The effects of chopping grass silage and of mixing grass silage with concentrate on feed intake and performance in pregnant and lactating ewes, and in growing lambs were studied in two experiments (Exp. 1 and Exp. 2). The three experimental diets used in both experiments were: (1) unchopped grass silage and 0.8 kg/d concentrate, fed separately (US); (2) chopped grass silage and 0.8 kg/d concentrate, fed separately (CS); and (3) chopped grass silage mixed with concentrate to the same forage:concentrate ratio as in the CS treatment (CM). Twin bearing/suckling ewes ( n = 7 per treatment) were individually penned and individually fed during the experiments. The lambs were penned and fed in twin pairs after weaning. The silages used in Experiments 1 and 2 contained 583 and 353 g dry matter (DM) per kg, and 10.9 and 11.4 MJ ME, 139 and 193 g CP, and 580 and 483 g NDF per kg DM, respectively. In Exp. 1, daily DM intake (DMI) by ewes and LWG of lambs were unaffected by chopping silage or mixing silage and concentrate ( P > 0.05). In Exp. 2, the daily DMI by lactating ewes was 0.6 kg higher in the mixed diet compared with the separate diets (4.4 vs. 3.8 kg; P < 0.05). Suckling lambs on the chopped diets in Exp. 2, had 38 g higher daily live weight gain (LWG) than those on the unchopped diet (424 vs. 386 g; P < 0.05), whereas suck-ling lambs on the mixed diet had 63 g higher daily LWG than those on the separate diets (454 vs. 391 g; P < 0.001) resulting in 11 days younger age at slaughter ( P < 0.01). Weaned lambs fed the chopped diets in Exp. 2, had 71 g higher daily LWG than those on the unchopped diets (444 vs. 373 g; P < 0.01) resulting in 9 days younger age at slaughter ( P < 0.05). Aver-aged over treatments, the daily silage DMI of ewes increased from 1.9 to 2.8 kg in Exp. 1 and from 2.0 to 3.3 kg in Exp. 2 from late pregnancy to lactation. It was concluded that chopping highly digestible grass silage and mixing it with concentrate can increase the DMI of ewes and improve the performance of their lambs.


Software for estimating breeding values within a single step system has become available in the last years. However, approaches to approximate reliabilities for those breeding values in routine dimensions have been rare. Last year, the Genomic Reliability Working Group of Interbull presented a general step-wise framework (Interbull Standardized Genomic Reliability Method, ISGRM) for approximating reliabilities which is applicable to two-step as well as to single-step models. For assessing the accuracy of the approach and its performance in the different steps, a small test data set (16.5k individuals in the pedigree, 4.3k of them with phenotypes, 5.8k of them genotyped) was created. Exact theoretical single step reliabilities could be obtained for this set via numerical inversion of the total system. These reliabilities were compared with values obtained with ISGRM. Results looked very promising for the genotyped individuals, while they were not completely satisfying for non-genotyped individuals in this data set. The lines of action of calculating effective record contributions for the genomic reference set and of considering the residual polygenic contribution were identified to have an influence on the performance. For larger routine data sets, however, not only the quality of the results, but also the possibility that all necessary calculations can be performed in a reasonable time frame with given hardware and software configurations is important. We thus assessed approximation options for different steps of ISGRM with the software ApaX99 and options to calculate reliabilities of direct genomic values via SNP reliabilities with the snp_blup_rel program. Performance testing in a routine data set for conformation traits in Fleckvieh cattle (~ 3.3M individuals in pedigree, ~ 1.4M of them with phenotypes, 78k of them genotyped) revealed that only the first step, namely the numerical inversion of a system with dimension n SNPs x n SNPs , is computationally demanding (took ~ half an hour time and 38 GB RAM in the given data set). All other steps could be performed without any larger memory or CPU requirements in very short time.


Polyclonal antilymphocytic preparations, heterologous antibodies to human lymphoid cells, have been administered to heart transplant recipients prophylactically in the immediate perioperative period to avert rejection. The current status of the three classes of polyclonal preparations (antilymphoblast globulins, antithymocyte globulins, and antithymocyte sera) and their clinical role for prophylaxis in heart transplantation are summarized.


Multiwall and singlewall carbon nanotubes were synthesized on Fe-Co/CaCO3 and a Fe-Co/MgO catalyst systems, respectively, by using two different catalytic chemical vapor deposition methods, external furnace (EF) heating and radio frequency (RF) excitation. The carbon nanotubes synthesized with radio frequency excitation have a smaller outer diameter, fewer layers (smaller outer/inner diameter ratio), and better crystalline properties, compared to the nanotubes grown with external furnace heating. The radio frequency process was found to be responsible for a faster growth rate of the carbon nanotubes over longer periods of time due to a higher localized heating. These findings can be explained by the skin currents induced in the metallic catalytic clusters, which keep the catalysts active for longer periods of time and diminishes the amount of non-crystalline carbon formed in the synthesis process. A direct correlation between the frequency of the electromagnetic field and the morphology of the nanotubes was also found.


The long-term effects of impairment have a negative impact on the quality of life of stroke patients in terms of not using the affected limb even after some recovery (i.e., learned non-use). Immersive virtual reality (IVR) has been introduced as a new approach for the treatment of stroke rehabilitation. We propose an IVR-based therapeutic approach to incorporate positive reinforcement components in motor coordination as opposed to constraint-induced movement therapy (CIMT). This study aimed to investigate the effect of IVR-reinforced physical therapy that incorporates positive reinforcement components in motor coordination. To simulate affected upper limb function loss in patients, a wrist weight was attached to the dominant hand of participant. Participants were asked to choose their right or left hand to reach toward a randomly allocated target. The movement of the virtual image of the upper limb was reinforced by visual feedback to participants, that is, the participants perceived their motor coordination as if their upper limb was moving to a greater degree than what was occurring in everyday life. We found that the use of the simulated affected limb was increased after the visual feedback enhancement intervention, and importantly, the effect was maintained even after gradual withdrawal of the visual amplification. The results suggest that positive reinforcement within the IVR could induce an effect on decision making in hand usage.


Discovering molecules with a desired biological function is one of the great challenges in drug research. To discover new lead molecules, virtual screens (VS) are often conducted, in which databases of molecules are screened for potential binders to a specific protein, using molecular docking. The choice of docking software and parameter settings within the software can significantly influence the outcome of a VS. In this study, we have applied chemometric methods such as design of experiments, principal component analysis and partial least‐square projections to latent structure (PLS) to simulated VS experiments to find and compare suitable conditions for performing VS against six protein targets selected from the DUD databases. The docking parameters in FRED, and scoring functions in both FRED and GOLD docking software, were varied according to a statistical experimental design and a PLS model was calculated to correlate the experimental setup to the VS outcome. The study revealed that the choice of scoring function has the greatest influence on VS outcome, and that other parameters have varying influence, depending on the protein target. We also found that substantial bias can be introduced by the lack of variation of molecular properties in the databases used in the screening. Our results provide indications that docking experiments could be tailored to the protein target in order to obtain satisfactory VS results. Copyright © 2010 John Wiley & Sons, Ltd.


The purpose of this study is to identify which personal, familial, environmental, and social factors are associated with the utilization of child protection services, including parental support programs, by mothers who misuse illicit substances. Participants are 56 mothers with substance use and addiction-related problems, of whom 32 were receiving, voluntarily or otherwise, child protection services while 24 mothers had psychotropic drug use-related problems but were receiving no psychosocial services. Data were collected in the province of Quebec, Canada, between August 1998 and August . Results indicate that mothers who receive services are younger, have fewer interpersonal resources, live in lower socioeconomic conditions, and have greater family dysfunction (less parental supervision and more inconsistent discipline) than mothers who do not receive services from child protection agencies. However, there are no significant differences between groups with regards to maternal childhood trauma, psychological distress, antisocial behavior and the quality of the parent–child bond. The results of this study suggest that although both groups misuse drugs and have personal difficulties, some mothers will not need support from social services to take care of their children. Implications of these findings for prevention are discussed. The study's limitations are noted.


This short monograph in English details the legal problems inherent in the management of alcoholism. The background of increasing alcohol consumption, particularly of spirits, is described and this is followed by a discussion of the criminal responsibility of those who commit crimes whilst under the influence of alcohol. Familiar models in English law appear in less familiar, but still recognizable, guises in Polish law. The author is driven to the conclusion that the fact that a criminal act is committed when under the influence of alcohol should not be regarded as a mitigation, but an aggravation of the offence. Other conclusions from this approach follow, particularly the need for rehabilitation of the alcoholic offender. The author deals too with the problem of prevention and the activities of the rights of the representative of the anti-alcoholic social committee — a peculiarly Polish institution. D. R. CHAMBERS


High retrieval precision in content-based image retrieval can be attained by adopting relevance feedback mechanisms. These mechanisms require that the user judges the quality of the results of the query by marking all the retrieved images as being either relevant or not. Then, the search engine exploits this information to adapt the search to better meet user's needs. At present, the vast majority of proposed relevance feedback mechanisms are formulated in terms of search model that has to be optimized. Such an optimization involves the modification of some search parameters so that the nearest neighbor of the query vector contains the largest number of relevant images. In this paper, a different approach to relevance feedback is proposed. After the user provides the first feedback, following retrievals are not based on k-nn search, but on the computation of a relevance score for each image of the database. This score is computed as a function of two distances, namely the distance from the nearest non-relevant image and the distance from the nearest relevant one. Images are then ranked according to this score and the top k images are displayed. Reported results on three image data sets show that the proposed mechanism outperforms other state-of-the-art relevance feedback mechanisms.


Health prophylaxis is a strategic priority in every health care system. This research aims at surveying the prophylactic and medical activity of the elderly and the old. An anonymous survey of 340 people aged 60 and over was conducted in "Haskovo Hospital" for a period of one year. The collected data provide grounds for concluding that health prophylaxis as a direct reflection of health education, and health awareness is not adequately utilized or offered medical activity, which is fundamental to achieving better health, preventing diseases and premature ageing. The percentage of elderly and old people who go through regular preventive medical check-ups is highly unsatisfactory. This puts forward significant problems connected with the organization of prophylaxis, the lack of health motivation, negligence towards prophylaxis, passive and irresponsible attitude.


Machine Learning (ML) adoption in the enterprise requires simpler and more efficient software infrastructure---the bespoke solutions typical in large web companies are simply untenable. Model scoring, the process of obtaining predictions from a trained model over new data, is a primary contributor to infrastructure complexity and cost as models are trained once but used many times. In this paper we propose HUMMINGBIRD, a novel approach to model scoring, which compiles featurization operators and traditional ML models (e.g., decision trees) into a small set of tensor operations. This approach inherently reduces infrastructure complexity and directly leverages existing investments in Neural Network compilers and runtimes to generate efficient computations for both CPU and hardware accelerators. Our performance results are intriguing: despite replacing imperative computations (e.g., tree traversals) with tensor computation abstractions, HUMMINGBIRD is competitive and often outperforms hand-crafted kernels on micro-benchmarks on both CPU and GPU, while enabling seamless end-to-end acceleration of ML pipelines. We have released HUMMINGBIRD as open source.


Urban rats present a global public health concern as they are considered a reservoir and vector of zoonotic pathogens, including Escherichia coli. In view of the increasing emergence of antimicrobial resistant E. coli strains and the on-going discussion about environmental reservoirs, we intended to analyse whether urban rats might be a potential source of putatively zoonotic E. coli combining resistance and virulence. For that, we took fecal samples from 87 brown rats (Rattus norvegicus) and tested at least three E. coli colonies from each animal. Thirty two of these E. coli strains were pre-selected from a total of 211 non-duplicate isolates based on their phenotypic resistance to at least three antimicrobial classes, thus fulfilling the definition of multiresistance. As determined by multilocus sequence typing (MLST), these 32 strains belonged to 24 different sequence types (STs), indicating a high phylogenetic diversity. We identified STs, which frequently occur among extraintestinal pathogenic E. coli (ExPEC), such as STs 95, 131, 70, 428, and 127. Also, the detection of a number of typical virulence genes confirmed that the rats tested carried ExPEC-like strains. In particular, the finding of an Extended-spectrum beta-lactamase (ESBL)-producing strain which belongs to a highly virulent, so far mainly human- and avian-restricted ExPEC lineage (ST95), which expresses a serogroup linked with invasive strains (O18:NM:K1), and finally, which produces an ESBL-type frequently identified among human strains (CTX-M-9), pointed towards the important role, urban rats might play in the transmission of multiresistant and virulent E. coli strains. Indeed, using a chicken infection model, this strain showed a high in vivo pathogenicity. Imagining the high numbers of urban rats living worldwide, the way to the transmission of putatively zoonotic, multiresistant, and virulent strains might not be far ahead. The unforeseeable consequences of such an emerging public health threat need careful consideration in the future.


There is increasing observational and theoretical evidence for a correlation between the metallicity and the mass of the stellar halo for galaxies with Milky Way-like stellar masses. Using the Illustris cosmological hydrodynamical simulations, we find that this relationship arises because a single massive massive progenitor contributes the bulk of the mass to the accreted stellar component as well as sets its metallicity. Moreover, in the Illustris simulations, this relationship extends over 3 orders of magnitude in accreted stellar mass for central galaxies. We show that for Milky Way-like mass galaxies, the scatter in accreted metallicity at a fixed accreted stellar mass encodes information about the stellar mass of the dominant accreted progenitor, while the radial density and metallicity gradients of the accreted stellar component encodes information about the time of accretion of the dominant progenitor. We demonstrate that for Milky Way-like mass galaxies, the Illustris simulations predict that the metallicity and the stellar mass of the total accreted stellar component can be reconstructed from aperture measurements of the stellar halo along the minor axis of edge-on disk galaxies. These correlations highlight the potential for observational studies of stellar halos to quantify our understanding of the most dominant events in the growth history of galaxies. We explore the implications of our model for our understanding of the accretion histories of the Milky Way, M31 and NGC 5128. In particular, a relatively late and massive accretion is favoured for M31; additionally, we provide a first estimate of the accreted stellar mass for NGC 5128.


A direct problem consists in evaluating the optimal control to apply to an object directed towards its destination point (DP) by minimizing a pre-defined cost functional. An inverse problem can also be considered by estimating the DP of an object directed towards a complex environment when no possibility is given to control it. The control behavior of the object can be simulated by processing its kinematic data. So, the application of optimal control theory to solve this problem is quite unusual: the main contribution of this work is to use the hypothesis of a conventional control law for the object (proportional navigation law) and to compare it to advanced control laws derived from the optimal control theory. Moreover the use of optimal control in DP estimation seems to be a convenient way to detect particular behaviors discriminating the DP among possible ones.<<ETX>>


Utilizing large-scale Monte Carlo simulations, we investigate an unconventional two-component classical plasma in two dimensions which controls the behavior of the norms and overlaps of the quantum-mechanical wave functions of Ising-type quantum Hall states. The plasma differs fundamentally from that which is associated with the two-dimensional XY model and Abelian fractional quantum Hall states. We find that this unconventional plasma undergoes a Berezinskii-Kosterlitz-Thouless phase transition from an insulator to a metal. The parameter values corresponding to Ising-type quantum Hall states lie on the metallic side of this transition. This result verifies the required properties of the unconventional plasma used to demonstrate that Ising-type quantum Hall states possess quasiparticles with non-Abelian braiding statistics.


BACKGROUND: Extensive efforts have been made toward reducing postoperative opioid use in children. In this study, we assessed whether propacetamol, or a nonsteroidal anti-inflammatory drug (NSAID), or their combination could effectively reduce opioid use in children after laparoscopic inguinal hernia repair. METHODS: This randomized, double-blind clinical trial included 159 children aged 6 months to 6 years. Children were allocated into 1 of the following 3 groups: group I was treated with 10 mg·kg−1 ibuprofen, group P was treated with 30 mg·kg−1 propacetamol, and group I + P was treated with both drugs in their respective concentrations. If the face–legs–activity–crying–consolability (FLACC) score was ≥4 during the postanesthesia care unit stay, 1.0 µg·kg−1 fentanyl was administered as a rescue analgesic. The number of patients who received rescue fentanyl in the postanesthesia care unit was defined as the primary outcome; this was analyzed using the χ2 test. The secondary outcomes included the FLACC and the parents' postoperative pain measure (PPPM) scores until the 24-hour postoperative period. RESULTS: Among the 144 enrolled patients, 28.6% in group I, 66.7% in group P, and 12.8% in group I + P received rescue fentanyl in the postanesthesia care unit (P < .001). The highest FLACC score was lower in group I + P than in either group I or P (P = .007 and P < .001, respectively). Group I + P presented significantly lower PPPM scores than group P at 4 and 12 hours postoperative (P = .03 and .01, respectively). CONCLUSIONS: The use of ibuprofen plus propacetamol immediately following laparoscopic hernia repair surgery in children resulted in the reduced use of an opioid drug compared with the use of propacetamol alone.


Reducing emissions from deforestation and forest degradation in developing countries, and the role of conservation, sustainable management of forests, and enhancement of forest carbon stocks in developing countries (REDD+) is a potentially powerful international policy mechanism that many tropical countries are working towards implementing. Thus far, limited practical consideration has been paid to local rights to forests and forest resources in REDD+ readiness programs, beyond noting the importance of these issues. Previous studies have shown that community members can reliably and cost-effectively monitor forest biomass. At the same time, this can improve local ownership and forge important links between monitoring activities and local decision-making. Existing studies have, however, been static assessments of biomass at one point in time. REDD+ programs will require repeated surveys of biomass over extended time frames. Here, we examine trends in accuracy and costs of local forest monitoring over time. We analyse repeated measurements by community members and professional foresters of 289 plots over two years in four countries in Southeast Asia. This shows, for the first time, that with repeated measurements community members' biomass measurements become increasingly accurate and costs decline. These findings provide additional support to available evidence that community members can play a strong role in monitoring forest biomass in the local implementation of REDD+.


Pazopanib, under the trade name of votrient, is a potent tyrosine-kinase growth factor receptor inhibitor used in the treatment of late-stage kidney cancer and soft tissue sarcoma. Rarely this drug has been associated with gastrointestinal perforations; however, prior studies have not shown an association with necrotizing fasciitis. We present a case of suspected pazopanib-induced extensive colonic perforation resulting in a severe necrotizing fasciitis. As this is a potentially rare complication of this targeted therapy, our goal is to heighten the awareness of colonic perforation as it is only seen in 0.9% of patients on pazopanib. The staged operative management and multidisciplinary approach throughout this patient's care allowed for complete recovery from a life-threatening diagnosis. J Curr Surg. 2020;10(3):54-58 doi: https://doi.org/10.14740/jcs416


The junior level control lab is an important component of the electrical engineering curriculum at the University of Nevada, Reno. Its serves to familiarize the student with the design simulation and analysis of control systems. The emphasis is on the basics and advanced theoretical concepts are avoided. The electronic instruments used in the lab are all capable of interaction with personal computers through the HP interface bus. This creates an integrated lab environment that combines data acquisition and analysis. The major topics considered in the lab are transducers, circuit implementation of controllers, mathematical modeling, computer aided design and simulation of control systems.


The aim of this study was to perform a clinical and immunohistochemical comparison between simultaneous independent tumors involving endometrium and ovary and metastatic endometrial tumors, and to try to find clinical and /or immunohistochemical parameters differentiating between these two entities. Sixteen cases of simultaneous independent primaries of endometrium and ovary, presenting the same histologic type, were compared with 12 cases of primary endometrial cancer, demonstrating ovarian metastases. The comparison related to patients' characteristics and immunohistochemical expression of estrogen and progesterone receptors (ER,PR), bcl-2, HER-2 /neu, p53, and cell proliferation marker Ki-67 in endometrial and ovarian tumors. The only clinical parameter differentiating significantly between the groups was the prevalence of familial cancer, being more frequent in the group of metastatic tumors (P = 0.03). Immunohistochemical analysis demonstrated the same immunostaining in endometrium and ovary for all immunohistochemical parameters in cases of metastatic endometrial cancer. Conversely, 62.5% of cases with simultaneous tumors of endometrium and ovary could be differentiated from metastatic tumors by distinct immunohistochemical expression of ER and PR in endometrial and ovarian tumors (P = 0.0006), and 31.3% of cases could be differentiated by distinct immunostaining for bcl-2 (P = 0.03). Immunohistochemical parameters HER–2 /neu, p53 and Ki-67 were not appropriate for the distinction between the two study groups. We conclude that the application of immunohistochemical analysis may play an important role in the differentiation between cases of simultaneous independent carcinomas of endometrium and ovary vs. cases of endometrial carcinoma with ovarian metastases.


In this study, classification of Normal and Extra systolic heart sounds (HS) have been carried out using in PASCAL Heart Sounds (HS) data base. The extrasystole is the HS that is produced by performing an extra beat in each heart cycle, unlike the heartbeat normal cycle. It can be felt by people as palpitations. Occurrence of these sounds in certain age groups may be the indication of tachycardia. In this study, firstly HS have been normalized at first. Then an elliptic filter has used for noise reduction. HS features have been obtained using Mel-Frequency Cepstrum Coefficients. These features have classified using Artificial Neural Network. In this study, 45 extra systoles heart sounds have used. 30 of them have been used as training data for classification while remaining 15 ones have been used for the test. Certainty, sensitivity, accuracy values have been calculated using confusion matrix. Classification success has been calculated as 90%.


Summary The glucose analog, 2-desoxy-d-glucose (2DG), has been shown to inhibit the anaerobic and aerobic glycolysis of glucose (glucolysis) by slices of the rat tumors, Flexner-Jobling carcinoma and Walker 256 carcinoma. The anaerobic glucolysis of slices of rat brain and sections of rat diaphragm was also inhibited by 2DG. Brain was about 7.5 times more sensitive to 2DG than was tumor. Diaphragm was intermediate between brain and tumor in sensitivity toward 2DG. The type of inhibition appeared to be competitive, since inhibition was reversed by increased glucose in the case of tumor and brain. 2DG also inhibited the anaerobic glycolysis of fructose (fructolysis) by tumor tissue slices. Tumor fructolysis was at least 50 times more sensitive to 2DG than was tumor glucolysis. The anaerobic fructolysis of liver was also inhibited by 2DG, but was about 100 times less sensitive to 2DG than was tumor fructolysis. 2DG did not significantly inhibit the endogenous respiration in any of the tissues studied. Oxidation of glucose by brain tissue slices was inhibited only by a very high proportion of 2DG to glucose, while oxidation of fructose was about 100 times more sensitive to 2DG than was oxidation of glucose. The possibility is discussed that 2DG in vivo might have a selective inhibitory effect on tumor metabolism.


AbstractThis paper presents a comparison of three methods used to load rate the Powder Mill Bridge based on the load and resistance factor rating (LRFR) approach. This is a typical three-span continuous bridge with steel girders in composite action with the RC bridge deck. The three methods are as follows: (1) employing the conventional design office load rating technique using a simplified line girder analysis, (2) using strain measurements from a diagnostic load test to adjust the design office rating to account for in-situ bridge behavior, and (3) using a finite-element (FE) model of the bridge, which accounts for three-dimensional (3D) structural system behavior. Advantages and disadvantages of each method are related to speed, ease of use, reviewability, cost, accuracy, and type of use intended. Similarities and differences in utilizing these three methods are discussed. The advanced load rating methods are shown to produce higher ratings in comparison with the conventional approach.


The feasibility of pegylating peptides by the solid-phase procedure was examined. Although polyethyleneglycol (PEG) was shown to be partially degraded by HF, the use of TFA was fully compatible with the PEG system. Therefore, the Fmoc/tBu solid-phase strategy was utilized for the synthesis of a series of model tetra-, octa- and dodecapeptides, and the corresponding N alpha-pegylated peptides, which were prepared from common peptide-resin intermediates. PEG-OCH2-CO-Nle-OH, 3, proved to be an ideal reagent for N-terminal pegylation. This intermediate served as a diagnostic for the determination of the number of PEG units/mole of peptide. Solid-phase coupling reactions proceeded by standard procedures using BOP-activation. The authentic pegylated peptides (readily purified by conventional methods of preparative HPLC) were fully characterized by amino acid analysis, 1H-NMR spectroscopy, analytical HPLC and laser desorption ionization mass spectrometry, leading to the values that are identical with the expected structures.


This clinical study of 382 patients with temporomandibular dysfunction (TMD) details how successful treatment can be achieved in a rural area without the support and services of specialized TMD clinics. Successful treatment is within the scope of the general dentist, provided the practitioner understands the patient's total problem and treatment options. The study spanned a 10-year period, including follow-up at one, five, and eight-year intervals.


Amsterdam, as distinguished from Ian McEwan"s other novels, stands out for its highlight of temporality and the implied urgency to tackle one"s moral identity. Namely, the novel is concerned with waiting: McEwan shows Clive consistently pressurized by the deadlines of submitting his symphony for rehearsal and Vernon rather obsessed with the day of exposing Garmony"s pictures. Such waiting forces them to make decisions, and the decisions invariably suggest applications of values and attitudes. The overriding temporal frame of the novel is even more evocative. Readers are reminded over and again, along with Clive, that a new millennium is ahead (the novel itself was first published in 1998). In light of this, the author appears to juxtapose two temporal structures: the time of mundanity for the characters and a time that is messianic and affranchising, thus stressing an ethical vision, possibly beyond what the self-centered British society in the novel can foresee. All the underlying attention to temporal expressions and the foregrounded contingency of life only reinforces the author"s call for moral inquiries and search for accountable, ethical stances in an era of flux and disintegration. To study the ethical terrain as depicted in the novel, this paper focuses on the ideas of friendliness and enmity and analyzes the interaction between its four male characters. They remain friends, Clive and Vernon in particular, but underneath are the on-going processes of defining and re-defining friendship and the tempting of ethical limits. It is then contended that the author"s moral position in the novel tends toward the Derridean unconditional hospitality and, therein conventional understanding of friends and enemies is hardly tenable, requiring, therefore, conceptual revision. To bring home this view, this paper first interprets friendliness and enmity by virtue of Jacques Derrida"s theorization of hospitality and next examines the characters" mutual engagement following the Derridean perspective. One comes to realize that the novel is aptly a tale of hospitality, with friendship


On the 10th of October 1881 the Brisbane, a large, modern and well equipped steamship carrying passengers and cargo struck Fish Reef, approximately 25 nautical miles from Port Darwin, and became permanently stranded. What followed over the next three months was an organised salvage programme in which the ship was salvaged of cargo, equipment and fittings. These goods were sold to Port Darwin locals through a series of auctions. The wreck provided a wide selection of second-hand goods to a small isolated community. Approximately one hundred years later locals return to this wreck to take objects they considered of value. This thesis is a case study in material culture salvage and reuse of material from the Brisbane. Local men purchased the wreck in 1881 and presided over an extensive salvage programme in which maritime technical equipment and a range of other equipment, furnishings and fittings were removed, sold and reused. Some items were not salvaged and were left on the wreck site, these being visible today. The decision of salvors to not reuse some machinery and equipment challenges broad assumptions that isolated pioneer settlements, with poor access to goods, without fail practiced full scale salvage and reuse out of necessity. This thesis examines what was taken, why it was selected and how it was used. Recent cases of salvage in which objects are valued as historic ornaments are analysed in detail to demonstrate that there is no consensus to either the historic value of this wreck or its objects. Analysing the kinds of qualities attributed to historic ornaments, identifying them for example as antiquities or curios, reflect different ways in which people engage with the past. A comparison of salvage in 1881 to that more recent shows change in how salvage and reuse have functioned as social mechanisms. This thesis emphasises that object transformations may not involve physical modification, and that object meaning is relevant to a specific time and place.


Effects related with the attenuation and deflection suffered by an electron beam when it passes through a carbon conductive coating and an oxide film layer on the surface of bulk samples are studied by Monte Carlo simulations and energy dispersive spectroscopy with electron excitation. Analytical expressions are provided for the primary beam energy and intensity losses and for the deflection of the incident electrons in both layers, in terms of the incidence energy, the film mass thicknesses, and the atomic number of the oxidized element. From these analytical expressions, suitable corrections are proposed for the models used to describe the X-ray spectrum of the substrate, including also the contribution of the X-rays generated in the oxide and conductive films and the characteristic X-ray absorption occurring in those layers. The corrections are implemented in a software program for spectral analysis based on a routine of parameter refinement, and their influence is studied separately in experimental spectra of single-element standards measured at different excitation energies. Estimates for the layer thicknesses are also obtained from the spectral fitting procedure.


Sequential decision making for lifetime maximization is a critical problem in many real-world applications, such as medical treatment and portfolio selection. In these applications, a "reneging" phenomenon, where participants may disengage from future interactions after observing an unsatisfiable outcome, is rather prevalent. To address the above issue, this paper proposes a model of heteroscedastic linear bandits with reneging, which allows each participant to have a distinct "satisfaction level," with any interaction outcome falling short of that level resulting in that participant reneging. Moreover, it allows the variance of the outcome to be context-dependent. Based on this model, we develop a UCB-type policy, namely HR-UCB, and prove that it achieves $\mathcal{O}\big(\sqrt{{T}(\log({T}))^{3}}\big)$ regret. Finally, we validate the performance of HR-UCB via simulations.


The study investigated the knowledge produced by the Brazilian masters degree programs in Nursing about the elderly's thematic, between 1979 and 2004. The bibliographical research consulted the summaries of dissertations and theses on elderly classified by the Center of Studies and Researches in Nursing. Of 118 found studies, 81% were dissertations and 19% were theses. Between 2000 and 2004 there was the largest presentations/defenses number (59) and the University of São Paulo revealed the largest number of researches (43.6%). More than 70% of the authors used qualitative approach and about 58% approached the elderly individually, emphasizing him under the optics of some disease or disturbance (28%), and hospitalized elderly. Researches involving ethics or promoting your development social or intellectual was not evidenced. It's ended that gaps exist in the Brazilian nurse's scientific production, that should seek better contribution in the search of solutions for the problems of the elderly population.


ABSTRACT In this paper, we take a fresh look at the magnitude of the trade-off between caring informally for a parent and paid work. We adopt a simultaneous approach with a primary focus on how hours of care are influenced by hours of work rather than the other way round. We also investigate the role that filial obligations play in choices of caring versus working. Using the SHARE data (2004 and 2006) we find that the elasticity of informal care hours in response to working hours is between −0.17 in the caregivers sample and −0.19 in the women-only caregivers sample; small but not negligible. Moreover, we find that a 10%increase in the index measuring the strength of filial obligations increases weekly hours of care by about two and a half hours.


In recent literature, different approaches have been proposed to use graphemes as subword units with implicit source of phoneme information for automatic speech recognition. The major advantage of using graphemes as subword units is that the definition of lexicon is easy. In previous studies, results comparable to phoneme-based automatic speech recognition systems have been reported using context-independent graphemes or context-dependent graphemes with decision trees. In this paper, we study both context-independent and context-dependent grapheme-based automatic speech recognition systems. Experimental studies conducted on American English continuous speech recognition task show that systems using context-independent grapheme units perform fairly poor, while their performance can be improved by incorporating phonetic knowledge. However, systems using only context-dependent graphemes can yield competitive performance (even better) when compared to state-of-the-art phoneme-based automatic speech recognition.


A backlash compensator is designed for systems using the fuzzy logic. The classification property of fuzzy logic systems makes them a natural candidate for the rejection of errors induced by the backlash, which has regions in which it behaves differently. A tuning algorithm is given for the fuzzy logic parameters, so that the backlash compensation scheme becomes adaptive, guaranteeing small tracking errors and bounded parameter estimates. Formal nonlinear stability proofs are given to show that the tracking error is small. The fuzzy logic backlash compensator is simulated on a system to show its efficacy.


Necrotizing histiocytic lymphadenitis (NHL) or Kikuchi-Fujimoto disease is an infrequent seen clinicopathologic entity that affects most frequently young women and individuals of eastern races, and that is characterized by fever and adenopathies (basically cervical) and systemic disease even though occasional patients present extranodal disease. We present two young women with NHL and cutaneous affectation, and with lymphocytic meningitis in one of the patients. We discuss the etiology of NHL, the relation of NHL with collagen-vascular diseases (basically systemic erythematous lupus) the problem of the pathologic diagnosis, and the therapeutic possibilities in these patients.


A program of respiratory muscle sparing in 9 patients with late stage Duchenne muscular dystrophy is presented. Results indicate that regular efficient night-time support by body respirator provides a constant significant improvement in daytime gas exchange for periods averaging up to 2 years following the occurrence of moderately severe respiratory failure. Until now, the longest survival is more than 4 years at the age of 28. the average PaCO2 and PaO2 before night ventilation were 60.8mmHg and 59.3mmHg, respectively. The levels after the program was begun were 45.5 (PaCO2) and 74.6 (PaO2). These arterial blood gas levels are acceptable for good cardiopulmonary homeostasis. There have been no deaths or episodes of cardiac failure since the program began. The ease of integrating the program into the patient's lifestyle and home are important advantages. Cost of equipment is discussed. The view that these patients are terminal must be qualified. A case is also made for early aggressive conservative measures including body respirators, postural drainage, chest physiotherapy with abdominal assisted coughing, intratracheal suctioning and bronchoscopy to combat respiratory infection, and decreasing the need of tracheostomy and volume ventilators which can be so disabling to the chronic restrictive lung disease (CRLD) patient. Research and development into better design of body respirators is vitally needed. Acute care hospitals must prepare themselves for such patients who now attain more independent living and longer lifespan. For this reason there is a growing need for these facilities to acquire tank ventilators for handling such patients who may need hospitalization for acute medical complications.


A four year old Mexican American girl is taken away from her parents because she is obese and experiencing health problems related to her weight. Such a measure, once seen as extreme, quickly comes to be seen as a logical means of addressing a problem viewed as nothing short of child abuse. And yet, for all the purported concern for these children s welfare, little if any mention is ever made of the psychological ramifications of removing children from their families. They are simply the latest victims of the war on obesity a war declared on a disease but conducted, April Herndon contends in this book, along cultural lines. "Fat Blame" is a book about how the war on obesity is, in many ways, shaping up to be a battle against women and children, especially women and children who are marginalized via class and race. While conceding that fatness can be linked to certain conditions, or that some populations might be heavier than others, Herndon is more interested in the ways women and children are blamed for obesity and the ways interventions aimed at preventing obesity are problematic in and of themselves. From bariatric surgeries being performed on children to women being positioned as responsible for carrying to term a generation of thin children, her book looks closely at the stories of real people whose lives are drastically altered by interventions that are supposedly for their own good. As with so many practices surrounding bodies and health, like dieting, people are often simultaneously blamed and empowered through policies and interventions, especially those that seem to offer them choices. What Herndon reveals is how such choices only offer the illusion of being empowering. Rather, she shows how woman and children are pushed, pulled, and sometimes victimized by interventions such as bariatric surgeries, limits on reproductive technologies, and having their families broken up by the courts. Only by identifying members of this group as victims of discrimination, she argues, can we hope to return them to a fuller and richer kind of agency. In declaring a war on obesity, the United States has said that fat is one of the most serious enemies it faces. "Fat Blame" asks us to confront the real enemy the moral, political, and ideological significance of our every move in this war. "


This research introduces a newly developed continuous improvement methodology called Design for Availability that uses principles of Lean Sigma and Design for X to cost-effectively optimize the availability of capital goods, i.e. systems used in the production of other end-products or -services, throughout their entire lifetime. The absence of such a methodology in the literature is remarkable because many users of capital goods increasingly insist on high system availability levels against lower lifetime costs. Against this background this study develops an analytical framework that allows manufacturers to determine the current status of system availability and associated lifetime costs, and to identify opportunities to create additional value for both the manufacturer and its customers. The applicability of this Design for Availability framework is tested through a case study at a global manufacturer of capital goods in the food processing industry. The results show that applying the Design for Availability framework can provide substantial benefits for the manufacturer as well as its customers, as long as a number of critical key success factors are taken into account during implementation, such as organizational commitment to Design for Availability, good leadership and communication, and creating system availability and lifecycle awareness.


: Rats hypophysectomized at the age of four weeks continued to grow at a delayed rate during the whole fourteen month's observation period. A spontaneous development of the sexual apparatus was noted in some of the hypophysectomized animals: an increase in the weight of the testes, of the ventral prostate and of the seminal vesicles. In fourteen months the peripheral endocrine glands retained their sensitivity to the tropic hormones of the hypophysis; a ten-day adminstration of a corresponding tropic hormone led to a double increase in weight of the dependent endocrine gland and a sharp elevation of its functional activity.


In "History of Animals," Aristotle analyzes differences in parts, activities, modes of life, and character across the animal kingdom, in preparation for establishing their causes, which are the concern of his other zoological works. Over 500 species of animals are considered: shellfish, insects, birds, fish, reptiles, amphibians, and mammals including human beings. In Books I IV, Aristotle gives a comparative survey of internal and external body parts, including tissues and fluids, and of sense faculties and voice. Books V VI study reproductive methods, breeding habits, and embryogenesis as well as some secondary sex differences. In Books VII IX, Aristotle examines differences among animals in feeding; in habitat, hibernation, migration; in enmities and sociability; in disposition (including differences related to gender) and intelligence. Here too he describes the human reproductive system, conception, pregnancy, and obstetrics. Book X establishes the female s contribution to generation. The Loeb Classical Library(r) edition of "History of Animals" is in three volumes. A full index to all ten books is included in the third (Volume XI of the Aristotle edition


Synopsis: What are the consequences of the rise of mediated or indirect channels linking parties and the electorate in modern and post-modern campaigns? Critics commonly blame the mass media (and particularly the role of television) for many of the supposed ills of representative democracy, from public disenchantment with elected leaders to increasing detachment from party loyalties, lack of awareness of public affairs, and half-empty empty ballot boxes. The argument presented in this study has three core components. Firstly, long-term evidence of trends in American elections over the last fifty years demonstrates that reports of the ill health, or even death, of traditional partisan channels of campaign communication are grossly exaggerated. Secondly evidence from the 2000 Bush-Gore US presidential elections confirms that far from 'blaming the messenger', the role of exposure to campaign information from parties, newspapers, television news, talk radio, and the Internet has been to strengthen civic engagement in America. Lastly, expanding upon previous work, the study considers the role of popular television entertainment in this process. P O L I T E I A C O N F E R E N C E — M A Y 3 2 0 0 2


BACKGROUND: Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value. OBJECTIVES: To systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome. METHODS: PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR+, LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed. RESULTS: We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR=2.08, 95%CI=1.48-2.94, I2=93%, N=8), hypernatremia (OR=4.32, 95%CI=3.17-5.88, I2=45%, N=7) and hypocalcemia (OR=3.31, 95%CI=2.24-4.88, I2=25%, N=6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR+ 4.0, PPV=55%, AUC=0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV=87%, AUC=0.71). Overall quality of evidence ranged from very low to moderate. CONCLUSION: Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.


The organizational capabilities to interact with others have been greatly improved as a result of modern information and communications technologies: Nowadays a company can maintain more relationships with more companies at much lower costs than before. What impact does this increased interaction capability have on the company's choice to perform tasks itself or to 'outsource' such tasks to others (the trade-off between 'make' or 'buy')? Business network theory places the company in a 'business network', a web of business partners linked together in a flexible way to produce different outputs depending on the customer requirements. Previous research suggests that such business networks require modularization of the products, the processes and the firm in order to be effective. Firms would be able to share their core capabilities and therefore can respond faster, and more effective, to different requirements. Are business networks indeed more dynamic and more 'agile' than other forms of inter-organizational co-operation like alliances, joint-ventures or markets? More precisely, what is the impact of the structure of a business network on the performance of the participating actor organizations? The objective of this study is to define and understand this relationship: business network structure and organizational performance. In this Research in Progress Paper we present our preliminary set of hypotheses and our testing instrument, a management game called the Business Networking Game that simulates modular business networks.


We examine the development and investigate the performance of exchange-correlation functionals constructed from the adiabatic connection. Our method is based on a direct modeling of the adiabatic connection curve in the coupling-constant space and is very flexible in the models. Several different models are investigated in the construction of new families of exchange-correlation functionals. Also the performance of two of these models (MCY1 and MCY2) is investigated over a wider range of systems and properties, with comparison made to the performance of established functionals. Overall, the adiabatic functionals improve upon widely used hybrid and generalized gradient approximation functionals, particularly in correctly describing one-electron systems and reaction energy barriers.


Aim: To investigate the validity and sensitivity of an automatic movement detection system developed by our laboratory for the formalin test in rats. Methods:The effects of systemic morphine and local anesthetic lidocaine on the nociceptive behaviors induced by formalin subcutaneously injected into the hindpaw were examined by using an automated movement detection system and manual measuring methods. Results: Formalin subcutaneously injected into the hindpaw produced typical biphasic nociceptive behaviors (agitation). The mean agitation event rate during a 60-min observation period increased linearly following increases in the formalin concentration (0.0%, 0.5%, 1.5%, 2.5%, and 5%, 50 μL). Systemic application of morphine of different doses (1, 2, and 5 mg/kg) 10-min prior to formalin injection depressed the agitation responses induced by formalin injection in a dose-dependent manner, and the antinociceptive effect induced by the largest dose (5 mg/kg) of morphine was significantly antagonized by systemic application of the opioid receptor antagonist naloxone (1.25 mg/kg). Local anesthetic lidocaine (20 mg/kg) injected into the ipsilateral ankle subskin 5-min prior to formalin completely blocked the agitation response to formalin injection. These results were comparable to those obtained from manual measure of the incidence of flinching or the duration time of licking/biting of the injected paw. Conclusion: These data suggest that this automated movement detection system for formalin test is a simple, validated measure with good pharmacological sensitivity suitable for discovering novel analgesics or investigating central pain mechanisms.


The author claims that for the cultural sector the same problem is posed by public intervention in general: this must be judged by its macroeconomic effects, above all by trying to measure the effect produced by using appropriate measurement methodologies. Evaluating public programs and projects also aims to demonstrate that public intervention can be more effective than the private market. According to the author, a substitution of the public sector with the private sector would have the opposite result: a lower amount of employment and profits. The author deals with other themes, such as the economic dimensions of the cultural heritage sector, the value of cultural heritage in itself, a critical examination of the comparison between the cultural heritage and the oil fields.


Estimates of crop evapotranspiration (ET) to measure the freshwater use indicator water footprint (WF) have undoubtedly been popular and implemented (Chapagain and Hoekstra, 2004), as well as the more recent extension to subnational regions and watersheds (Mekonnen and Hoekstra, 2010a; Hoekstra and Mekonnen, 2012; Mekonnen and Hoekstra, 2012). As reviewed by (Chenoweth et al., 2014; Lovarelli et al., 2016), these studies have gone from estimating products' water trade on a global scale, to rigorous quantification for specific crops and geographical areas. Many studies have extended the coverage and precision of estimates. However, when it comes to the implementation of these improvements in local and river-basin water management, we find management problems that are ultimately unaddressed. It is here that, in our opinion, the Plant Water Sciences (PWS) have to shed light on these "blind spots." We also illustrate these general ideas with two examples.


This handbook presents industry-accepted guidelines for planning and conducting a wind resource measurement program to support a wind energy feasibility initiative. These guidelines, which are detailed and highly technical, emphasize the tasks of selecting, installing, and operating wind measurement equipment, as well as collecting and analyzing the associated data, once one or more measurement sites are located. The handbook's scope encompasses state-of-the-art measurement and analysis techniques at multiple heights on tall towers (e.g., 40 m) for a measurement duration of at least one year. These guidelines do not represent every possible method of conducting a quality wind measurement program, but they address the most important elements based on field-proven experience. The intended audience for this handbook is any organization or individual who desires the planning framework and detailed procedures for conducting a formally structured wind measurement program. Personnel from the management level to field technicians will find this material applicable. The organizational aspects of a measurement program, including the setting of clear program objectives and designing commensurate measurement and quality assurance plans, all of which are essential to ensuring the program's successful outcome, are emphasized. Considerable attention is also given to the details of actually conducting the measurement program in its many aspects, from selecting instrumentation that meets minimum performance standards to analyzing and reporting on the collected data. 5 figs., 15 tabs.


The current opioid crisis in the United States has emerged from higher demand for and prescribing of opioids as chronic pain medication. This led to massive diversion of prescription opioids into illicit markets. A peculiar tragedy is that many health professionals prescribed opioids in a misguided response to legitimate concerns that pain was under-recognized and undertreated. The crisis grew not only from over-prescribing, but also from other sources, including a lack of research into non-opioid pain management, ethical lapses in corporate marketing, historical stigmas directed against people who use drugs, and failures to deploy evidence-based therapies for opioid addiction and to comprehend the limitations of supply side regulatory approaches. Regulations that restricted opioid prescribing perversely accelerated narco-trafficking of heroin and fentanyl with consequent increases in opioid overdose mortality As injection replaced oral consumption, outbreaks of hepatitis B and C virus and HIV infections have resulted. This viewpoint explores the origins of the crisis and directions needed for effective mitigation.


Intergovernmental cooperation comes along with a trade-off between the autonomy of a political community and the effectiveness with which it can provide policies. Existing research has investigated this trade-off by analyzing political communities through an actor-centered perspective.
We argue that this perspective should be complemented by a policy-centered one. We understand political communities as a compound of different policies and for each of these policies the trade-off for engaging in intergovernmental cooperation has different implications. More precisely, we make a case for disaggregating policies into three dimensions, i.e. participation, competences & capacity,
and resources (PCR). An analysis of media reporting on Swiss concordats by the use of dictionary coding indicates that the salience with which these three concepts are mentioned in newspaper articles varies systematically with the policy field that is covered. While participation is salient for education and security, resources matter for public finance and health policies.


RC structures around the world require rehabilitation or strengthening for various reasons, such as increased load, the repair of damaged members, modification of the structural system, improvement of the structure, or errors in design and construction. In recent decades, strengthening has inevitably been a good choice in terms of structural efficacy as well as from an economic point of view. The near surface mounted (NSM) and the proposed side near surface mounted (SNSM) with steel or carbon fibre reinforced polymer (CFRP) bars provide suitable approaches for the enhancement of the flexural performance of RC beams. However, the NSM-steel technique has only been implemented in very few existing research, and, hence, is still an interesting issue. Furthermore, the SNSM approach to strengthening is a new concept. The main goal of this study is to investigate the experimental behaviour of RC rectangular beams strengthened using the NSM and newly developed SNSM techniques.
To strengthen RC beams, CFRP composites (bars and fabric) and steel bars were used as the strengthening materials. Twenty-five (25) RC beams were fabricated for the experimental programme. The RC beams were cast in the concrete laboratory and divided into seven groups. The first group consisted of one unstrengthened beam as the control beam (CB) to represent the existing structural member. The other groups were strengthened by incorporating NSM, NSM with end anchorage (CFRP fabrics) and the proposed SNSM technique, with different configurations of CFRP and steel bars subjected to gradually increasing static load. All the representative RC beams were tested by a highly precise Instron Universal testing machine and the results were recorded using an automatic data logger. The experimental results showed that the ultimate capacity of the RC beams strengthened with NSM steel bars increased 96% more than the control beam. When the RC beams were strengthened using NSM steel bars and end anchorage using CFRP fabric, the ultimate capacity was enhanced by 132%. Moreover, a 93% and 138% increase in the ultimate capacity was achieved by strengthening the RC beams with SNSM steel and CFRP bars, respectively. An improvement of 130% in the ultimate capacity was achieved once the pre-cracked beams were strengthened with SNSM CFRP bars. An analytical model has been developed to predict the load, deflection and compressive strain in concrete; the tensile strain in the main reinforcement; and the strain in the NSM bars of the RC beams (control and strengthened) under static loading using sectional analysis. The flexural crack spacing of the RC beam specimens was predicted from existing models. The experimental results showed good agreement with the results obtained from the analytical models. It has been revealed that the deflection of the strengthened beams was significantly smaller than that of the unstrengthened beams. In addition, strengthening using the NSM and SNSM technique decreased the spacing of the cracks and increased the number of cracks. The crack widths also reduced with the increasing number of cracks.


Purpose of review Inhibition of the renin–angiotensin–aldosterone system has become a cornerstone of modern heart failure and myocardial infarction therapy. This article will review the background and major clinical trials that have shaped this field over the past 15 years. Recent findings Major clinical trials have firmly established angiotensin converting enzyme (ACE) inhibitors as the standard of care in patients with heart failure and following myocardial infarction. Over the past several years, a number of trials have tested the hypothesis that an angiotensin II receptor blocker (ARB) could be as effective as, or more effective than, ACE inhibitors in these clinical settings. The results of these trials, while establishing a clear role for ARBs, have been subtly different in distinct patient populations. Summary The most recent trials of ARBs in heart failure and myocardial infarction patients suggest a role for angiotensin receptor blockers in patients with heart failure who are intolerant to ACE inhibitors and who are on optimal ACE inhibitor therapy. In patients with acute high-risk myocardial infarction, the VALIANT trial has established that the ARB was as effective as an ACE inhibitor following myocardial infarction. These studies have thus provided clinicians with alternatives to ACE inhibitors in these important clinical syndromes.


Copper and nitrogen compounds and silver and nitrogen compounds have been researched with the first‐principle linear combination of the atomic orbitals in full‐screen basis with the local gradient and hybrid potential of the density functional theory (DFT) realized in the CRYSTAL09 program code. We have found the structural N2MN (M: Cu, Ag) dinitride–nitride phase having an orthorhombic structure, the spatial group of the Ibam symmetry and four formula units in the primitive cell that have not been reported before. The structure was found to be layered, the metal atoms are linearly circled by the nitride N atoms, whereas, the other two atoms make a molecule with a small negative charge of ∼0.02 e. The volume elastic modules in N2CuN, N2AgN crystals are equal to 4.3 and 6.6 GPa, respectively, and their pressure derivatives are equal to 6.7 and 5.3, respectively. The electron energy spectrum makes a superposition of weakly interacting molecular states of N2 and metal states of MN. The bandgap width equals ∼0.05 eV. The estimations of the enthalpy energies show that N2MN possess large energy content and in its decomposition into metal and gaseous nitride the energy release can reach 8 eV cell−1, which appears to be higher than that in the known metal azides. Thus, the new structure of the dinitride–nitride N2MN combines the properties of molecular and semiconductor crystals: high compressibility, strong mechanical anisotropy, localized vacant states in the zone spectrum, and small bandgap. The unique physical properties can ensure their application as energy materials, the source of chemically pure nitride, and in semiconductor and optical material science.


The dynamical degradation of digital chaotic systems (DCSs) often has serious negative influences on some digital chaos-based systems and then becomes one of the bottleneck problems stopping chaos from some applications. In this paper, we first restrict the Devaney's chaos definition to finite state sets to describe the chaotic motion of digital systems. Then, we propose a novel control method for DCSs based on the differential mean value theorem and state feedback technology. Simulation results show the effectiveness, robustness, and superiority of the proposed method. Finally, we construct a new pseudorandom number generator (PRNG) and evaluate its randomness via NIST SP800-22 and TestU01 test suites. Statistical test results show that the proposed PRNG has high reliability of randomness, thus it can be used for cryptography and other potential applications.


Child maltreatment research is increasingly recognizing the need to capture patterns of co-occurrence between different types of abuse/neglect and to consider their associations with psychosocial functioning. Few studies have examined these issues in justice-involved youth despite the fact that rates of maltreatment and trauma-related psychopathology are disproportionately high among this population. This study examined profiles of self-reported child physical abuse, sexual abuse, emotional abuse, and neglect among incarcerated juveniles in Victoria, Australia, using latent class analysis. We also investigated associations between maltreatment profiles and mental health and behavioral problems. Data pertaining to juveniles' experiences of maltreatment and mental health and behavioral functioning were collected from interviews, questionnaires, files, and administrative datasets. A three-class solution provided the best fit for the data and was conceptually meaningful: a "low/rare maltreatment" class (41%); "high physical and emotional abuse" class (23%); and a "poly-victimization" class (36%). Youth in the "poly-victimization" class experienced especially serious mental health and behavioral disturbances, including higher rates of mental illness, greater severity of internalizing and externalizing symptoms, impulsivity, substance abuse, self-harm and suicidal behavior, irritability, and early-onset violence. Results suggest there may be benefit in considering screening and assessment procedures in youth justice settings to identify poly-victimized youth in need of more intensive monitoring and treatment to address their complex clinical and behavioral profiles.


More and more board and chip package RF designs require high-signal density while delivering frequencies in the tens of gigahertz. The challenges for organic substrate in meeting these electrical requirements include using high-speed, low-loss materials, manufacturing precise structures, and making a reliable finished product. In addition, many RF systems have mechanical and environmental requirements like lightweight and low- moisture absorption. This paper describes a procedure used to fabricate RF circuits in a package composed of laminated substrates. A highly versatile laminated structure is enabled by the presence of Z-interconnects that are included between the layers. These interconnects are normal to the surfaces of the substrates which is considered to be the 'Z' direction. Such Z-interconnects hold promise for increasing signal density at microwave frequencies in a given package. The manufacture of Z- interconnect structures involves building mini-substrates of 2 or 3 layers each, then assembling several mini- substrates together to make the finished product. Final lamination includes connecting metal layers vertically, using a conductive paste. Designing and manufacturing the mini-substrates separately makes it possible to reliably manufacture substrates with no via stubs, very low-loss materials, nearly arbitrary transmission line structures and versatility in optimizing features to reduce signal loss. Examples of circuits, that were fabricated using the Z- interconnect process, are given and test results shown. These circuits are tested for electrical performance consisting of S-parameter measurements. Equivalent low-loss performance to typical ceramic substrates will be shown up to 25 GHz. These results compare the use of the technique with liquid crystal polymer (LCP) substrate material with the use of Teflon-based material. Teflon- based circuits are compared to low temperature co-fired ceramic (LTCC) substrates. Due to its design flexibility, lighter weight and hermeticity, the organic-material based Z-interconnect is shown as an improvement over ceramic substrates.


As human cases of tick-borne disease continue to increase, there is a heightened imperative to collect data on human-tick encounters to inform disease prevention. Passive tick surveillance programs that encourage members of the public to submit ticks they have encountered can provide a relatively low-cost means of collecting such data. We report the results of 11 years of tick submissions (2006–2016) collected in Monmouth County, New Jersey, an Atlantic coastal county long endemic for Lyme disease. A total of 8,608 ticks acquired in 22 U.S. states were submitted, 89.7% of which were acquired in Monmouth County, from 52 of the County's 53 municipalities. Seasonal submission rates reflected known phenology of common human-biting ticks, but annual submissions of both Amblyomma americanum and Dermacentor variabilis increased significantly over time while numbers of Ixodes scapularis remained static. By 2016, A. americanum had expanded northward in the county and now accounted for nearly half (48.1%) of submissions, far outpacing encounters with I. scapularis (28.2% of submissions). Across all tick species and stages the greatest number of ticks were removed from children (ages 0–9, 40.8%) and older adults (ages 50+, 23.8%) and these age groups were also more likely to submit partially or fully engorged ticks, suggesting increased risk of tick-borne disease transmission to these vulnerable age groups. Significantly more people (43.2%) reported acquiring ticks at their place of residence than in a park or natural area (17.9%). This pattern was more pronounced for residents over 60 years of age (72.7% acquired at home). Education that stresses frequent tick checks should target older age groups engaged in activity around the home. Our results strongly suggest that encounter rates with ticks other than I. scapularis are substantial and increasing and that their role in causing human illness should be carefully investigated.


In this letter, we address the problem of element placement in a linear aperiodic array for use in spatial spectrum estimation. By making use of a theorem by Caratheodory, it is shown that, for a given number of elements, there exists a distribution of element positions which, for uncorrelated sources, results in superior spatial spectrum estimators than are otherwise achievable. The improvement is obtained by constructing an augmented covariance matrix, made possible by the choice of element positions, with dimension greater than the number of array elements. The augmented matrix is then used in any of the known spectrum estimation methods in conjunction with a correspondingly augmented search pointing vector. Examples are given to show the superior detection capability, the larger dynamic range for spectral peak to background level, the lower sidelobes, and the relatively low bias values, when one of the known spectrum estimation techniques based on eigenstructure is used.


A new type of tracer is making its entry in the scenario of wind-tunnel measurements: helium-filled soap bubbles (HFSB). The present work discusses the main fluid-dynamic and optical properties of HFSB to evaluate their use for quantitative measurements in aerodynamic experiments. In the past three decades, particle image velocimetry (PIV) has become a standard measuring technique in experimental fluid mechanics. Advances in both hardware components and software analysis have allowed achieving many milestones in flow diagnostics, mainly time-resolved and instantaneous volumetric measurements. In particular, the extension to the third dimension in space, i.e. tomographic PIV and 3D particle tracking velocimetry (PTV), has been used to provide quantitative visualizations of the coherent structures occurring in various turbulent flows and have provided insight in the spatial organization of the turbulent motions at different scales. The extension of the aforementioned techniques towards industrial practice in wind tunnel testing requires the development of a more efficient approach in terms of scaling and versatility. The present dissertation tackles the upscaling of PIV experiments towards industrial wind tunnels with the use of HFSB as tracing particles. The reasons and motivations behind this choice are addressed in the first chapter and followed by a description of the state-of-the-art of PIV. The second chapter aims at familiarising the reader with the working principles of PIV, which will be later recalled when presenting the advances towards large-scale experiments. Information on the mechanical behaviour of tracer particles and on the underlying physics are discussed in the third chapter, where also the case of HFSB is examined for use during quantitative measurements in the low-speed flow regime. The problem of seeding in wind tunnels is discussed in chapter 4, where a system for the injection of HFSB in a large wind tunnel is presented. Here, the relationship between HFSB production rate and the resulting spatial concentration and dynamic spatial range (DSR) are discussed. Specific experiments that examine the tracing fidelity of sub-millimetre HFSB tracers are presented in chapter 5. The behaviour of HFSB is compared to micro-size droplets, yielding a characteristic response time in the range of 10 μs. The latter milestone opens up to the applicability of HFSB tracers for quantitative velocimetry in wind tunnel flows. In chapter 6, a specific case of interest is presented whereby HFSB tracers are used to measure the flow velocity within steady vortices such as those released at the tip of wings. A dedicated experiment shows that the neutrally or slightly buoyant HFSB return a rather homogeneous spatial concentration within the core of vortices, solving the long-standing issue encountered for small heavy tracers, such as fog droplets, that are systematically ejected from highly vortical regions. An analysis of the light scattering by HFSB was conducted with theoretical and experimental approaches, as described in chapter 7. The light intensity scattered by the HFSB is characterised by two source points: the glare points. The overall scattered light appears to be 104-105 times more intense with respect to the oil-based micro-size droplets. This information is used to retrieve the maximum size of the measurement volume for a given light source. Chapter 8 closes this dissertation presenting a survey of all the experiments that have been conducted during this PhD research. The scale of experiments varies from the more academic case of a circular cylinder up to the one of a ship model installed in one of the large industrial wind tunnels operated at the German-Dutch Wind Tunnels laboratories (DNW), going through the visualization and quantification of large structures in the rotor region of a vertical axis wind turbine (VAWT).


Introduction: After partial-thickness skin graft (PTSG) harvesting, a dermal surface is exposed and an iatrogenic wound is created. Application of various agents has been studied for enhancement of healing process in PTSG donor area. The ideal agent should accelerate healing, provide comfort to the patient, not allow infection, and be easily applicable and cheap. Materials and Methods: The Cochrane Central Register of Controlled Trials, PubMed, Scopus. and EMBASE databases were screened for words ("skin graft" + "donor"), by using time limits between 1989 and 2018. This study involved a total of 5 systematic reviews and 43 original articles which met the inclusion criteria. Articles were reviewed and parameters such as healing time, pain, infection rate, cosmetic result, and cost were extracted. Results: Systematic reviews favor moist dressing materials over dry ones considering healing time and patient comfort. Hydrocolloids provide rapid wound healing, and dressing changes do not cause any disruption to the newly regenerated epithelium. Alginates seem to have a longer healing time than hydrocolloid materials. Polyurethane films are characterized by rapid epithelialization and painless monitoring as well as low costs. The epithelialization time of MEBO®, a cosmeceutical product, is reported to be faster than polyurethane films. Local and systemic drug applications warrant further research before routine clinical usage. Conclusion: Dressing materials are the most commonly used and appropriate group according to the studies performed to date. It is seen that moist dressing materials are more favorable. Although there is not a subgroup with a clear superiority, it can be seen that the hydrofiber and polyurethane film groups are one step ahead in terms of ease of use, patient comfort, epithelialization speed, and scar quality. Polyurethane films have a cost advantage to the hydrofiber group.


Src homology 2 (SH2) domains mediate selective protein–protein interactions with tyrosine phosphorylated proteins, and in doing so define specificity of phosphotyrosine (pTyr) signalling networks. SH2 domains and protein-tyrosine phosphatases expand alongside protein-tyrosine kinases (PTKs) to coordinate cellular and organismal complexity in the evolution of the unikont branch of the eukaryotes. Examination of conserved families of PTKs and SH2 domain proteins provides fiduciary marks that trace the evolutionary landscape for the development of complex cellular systems in the proto-metazoan and metazoan lineages. The evolutionary provenance of conserved SH2 and PTK families reveals the mechanisms by which diversity is achieved through adaptations in tissue-specific gene transcription, altered ligand binding, insertions of linear motifs and the gain or loss of domains following gene duplication. We discuss mechanisms by which pTyr-mediated signalling networks evolve through the development of novel and expanded families of SH2 domain proteins and the elaboration of connections between pTyr-signalling proteins. These changes underlie the variety of general and specific signalling networks that give rise to tissue-specific functions and increasingly complex developmental programmes. Examination of SH2 domains from an evolutionary perspective provides insight into the process by which evolutionary expansion and modification of molecular protein interaction domain proteins permits the development of novel protein-interaction networks and accommodates adaptation of signalling networks.


In WSNs, energy efficiency are considered as the key issues in designing routing protocol. This paper proposes a clustering protocol F-LEACH based on the probability fading strategy. It makes further improvement over LEACH, which gives a better performance on energy consumption and system lifetime. In F-LEACH, nodes are preassigned different cluster- head probability values for cluster-head election in terms of their corresponding distances to the base station (BS). BS can carry out the assignment task. Nodes far from BS get little probability while nodes near BS get great probability. Then nodes elect cluster-heads using their different probability in a self-organizing manner. As a result, less cluster-heads appear in the area far from BS while the total number of cluster-heads is still keep optimal. This help saving the energy consumption by reducing long distance transmission from distant cluster-heads to BS. Simulation results show that F-LEACH performs better than LEACH in terms of energy consumption and system lifetime.


Kinetics of nutrient degradation in the rumen is an important component of feed evaluation systems for ruminants. The in situ technique is commonly used to obtain such dynamic parameters, but it requires cannulated animals and incubations last several days limiting its application in practice. On the other hand, feed industry relies strongly on NIRS to predict chemical composition of feeds and it has been used to predict nutrient degradability parameters. However, most of these studies were feedstuff specific, predicting degradability parameters of a particular feedstuff or category of feedstuffs, mainly forages or compound feeds and not grains and byproducts. Our objective was to evaluate the potential of NIRS to predict degradability parameters and effective degradation utilizing a wide range of feedstuffs commonly used in ruminant nutrition. A database of 809 feedstuffs was created. Feedstuffs were grouped as forages (FF; n=256), non-forages (NF; n=539) and of animal origin (n=14). In situ degradability data for dry matter (DM; n=665), CP (n=682) and NDF (n=100) were collected. Degradability was described in terms of washable fraction (a), slowly degradable fraction (b) and its rate of degradation (c). All samples were scanned from 1100 to 2500 nm using an NIRSystems 5000 scanning in reflectance mode. Calibrations were developed for all samples (ALL), FF and NF. Equations were validated with an external validation set of 20% of total samples. NIRS equations to predict the effective degradability and fractions a and b of DM, CP and NDF could be evaluated from being adequate for screening (r(2)>0.77; ratio of performance to deviation (RPD)=2.0 to 2.9) to suitable for quantitative purposes (r(2)>0.84; RPD=3.1 to 4.7), and some predictions were improved by group separation reducing the standard error of prediction. Similarly, the rate of degradation of CP (CP(c)) and DM (DM(c)) was predicted for screening purposes (RPD⩾2 and 2.5 for CP(c) and DM(c), respectively). However, the rate of degradation of NDF was not predicted accurately (NDF(c) : r(2)<0.75; RDP<2).


THE RELATIVELY recent discovery of the fact that procaine can be administered intravenously to people without serious results and even with benefit in some circumstances, has stimulated renewed interest in the pharmacology of this drug. It has been taught for some years that inadvertent intravenous injection of procaine hydrochloride was very dangerous because of its tendency to produce serious systemic reactions in the form of either circulatory depression or generalized convulsions. While these teachings were not entirely erroneous, they must be revised to take into account the rate and concentration of injection. Experiments carried out by Eggleston and Hatcher, 1 published in 1916 and 1919, furnished a background for the possibility of the intravenous administration of procaine. They reported that cocaine and holocaine® were destroyed rather slowly when administered intravenously but that procaine and several other drugs used for local anesthesia were rapidly destroyed when administered intravenously to animals. They


Roots and shoots of higher plants change their growth patterns in response to physical stimuli such as gravity, light, humidity, and obstacles. One of the earliest studies of the stimulus-response interactions in young seedlings was done by Charles Darwin, who was interested in the circular movement of hypocotyls and roots, and who examined effects of light, gravity, and touching stimulation using experimental devices designed by himself (1880). Since the pioneering studies of Darwin, much information on the mechanism of root behavior triggered by several kinds of physical stimuli has been accumulated from physiological as well as anatomical analyses of roots (for review, see Wilkins 1966; Juniper 1976; Jackson and Barlow 1981; Evans 1991). Extensive studies on the genetic network of stimulus-response interactions in root systems have started recently with the isolation and analysis of mutants of aberrant morphology or of abnormal growth pattern. We have used Arabidopsis thaliana for the molecular genetic approach to elucidate the genetic network ruling the signaling pathways in roots, because roots of young seedlings show a variety of responses to several physical and chemical stimuli, and the structure of Arabidopsis roots is simpler than that of other plants (Schiefelbein and Benfey 1991; Dolan et al. 1993). To analyze the responses and to obtain mutant plants that show aberrant responses, we have developed a series of experimental procedures using agar plates (Fig. 1) (Okada and Shimura 1992a). The agar medium contains 1.5% agar and 0.5× Arabidopsis mineral nutrient solution. Young seedlings grow well on the surface...


Many SOCs today contain both digital and analog embedded cores. Even though the test cost for such mixed-signal SOCs is significantly higher than that for digital SOCs, most prior research in this area has focused exclusively on digital cores. We propose a low-cost test development methodology for mixed-signal SOCs that allows the analog and digital cores to be tested in a unified manner, thereby minimizing the overall test cost. The analog cores in the SOC are wrapped such that they can be accessed using a digital test access mechanism (TAM). We evaluate the impact of the use of analog test wrappers on area overhead and test time. To reduce area overhead, we present an analog test wrapper optimization technique, which is then combined with TAM optimization in a cost-oriented heuristic approach for test scheduling. We also demonstrate the feasibility of using analog wrappers by presenting transistor-level simulations for an analog wrapper and a representative core. We present experimental results on test scheduling for an ITC'02 benchmark SOC that has been augmented with five analog cores.


[ill] the Editor .—As indicated in the [ill]ticle by Danziger and Horn, 1 urinary [ill]tention is a relatively common side [ill]fect of disopyramide phosphate ther[ill]y in middle-aged men with prostatic [ill]pertrophy, reflecting the drug's [ill]ticholinergic action. Urinary tract [ill]fection and septicemia could be addi[ill]onalnal anticipated complications in [ill]ch patients. 2 Urinary retention sec[ill]dary to disopyramide therapy is less [ill]mmon in women because of the ana[ill]mically short urethra and the ab[ill]nce of the prostate gland. In women [ill]th long-standing diabetes mellitus, [ill]wever, visceral neuropathy may [ill]mpromise the contractile strength of le detrusor muscle. The addition of le anticholinergic effect of disopyra[ill]ide in such cases could lead to uri[ill]ryy retention. The following cases [ill]ustrate that disopyramide may pre[ill]pitate urinary retention and lead to [ill]nary tract infection and septicemia diabetic women. Report of Cases .—Case1.—A 69-year[ill] woman with chronic diabetes was given sopyramide therapy beginning on Nov 7, 77, for the


Insulinoma is rare pancreatic neuroendocrine tumor that is usually described as benign and sporadic. It is seen mostly in women at the ages between 40 and 60 years. Insulinoma can cause hypoglycemic attacks which may lead to serious consequences. Here we report a case of an 82 years old woman with the diagnosis of insulinoma presented by cerebrovascular disease due to severe hypoglycemia. Early diagnosis of the disease is essential to prevent lethal hypoglycemia. The first choice of treatment is surgery. However in the elderly, medical treatments may be preferred as primary treatment due to the existing comorbidities. For this case, it was possible to control the hypoglycemic attacks by using diazoxide and octreotide treatment. So that continous dextrose infusion is not necessary.


Secondary active transporters move molecules across cell membranes by coupling this process to the energetically favourable downhill movement of ions or protons along an electrochemical gradient. They function by the alternating access model of transport in which, through conformational changes, the substrate binding site alternately faces either side of the membrane. Owing to the difficulties in obtaining the crystal structure of a single transporter in different conformational states, relatively little structural information is known to explain how this process occurs. Here, the structure of the sodium-benzylhydantoin transporter, Mhp1, from Microbacterium liquefaciens, has been determined in three conformational states; from this a mechanism is proposed for switching from the outward-facing open conformation through an occluded structure to the inward-facing open state.


Abstract This article reports an investigation into the pedagogical content knowledge (PCK) of Dutch specialist preschool music teachers with regard to teaching and learning rhythm skills from an embodied cognition perspective. An embodied cognition perspective stresses the intimate relationship between body, mind and environment. Through stimulated recall interviews, video analysis tasks, notebooks and semi-structured interviews, the PCK of six music teachers was explored. Regarding the content, a new form of bodily based PCK was found in the data: instructional gestures, representational gestures and guiding gestures that facilitate the learning of rhythm skills of preschoolers. Regarding its nature, this study demonstrated that the music teacher's PCK presents itself as a multimodal form of knowing, distributed over language, sound, gestures, body positioning and physical actions. This study raises the question whether the body is marginalised in current conceptualisations of PCK.


Usually, managers or technical leaders in software projects assign issues manually. This task may become more complex as more detailed is the issue description. This complexity can also make the process more prone to errors (misassignments) and time-consuming. In the literature, many studies aim to address this problem by using machine learning strategies. Although there is no specific solution that works for all companies, experience reports are useful to guide the choices in industrial auto-assignment projects. This paper presents an industrial initiative conducted in a global electronics company that aims to minimize the time spent and the errors that can arise in the issue assignment process. As main contributions, we present a literature review, an industrial report comparing different algorithms, and lessons learned during the project.


Cranberry (Vaccinium macrocarpon Ait. Ericaceae) fruits and juice are widely used for their antiadherence and antioxidative properties. Little is known however about their effects on clinical chemistry markers after long-term consumption. This study was conducted to evaluate the effect of three commercial cranberry products, NUTRICRAN90S, HI-PAC 4.0, and PACRAN on the antioxidative status of rodents, divided into three experimental groups. The products were given as dietary admixtures (1500 mg of product/kg of stock feed) for 14 weeks to male Wistar rats (Groups 2-4) and a control Group 1 which received only stock feed. There were no significant cranberry treatment-related effects on oxidative stress parameters, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, total antioxidant capacity, thiobarbituric acid reactive substances, advanced oxidation protein products, total SH-groups, or any other measured clinical chemistry markers. Hematological parameters, body weight, and food consumption were also unaffected by intake of cranberries. Only liver glutathione reductase activity and glutathione levels were significantly lower in Group 4 than in Group 1. Plasma alkaline phosphatase alone was significantly decreased in Group 2. No gross pathology, effects on organ weights, or histopathology were observed. No genotoxicity was found, and total cytochrome P450 level in liver was unaffected in all groups. The levels of hippuric acid and several phenolic acids were significantly increased in plasma and urine in Groups 2-4. The concentration of anthocyanins was under the detection threshold. The dietary addition of cranberry powders for 14 weeks was well tolerated, but it did not improve the antioxidative status in rats.


Opioid receptors are expressed in a cell type-specific manner. Here we show that the mouse δ-opioid receptor (mDOR) gene is regulated by promoter region CpG methylation. The mDOR promoter containing a putative CpG island is highly methylated in Neuro2A cells, correlating with the repression of this gene in these cells. This is in contrast with the unmethylated state of the mDOR promoter in NS20Y cells, which express a high level of mDOR. Repression of mDOR transcription in Neuro2A cells could be partially relieved by chemically induced demethylation with 5-aza-2′-deoxycytidine. In addition, in vitro methylation of the luciferase reporter gene driven by the mDOR promoter resulted in an inhibition of transcription in NS20Y cells. Methyl-CpG-binding protein complex 1 (MeCP1) has been implicated in methylation-mediated transcriptional repression of several genes. Electrophoretic mobility shift assays showed that fully methylated, but not unmethylated, mDOR promoter fragment formed a MeCP1-like protein complex that contained methyl-CpG-binding domain protein 2 (MBD2) and Sp3. Furthermore, the expression level of Sp3 was decreased when Neuro2A cells were demethylated with 5-aza-2′-deoxycytidine, and increasing Sp3 levels in Schneider's Drosophila line 2 cells led to the repression of mDOR promoter activity when the promoter was methylated. These results demonstrate that Sp3 and MBD2 are involved in the transcriptional repression of mDOR in Neuro2A cells through binding to the methylated CpG sites in the promoter region and may play a role in the cell type-specific expression of mDOR.


Within-host evolution of S. Typhimurium may lead to pathovars adapted to specific hosts. ABSTRACT Salmonella enterica serovar Typhimurium is typically considered a host generalist; however, certain isolates are associated with specific hosts and show genetic features of host adaptation. Here, we sequenced 131 S. Typhimurium isolates from wild birds collected in 30 U.S. states during 1978–2019. We found that isolates from broad taxonomic host groups including passerine birds, water birds (Aequornithes), and larids (gulls and terns) represented three distinct lineages and certain S. Typhimurium CRISPR types presented in individual lineages. We also showed that lineages formed by wild bird isolates differed from most isolates originating from domestic animal sources, and that genomes from these lineages substantially improved source attribution of Typhimurium genomes to wild birds by a machine learning classifier. Furthermore, virulence gene signatures that differentiated S. Typhimurium from passerines, water birds, and larids were detected. Passerine isolates tended to lack S. Typhimurium-specific virulence plasmids. Isolates from the passerine, water bird, and larid lineages had close genetic relatedness with human clinical isolates, including those from a 2021 U.S. outbreak linked to passerine birds. These observations indicate that S. Typhimurium from wild birds in the United States are likely host-adapted, and the representative genomic data set examined in this study can improve source prediction and facilitate outbreak investigation. IMPORTANCE Within-host evolution of S. Typhimurium may lead to pathovars adapted to specific hosts. Here, we report the emergence of disparate avian S. Typhimurium lineages with distinct virulence gene signatures. The findings highlight the importance of wild birds as a reservoir for S. Typhimurium and contribute to our understanding of the genetic diversity of S. Typhimurium from wild birds. Our study indicates that S. Typhimurium may have undergone adaptive evolution within wild birds in the United States. The representative S. Typhimurium genomes from wild birds, together with the virulence gene signatures identified in these bird isolates, are valuable for S. Typhimurium source attribution and epidemiological surveillance.