how many of those under construction will be available in the coming years? Since development of science and technology as well as innovation and management system are strategic components to drive changes in a country, understanding the status and the impact of large research facilities is fundamental to estimate how China will grow toward the frontiers of science and innovation, and what will be the role of this country in many key disciplines at mid‐century. Research infrastructures increase the prestige of a nation and its technology capabilities. Moreover, in the case of China, they even represent one of the key issues to understand the extraordinary growth of this country.


Double strand breaks (DSBs) and interstrand crosslinks (ICLs) are toxic DNA lesions that can be repaired through multiple pathways, some of which involve shared proteins. One of these proteins, DNA Polymerase θ (Pol θ), coordinates a mutagenic DSB repair pathway named microhomology-mediated end joining (MMEJ) and is also a critical component for bypass or repair of ICLs in several organisms. Pol θ contains both polymerase and helicase-like domains that are tethered by an unstructured central region. While the role of the polymerase domain in promoting MMEJ has been studied extensively both in vitro and in vivo, a function for the helicase-like domain, which possesses DNA-dependent ATPase activity, remains unclear. Here, we utilize genetic and biochemical analyses to examine the roles of the helicase-like and polymerase domains of Drosophila Pol θ. We demonstrate an absolute requirement for both polymerase and ATPase activities during ICL repair in vivo. However, similar to mammalian systems, polymerase activity, but not ATPase activity, is required for ionizing radiation-induced DSB repair. Using a site-specific break repair assay, we show that overall end-joining efficiency is not affected in ATPase-dead mutants, but there is a significant decrease in templated insertion events. In vitro, Pol θ can efficiently bypass a model unhooked nitrogen mustard crosslink and promote DNA synthesis following microhomology annealing, although ATPase activity is not required for these functions. Together, our data illustrate the functional importance of the helicase-like domain of Pol θ and suggest that its tethering to the polymerase domain is important for its multiple functions in DNA repair and damage tolerance.


To help prevent the use of manual resuscitators without supplemental oxygen we developed a device that automatically starts the flow of oxygen when the resuscitators is put into use and then stops the oxygen flow when the resuscitator is returned to its assigned resting place. This instant oxygen delivery valve does not compromise oxygen flowrates from the gas source. We have used this device without problems for several months in our intensive care until.


We report a study of the reactions of pure metal clusters Nbn- with dioxygen in the gas phase. It is found that the presence of low-concentration dioxygen reactants results in oxygen-addition products, whereas sufficient high-concentration dioxygen enables oxygen-etching reactions giving rise to molecular niobium oxides. Interestingly, in the presence of a suitable gas flow rate of an intermediate dioxygen concentration, a highly selective product Nb11O15- shows up in the mass spectra. Utilizing density functional theory (DFT) calculations, we have discussed the reactivities of Nbn- (3 ≤ n ≤ 14) clusters with oxygen, and unveiled the reasonable stability of Nb11O15- pertaining to its unique geometric structure with a D5h Nb@Nb10 core fully protected by 15 bridge-oxygen atoms. The oxygen-passivated Nb@Nb10O15- cluster exhibits a large HOMO-LUMO gap (1.46 eV) and effective multicenter bonds with remarkable superatom orbitals for all the 26 valence electrons of the Nb@Nb10 core corresponding to well-staggered energy levels. We illustrate the superatomic features in the Nb@Nb10 metallic core for which the adaptive natural density partitioning (AdNDP) analysis unveils thirteen 11c-2e bonds. Among them, one of the 11c-2e bonds accounts for the superatomic S orbital, three bonds correspond to superatomic P orbitals, another five display vivid D orbital characteristics, and the remaining four 11c-2e bonds are assigned to F orbital features. In addition, the net atomic charge of the center Nb atom is as high as -0.804 |e| rendering core-shell electrostatic interactions and the shielding effect of the Nb10O15 shell.


Carbohydrate – receptor interactions are an integral part of biological events. They play an important role in many cellular processes, such as cell-cell adhesion, cell differentiation and in-cell signaling. Carbohydrates can interact with a receptor by using several types of intermolecular interactions. One of the most important is the interaction of a carbohydrate's apolar part with aromatic amino acid residues, known as dispersion interaction or CH/π interaction. In the study presented here, we attempted for the first time to quantify how the CH/π interaction contributes to a more general carbohydrate - protein interaction. We used a combined experimental approach, creating single and double point mutants with high level computational methods, and applied both to Ralstonia solanacearum (RSL) lectin complexes with α-l-Me-fucoside. Experimentally measured binding affinities were compared with computed carbohydrate-aromatic amino acid residue interaction energies. Experimental binding affinities for the RSL wild type, phenylalanine and alanine mutants were −8.5, −7.1 and −4.1 kcal.mol−1, respectively. These affinities agree with the computed dispersion interaction energy between carbohydrate and aromatic amino acid residues for RSL wild type and phenylalanine, with values −8.8, −7.9 kcal.mol−1, excluding the alanine mutant where the interaction energy was −0.9 kcal.mol−1. Molecular dynamics simulations show that discrepancy can be caused by creation of a new hydrogen bond between the α-l-Me-fucoside and RSL. Observed results suggest that in this and similar cases the carbohydrate-receptor interaction can be driven mainly by a dispersion interaction.


This paper presents an optimal internal model control (OIMC) algorithm for heading control problem of Autonomous Underwater Vehicle (AUV) affected by irregular wave forces. Firstly, the AUV system model is proposed, and the exosystem of irregular wave forces is obtained based on the Morison equation. Secondly, the disturbances compensator is designed by using internal model. And a new augmented system is constructed, by taking the system and the disturbances compensator in series. Then the optimal control problem of AUV nonlinear system is transformed into the optimal regulator design problem of an augmented system. The OIMC law is designed according to the theory of the quadratic optimal control and stability degree constraint. Finally, the controller is applied to the heading control of AUV with irregular wave forces disturbances, and the results demonstrate the effectiveness and robustness of the controller.


In this paper the electron density and temperature of atmospheric helium and argon plasmas operated under similar experimental conditions are compared. The conditions are chosen such that both plasmas are ionizing. It is found that a helium plasma has a higher electron temperature and a lower electron density than an equi-operational argon plasma, i.e. an argon plasma that is operated at the same external conditions. This is mainly caused by the higher excitation potential of the first excited state and the lower mass of helium, respectively. Due to these differences in electron density and temperature the densities of the helium ground state and of the excited states are much larger than their corresponding Saha equilibrium values for a wide range of conditions. The consequence of this is that the spectroscopic methods, which are used to determine the electron density and temperature, have a very limited validity region in the case of helium. For argon the deviations are much smaller so that these methods can often be applied safely.


Trabecular bone remodels during life in response to loading and thus should, at least in part, reflect potential variation in the magnitude, frequency and direction of joint loading across different hominid species. Here we analyse the trabecular structure across all non‐pollical metacarpal distal heads (Mc2‐5) in extant great apes, expanding on previous volume of interest and whole‐epiphysis analyses that have largely focused on only the first or third metacarpal. Specifically, we employ both a univariate statistical mapping and a multivariate approach to test for both inter‐ray and interspecific differences in relative trabecular bone volume fraction (RBV/TV) and degree of anisotropy (DA) in Mc2‐5 subchondral trabecular bone. Results demonstrate that whereas DA values only separate Pongo from African apes (Pan troglodytes, Pan paniscus, Gorilla gorilla), RBV/TV distribution varies with the predicted loading of the metacarpophalangeal (McP) joints during locomotor behaviours in each species. Gorilla exhibits a relatively dorsal distribution of RBV/TV consistent with habitual hyper‐extension of the McP joints during knuckle‐walking, whereas Pongo has a palmar distribution consistent with flexed McP joints used to grasp arboreal substrates. Both Pan species possess a disto‐dorsal distribution of RBV/TV, compatible with multiple hand postures associated with a more varied locomotor regime. Further inter‐ray comparisons reveal RBV/TV patterns consistent with varied knuckle‐walking postures in Pan species in contrast to higher RBV/TV values toward the midline of the hand in Mc2 and Mc5 of Gorilla, consistent with habitual palm‐back knuckle‐walking. These patterns of trabecular bone distribution and structure reflect different behavioural signals that could be useful for determining the behaviours of fossil hominins.


The truck system was a global phenomenon in the period 1865-1920, where workers were paid through the company store. In Beyond Racism and Poverty Karin Lurvink looks at how this system functioned on plantations in Louisiana in comparison with peateries in the Netherlands. In the United States, the system is often viewed as a 'second slavery' and strongly associated with racism. In the Netherlands, however, not racism but poverty has been seen as the main reason for its continued existence. By using a variety of historical sources and by analyzing the perspectives of both employers and workers, Lurvink provides new insights into how the truck system worked and can be explained. She reveals how the system was not only coercive but had advantages for the workers as well, which should not be overlooked.


Hybrid organic-inorganic perovskites (HOIPs) have attracted much attention due to their excellent properties and easy synthesis. As far as we know, most documented ferroelastics mainly focus on the 3D (three-dimensional) perovskites, the 2D monolayer perovskite ferroelastics are rarely reported before. In this work, we synthesized a 2D lead-based perovskite (C5NH13Br)2PbBr4 (1) (C5NH13Br = 5-bromoamylamine cation) by introducing flexible chain organic cations. The evolution of ferroelastic domains observed by a polarized light microscope confirms that compound 1 undergoes a ferroelastic phase transition at 392/384 K. In addition, its direct band gap is 2.877 eV. Interestingly, the material emits an attractive blue light (quantum yield 5.06%) under UV light. Three structural descriptors are introduced to quantitatively analyze the relationship between structural distortion and the shape of emission peak. This work provides a way to design multifunctional perovskite-type materials.


We study the peristaltic mechanism of an incompressible non-Newtonian biofluid (namely, Maxwell model) in the annular region between two coaxial tubes. The inner tube represents the endoscope tube. The system of the governing nonlinear PDE is solved by using the perturbation method to the first order in dimensionless wavenumber. The modified Newton-Raphson method is used to predict the flow separation points along the peristaltic wall and the endoscope tube. The results show that the presence of the endoscope (catheter) tube in the artery increases the pressure gradient and shear stress. Such a result seems too reasonable from the physical and medical point of view.


CONTEXT
Cancer-testis antigens are the unique class of testis proteins expressed in tumor but not healthy tissue except testis and might represent ideal targets for the development of novel diagnostics and therapeutic methods in thyroid cancer, which is the most common malignancy of the endocrine system.

OBJECTIVE
Our objective was to investigate the clinical relevance of cancer-testis antigen sperm-associated antigen 9 (SPAG9) as early diagnostic and therapeutic target in thyroid cancer.

DESIGN, SETTING, AND SUBJECTS
SPAG9 gene and protein expression was determined in thyroid cancer cell lines in 138 thyroid tumor specimens, 60 adjacent noncancerous tissues (ANCT), 22 multinodular goiters (nonneoplastic hyperplasia), and 20 follicular adenoma tissue samples by RT-PCR, in situ RNA hybridization, and immunohistochemistry. Gene silencing approach was used to examine the effects of suppression of SPAG9 protein on cellular growth and colony formation. Humoral immune response against SPAG9 in thyroid cancer patients was analyzed using ELISA.

RESULTS
SPAG9 mRNA and protein expression was detected in 78% of the thyroid cancer patients but not multiple goiters and follicular adenoma disease patients. It is interesting to note that majority of early-stage (T1) thyroid cancer patients exhibited higher antibody response against SPAG9. Small interfering RNA-mediated knockdown of SPAG9 expression in thyroid cancer cell significantly reduced cellular growth and colony formation.

CONCLUSIONS
SPAG9 expression may play a role in cellular growth and thyroid carcinogenesis. These findings support a potential role for SPAG9 as diagnostic biomarker as well as a possible therapeutic target in thyroid cancer treatment.


Website morphing infers latent customer segments from clickstreams and then changes websites' look and feel to maximize revenue. The established algorithm infers latent segments from a preset number of clicks and then selects the best "morph" using expected Gittins indices. Switching costs, potential website exit, and all clicks prior to morphing are ignored. We model switching costs, potential website exit, and the potentially differential impact of all clicks to determine when to morph for each customer. Morphing earlier means more customer clicks are based on the optimal morph; morphing later reveals more about the customer's latent segment. We couple this within-customer optimization to between-customer expected Gittins index optimization to determine which website "look and feel" to give to each customer at each click. We evaluate the improved algorithm with synthetic data and with a proof-of-feasibility application to Japanese bank card loans. The proposed algorithm generalizes the established algorithm, is feasible in real time, performs substantially better when tuning parameters are identified from calibration data, and is reasonably robust to misspecification.

Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2014.1961 .

This paper was accepted by Eric Bradlow, special issue on business analytics.


The decaying behaviour of the axial temperature distribution in the post-arc channel after current zero is measured around the nozzle throat in a flat-type SF6 gas-blast quenching chamber. In the quenching chamber, iron is intentionally used as the electrode material. Two iron atom spectral lines at wavelengths 426 and 443 nm are detectable even up to 100 mu s after current zero for an arc with peak value of 5 kA. This is because the spectral lines for iron have higher radiation intensities than those for other species such as sulphur ions or copper atoms. From the radiation intensities measured at each of the five axial positions around the nozzle throat, the temperatures are estimated by means of the two-line method. The axial temperature distribution shows a local maximum at the nozzle throat up to a time of 20 mu s after current zero. However, the temperature at the nozzle throat decays more rapidly than at the other axial positions. At 100 mu s after current zero, the temperature at the nozzle throat reaches 3500 K, the lowest magnitude among the axial positions.


We consider estimating the edge-probability matrix of a network generated from a graphon model when the full network is not observed---only some overlapping subgraphs are. We extend the neighbourhood smoothing (NBS) algorithm of Zhang et al. (2017) to this missing-data set-up and show experimentally that, for a wide range of graphons, the extended NBS algorithm achieves significantly smaller error rates than standard graphon estimation algorithms such as vanilla neighbourhood smoothing (NBS), universal singular value thresholding (USVT), blockmodel approximation, matrix completion, etc. We also show that the extended NBS algorithm is much more robust to missing data.


A computational model of nervous activity in the auditory nerve, cochlear nucleus, and inferior colliculus is presented and evaluated in terms of its ability to simulate psychophysically-measured pitch perception. The model has a similar architecture to previous autocorrelation models except that the mathematical operations of autocorrelation are replaced by the combined action of thousands of physiologically plausible neuronal components. The evaluation employs pitch stimuli including complex tones with a missing fundamental frequency, tones with alternating phase, inharmonic tones with equally spaced frequencies and iterated rippled noise. Particular attention is paid to differences in response to resolved and unresolved component harmonics. The results indicate that the model is able to simulate qualitatively the related pitch-perceptions. This physiological model is similar in many respects to autocorrelation models of pitch and the success of the evaluations suggests that autocorrelation models may, after all, be physiologically plausible.


BACKGROUND
In 2016, the World Health Organization (WHO) introduced global targets for the elimination of hepatitis C (HCV) by 2030. We conducted a nationwide HCV micro-elimination program among men who have sex with men (MSM) living with HIV from the Swiss HIV Cohort Study (SHCS) to test whether the WHO goals are achievable in this population.

METHODS
During phase A (10/2015-06/2016), we performed a population-based and systematic screening for HCV-RNA among MSM from the SHCS. During phase B (06/2016-02/2017) we offered treatment with HCV direct-acting agents (DAAs) to MSM identified with a replicating HCV infection. During phase C (03/2017-11/2017), we offered re-screen to all MSM for HCV-RNA and initiated DAA treatment in MSM with replicating infections (Clinicaltrials.gov NCT02785666).

FINDINGS
We screened 3'715/4'640 (80%) MSM and identified 177 with replicating HCV infections (4.8%); 150 (85%) of which started DAA treatment and 149 (99.3%) were cured. We re-screened 2'930/3'538 (83%) MSM with a prior negative HCV-RNA and identified 13 (0.4%) with a new HCV infection. At the end of the micro-elimination program, 176/190 MSM (93%) were cured, and the HCV incidence rate declined from 0.53 per 100 patient-years (95% confidence interval [CI] 0.35, 0.83) prior to the intervention to 0.12 (CI 0.03, 0.49) by the end of 2019.

INTERPRETATION
A systematic and population-based HCV micro-elimination program among MSM living with HIV was feasible and resulted in a strong decline in HCV incidence and prevalence. Our study can serve as a model for other countries aiming to achieve the WHO HCV elimination targets.


For pt.I see ibid., vol.17, pt.1 (1984). The transverse Cartesian components By and Bz of the magnetic field of cylindrical saddle-shaped coils are evaluated in a series expansion. The terms of the series are written in the form Almnxlymzn, where the coefficients Almn are functions of the coil size and shape parameters R0, Z0, Phi 0 (R0 and 2Z0 are the radius and height of the cylinder defining the geometry of the saddle-shaped coil, Phi 0 is the angle of the arcs). The y component of the magnetic field is determined to the fourth order (l+m+n=4); the z component was evaluated including the sixth-order terms. The existence or non-existence of the second-order terms determine the limiting properties of By and Bz for r to 0. the analysis of the second-order terms as a function of the coil parameters reveals some general properties of the magnetic field at the coil centre.


This paper presents a novel concept of Static Var Compensator (SVC) damping control using a weighted sum of bus voltage angles of remote generators that are responsible for causing inter-area oscillations in power systems. These remote bus voltage angle signals are acquired through Phasor Measurement Units (PMUs). A time domain simulation study on a 39-bus New England multi-machine system is utilized to show that an SVC auxiliary damping control, based on the derivative of these remote bus voltage angles, is superior to the conventionally employed local signals in damping inter-area oscillations. The effect of transmission delay in the acquisition of remote signals is also presented and a simple mechanism to compensate this delay is proposed and validated. The robustness of the delay compensator is finally shown for a wide range of signal transmission delays. The designed SVC controller shows a superior performance in damping the inter-area oscillations despite the signal transmission delays.


Currently, there is a lack of understanding of why many patients with thyroid dysfunction remain symptomatic despite being biochemically euthyroid. Gastrointestinal (GI) health is imperative for absorption of thyroid-specific nutrients as well as thyroid function directly. This comprehensive narrative review describes the impact of what the authors have conceptualized as the "nutrient–GI–thyroid axis". Compelling evidence reveals how gastrointestinal health could be seen as the epicenter of thyroid-related care given that: (1) GI conditions can lower thyroid-specific nutrients; (2) GI care can improve status of thyroid-specific nutrients; (3) GI conditions are at least 45 times more common than hypothyroidism; (4) GI care can resolve symptoms thought to be from thyroid dysfunction; and (5) GI health can affect thyroid autoimmunity. A new appreciation for GI health could be the missing link to better nutrient status, thyroid status, and clinical care for those with thyroid dysfunction.


Using one field and two online lab experiments, this article shows that congruency between shelf layout and a consumer's internal product categorization increases the perceived variety of the assortment and reduces the perceived complexity of the shelf layout. These assortment perceptions, in turn, heighten purchase intention and satisfaction toward the chosen item. Results are robust across internal categorization measurements (planogram design vs. sorting tasks), congruency measures (distance- vs. matching-based), and products (biscuits vs. yogurt snacks). In the field study, familiarity—operationalized as either consumption frequency or subjective product knowledge—increased the overall effect of categorization congruency and strengthened its pathway through perceived variety (vs. the one through complexity). The authors show how their research can be exploited to improve shelf layouts by optimizing the external categorization. They demonstrate the value of a unifying Bayesian framework for research on behavioral decision making that uses the same set of posterior parameter draws for parameter inference, moderated mediation analysis, and optimization under uncertainty.


Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disease initially caused by mutations in the DHCR7 gene (OMIM# 602858); this gene encodes the penultimate enzyme in the cholesterol biosynthetic pathway, 7-dehydrocholesterol reductase (3β-hydroxysterol-Δ7-reductase; EC 188.8.131.52) [1,2]. Such mutations give rise to a catalytically defective enzyme, resulting in an inefficient conversion of 7-dehydrocholesterol (7DHC), the immediate biogenic precursor of cholesterol, to cholesterol. This causes aberrant accumulation of 7DHC (and, typically to a far lesser extent, its isomer, 8-dehydrocholesterol (8DHC)) and reduced levels of cholesterol in bodily tissues and fluids [3]. [Notably, there are no reports of an "all-or-none" effect, where cells or tissues from affected individuals or unborn fetuses contain no detectable residual cholesterol. More typically, the cholesterol levels are far below normal, while the dehydrosterol precursors are the dominant sterol species present.] The biological consequences of this biochemical defect, unlike many other monogenic diseases, can vary dramatically, with the severity of phenotypic abnormalities ranging from relatively mild to severe, even including embryonic or early neonatal lethality [1]. SLOS is considered a pediatric disorder, since the disease manifests in early childhood and few affected individuals survive beyond the teenage years.


This report statistically introduces the current state and recent trends regarding resource circulation, industrial and municipal waste and recycling in Japan. Also recycling systems for home appliance waste and ELV (end of life vehicle) waste are discussed. The ratio of the total amount of recirculated resources in Japan to the national total material input was 15.8% in the 2014 fiscal year. This ratio has been increasing continuously over the past 20 years mainly due to steady progress in the industrial waste recycling and to gradual shrinkage of the domestic natural resource input. Japanese total waste volume in the 2014 fiscal year was 437 Mt (million tons), with 89.9% industrial waste and 10.1% municipal waste. The amount of recirculated resources derived from this waste was 50.6% of the total waste volume. The final landfill amount of the total waste was only 3.4%. When comparing the breakdown of waste treatment with the three major EU countries, Germany, France and the UK, the ratio of recirculated resource was not significantly different. But a characteristic feature of Japan was that the ratio of reduction amount by dewater and drying was very large, and the ratios of backfilling and final disposal amounts are considerably smaller. With regard to the recycling of major used products disposed of by consumers in Japan, the current status of home appliance recycling and ELV recycling are discussed. With an individual recycling system constituted in each product area, manufacturers and distributors are obliged to implement recycling, and consumers are charged with recycling costs. At the moment these are successful models that are promoting recycling with high steady recycling rates.


Mathematical morphology has produced an important class of non-linear filters. Unfortunately, few design methods exist for these filters. Those existing tending to be computationally intractable or require some expert knowledge of mathematical morphology. The paper describes research into methods by which different classes of morphological filters can be designed by employing genetic algorithms.


†*** *** **** * Flake-polymer composites are commonly used in protection and barrier applications due to its low effective diffusivity. Effective diffusivity through flake-polymer composites depends on the local accelerated transport along the flakematrix interphase. This paper describes analytical models for predicting the effective diffusivity through the flake-polymer composite as a function of flake orientation, volume fraction, aspect ratio, and interphase properties. Estimates of effective diffusivity were also generated using random walk simulations. Results from the two methods agree well with each other. Using model-predicted effective diffusivities, solute penetration depths in systems with flakes aligned either orthogonal or parallel to the diffusion direction are calculated and compared to experimentally obtained penetration depths of acid


The high-resolution (full width at half maximum = 0.11 A) emission spectrum of the deuterium molecule produced by electron-impact excitation at 100 eV has been measured in the wavelength range 1200 - 1660 A. In conjunction with the experimental measurement, transition probabilities of and D band systems are calculated. Synthetic spectra based on the calculated transition probabilities are in very good agreement with the optically thin experimental spectra. While centrifugal effects on the overall Lyman band emission intensity in D2 and H2 are similar, the effect of rotation-vibrational perturbations between the B 1u+ and C 1u+ states on spectral intensities is found to be less significant in D2. Excitations via isotropic ( J = 0) and anisotropic ( J = ±2, and 0) interactions for the dipole forbidden E, F 1g+-X 1g+ transition are inferred from the measured spectra. Excitation cross sections of the B 1u+-X 1g+ and C 1u-X 1g+ bands, along with the estimated E, F 1g+-B 1u+ cascade cross section, for D2 are obtained.


The complex fracture behavior of a cross-ply composite cantilever beam with artificially embedded delamination is investigated analytically, numerically, and experimentally. The analysis of the cantilever beam is divided into two geometric configurations: the global bending of the widelaminated cantilever, and the local buckling of the delaminated part. A finite element model developed in ANSYS is used to concurrently analyze the effects of contact zone and determination in the aforementioned asymmetrically loaded structure. The obtained experimental data are correlated and compared with the findings of the FEM simulations. All numerical, analytical, and experimental results illustrate that the fracture behavior of the laminate cantilever beam is dominated by mode II, mainly due to the effect of a large contact zone. The latter is determined by geometric and loading parameters. The dominance of mode II over mode I, leads to the initiation and propagation of an interfacial crack rather than an intralayer one. Furthermore, experimental evidence indicates that crack kinking during propagation depends on the architecture of the specimens.


Stilbene phytoalexins are among the most accumulated compounds during grapevine-pathogen interactions. However, their steady-state accumulation level and spatial distribution within the tissues to counteract Botrytis cinerea infection remain to be explored. In this work, matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to determine the spatial distribution of different phytoalexins in grapevine leaves upon infection with B. cinerea. Ultraperformance liquid chromatography-fluorescence (UPLC-FL) was also employed to monitor the accumulation pattern of these phytoalexins. This study showed that stilbene compounds accumulate in areas close to the pathogen infection sites. It was also revealed that the accumulation patterns of the stilbene phytoalexins can vary from one time point postinfection to another with specific accumulation patterns within each time point. To the best of our knowledge, this is the first time that the separate localization of grapevine stilbene phytoalexins has been revealed following B. cinerea infection.


This paper describes an efficient exact algorithm to solve Preemptive Resource Constrained Project Scheduling Problem (Preemptive RCPSP). We propose a very original and efficient branch and bound procedure based upon minimal interval order enumeration, which involves column generation as well as constraint propagation and which is implemented with the help of the generic SCIP software. We perform tests on the famous PSPLIB instances which provide very satisfactory results. To the best of our knowledge it is the first algorithm able to solve at optimality all the set of j30 instances of PSPLIB in a preemptive way. Moreover, this algorithm allows us to update several best known lower bounds for the j60, j90 and j120 instances of PSPLIB.


In this meta-analysis of 75 studies on more than 3,888 children in 19 different countries, the intellectual development of children living in children's homes (orphanages) was compared with that of children living with their (foster) families. Children growing up in children's homes showed lower IQ's than did children growing up in a family (trimmed d = 0.74). The age at placement in the children's home, the age of the child at the time of assessment, and the developmental level of the country of residence were associated with the size of the delays. Children growing up in children's homes show a substantial lower level of IQ (average IQ of 84) than their peers reared in (foster) families (average IQ of 104), and the difference amounted to 20 IQ points. More research is needed to detect the causes of the large IQ delays and to test ways of improving the intellectual development of millions of children in orphanages around the world.


The problem of practical realization of the optimal fixed-delay symbol-by-symbol detection algorithm, which is optimum in the sense of minimizing the symbol error probability, given a delay constraint D, is investigated. A fully-parallel structure is developed, and through systematic reformulations of the algorithm, the computational requirements are reduced considerably. In addition, the problems associated with a large dynamic range such as overflow (or underflow) are (practically) removed. A number of approximations are applied to this simplified parallel symbol (SPS) detector that lead to the derivation of suboptimal detectors. One such suboptimal detector is shown to be the same as the minimum-metric Viterbi detector. A brief comparison of the SPS detector and the Viterbi detector shows that the former has a slightly better performance at low values of signal-to-noise ratio (SNR) and the latter performs a smaller number of computations (particularly) at higher values of SNR; otherwise, the two detectors are comparable in performance and complexity. >


Siddha is considered to be one of the oldest medicines with its own benefits. In this modern era, people are more aware towards their health. At many circumstances of illness, people use Siddha medicines to cure their disease. Siddha is preferred for its own specialties. This paper has attempted to reveal the awareness towards Siddha medicines taking 52 respondents from Dharmapuri City. The results were analysed by using various statistical techniques like percentage analysis, chi-square and t test. Siddha focuses on the eight supernatural powers called as 'Ashtaamahasiddhi' and those who achieved these powers were known as siddhars. Hence it is called as siddha medicine. The siddhars knowledge was found in palm leaf manuscripts and their fragments were found in some parts of south India.


The possibility of building a computer that takes advantage of the most subtle nature of quantum physics has been driving a lot of research in atomic and solid state physics for some time. It is still not clear what physical system or systems can be used for this purpose. One possibility that has been attracting significant attention from researchers is to use the spin state of an electron confined in a semiconductor quantum dot. The electron spin is magnetic in nature, so it naturally is well isolated from electrical fluctuations that can a loss of quantum coherence. It can also be manipulated electrically, by taking advantage of the exchange interaction. In this work we describe several experiments we have done to study the electron spin properties of lateral quantum dots. We have developed lateral quantum dot devices based on the silicon metal-oxide-semiconductor transistor, and studied the physics of electrons confined in these quantum dots. We measured the electron spin excited state lifetime, which was found to be as long as 30 ms at the lowest magnetic fields that we could measure. We fabricated and characterized a silicon double quantum dot. Using this double quantum dot design, we fabricated devices which combined a silicon double quantum dot with a superconducting microwave resonator. The microwave resonator was found to be sensitive to two-dimensional electrons in the transistor channel, which we measured and characterized. We developed a new method for extracting information from random telegraph signals, which are produced when we observe thermal fluctuations of electrons in quantum dots. The new statistical method, based on the hidden Markov model, allows us to detect spin-dependent effects in such fluctuations even though we are not able to directly observe the electron spin. We use this analysis technique on data from two experiments involving gallium arsenide quantum dots and use it to measure spin-dependent tunneling rates. Our results advance the understanding of electron spin physics in lateral quantum dots, in silicon and in gallium arsenide.


Rice (Oryza sativa L.) 'KDML105' is the most popular aromatic rice originating in Thailand. This cultivar is highly susceptible to abiotic stresses, especially drought and salt stress during the seedling stage. The objective of this study was to investigate the photosynthetic performance in response to drought and salt stress of four improved breeding lines, specifically CSSL94 and CSSL103 (containing drought-tolerant quantitative trait loci: DT-QTLs) and RGD1 and RGD4 (containing a salt-tolerance gene, SKC1), with 'KDML105' (susceptible) and DH103 (tolerant to drought and salt stress) as the controls. Rice seedlings were grown for 21 days in hydroponic solutions and then exposed to salt stress (150 mM NaCl) or drought stress (20% PEG6000) for 10 days. The results indicated that when subjected to drought and salt stress, all rice lines/cultivar exhibited significant Dechudom Pamuta, Meechai Siangliw, Jirawat Sanitchon, Jarunjit Pengrat, Jonaliza L. Siangliw, Theerayut Toojinda and Piyada Theerakulpisut 654 Pertanika J. Trop. Agric. Sci. 43 (4): 653 675 (2020) reductions in net photosynthesis rate (PN), stomatal conductance (gs), transpiration rate (E), the maximal quantum yield of PSII photochemistry (Fv/Fm), the effective quantum yield of PSII photochemistry (Fv'/Fm'), photosynthetic pigments, and SPAD readings, whereas water use efficiency (WUE) and non-photochemical quenching (NPQ) increased. Compared with 'KDML105', CSSL94, and CSSL103 were more tolerant to both drought and salinity, showing less reduction in all photosynthetic parameters. For RGD1 and RGD4, it was confirmed that these lines had a higher level of salt tolerance than 'KDML105' based on better photosynthetic performance under salt stress, demonstrating that these lines were also more tolerant to drought stress.

http://www.pertanika.upm.edu.my/resources/files/Pertanika PAPERS/JTAS Vol. 43 (4) Nov. 2020/17 JTAS-1978-2020.pdf


Background: NSD2 (nuclear receptor binding SET domain protein 2) is a histone methyltransferase specific for dimethylation of histone H3 lysine 36 (H3K36me2), a modification associated with gene activation. In pediatric acute lymphoblastic leukemia (ALL), particularly at relapse, a gain of function mutation (E1099K) of NSD2 is found in 10-15% of cases. The NSD2 mutation is found in addition to fusion proteins such as E2A-PBX and ETV6-RUNX1. The mutation can be subclonal at diagnosis and dominant at relapse, suggesting a link to therapeutic resistance. The NSD2-E1099K mutation affects gene expression through an increase in H3K36me2 and a decrease in H3K27me3. Using CRISPR/Cas9-edited isogenic ALL cell lines, we found that NSD2-E1099K mutation drove oncogenic programming by altering chromatin architecture, gene expression and enhancing cell growth, migration and infiltration to the central neural system (CNS). NSD2 mutation caused resistance of ALL cells to glucocorticoids (GC) by blocking genome wide binding of the glucocorticoid receptor (GR, encoded by NR3C1 gene) preventing GC-mediated induction of pro-apoptotic genes. NR3C1 levels were depressed in NSD2-E1099K cells and GC failed to induce autoactivation of NR3C1. While H3K27me3 was globally decreased by NSD2-E1099K, increased H3K27me3 was noted at the promoter of NR3C1, suggesting a novel role of polycomb repressive complex 2 as a therapeutic target for relapsed ALL with NSD2 mutation. While NSD2 is highly expressed in B cells and NSD2 knockout causes defects in B cell development, how the NSD2 mutation affects B cell development and leukemia occurrence in vivo is uncertain.
 Aims: To determine the role of NSD2 mutation in the pathogenesis of lymphocytic malignancies and GC resistance in a mouse model.
 Methods: We generated a conditional NSD2-E1099K knock-in mouse model in which the NSD2-E1099K allele was placed in the Rosa26 locus and expressed in B cells under the control of Cd19-Cre (Cd19+/-NSD2E1099K/WT). The resulting phenotype was characterized through peripheral blood counts, cellular morphology and histology of blood smears, bone marrow (BM), spleen and liver, flow cytometric analysis, germinal center B cells (GCB) immunization, BM transplantation, and hematopoiesis analysis in a CD3-/- background. We further established mouse leukemia cell lines with NSD2 mutation for functional analysis. RNA-Seq, real time PCR, immunoblotting, and apoptosis analysis (Annexin V/PI staining) following GC treatment were performed to demonstrate the effects of NSD2 mutation on histone modifications, transcriptome and GC resistance.
 Results: The NSD2-E1099K mutation increased H3K36me2 and decreased H3K27me3 in isolated B cells from mouse BM and spleen. Mice were aged and did not develop signs of malignancy and RNA-sequencing showed few differences between B cells with or without the NSD2 mutation. However, after immunizing the mice with sheep red blood cells (SRBC), more GCBs were seen in the spleen of NSD2 mutant mice, suggesting mutant NSD2 stimulated germinal center hyperplasia. Transplantation of BM cells from mice expressing NSD2-E1099K into lethally irradiated recipients lead to an expansion of B cells while myeloid and T cells and life span of the recipients impaired. The NSD2 knock-in mouse model was crossed with Cd3-/- mice to create Cd19+/-Cd3-/-NSD2E1099K/WT mice, which within 2 months of birth developed a disease resembling an immature B lymphocytic leukemia (B220+CD19+IgM+IgD-CD5-) with infiltration of the spleen, liver and CNS and a median survival of 4.8 months. These tumors could be transplanted into immunodeficient mice but not immunocompetent mice. RNA seq analysis of these cells revealed 6,815 genes (3,295 upregulated and 3,520 downregulated) differentially expressed in NSD2 mutant B cells compared to normal B cells. The upregulated genes were related to abnormal immunoglobulin level , B cell activation, T-helper 1 physiology, and decreased B cell apoptosis. Importantly, the NSD2 mutant leukemic cells displayed depressed level of NR3C1 gene expression and GC resistance.
 Conclusions: The NSD2 mutation alters B cell development, particularly in an immunodeficient background and causes B cells to become resistant to glucocorticoids. The inability of the mutation to generate disease on its own except in an immunodeficient background suggests genes that collaborate with NSD2 in ALL may play a role in immune escape.

 No relevant conflicts of interest to declare.


We have synthesized a convenient azido amine linker 3 and demonstrated its use in the synthesis of a carbohydrate-fluorescein conjugate for studying carbohydrate-binding proteins. The linker is easily prepared from tetraethylene glycol, and the synthesis can be applied to other PEG derivatives of various lengths


The results of the research on the functional properties of waxy wheat flour, obtained from the spring waxy wheat grain of the Biskvitna variety, adapted for agro-climatic conditions of the Kharkiv region, in comparison with white wheat flour, are presented. It is found that waxy wheat flour contains 16.8% less raw gluten than the reference sample, the gluten is 18.8% less elastic and 21.4% more stretchy, has a light gray color and can be attributed to the II group of quality. Waxy wheat flour has a 1.8 times higher water-holding capacity, its starch begins to gelatinize at a lower temperature, while the maximum viscosity of the waxy wheat flour starch paste is almost 1.6 times higher than that of the reference sample. It is established that falling number of waxy wheat flour is only 68 s that more than 5 times lower than that one of wheat flour. The model dough system prepared from the waxy wheat flour has a 6.9% better lifting power in comparison to the system prepared from the wheat flour. Baking tests for sponge cakes, biscuits, fruitcakes and muffins with the substitution 25.0 to 75.0% of white flour to waxy wheat flour was performed. With an increasing of the dosage of waxy wheat flour a tendency of the increasing of the dough stickiness in all samples tested was observed. The baked goods tested were distinguished by good quality indicators, although in fruitcakes and muffins with a dosage of waxy wheat flour of more than 50.0%, the formation of large gas cells unevenly distributed in the crumb was noticed. Addition of 25.0% of waxy wheat flour causes an increase of the specific volume and porosity of sponge cakes by 11.1 and 9.3% respectively. With a further increase in the dosage of waxy wheat flour, the specific volume and porosity of the samples tested are verging to the reference sample. All samples of fruitcakes and muffins were not differ significantly in terms of specific volume and porosity. According to the results of the research conducted, it is suggested to use waxy wheat flour, obtained from the grain of Biskvitna variety, for the production of sponge cakes and biscuits in an amount of up to 75.0%, for fruitcakes and muffins – in an amount of up to 25.0% instead of wheat flour.


Batcho's 1995 Nostalgia Inventory was completed by 210 respondents, 88 males and 122 females, ranging in age from 5 to 79 years old. Subjects scoring high on the Nostalgia Inventory rated the past more favorably than did subjects scoring low on the inventory but did not differ in ratings of the present or future. High-scoring individuals rated themselves more emotional, with stronger memories, need for achievement, and preference for activities with other people, but not as less happy, risk or thrill seeking, religious, logical, easily bored, or expecting to succeed. In a second study, 113 undergraduates, 32 men and 81 women, completed measures of nostalgia, memory, and personality. High-scoring subjects showed no advantage in free recall over low-scoring subjects but recalled more people-oriented autobiographical memories. Individuals scoring high on nostalgia were no more optimistic, pessimistic, or negatively emotional but scored higher on a measure of emotional intensity. Personal nostalgia was distinguished from social-historical nostalgia and world view. Results were discussed with respect to major theoretical approaches.


According to the United Nation's World Water Development Report, by 2050 more than 50% of the world's population will be under high water scarcity. To avoid water stress, water resources are needed to be managed more securely. Smart water technology (SWT) has evolved for proper management and saving of water resources. Smart water system (SWS) uses sensor, information, and communication technology (ICT) to provide real-time monitoring of data such as pressure, water ow, water quality, moisture, etc. with the capability to detect any abnormalities such as non-revenue water (NRW) losses, water contamination in the water distribution system (WDS). It makes water and energy utilization more efficient in the water treatment plant and agriculture. In addition, the standardization of data format i.e., use of Water Mark UP language 2.0 has made data exchange easier for between different water authorities. This review research exhibits the current state-of-the-art of the on-going SWT along with present challenges and future scope on the mentioned technologies. A conclusion is drawn that smart technologies can lead to better water resource management, which can lead to the reduction of water scarcity worldwide. High implementation cost may act as a barrier to the implementation of SWT in developing countries, whereas data security and its reliability along with system ability to give accurate results are some of the key challenges in its field implementation.


The transfer of energy and angular momentum in the magnetic coupling (MC) of a rotating black hole (BH) with its surrounding accretion disc is discussed based on a mapping relation derived by considering the conservation of magnetic flux with two basic assumptions: (i) the magnetic field on the horizon is constant, (ii) the magnetic field on the disc surface varies as a power law with the radial coordinate of the disc. The following results are obtained: (i) the transfer direction of energy and angular momentum between the BH and the disc depends on the position of a co-rotation radius relative to the MC region on the disc, which is eventually determined by the BH spin; (ii) the evolution characteristics of a rotating BH in the MC process without disc accretion are depicted in a parameter space, and a series of values of the BH spin are given to indicate the evolution characteristics; (iii) the efficiency of converting accreted mass into radiation energy of a BH-disc system is discussed by considering the coexistence of disc accretion and the MC process; (iv) the MC effects on disc radiation and the emissivity index are discussed and it is concluded that they are consistent with the recent XMM-Newton observation of the nearby bright Seyfert 1 galaxy MCG-6-30-15 with reference to a variety of parameters of the BH-disc system.


Staphylococcus aureus is a major cause of ocular infections, often resulting in devastating vision loss. Despite the significant morbidity associated with these infections, little is yet known regarding the specific strain types that may have a predilection for ocular tissues nor the set of virulence factors that drive its pathogenicity in this specific biological niche. Whole genome sequencing (WGS) can provide valuable insight in this regard by providing a prospective, comprehensive assessment of the strain types and virulence factors driving disease among specific subsets of clinical isolates. As such, a set of 163-member S. aureus ocular clinical strains were sequenced and assessed for both common strain types (multilocus sequence type (MLST), spa, agr) associated with ocular infections as well as the presence/absence of 235 known virulence factors in a high throughput manner. This ocular strain set was then directly compared to a fully sequenced 116-member non-ocular S. aureus strain set curated from NCBI in order to identify key differences between ocular and non-ocular S. aureus isolates. The most common sequence types found among ocular S. aureus isolates were ST5, ST8 and ST30, generally reflecting circulating non-ocular pathogenic S. aureus strains. However, importantly, ocular isolates were found to be significantly enriched for a set of enterotoxins, suggesting a potential role for this class of virulence factors in promoting ocular disease. Further genomic analysis revealed that these enterotoxins are located on mobile pathogenicity islands, thus horizontal gene transfer may promote the acquisition of enterotoxins, potentially amplifying S. aureus virulence in ocular tissues.


Discriminantly separable polynomials of degree two in each of the three variables are considered. Those polynomials are by definition polynomials which discriminants are factorized as the products of the polynomials in one variable. Motivating example for introducing such polynomials is the famous Kowalevski top. Motivated by the role of such polynomials in the Kowalevski top, we generalize Kowalevski's integration procedure on a whole class of systems basically obtained by replacing so called the Kowalevski's fundamental equation by some other instance of the discriminantly separable polynomial. We present also the role of the discriminantly separable polynomils in twowell-known examples: the case of Kirchhoff elasticae and the Sokolov's case of a rigid body in an ideal fluid.


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To assess the reliability of predicting plasma concentrations of enoxacin, ciprofloxacin, and theophylline from drug concentrations in saliva, six healthy volunteers received single oral doses of enoxacin, ciprofloxacin, and theophylline administered in combination on each of four separate study days, with different, doses separated by at least 5 days. Drug concentrations were determined by a newly developed high-performance liquid chromatography (HPLC) assay, which could measure simultaneously all three drugs in plasma or saliva. Saliva data from the postabsorptive phase after drug administration were used to minimize the effects of variation in absorption. There were good correlations between saliva and plasma concentrations of enoxacin, ciprofloxacin, and theophylline (r = 0.91, 0.88, and 0.98, respectively). The mean (+/-SD) saliva-to-plasma (S/P) ratio for theophylline was 0.63 +/- 0.06 with a coefficient of variation (CV) of 7.9 +/- 2.7%. In contrast, the S/P ratios and CV values for enoxacin and ciprofloxacin were 0.72 +/- 0.21 and 28.9 +/- 11.1%, and 0.58 +/- 0.15 and 25.3 +/- 6.7%, respectively. Because of the large inter- and intraindividual variability, saliva concentrations of enoxacin and ciprofloxacin are not reliable for predicting plasma concentrations. However, saliva may be used reliably for predicting plasma concentrations of theophylline.


With the use of special additives, the concrete benefits over its product life increase, both in terms of mechanical properties and durability. Zeolites are used in the field of building work for, thank to their properties, they lend to the concrete enhanced features. This paper explores the physical and mechanical properties improvements of hardened concrete and its permeability. To this aim, on the one hand a concrete of control and another with Zeolite additions between 5% and 10% have been measured out with respect to the weight of cement, while on the other Compressive strength and permeability testing have been carried out through the Mercury intrusion porosimetry test. After these tests, it was possible to obtain concrete with Zeolite proportions of 5% and 10% that showed a suitable workability. With respect to the already analyzed mechanical properties, the inclusion of Zeolites as an additive was an improvement. In that respect, the durable features related to this type of concrete were also similarly improved, being also remarkable the lack of alkali-silica reactions.


This is a topical book on tropical cyclones, known more popularly as hurricanes in the Americas and typhoons in eastern Asia. The subject may appeal to academics and researchers as well as to the general public.

The best way to predict the future variability of tropical cyclones is by examining their past record. Prehistoric records can be obtained from geological or archeological studies while historical records are provided by documentation and instrumentation. Of particular interest now are the changes in frequency and landfall pattern of tropical cyclones during El Nino years, La Nina years, and neutral years, extending back in time to cover the past 8,000 years for disaster planning.


Phase-change materials, including metals, semiconductors and liquid crystals, have played a key role in the evolution of active nanophotonic and plasmonic functionalities. They present unique opportunities at the nano- (i.e. subwavelength) scale as a source of optical nonlinearity and a platform for high-contrast, low-energy electro-and all-optical switching / memory devices. I will review Southampton's work in this field: from the demonstration of exceptionally large (including metamaterial-enhanced) phase-change nonlinearities underpinned by light-induced, surface-mediated structural transitions in confined gallium; through the harnessing of non-volatile optically-induced amorphous/crystalline transitions in chalcogenides (such as Ge:Sb:Te) to realize plasmonic hybrid and all-dielectric switchable and laser re-writable metasurfaces; to the recent revelation that germanium and bismuth-based chalcogenide alloys can themselves present switchable and compositionally-tunable plasmonic properties in the UV-VIS spectral range.


Dhaka, capital of Bangladesh, is a megacity dependant on groundwater for the majority of its water supply, pumped from 420 boreholes distributed throughout the city. Recharge to the groundwater aquifer is insufficient to balance abstraction, groundwater levels are in decline and water quality is compromised by seepage from areas of urban and industrial contamination and leakage from polluted rivers. The strategic importance of the naturally high-quality groundwater resource demands a targeted programme of aquifer protection. Repeated surveys at over 100 boreholes demonstrate the patterns and trends of deteriorating groundwater quality. Groundwater modelling and environmental isotope distributions have been used independently to evaluate the significance of potential sources of pollution. Both approaches identify the polluted River Buriganga as the main threat to groundwater quality, indicating priorities for monitoring and aquifer protection.


Monochromatic cathodoluminescence (CL) imaging of metal-organic vapour phase epitaxy (MOVPE) grown In(0.1)Ga(0.9)N single quantum wells (QW) has been performed in a scanning transmission electron microscope (STEM). Spatially resolved fluctuations in the CL emission wavelength and intensity of the QW luminescence were recorded. The presence of regions with luminescent features asymmetrically distributed either side of the QW peak emission was inferred. These fluctuations may be attributed to, by for example, variations of ±0.01 in the In fraction of the In(0.1)Ga(0.9)N alloy, to changes of up to 0.6nm in the QW thickness. However these factors do not explain the gross fluctuations in QW emission intensity observed in TEM-CL on the scale of approximately one micron.


Abstract The mechanism by which ATO induces hematologic responses in patients with MDS is not well defined, and a better understanding might help to optimize the efficacy of ATO. Among other effects ATO induces apoptosis via inhibition of NFkB by interfering with IkB kinases. TNFa, a potent NFkB stimulus, is upregulated in MDS. ATO has been shown to prevent TNFa-induced NFkB activation, and to induce apoptosis in various neoplastic cells. Methods: 1) We used eletrophoretic mobility shift assays (EMSA) to determine NFkB activation in marrow mononuclear cells (MMC) from MDS and normal marrows. 2) Apoptosis was determined by Annexin V and propidium iodide following treatments with ATO (2-200uM), Enbrel, a soluble TNF-receptor (5ug/ml), and TNFa (20ng/ml), alone or in combination, in marrows from healthy donors, patients with MDS, and in ML1 cells. 3) The effect of ATO and Enbrel on NFkB inhibition was evaluated by EMSA, and phosphorylation of IKBα was determined using western blots. 4) To define the role of TNFa receptor (R) 1 and 2 signaling for ATO activity, apoptosis and NFkB activation were determined while blocking TNFR 1 and 2 respectively. 5) Levels of FLIP, an NFkB-dependent gene that modulates death signaling, were determined in response to treatment using real-time PCR. 6) Apoptosis in response to ATO/TNF/Enbrel was also determined in ML1 cells transduced to overexpress FLIP long. Results: MMC from 7 of 8 patients, and CD34+ cells from all patients with RAEB tested showed high constitutive NFkB activation (compared to RA/RARS marrows, which showed low activity comparable to normal marrows). Treatment with ATO induced similar patterns of NFκB inhibition in normal, ML1 and primary MDS (RAEB) cells, even in the presence of exogenous TNFa. Interestingly, Enbrel failed to prevent TNF-induced NFkB activation, and did not enhance ATO-induced NFkB inhibition (Figure B: EMSA;Western blot for P-IKB). However, there were distinct patterns of apoptosis: ATO induced apoptosis in ML1 and in primary MDS cells to a greater extent than in normal controls. While addition of (exogenous) TNF to ATO treated cells enhanced apoptosis in ML1 and RAEB cells (less in RA marrow), apoptosis was decreased in normal cells (Figure A). TNF-a induced NFkB activation in ML1 and primary MDS cells was mediated through TNFR 1, and blocking of TNFR 1 (but not TNFR2) resulted in a significant reduction of apoptosis in ML1 cells in response to ATO + TNFa, suggesting a role of TNF-α/TNFR1 in ATO-induced apoptosis. FLIP levels were down regulated in ML1 and primary MDS cells treated with ATO (or ATO plus Enbrel) in the presence of exogenous TNF; overexpression of FLIPlong in ML1 cells failed to significantly reduce ATO induced apoptosis. Conclusions: These studies show complex interactions of TNFa and ATO in MDS cells. ATO and TNF-a (TNFR1) signals may interact at the level of IkB, but the exact mechanism remains to be determined. The data obtained with Enbrel suggest that additional pathways are involved. The data also suggest that combinations of ATO and Enbrel may be exploited therapeutically in patients with MDS (showing up-regulation TNFa) by eliminating primarily clonal cells while protecting normal hemopoiesis. Download : Download high-res image (112KB) Download : Download full-size image Figure


The changing role of the Internet reader from consumer to producer of textual meanings is analyzed in the context of changing attitudes towards authors and literary works.


We review recent developments of the statistical properties of complex atomic spectra, based on the pioneering work of Claire Bauche-Arnoult and Jacques Bauche. We discuss several improvements of the statistical methods (UTA, SOSA) for the modeling of the lines in a transition array: impact of high-order moments, choice of the distribution (Generalized Gaussian, Normal Inverse Gaussian) and corrections at low temperatures. The second part of the paper concerns general properties of transition arrays, such as propensity rule and generalized J-file sum rule (for E1 or E2 lines), emphasizing the particular role of the G1 exchange Slater integral. The statistical modeling introduced by J. Bauche and C. Bauche-Arnoult for the distribution of the M values (projection of total angular momentum J) in an electron configuration, written P(M), was extended in order to account for configurations with a high-l spectator and a new analytical formula for the evaluation of the number of E1 lines with a wider range of app...


This study examined the effect of gold nanoparticles (AuNPs) on doxorubicin (DOX)-induced liver damage and steatosis in rats and tested its effect mechanism. Wistar male rats were divided into four groups (each of eight rats) as control, AuNPs (50 µL of 10 nm), DOX (15 mg/kg; 3 mg/kg/week), and DOX + AuNPs-treated rats. DOX is known to induce fasting hyperglycemia and hyperinsulinemia in treated rats. Individual treatment of both DOX and AuNPs also promoted liver damage, increased circulatory levels of ALT and AST, and stimulated serum and liver levels of TGs, CHOL, LDL-c, and FFAs. They also stimulated MDA, TNF-α, and IL-6, reduced GSH, SOD, HO-1, and CAT, upregulated mRNA levels of Bax and caspases-3 and -8 and downregulated mRNA levels of Bcl2 in the livers of rats. However, while DOX alone reduced hepatic levels of PPARα, both AuNPs and DOX stimulated mRNA levels of SREBP1, reduced the mRNA, cytoplasmic and nuclear levels of Nrf2, and increased mRNA, cytoplasmic, and nuclear levels of NF-κB. The liver damage and the alterations in all these parameters were significantly more profound when both AuNPs and DOX were administered together. In conclusion, AuNPs exaggerate liver damage, hyperlipidemia, and hepatic steatosis in DOX-treated rats by activating SREBP1 and NF-κB and suppressing the Nrf2/antioxidant axis.


Selection and integration of information based on current goals is a fundamental aspect of flexible goal-directed behavior. Motivation has been shown to improve behavioral performance across multiple cognitive tasks, yet the underlying neural mechanisms that link motivation and control processes, and in particular its effect on context-dependent information processing, remain unclear. Here, we used functional magnetic resonance imaging (fMRI) in 24 human volunteers to test whether reward motivation enhances the coding of behaviorally relevant category distinctions across the frontoparietal cortex. In a cued-detection categorization task, participants detected whether an object from a cued visual category was present in a subsequent display. Objects from one of two cued categories could serve as either Targets or High-conflict nontargets, depending on the cue on a given trial. Objects from a third category were never cued and served as Low-conflict nontargets, thus yielding three levels of behavioral status for the displayed categories (Targets, High-conflict nontargets, and Low-conflict nontargets). Half of all trials offered the possibility of a substantial reward. Multivariate pattern analysis (MVPA) showed a conflict-contingent enhancement effect of reward across the frontoparietal cortex. Reward increased the discrimination between highly conflicting behavioral status conditions, but not between less conflicting distinctions, and this selective effect was not driven by visual differences. In contrast, reward did not modulate these task-related distinctions in the high-level general object visual region, the lateral occipital complex. These findings suggest that reward modulates the representation of behaviorally relevant information only when it is most needed to successfully complete a task, and therefore facilitates an efficient allocation of attentional resources.


A liquid metal filament supported on a dielectric substrate was directed to fragment into an ordered, mesoscale particle ensemble. Imposing an undulated surface perturbation on the filament forced the development of a single unstable mode from the otherwise disperse, multimodal Rayleigh-Plateau instability. The imposed mode paved the way for a hierarchical spatial fragmentation of the filament into particles, previously seen only at much larger scales. Ultimately, nanoparticle radius control is demonstrated using a micrometer scale switch.


University spin-off firms are believed to contribute to innovation of the (regional) economy through entrepreneurship, knowledge transfer and linkages with larger firms. Social networks play a vital role in the early years of spin-off firms, but there is virtually no knowledge on the critical characteristics of these networks, and on differences between highly innovative and medium-to-low innovative spin-offs in this respect. First, we highlight theoretical viewpoints on social network formation, Next, we discuss the methodological aspects of the empirical study. This is followed by a comparative descriptive analysis of social networks and two separate estimations of job growth for highly innovative spin-offs (HIS) and medium-to-low innovative spin-offs (MLIS). The results indicate an overall smaller role of social networks for HIS, as well as a different role of strength of relationships and importance of local partners for HIS compared with MLIS.


The Modular Inversion Program (MIP) is a processing and development tool designed for retrieval and mapping of hydro-biological parameters obtained from multiand hyperspectral remote sensing measurements. The architecture of the program binds a set of general and transferable computational schemes in a chain, connecting bio-physical parameters with the measured reflected radiance. The radiative transfer is simulated in MIP for a multilayer atmosphere-ocean system using the FEM method. Results of radiative transfer calculations are stored in a sensor independent form on hard disks avoiding in this way repeated solutions of radiative transfer equation. The adjustment of algorithms to sensor specifications is supported automatically in MIP. The program modules provide for the retrieval of atmosphere and water constituents, estimation of phytoplankton primary production, water column correction and classification of surface substrates. The processing system has been tested and validated on data of surveys of German inland waters performed by several airborne and satellite sensors.


Floating wind technology is being developed rapidly with the aim of harvesting high-energy wind resources in medium and deep water areas, unreachable using fixed bottom solutions. Given the complexity of these systems, the interactions between the structure and incident hydro-aerodynamic forces need to be well understood. While numerous solutions are being explored, an optimal design is yet to be established within the industry.
 This study explores the effects of tendon inclination on the dynamic behaviour of a 10MW tension-leg platform (TLP) floating offshore wind turbine (FOWT), and the interaction of different design solutions with higher-order hydrodynamic loading. The model was subject to an extreme sea state in order to capture second and third-order wave effects, and the nonlinear waves were generated via the high-order spectral (HOS) method. The analysis was performed using the hydrodynamic engineering tool CALHYPSO, in-house developed by EDF Lab.
 Second and third order inertial hydrodynamic loads were included in the time-domain simulations in order to capture low frequency loads and ringing effects respectively. Results show that difference-frequency second order effects have a negligible impact on motions and tendon tensions of the analysed floating wind turbine model, while third order terms can significantly enhance the dynamic response of the system to extreme incident waves. While inclined-leg floater configurations presented improved motion and tendon tension responses under linear loading, the inclusion of quadratic and triple-frequency contributions showed that tendon inclination can in fact increase tension variations in the mooring lines when subject to extreme wave climates. This can lead to slacking in the mooring lines being observed more frequently in inclined-leg configurations. The results therefore suggest that neglecting third order effects, as commonly done in industry, can lead to significant underestimations of motion and tendon tension responses of tension-leg platform wind turbines.


SINGAPORE AND THE NEW REGIONALISM: BILATERAL TRADE LINKAGES WITH JAPAN AND THE US Free Trade Areas (FTAs) have recently become an integral part of Singapore trade policy. This paper discusses the reasons behind Singapore's recent embracement of "new regionalism" with particular reference to the proposals to form FTAs with Japan and the US. The paper goes on to examine various aspects of Singapore's trade linkages with the two economic superpowers in some detail. Popular discussion of FTAs gives one the appearance that such a trade policy is entirely benign. The paper sounds a cautionary note, highlighting some reasons to be concerned with Singapore's recent embracement of the "new regionalism".


This study aims to demonstrate how PTP-3 regulates SYD-2 to control UNC-104-mediated axonal transport. UNC-104 is the C. elegans homolog of kinesin-3 KIF-1A known for its fast shuttling of STVs (synaptic vesicle protein transport vesicles) in axons. SYD-2 is the homolog of liprin-α in C. elegans known to directly regulate UNC-104 as well as being a substrate of LAR PTPR (leukocyte common antigen-related (LAR) protein tyrosine phosphatase (PTP) transmembrane receptor) with PTP-3 as the closest homolog in C. elegans. CoIP assays revealed increased interaction between UNC-104 and SYD-2 in lysates from ptp-3 knockout worms. Intramolecular FRET analysis revealed that SYD-2 predominantly exists in an open conformation state in ptp-3 mutants. These assays also revealed that non-phosphorylatable SYD-2 (Y741F) exists predominately in folded conformations while phosphomimicking SYD-2 (Y741E) exists predominantly in open conformations. In ptp-3 mutants, SNB-1 cargo accumulates in soma while at the same time UNC-104 motors increasingly cluster along initial segments of axons. Interestingly, the unc-104 gene is downregulated in ptp-3 mutants that might explain the vesicle retention phenotype. More strikingly, the few visibly moving motors and STVs were overly active in neurons of these mutants. We propose a model in which the lack of PTP-3 promotes increased open conformations of SYD-2 that in turn facilitates UNC-104/SYD-2 interactions boosting motor and STVs moving speeds.


Abstract Climatic changes inferred from lacustrine deposits and lake-level fluctuations in northwestern and central China are mainly based on paleoclimatic records from the Tibetan Plateau, while there is still a lack of data relating to the semiarid/arid desert regions of Inner Mongolia. In the Tengger Desert, different paleolake levels at Baijian Hu are documented by six paleoshorelines and stratified lake carbonates. The highest lake level occurred ca. 39,000 14C yr B.P. and prevailed over about 16,000 km2. From sediment structure, geochemical composition, and ostracods we infer humid/cool conditions until 23,000 14C yr B.P. In the northern Badanjilin Desert at Gaxan Nur/Sogu Nur, high lake levels can be deduced from mollusc-bearing paleobeaches and lake carbonates, which have been dated to 34,000 14C yr B.P. and indicate a lake that covered some 32,000 km2. After ca. 20,000 yr B.P. the climate became dry with increased eolian activity and decreasing lake levels. Reestablishment of wet conditions occurred ca. 13,000 yr B.P. The Holocene is represented by stratified lake deposits that alternate with fluvial and eolian deposits, indicating a longterm oscillating trend toward arid conditions. The existence of widespread freshwater lakes during the late Pleistocene indicates a semihumid climate without an accompanying fall in temperature to arctic conditions.


BACKGROUND
As the number of women in medicine and the emphasis on prevention and primary care increase in the United States, it is important to know the extent to which female and male physicians advise patients about prevention. It is also important to know whether any gender-based differences are attributable to women's higher rates of choosing primary care specialties. Prior studies have examined only small populations of physicians, limited physician specialties, or few prevention-related outcomes.

METHODS
Telephone survey from a systematic random sample of the Physician Masterfile maintained by the American Medical Association. One thousand US physicians (167 women and 833 men); a 48% response rate. Self-reported frequency with which physicians review patients' health behaviors and initiate counseling about unhealthy behaviors.

RESULTS
Of the surveyed physicians, 44% stated that they always reviewed the patient health behaviors in question, and 36% usually systematically counseled patients when unhealthy behaviors were known. Female physicians were significantly more likely than were male physicians to report systematic counseling about unhealthy behaviors (52% vs 37.8%, P < .001, chi 2). We also analyzed our data by adjusting for age and including only family and general physicians and internists. After these adjustments, gender-based differences remained in the direction of female physicians being more likely than male physicians to report reviewing patients' health practices and providing systematic counseling, although these differences no longer reached statistical significance. Gender-related differences were greatest for more sensitive behaviors (ie, drug use and sexual behaviors). Primary care physicians were more likely than other physicians to review and counsel patients about health behaviors. This specialty-based difference was more significant among male than among female physicians.

CONCLUSIONS
In this random sample, although all physicians counseled patients inconsistently about prevention, female physicians reported systematically counseling patients more than did male physicians, and primary care physicians reviewed and counseled more often than did physicians in other specialties.


Treatment outcomes of malignant lymphoma have improved due to the discovery of novel chemotherapeutic and molecular targeted agents as well as advances in their combination uses. However, the prognosis of T-cell lymphoma remains poorer than that of B-cell lymphomas, and progress is slow. The reasons include their chemotherapeutic resistant nature and the absence of effective antibody agents for T-cell lymphomas. The number of T-cell lymphoma subtypes increased from 21 in the WHO classification 2008 to 29 in the WHO classification 2016. This means that T-cell lymphomas are heterogeneous. T-cell lymphomas can be divided to ALK-positive anaplastic lymphoma (ALCL) with a good prognosis and others with poorer prognoses. ALK-positive ALCL can be successfully treated with CHOP, but the others cannot. P-glycoprotein resistant anthracyclines, etoposide, or hematopoietic stem cell transplantations are increasingly applied to improve outcomes, but no standard treatment approach has yet been established. Regarding relapsed/refractory T-cell lymphoma, many novel agents are currently under development. The treatment outcomes of T-cell lymphoma need to be improved by applying innovative strategies including further novel agents.


The theory of holography is presented with special emphasis on the reconstruction process. The directions of the reconstructed beams and the nature of the two images are examined in detail by choosing particularly simple object beams. An interpretation in terms of phase shifts is also included.


In this case report a 10 year old Freiberger mare with a Mycobacterium avium subsp. avium infection is presented. This infection leads to a tuberculosis like disease with granulomatous alterations particularly of the intestines and lungs and is only sporadically reported in horses of Central Europe. Diarrhoea, mastitis and neck stiffness as well as dyspnoea and chronic cough are more specific symptoms of the infection, while weight loss, weakness and lethargy are nonspecific signs. As these clinical signs can occur in many other diseases, the diagnosis of mycobacterial infection is difficult and consists of rectum or distal colon biopsies and staining for acid-fast bacilli and bacteriological culture of granulomatous lesions. Classification of M. avium subsp. avium was achieved by PCR-RFLP. Even though an infection with Mycobacterium avium subsp. avium is rare, it belongs to the differential diagnosis of granulomatous diseases.


This article traces the history of the development and construction of the first prototypes and operating nuclear power plants, all as part of the Manhattan Project. Beginning with CP-1, the first self-sustained nuclear chain reaction in 1942, it details subsequent Manhattan Project reactors and then examines the construction and operation of the first modern nuclear power plants built at Hanford, Washington. These were built for the sole purpose of manufacturing plutonium for nuclear weapons. The article argues that nuclear power was born violent: it was invented as part of the manufacturing process of nuclear weaponry. This argument goes beyond previous historiography focusing on the technological development of nuclear power to emphasize the purpose of its development, the mass and indiscriminate killing of human beings.


The issue of antimicrobial resistant bacteria is a globally significant problem. At the Annual Meeting of the World Health Organization (WHO) in 2011, antimicrobial resistance (AMR) was featured as a major agenda topic. Since then, activities to recognize AMR as a global health cri-sis and to develop measures taken to combat this threat have been developed centered around the WHO. In May 2015, the World Health Assembly endorsed the Global Action Plan on AMR, and urged all member states to develop relevant national action plans within two years. In re-sponse to this, in Japan, the National Action Plan on AMR was developed accordingly by the Ministerial Meeting in April 2016. This Plan will drastically change the scope of measures taken to combat infectious diseases in the future. The framework for regional cooperation will be supported not only by an in-hospital network, but by a comprehensive regional network that involves the broad cooperation of the wider regional community. Within this framework, regional surveillance on infection control will be further improved, and will be utilized in the regional network. This will lead to further im-provements in the quality of practices taken to contain infectious diseases. On the medical front, the implementation of the Action Plan will bring significant changes to established standards for infection control in Japan. The systems and measures being developed for AMR include infection control measures not only in hospitals, but a variety of other medical settings as well, and they are being structured in a way that involves not only AMR, but a num-ber of other issues related to infectious diseases overall. This will undoubtedly have a significant impact on the establishment of a better and more sustainable healthcare environment for the fu-ture. AMR control is deeply associated with the improvement of healthcare quality and medical safety issues, and as such, the sheer importance of the critical role that infection control experts play in this effort cannot be overemphasized.


Background. Children with autism disorder show atypical preference for non-social stimuli. Therefore, the deficits of social communication and social interest are primary and usually named features for the Autism Spectrum Disorder (ASD). The main idea of the present work was to show that the physiotherapy sessions (PS) were some of the ways that could improve the physical condition of children with ADS. Moreover, the application of such programs increased self-esteem, communication skills and permitted a better adaptation and integration within society. Methods. Eleven children attending kindergarten for children with special needs participated in this investigation. The inclusion criteria were a clinical diagnosis of ASD. All participants had F 84.0 code in their cases and were specified for grade II autism disorder according to the American Psychiatric Association (2014). The investigation process consisted of four stages: the initial testing, the application of the physiotherapy program (PS), the postapplication testing and the analysis, interpretation and comparison of obtained results. The investigation process was applied for six weeks. Results. After PS applications, the children's balance improved by 21.32%, coordination – 23.36%, physical and functional abilities such as speed (13.18%) and explosive leg strength (37.14%). Conclusions. The physiotherapy sessions improved the physical condition of children with ADS: balance, coordination, functional abilities and the explosive leg strength. The capability to do physical exercises in a group, at home or in individual sessions with specialist improved as well.


CD134 (OX40), a member of the tumour necrosis factor receptor family, is expressed on activated T cells and mediates T and B cell costimulation. Its expression is increased after exposure to the thiol-binding compound HgCl2 in BN rats, but not in Lewis rats, in association with induction of a T cell-dependent systemic autoimmune syndrome only in BN rats. Intracellular thiols are involved in regulation of activation and death in T lymphocytes. Therefore, we examined intracellular thiol levels in CD134-defined T cell subsets from BN and Lewis rats. Levels of total thiols and glutathione (GSH) were significantly higher in CD134+CD4+ cells than in CD134+CD4+ cells in both strains. In Lewis rats, total thiol levels in CD4+CD134+ cells, but not in CD4+CD134+ cells, were higher than in BN rats. In contrast, BN rats showed higher GSH levels in CD4+CD134+ cells, but not in CD4+CD134+ cells. In vitro exposure to HgCl2 decreased intracellular thiol levels, predominantly in CD4+CD134+ cells. Furthermore, HgCl2-induced enrichment of CD134+ viable cells was inversely correlated to HgCl2-induced cell death. Strain-dependent differences in thiol levels in CD134-defined subsets of CD4+ lymphocytes and subset-specific modification of thiol levels may contribute to differential lymphocyte activation by oxidizing chemicals.


Because of its importance in the Andalusian business, I made a web analysis of 35 SMEs from different sectors of the PTA Malaga and it´s implementation of SMO (Social Media Optimization) to know what is the state in these SMEs. The technique used to analyze the websites of SMEs in various sectors of the PTA has been the method of content analysis. For the analysis of the sites of PTA in the implementation of the SMO, we have identified the presence or absence (presence = 1, no = 0) of eight units of analysis set out to measure the SMO: social bookmarking, web feed, blogs, broadcast content, mashups, widgets, social media buttons.  According to the results obtained by the surveyed companies, particularly SMEs PTA Malaga, have a low implementation of social media optimization in its websites.


In this chapter we want to look at different approaches to the issue of whether, and how, the international system might be changing. In doing this we concentrate on three areas of inquiry. The first is to look at how the different mainstream models of international order address the issue of transformation and we shall review realism (in the remainder of this section), liberalism (in Section 2) and Marxism (in Section 4). In between our consideration of liberalism and Marxism, however, we pause to reflect on the fact that theories of transformation inevitably acknowledge that the existing state of affairs does not exhaust the possibilities of how our world is ordered. This critical dimension of theories of transformation forms our second area of inquiry. The idea of a critical theory is first introduced as part of our discussion of liberalism in Section 2.2. Section 3 then takes up the question of the "standpoints" from which critiques are made and discusses this question in relation to post-colonial and feminist critiques of liberal claims to universality. Our third area of inquiry is concerned with those theories of transformation that take the cultural and technological sectors of the international system as their starting point. We review claims of theorists who focus on culture in Section 5 and on the technological basis of globalization in Section 6.


For multivariate functional data recorded from a sample of subjects on a common domain, one is often interested in the covariance between pairs of the component functions, extending the notion of a covariance matrix for multivariate data to the functional case. A straightforward approach is to integrate the pointwise covariance matrices over the functional time domain. We generalize this approach by defining the Frechet integral, which depends on the metric chosen for the space of covariance matrices, and demonstrate that ordinary integration is a special case where the Frobenius metric is used. As the space of covariance matrices is nonlinear, we propose a class of power metrics as alternatives to the Frobenius metric. For any such power metric, the calculation of Frechet integrals is equivalent to transforming the covariance matrices with the chosen power, applying the classical Riemann integral to the transformed matrices, and finally using the inverse transformation to return to the original scale. We also propose data-adaptive metric selection with respect to a user-specified target criterion, such as fastest decline of the eigenvalues, establish consistency of the proposed procedures, and demonstrate their effectiveness in a simulation. The proposed functional covariance approach through Frechet integration is illustrated by a comparison of connectivity between brain voxels for normal subjects and Alzheimer's patients based on fMRI data.