The room-temperature stability of nanometre-sized silver clusters in silica matrices has been investigated by following the temporal evolution of their surface plasmon absorption. Ag clusters in SiO2 were prepared by either annealing silica samples doped with atomic silver or by co-deposition of preformed clusters of defined size. Clusters were found to be unstable at ambient conditions on a timescale of days to weeks, independent of preparation conditions. The disappearance of the plasmonic resonance is explained by successive oxidation of the clusters even inside the matrix.


The traditional construction industry has a significant and far-reaching impact on the environment, economy, and society. Green-certified buildings, with LEED (Leadership in Energy and Environmental Design), BREEAM (Building Research Establishment Environmental Assessment Method), DGNB (Deutsches Gütesiegel Nachhaltiges Bauen), or other certifications during the design stage, have great potential for increasing the effective use of resources and energy, reducing pollution, etc., and so their number has increased greatly in recent years. The post-occupancy evaluation (POE) of green buildings involves assessing whether they meet expected performance during the in-use phase and comprises four steps: (i) carrying out the research purpose/goal; (ii) determining the research objectives; (iii) conducting data collection, analysis, and visualization; and (iv) obtaining the results and drawing conclusions. However, there is a lack of reviews of POE research and analysis of reasons for actual performance gaps. In response and through a comprehensive literature review/analysis, this article summarizes the actual performance gaps of various greencertified projects, analyzes the reasons for failures, and proposes potential solutions. It is found that 74%, 12%, and 14% of the projects perform better, similar, and worse, respectively, than their non-green counterparts. Future POE green building projects can be optimized from the perspective of the building, user, and POE system. To optimize green building actual performance, it is important to ensure the sufficient education of installation and maintenance personnel and occupants' green behavior, while interior design and decoration, the impact of user demographics, and POE performance indicators are key factors to be considered in green building design strategies and lifecycle evaluation systems.


Sera from 86 Colombian patients with parasitologically confirmed cutaneous leishmaniasis were studied by immunoblot analysis in order to identify a specific pattern for Leishmania infection. A soluble extract of Leishmania panamensis was used as the antigen. Sera from patients with Chagas' disease and sera from patients with no record of infection with trypanosomatids were also studied. The sera from patients with cutaneous leishmaniasis specifically recognized fractions of 120 kDa (76.7%), 123 and 129 kDa (69.7%), 138 kDa (61.6%), 141 kDa (53.4%), and 78 kDa (44.1%). No band common to all patients infected with Leishmania parasites was found at the time of diagnosis. Likewise, the pattern of immunoblot change after the patients were treated and apparently cured with meglumine antimoniate (Glucantime) was studied by evaluating sera pretreatment and 1 year posttreatment. Only minor changes in the color intensity at the same serum dilution between pre- and posttreatment sera were found, although the antibody titers by indirect immunofluorescence were negative for the posttreatment sample. This study shows that Western blot analysis is a more sensitive test for the detection of anti-Leishmania antibodies. However, the importance of whether the presence of antibodies correlates with the presence of Leishmania antigens could not be resolved by the data obtained from this study.


ABSTRACT Background: Metaphorical language has long been used by patients and providers to explain health experiences. Still, some studies indicate that metaphors can be counterproductive and inhibit patients' willingness to try new treatments, especially those that are unfamiliar, complex, or stigmatized. This is particularly complex in integrative settings where conventional medicine providers (family medicine physicians) offer patients complementary and alternative therapies, like acupuncture. To fully determine the potential translational value of metaphor, scholars argue that we must 'prepare, test, and practice' metaphors that represent both patients' and providers' preferences. Method: We conducted a thematic analysis, informed by metaphor theory, of 32 interview transcripts from physicians (N = 15) and patients (N = 17) in which they described patient-provider communication experiences for a study on acupuncture integration. We separated thematic analyses by group, keeping in mind that providers and patients may gravitate toward different metaphorical language. Results: Patients and providers used metaphor to explain (1) why they accept acupuncture as a treatment (by validating acupuncture as a viable treatment option); (2) why the body needs acupuncture (by illustrating an unhealthy state of the body); and (3) how acupuncture affects the body (by highlighting the healthier state of the body as a result of acupuncture). Conclusions: This study provides both physician- and patient-generated metaphorical explanations of acupuncture treatment, thereby illustrating how conventional medicine physicians and patients make sense of a traditionally Eastern medical practice by using concepts familiar to them. The results could be used to develop interventions or translational tools.


The area of mangrove forests in Indonesia is currently only spanning as much as 3.4 milion acres, so there is a need for the participation of the government and community to maintain its sustainability. South Halmahera is the district with the largest mangrove area in the North Maluku Province. One of the mangrove areas in the District of South Halmahera is located at Sayoang Village, East Bacan Subdistrict Up until its eleventh founding anniversary, this district have never conducted an inventorizing of its mangroves, both ecological and social studies in the field of public. This study aims to analyze the compotition of mangrove species in Sayoang Village, East Bacan Subdistrict, South Halmahera, and identify the knowledge of surrounding communities of mangrove areas as protected areas. Data were retrieved using sampling method with applications terraced paths, and analyzed by calculating its important value index (INP) and its index value diversity (IVD). The public social data were taken using in-depth interviews and questionnaires. Results obtained from this study show that the mangrove forest in Sayoang Village, East Bacan District, Halmahera, consists of major mangrove species with as many as eleven species belonging to families Rhizophoraceae, Sonneratiaceae, Avicenniaceae, Meliaceae and Myrtaceae, and as many as three species of minor mangrove belonging to families of Loranthaceae, Acanthaceae, and Pteridaceae. The mangrove's species diversity and richness is and low, but it has high evenness. The results showed that 60% of total respondents know the benefit of mangrove as fish habitat, while for mangrove area as conserving areas, 50% of total respondent don't know the status of the area. The cutting problems happened in mangrove areas, 90% of total respondent know the activity and 85% of total respondent think that the logging activities in mangrove area is still allowed. The management activity of mangrove area in Sayoang village hasn't been conducted, either by the community or by local Dinas Kehutanan, and 53% of total respondent still wishing the mangrove can give more benefit economically.Key words: Mangrove forest, mangrove protected areas, community knowledge


In this paper, we present a novel 128/64 point fast Fourier transform (FFT)/ inverse FFT (IFFT) processor for the applications in a multiple-input multiple-output orthogonal frequency-division multiplexing based IEEE 802.11n wireless local area network baseband processor. The unfolding mixed-radix multipath delay feedback FFT architecture is proposed to efficiently deal with multiple data sequences. The proposed processor not only supports the operation of FFT/IFFT in 128 points and 64 points but can also provide different throughput rates for 1-4 simultaneous data sequences to meet IEEE 802.11n requirements. Furthermore, less hardware complexity is needed in our design compared with traditional four-parallel approach. The proposed FFT/IFFT processor is designed in a 0.13-mum single-poly and eight-metal CMOS process. The core area is 660times2142 mum2 , including an FFT/IFFT processor and a test module. At the operation clock rate of 40 MHz, our proposed processor can calculate 128-point FFT with four independent data sequences within 3.2 mus meeting IEEE 802.11n standard requirements


Renowned forensic physical anthropologist Dr. T. Dale Stewart traveled extensively to countries all over the world. The reasons for his journeys were manifold. He did fieldwork, took part in congresses, visited scientific institutions, and lectured by invitation at various universities. This paper deals with his journeys in general and with his four visits to Czechoslovakia in particular. Three of them were undertaken in connection with scientific congresses dedicated to Dr. Ales Hrdlicka. Dr. Stewart, as Hrdlicka's successor in the Smithsonian Institution, always chose an appropriate topic for his lecture. His visits to Hrdlicka's native country and town contributed to better mutual understanding and exchange of ideas between physical anthropologists and anatomists from both countries, the USA and Czechoslovakia (the today separate Czech and Slovak Republics).


The transplantation of neural tissue into the brain has the potential to repair the effects of trauma and of congenital abnormalities and to replace tissue that has ceased to function as the result of disease. The brain is not an immunologically privileged site in the strict sense; under certain carefully defined circumstances, grafts can last for long periods of time, but many such grafts are rejected naturally or following various types of provocation. Factors important to the survival of neural grafts are the use of embryonic tissue, the immunogenetic match, the level of expression of major histocompatibility complex antigens in brain cells close to the graft, and the presence of neural degeneration near the graft. Much additional basic experimental work must be done, however, before a rational approach to the clinical use of neural grafts can be undertaken.


Uther Charlton-Stevens presents an extensive review essay on Rochelle Almeida's recent book, Britain's Anglo-Indians (Lexington, 2017).  He considers her work on first generation Anglo-Indians who migrated 'home' to Britain both important and heretofore understudied. Finding Almeida's thesis persuasive, that these first generation migrants to Britain formed a hybrid sub-culture of British Anglo-Indianness in contrast to those who went Canada or Australia, Charlton-Stevens highlights possible intersection points with other scholarship and new areas for further inquiry.


Background
Sauropus androgynus leaves is the substance which has the potency to prevent degenerative processes. Sauropus androgynus leaves has flavonoid as the main component. Flavonoid has antioxidant and anti neuro-inflammation that can be used to prevent Alzheimer dementia. Research purpose is knowing the effect of Sauropus androgynus leaves for the cognitive function and β-amyloid expression in the hippocampus of wistar rats.
Methods
Reseacrh was done by in vivo method, where male wistar rats (n=24) were distributed to six groups which consisting of four rats. Group 1: Normal control, group 2: positive control, group 3: standard treatment (B12 vitamin), group 4, 5 and 6 were give Sauropus androgynus leaves extract with the dose of 75 mg/kgBB, 150 mg/kgBB and 300 mg/kgBB, respectively for 28 days. Cognitive function was evaluated by t-maze test, where hippocampal β-amyloid expression was tested by immunohistochemistry.
Results
Time differences (day 0-28), alternation ratio distinction (day 0-28) and β-amiloid expression were: group 1 (1,84 second; 0,23 unit; 0,518%), group 2 (56,78 second; -0,42 unit; 40,036%), group 3 (34,46 second; -0,25 unit; 33,08%), group 4 (32,83  second; -0,09 unit; 28,88%), group 5 (-3,91 second; 0,42 unit; 14,728%), group 6 (24,25 second; 0,42 unit; 9,4%).
Conclusion
Sauropus androgynus leaves extract at the dose of 150 mg/kgBB and 300 mg/kgBB can maintain cognitive function by decreasing hippocampal β-amyloid formation.


Irrigation management in Greenhouse Nursery Production (GNP) is based on empiric methods based on farmer personal experiences with over-irrigation results. The effects of irrigation volume and daily application were studied in a pot experiment carried out on rooted cuttings in a greenhouse The irrigation volume treatment was performed on Full and reduced Treatment. The treatment of water application was carried out with split supply and unsplit supply. The effects of the treatments were evaluated in terms of biomass accumulation and partitioning, leaf area, photosynthesis and stomatal response, chlorophyll content, and water productivity. Callistemon showed a good adaptation to the different treatments tested during the experiment. A positive relation was found between biomass accumulation and irrigation volume, moreover split water application increased plant Dry Weight. Therefore, the highest biomass accumulation was registered in full irrigation volume in split application treatment, and this behavior was confirmed by the photosynthetic rate. No statistical differences were found, in terms of Relative Water Content (RWC), between the treatments. Stem water potential and stomatal conductance values suggest in Callistemon an anysohidric water stress response behavior. Our results evidenced that, in Callistemon potted plants, an irrigation volume reduction is possible when a split application occurs during the daytime. A full irrigation volume amounts to 10.8 L per plant during the trial period of 90 days while the reduced volume amounts to 8.2 L per plant. Therefore, an increased water productivity can be obtained if the daily water requirement is split on two applications during the daytime. Our results highlighted a possible reduction in environmental impact of Callistemon greenhouse pot production, through the 25% reduction of the volume irrigation.


A cDNA library was constructed to 10‐15 S poly(A) RNA from tobacco mosaic virus (TMV)‐infected Samsun NN tobacco. By differential colony hybridization of 1400 transformants, 32 clones were obtained corresponding to TMV‐inducible tobacco mRNAs. These clones were subdivided into six clusters on the basis of cross‐hybridization of the inserts. By Northern blot hybridization it was shown that three of the corresponding mRNAs were strongly induced by spraying tobacco plants with salicylic acid, whereas one mRNA was weakly induced by this treatment. All mRNAs were systemically induced in plants in which only the lower leaves were locally infected by TMV. Hybrid‐selected translation was performed, using six clones representing one cluster each, followed by immunoprecipitation using an antiserum to purified pathogenesis‐related (PR) proteins. Four clones yielded precipitable translation products. One of these clones represented a cluster of PR‐1 clones, another clone encoded the thaumatin‐like (TL) protein of tobacco which may correspond to PR‐P or −Q.


A 5.2-GHz CMOS receiver employs a double downconversion heterodyne architecture with a local oscillator frequency of 2.6 GHz and applies offset cancellation to the baseband amplifiers. Placing the image around the zero frequency, the receiver achieves an image rejection of 62 dB with no external components while minimizing the flicker noise upconversion in the first mixing operation. Realized in a 0.25-/spl mu/m digital CMOS technology, the circuit exhibits a noise figure of 6.4 dB, an IP/sub 3/ of -15 dBm, and a voltage conversion gain of 43 dB while draining 24 mW from a 2.5-V supply.


PURPOSE
To examine the reliability, quality and content of YouTube videos on exercises that can be performed after breast cancer (BC) surgery.

METHODS
Videos selected from YouTube using the search terms 'shoulder exercise and BC surgery', 'arm exercise and BC surgery' and 'physiotherapy/physical therapy and BC surgery' were categorised as useful or misleading by a surgeon and a physiotherapist. The videos were analysed using the 5-point DISCERN scale for reliability, the Global Quality Scale for quality and a 10-item scale for comprehensiveness.

RESULTS
Of the 180 videos initially analysed, 82 were included in the study, and 42 (51.2%) were classified as having misleading information and 40(48.8%) as having useful information. The reliability, quality and content scores of the videos containing useful information were higher (p < 0.001). Most of the videos in the useful information group (80%) were uploaded by universities/professional organisations/physicians/physiotherapists, while the majority of those in the misleading information group (47.6%) were uploaded by websites providing independent healthcare information.

CONCLUSION
YouTube can be an important instrument to protect patients from musculoskeletal system complications after BC treatment and improve existing complications. Universities, physicians and physiotherapists should be encouraged to prepare more videos containing full and accurate information on this subject.


It needs much effort to encode a planning domain model for complex applications. It includes getting the domain knowledge, creating and validating the correctness of knowledge and then maintaining it. The major product is the domain model which consists of a set of operators [1] (also called action schema) written in certain modelling languages. In this paper we briefly review a variety of automated knowledge engineering tools that automatically produce domain models, and discuss the motivation
behind the development of these tools with three major concerns that differentiate these tools from
one another. The results of the review give insights into the strengths and weaknesses of the
considered systems, and point to needs in future work to enhance the capabilities and overcome their short comings.


Summary form only given:In November 2006, ministers representing the world's major fusion communities signed the agreement formally establishing the international project ITER. Sited at Cadarache in France, the project involves the European Union, China, India, Japan, the Russian Federation, South Korea and the United States. ITER is a critical step in the development of fusion energy: its role is to confirm the feasibility of exploiting magnetic confinement fusion for the production of energy for peaceful purposes by providing an integrated demonstration of the physics and technology required for a fusion power plant. The ITER tokamak is designed to achieve a fusion amplification factor, Q, of 10 for several hundreds of seconds with a nominal fusion power output of 500MW. It is also intended to allow the study of steady-state plasma operation at Q=5 by means of non- inductive current drive, in anticipation of a requirement for fusion power plants to operate continuously. Accompanying the ITER engineering design activities, an extensive international physics collaboration has addressed the key physics issues for ITER and has assembled a comprehensive physics basis which supports the design. Nevertheless, several key operational aspects remain the subject of focussed R&D activities which aim to ensure the reliable operation of the device at or beyond its design capability. These include control of plasma-wall interactions to ensure that plasma facing components achieve their design lifetime under the stationary and transient loads expected in ITER, the mitigation or stabilization of mhd instabilities to guarantee long duration operation, and the development of candidate steady-state regimes towards ITER-relevant parameters. Operation of ITER will open new frontiers in fusion research involving the influence of a significant a-particle population on plasma heating, confinement properties and stability. Studies in steady-state scenarios will be of particular significance and should provide access to novel aspects of non-linear phenomena in magnetically confined plasmas. To develop plasma scenarios in which high fusion power production is combined with high confinement and plasma pressure, control of heat and particle fluxes, active control of mhd stability and fully non-inductive current drive, the fusion community will need to confront a range of challenges involving plasma physics understanding, plasma measurement techniques, auxiliary heating and current drive systems, and plasma control. The presentation will summarize the current status of the project, discuss key physics issues which are the subject of ongoing R&D, and review the opportunities and challenges involved in successful operation of ITER.


This folio of compositions represents four years of practice-led research into the relationship between musical context and musical content. The outcome is a spectrum of pieces through which the usefulness of terms such as 'jazz', 'classical', 'Experimental', 'composed', and 'improvised' music is surveyed. The purpose of the research is to find ways in which to express my own individuality as a composer through a very personal exploration of relationships between jazz and classical music contexts – to blur distinctions between them, to invent new musical materials (or, to situate existing musical materials differently), and to explore new relationships between composition, improvisation and indeterminacy.

This commentary is in two parts: Part One, 'Categories' provides a context for my research and includes an evaluation of relevant musical terms and categories, before situating the folio of compositions accordingly; Part Two, 'Materials, Methods and Techniques' explores two distinct approaches to the organisation of pitch materials in the music: the first section is titled 'Interval Cycles, Integration and 'Extra-contextuality'', the second 'Modes, Form, and Narratives of Difference'. A third section, 'Composed and Improvised Musical Material', explores some of the ways in which distinctions between specified and unspecified musical content are blurred in the music.

Part Two emphasises the combination of methods and techniques necessary to deal with multiple perspectives in the music, and the search for a common ground through which to explore relationships between musical styles and genres authentically and creatively.


Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in inflammation and cancer targeted by nonsteroidal anti-inflammatory drugs. COX-2 is also expressed constitutively in discreet locations where its inhibition drives gastrointestinal and cardiovascular/renal side effects. Constitutive COX-2 expression in the kidney regulates renal function and blood flow; however, the global relevance of the kidney versus other tissues to COX-2–dependent blood flow regulation is not known. Here, we used a microsphere deposition technique and pharmacological COX-2 inhibition to map the contribution of COX-2 to regional blood flow in mice and compared this to COX-2 expression patterns using luciferase reporter mice. Across all tissues studied, COX-2 inhibition altered blood flow predominantly in the kidney, with some effects also seen in the spleen, adipose, and testes. Of these sites, only the kidney displayed appreciable local COX-2 expression. As the main site where COX-2 regulates blood flow, we next analyzed the pathways involved in kidney vascular responses using a novel technique of video imaging small arteries in living tissue slices. We found that the protective effect of COX-2 on renal vascular function was associated with prostacyclin signaling through PPAR&bgr;/&dgr; (peroxisome proliferator-activated receptor-&bgr;/&dgr;). These data demonstrate the kidney as the principle site in the body where local COX-2 controls blood flow and identifies a previously unreported PPAR&bgr;/&dgr;-mediated renal vasodilator pathway as the mechanism. These findings have direct relevance to the renal and cardiovascular side effects of drugs that inhibit COX-2, as well as the potential of the COX-2/prostacyclin/PPAR&bgr;/&dgr; axis as a therapeutic target in renal disease.


It is argued that the development of semiconductor memories has reached a turning point. In the multimegabit dynamic random access memories (DRAMs) of the future, major factors contributing to the chip cost are process complexity, die size, equipment cost, and test cost. If conventional test methods are used, test costs will grow at an especially rapid rate. A memory test concept called the testing acceleration chip, which could reduce future test costs a hundredfold and yet maintain AC testing reliability, is presented.<<ETX>>


In this paper, we study factors that influence tag reuse behavior in social tagging systems. Our work is guided by the activation equation of the cognitive model ACT-R, which states that the usefulness of information in human memory depends on the three factors usage frequency, recency and semantic context. It is our aim to shed light on the influence of these factors on tag reuse. In our experiments, we utilize six datasets from the social tagging systems Flickr, CiteULike, BibSonomy, Delicious, LastFM and MovieLens, covering a range of various tagging settings. Our results confirm that frequency, recency and semantic context positively influence the reuse probability of tags. However, the extent to which each factor individually influences tag reuse strongly depends on the type of folksonomy present in a social tagging system. Our work can serve as guideline for researchers and developers of tag-based recommender systems when designing algorithms for social tagging environments.


Two methods have been used to measure the effects of wavelength of light upon visual perfonnance of subjects over the age of 60. Subjects between the ages of 20 and 35 served as a control group. We used four luminance-matched conditions: white (Tc = 6300 K), blue, green and red (maximum transmission at respectively 450, 550 and 650 om). The first method was a search task in a pseudotext. In addition, the luminance contrast of the text was varied. The second experiment was the measurement of the contrast-sensitivity function for the four colour conditions. No wavelength effects were found in the young age group. Above the age of 60, wavelength effects were found at low contrast in both experiments. The performance and contrast sensitivity were worst with blue light. This effect increased with age. The founded wavelength effects are ascribed to the wavelength-dependent increase of absorption with age.


For the first time the photochemistry of the trans, trans
(TT) to trans, cis
(TC) isomerisation for merocyanines (MCs) of a chromene (CHR) compound has been investigated using steady-state nanosecond and time-resolved femtosecond irradiation. The dominant photo-transformation of the TT isomer by these irradiations is conversion to TC. The yield of the TT to TC photoreaction is inherently low in all solvents studied due to efficient ground state recovery in competition with inter-system crossing, but it is lowest of all in polar solvents. Several intermediate states have been identified in the first 6 ns of the reaction that we tentatively assigned, including a possible twisted MC T1 state. We assign other distinct states to TT S1, TT T1 and a further species to TC T1. The full photochemical conversion from TT to TC is a slower process than 6 ns. The presence
of oxygen marginally increases the overall bleaching of the TT isomer and slightly enhances TC formation.


This article -based on the study of contemporary wills, lawsuits, letters, newspapers and memoirs- reconstructs certain aspects of the privae life of the upper class of Valparaiso in the 19th century: their houses, their marriages, their values and ideals, and their home life and pastimes. During the period covered by this study it is possible to observe certain changes in a significant part of this group. Thus, during the last third of the century the plain hose gave way to the mansion: money and ostentation became increasingly important, weakening the old alues of hard work, sobriety and family unity among the Valparaiso elite. Without exploring the more profound reasons for this evolution, the author suggests that this could be due to the admiration with which that sector regarded the upper class of Santiago, given that the new Iifestyle adopted was practically the same as the one of the elites in the capital.


This paper suggests that Alfred Schutz's account of systems of typification together with Sara Ahmed's account of the proximity of the stranger allows for a different understanding of social integration. The paper proposes to rethink the political and social relationship of the in-group and the stranger, approached through the face-to-face encounter between an integration counselor and an immigrant. The encounter offers a disruption of what is taken for granted by the in-group and functions as a catalyst for a system of reference to appear at all. Through Ahmed's account on the familiarity and proximity of the stranger, I argue that integration practices are considered to produce, rather than translate, a coherent system of reference for an in-group. The institutionalization of social integration is consequently risking concealing the "unintegratable" stranger rather than offering a solution for the more epistemological dimensions of social exclusion that we find in the experience of sameness and difference.


The remote marine aerosol and the cloud droplet number concentration (CDNC) are examined with an aerosol microphysics box model in an attempt to better understand the processes involved in the formation and transformation of the marine aerosol. Emission of submicrometre sea-salt and dimethylsulfide (DMS) have been included together with aerosol dynamics, gas and liquid phase chemistry and cloud processing representative for the marine boundary layer atmosphere. Our simulations are able to reproduce a bimodal submicrometre size distribution with realistic number concentrations even when new particle formation by nucleation is neglected. This indicates that ultrafine primary sea-salt flux is an important source of Aitken mode particles and CDNC. However, sulphate still constitutes 20–80% of the Aitken and accumulation mode masses. The temperature dependence of the sea-salt source function leads to a 23% decrease in total number concentration when the temperature increases from 12 to 20 ◦C. The influence of DMS emission on the aerosol and CDNC is minimal but the size distribution and mass concentration of sulphate is changed, mostly due to in-cloud processes. The wind speed is the dominant factor determining the CDNC, although entrainment of aerosols from free troposphere can have a substantial effect.


Fundamental understanding of the goaf gas distribution in a gassy coal mine is necessary for developing effective goaf gas drainage strategies in the longwall coal mine. The goaf gas was subjected to the surface and body forces that were classified depending upon whether they acted on the surface area or the volume of the gas element. Of these forces, the body forces were more predominant in displacing the goaf gas present in the underground mine. The buoyancy forces were classified as the body forces; they are the predominant forces acting on the goaf gas. The buoyancy forces depend mainly upon the density variation in the gas species and the panel orientation or panel geometry. If the temperature variations are neglected, the buoyancy forces that cause the displacement of the goaf gas depend mainly upon the panel orientation. In this work, numerical investigations were carried out using the computational fluid dynamics (CFD) techniques for the fundamental understanding of the goaf gas displacement for various panel orientations. The numerical results obtained for various panel orientations indicated that the goaf gas is displaced towards the tailgate (TG) side when the maingate (MG) was downdip, towards the MG side when MG was updip, towards the start-up of the panel when the face was downdip, and towards the face when the face was updip.


Does a bottle elicit a gender-specific emotion response that varies as a function of its shape? The answer to this question is of basic interest as well as of specific interest to the industry. We introduced startle reflex modulation to objectively measure emotion-related aspects of different bottles. This approach was chosen to complete behavioural data with objective physiological data. Three bottles differing only in shape were used as test stimuli. It is well known that the magnitude of an eye blink as a response to acoustic startle stimulation reflects current emotion elicited by a foreground stimulus. Reduced eye blink amplitudes reflect positive emotion, whereas enhanced eye blink amplitudes reflect negative emotion. No significant main effect of bottle shape on eye blink amplitudes was found, but a significant gender effect occurred for one specific bottle shape. Presentation of a medium-sized, polygonal bottle was associated with significantly larger eye blink amplitudes in male participants compared to female participants. We interpret that due to the nature of startle reflex modulation this particular bottle shape elicited a significantly more negative emotion in males than in females. Interestingly, although both genders rated this bottle least attractive only males demonstrated increased negative emotion as assessed with startle reflex modulation. It is difficult to further interpret this finding at this stage, but we discuss it in terms of providing evidence that startle reflex modulation is sensitive to subtle emotion-related differences of different bottle shapes. Thus, this method may become an important tool for product evaluation procedures. We can only speculate on what the gender effect means in terms of psychology. A link between emotion and the appreciation of aesthetics can be made.


Anxiety and eating disorders (EDs) often co-occur, prompting calls to explore anxiety-related maintenance processes in ED samples. Safety behaviors, which function to prevent a feared outcome from occurring or to reduce anxiety associated with a feared stimulus, are observed across anxiety disorders and, along with overt avoidance behaviors, are an important target in treatment. Data suggest that individuals with EDs also engage in safety behaviors. However, no existing assessments provide a comprehensive measure of eating-disorder-specific overt avoidance and safety behaviors. The goal of this Stage 1 Registered Report is to develop a comprehensive self-report measure of ED-specific safety behaviors. In Study 1, we will recruit 50 women with EDs to complete the scale and provide feedback on the response scale. Feedback from these participants will be used to refine the measure. In Study 2, we will evaluate the psychometric properties of the measure in a large sample of women with EDs (n dependent on the size of measurement) and a community sample without current or a history of ED symptoms. We will explore the measure factor structure, known-groups validity by comparing scores from women with EDs to healthy controls, internal consistency, and convergent and divergent validity with other psychological instruments.


The Alaska Amphibious Community Seismic Experiment (AACSE) is a shoreline-crossing passive- and active-source seismic experiment that took place from May 2018 through August 2019 along an ∼700  km long section of the Aleutian subduction zone spanning Kodiak Island and the Alaska Peninsula. The experiment featured 105 broadband seismometers; 30 were deployed onshore, and 75 were deployed offshore in Ocean Bottom Seismometer (OBS) packages. Additional strong-motion instruments were also deployed at six onshore seismic sites. Offshore OBS stretched from the outer rise across the trench to the shelf. OBSs in shallow water (<262  m depth) were deployed with a trawl-resistant shield, and deeper OBSs were unshielded. Additionally, a number of OBS-mounted strong-motion instruments, differential and absolute pressure gauges, hydrophones, and temperature and salinity sensors were deployed. OBSs were deployed on two cruises of the R/V Sikuliaq in May and July 2018 and retrieved on two cruises aboard the R/V Sikuliaq and R/V Langseth in August–September 2019. A complementary 398-instrument nodal seismometer array was deployed on Kodiak Island for four weeks in May–June 2019, and an active-source seismic survey on the R/V Langseth was arranged in June 2019 to shoot into the AACSE broadband network and the nodes. Additional underway data from cruises include seafloor bathymetry and sub-bottom profiles, with extra data collected near the rupture zone of the 2018 Mw 7.9 offshore-Kodiak earthquake. The AACSE network was deployed simultaneously with the EarthScope Transportable Array (TA) in Alaska, effectively densifying and extending the TA offshore in the region of the Alaska Peninsula. AACSE is a community experiment, and all data were made available publicly as soon as feasible in appropriate repositories.


: The lecture presents the history of the pharmacotherapy of epilepsy and analyzes the current situation at the pharmaceutical market related to the appearance of new, high-cost antiepileptic drugs in recent decades. The lecture substantiates the need of pharmacoepidemiology studies for the objective assessment of efficacy, safety and economical impact of new antiepileptics, especially in children, taking into account limited randomized preclinical trials in this group of patients. The lecture describes the role of pharmacoepidemiology in supplementing the findings of randomized controlled trials with new real-life evidence, in quantitative evaluation of adverse reactions, and in discovery of new adverse effects, as well as in the development of cost-effective strategies for rational antiepileptic therapy of children and in the overall improvement of public health economics.


This library research guide provides TU Nursing students with suggestions for resources to use in completing the transcultural nursing assignment for NSG 1012.


Renewable energy-driven methanol synthesis from CO2 and green hydrogen is a viable and key process in both the "methanol economy" and "liquid sunshine" visions. Recently, In2O3-based catalysts have shown great promise in overcoming the disadvantages of traditional Cu-based catalysts. Here, we report a successful case of theory-guided rational design of a much higher performance In2O3 nanocatalyst. Density functional theory calculations of CO2 hydrogenation pathways over stable facets of cubic and hexagonal In2O3 predict the hexagonal In2O3(104) surface to have far superior catalytic performance. This promotes the synthesis and evaluation of In2O3 in pure phases with different morphologies. Confirming our theoretical prediction, a novel hexagonal In2O3 nanomaterial with high proportion of the exposed {104} surface exhibits the highest activity and methanol selectivity with high catalytic stability. The synergy between theory and experiment proves highly effective in the rational design and experimental realization of oxide catalysts for industry-relevant reactions.


Increases in high-end microprocessor performance are becoming increasingly reliant on simultaneous issuing of instructions to multiple functional units on a single chip. As the number of functional units increases, the chip area, wire lengths, and delays required for a monolithic register file become unreasonable. Future microprocessors will have partitioned register files. The correctness of contemporary super-scalar processors relies on synchronized accesses to registers. This issue will be critical in systems with partitioned register files. Current techniques for managing register access ordering, such as register scoreboarding and register renaming, are inadequate for architectures with partitioned register files. This thesis demonstrates the difficulties of implementing these techniques with a partitioned register file, and introduces a novel compiler algorithm which addresses this issue.
Whenever a processor using register scoreboarding or register renaming issues an instruction, either the scoreboard or the register name table must be accessed to check the instruction's sources and destination. If the register file is partitioned, checking the scoreboard or name table for a remote register is difficult. One functional unit cannot determine at runtime when it is safe to write to a register in another functional unit's register file. While these techniques can be supported through use of a global or partitioned scoreboard, such an implementation would be complex, and have latency problems similar to those of a monolithic register file.
This work discusses the organization of multiple functional units into loosely-coupled groups of functional units that can communicate via direct register writes, but with purely local hardware interlocks to force synchronization. A novel compiler algorithm, Software Register Synchronization (SRS), is introduced. A comparison between SRS and existing hardware mechanisms is conducted using the Multiflow compiler modified to generate code for the MIT M-Machine. Experiments to evaluate the SRS algorithm are run on the M-Machine simulator being used for architectural verification.
In order to support partitioned register file architectures, an alternative to traditional hardware methods for managing register synchronization needs to be developed. This thesis presents a novel compiler algorithm to address this need. The SRS algorithm is described, demonstrated to be correct, and evaluated. Details of the implementation of the SRS algorithm within the Multiflow compiler for the MIT M-Machine are provided.


The purpose of the researcher was to investigate the opinions of public school administrators and teachers concerning the four-day school week. A status survey factorial design was employed. The independent variables investigated were: position (administrator and teacher), gender (administrator and teacher), age (administrator and teacher), years experience in public school (administrator and teacher), school size (administrator and teacher), and highest level of formal education (administrator and teacher). The dependent variables were scores from the following subscales of the Opinionnaire Concerning Four-Day School Week: Students' Academic Learning, Scheduling Activities, Bus Transportation Time, Parents' Needs, Students' Needs, Discipline, Teaching Time, Overall Opinion, and Total Score. The sample consisted of 122. Five composite null hypotheses were tested at the .0500 level employing a three-way analysis of variance (general linear model). A total of 180 comparisons were made plus 35 recurring. Of the 180 comparisons 54 were for the main effect and 126 were for interactions. Of the 54 main effect, none was statistically significant at the .0500 level. Of the 126 interactions, 2 were statistically significant at the .0500 level. The following interactions were statistically significant: 1. The independent variables position and gender for the dependent variable Students' Academic Learning; and 2. The independent variable position, gender, and age for the dependent variable Discipline. The results of the present study appeared to support the following generalizations: 1. Position and gender should be interpreted concurrently for Students' Academic Learning, 2. Position, gender, and age should be interpreted concurrently for Discipline, 3. Kansas administrators and teachers are neither positive nor negative toward a four-day school week, and 4. Kansas administrators and teachers are of the opinion that a four-day school would decrease discipline problems.


Purpose: Chromosome abnormalities are an important prognostic factor in childhood acute lymphoblastic leukemia (ALL). Recently, a subset of patients with hyperdiploid ALL and trisomy of chromosomes 4 and 10 has been reported to have a very favorable event-free survival. Rapid and accurate detection of these patients will allow them to be treated with highly effective and relatively nontoxic antimetubolitc therapy. Because of inherent problems associated with conventional cancer cytogenetics, we examined the efficacy of fluorescence in situ hybridization (FISH) to identify this ALL subgroup. Patients and Methods: Fifty uncultured bone marrow specimens from children with newly diagnosed ALL were examined for chromosomes 4 and 10 aneuploidy with FISH. These results were compared with routine cytogenetics and DNA Index (DI). Results: Interphase FISH cytogenetics identified the abnormal cell line(s) in all cases in which cytogenetics showed aneuploidy of chromosomes 4 and 10. In cases in which cytogenetics was not informative, FISH identified the presence of an aneuploid chromosome 4 and/or 10 cell line in concordance with the DI. Conclusions: FISH interphase cytogenetics can accurately detect chromosome 4 and 10 aneuploidy in leukemic cells. It is a rapid and clinically applicable technique that can reliably identify childhood ALL cases who have trisomy of chromosomes 4 and 10 and who have very favorable event-free survival.


Distributed Hash Table (DHT)-based peer-to-peer information discovery systems have emerged as highly scalable systems for information storage and discovery in massively distributed networks. Originally DHTs supported only point queries. However, recently they have been extended to support more complex queries, such as multiattribute range (MAR) queries. Generally, the support for MAR queries over DHTs has been provided either by creating an individual index for each data attribute or by creating a single index using the combination of all data attributes. In contrast to these approaches, we propose to create and modify indices using the attribute combinations that dynamically appear in MAR queries in the system. In this paper, we present an adaptive information discovery system that adapts the set of indices according to the dynamic set of MAR queries in the system. The main contribution of this paper is a four-phase index adaptation process. Our evaluations show that the adaptive information discovery system continuously optimizes the overall system performance for MAR queries. Moreover, compared to a non-adaptive system, our system achieves several orders of magnitude improved performance.


Recent publications in Gut 1 ,2 have highlighted the beneficial role of the National Institute for Health Research (NIHR) Clinical Research Network in supporting clinical gastroenterology research in the UK.3 On an European level, the European Clinical Research Infrastructures Network provides integrated support to multinational clinical research projects in partner countries. The overarching aim of the NIHR Clinical Research Network is to maximise clinical research delivery by providing the infrastructure that allows high-quality studies to be undertaken in the NHS. The support available encompasses many aspects of the study life-cycle, including study set-up, researcher training and aiding study delivery, for example by providing protected clinician research time and research nurse support at individual study sites in NHS institutions. All clinical gastroenterology research studies entered onto the NIHR Clinical Research Network Portfolio are eligible for support.3

The performance of the NIHR Clinical Research Network Portfolio is closely monitored using several High Level Objectives, one of which is increasing the proportion of studies that deliver in line with their planned delivery time and patient recruitment targets. The progress of each study during the recruitment phase is rated on a BRAG (black/red/amber/green) system, with studies deemed to be on target ('green') if recruitment is running at least 80% of that expected according to each study's self-determined recruitment schedule.4 Upon closure, studies which successfully recruited to their …


Background & Aims This creative therapy project raises awareness for the 2013 National Dying Matters Campaign. It's an experimental collaboration between hospice patient and artist Julie Williams, local artist Chantelle Townley, Advance Care Planning Facilitator, Lisa Gallagher and Holistic Therapist Lucy Scriven. Funding was kindly provided by St Helens Council. The artwork collage, entitled 'It's Not Over 'Til It's Over…' depicts the richness of Julie's life using beautiful photographs, steeped in memories and personal story telling. Safety measures over the five outpatient sessions included: on-going discussion and emotional support, regular 'time outs' to reduce impact on lethargy, and positive reflection. The artwork was officially unveiled at a celebration, in essence a living wake, hosted at Willowbrook, attended by family, friends and the local press. Results Strengthened interdepartmental working within Willowbrook. Stronger links for partnership working in the local community. Promotion of the value of creative therapies for patients and families. Promotion of the Dying Matters Campaign, and advance care planning within the hospice, locally and nationally. Conclusion This project has helped to raise awareness for the Dying Matters Campaign; it's also strengthened partnership working within the hospice and with the local community. Through artistic expression Julie was helped to share with the world everything she held dear and has been of great value in connecting positively with meaning in her life. Julie experienced the opportunity to develop her undiscovered artistic potential, and explore new coping strategies by moving away from denial into a place of acceptance. Importantly, through participation with the project, Julie actively engaged in her end of life care planning and inspired others to also engage. She also created a celebratory legacy that will now support her loved ones in their sadness and grief.


Intradural AVF below the conus medullaris may develop either on the filum terminale or the cauda equina (lumbosacral and coccygeal radicular nerves). Only 3 detailed cauda equina AVFs have been reported in the literature. The authors present the angiographic and MR imaging findings of cauda equina and filum terminale AVF cases, supplemented with literature research to characterize the radiologic features of the 2 entities. On angiography, filum terminale AVFs were invariably supplied by the extension of the anterior spinal artery accompanied by a closely paralleling filum terminale vein. Cauda equina AVFs were fed by either a radicular or a spinal artery or both arteries, often with a characteristic wavy radicular-perimedullary draining vein. SUMMARY: Intradural AVF below the conus medullaris may develop either on the filum terminale or the cauda equina (lumbosacral and coccygeal radicular nerves). Although not a few filum terminale AVFs are found in the literature, only 3 detailed cauda equina AVFs have been reported. Here, we analyze the angiographic and MR imaging findings of our cauda equina and filum terminale AVF cases, supplemented with literature research to characterize the radiologic features of the 2 entities. On angiography, filum terminale AVFs were invariably supplied by the extension of the anterior spinal artery accompanied by a closely paralleling filum terminale vein. Cauda equina AVFs were fed by either a radicular or a spinal artery or both arteries, often with a characteristic wavy radicular-perimedullary draining vein. On thin-section axial MR imaging, the filum terminale AVF draining vein joined the spinal cord at the conus medullaris apex, but that of the cauda equina AVF joined above the conus medullaris apex.


Purpose: To examine the enzyme kinetics of gefitinib and erlotinib metabolism by individual cytochrome P450 (CYP) enzymes, and to compare their effects on CYP3A activity, with the aim to better understand mechanisms underlying pharmacokinetic variability and clinical effects. Experimental Design: Enzyme kinetics were examined by incubating gefitinib or erlotinib (1.5-50 μmol/L) with recombinant human CYP3A4, CYP3A5, CYP2D6, CYP1A1, CYP1A2, and CYP1B1 (10-160 pmol/mL). Their effects on CYP3A activity were examined by comparing midazolam metabolism in the presence and absence of gefitinib or erlotinib in human liver and intestinal microsomes. Parent compounds and metabolites were monitored by high-performance liquid chromatography with a photodiode detector or tandem mass spectrometer. Results: Both drugs were metabolized primarily by CYP3A4, CYP3A5, and CYP1A1, with respective maximum clearance (Clmax) values for metabolism of 0.41, 0.39, and 0.57 mL/min/nmol for gefitinib and 0.24, 0.21, 0.31 mL/min/nmol for erlotinib. CYP2D6 was involved in gefitinib metabolism (Clmax, 0.63 mL/min/nmol) to a large extent, whereas CYP1A2 was considerably involved in erlotinib metabolism (Clmax, 0.15 mL/min/nmol). Both drugs stimulated CYP3A-mediated midazolam disappearance and 1-hydroxymidazolam formation in liver and intestinal microsomes. Conclusions: Gefitinib is more susceptible to CYP3A-mediated metabolism than erlotinib, which may contribute to the higher apparent oral clearance observed for gefitinib. Metabolism by hepatic and extrahepatic CYP1A may represent a determinant of pharmacokinetic variability and response for both drugs. The differential metabolizing enzyme profiles suggest that there may be differences in drug-drug interaction potential and that stimulation of CYP3A4 may likely play a role in drug interactions for erlotinib and gefitinib.


Nanocrystalline Ni and Ni-P alloy with grain size down to 6 nm were processed by pulsed electrodeposition. The as-deposited materials, possessing a strong fiber texture, were tested in tension at different temperatures and strain rates. Both materials exhibited low temperature superplasticity but with significant differences in mechanical characteristics. In comparison with nano-Ni, the nano Ni-P alloy exhibited significant strain hardening in flow behavior and lower superplastic elongations at relatively low strain rates, although the grain size was finer at test temperatures with limited grain growth in nano Ni-P alloy. Texture study as a function of strain and strain rate by bulk X-ray Schultz reflection and electron back scattered diffraction (EBSD) revealed development of cube components {001} and {013} with negligible deformation texture components (Cu or brass type) and limited fraction of low angle grain boundaries (< 10 %) in superplastically deformed samples. The reasons for the formation of cube components and their influence on flow behavior of electrodeposited materials were critically analyzed. Additional microstructural investigation by transmission electron microscopy revealed dislocations movement constrained by intragranular particles, leading to strain hardening and cavitation in the nano Ni-P alloy.


This volume illustrates the process of conducting interdisciplinary, multi-cultural research into the relationship between patient language use and chronic disease management. The ten chapters in this book provide a model for interdisciplinary research in health discourse from start to finish. Part I describes in detail the conceptualization and design of a multi-year research project exploring language use among people living with diabetes. Part II offers a sampler of a variety of qualitative, quantitative, and contrastive methodologies that have considerable potential in the study of health discourse. Part III brings the research process full circle by discussing issues related to adapting research protocols to diverse cultural contexts, translating results into practice, and working in interdisciplinary teams.


Volume 1 1. Introduction Willis F. Overton and Peter C. M. Molenaar 2. Relational Developmental Systems and Developmental Science Willis F. Overton 3. Dynamic Systems and Developmental Science David C. Witherington 4. The Dynamic Development of Thinking, Feeling, and Acting: Infancy through Adulthood Michael F. Mascolo and Kurt W. Fischer 5. Biology, Development, and Human Systems| Robert Lickliter and Hunter Honeycutt 6. Human Evolution and Development: An Ethological Perspective Patrick Bateson 7. Neuroscience, Embodiment, and Development Peter J. Marshall 8. The Development of Agency Bryan W. Sokol, Stuart Hammond, Janet Kuebli, and Leah Sweetman 9. Dialectical Models of Socialization Leon Kuczynski and Jan De Mol 10. Human Development and Culture: Conceptual and Methodological Issues Jayanthi Mistry and Ranjana Dutta 11. Emotional Development and Consciousness Michael Lewis 12. Personal and Cultural Identities: Development and Persistence Michael J. Chandler and William L. Dunlop 13. Moral Development Elliot Turiel 14. Development and Self-Regulation Megan M. McClelland, G. John Geldhof, Claire E. Cameron, and Shannon B. Wanless 15. Developmental Psychopathology E. Mark Cummings and Kristin Valentino 16. Positive Youth Development: A Relational Developmental Systems Model Richard M. Lerner, Jacqueline V. Lerner, Edmond Bowers, and G. John Geldhof 17. Systems Methods for Developmental Research Peter C. M. Molenaar and John R. Nesselroade 18. Neuroscientific Methods with Children Michelle de Haan 19. Qualitative/Mixed Models Patrick H. Tolan, Steven M. Boker, and Nancy L. Deutsch 20. Growth Curve Modeling and Longitudinal Factor Analysis Nilam Ram and Kevin J. Grimm 21. Person-Oriented Methodological Approaches in Developmental Science Alexander von Eye, Lars R. Bergman, and Chueh-An Hsieh Volume 2 1. Introduction Lynn S. Liben and Ulrich M. Muller 2. Brain and Cognitive Development Joan Stiles, Timothy T. Brown, Frank Haist, and Terry L. Jernigan 3. Perceptual Development Scott P. Johnson and Erin E. Hannon 4. Motor development Karen Adolph 5. Attentional Development: The past, the present, and the future Jelena Ristic and James T. Enns 6. The Development of Symbolic Representation Tara Callaghan and John Corbit 7. Conceptual Development Vladimir Sloutsky 8. Language Development Brian MacWhinney 9. Early Literacy Christopher J. Lonigan 10. Nonverbal Communication: The Hand s Role in Talking and Thinking Susan Goldin-Meadow 11. Development of executive function Ulrich Muller and Kimberly Kerns 12. Development of Reasoning Robert B. Ricco 13. An Adaptive View of Memory Development Mark L. Howe 14. The Development of Mathematical Reasoning Terezinha Nunes and Peter Bryant 15. Development of spatial cognition Lynn Liben and Roger Downs 16. The Development of Play Angeline S. Lillard 17. The Developmental Psychology of Time Teresa McCormack 18. Development of scientific thinking Richard Lehrer and Leona Schauble 19. Artistic Development in the Visual Arts and Music Constance Milbrath, Gary McPherson, and Margaret Osborne 20. Cognitive Development through Media Daniel R. Anderson and Heather L. Kirkorian 21. The Development of Social Understanding Jeremy I. M. Carpendale and Charlie Lewis 22. Cognition in developing social identities and beliefs Rebecca Bigler 23. Gender Development from a Social-Cognitive Perspective Campbell Leaper 24. Cognitive Development in the Context of Culture Mary Gauvain and Susan Perez 25. Atypical Cognitive Development Bruce F. Pennington Volume 3 1. Unraveling the Processes that Underlie Social, Emotional, and Personality Development: A Preliminary Survey of the Terrain Michael E. Lamb 2. Measuring Socio-emotional Behavior and Development Celia A. Brownell, Elizabeth A. Lemerise, Kevin A. Pelphrey, and Glenn I. Roisman 3. The Prenatal Environment and its Implications for Development: An Evolutionary David A. Coall, Anna Callan, Thomas E. Dickins, and James S. Chisholm 4. Psychoneuroendocrinology of Stress: Normative Development and Individual Differences Megan R. Gunnar, Jenalee R. Doom, and Elisa A. Esposito 5. Temperament and Personality Xinyin Chen and Louis A. Schmidt 6. Relationships, Regulation, and Early Development Ross A. Thompson 7. Resilience in the Face of Adversities Suniya S. Luthar, Elizabeth J. Crossman, and Phillip J. Small 8. Socio-emotional consequences of illness and disability Keith Crnic and Cameron Neece 9. The Implications of Discrimination for Child and Adolescent Development Amy K. Marks, Kida Ejesi, Mary Beth McCullough, and Cynthia Garcia Coll 10. Race, class and ethnicity as they affect emergent adulthood Vonnie McLoyd, Kelly M. Purtell, and Cecily R. Hardaway 11. Socio-emotional Development in Changing Family Contexts Susan Golombok and Fiona Tasker 12. Children and the Law Michael E. Lamb, Lindsay C. Malloy, Irit Hershkowitz, and David La Rooy 13. A Multilevel Perspective on Child Maltreatment Dante Cicchetti and Sheree L. Toth 14. Individual Differences in Theory of Mind: A Social Perspective Claire Hughes and Rory T. Devine 15. Prosocial Development Nancy Eisenberg, Tracy L. Spinrad, & Ariel Knafo 16. Development of Achievement Motivation and Engagement Allan Wigfield, Jacquelynne S. Eccles, Jennifer Fredricks, Sandra Simpkins, Robert Roeser, and Ulrich Schiefele 17. Morality: Origins and Development Melanie Killen and Judith G. Smetana 18. Conceptualizing the Self: Contributions of Normative Human Processes, Diverse Contexts and Opportunity Margaret Beale Spencer, Dena Phillips Swanson, and Vinay Harpalani 19. Aggressive and Violent Behavior Manuel Eisner and Tina Malti 20. Gendered development Melissa Hines 21. The Development of Sexuality Lisa M. Diamond, Susan B. Bonner, and Janna A. Dickenson 22. Friendships, Romantic Relationships, and Other Dyadic Peer Relationships in Childhood and Adolescence: A Unified Relational Perspective Wyndol Furman and Amanda J. Rose 23. The Nature and Functions of Religious and Spiritual Development in Childhood and Adolescence Pamela Ebstyne King and Chris J. Boyatzis Volume 4 1. Children in Bioecological Landscapes of Development Marc H. Bornstein and Tama Leventhal 2. Human Development in Time and Place Glen H. Elder, Jr., Michael J. Shanahan, and Julia A. Jennings 3. Children and their Parents Marc H. Bornstein 4. Children in Diverse Families Lawrence Ganong, Marilyn Coleman, and Luke Russell 5. Children in Peer Groups Kenneth H. Rubin, William M. Bukowski, and Julie Bowker 6. Early Child Care and Education Margaret Burchinal, Katherine Magnuson, Douglas Powell, and Sandra Soliday Hong 7. Children at School Robert Crosnoe and Aprile D. Benner 8. Children s Organized Activities Deborah Lowe Vandell, Reed W. Larson, Joseph L. Mahoney, and Tyler W. Watts 9. Children at Work Jeremy Staff, Arnaldo Mont'Alvao, and Jeylan T. Mortimer 10. Children and Digital Media Sandra L. Calvert 11. Children in Diverse Social Contexts Velma McBride Murry, Nancy E. Hill, Dawn Witherspoon, Cady Berkel, and Deborah Bartz 12. Children s Housing and Physical Environments Robert H. Bradley 13. Children in Neighborhoods Tama Leventhal, Veronique Dupere, and Elizabeth Shuey 14. Children and Socioeconomic Status Greg J. Duncan, and Katherine Magnuson, and Elizabeth Votruba-Drzal 15. Children in Medical Settings Barry Zuckerman and Robert D. Keder 16. Children and the Law Elizabeth Cauffman, Elizabeth Shulman, Jordan Bechtold, and Laurence Steinberg 17. Children and Government Kenneth A. Dodge and Ron Haskins 18. Children in War and Disaster Ann S. Masten, Angela J. Narayan, Wendy K. Silverman, and Joy D. Osofsky 19. Children and Cultural Context Jacqueline J. Goodnow and Jeanette A. Lawrence 20. Children in History Peter N. Stearns 21. Assessing Children from a Bioecological Perspective Theodore D. Wachs


I. INTRODUCTION. In June and July, 1935 the author visited Great Britain to study the igneous phenomena of Scotland. The main purpose of this work was to compare the deeply-eroded igneous intrusions and roots of former volcanism in Scotland with the active volcanoes studied by him during a journey through Italy in 1927 and throughout his geological field-work in the Dutch East Indies (1927-34). In the following pages the main principles ruling the ascent of magma will be discussed in connection with the Undation Theory which has been developed by the author since 1931. Acknowledgement is due to E. B. Bailey, R. Campbell, W. Q. Kennedy, J. E. Richey and G. W. Tyrrell, for their information and invaluable help in the field, The author wishes to express his special indebtedness to Dr. G. W. Tyrrell1 and Dr. W. Q. Kennedy for their help with the preparation and correction of this paper. Acknowledgements are also due: to the Controller of H.M. Stationery Office for permission to reproduce Fig. 8 from "The Geology of Ardnamurchan, North-west Mull and Coll" (Mem. Geol. Surv., 1930, Fig. 4, p. 53) and for the loan of the relative block; to Professor E. B. Bailey and the Editor of the Geological Magazine for similar authority in regard to Fig. 2 (Geol. Mag., 1926, p. 482, Fig. 1); and to Dr. J. E, Richey and the Council of the Geological Society of Glasgow for the use of the blocks of Plate VI and Fig. 5, both of which This 250-word extract was created in the absence of an abstract


This study describes the preparation of a composite material [1] from synthetic nano-scaled hydroxyapatite (nHA) and a gelatin matrix (80% nHA, 20% gelatin). This composite material is intended to extend the range of biological hydroxyapatite-based defect-filling materials for bone replacement. Ostim® (aqueous suspension of nHA having a crystallite size of about 20nm) was used as the inorganic component whereas porcine gelatin (type A, 180 Bloom) composed the organic part. Both components were homogenized during a spray-drying process. Cylindrical samples of the spray-dried granulate (HG 80/20) produced by pressing had adequate mechanical stability for storage, transport and handling in the surgery. The flexural strengths for the samples were determined on dry samples as well as after storing in media (distilled water, SBF solution) for 60 minutes. After staying 30 minutes in a SBF solution or in water, flexural strength dropped off about 30% while the shape of the sample was retained. Temperature treatments of both granulate and pressed samples resulted in reduction of the sample swelling from 70vol-% to 50vol-%. The sample produced by pressing can be machined (turned, drilled, milled).


The utilization of online stochastic algorithms is popular in large-scale learning settings due to their ability to compute updates on the fly, without the need to store and process data in large batches. When a constant step-size is used, these algorithms also have the ability to adapt to drifts in problem parameters, such as data or model properties, and track the optimal solution with reasonable accuracy. Building on analogies with the study of adaptive filters, we establish a link between steady-state performance derived under stationarity assumptions and the tracking performance of online learners under random walk models. The link allows us to infer the tracking performance from steady-state expressions directly and almost by inspection.


In this paper, we propose a novel pipeline that leverages language foundation models for temporal sequential pattern mining, such as for human mobility forecasting tasks. For example, in the task of predicting Place-of-Interest (POI) customer flows, typically the number of visits is extracted from historical logs, and only the numerical data are used to predict visitor flows. In this research, we perform the forecasting task directly on the natural language input that includes all kinds of information such as numerical values and contextual semantic information. Specific prompts are introduced to transform numerical temporal sequences into sentences so that existing language models can be directly applied. We design an AuxMobLCast pipeline for predicting the number of visitors in each POI, integrating an auxiliary POI category classification task with the encoder-decoder architecture. This research provides empirical evidence of the effectiveness of the proposed AuxMobLCast pipeline to discover sequential patterns in mobility forecasting tasks. The results, evaluated on three real-world datasets, demonstrate that pre-trained language foundation models also have good performance in forecasting temporal sequences. This study could provide visionary insights and lead to new research directions for predicting human mobility.


Shope fibroma virus (SFV) causes a localized, self-limited, fibroblastic proliferation in adult rabbits. Extracts of Shope fibroma tumors were found to contain a second virus that induces a rapidly progressive disseminated tumor. Dissemination of this malignant fibroma is associated with activation of commensal mucosal infection with Pasteurella multocida, causing purulent conjunctivitis and rhinitis and resulting in death from nasal obstruction. We have isolated this new agent by two cycles of plaque purification. It is a poxvirus that is antigenically virtually identical to SFV as measured by a plaque reduction assay, but behaves differently both in vivo and in vitro. We have called this virus malignant rabbit fibroma virus (MV). Electrophoresis of restriction digests made with HIND III indicates that despite the antigenic similarity of SFV and MV, the locations of HIND III sites in the two viral genomes are quite different. These experiments have enabled us to determine that MV was present in small quantities in our initial uncloned stock of Patuxent strain SFV. Lymphocytes from rabbits bearing MV-induced tumors responded poorly to both B and T lymphocyte mitogens. This nonspecific immunologic dysfunction is evident at or before the time when metastases and Gram-negative infection develop, and it becomes more profound as the disease progresses. MV-induced tumors may provide a model for Gram-negative infection and decreased immunologic responsiveness associated with malignancies.


Non-adherence to oral contraception regimens can have serious consequences: oral contraception misuse or discontinuation is often caused by forgetfulness, and results in over 1 million unwanted pregnancies in the US each year. Due to its simplicity and habitual nature, taking the Pill can be easily incorporated into a daily routine. However, technology-based interventions aimed at improving adherence only focus on just-in-time reminders and taking the Pill at a specified time; the routine aspect of the task is neglected. We argue that technology that facilitates the creation of sustainable habits and supports women when their routine changes could reduce forgetfulness and would be more effective at reducing non-adherence than existing reminder-based solutions.


The Lough Nafooey arc, in the western Irish Caledonides, collided with Laurentia during the Early Ordovician. This event is recorded in the stratigraphy of the South Mayo trough, the preserved forearc basin of this system. Lavas at the base of the oldest Lough Nafooey Group show intraoceanic arc composition. eNd(t) decreases and light rare earth elements (REEs) become more enriched upsection in the Lough Nafooey Group (ca. 495‐ 481 Ma), reflecting early collision with Laurentia. The subsequent Tourmakeady Group (ca. 481‐470 Ma) is rhyolitic, light REE enriched, and has strongly negative eNd(t). These rocks were erupted during the Grampian orogeny. The Rosroe and Mweelrea Formations (,470 Ma) show wide scatter of La/Sm and Nb/Zr values, suggesting mixed mantle sources. This correlates with rapid exhumation of the adjacent Connemara metamorphic terrane. The chemical evolution of the arc supports models of collision, orogeny, and tectonic unroofing within ;15 m.y., and shows that genesis of magmas more enriched than continental crust can occur during arc-continent collision, clarifying the potential role of arc volcanism in continental crust formation.


Volume 193, no. 22, p. 6375– 6378, 2011, https://doi.org/10.1128/JB.05949-11. There were errors in the construction of Fig. 2A and C, where the incorrect panels were used to represent K279a, K279a AX21, raxH AX21, and ax21 (p0387Y22A). We apologize for these errors and retract this paper due to this data misrepresentation. Citation McCarthy Y, Dow JM, Ryan RP. 2017. Retraction for McCarthy et al., "The Ax21 protein is a cell-cell signal that regulates virulence in the nosocomial pathogen Stenotrophomonas maltophilia." J Bacteriol 199:e00156-17. https://doi.org/10.1128/JB .00156-17. Copyright © 2017 American Society for Microbiology. All Rights Reserved. RETRACTION


Abstract : We aim to investigate advancing the state of the art of detection, classification and localization (DCL) in the field of bioacoustics. The two primary goals are to develop transferable technologies for detection and classification in: (1) the area of advanced algorithms, such as deep learning and other methods; and (2) advanced systems, capable of real-time and archival and processing. This project will focus on long-term, continuous datasets to provide automatic recognition, minimizing human time to annotate the signals. Effort will begin by focusing on several years of multi-channel acoustic data collected in the Stellwagen Bank National Marine Sanctuary (SBNMS) between 2006 and 2010. Our efforts will incorporate existing technologies in the bioacoustics signal processing community, advanced high performance computing (HPC) systems, and new approaches aimed at automatically detecting-classifying and measuring features for species-specific marine mammal sounds within passive acoustic data.


The effect of pH on the glucose metabolism of non-growing cells of L. lactis MG1363 was studied by in vivo NMR in the range 4.8 to 6.5. Immediate pH effects on glucose transporters and/or enzyme activities were distinguished from transcriptional/translational effects by using cells grown at the optimal pH of 6.5 or pre-adjusted to low pH by growth at 5.1. In cells grown at pH 5.1, glucose metabolism proceeds at a rate 35% higher than in non-adjusted cells at the same pH. Besides the upregulation of stress-related genes (such as dnaK and groEL), cells adjusted to low pH overexpressed H+-ATPase subunits as well as glycolytic genes. At sub-optimal pHs, the total intracellular pool of lactic acid reached approximately 500 mM in cells grown at optimal pH and about 700 mM in cells grown at pH 5.1. These high levels, together with good pH homeostasis (internal pH always above 6), imply intracellular accumulation of the ionized form of lactic acid (lactate anion), and the concomitant export of the equivalent protons. The average number, n, of protons exported with each lactate anion was determined directly from the kinetics of accumulation of intra- and extracellular lactic acid as monitored online by 13C-NMR. In cells non-adjusted to low pH, n varies between 2 and 1 during glucose consumption, suggesting an inhibitory effect of intracellular lactate on proton export. We confirmed that extracellular lactate did not affect the lactate: proton stoichiometry. In adjusted cells, n was lower and varied less, indicating a different mix of lactic acid exporters less affected by the high level of intracellular lactate. A qualitative model for pH effects and acid stress adaptation is proposed on the basis of these results.


Background: Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of visual disturbance in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.
Results: MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1 + macrophages/microglia and CD4 + T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, reduced numbers of apoptosis in retinal ganglion cells (RGCs), and reduced numbers of Iba1 + macrophages/microglia and CD4 + T cells were also observed in the retina after MAT treatment.
Conclusions: Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that may result in blindness.


We examined the hypothesis that dolphins increase their rate of sound production during feeding events to recruit new individuals. We recorded 135.5 min of underwater sounds from bottlenose dolphins (Tursiops truncatus) near Isla del Coco, Costa Rica. Data were collected from eight feeding groups and three nonfeeding groups. We classified sounds as whistles, click trains, or pulse bursts. The number of whistles per min per dolphin was higher in feeding groups than in nonfeeding groups. More whistles than click trains or pulse bursts were produced when dolphins were feeding. On the other hand, there was no difference in the proportion of each sound type produced when dolphins were not feeding. New dolphins joined the feeding events for which we recorded dolphin sounds. Results supported the hypothesis that dolphin group size increases in response to an increase in the number of whistles by conspecifics; however, confounding factors, such as the use of specific feeding calls, need to be accounted for to support the increased sound-rate hypothesis.


We study the problem of weakly supervised grounded image captioning. That is, given an image, the goal is to automatically generate a sentence describing the context of the image with each noun word grounded to the corresponding region in the image. This task is challenging due to the lack of explicit fine-grained region word alignments as supervision. Previous weakly supervised methods mainly explore various kinds of regularization schemes to improve attention accuracy. However, their performances are still far from the fully supervised ones. One main issue that has been ignored is that the attention for generating visually groundable words may only focus on the most discriminate parts and can not cover the whole object. To this end, we propose a simple yet effective method to alleviate the issue, termed as partial grounding problem in our paper. Specifically, we design a distributed attention mechanism to enforce the network to aggregate information from multiple spatially different regions with consistent semantics while generating the words. Therefore, the union of the focused region proposals should form a visual region that encloses the object of interest completely. Extensive experiments have demonstrated the superiority of our proposed method compared with the state-of-the-arts.


Biomass residual from forest has been utilized in a large scale in Sweden after full speed development over the past decade, which contributes about 20% of the total energy consumption. This is a big event for an industrial country to shift fossil fuel-based society to a sustainable society. The well established biofuel market in Sweden is, in principle, attributed to the good synergy of a strong forest industry with the energy sector, to a good district heating system, and to a favorable tax system. In this paper, the authors are trying to present a picture of how biomass residual is shaping the Swedish energy system in the past and for the future. The production of heat, electricity and transportation fuels will be discussed. A number of critic points associated to biofuel potential, economy, environmental impact, end-use, as well as to biomass conversion technologies such as combustion, gasification and biological processes will be discussed. The advances of research and technology development in Sweden will be overviewed. Swedish bioenergy industry shows a good example in the world regarding biomass residual utilization as a renewable energy. The practices and experiences might be useful to other countries.


Abstract Many studies have found that the longer a drug user remains in treatment, the more positive the outcome. The majority of studies on the effects of time in treatment have followed subjects from the time they enter treatment. The subjects of the present study are injection drug users and crack users who were out of treatment at the time of their recruitment to the study. Between the initial and six-month follow-up interviews, some chose to enroll in drug treatment. The more time a subject spent in treatment during the follow-up period, the more likely it was that s/he was not using heroin or cocaine at follow-up (OR=.51; 95% C.I., .39–.67; p<.00l). Unlike the results of some prior studies, positive effects of time in treatment were found even when time in treatment was less than 90 days. The findings of the present study strongly suggest that treatment is beneficial even for those who remain for less than 90 days. Those who provide treatment services to drug users should attempt to maintain contact with dropouts, and support their return to treatment.


As the multiple-decade long increase in clock rates starts to slow down, main-stream general-purpose processors evolve towards single-chip parallel processing. On-chip interconnection networks are essential components of such machines, supporting the communication between processors and the memory system. This task is especially challenging for some easy-to-program parallel computers, which are designed with performance-demanding memory systems.
This study proposes an interconnection network, with a novel implementation of the Mesh-of-Trees (MoT) topology. The MoT network is evaluated relative to metrics such as wire area complexity, total register count, bandwidth, network diameter, single switch delay, maximum throughput per area, trade-offs between throughput and latency, and post-layout performance. It is also compared with some other traditional network topologies, such as mesh, ring, hypercube, butterfly, fat trees, butterfly fat trees, and replicated butterfly networks. Concrete results show that MoT provides higher throughput and lower latency especially when the input traffic (or the on-chip parallelism) is high, at comparable area cost. The layout of MoT network is evaluated using standard cell design methodology. A prototype chip with 8-terminal MoT network was taped out at 90nm technology and tested. In the context of an easy-to-program single-chip parallel processor, MoT network is embedded in the eXplicit Multi-Threading (XMT) architecture, and evaluated by running parallel applications. In addition to the basic MoT architecture, a novel hybrid extension of MoT is proposed, which allows significant area savings with a small reduction in throughput.


As more women serve in the U.S. military, the proportion of females among homeless veterans is increasing. The current study compares the individual characteristics and 1-year outcomes of homeless female and male veterans in the Housing and Urban Development-Veterans Affairs Supportive Housing (HUD-VASH) program nationally. Administrative data on 43,853 veterans (10.69% females; 89.31% males) referred to HUD-VASH were analyzed for gender differences at baseline and over a 1-year period. Homeless female veterans were younger, had shorter homeless and incarceration histories, and were less likely to have substance use disorders than men. However, despite being less likely to report combat exposure, female veterans were more likely to have posttraumatic stress disorder. Homeless female veterans were also much more likely to have dependent children with them and to plan to live with family members in supported housing. Once admitted to HUD-VASH, there were no gender differences in attrition or main housing outcomes. Case managers were faster to admit female veterans to the program, reported better working alliances, and provided more services related to employment and income than male veterans. These findings suggest homeless female veterans may have certain strengths, including being younger, less involved in the criminal justice system, and more adept at relating to professional and natural supports; but special attention to noncombat trauma and family-oriented services may be needed.


Many fragments of archaeological textiles have been found in the Netherlands during the last century. This article focuses on the way these textiles were made and used. How and where were textiles and clothes made and by whom? Was cloth production already a practice of specialists, acting in an extensive trade network, or was it a craft that mainly took place at the household level? To answer these questions  fragments of  different textiles, from  sites have been examined. Without exception these textiles were discovered in settlement context, mostly in the north of the country. The analysis of the remnants has resulted in the distinction of the different steps in the production process and insight in the way the textile products were used. The results show that many textiles are likely to have been produced at a household level. Only in a few cases were they made using special skills and tools or did the production process require much time. Some products, such as the finer fabrics, the fine needlework on several hats, fabrics with a raised nap, piled weaves and a veil-like garment, may be considered as the work of textile specialists. In this article it is argued that these specialists were either working for a patron or in an independent workshop.


This paper characterizes the optimal income and wealth tax schedules when rates of return are endogenous. Individuals exert investment effort in order to increase the return on their investments. Agents are heterogeneous along two dimensions: their investment ability and their labour market productivity. I show that when individuals can exert investment effort, the Atkinson-Stiglitz theorem that capital income should not be taxed does not hold. When the government observes wealth and capital income, it is optimal to tax capital income and subsidize wealth. When wealth is not observed, it is optimal to tax capital Income. The marginal tax rates on labour and capital income should not be equal, but they should be positively related to each other. The results extend to a model where individuals can hire investment advisors to increase the rate of return and also to a model with heterogeneous inheritance, in which case both capital Income and wealth should be taxed.


The mechanism by which interfaces in solution can be polarised depends on the nature of the charge carriers. In the case of a conductor, the charge carriers are electrons and the polarisation is homogeneous in the plane of the electrode. In the case of an insulator covered by ionic moieties, the polarisation is inhomogeneous and discrete in the plane of the interface. Despite these fundamental differences, these systems are usually treated in the same theoretical framework that relies on the Poisson–Boltzmann equation for the solution side. In this perspective, we show that interfaces polarised by discrete charge distributions are rather ubiquitous and that their associated potential drop significantly differs from those of conductor–electrolyte interfaces. We show that these configurations, spanning liquid–liquid interfaces, charged silica–water interfaces, metal oxide interfaces, supercapacitors, ion-exchange membranes and even biological membranes can be uniformly treated under a common "Discrete Helmholtz" model where the discrete charges are compensated by a single layer of correlated counter-ions, thereby generating a sharp potential drop at the interface.


OBJECTIVE
We conducted an experiment to test the applicability of integrating individual perceptions of unprotected sex consequences with alcohol's myopic effects as an explanatory framework for risky sexual decision making in young heterosexual men and women.

METHOD
Male and female participants (N = 61) rated their perceptions of unprotected sex consequences, received alcoholic (target breath alcohol concentration = .10%) or nonalcoholic drinks, and completed a risky sexual decision-making task that included a quantitative measure of sexual decision-making cue attention.

RESULTS
Intoxicated participants were more attentive to impelling cues and reported greater sexual risk intentions than sober participants. Mediational analyses indicated that attention to cues fully mediated the alcohol-sexual risk intention relationship. Moderational analyses revealed that alcohol's focusing effect acts in conjunction with pre-existing individual perceptions to influence cue salience directly and sexual risk intentions indirectly.

CONCLUSIONS
Findings demonstrate the importance of examining predispositional tendencies when investigating alcohol myopia as a mediating mechanism underlying the alcohol-risky sex relationship.


While many diseases of aging have been linked to the immunological system, immune metrics capable of identifying the most at-risk individuals are lacking. From the blood immunome of 1,001 individuals aged 8-96 years, we developed a deep-learning method based on patterns of systemic age-related inflammation. The resulting inflammatory clock of aging (iAge) tracked with multimorbidity, immunosenescence, frailty and cardiovascular aging, and is also associated with exceptional longevity in centenarians. The strongest contributor to iAge was the chemokine CXCL9, which was involved in cardiac aging, adverse cardiac remodeling and poor vascular function. Furthermore, aging endothelial cells in human and mice show loss of function, cellular senescence and hallmark phenotypes of arterial stiffness, all of which are reversed by silencing CXCL9. Importantly, we identify a key role of CXCL9 in age-related chronic inflammation and derive a metric for multimorbidity that can be utilized for the early detection of age-related clinical phenotypes.


Abstract Aberrant activation of the FMS-like tyrosine kinase-3 (FLT3) is driven by internal tandem duplication (ITD) mutations in the FLT3 gene, which are commonly observed in patients with acute myeloid leukemia (AML). Hence, FLT3 represents an attractive therapeutic target in AML (Weisberg et al., 2002). Indeed, several small molecule FLT3 inhibitors including sorafenib have showed encouraging efficacy in reducing leukemia blasts in the peripheral blood in FLT3 mutated AML patients. However, these agents have little effect on leukemic stem cells in the bone marrow (BM) microenvironment (Borthakur et al., 2011; Fathi and Chabner, 2011; Zhang et al., 2008). The BM microenvironment is enriched with cytokines and adhesion molecules, such as CXCR4 and E-selectin, which are believed to provide AML cells protection against chemotherapeutic agents (Horacek et al., 2013; Peled and Tavor, 2013). In fact, treatment with sorafenib markedly upregulated CXCR4 levels in FLT3 -mutated cells. In addition, leukemia cells can activate endothelial cells (EC) that induce adhesion of a sub-set of the leukemia cells through E-selectin. The adherent AML cells are sequestered in a nonproliferative state that further protects them from chemotherapy (Pezeshkian et al., 2013). Therefore, blocking CXCR4 and E-selectin in parallel could theoretically eliminate the protection provided by the interaction of leukemic cells with their BM microenvironment and enhance effectiveness of chemotherapy in FLT3-mutant AML patients. In the present study, we evaluated the effectiveness of a dual CXCR4 and E-selectin antagonist, GMI-1359 (GlycoMimetics, Inc., Rockville, MD), in targeting FLT3-ITD-mutant AML in vitro and in vivo. High levels of CXCR4 expression were observed in several human and murine AML cell lines, which was further increased in hypoxic (i.e., 1% oxygen) conditions that mimic the BM microenvironment. These FLT3 -ITD leukemic cell lines also expressed hypoxia-responsive, functional E-selectin ligands identified by reactivity with an antibody (HECA452) that binds the same carbohydrate epitope required for binding to E-selectin. One such E-selectin ligand CD44 increased in FLT3 -ITD cells cultured in hypoxia compared to those cultured in normoxia (i.e. 21% oxygen). In addition, hypoxia also enhanced CXCR4 expression on mesenchymal stem cells (MSC) and EC such as HUVEC. In hypoxic co-cultures of the FLT3 -ITD-mutant leukemia cells MV4-11 or MOLM14 with MSCs and ECs (i.e., HUVEC or TeloHAEC), the presence of the dual E-selectin/CXCR4 inhibitor GMI-1359 effectively reduced leukemic cell adhesion by ~ 50% to the MSC/EC feeder layer compared to the PBS-treated control (p The significance of these in vitro findings were studied in vivo. Female SCID beige mice were injected iv with MV4-11 and followed for survival. Beginning 14 days post tumor injection, cohorts of mice (n=10/group) were treated with saline, GMI-1359 (40 mg/kg), standard chemotherapy cytarabine plus daunorubicin, or a combination of GMI-1359 and chemotherapy. Combined treatment of mice with GMI-1359 (40 mg/kg) and chemotherapy demonstrated a profound survival benefit compared to controls or chemotherapy alone at day 135 after leukemia cell injection (i.e., 67% vs. 11% or 30%, p=0.0011 and 0.0406, respectively). Single agent treatment with GMI-1359 was statistically indistinguishable from saline alone or chemotherapy alone. In a separate cohort of MV4.11-engrafted mice, the single administration of GMI-1359 increased circulating WBC and leukemic MV4-11cells, which persisted for at least 8 hrs. This effect was consistent with GMI-1359 disrupting the protective effects of the tumor microenvironment and mobilizing MV4-11 cells from the BM niche.. These findings provide the pre-clinical basis for the evaluation of GMI-1359 in patients with FLT3 -mutant AML. Download : Download high-res image (83KB) Download : Download full-size image Figure 1 . Disclosures Zhang: Karyopharm: Research Funding. Fogler: GlycoMimetics, Inc.: Employment. Magnani: GlycoMimetics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.


D are structures designed by humans to capture water and modify the magnitude and timing of its movement downstream. The damming of streams and rivers has been integral to human population growth and technological innovation. Among other things, dams have reduced flood hazard and allowed humans to settle and farm productive alluvial soils on river floodplains; they have harnessed the power of moving water for commerce and industry; and they have created reservoirs to augment the supply of water during periods of drought. In the 5000 or so years that humans have been building dams, millions have been constructed globally, especially in the last 100 years (Smith 1971, WCD 2000). If dams have successfully met so many human needs, why is there a growing call for their removal? The answers to this question require an appreciation of society's changing needs for, and concerns about, dams, including the emerging recognition that dams can impair river ecosystems (Babbit 2002). But decisions about dam removal are complex, in no small part because great scientific uncertainty exists over the potential environmental benefits of dam removal. Certainly, the scarcity of empirical knowledge on environmental responses to dam removal contributes to this uncertainty (Hart et al. 2002). More fundamentally, however, a scientific framework is lacking for considering how the tremendous variation in dam and river attributes determines the ecological impacts of dams and the restoration potential following removal. Such an ecological classification of dams is ultimately needed to support the emerging science of dam removal. In this article, we develop a conceptual foundation for the emerging science of dam removal by (a) reviewing the ways that dams impair river ecosystems, (b) examining criteria used to classify dams and describing how these criteria are of limited value in evaluating the environmental effects of dams, (c) quantifying patterns of variation in some environmentally relevant dam characteristics using governmental databases, (d) specifying a framework that can guide the development of an ecological classification of dams, and (e) evaluating the ways that dam characteristics affect removal decisions and the future of dam removals. We restrict our analysis to the United States, where dam removals are currently hotly debated; however, the ecological framework we advocate could also be generalized to other parts of the world.


Anti-citrullinated peptide antibody (ACPA) is a highly specific serological marker for rheumatoid arthritis (RA).1,–,3 Different HLA-DRB1 alleles have been shown to be associated with the susceptibility to ACPA-positive RA.4 5 Former studies demonstrated that HLA-DRB alleles carrying a shared epitope (SE),6 consisting of a conserved amino acid motif at positions 70–74 of the HLA-DRβ chain, were strongly associated with ACPA-positive RA and with higher ACPA levels in European and Japanese populations.7,–,9 On the other hand, HLA-DRB1*09:01 was recently found to be negatively associated with ACPA levels in the Japanese.9 These observations imply that combinations of HLA-DRB1 alleles differentially influence ACPA levels in ACPA-positive RA.

To address this question, we conducted a genetic association study employing 2457 ACPA-positive Japanese RA patients. ACPA was quantified by MESACUP CCP ELISA kit (MBL Co Ltd, Nagoya, Japan) with a cut-off level of 4.5 U/ml. The patients were then divided into three groups …