Background Crystal deposition in joints leads to leukocyte recruitment and a massive release of various inflammatory mediators, in particular cytokines and chemokines. These events are well reproduced by in vitro models in which the inflammatory response has been studied in different cell type. However, it has not yet determined the exact contribution of various articular cell populations when activated by different types of crystals. Objectives To evaluate the in vitro response of different types of human cells, respectively polymorphonuclear cells (PMN), monocytes (M) and lymphocytes (L) for the production of cytokines in the presence of monosodium urate (MSU), calcium pyrophosphate (CPP) and basic calcium phosphate (BCP) crystals. Methods MSU, CPP and BCP crystals were prepared according to Denko's, Cheng's and McCarthy's method respectively, and sterilized by heating at 180°C for 2 h before each experiment. PMN, M and L were isolated from peripheral blood of 4 healthy volunteers by density gradient centrifugation and differential adhesion. Cells were stimulated, in presence of polymyxin B, with increasing concentrations of crystals (0.01, 0.05, 0.1, 0.5, 1 mg/ml) for increasing time periods (0, 1, 2, 3, 9, 18, 24 h). Culture supernatants were tested by ELISA for the production of IL-1β, IL-8, IL-6, CCL2 and IL-1Ra. Results Exposure of PMN to different crystals induced a low IL-8 production, but no detectable level of other cytokines evaluated. IL-8 levels peaked at 18 h after treatment with 0.5 mg/ml MSU (215.62±17.89 pg/ml), 0.01 mg/ml CPP (175.21±15.97 pg/ml) and 1 mg/ml BCP (105.75±6.31 pg/ml) crystals. In contrast, stimulation of M by MSU, CPP and BCP crystals resulted in a significant increase in the release of all cytokines assessed. The highest levels of IL-1β, IL-8 and IL-6 were observed with MSU at 0.5 mg/ml (201.09±6.10; 3190.00±74.81; 52.82±8.48 pg/ml respectively), CPP at 0.05 mg/ml (169.89±4.02; 1232.7±63.07; 36.94±9.47 pg/ml) and BCP at 1 mg/ml (146.01±6.36; 4133.2±56,57; 49.5±2.69 pg/ml) after 18 h of treatment and then decreased after 24 h, whereas those of CCL2 reached a maximum at 3h (MSU: 153.96±11.35; CPP: 99.6±6.85; BCP: 59.42±4.13 pg/ml) and diminished at 9 h. IL-1Ra release induced by MSU, CPP and BCP crystals continued to increase until 24 h (100.03±14.66; 80.44±3.98; 70.85±2.13 pg/ml). MSU crystal-induced production of IL-1β and IL-1Ra was greater than that induced by other crystals. Stimulation of M by different crystals caused high secretion of IL-8 at all concentrations used. The production of IL-6 and CCL2 was similar in supernatants of M treated with the three types of crystals. Exposure of L to different crystals did not induce cytokine release. Conclusions This study demonstrates that the three types of leukocytes from the same donor behave differently after stimulation with the crystals. IL-8, the only detectable cytokine in stimulated PMN, is induced by all types of crystals. In contrast, as compared to PMN, M produce many cytokines when stimulated with all types of crystals and represent the major target cells in this type of inflammation. No detectable levels of cytokines are found in crystal-stimulated L. Crystals induce a rapid increase of pro-inflammatory cytokines, whereas longer periods could be required to release high levels of anti-inflammatory cytokines such as IL-1Ra. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4996


High shear enhances the adhesion of Escherichia coli bacteria binding to mannose coated surfaces via the adhesin FimH, raising the question as to whether FimH forms catch bonds that are stronger under tensile mechanical force. Here, we study the length of time that E. coli pause on mannosylated surfaces and report a double exponential decay in the duration of the pauses. This double exponential decay is unlike previous single molecule or whole cell data for other catch bonds, and indicates the existence of two distinct conformational states. We present a mathematical model, derived from the common notion of chemical allostery, which describes the lifetime of a catch bond in which mechanical force regulates the transitions between two conformational states that have different unbinding rates. The model explains these characteristics of the data: a double exponential decay, an increase in both the likelihood and lifetime of the high-binding state with shear stress, and a biphasic effect of force on detachment rates. The model parameters estimated from the data are consistent with the force-induced structural changes shown earlier in FimH. This strongly suggests that FimH forms allosteric catch bonds. The model advances our understanding of both catch bonds and the role of allostery in regulating protein activity.


Online learning is now a common practice in higher education.  Because of the continued growth in enrollments, higher educational institutions must prepare faculty throughout their teaching tenure for learning theory, technical expertise, and pedagogical shifts for teaching in the online environment. This study presents best practices for professional development for faculty teaching online. In this study, the Delphi Method was used to gain consensus from a panel experts on the essentiality of professional development items to help faculty prepare for teaching in the online environment. This study included four survey rounds with a panel experts to develop consensus and identify best practices consisting of essential professional development and institutional/organizational strategies for supporting faculty teaching online. These results are significant for planning new or improving existing faculty development programs that enhance teaching and learning in the online classroom.


Mucopolysaccharide polysulfate (MPS) represents a mammalian tracheal preparation, which mimics many of the properties of heparins including its anti-inflammatory actions. MPS is used topically for the treatment of inflammatory disorders. This study was designed to test the hypothesis that topical administration of MPS mobilizes many substances to mediate its therapeutic effects. A group of four non-human primates (Macaca Mulatta) were administered 4.5% MPS ointment in a dosage of 45 mg/kg, another four monkeys were administered placebo ointment at a dosage of 1.0 g/kg for 10 days. Citrated blood samples were drawn at baseline, 2, 4, 8 and 24 hours on days 1, 2, 5, 7 and 10. Markers of inflammation including thrombin activatable fibrinolytic inhibitor (TAFI), C-reactive protein (CRP), CD-40 Ligand (CD-40L), plasminogen activator inhibitor (PAI-1) and monocyte chemotactic protein (MCP-1) utilizing ELISA based methods, were used to measure the anti-inflammatory response. In the MPS treated group, a down regulation of all of these markers was observed over the 10 day period. CRP (baseline, 10.2 ±3.6; day 10, 5.1 ± 2.4 μg/ml), CD-40L (baseline, 298 ± 52; day 10, 138 ± 38 pg/ml) and MCP-1 (baseline, 350 ±68; day 10, 178 ± 42 pg/ml) showed a 50% decrease in the levels of these markers at day 10 in comparison to baseline. The PAI-1 (baseline, 65.1 ±21.2; day 10, 48.2 ±12.1 ng/ml) and TAFI (baseline, 138 ±25; day 10, 99 ± 12 % NHP) levels showed a slightly lesser effect. These results suggest that the topical administration of MPS leads to a decrease in the markers of inflammation that may result in promotion of the healing of inflammatory lesions.


Feminist self-identification influences women's voting practices, perceptions of gender discrimination, and views about their bodies. However, there is little information on how feminist self-identification influences women's experiences of high-risk pregnancy, if at all. The article focuses on women's identification with feminism within a neoliberal US context to examine how women make sense of and experience the medical prescription of pregnancy bed rest. Each year, medical professionals prescribe pregnancy bed rest for 700,000 to 1 million women in the United States. On the one hand, women's overwhelming expectation of control over their bodies and reproduction suggests that they cannot easily be divided into feminist and nonfeminist camps; on the other, preliminary findings from a small-scale qualitative study suggest ways in which feminist identification may affect women's experiences of pregnancy bed rest. Feminists were more likely to be in an egalitarian relationship that facilitated the redistribution of household chores during bed rest.


The paper summarizes the requirements necessary for the management of multimedia objects. It also analyzes the issues related to these requirements and proposes solutions that permit a high degree of media integration in a data model. The authors show how some of the requirements can be implemented using concepts from the object oriented paradigm and database systems. A brief description of the storage model MEDIAFILE is given. Finally, the authors illustrate the proposed solutions by describing the multimedia database servers architecture.


In this paper, we investigate the ideological background of Christopher Alexander's theory of design by examining his research papers on cognitive psychology by the 1960s. First, we briefly show the outline of his research history in the 1960s and examine the experiments and outcomes of the research in the papers. After the examination, we show the commonly-observed features in the papers, namely, influences from Jerome S. Bruner and Gestalt psychology. It is clear that he tried to explain how we recognize "good" forms based on the gestalt account of perception, and it seems reasonable to suppose that Alexander followed the framework of Bruner's "three modes of representation" to construct his research programs.


An experimental comparison is made between two turbulent boundary layers
produced in a low-speed water channel subjected to different pressure gradient
distributions. Both
flows involve identical favourable streamwise components, generated
via a lateral contraction of the
flow area; and in the second case, an additional
spanwise gradient is imposed by curving the walls.
The measurement system and methods are developed in full, with rigorous
testing and validation allowing the uncertainty and accuracy of the results to be
estimated. Hot-wire anemometry is employed to take measurements of velocity
using miniature single-film probes. A Hydrogen bubble visualisation system enables
an inspection of the coherent turbulent structures in the boundary layer near the
wall.
The mean-velocity measurements show a continued rise in the Reynolds number
downstream accompanied by a fall in the coefficient of friction, in spite of a relatively
high streamwise acceleration. This unorthodox behaviour was found to occur
for both
flows. In response to the acceleration, changes in the statistical moments of
streamwise velocity show an increased dominance of high velocity
fluctuations near
the wall. This corresponds with the results of the structure visualisations which
reveal a rise in the mean spanwise spacing of the low-speed
fluid elements.
The pressure gradients of the two cases are generated using a novel approach
which aims to make the effects from each strain easier to evaluate. The additional
spanwise component in the second case induced a cross
ow in the boundary layer
which reached 11% that of the local external velocity. Despite this, the measurements
and low-speed streaks show the turbulence to be relatively insensitive to this
level of three-dimensionality.
A simple numerical method is presented to model the development of the
low-speed
fluid streaks in different mean-velocity distributions. Using this model,
greater cross
flow magnitudes in the boundary layer are tested for which a positive
streak dependence is found.


In this paper, we investigate the influence of quasiperiodic perturbations on one-dimensional non-Hermitian diamond lattices that possess flat bands with an artificial magnetic flux $\theta$. Our study shows that the symmetry of these perturbations and the magnetic flux $\theta$ play a pivotal role in shaping the localization properties of the system. When $\theta=0$, the non-Hermitian lattice exhibits a single flat band in the crystalline case, and symmetric as well as antisymmetric perturbations can induce accurate mobility edges. In contrast, when $\theta=\pi$, the clean diamond lattice manifests three dispersionless bands referred to as an"all-band-flat"(ABF) structure, irrespective of the non-Hermitian parameter. The ABF structure restricts the transition from delocalized to localized states, as all states remain localized for any finite symmetric perturbation. Our numerical calculations further unveil that the ABF system subjected to antisymmetric perturbations exhibits multifractal-to-localized edges. Multifractal states are predominantly concentrated in the internal region of the spectrum. Additionally, we explore the case where $\theta$ lies within the range of $(0, \pi)$, revealing a diverse array of complex localization features within the system.


Literature suggests that there is limited awareness and understanding of international concepts among high school and college students. This study assessed global awareness and understanding of 252 high school juniors and seniors who participated in the Pennsylvania Governor School for Agricultural Sciences (PGSAS) program during the years 1995, 1996, 1997, and 1998. A survey on international concepts relative to agricultural policies and products, people and culture, world geography, and world organizations was developed. The survey was administered during a regular class period. Findings from this four-year study suggest that governor school scholars possess limited awareness and understanding about international concepts. However, scholars scored over 70 percent of the questions correct in the world geography section. In addition, scholars= scores on the survey for the four years did not show any marked difference. Overall, scholars answered only a little over one-half of the total questions correct. The results of this study have provided ample justification to hasten curricular changes relative to international education in our schools, colleges and universities.


The aim of this study was to describe motor performance in Parkinson patients in relation to controls. Gait, concentric isometric and eccentric strength in the ankle dorsiflexors were investigated in 25 patients with Parkinson's disease and in 37 control subjects of the same age. In patients concentric torque was significantly lowered but, eccentric torque was significantly lowered in male patients only. Among controls a significant difference in strength was found between sexes. This was not found in the patient group. No correlation between strength tests and clinical ratings was found in the patient group. Patients walked with significantly lower maximum and ordinary velocity, compared with controls. At constant velocity, stride length was shorter, single support had a shorter duration. The duration for heel on to ball on in males was shorter, reflecting the flat foot strike of Parkinson patients. Single support and the duration of heel on to ball on correlated significantly to the clinical ratings in male but not in female patients. In the male group of patients there was a relation between concentric strength on the one hand and gait velocity, stride length and stride frequency on the other. Female patients generally had fewer symptoms and less deviation from their respective controls in the measurements. The comparatively simple neurophysiological tests presented here may be suitable for evaluation of patients with Parkinson's disease.


It is widely believed that Amontons' law of friction holds well in various systems. Here we show based on a numerical calculation and analytical theory that Amontons' law breaks in viscoelastic materials under certain condition due to the precursor slip prior to the bulk sliding. It is also shown that instead of Amontons' law new friction law holds, which states that the static friction coefficient decreases as a power functionof load with the power-1/3. The new friction law is verified by the experiment employing polymethyl-methacrylate. The relation between the critical length of the precursor and the static friction coefficient predicted by numerical calculation and analytical theory is also verified.


In a prospective study we evaluated myoglobin (MG) and serum creatine kinase (CK) levels in two groups of subjects different in age and carrier status. CK and MG values were significantly lower in the older group. Whereas both parameters fully coincided in the younger group, CK was detected in a higher number of carriers in the older group. MG was always kept within the limits of normality when CK values were normal. We conclude that simultaneous determination of CK and MG does not improve carrier detection rate, the behavior of both biological parameters is similar in the younger age, and CK is more effective than MG for this purpose in the older subjects.


In this study, new classification models were developed which can be used in the solution to the problems of Discriminant Analysis having two groups. For the solution of these type of problems, Lam, Choo and Moy (1996) proposed a model regarding the minimization of deviations from the group means. The model examined by these authors loses its efficiency in respect of the hit ratio as the distributions of populations of samples considered go away from the normal distribution. For the samples drawn from non normal or skewed distributions, the median is a much more suitable descriptive statistic than the mean. The aim of the study is to consider the models of two-group classification problems by minimizing the deviations from the group medians. When these proposed approaches are applied to the data of real life or of simulation drawn from different distributions, it is observed that the attained performance of classification is better than both some important classification approaches in the literature and especially the classification performance minimizing the deviations from group means proposed by Lam, Choo and Moy. Key Words: Statistical Discriminant Analysis, Goal Programming, median scores


Hepatitis C virus (HCV) is predominantly a hepatotropic virus. Nonetheless, there is mounting evidence that hematopoietic cells may support HCV replication. The HCV 5' untranslated region (5'UTR), responsible for initiation of viral translation, via an internal ribosome entry site (IRES), has been previously described to contain specific nucleotide substitutions when cultured in infected lymphoid cells. Our purpose was to establish whether the 5'UTR polymorphism of quasispecies from 3 cell compartments (liver, peripheral blood mononuclear cells [PBMG], and monocyte-derived dendritic cells [DCs]) of a patient chronically infected with HCV1b affects the corresponding translational efficiencies and thus the capacity for replication. The 5'UTR polymorphism was characterized by identification of changes at 3 crucial sites as compared with the reference nucleotide (nt) sequence: a G insertion between positions 19 and 20, a C>A substitution at position 204 and a G>A substitution at position 243. The quasispecies detected in DCs was unique and differed from those present in the liver, suggesting a particular tropism of HCV quasispecies for DCs. Moreover, its translational activity was significantly impaired when compared with those from liver and PBMCs in different cell lines. This impairment was thoroughly confirmed in primary cultures of both human hepatocytes and monocyte-derived DCs. Taken together, our data lend support both to a specific location and impaired replication of HCV quasispecies in DCs, which could be related to viral persistence and perturbation of DC function in chronically infected patients.


The role of tourism discourse through verbal and visual elements in creating tourists' destination image has great significance. Most tourism discourse researchers focus on the linguistics and visual parts, but rarely have looked at measuring the elements of destination image associated with tourism discourse. Furthermore, destination image research in the context of some Middle East countries with high potential tourism attractions like Iran has been rather limited. This study tries to address this gap by attempting an in-depth understanding of Iran's image as a tourist destination worldwide, on the basis of data collected from printed and online brochures and travel guides, and by analyzing the images of the tourists who intended to visit Iran through three open-ended structured questions. The findings of this study revealed that the dominant discourse on tourism texts aim to promote the image of Iran as a safe, peaceful, and a rich land in terms of natural scenery, historical relics, gastronomy, museums and architecture; however, the image of the country has been appeared relatively negative and unfamiliar, as this country are usually classified as Arabs and Iranian culture is not distinctive among most respondents. This research further identifies the distinctive features of Iranian tourism discourse which portray various types of destination images of the country. It is concluded that a realistic communication with prospective tourists through the texts has essential influence on the formation of a positive image and consequently, the success of tourism destinations.


Background Vesicovaginal fistulas (VVF) are an unusual problem that may significantly affect a patient's quality of life. The main causes for this condition are labour complications (mostly in developing countries) and pelvic surgeries (in industrialised countries). Treatment may be conservative or surgical. Regarding surgical treatment, there is still debate about the best approach and surgical technique. Objective To demonstrate a correction of a VVF guided by cystoscopy using intravesical laparoscopic instruments. Methods Case report and surgical video of a recurrent VVF treated with a hybrid technique involving direct transvesical insertion of 3 mm laparoscopic trocars and instruments guided by cystoscopy. As far as we know, although there are some reported techniques that use a combination of transvesical laparoscopic instruments and cystoscopy, this is the least invasive and most ergonomic technique described. Results Two years after surgery, the patient remains asymptomatic and with no fistula recurrence. Conclusion The transvesical approach guided by cystoscopy seems to be an effective, safe and ergonomic minimally invasive procedure for VVF repair.


The spatial transformation of new urban areas into industrial urban areas impacts spatial structure, spatial patterns, and environmental degradation. This study aims to analyze the spatial transformation work as a determinant of the development of the new urban area of Metro Tanjung Bunga Makassar and analyze the relationship of spatial expansion, land use change and population increase for the growth of new city areas and the sustainable development of the Metro Tanjung Bunga area, Makassar city. The data for this study has been obtained through observation, surveys and documentation. The research approach used is a sequential explanation. According to the results, that excessive urbanization and maximum compaction led to spatial expansion towards the development of the new urban area of Metro Tanjung Bunga. Moreover, the increase in number has a dominant influence with a value of 32.3% on the growth of the new city area of Metro Tanjung Bunga, Makassar City. Spatial expansion, land use change, and population increase were determinants of growth factors in the new urban areas and they also had a significant impact on environmental quality degradation. This study recommends the importance of considering the impact of new urban spatial areas for the formulation of strategic policies on sustainable development as an effort to meet national development targets for the case of Metropolitan Cities in Indonesia.


Previous studies have found that long noncoding RNA (lncRNA) protein tyrosine phosphatase, receptor type, G, antisense (PTPRG-AS1) was upregulated in glioma cells. Our study aimed to explore the detailed molecular mechanisms of PTPRG-AS1 involved in glioma progression. qRT-PCR assay was performed to measure the expressions of PTPRG-AS1 and microRNA-185-5p (miR-185-5p). Cell viability, migration, invasion, and apoptosis were determined by CCK-8 assay, colony formation assay, transwell assay, and flow cytometry assay. Autophagy was evaluated using GFP-LC3 puncta analysis and western blot. Luciferase reporter and RIP assays were employed to explore the association between PTPRG-AS1 and miR-185-5p. Our data showed PTPRG-AS1 was upregulated in glioma cells and tissues. Besides, high expression of PTPRG-AS1 was positively associated with a low survival rate. Upregulation of PTPRG-AS1 promoted proliferation, migration, invasion, colony formations, and autophagy, and inhibited cell apoptosis in U373-MG cells. By contrast, PTPRG-AS1 downregulation had the inverse effect in SHG44 cells. PTPRG-AS1 negatively regulated the expression of miR-185-5p in U373-MG and SHG44 cells and the expression of miR-185-5p was decreased in glioma tissues and cells. In addition, miR-185-5p overexpression suppressed proliferation, metastasis, colony formations, and autophagy, while inducing cell apoptosis in SHG44 cells. As expected, miR-185-5p depletion exhibited the inverse effect in U373-MG cells. Enhanced expression of miR-185-5p attenuated the effect of PTPRG-AS1 upregulation on U373-MG cells, while silencing of miR-185-5p undermined the effect of downregulation of PTPRG-AS1 on SHG44 cells. Our data disclosed that LncRNA PTPRG-AS1 was upregulated in glioma cells and tissues. PTPRG-AS1 regulated glioma proliferation, invasion, migration, apoptosis and autophagy by sponging miR-185-5p in vitro. A new signaling pathway PTPRG-AS1/miR-185-5p was first observed in glioma.


We postulated that atrial fibrillation (AF) induced electrical remodelling in electrically heterogeneous human atria facilitates chronic AF. A modern biophysically detailed mathematical model of human atrial action potential was modified to incorporate electrophysiological properties of different cell types present within the atria. The heterogeneous cell models were then further modified to incorporate data on AF induced electrical remodelling (AFER) of ion channel kinetics and current densities. These modified models were used to simulate electrical activity in cells, ID strands and 2D heterogeneous sheets. AFER heterogeneously reduced action potential duration in all cell types. The theme of inhomogeneous response to AFER was observed through all cell and ID simulations. Sheet simulations showed that whilst re-entry self terminated in the control case, it persisted under AFER conditions.


Several thin, Keplerian, sub-parsec megamaser disks have been discovered in the nuclei of active galaxies and used to precisely determine the mass of their host black holes. We show that there is an empirical linear correlation between the disk radius and the black hole mass. We demonstrate that such disks are naturally formed by the partial capture of molecular clouds passing through the galactic nucleus and temporarily engulfing the central supermassive black hole. Imperfect cancellation of the angular momenta of the cloud material colliding after passing on opposite sides of the hole leads to the formation of a compact disk. The radial extent of the disk is determined by the efficiency of this process and the Bondi–Hoyle capture radius of the black hole, and naturally produces the empirical linear correlation of the radial extent of the maser distribution with black hole mass. The disk has sufficient column density to allow X-ray irradiation from the central source to generate physical and chemical conditions conducive to the formation of 22 GHz H2O masers. For initial cloud column densities ≲ 1023.5 cm−2 the disk is non-self-gravitating, consistent with the ordered kinematics of the edge-on megamaser disks; for higher cloud columns the disk would fragment and produce a compact stellar disk similar to that observed around Sgr A* at the galactic center.


Through the innovative use of a special set of Holtzman inkblots, several variables of the Personality Research Form were shown to be correlates of the Abstract response for 30 male and 33 female undergraduates. For males, positive correlations were obtained between Abstract and Achievement, Endurance and Sentience; while negative correlations were obtained between Abstract and Harmavoidance and Order, respectively. For females, Abstract was positively correlated with Dominance, Nurturance, Exhibition, and Social Recognition; and negatively correlated with Abasement and Affiliation.


© Emerald Group Publishing Limited. Purpose - The purpose of this paper is to understand how an advertising campaign incorporating an ecological message affects heuristic structure of consumer preferences for hedonic (design and aesthetics) and utilitarian benefits (functionality and performance) provided by the product advertised. Also, the second objective is to reach an understanding of how brand equity moderates these relationships. Design/methodology/approach - The paper proposes a two-stage study: a qualitative and exploratory part, in which the authors seek to determine the most important hedonic and utilitarian attributes as well as strong and weak brands, and a quantitative and causative part to test the hypothesis proposed. Findings - The results show that when the brand advertised incorporates an ecological message, consumers show a greater preference for hedonic attributes than when the advertisement does not incorporate this message. On the other hand when the brand incorporating the sustainable message is weaker, consumers show a greater preference for hedonic attributes than when it is stronger. Practical implications - The result shows important managerial implications for companies with weaker brands, since it indicates that it is much more profitable, in terms of consumer's perceived usefulness, to invest in social and ecological actions than stronger brands. Originality/value - Analyse how the used of ecological messages can modify consumer's heuristic according to utilitarian and hedonics attributes.


To assess the use of anti-CD34 and anti-factor-XIII a antibodies for the differential diagnosis of dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP), we stained 40 DFs and 13 DFSPs. A significant population of dendritic and spindle cells was reactive with anti-factor-XIII a in 90% of DFs. In DFSP, most cases had very few or no reactive cells for this antiserum and reactivity was confined to the infiltrating edges of the neoplasm or to a very low percentage of cells within the bulk of the tumor. A significant overlap was detected, a reason why the stain is useful but lacks absolute specificity for this purpose. Human progenitor cell antigen (CD34) was found in all cases of DFSP that had 50–100% of reactive e cells, but in only five DFs. In DFs, the reactivity for CD34 was focal, with only ≤20% positive cells. When used together with other histopathological criteria, factor-XIIIa antibody and particularly CD34 may help to differentiate these two processes.


The Lemaitre's continuum damage model is well known in the field of damage mechanics. The anisotropic damage model given by Lemaitre is relatively simple, applicable to nonproportional loads and uses only four damage parameters. The hypothesis of strain equivalence is used to map the effective stress to the nominal stress. Both the isotropic and anisotropic damage models from Lemaitre are implemented in an in-house implicit finite element code. The damage model is coupled with an elasto-plastic material model using anisotropic plasticity (Hill-48 yield criterion) and strain-rate dependent isotropic hardening. The Lemaitre continuum damage model is based on the small strain assumption; therefore, the model is implemented in an incremental co-rotational framework to make it applicable for large strains. The damage dissipation potential was slightly adapted to incorporate a different damage evolution behavior under compression and tension. A tensile test and a low-cycle fatigue test were used to determine the damage parameters. The damage evolution was modified to incorporate strain rate sensitivity by making two of the damage parameters a function of strain rate. The model is applied to predict failure in a cross-die deep drawing process, which is well known for having a wide variety of strains and strain path changes. The failure predictions obtained from the anisotropic damage models are in good agreement with the experimental results, whereas the predictions obtained from the isotropic damage model are slightly conservative. The anisotropic damage model predicts the crack direction more accurately compared to the predictions based on principal stress directions using the isotropic damage model. The set of damage parameters, determined in a uniaxial condition, gives a good failure prediction under other triaxiality conditions.


Policy Points:
Public and private insurers are implementing payment mechanisms to improve coordination and reduce the cost of drug, hospital, and ancillary services for cancer patients. Some target unnecessary hospitalization, while others create incentives for prescribing lower-cost chemotherapies and biologics.
Physician payment methods in oncology require a balance between incentives for cost control and incentives for patient access to expensive specialty drugs.
None of the initiatives adopt bundled methods out of concern for shifting excessive financial risk onto physicians in the context of rapid pharmaceutical innovation.

Context
High-value oncology requires physicians to monitor and coordinate all aspects of care, educate and engage their patients, and adopt cost-effective drug treatments. However, oncology practices in the United States traditionally have been reimbursed based on the number of office visits performed and through cost-plus margins from prescription of expensive drugs. Public and private payers now are experimenting with methods of payment that include monthly care management fees, annual bonuses, and incentives for conservative choice among alternative drug regimens.

Methods
This paper uses case study methods to examine oncology payment initiatives at Medicare, Anthem, Aetna, and UnitedHealthcare, the nation's largest public and private health insurance plans.

Findings
The 4 insurers supplement traditional fee-for-service payment with payment methods designed to promote coordination of care and conservative use of health care resources. Medicare, Aetna, and UnitedHealthcare reward oncology practices that reduce per-patient spending, targeting unnecessary patient visits to emergency departments and hospitals. Anthem offers monthly payments to practices that adhere to lower-cost drug treatment pathways; Aetna increases the percentage markup on low-cost generic chemotherapies but not on high-cost biologics; and UnitedHealthcare removes the linkage between physician payment and spending on office-infused drugs. As a condition for receiving the new payments, each of the initiatives requires participating practices to report and, in some cases, improve performance on quality metrics. None of the initiatives bundles payment for oncology drugs together with payment for other oncology services, out of concern for shifting financial risk onto physicians and creating access barriers for patients.

Conclusions
The emerging "value-based" methods of oncology payment supplement fee-for-service and cost-based reimbursements with per-month and per-episode payments, but none of the payers bundle spending on cancer drugs with payments for other services. Payers recognize that bundled payment could create access barriers for patients and undermine innovation in effective but expensive new pharmaceuticals.


The study site lies in a semi arid climatic zone in the south eastern part of Zimbabwe. The
overall climate, with a mean annual rainfall of 350 mm/annum is not generally suitable for
farming, but groundwater from alluvial aquifers is a possible resource for supplementary
irrigation. The main source of water for most purposes is surface water, but its scarcity
causes problems for general livelihoods. The Mzingwane river is ephemeral and thus only
flows for a limited period of time during the year. The local community as such has to rely
on groundwater from alluvial aquifers for domestic purposes and food production. Alluvial
aquifers have the advantage that when they are deeper than 1m, less water is lost to
evaporation. However, the main challenge with such aquifers is that abstraction for large
scale use is expensive and usually requires investment in motorized pumps which can be
expensive for the local communities
This study evaluated groundwater resources at a local scale by characterizing the Malala
alluvial aquifer, which covers a stretch of 1000 m of the Mzingwane river and is on average
200 m wide. The aquifer is recharged, naturally, by flood events during the rainy season and,
artificially, by managed dam releases from Zhovhe dam during the dry season. The Malala
site was selected from geological mapping and resistivity studies.
The site shows indications of deeper sand layers and hence would be expected to have a
higher potential of storing more groundwater. Piezometers were installed in the river channel
to monitor the water level fluctuations in the alluvial aquifer. Water samples were collected
from Zhovhe dam, Mazunga area and Malala alluvial aquifer in order to analyse the major
ion chemistry of the water at the aquifer and at the source of recharge. A piper diagram
analysis showed that the water in the alluvial aquifer can be classified as sodium sulphate.
The water is also of a low sodium hazard and can therefore be used for irrigation without
posing much risk to the compaction of soils.
Laboratory tests were carried out to characterize the Malala alluvial aquifer material for the
porosity, hydraulic conductivity and specific yield of the aquifer. The porosity of the alluvial
aquifer was calculated to be 39% with a hydraulic conductivity of 59.76 md-1 and a specific
yield value of 5.4 %. The slope of the alluvial aquifer was measured as 0.38 %.
Resistivity surveys showed that the alluvial aquifer has an average depth of 13.4 m. The
alluvial aquifer is more enhanced on the upstream part of the dolerite dyke. The bedrock is
metamorphic rock mainly tonalitic and granodioritic gneisses. A sieve analysis experiment
showed that the alluvial aquifer is sand. Water level observations from the installed
piezometers indicated that the water levels dropped on average by 0.75 m within 97 days
after the observed dam release.
The alluvial aquifer system can store approximately 1 035 000 m3 of water per km length of
the river. 116 000 m3 of this water is readily available for abstraction and has a potential of
irrigating at least 11.6 ha/annum. An increase in the number of timed releases can lead to an
increase in the groundwater potential. 46.4 ha of land can be irrigated from the alluvial
aquifer from at least four releases per annum which saturate the aquifer. The alluvial aquifer
can thus store a significant amount of water and has a high groundwater potential to sustain
both domestic and irrigation water supply through out the year.,WATERnet


Generation of ultra-broadband beams with a non-trivial wave-front is a major challenge [1,2]. Such beams are of interest in many fields ranging from bio-medical applications to materials processing and optical telecommunications. Recently a novel type of accelerating, non diffracting beams where the distribution is described by an Airy function, was introduced [3,4]. In order to generate such complex beams, a Gaussian beam is spatially shaped by imprinting a cubic phase [3]. Usually this is performed by using a phase spatial light modulator (SLM) which although tunable it lucks in spectral bandwidth and intensity threshold.


Based on benzo[i]dipyrido[3,2-a:2',3'-c]phenazine (dppn) with photo-oxidation activity, complexes [Ir(pbt)2(dppn)]Cl (1) and [Ir(pt)2(dppn)]Cl (2) have been synthesized (pbtH = 2-phenylbenzothiazole, and ptH = 2-phenylthiazole), with two aims, including studying the influence of the cyclometalating ligands (pbt- in 1, pt- in 2) on the photo-oxidation activity of these complexes and exploring their photo-oxidation-induced luminescence. Both 1H nuclear magnetic resonance (NMR) and electrospray (ES) mass spectrometry indicate that the benzo[g]quinoxaline moiety in complex 1 can be oxidized at room temperature upon irradiation with 415 nm light. Thus, this complex in CH2Cl2 shows photo-oxidation-induced turn-on yellow luminescence. In contrast, complex 2 reveals significant structural decomposition during the process of photo-oxidation due to incorporating a cyclometalating ligand pt- instead of pbt- in complex 1. In this paper, we report the photo-oxidation behaviors and the related luminescence modulation in 1 and 2 and discuss the relationship between structure and photo-oxidation activity in these complexes.


In today's world, the digital information retrieval experience is inherently a sparse device-centric activity. Users rely on the ability of the currently used device to supply the requested information, in some disconnection from past activities on other devices. There is a growing need to develop new methods of connecting cross-context information retrieval sessions. We present PalimPost, a converged system for storing, searching, and sharing digital and physical world information using sticky notes and mobile devices. PalimPost extracts contextual cues from a user's physical environment and activities, and connects them to the user's digital world research. Subsequently, the system presents systematically categorized information that is relevant to the moment of interaction in a just-in-time manner. PalimPost uses physical sticky notes with embedded QR codes, as well as virtual sticky notes on mobile devices. The system incorporates Automatic Speech Recognition (ASR), Optical Character Recognition (OCR), and Natural Language Processing (NLP) techniques for understanding and categorizing the content.


The credit crunch and economic crisis have demonstrated the need to properly understand, characterize and assimilate risk in business activities. Failure 10 do this has resulted in serious consequences to the users involved. So the analysis and management of risk is one of the important pre·requisites to ensure a successful outcome in a business activity in any domain. In this paper we propose an approach by which an interaction initiating user in the domain of e·business ascertains beforehand the level of transactional risk in the successful completion of its business activity and utilizes it to determine on an interaction. The proposed model considers the different sub·categories and characteristics of transactional risk and ascertains in numeric and semantic terms the different levels and severities of its occurrence. It then utilizes the determined analysis of transactional risk to recommend on an informed int!;'raction·based decision to the interaction initiating user.


ABSTRACT Colloids are frequently used for fluid expansion in the intensive care unit, although its use on several clinical scenarios remains unproven of any relevant clinical benefit. The purpose of this article was to carry out a narrative review regarding the safety and efficacy of colloids in patients with sepsis and septic shock, with emphasis on the most commonly used colloids, albumin and starches. Colloids are effective fluid expanders and are able to restore the hemodynamic profile with less total volume than crystalloids. These properties appear to be preserved even in patients with sepsis with increased capillary permeability. However, some colloids are associated with renal impairment and coagulation abnormalities. Starch use was associated with increased mortality in two large clinical trials. Also, starches probably have significant renal adverse effects and may be related to more need for renal replacement therapy in severe sepsis. Albumin is the only colloid that has been shown safe in patients with sepsis and that may be associated with improved outcomes on specific subpopulations. No trial so far found any robust clinical end point favoring colloid use in patients with sepsis. Because there is no proven benefit of the use of most colloids in patients with sepsis, its use should not be encouraged outside clinical trials. Albumin is the only colloid solution that has proven to be safe, and its use may be considered on hypoalbuminemic patients with sepsis. Nevertheless, there are no robust data to recommend routine albumin administration in sepsis. Starch use should be avoided in patients with sepsis because of the recent findings of a multicenter randomized study until further evidence is available.


Parengyodontium album is a very rarely encountered opportunistic fungal pathogen. A severely neutropenic 11-year-old boy with acute T-cell lymphoblastic leukemia/lymphoma was febrile and lethargic during his admission for elective chemotherapy. No cutaneous lesion or obvious source of infection was noted, and clinical examination was otherwise unremarkable. A blood specimen was sent for culture and fungal elements were visualized. Amphotericin B was administered empirically while awaiting fungal identification. Morphologically, a hyaline mould with thin septate hyphae plus smooth-walled conidiophores and conidiogenous cells arranged in whorls of up to four was cultured. Internal transcribed spacer region sequencing identified the fungus conclusively as P. album. Repeat blood culture was also positive for the same fungus. Following a two-week course of amphotericin B, fungemia clearance was attained.


Author(s): Amoon, Aryana Turandot | Advisor(s): Kheifets, Leeka I; Arah, Onyebuchi A | Abstract: Aims: While studies have consistently found an association between childhood leukemia risk and magnetic fields, similar associations between childhood leukemia and distance to overhead power lines suggest that other factors associated with magnetic fields and proximity to overhead power lines may be responsible for observed associations including bias, confounding, or other methodologic challenges, particularly when it comes to residential mobility and dwelling type. Methods: First, we pooled data from multiple studies to assess the association with distance and evaluate whether it is due to magnetic fields or other factors associated with distance from lines. We then analyzed a single study from California to assess predictors of residential mobility between birth and diagnosis, and account for potential confounding due to residential mobility. Next, we simulated a synthetic dataset based on that study and used it to assess the sensitivity of electromagnetic field (EMF)-leukemia associations to different scenarios of uncontrolled confounding by mobility under two major hypotheses of the infectious etiology of childhood leukemia; then used the findings to conduct sensitivity analysis and empirically offset the potential bias due to unmeasured mobility in the actual California study. Finally, we assessed whether dwelling type is a risk factor for childhood leukemia, what covariates are related to dwelling type, whether dwelling type behaves as a confounder or as a potential effect measure modifier in the EMF-leukemia relationship.Results: Although we found no material association between childhood leukemia and distance to nearest overhead power line of any voltage, there was a slight increase in risk of leukemia among children living l50 m from 200+ kilovolt power lines, consistent with some previous findings. There was no association found with calculated magnetic fields in this set of studies, however, and odds ratios (ORs) remained unchanged with adjustment for potential confounders in the pooled analysis.In the California study, we found that mobility was strongly associated with age, dwelling type, and SES. Both EMF-leukemia associations were stronger in the stratum of non-movers, too, but adjustment for proxy variables had no effect. In the hybrid-simulation study, as expected, the stronger the assumed relationship between mobility and exposure and outcome, the greater the potential bias. However, no scenario created a bias strong enough to completely explain away previously observed associations. In all mobility analyses, only dwelling type seemed to affect the relationship based on a small subset of subjects, However, when expanded to a larger subset, dwelling type was neither associated with childhood leukemia risk, nor functioned as a confounder. Stratification revealed potential effect measure modification by dwelling type only.Conclusion: Although uncontrolled confounding by residential mobility had some impact on the estimated effect of EMF exposures on childhood leukemia, it is unlikely to be the primary explanation for the associations observed between power lines exposure and childhood leukemia. Similarly, dwelling type does not appear to play a significant role as either a risk factor or confounder. Future research should explore the role of dwelling and mobility as an effect measure modifier and potential interaction effects.


The focus of this Perspective article is on the comparison of two of the most popular initial applicant screening methods: Resumes and application forms. The viewpoint offered is that application forms are superior to resumes during the initial applicant screening stage of selection. This viewpoint is supported in part based on criterion-related validity evidence that favors application forms over resumes. For example, the biographical data (biodata) inventory, which can contain similar questions to those used in application forms, is one of the most valid predictors of job performance (if empirically keyed), whereas job experience and years of education, which are often inferred from resumes and cover letters, are two of the least valid predictors of job performance (among commonly used screening criteria). In addition to validity evidence, making decisions based on application forms as opposed to resumes is likely to help organizations defend against claims of discriminatory hiring while enhancing their ability to hire in a more diverse, equitable, and inclusive manner. For example, applicant names on resumes can lead to screening bias against members of identifiable subgroups, whereas an applicant's name can be easily and automatically hidden from decision-makers when reviewing application forms (particularly digital application forms). Despite these convincing arguments focused on applicant quality and diversity, a substantial research–practice gap regarding the use of resumes and cover letters remains.


Inflammatory diseases remain critical health problems worldwide. The search for anti-inflammatory drugs is a primary activity in the pharmaceutical industry. Cacalol is a sesquiterpene with anti-inflammatory potential that is isolated from Psacalium decompositum, a medicinal plant with several scientific reports supporting its anti-inflammatory activity. Cacalol acetate (CA) is the most stable form. Nevertheless, the participation of CA in the main signaling pathway associated with inflammation is unknown. Our aim was to study the anti-inflammatory effect of CA and to determine its participation in NF-κB signaling. In TPA-induced edema in mice, CA produced 70.3% inhibition. To elucidate the influence of CA on the NF-κB pathway, RAW 264.7 macrophages were pretreated with CA and then stimulated with LPS, evaluating NF-ΚB activation, IKK phosphorylation, IΚB-α, p65, cytokine expression, and COX-2 release and activity. CA inhibited NF-κB activation and its upstream signaling, decreasing phosphorylation IKB-α and p65 levels. CA also reduced expression and secretion of TNF-α, IL-1β, and IL-6. Additionally, it decreased the activity and expression of COX-2 mRNA. These data support that CA regulates the NF-κB signaling pathway, which might explain, at least in part, its anti-inflammatory effect. CA is a bioactive molecule useful for the development of anti-inflammatory agents with innovative mechanisms of action.


The temperature dependences of 35Cl nuclear quadrupole resonance frequencies nu Q, spin-lattice relaxation times T1, linewidth Delta nu and spin-spin relaxation time T2 of the solid 2,3,6-trichloroanisole are reported. Three resonance lines are observed and the experimental measurement of nu Q(T) data are analysed by means of the Bayer-Kushida theory. It appears that only low-frequency lattice modes contribute to the temperature dependence of nu Q(T). The T1(T) relaxation data show a normal behaviour and no thermally activated motion is detected. The linewidth measurements reveal that the electric field gradient affecting the Cl atoms of the molecule undergoes some sort of thermally activated motional narrowing. The T2(T) data are somewhat scarce, showing only a normal temperature behaviour for one of the chlorine atoms of the molecule while for the others it is of the order of T2*.


A combination of massive royalty funds and institutional context influenced biased funding choices by local government in the case of the Malampaya natural gas project in Palawan, Philippines. A public inquiry into the Malampaya scandal demonstrated the vulnerabilities of existing governance arrangements to undue political and personal interests. This case reflects the importance of alternative and strategic mechanisms of natural resource revenue sharing that can prevent funds from falling prey to the self-interest of local politicians. Keywords: Philippines, natural gas, royalty funds, revenue sharing, corruption, local politics


Abstract A diary is often a personal and private matter, a well-kept secret. This article discusses findings from ethnographic research in which language diaries and diary-based interviews were used as a means to collect qualitative data. The article is based on case studies of six high school students who at the time of the study were enrolled at an international boarding school in Sweden. During the interviews, the students spoke about personal matters associated with languages, identities and discriminatory practices in school and in society. The aim of the paper is twofold: (1) to investigate and describe the students' language practices, their translanguaging practices and their multilingual literacies, and (2) to analyze diary-based case studies – based on language diaries and diary-based interviews – from a methodological viewpoint as a means to collect data. The study wishes to contribute to the growing body of ethnographic research on literacy that highlights and nuances the intricate ways in which languages are being used by bilingual and/or multilingual adolescents in their everyday lives in a globalized world. The diaries together with the diary-based interviews reveal significant findings about multilingualism both on a micro and macro level. On a micro level these findings relate to, for instance, the use of translanguaging that forms part of the students' multilingual repertoires and the construction of identities in a transnational space such as the school. On a macro level, the findings relate to, for instance, language ideologies, language policies and teaching and learning in a transnational space. The results of the study have implications for language policies and teaching practices in schools with bilingual/multilingual students. The study shows how the students' language practices differ from that of the school. Furthermore the study contributes to the methodological advancement of ethnographic research methods and shows how the use of language diaries can enable the production of self-reflection based on students' language practices.


Welcome to the 10th Pan American Health Care Exchanges Conference- PAHCE 2015. This event reinforces the tradition of the PAHCE in our continent. The purpose of this event is to create cooperation, collaboration and knowledge sharing opportunities between professionals and researchers in the areas of health care, biomedical engineering and medical technology industries. The conference will cover various subjects ranging from engineering and medical research to industrial practices. It will examine the latest progress and developments in biomedicine, bioengineering, clinical engineering and the health industry.


We propose and demonstrate a novel optoelectronic phase-locked loop (OEPLL). The key element of the OEPLL is an electro-optic harmonic mixer consisting of a square-wave phase-modulated static fiber-optic gyroscope (FOG) with an intensity-modulated laser diode as the light source. As a first demonstration, we have phase-locked a target electronic oscillator modulating the laser diode at the 10th harmonic frequency of the reference oscillator which modulates the phase of the FOG.


Technetium 99m diethylenetriaminepentaacetic acid renoscintigraphy was applied to 14 patients to obtain comprehensive information on the kidney and urinary tract 12.6 8.8 months (mean SD) after uretero‐ileoceco‐proctostomy (ileocecal rectal bladder) diversion. The total glomerular filtration rate (GFR) was within the normal range in all patients, and the diuretic renogram was normal in 19 of 28 kidneys, dilated‐nonobstructive in 7 and obstructive‐intermediate in 2. The mean colonic reflux was 16.6 18.4% of total excretion and the mean total residual in the colon and rectum was 38.815.5%. In the second study, performed 12.4 3.5 months later in 9 patients, the GFR of bilateral and individual kidneys remained stable, 17 of 18 kidneys were normal as judged by both renography and pyelography, and the occurrence and degree of colonic reflux decreased. There was a tendency for the rectal capacity to increase, while the total residual tended to decrease solely due to the decrease in colonic residual. These results indicate that the ileocecal rectal bladder functions well as an internal continent reservoir and that radionuclide investigation is a valuable and cost‐beneficial means for the follow‐up of urinary diversions.


Visible-light photoredox catalysis has been successfully used in the functionalization of inert C-H bonds including C(sp2 )-H bonds of arenes and C(sp3 )-H bonds of aliphatic compounds over the past decade. These transformations are typically promoted by the process of single-electron-transfer (SET) between substrates and photo-excited photocatalyst upon visible light irradiation (household bulbs or LEDs). Compared with other synthetic strategies, such as the transition-metal catalysis and traditional radical reactions, visible-light photoredox approach has distinct advantages in terms of operational simplicity and practicability. Versatile direct functionalization of inert C(sp2 )-H and C(sp3 )-H bonds including alkylation, trifluoromethylation, arylation and amidation, has been achieved using this practical strategy.


This study investigates whether there is a relationship between corporate governance and derivatives, whether corporate governance influence in firms impacts the association between derivatives and firm value, and whether corporate governance influence affects the association between derivatives and cash flow volatility, stock return volatility and market risk. This study uses two different data samples of publicly traded firms listed on the New York Stock Exchange. The first sample comprises a panel of 6900 firm year observations and the other consists of a panel of 6234 firm year observations both over the eight-year period from 2004-2011.  With regard to whether there is a relationship between corporate governance and derivatives, the findings from the empirical results show that corporate governance does influence derivatives and therefore is an important determinant in the firm's decisions to use derivatives. Of the thirteen corporate governance variables examined, board size, institutional shareholders, CEO age, CEO bonus, CEO salary, insider shareholders and total CEO compensation show significant association with derivatives.  This study finds that derivative users exhibit higher firm value on account of the corporate governance influence, which is correspondingly largely insignificant for derivative non-users. Further the research indicates that the impact of corporate governance varies according to the different types of risks examined. Generally, the board of directors and CEO governance mechanisms reduce stock return volatility to achieve hedging effectiveness. This supports the view that directors and management take actions to reduce stock return volatility to protect their personal portfolios without having to bear the costs of hedging themselves.  With respect to cash flow volatility, the board of directors and CEO related corporate governance mechanisms largely exhibit increased risk to show evidence of speculative behavior. It supports the perceptions that managers and directors have a strong motivation to show higher earnings to protect jobs and reputation and to enhance compensation.  All the shareholder governance mechanisms encourage risk taking with respect to stock return volatility, without any increase in firm value. This is in line with research findings of market granularity by institutional and other larger block holders to indicate that these investors increase stock price volatilities and play the markets for their own financial gain. Besides they have little interest in diversifying firm risk as they already have well protected portfolios and would not want to incur additional costs of hedging.  The study finds evidence of association between corporate governance and hedging, speculation and selective hedging. Of the thirteen corporate governance variables examined in the study board diversity consistently shows hedging effectiveness, with accompanying increase in firm value. While board meetings, institutional shareholders, block shareholders, CEO age, CEO base salary and CEO compensation exhibit exclusive speculative behavior. The remaining corporate governance mechanisms: board size, insider shareholding, CEO tenure, CEO bonus and audit committee size, show evidence of selective hedging behavior.  The concurrent hedging and speculative behavior evidenced in this study supports literature in respect of selective hedging by non-financial firms. It also validates the idea that corporate governance delves in risk allocation strategies that have been evidenced by past research. The results remain unchanged, after using alternative measures for firm value and firm risk, and alternative methods of analyses.


The introduction of Medicare Part D in 2006 provided access to prescription drug coverage to all Medicare beneficiaries, including those under 65 who were eligible through the Social Security Disability Insurance (SSDI). We used data from the Medical Expenditure Panel Study (MEPS) from 2001-2009 to examine the impact of Part D coverage on prescription drug spending, drug utilization and health of SSDI beneficiaries. We also considered the effect on other healthcare utilization and self-reported health. Using a difference-in-differences design, we compared outcomes between SSDI beneficiaries and those with private insurance to estimate the net impact of the program and to over 65 Medicare beneficiaries to estimate the differential impact between aged and disabled beneficiaries. We found that Part D increased spending on prescription drugs by SSDI beneficiaries by $909.5 compared to the privately insured and by $524 compared to aged Medicare beneficiaries. However, there was no increase in the number of medication fills, suggesting potential substation to more expensive medications. The effects were similar between those with and without dual Medicaid eligibility. Out-of-pocket spending decreased significantly for SSDI beneficiaries, particularly for those without dual-eligibility. Healthcare utilization decreased and self-reported health improved. There was no indication that the pool of SSDI beneficiaries changed because of the availability of prescription drug coverage based on observable factors.


Inclusion of soaked or roasted Meskit pods at high level in concentrate diets for sheep to improve feed intake and reduce production cost has not been studied. The novelty of this study was to evaluate the effect of incorporating soaked or roasted Meskit pods at 50% level in formulated concentrates on digestibility, cost of production, performance, health status and carcass and meat quality of Omani sheep. A locally developed roasting machine was used to roast the Meskit pods at 150 оC for 30 minutes, and tap water was used in soaking the Meskit pods for 24 hours. Formulation of the Meskit pod concentrates was done using, 500 g/kg ground Meskit pods, 240 g/kg wheat bran, 200 g/kg barley, 50 g/kg dried sardine and10 g/kg of salt. All feeds were evaluated using in vitro gas production method. Four groups of intact male Omani sheep at age of 10 months-old with an average of initial weights of 27.43 ± 2.47 kg were used in feeding trial. Each group comprising of six sheep was allocated to receive either 500g/day of commercial concentrate (Oman Feed Mills) or one of the formulated Meskit pods based concentrates; commercial concentrate (CC); roasted Meskit pods based concentrate (ROMPC); raw Meskit pods based concentrate (RMPC) or soaked Meskit pods based concentrate (SMPC). All sheep were allowed free access to Rhodes grass hay and water. Daily feed intakes and bi-weekly body weights were recorded for 84 days. Later, a total of 12 sheep (3 animals per diet) underwent a digestibility experiment comprising of 10 adaptation days and 10 days for sample collection. Blood samples were collected three times during the experimental period, day one, day 42nd and on the last day of the experiment (day 84). At the end of the experiment, the sheep were slaughtered to evaluate carcass and meat quality. The collected blood samples were analysed for hematological and serum biochemistry levels, liver and kidney samples for histopathology to determine the health status of the animals. The outcome of the analysis revealed a higher CP in RMPC (14.69%) and had higher ADF and NDF in ROMPC (18.28% and 34.74%, respectively) in comparison to the rest of Meskit pods based concentrates. The RMPC indicated higher condensed tannin (2.18%) and saponin (4.12%) in comparison to other Meskit pods based concentrates whereas CC revealed non-detectable tannin. In vitro gas production results showed that raw pods (0.087 ml/h) had the lowest gas production compared to treated Meskit pods. There were no signs of illness and microscopic results of kidney and livers samples of sheep did not show any abnormalities. There were no considerable variations of digestibility coefficients of all aspects, and rumen condition had no diets effect with an exception of increased acetic acid in ROMPC group. Roasting of Meskit pods significantly increased feed intake and body weight gain by sheep as compared to use of raw or soaked Meskit pods and were comparable to those fed CC. The carcass characteristics and meat quality indicated no significant differences with an exception that sheep fed with ROMPC and CC had increased carcass weights, and ROMPC fed animals had carcass with higher expressed juice. The use of ROMPC for sheep significantly maximized the profit of the feedlot operation. This study indicated that raw and treated Meskit pods could be used at level of 50% in concentrates for feeding Omani sheep without adverse impacts on health, digestibility, performance or carcass and meat quality and roasting the Meskit pods is highly recommended as a strategy to improve the feed intake and growth rate of Omani sheep and might be an alternative feed compared to the highly priced commercial concentrate.


Using a simplified time domain modeling approach, the temperature dependent performance characteristics, such as multiplication gain, breakdown voltage, -3 dB bandwidth, gain bandwidth product and excess noise factor, have been systematically investigated for InP/InGaAs separate absorption, grading, charge and multiplication avalanche photodiodes as a function of temperature from -50/spl deg/C to 110/spl deg/C. In order to model the -3 dB bandwidth versus gain dependence based on the simplified approach, empirical expressions have been proposed to consider the effects of hole diffusion, hole trapping, RC (resistance-capacitance) and gain-bandwidth product limit together with the fast Fourier transform component of the impulse response from the time domain modeling. The modeling results generally agree with or can explain the corresponding experimental results. The effects of changing material parameters on the modeling results are also discussed. In addition, we have found that E/sub rO/, the average energy loss per collision due to optical phonon scattering at 0 K, plays a dominant role in determining the -3 dB bandwidth near breakdown and the slope of the temperature dependence of the breakdown voltage. Further, the improved performance characteristics at decreased temperatures indicate the potential application prospects of the InP/lnGaAs APDs in low temperature environments.


A number of studies were performed to assess the association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and susceptibility to type 2 diabetes (T2DM). However, the results were inconsistent and inconclusive. In the present study, the possible association was investigated by a meta-analysis. Eligible articles were identified for the period up to June 2013. Pooled odds ratios (OR) with 95% confidence intervals (CI) were appropriately derived from random-effects models or fixed-effects models. Fourteen case-control studies with a total of 2487 cases and 3538 controls were eligible. In recessive model, PAI-1 4G/5G polymorphism was associated with T2DM risk (OR = 1.23; 95% CI 1.07-1.41; P = 0.004). In the subgroup analysis by ethnicity, a significant association was found among Asians (OR = 1.27; 95% CI 1.08-1.51; P = 0.005). This meta-analysis suggested that PAI-1 4G/5G polymorphism may be associated with T2DM development.


A high-performance processing facility for synthetic aperture radar (SAR) is described. The SAR processor is designed for the ERS-1 remote sensing satellite and will process a 100-km by 100-km scene in less than eight minutes. This is three times the throughput of comparable facilities. The SAR processor is built around a 320-MFLOP parallel processor. The front-end processor is a superminicomputer, which provides the input/output capacity necessary to avoid idle time in the parallel processor, and more than 1-Gbyte storage. The design of hardware and software for the front-end processor is given as well as a brief description of the parallel processor. The output products and processing algorithms are also given along with system design philosophy.<<ETX>>


In this paper, we present a practical implementation of the parametric multi-channel Wiener filter (PMWF) noise reduction algorithm. In particular, we extend on methods that incorporate the multi-channel speech presence probability (MC-SPP) in the PMWF derivation and its output. The use of the MC-SPP brings several advantages. Firstly, the MC-SPP allows for better estimates of noise and speech statistics, for which we derive a direct update of the inverse of the noise power spectral density (PSD). Secondly, the MC-SPP is used to control the trade-off parameter in PMWF which, with proper tuning, outperforms the traditional approach with a fixed trade-off parameter. Thirdly, the MC-SPP for each frequency-band is used to obtain the MMSE estimate of the desired speech signal at the output, where we control the maximum amount of noise reduction based on our application. Experimental results on a large number of simulated scenarios show significant benefits of employing MC-SPP in terms of SNR improvements and speech distortion.


Abstract : The Report projects to 1990 the potential demand for a US SST in competition with the British-French Concorde, and examines the effects on the US balance of payments of these projections and the resulting international fleet mixes. The analysis is in three parts: (1) Passenger demand is projected by first estimating the total demand for air travel in terms of revenue passenger miles and then the extent of passenger preference for supersonic over subsonic travel. (2) Passenger demand is converted into aircraft demand and fleet mixes under various assumptions as to boom restriction, passenger valuation of travel time, and fares; and international fleet mixes are determined. (3) The US balance-of-payments implications of these aircraft and travel demands are then projected. Results are, in general, presented for a variety of conditions intended to bracket the range of possibilities. These results are given on two volumes. The present volume (Volume II) contains the appendixes to the main volume (Volume I, AD-652 309).


Methods of automatically positioning tuned circuits for rapid frequency changes are discussed. Equipment ranging from low level single-sideband exciter-receivers to high power linear rf amplifiers are considered with attention given to the correlation of positioning accuracy, tuning change time, and ultimate cost of equipment. The merits and limitations of mechanical positioning, follow-up potentiometer servo systems, and phase servo systems, are noted. Special emphasis is placed upon the adjustment of tank circuits in linear power amplifiers. The problem of obtaining phase information for the servo systems is presented and several improved circuits for tuning and loading detection are explained. The paper is concluded with a general discussion of gain control, sequencing of control circuits, and protection of tubes during tuning cycles.


OBJECTIVE
The objective of our study was to help clarify the role of CT-guided pudendal nerve blocks in the problematic and poorly understood entity of pudendal neuralgia (PN).

SUBJECTS AND METHODS
Over a 1-year period, 52 CT-guided pudendal nerve blocks were performed in 31 patients (28 women, three men; age range, 22-80 years) who suffered from chronic pelvic pain with a presumed diagnosis of PN. A combination of anesthetic and steroid was injected into the pudendal (Alcock) canal. Pre- and postprocedural pain scores (0-10) were tallied and assessed by Student t tests. A p value < 0.05 was indicative of a significant difference.

RESULTS
All procedures were successful technically, which was defined as contrast material filling the pudendal canal on CT and subsequent infusion of anesthetic and steroid. Pre- and postprocedural pain scores ranged from 2 to 10 (mean score, 6.13) and 0-10 (mean score, 2.14), respectively; the difference was statistically significant for each nerve block session (first session, p < 0.001; second session, p < 0.001; third session, p = 0.049). Of the 31 patients, two had long-term relief with pudendal nerve blocks alone. Fourteen had subsequent surgery based on initial improvement with block(s), and all 14 patients improved with surgical nerve release. Two patients had no diagnostic response and the diagnosis of PN was excluded. The gynecologic service followed the remaining 13 patients clinically.

CONCLUSION
CT-guided pudendal nerve blocks appear to be valuable diagnostically for PN and uncommonly therapeutically. On the basis of these preliminary results, we have developed an algorithm for the role of the procedure for PN.


Decision making in case of any emergency is associated with uncertainty of input data, model data and changing preferences in the decision making process. Uncertainty handling was from the beginning an integral part of the decision support system RODOS for the off-site emergency management following nuclear or radiological emergencies. What is missing so far is the visualisation of the uncertainties in the results of the model calculations. In this paper we present the first attempt to visualise uncertain information in the early and late phase of the decision making process. For the early phase, the area of sheltering was selected as example. For the later phase, the results of the evaluation subsystem of RODOS were selected being used for the analysis of remediation measures such as agricultural management options. Both attempts are still under discussion but the presentation of the early phase uncertainty will be realised in the next version.


Type 2 diabetes mellitus is a common chronic disease that causes significant morbidity and mortality worldwide. Diabetes results from a combination of increased hepatic glucose production, decreased insulin secretion from beta cells, and insulin resistance in the peripheral tissues. Currently available antidiabetic agents work by different mechanisms to lower blood glucose levels. Available treatments (such as metformin, sulfonylureas, glitazones, and insulin) have proven unsatisfactory in producing a
long-lasting impact on glycemic control. In addition, most of these treatments have undesirable side effects such as weight gain and hypoglycemia. As a result, exploring new treatment targets and new therapies is mandatory in order to treat this condition. The incretin pathway, in particular glucagon-like peptide (GLP-1), plays an important pathological role in the development of T2DM, and treatments targeting the incretin system have recently become available. These can mainly be divided into two
broad categories; GLP-1 agonists/analogs (exenatide, liraglutide), and dipeptidyl peptidase- 4 inhibitors
(sitagliptin, vildagliptin). Saxagliptin is a novel DPP-4 inhibitor that has recently approved by US FDA.
Saxagliptin is a potent and specific inhibitor of DPP-4 (in comparison with other dipeptidyl peptidase enzymes). Current data suggest that saxagliptin as monotherapy or in combination with metformin, glyburide, or a glitazone results in significant reductions in fasting and postprandial plasma glucose and hemoglobin A1c (HbA1c). Saxagliptin is well tolerated and does not increase hypoglycemia compared with the placebo, and is probably weight neutral. Saxagliptin, a DPP-4 inhibitor, offers a novel treatment option for patients with type 2 diabetes mellitus.


Identification of protein-protein interactions is crucial for unraveling cellular processes and biochemical mechanisms of signal transduction. Here we describe, for the first time, the application of the tandem affinity purification (TAP) and LC-MS method to the characterization of protein complexes from transgenic mice. The TAP strategy developed in transgenic mice allows the emplacement of complexes in their physiological environment in contact with proteins that might only be specifically expressed in certain tissues while simultaneously ensuring the right stoichiometry of the TAP protein versus their binding partners and represents a novelty in proteomics approaches used so far. Mouse lines expressing TAP-tagged 14-3-3ζ protein were generated, and protein interactions were determined. 14-3-3 proteins are general regulators of cell signaling and represent up to 1% of the total brain protein. This study allowed the identification of almost 40 novel 14-3-3ζ-binding proteins. Biochemical and functional characterization of some of these interactions revealed new mechanisms of action of 14-3-3ζ in several signaling pathways, such as glutamate receptor signaling via binding to homer homolog 3 (Homer 3) and in cytoskeletal rearrangements and spine morphogenesis by binding and regulating the activity of the signaling complex formed by G protein-coupled receptor kinase-interactor 1 (GIT1) and p21-activated kinase-interacting exchange factor β (βPIX).


We apply an exponential time integration scheme combined with a central difference scheme on a piecewise uniform mesh with respect to the spatial variable to evaluate a generalized Black-Scholes equation. We show that the scheme is second-order convergent for both time and spatial variables. It is proved that the scheme is unconditionally stable. Numerical results support the theoretical results.


We propose to encode a register of quantum bits in different collective electron spin wave excitations in a solid medium. Coupling to spins is enabled by locating them in the vicinity of a superconducting transmission line cavity, and making use of their strong collective coupling to the quantized radiation field. The transformation between different spin waves is achieved by applying gradient magnetic fields across the sample, while a Cooper pair box, resonant with the cavity field, may be used to carry out one- and two-qubit gate operations.


The proportionality of a transphasor signal to the photoexcited carrier density has been utilized to measure the transfer of the signal between adjacent optical channels and to estimate practical transphasor packing densities (~10(3) cm(-2)) for a pure, bulk étalon of InSb, 280 microm thick. By using the transphasor as a probe of the carrier population distribution produced by an adjacent beam, the ambipolar diffusion length was measured as 74 microm.


Background: Triple negative breast cancer (TNBC) is a heterogeneous group of disease. TNBC is closely related to epithelial-mesenchymal transition (EMT) and breast cancer stem cell (BCSC) phenotype. Recent studies have shown that TNBC can be classified into six subtypes including basal-like, mesenchymal–like and mesenchymal stem-like. However, clinical significance of EMT phenotype in TNBC is not clear. Methods: We performed immunohistochemical analyses of EMT markers (expression of vimentin, smooth muscle actin, osteonectin and N-cadherin; loss of E-cadherin), BCSC markers (CD44+/CD24- and ALDH1) and EMT inducers (CD146 and ZEB1) in 173 TNBCs using tissue microarrays, and correlated their expressions with clinicopathologic features of the tumor. Results: Expression of vimentin, CD44+/CD24- and CD146 was significantly higher in basal-like TNBCs (TNBC with expression of CK5/6 and/or EGFR) than in non-basal-like TNBCs. Expression of EMT markers was commonly correlated with high histologic grade, CD44+/CD24- phenotype and metaplastic carcinoma. CD146 expression was related to the expression of EMT markers and CD44+/CD24- phenotype. ZEB1 expression showed an association with the expression of smooth muscle actin, but not with BCSC markers. And it was closely correlated with high histologic grade and metaplastic carcinoma. In survival analyses, although expression of EMT and BCSC makers was not associated with the survival of the patients, ZEB1 expression was found to be an independent prognostic factor for poor disease-free survival of the patients. Conclusion: EMT phenotype can be a signature of certain subgroup of TNBC. Especially, ZEB1 expression can be used as a potential biomarker to define a subgroup of TNBC associated with poor clinical outcome. Citation Format: Min Hye Jang, Hyun Jeong Kim, Eun Joo Kim, Hee Jin Lee, So Yeon Park. Epithelial-mesenchymal transition phenotype in triple negative breast cancer: ZEB1 as a potential biomarker for poor clinical outcome [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-39.


Korea's first Naro-Science small class satellite was launched by Naro launcher in 2013. The structure of the satellite is mostly composed of aluminum honeycomb and frame. The honeycomb structure is homogenized with asymptotic homogenization method and its mechanical properties were used for the numerical analysis. There have been some difficulties to modeling the honeycomb sandwich panels for FEA. In the present study, the mechanical characteristics of the sandwich panel composite were numerically computed and used for the simulation. This methodology makes it easy to overcome the weakness of modeling of complicated sandwich panels. Both an experiment of vibration test and numerical analyses were conducted simultaneously. The analysis results from the current homogenization were compared with that of experiment. It shows a good agreement on the dynamic responses and certified the reliability of the present methodology when manipulate sandwich panel structure.


The ability of adenosine A(1) receptors to activate type 2a protein phosphatase (PP2a) and account for antiadrenergic effects was investigated in rat myocardial preparations. We observed that the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA) significantly reduces the isoproterenol-induced increase in left ventricular developed pressure of isolated heats, and this effect is blocked by pretreatment of hearts with the PP2a inhibitor cantharidin. CPA alone or given in conjunction with isoproterenol stimulation decreases phosphorylation of phospholamban and troponin I in ventricular myocytes. These dephosphorylations are blocked by an adenosine A(1) receptor antagonist and by PP2a inhibition with okadaic acid. Adenosine A(1) receptor activation was also shown to increase carboxymethylation of the PP2a catalytic subunit (PP2a-C) and cause translocation of PP2a-C to the particulate fraction in ventricular myocytes. These results support the hypothesis that adenosine A(1) receptor activation leads to methylation of PP2a-C and subsequent translocation of the PP2a holoenzyme. Increases in localized PP2a activity lead to dephosphorylation of key cardiac proteins responsible for the positive inotropic effects of beta-adrenergic stimulation.


Questions

Can herbaceous above-ground net primary production (ANPP) be estimated from remote sensing when woody and herbaceous plants are intermingled? How does herbaceous ANPP change in space and time in an ecosystem dominated by woody species? What are the main controls of herbaceous ANPP to paddock scale?

Location

Native plant communities and buffelgrass roller chopped pastures of the Arid Chaco, western Argentina (28–32° S, 64–67° W; area: 100 000 km2).

Methods

We decomposed normalized difference vegetation index (NDVI) data from MODIS (pixel size: 250 m × 250 m) into woody (W) and herbaceous (H) components. We calibrated the relationship between field estimates of herbaceous ANPP and the H component of NDVI using linear regression. The regression model fitted was applied to a 10-yr MODIS database for four paddocks to estimate herbaceous ANPP. We analysed the relationship between herbaceous ANPP and watering point distance and growing season precipitation.

Results

The annual integral of NDVI × proportion of the herbaceous component [H/(H + W)] explained 71% and 91% of herbaceous ANPP variation in native plant communities and buffelgrass roller chopped pastures, respectively. The regression model fitted, however, differed (P < 0.05) between the two types of system. The NDVI annual integral explained a higher proportion of herbaceous ANPP variations than the NDVI annual peak or the growing season (December–April) integral. For native plant communities, herbaceous production increased significantly (P < 0.05) with watering point distance, and marginally significantly (P < 0.10) with growing season precipitation. For buffelgrass roller chopped pastures, the herbaceous production increased significantly (P < 0.05) with growing season precipitation.

Conclusion

Our model was able to estimate herbaceous ANPP from the decomposition of an NDVI time series that included woody components. Thus, the model provides the basis for more accurate monitoring of spatial and temporal variability of herbaceous ANPP in areas where herbaceous and woody plant components co-exist. Applying our models, we detected clear spatial and temporal patterns of herbaceous ANPP. The possibility of describing in a spatially explicit way the past 14 yrs of herbaceous ANPP allows designing livestock management strategies and devise alternatives to control degradation processes in the Arid Chaco.


Aiming at the difficulty of extracting image features and estimating the Jacobian matrix in image based visual servo, this paper proposes an image based visual servo approach with deep learning. With the powerful learning capabilities of convolutional neural networks(CNN), autonomous learning to extract features from images and fitting the nonlinear relationships from image space to task space is achieved, which can greatly facilitate the image based visual servo procedure. Based on the above ideas a two-stream network based on convolutional neural network is designed and the corresponding control scheme is proposed to realize the four degrees of freedom visual servo of the robot manipulator. Collecting images of observed target under different pose parameters of the manipulator as training samples for CNN, the trained network can be used to estimate the nonlinear relationship from 2D image space to 3D Cartesian space. The two-stream network takes the current image and the desirable image as inputs and makes them equal to guide the manipulator to the desirable pose. The effectiveness of the approach is verified with experimental results.


The accuracy of genomic prediction determines response to selection. It has been hypothesized that accuracy of genomic breeding values can be increased by a higher density of variants. We used imputed whole-genome sequence data and various single nucleotide polymorphism (SNP) selection criteria to estimate genomic breeding values in Brown Swiss cattle. The extreme scenarios were 50K SNP chip data and whole-genome sequence data with intermediate scenarios using linkage disequilibrium-pruned whole-genome sequence variants, only variants predicted to be missense, or the top 50K variants from genome-wide association studies. We estimated genomic breeding values for 3 traits (somatic cell score, nonreturn rate in heifers, and stature) and found differences in accuracy levels between traits. However, among different SNP sets, accuracy was very similar. In our analyses, sequence data led to a marginal increase in accuracy for 1 trait and was lower than 50K for the other traits. We concluded that the inclusion of imputed whole-genome sequence data does not lead to increased accuracy of genomic prediction with the methods.


Edge bundling methods reduce visual clutter of dense and occluded graphs. However, existing bundling techniques either ignore edge properties such as direction and data attributes, or are otherwise computationally not scalable, which makes them unsuitable for tasks such as exploration of large trajectory datasets. We present a new framework to generate bundled graph layouts according to any numerical edge attributes such as directions, timestamps or weights. We propose a GPU-based implementation linear in number of edges, which makes our algorithm applicable to large datasets. We demonstrate our method with applications in the analysis of aircraft trajectory datasets and eye-movement traces.


Mutilation of the most extruding parts of the face (nose, ears, lips) has always meant a very severe impairment, not only of the body, but of the individual's personality, since it results in a permanent alteration in the most noble and expressive part of the human body. The nose, in particular, was considered, already in very ancient times, the principal element of one's physiognomy not only as far as concerns the strictly aesthetic aspects (and classic Greek art has offered us countless examples), but also because the form, the aspect itself, appeared to reflect particular qualities of the character, of the psychology of the individual, a topic which, in the past, fascinated many men of great culture, from Michele Savonarola to Gerolamo Cardano, from Giovanni Battista Della Porta to Cesare Lombroso.

The importance of the nose, purely as an aesthetic element, as a symbolic value or as an expression of the character of a subject, inspired, over the centuries, not only figurative or plastic art, but also the theatre (Edmond Rostand), poetry (Antonio Guadagnoli) (Fig. (Fig.1),1), philosophy (Blaise Pascal), narration (Edmond About, Laurence Sterne, Nicolai Gogol) and even music (Dimitri Shostakovich).

Fig. 1

An illustration from Il naso by Antonio Guadagnoli from Arezzo. Poesie giocose di Antonio Guadagnoli, Lugano, 1839.

Clearly, patients who, submitted to this type of mutilation, felt deprived of part of their very personality, attempted, in every possible way, to disguise the lesion, and already even in very ancient times, reconstructive surgery or application of a prosthesis were sought after.

While, today, severe loss of any part of the nasal arch is fairly rare and is observed only as a result of accidental traumatic events or destructive processes of neoplastic, specific or granulomatous processes, in ancient times, this type of mutilation was much more frequent. Contributing to this increased number were other causes related to certain historic periods and to the particular local customs. Often amputation of the nose was the result of judicial punishment, or may have resulted from a duel or from fighting in a battle, or, in some cases, was inflicted as revenge by a jealous lover, or in others was the consequence of a strange form of self mutilation.


Here we utilize a total chemical synthesis strategy and a mass spectrometry-based, combinatorial chemistry approach to identify key molecular interactions that contribute to the folding and stability of a model multimeric enzyme, 4-oxalocrotonate tautomerase (4OT). 4OT is a 41 kDa bacterial enzyme composed of six identical 62 amino acid subunits. A total of 16 different 4OT analogues containing various natural and unnatural N-terminal modifications were prepared by total chemical synthesis and then characterized by catalytic activity, size exclusion chromatography (SEC), and circular dichroism (CD) spectroscopy. The results of our mutational studies indicate that backbone−backbone hydrogen-bonding interactions involving the amide bond between Pro1 and Ile2 in 4OT's 62 amino acid polypeptide chain play an important role in specifying the conformation of this enzyme's native folded state. These results provide the first evidence that backbone−backbone hydrogen-bonding interactions can play such a major role...


There are many good reasons for turning co-located projects distributed, likewise there are many good reasons for turning traditional projects agile. In both cases there are many obstacles to overcome and pitfalls to avoid and the combination of agile and distributed does not make this situation any better. In general Configuration Management works as the infrastructure of any software project and its concepts and principles have to be implemented in different ways depending on the specific context. How to adapt Configuration Management for an agile context is well understood, how to adapt it for distribution is less understood -- and what changes and how to fix that when a co-located agile team goes distributed is unclear. In this position paper, we draw on our experience from academic and industrial agile projects to give our opinions on what to look out for and possibilities for solutions.


As molecular targets continue to be identified and more targeted inhibitors are developed for personalized treatment of non-small cell lung cancer (NSCLC), multigene mutation determination will be needed for routine oncology practice and for clinical trials. In this study, we evaluated the sensitivity and specificity of multigene mutation testing by using the Snapshot assay in NSCLC. We retrospectively reviewed a cohort of 110 consecutive NSCLC specimens for which epidermal growth factor receptor (EGFR) mutation testing was performed between November 2011 and December 2011 using Sanger sequencing. Using the Snapshot assay, mutation statuses were detected for EGFR, Kirsten rate sarcoma viral oncogene homolog (KRAS), phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA), v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), v-ras neuroblastoma viral oncogene homolog (NRAS), dual specificity mitogen activated protein kinase kinase 1 (MEK1), phosphatase and tensin homolog (PTEN), and human epidermal growth factor receptor 2 (HER2) in patient specimens and cell line DNA. Snapshot data were compared to Sanger sequencing data. Of the 110 samples, 51 (46.4%) harbored at least one mutation. The mutation frequency in adenocarcinoma specimens was 55.6%, and the frequencies of EGFR, KRAS, PIK3CA, PTEN, and MEK1 mutations were 35.5%, 9.1%, 3.6%, 0.9%, and 0.9%, respectively. No mutation was found in the HER2, NRAS, or BRAF genes. Three of the 51 mutant samples harbored double mutations: two PIK3CA mutations coexisted with KRAS or EGFR mutations, and another KRAS mutation coexisted with a PTEN mutation. Among the 110 samples, 47 were surgical specimens, 60 were biopsy specimens, and 3 were cytological specimens; the corresponding mutation frequencies were 51.1%, 41.7%, and 66.7%, respectively (P = 0.532). Compared to Sanger sequencing, Snapshot specificity was 98.4% and sensitivity was 100% (positive predictive value, 97.9%; negative predictive value, 100%). The Snapshot assay is a sensitive and easily customized assay for multigene mutation testing in clinical practice.


We present the Manifesto Machine, a collaborative writing environment for drafting and designing manifestos. In this instance, we report on a workshop with a group of local youths. We used the environment as a thought probe for provoking reflections on politics and civic participation. Our insights indicate that while there is a tendency to view youths as apolitical, there is scope for using such a tool to encourage active discussion and engage communities around the topics that affect them.


Children in the HOPE VI Panel Study sample face enormous challenges in becoming successful adults. Despite these challenges, some children do surprisingly well and seem able to cope effectively with the challenges in their environment. This report reviews existing research from a range of social science disciplines to identify key factors related to resiliency and to understand how these factors protect children from negative outcomes. Then, using data from the HOPE VI Panel Study, we explore which of these factors are related to resiliency in our sample of children from HOPE VI developments.