Multiple myeloma (MM) is an incurable haematological malignancy with  patients eventually exhausting all available therapeutic modalities and succumbing to the disease. Various lines of evidence have demonstrated that the Wnt/β-catenin pathway is frequently up-regulated in advanced MM. Tegavivint (BC2059), an inhibitor of the Wnt/β-catenin pathway, that we have previously shown to have anti-MM activity  in vitro, ex vivo and in vivo, is currently in clinical trials for the treatment of solid tumours. In this study, we further demonstrate the dose dependent pro-apoptotic activity of BC2059, including activity against the innately resistant human MM cell line (HMCL) LP1. We show that BC2059 causes down-regulation of β-catenin and it's down-stream target survivin, in parallel with reactive oxygen species (ROS) generation. Coincident with this, BC2059 induces autophagy with a rise in LC3II and fall in p62. Moreover, chemical inhibition of autophagy was highly synergistic with BC2059 in all HMCL tested, with evidence of pro-apoptotic potentiation of BC2059 activity, with enhanced generation of active caspases 8, 9 and 3. Consistent with this, BC2059 treatment of LP1 in combination with knock down of the autophagy related protein Atg5 markedly enhanced cell killing. In conclusion, our results demonstrate that resistance to BC2059 can be partially attributed to the induction of cytoprotective autophagy and that inhibition of autophagy enhances BC2059-induced MM cell killing.  The combination of Wnt/β-catenin pathway and autophagic inhibition represents a novel therapeutic strategy for advanced MM that warrants further evaluation.


Nitrous oxide has been widely employed by dentists as an anesthetic agent throughout its history of clinical use. While hypoxic general anesthetic techniques using nitrous oxide are rarely if ever employed today in the United States, and appear to be on the decline abroad, nitrous oxide is extensively and successfully used in dentistry as a conscious sedative to reduce anxiety and provide some supplemental analgesia. Less frequently it is used as a co-agent with intravenous anesthetics or sedatives during oral surgery or restorative dentistry. Considering the number of patients given this agent on a yearly basis, its relative lack of reported side effects when used appropriately is remarkable.


A new method has been developed to accurately measure apurinic and apyrimidinic (AP) DNA damage sites, which are lesions in DNA formed by loss of a nucleobase from oxidative stress or carcinogen adducts. If AP sites are left unrepaired (or if improperly repaired), these sites can lead to DNA mutations that may ultimately result in the formation of cancer. Hence, detection of AP sites may provide a useful indicator of exposure and susceptibility to chemical carcinogens and oxidative stress. AP detection is currently accomplished by immunodetection methods using an aldehyde reactive probe [Nakamura, J., Walker, V. E., Upton, P. B., Chiang, S.-Y., Kow, Y. W., and Swenberg, J. A. (1998) Cancer Res. 58, 222-225; Atamna, H., Cheung, I., and Ames, B. N. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 686-691]; however, these approaches lack the specificity required for unequivocal identification of the AP site. Therefore, we have developed an accurate method based on mass spectrometry detection of AP sites from AP DNA that have been prelabeled with O-4-nitrobenzylhydroxylamine (NBHA). Once labeled and once the excess labeling agent has been removed, enzymatic digestion of DNA to monomeric subunits can be accomplished, followed by isolation and detection with high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Optimization and validation of the experimental procedures and detection limits have been established using a model DNA oligomer (11-mer) containing uracil. Enzymatic removal of uracil with uracil glycosylase generates well-defined AP sites in both single- and double-stranded DNA. The addition of NBHA labels the AP site in the oligomer, creating a labeled 11-mer. HPLC-ESI-MS/MS in the negative ionization mode was used to monitor and confirm binding of NBHA to the AP oligomer. The NBHA-tagged oligomer underwent endo- and exonuclease digestion to the 5'-deoxyribose monophosphate (5'-dRp) level, thereby releasing free 5'-dRp-NBHA. The 5'-dRp-NBHA product was partially purified by solid phase extraction and quantified by LC-MS/MS using several transitions of the deprotonated molecule ([M - H]- at m/z 363) and isotopically labeled 5'-dRp-NBHA as an internal standard. Further experiments with 5',3'-bisphosphate-deoxyribose and heat/acid-treated calf thymus DNA showed similar labeling, digestion, and detection results. Initial results show a quantification limit with 100 mug of DNA to be 100 fmol (three abasic sites per 10(7) bases).


The thiol RTEM-1 beta-lactamase [Sigal, Harwood & Arentzen (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 7157-7160] is inactivated by 6-beta-bromopenicillanic acid with formation of a characteristic chromophore, absorbing maximally at 350 nm, which is covalently bound to the enzyme. Model studies suggest that the chromophore is that of a 6-carboxylate thiol ester of 2,3-dihydro-2,2-dimethyl-1,4-thiazine-3,6-dicarboxylate, which can arise by rearrangement of the thiol-penicilloate obtained by thiolysis of the beta-lactam of 6-beta-bromopenicillanate. Loss of activity of the enzyme is also concerted with disappearance of its single (cysteine) thiol group. These results indicate that the thiol group of this enzyme is indeed a nucleophilic catalyst in beta-lactam turnover. The thiol beta-lactamase is also inactivated by clavulanic acid with formation of a chromophore, presumably a 3-aminoacrylate thiol ester, at 308 nm. Both 6-beta-bromopenicillanate and clavulanate are hydrolysed more slowly by the thiol enzyme than by the native serine beta-lactamase, but, probably as a consequence of this, both compounds inactivate the former enzyme more efficiently. Cefoxitin, a poor substrate of the native enzyme, does not appear to interact covalently with the thiol beta-lactamase.


The Dutch railway system is equipped with a 1500 V direct current (DC) system. In order to facilitate further growth, the 1500 V system has needed and will need significant investments in substations. In 2001 the railway sector analysed the system and decided to continue with the system until at least 2017 and to re-evaluate the system performance again a decade later. 25 kV alternating current (AC) was considered the best option but difficult to realised in a "brownfield situation" on existing tracks. ProRail started a quick-scan study in 2011 and 2012 in which the actual existing options for power supply as described in European standards (TSI Energy) were put to the test. It led to new insights, which were not available back in 2001, and related to updated traffic development insights and a new possibility and importance of sustainable power consumption. A migration path to an alternative traction system was subsequently elaborated in 2013, the so-called 3 kV DC alternative, which was developed jointly with a societal business case. It was found that the current 1500 V DC system can still be improved in terms of efficiency but that a 3 kV alternative can achieve a step change in energy savings as well as travel time savings. The draft business case and migration plan will be the start for discussions with the operators and development of a joint business case and recommendation of the railway sector. The process has not been finished but key results from the analysis and lessons learned from this process will be discussed in this paper.


The loss of species diversity and plant community structure throughout the temperate deciduous forests of North America have often been attributed to overbrowsing by white-tailed deer (Odocoileus virginanus). Slow species recovery following removal from browsing, or reduction in deer density, has been termed a legacy effect of past deer herbivory. However, vegetation legacy effects have also coincided with changes to soil chemistry throughout the north-eastern USA. In this paper, we assess the viability of soil chemistry (i.e. pH, extractable nutrients and extractable metals) and other factors (topography, light, overstory basal area and location) as alternative explanations for a lack of vegetation recovery. We compared the relative effects of soil chemistry, site conditions and short-term (1-2 year) deer exclusion on single-species occupancy probabilities of 10 plant taxa common to oak-hickory forests in central Pennsylvania. We found detection for all modelled species was constant and high ( p ^ > 0.65), and occupancy probability of most taxa was best explained by at least one soil chemistry parameter. Specifically, ericaceous competing vegetation was more likely to occupy acidic (pH < 3.5), base cation-poor (K < 0.20 cmolc kg-1) sites, while deer-preferred plants were less likely to occur when soil manganese exceeded 0.1 cmolc kg-1. Short-term deer exclusion did not explain occupancy of any plant taxon, and site conditions were of nominal importance. This study demonstrates the importance of soil chemistry in shaping plant community composition in the north-central Appalachians, and suggests soil as an alternative, or additional, explanation for deer vegetation legacy effects. We suggest that the reliance on phyto-indicators of deer browsing effects may overestimate the effects of browsing if those species are also limited by unfavourable soil conditions. Future research should consider study designs that address the complexity of deer forest interactions, especially in areas with complex site-vegetation histories.


The term "community hospital" has been used in most instances to indicate a hospital which serves a given center of population. The great majority of such hospitals are in small or medium-sized communities in which no medical school is located. For this reason, the word "community" has often been used instead of "non-university—affiliated" or "nonteaching" in describing the work of such a hospital, since it is much more convenient than "non-university—affiliated" and, to most of the staff of a large proportion of such hospitals, occupied as they are in the education of interns and residents, the term "nonteaching" is somewhat offensive. For these reasons, the words "community hospital" will be employed in this communication to mean a hospital which does not receive medical undergraduates for regular clinical instruction nor have any direct ties with medical schools, Many of them, of course, are privileged to have physicians from the faculties of


Heparin-derived oligosaccharides, prepared by using flavobacterial heparinase, having a high degree of heterogeneity (sequence variability) were resolved into sharp well-defined bands by using polyacrylamide gel electrophoresis (PAGE). The use of a stacking gel and a high-density-pore-gradient resolving gel was primarily responsible for the success of this separation. Low-Mr standards of known structure and having a degree of polymerization (dp) 2-6 were used to establish that the separation on gradient PAGE was primarily dependent on molecular size. High-Mr oligosaccharides (dp 8-20) were prepared using strong-anion-exchange h.p.l.c. and were used to help characterize the gradient PAGE separation. Kinetic profiles were obtained for the depolymerization of heparin and heparan sulphate with heparinase and heparitinase respectively. The utility of this approach in sequencing oligosaccharides derived from glycosaminoglycans is discussed.


A 33-year-old man was brought by ambulance to the emergency department from a local park with a right-sided headache and amnesia. He did not know his name, age, address, occupation or marital status. He could not remember how he came to be in the park, nor could he recall any autobiographical event before that morning. Despite this alarming deficit, he responded to all questions directly, showing surprisingly little distress at his predicament. Cognitive testing showed that he was orientated to time and place, and able to perform well on tests of attention, concentration and recall. He was afebrile, and his physical examination was unremarkable. We observed no signs of head trauma or substance intoxication or withdrawal. His blood alcohol concentration was 0 and a urinary drug screen was unremarkable. A white cell count showed mild neutrophilia, but all other haematological and biochemical indices were normal. Cerebral computed tomography and lumbar puncture …


We report an investigation of saturation effects on the unbalanced magnetic pull in a hydroelectric generator with 20% static eccentricity. We determine the magnetic pull force by the finite-element method in parallel with a simple analytical model for various no-load voltages and loads. Saturation significantly affects the magnitude of the unbalanced magnetic pull for high voltages and large loads.


Against Sally Haslanger's influential position, I argue that gender is not needed to ensure the just treatment of sexually differentiated human bodies. Gender is only needed if the just treatment of socially important sexual differences is most effectively realized through the use of gender terms, such as "woman" or "man." In light of this aforementioned condition, I assess the following phenomena: sex differences relevant to health and medicine, reproduction, and childcare. In all of these cases, compared to gender terms, non-gender terms, such as "female," "pregnant person," or "lactating person," more simply and accurately capture the morally relevant features of socially important sexually specific phenomena. For this reason, I find that the gender is not needed for justice.


—Estrogen exerts direct effects on vascular endothelial and smooth muscle cells that are important for vascular protection. Estrogen receptor- (cid:97) (ER (cid:97) ) is expressed in vascular cells from males and females and may mediate some of the effects of estrogen on vascular tissue. However, we recently found that estrogen is able to protect against vascular injury in ovariectomized female ER (cid:97) knockout mice. These mice express the newly described estrogen receptor- (cid:98) (ER (cid:98) ) in their aortas, suggesting that ER (cid:98) may also mediate some of the direct effects of estrogen on the vasculature. In this study, the level of expression of ER (cid:97) and ER (cid:98) mRNA in male rat aortas was examined before and after vascular injury using en face (Ha¨utchen) preparations and in situ hybridization. Little or no change in ER (cid:97) expression was observed after vascular injury in either vascular endothelial or smooth muscle cells at any time point. In contrast, ER (cid:98) mRNA was found to be expressed markedly after balloon injury. In endothelial cells, ER (cid:98) was increased by 2 days after injury, and high levels of expression were maintained at 8 and 14 days. Furthermore, ER (cid:98) expression was high in luminal smooth muscle cells at 8 and 14 days after injury and had decreased to low levels by 28 days after injury. These data demonstrate the presence of ER (cid:98) in male vascular tissues and the induction of ER (cid:98) mRNA expression after vascular injury, supporting a role for ER (cid:98) in the direct vascular effects of estrogen. ( Circ Res . 1998;83:224-229.) mg/kg, AnaSed, Lloyd Laboratories) and ketamine (50 mg/kg body wt, Ketaset, Aveco Co, Inc). Early time points of wounded endothelium (10 hours and 2 days) were studied in the partially denuded rat aorta by passing an uninflated catheter along the vessel. Later time points (8 days, 2 weeks, and 4 weeks) were examined in vessels from which the endothelium was removed completely by passing an inflated embolectomy catheter along the vessel as described by Clowes et al. 26 We have previously published illustrations of this procedure, 29,30 which in the aorta leads to outgrowth of endothelium from the intercostal arteries and the appearance of smooth muscle cells in the intima within 7 days after denudation. Since the normal rat aorta and carotid artery have no intimal smooth muscle cells, endothelial cells (and a rare inflammatory cell) are the only cell types present in the intima at time points earlier than 4 days. All rats were injected with Evans blue before they were killed to identify the areas of endothelial outgrowth. On en face preparations, endothelial cells were readily distinguished from smooth muscle cells by use of the following criteria: Endothelial cells are identifiable as a single coherent layer of cells originating from the intercostal arteries with oblong nuclei equidistant from each other and oriented with blood flow. 29,30 Smooth muscle cells, on the other hand, appear anywhere within the denuded area, have randomly oriented nuclei that fre-quently overlap, and appear in multiple layers. The Ha¨utchen technique reliably removes the entire luminal cell layer for exami-nation; smooth muscle cells appear on the en face preparations as they migrate into the region of the lumen, which occurs only after day 4 in this model. The vasculature of all animals was perfusion- fixed with phosphate (0.1 mol/L, pH 7.4) buffered with 4% parafor-maldehyde. For in situ hybridization and immunostaining, rats were killed at the indicated times after injury (between 4 hours and 4 weeks).


In many cases, preventing pollution and environmental destruction is cheaper than remedying these damages. In this sense, environmental cost allocation enables a better visualization and analysis of a product's profitability. However, the environmental allocation process involves estimated information and assumes linearity between activity consumption and product that is not real in many cases. In order to handle this not-linearity, this research presents a methodology based on fuzzy logic concepts in order to model both the subjectivity and uncertainty inherent in the environmental allocation process. A case from Hansen and Mowen (2001, p. 584) has been used as a reference for the construction of the fuzzy model. Following, new variables were incorporated, and a proposed solution was developed utilizing fuzzy logic concepts. A total of 126 inference rules were created with the help of the specific software FuzzyTECH®, which resulted in the new cost drivers that were used to allocate the environmental costs to the products. The results founded in the proposed model FuzzyABC (Fuzzy Activity Based Costing) show that fuzzy logic can be used as a helpful tool in environmental cost allocation due to the ambiguity and subjectivity inherent in these process. Key-words: Environmental Costs. Fuzzy Logic. Activity based Costing. Cost Allocation. Environmental Accounting.


One of the first steps taken by the newly elected Conservative-Liberal Democrat coalition government was to initiate a review of the national strategy of the United Kingdom. The review culminated in October 2010 in the publication of a revised National Security Strategy as well as a new Strategic Defence and Security Review. With the benefit of over twelve months of hindsight, this article is concerned with the formulation, the implementation and the longer-term implications of the 2010 strategy review. The first part of the article assesses the review as a national strategic plan. What were the strategic challenges addressed by the review, what decisions, judgements and misjudgements were made, and what was overlooked? In part two the authors turn to operational matters: how far was the UK's post-review strategic experience (i.e. in Afghanistan and Libya) consistent with the decisions and promises made in 2010? Part three discusses the review as a public statement of national policy, gauging the impression it has made on the national strategic narrative since 2010: how was the review received, what reputation has it acquired and what was/is the quality of the debate surrounding it? Finally, in part four the article asks what the 2010 review and its aftermath reveal of the formulation and implementation of national strategy in the United Kingdom. Was the 2010 review simply the latest in a long series of attempts by government to find a convincing and durable compromise between security challenges and national resources? Or was the review the beginning of something different altogether? Could UK national strategy henceforth be more of an adaptive, iterative process than a compressed period of analysis and reflection followed by the publication of a policy statement with an inevitably brief shelf-life?.


Junctin is a transmembrane protein of the cardiac junctional sarcoplasmic reticulum (SR) that binds to the ryanodine receptor, calsequestrin, and triadin 1. This quaternary protein complex is thought to facilitate SR Ca2+ release. To improve our understanding of the contribution of junctin to the regulation of SR function, we examined the age-dependent effects of junctin overexpression in the atrium of 3-, 6-, and 18-wk-old transgenic mice. The ratio of atrial weight and body weight was unchanged between junctin-overexpressing (JCN) and wild-type (WT) mice at all ages investigated (n=6-8). The protein expression of triadin 1 was decreased starting in 3-wk-old JCN atria (by 69%), whereas the expression of the ryanodine receptor was diminished in 6- (by 48%) and 18-wk-old (by 57%) JCN atria compared with age-matched WT atria. Force of contraction was decreased by 35% in 18-wk-old JCN compared with age-matched WT left atrial muscle strips, which was accompanied by a prolonged time of relaxation (48.1 +/- 0.9 vs. 44.2 +/- 0.8 ms, respectively, n=6-8, P <0.05). The spontaneous beating rate of isolated right atria was higher in 18-wk-old JCN mice compared with age-matched WT mice (389 +/- 10 vs. 357 +/- 6 beats/min, respectively, n=6-8, P <0.05). Heart rate was lower by 9% in telemetric ECG recordings in 18-wk-old JCN mice during stress tests. Three-week-old JCN atria exhibited a higher potentiation of force of contraction at rest pauses of 30 s (by 13%) and of 300 s (by 35%), suggesting increased SR Ca2+ content. This was consistent with the higher force of contraction in 3-wk-old JCN atria (by 29%) compared with age-matched WT atria (by 10%) under the administration of caffeine. We conclude that in 3-wk-old atria, junctin overexpression was associated with a reduced expression of triadin 1 resulting in a higher SR Ca2+ load without changes in contractility or heart rate. In 6-wk-old JCN atria, the compensatory downregulation of the ryanodine receptor may offset the effects of junctin overexpression. Finally, the progressive decrease in ryanodine receptor density may contribute to the decreased atrial contractility and lower heart rate during stress in 18-wk-old JCN mice.


Albert Camus' existential trajectory is influenced by tragic events in the world particularly in Europe. His milieu seems to dialogue with our present context. Scholarly consensus has it that an emerging optimism slowly unfolded through his writings prior to his death. To present Camus' philosophy in terms of the meaning of life is therefore an interesting inquiry considering this surprising shift. His thoughts remain until now relevant considering the horrendous impact of negative realities that beset humanity today similar to his time. The disturbing consequences of life throbs in the spirit of every well-meaning individual. The question of meaninglessness remains a relevant question especially among the young as well as the older generation struggling to integrate life's experiences. Hence this paper is an attempt to re-articulate his thoughts to underscore the meaning of life from his classic works. In doing so, we propose to re-read Camus for religion and existential psychotherapeutic practice in general. The whole analysis will revolve around his classic works with additional references from other commentators. This re-reading of Camus' works brings to dialogue the traditional tension between religious hope and Camus' radical creative views.


We have explored the technical utility of analyzing massive sets of digital 2D seismic data, collected and processed in dozens of different surveys, conducted more than 25 years ago, using batch, automated and unsupervised pattern recognition techniques to produce a basin-wide map of the top of salt. This workflow was developed for the United States portion of the Gulf of Mexico to detect top-salt boundaries on 2D poststack migrated lines. Texture-based attributes as well as novel, reflector-based attributes were used to discriminate between salt and nonsalt on each seismic line. Explicit measures of accuracy were not calculated because the data are unlabeled, but an assessment of confidence was used to score the boundaries. The depth to the top of the salt was estimated for more than 67% of the study area ([Formula: see text] or [Formula: see text]), 17% of the study area had insufficient data for processing and analysis, and 16% of the area did not meet confidence requirements for inclusion. The final results compared well with published maps of salt and the locations of salt-trapped fields. Reliable mapping of salt deeper than 6 s two-way time could not be achieved with this data set and approach because many seismic images had indistinguishable features at this depth. The computing time was greater than linear in the number of lines, but parallelization and changes in hardware configuration could reduce the run time of about three weeks to about three days.


At the beginning of the twenty‐first century, the large democracies of Western Europe experienced some of the most prosperous and peaceful decades in human history. Specifically, the United Kingdom, France, Italy and Germany experienced high and stable quality of life, democratic accountability and state capacity between 2000 and 2019, according to the 2022 Berggruen Governance Index. While all four of these countries are among the top performers in the Index, substantial problems lurk beneath the surface. Notably, each failed to capitalise on the low interest rate environment in the decade following the global financial crisis of 2007–2009—albeit in different ways and for different reasons in each country. In particular, low investment in infrastructure and key technologies, the persistence of stubborn regional inequalities, and resulting sluggish GDP growth have prevented the 'Big Four' in Western Europe from improving further and future‐proofing their existing gains.


The modern approach of Virtual Engineering allows one to detect with some accuracy the
residual life of components especially free of cracks. The life estimation becomes cumbersome
when the components contain a crack. A straightforward formulation requires a parameter
that considers geometrical constraints and materials properties. The magnitude of the stress
singularity developed by the tip of a crack, needs to be expressed by the Stress Intensity
Factors (SIF). In order to prove the validity of the results, calibration by experimental and/or
analytical technique is required. To have a better understanding of this parameter, in the first
part of this paper an analytical model to compute the SIF connected to crack propagation
into Mode I has been implemented. The case study displays a pipeline component with a
crack defect submitted to internal pressure. Therefore, an appropriate correlation between
the analytical approach and numerical simulation has been established embedded.


The purpose of present study was to increase productivity and to promote the quality of the part in the forming system for hinge strap in automobile. So the roller-bending simulation was carried out to develop the forming system for the hinge strap. A square tube used in the roller-bending for the hinge strap was fabricated using process of the sheet forming and the welding. So study on the mechanical properties of the original metal sheet (SPCC 1.6t) and weld-line (including a HAZ) were performed before the roller-bending simulation. And the body forces of the roller (rigid body) in the roller-bending process simulation were calculated to make an accurate estimate the capacity of the oil pressure cylinder for a pressure device. Then the roller-bending process was divided into 5 steps for the simulation for validating the effect of the bending velocity on the springback. At the end, the shape after springback was estimated. The result was adopted in the design for the bending die.


The casting, sub-rapid solidified and rapidly solidified A1-5Fe alloys, with or without rare earth La have been respectively prepared by vacuum melting furnace, suction casting and melt spinning furnace. And the alloys were investigated with OM, TEM and XRD. The results show that the microstructure was apparently refined by the increasing of cooling rate. Meanwhile, the acicular Al3Fe phase transferred to flower-like phase in casting A1-5Fe alloy and the matrix morphology of the alloy also was changed in sub-rapidly solidified Al-5Fe alloy, while 1.5wt% La was added. The metastable phase A16Fe and Al11La3 phase with high melting point were found in Al-5Fe alloy and A1-5Fe-1.5La alloy.


Addition forms the basis of digital computer systems. A gate level self-timed full adder design, utilizing a pre-defined set of gates, available in a commercial synchronous standard cell library is discussed in this paper. The proposed adder satisfies Seitz's weak-indication specifications and exhibits reduced data path delay in comparison with other existing adders, which satisfy the property of indication. In terms of power and area, it is competitive to the best of other self-timed adders.


A continuous review perishable inventory system operating under the (s,S) policy is considered. Assuming a random shelf life with a general distribution, renewal arrivals and a negligible replenishment lead time, exact expressions for the expected cost rate function for unit and batch demands are derived. For unit demands, it is shown that the average cost rate function is quasi-convex in (s,S). Numerical findings indicate that the loss incurred by ignoring the randomness of the shelf life can be drastic. It is observed that the shape of the shelf life distribution has a significant impact on the costs and a precise estimation of shelf life distribution may result in substantial savings. Based on the presented analytical results, a new heuristic for positive lead times is proposed. Extensive numerical studies show that the proposed heuristic performs better than an existing one suggested for fixed shelf lives in most of the cases studied.


Delete relaxation is one of the most successful approaches to classical planning as heuristic search. The precision of these heuristics can be improved by taking some delete information into account, in particular through atomic conjunctions in the hCFF heuristic. It has recently been shown that this heuristic is especially effective when these conjunctions are learned online in a hill-climbing search algorithm. In this work, we devise a natural extension to this approach using novelty pruning, a recently-developed technique that prunes states based on whether they contain facts not seen before in the search. We evaluate our extension on the IPC benchmarks, where it beats LAMA, Mercury, and Dual-BFWS on many domains.


Space Plug-and-Play Architecture (SPA) is a set of standards to make it easier to build small satellites. Focus is put on improving the integration phase andthe time consuming validation and verification process by introducing plug-and-play functionality. From mission call-up to operational satellite it should only take six days.A SPA network consists of several different types of subnets with differentpros and cons. For each processing node there must be one Local Subnet Manager (SM-L). The SM-L can communicate over different communication protocols depending on how the respective local subnet is set up, one option is UDP/IP.In this thesis Ada Protected Objects is presented as a viable option for inter-process communication instead of UDP/IP in a SPA network. This thesis presents the initial work towards a SPA Local Subnet Adaptation that builds onlanguage constructs in Ada such as Ada Tasks and Protected Objects. The system design and implementation is verified deadlock free with UPPAAL but showsindications of livelock possibilities. The severity of these livelocksituations is discussed in the conclusion.


Background Many beneficial health outcomes for elderly are associated with sedentary (SED) and physical activity behavior (PA). However, research is scarce regarding how elderly-interventions can improve various SED- and PA-behavior. Purpose The aim with this study was to determine if eight-weeks of regular supervised exercise would have any effect on movement-patterns in elderly. For comparison, a control group, not receiving supervised exercise, performed similar pre- and end-tests intervals. Reliability of elderly accelerometer measures, in two separate pre-tests was also investigated. Methods Seventy-eight elderly exercised (65–91 years) and 43 participated in a control group (65–88 years). The exercise group had combined aerobic and strength-training, twice/w à 1 hour. Accelerometer assessments for the exercise group were performed three times; Pre-1 and Pre-2 and one test in the last week of the 8-week-exercise-period. The controls made one pre-test and one end-test at corresponding spring time intervals, without receiving any supervised physical activity. Results The exercise-group significantly improved from Pre-1 to End-test moderate-to-vigorous-PA-intensity (MVPA +41 min/week=+0.8% of-total-daily-wear-time), light-intensity (LPA +228 min/w=+3.9%), total-SED-time (−254 min/w=−4.7%) and SED-bouts-à−10 min (−320 min/w=−5.7%). The controls showed no significant improvements from pre-1-to-End-tests, except for LPA (+2.3%) and total-SED-time (and −2.7%). Total-daily-counts in the End-test increased for controls (+6,7%) but significantly more for the exercise group (+17,3%). Between the exercise groups´ two pre-tests, no significant difference was observed, except for total-PA (+4.6%) and SED-total (−2.4%). Conclusion Elderly participating in supervised exercise increase PA- and decrease SED-time, which is of importance because it is linked with improved health for elderly, longevity and potent socioeconomic gains.


Control signal networks in vehicles using dedicated communication cables such as twisted wires and fiber optics cables have been built in order to communicate between electronic control units (ECUs). However, there are problems such as the increase in weight of the cable harness and the difficulty to insure the reliability of complicated network architectures. Communication systems using in-vehicle power lines have been investigated. This paper proposes an impulse detection scheme and its four criteria to decide the impulse occurrence in a communication cycle by using the two-state hidden Markovian-Gaussian noise model for noise on in-vehicle power lines. The new scheme involves the maximum a posteriori (MAP) estimation using the Baum-Welch (BW) algorithm and the moment method to estimate the model parameters. The proposed scheme is applied to noise generated from the hidden Markov model and noise observed on in-vehicle power lines and investigate their detection accuracy. It is shown that the detection accuracy is substantially improved by using an impulse occurrence criterion based on the number of free parameters.


Senile plaques, the major neuropathological lesions of Alzheimer's disease (AD), are composed primarily of amyloid-beta (Abeta) peptide and contain high concentrations of iron (1.0 mM). We have previously shown that intracortical injections of 1.0 mM iron to adult rats produce significantly more neuronal loss than control injections of saline vehicle, whereas injections of Abeta do not. Because iron has been shown to increase the in vitro toxicity of Abeta, the present study was undertaken to determine whether iron can make Abeta neurotoxic in vivo. Abeta and 1.0 mM iron (as ferric ammonium citrate) were coinjected into rat cerebral cortex, and the neuronal loss was compared with that produced by pure Abeta or pure iron. The human and rat variants of Abeta(1-42) were compared to determine whether they produce the same amount of neuronal loss when combined with iron. Coinjection of iron with either Abeta variant caused significantly more neuronal loss than Abeta peptide alone, suggesting that iron may contribute to the toxicity associated with senile plaques. Rat Abeta(1-42) combined with iron was as toxic as iron alone, whereas iron combined with human Abeta(1-42) was significantly less toxic. This latter finding indicates that fibrillar human Abeta is able to reduce iron-induced neurotoxicity in vivo and raises the interesting possibility that senile plaques in AD may represent a neuroprotective response to the presence of elevated metal ions.


This essay, written as a response to Partha Chatterjee's on the same three concepts—nationalism, internationalism, and cosmopolitanism—in India (published in Comparative Studies of South Asia, Africa and the Middle East 36, no. 2), first considers the validity and terms of comparison and commensurability between the Indian and Ottoman/post-Ottoman cases. It then goes on to offer a sketch of how the three concepts play out in the more indeterminate political world of the Ottoman space, looking not to cases of formal colonialism in the Middle East, but to the beginning and endpoints of the devolution of the Ottoman world and its transformation into the many nation-states of the post-Ottoman world. It poses the emergence of Greece (in the 1820s) and of Turkey one century later as crystallizing moments in a different but related process to that of the colonization and decolonization of the Indian subcontinent. The goal of the exercise is to use the three concepts of nationalism, internationalism, and cosmopolitanism to arrive at a new kind of comparison, and perhaps a new kind of model of power in the nineteenth and twentieth centuries for areas that were not formally colonized but were nevertheless crucial to the formation of modern relations of power.


BACKGROUND
There is a growing interest in the use of digital technologies to foster learning in the health professions, along with the drive to expand teleconsultations arising from the COVID-19 pandemic. This study aims to explore whether telemedicine between levels of care can act as continuous medical education (CME) tool for general practitioners (GPs) and hospital consultants at the referral cardiology department.

METHODS
This qualitative study was embedded in an organizational case study of the introduction of a new service model in the Portuguese health system. Semi-structured interviews were audio-recorded and pseudonymized. The transcribed interviews were stored, coded, and content analysis was performed in MAXQDA.

RESULTS
A total of 11 physicians were interviewed. GPs and cardiologists recognized that telemedicine between levels of care could act as a CME tool. Although they departed with different expectations, telemedicine helped them collaborate as a multidisciplinary team, exchanging feedback about clinical decisions, and constructing knowledge collaboratively. Telemedicine also supplemented existing learning meetings. The consequences of technology adoption may be viewed as a result of the actors involved (including the technology itself), characteristics of the context (including the organization), and an interaction between such factors.

CONCLUSION
Teleconsultations can be a learning opportunity for the health professionals involved. Our findings suggest that, in the context of the Portuguese health system, telemedicine as a CME tool helped to build multidisciplinary teams which exchanged feedback and constructed shared knowledge to improve patients' outcomes. It also helped to identify practice-changing contents to be included in face-to-face educational meetings.


The newborn has a limited capacity to tolerate acute haemorrhage. Prompt diagnosis and therapy are essential for survival. Blood loss can occur in the newborn due to occult haemorrhage, prior to birth or during delivery, obstetric accidents, maternal haemorrhage, or secondary to recurrent blood sampling. Special precautions must be taken when events known to cause fetal haemorrhage have occurred during pregnancy. These include a maternal history of transfusion reaction in the absence of a transfusion, third trimester bleeding with placenta praevia, placenta abruptio and vasa praevia, emergency caesarean sections, twin pregnancies and amniocentesis. The clinical manifestations of post-haemorrhagic anaemia at birth depend on the extent and duration of blood loss. When acute massive blood loss has occurred, the infant is extremely pale and requires immediate transfusions or volume expanders. Although the haemoglobin may be normal initially, it rapidly falls within six to eight hours after birth. Other causes of extreme pallor in the newborn include asphyxia and anaemia secondary to haemolysis. Infants who have developed acute post-haemorrhagic anaemia are hypovolaemic, are neither jaundiced nor cyanotic, and respond to therapy with volume expanders. The clinical picture with chronic blood loss is usually mild and responds to conservative therapy with iron alone. Internal haemorrhage should be suspected when a 24 to 72 hour newborn rapidly deteriorates and has evidence for hypovolaemic shock without signs of external blood loss. The blood withdrawn for laboratory evaluation in the high risk newborn must be carefully monitored so that it can be replaced before the newborn becomes compromised.


Time series classification is a research area which has drawn much attention over the past decade. A novel approach for classification of time series uses shapelets. A shapelet is a subsequence extracted from one of the time series in the dataset which best separates between time series coming from different classes of the data set. A disadvantage of current shapelet- based classification approaches is their high time and memory consumption, which results from the examination of all possible subsequences. In this study, our initial goal was to find an evaluation order of the shapelets space which enables fast generation of an accurate classification model with a small memory footprint. The comparative analysis we conducted clearly indicates that a random evaluation order yields the best results. We present an algorithm for randomized model generation for shapelet-based classification that can generate a model with surprisingly high accuracy after evaluating only an exceedingly small fraction (∼ 10 −3 ) of the shapelets space and has modest memory requirements. We propose several methods for estimating the number of shapelets to examine, and present extensive evaluation on 51 data sets establishing the effectiveness of our approach.


Worldwide, local anthropogenic extinctions have recently been reported to induce trophic cascades, defined as perturbations of top consumers that propagate along food chains down to primary producers. This focus on the effects of top-consumer extinction (i.e. of species presence) ignores potential cascading effects of the rapid morphological changes that may precede extinction. Here, we show in an experimental, three-level food chain including medaka fish, herbivorous zooplankton and unicellular algae that varying body length of a single fish from large (36.3 mm) to small (11.5 mm) induced a stronger trophic cascade than varying an average-sized (23.8 mm) fish from being present to absent. The strength of fish predation on zooplankton scaled quasi linearly (not with a power exponent) with fish body length and associated gape width, suggesting that the resultant trophic cascade was morphology (not metabolism)-dependent. The effect of fish body length was stronger on phyto- than on zooplankton, because large-sized fish had the unique ability to suppress large-sized herbivores, which in turn had high grazing capacities. Hence, our results show that consumer body size, by setting diet breadth, can both drive and magnify the strength of trophic cascades. In contrast, fish body shape had no significant effect on fish predatory performances when its allometric component (the effect of size on shape) was removed. In the wild, human-induced body downsizing of top consumers is widespread, and mitigating the resultant perturbations to ecosystem function and services will require a paradigm shift from preserving species presence towards preserving species size structure.


Subduction zones produce the largest earthquakes on the planet, where rupture along the plate interface can result in the release of stress over large areas, with up to tens of meters of slip extending from below the surface to the trench. The regional stress field is a primary control on the faulting process, ergo understanding the regional stress field leads to a better understanding of the current and future faulting in the area.  Abundant new seismic and continuous Global Positioning System (cGPS) data in the southern North and northern South Island, New Zealand, make it possible to characterize stress and strain parameters throughout the southern Hikurangi subduction zone. Stress orientations calculated within the subducting plate, the overriding Australian plate, and due to gravitational forces reveal that stress throughout the subducting system varies across the southern North Island. Margin parallel motion is being accommodated by shear deformation west of theWairarapa fault, whereas margin perpendicular motion is being accommodated east of theWairarapa fault.  Stress parameters within the double Benioff zone (DBZ) were characterized in term of two bands of seismicity. In the deep region of the DBZ, inversion the upper band of seismicity shows down-dip tension, while the lower band shows compression. Tension in the upper band and compression in the lower band is consistent with bending stresses. In the shallow region of the DBZ, the inversion of both the upper and lower bands seismicity showed tension; this is indicative of slab pull.  Shear-wave splitting of stacked waveforms of local earthquakes recorded on 291 three-component stations showed an average fast azimuth of N-S to NNE-SSW, west of theWairarapa fault. A fast azimuth orientation of N-S to NNE-SSW is sub-parallel to the local major faults. This indicates that the observed anisotropy west of theWairarapa fault is structurally derived. East of the Wairarapa fault, within the Wairarapa Basin, the average fast azimuth orientation isNNW-SSE. Because the fast azimuth orientation showed no dependence on station-earthquake distance, depth, or back azimuth and is perpendicular to major local faults; it has been interpreted as being reflective of the SHmax orientation.  cGPS daily solutions for long-term and inter-slow slip events (inter-SSE) time periods show distinctly differing regions of shear strain rate in the southern North Island and northern South Island. Compression and positive (clockwise) rotation in the southern North and northern South Island was observed using both datasets. Inter-SSE time periods resulted in lower magnitude strain parameters than those calculated during time periods including SSEs. These datasets shows that strain parameters change on time scales of SSEs (< 10 years).


AIM: To investigate the effects of oxymatrine on the gene expression profile of hepatic stellate cell (HSC) and provide novel insights into the mechanism of oxymatrine against hepatic fibrosis. Methods: HSC was isolated from normal SD by in situ perfusion of collagenase and pronase and density Nycodenz gradient centrifugation. MTT colorimetry was used to study the effect of oxymatrine on the proliferation of HSC. Total RNA and mRNA of quiescent HSC, culture-activated HSC and oxymatrine treated HSC were extracted. Effect of oxymatrine on HSC gene expression profile was detected by oligonucleotide microarray analysis with Affymetrix gene chip rat U230A. Differentially expressed genes were annotated with Gene Ontology (GO) and analyzed with Kyoto encyclopedia of genes and genomes (KEGG) pathway using the Database for Annotation, Visualization and Integrated Discovery. Results: Oxymatrine could inhibit the proliferation of HSC in a dose-dependent manner. A total of 4641 differentially expressed genes were identified by cDNA chip between activated and quiescent HSC, among which 2702 genes were upregulated, and 1939 genes were down-regulated in activated HSC. cDNA microarray uncovered downregulation of 56 genes in response to oxymatrine, the representative genes including alpha 2 type I procollagen, alpha-1 type I collagen, tissue inhibitor of metalloproteinase 1, interleukin 1 beta, early growth response 1, chemokine ligand 2, chemokine ligand 1, CTGF, TGFβ1. The most enriched GO terms included response to wounding, inflammatory response, cell migration, cell motility, wound healing, TGFβ receptor signaling pathway. KEGG pathway analysis revealed that oxymatrine affected the ECM-receptor interaction, focal adhesion, cytokine-cytokine recaptor interaction, TGFβ signaling pathway, MAPK signaling pathway. There were 37 genes upregulated significantly following oxymatrine treatment. The most enriched GO terms included oxidation reduction, negative regulation of lipoprotein oxidation, regulation of lipoprotein oxidation, steroid metabolic process, regulation of lipase activity. Six genes were confirmed with QPCR, consistent with microarray. Conclusion: The mechanism of oxymatrine in inhibiting liver fibrogenesis is associated with multi-genes and multi-pathways regulation.


Composite materials consisting of amorphous magnetic microwires added to a matrix of paint have been proven to be very useful for electromagnetic absorption of microwave frequencies. The main goal of this article is to calculate the values of the electrical permittivity and the magnetic permeability of several such composites depending on the microwire mass fraction added. In order to analyze this dependency of electromagnetic parameters on microwire mass fraction, three composites with mass fractions 2, 3, and 4%, respectively, have been prepared. The values of the electromagnetic parameters have been extracted by S-parameter measurements using a rectangular waveguide at band X. Three different methods have been applied in the extraction of the electromagnetic parameter values: Nicolson–Ross–Wier, Impedances, and Optimization. It has been found that the real part of the electrical permittivity linearly increases with the mass fraction of microwires, while the imaginary component does not follow the same linear trend. Regarding the electrical permeability, the values calculated for both the real and imaginary components of composites with different concentrations are too similar to extract any relevant dependency.


This report is based on two different approaches that companies could use in order to develop their business. These approaches are: Social Media Marketing and Strategic Alliances. A detailed theory study explains what these approaches are and how they are used. This study was done from a startup company's point of view. Startup companies are also called startups and the results found are based on how these two approaches are and could best be utilized by startups.The results indicate that the majority of startups does not utilize the possibility of a business partnership, other than small "deals" made startup to startup. The startups however who are in a business partnership right now or are in the early stage of implementing one could not go into details of what said partnership were, but that terms and conditions had been set.Another result is the correlation between the two different approaches. Social media marketing is one of the first things that startups uses and if marketing and sales are operating at a good level then strategic alliances, or some other business partnership, could be exploited mainly in order to reach mainstream customers. Another result is also the order of how startups usually aims their business. This is described in chapter 4 where figure 3.0 visualizes these aims.Also found is that startups should use social media platforms in order to expose themselves. They should make a strategy revolving their exposure and have a Social Media Manager responsible for implementing the strategy. It's also important for a company that uses social media as a marketing tool to have a clear message towards its consumers and employees - a cohesive profile amongst all social media. Also, the strategizing procedure is connected to the specific company, meaning that every single company needs to make its own social media strategy.


Designed specifically for the classroom, this volume presents the accurate and definitive version of Sinners, accompanied by the tools necessary to study and teach this famous American sermon. With an introduction aimed at students and teachers and commentary that draws on fifty years of team editorial experience of Yale's Works of Jonathan Edwards, it provides both context and interpretation, and addresses the concerns and questions of a twenty-first century audience. The book contains questions for in-class discussion, a chronology of Edwards's life, and a glossary. In addition, curricular materials and video mini-presentations are available on a dedicated Web site. This casebook represents a innovative contribution to the art of teaching Edwards to a new generation of readers.


Purpose – The purpose of this study is to investigate the different types of innovation that are dominate in companies in the Albania services sector (telecommunication and bank), the praxis associated with the inquiry of innovation and their relationship with company performance. Design/methodology/approach – The study is a conceptual one with detailed review of literature and descriptive research design. This study collected quantitative data from 16 banks and 89 companies of telecommunications in Albania using a self-administered questionnaire. The questionnaires have been answered mainly by owners of businesses and sometimes by accountants of businesses. The article proceeds as follows. Section two and three offers the objectives of the study and the rational of the study. Next section offers the literature review. Also we try to give the performance of innovation in our country. Section six offers analysis and discussion of results in the context of other contributions to the topic. The final section presents a summary and tentative conclusion. Findings: Main findings show that more than 60% applies process and product innovation. Yet, these days Albania represents a deficit in innovation, with a poor performance, which becomes a handicap for the competitiveness of its enterprises. It ranks 123 out of 144 in Global Competitiveness Report 2012-2013. Research limitations: The period of the study is for six months from June 2013 to January 2014. The firm reports if it has introduced at least one innovation in the period from 2010 to 2012.


This Master thesis is about continuous authentication using keystroke dynamics. We will look to the typing characteristics in different applications and how those characteristics vary from one application to another. It is proved that there are differences in those typing characteristics when the user try to use different applications, However we need to investigate those differences to see if we can still authenticate a person regardless which application is used. In other words, by looking at a selected numbers of applications, we are trying to answer a question "'Does a template based on a certain application allow a person to use another application and still be authenticated by the system "'?. Furthermore we will look if it is possible to authenticate a person based on one general template or we need a set of application dependent templates?.


Responding to an opioid crisis in Canada, policy makers have implemented supply-side interventions seldom used in the US, regulating insurance reimbursement to discourage the prescribing of specified opioids. Using national databases of all opioids dispensed through provincial pharmaceutical programs and of opioid hospitalizations from January 2006 through March 2017, we found that requiring physicians to obtain prior authorization for patients to receive reimbursement for OxyContin prescriptions substantially reduced OxyContin fills, particularly among opioid-naive patients; it also reduced overall opioid prescriptions, suggesting limited substitution. "Grandfathering" OxyNeo (an abuse-resistant OxyContin variant), allowing previous OxyContin patients to obtain OxyNeo, increased OxyNeo fills but had no detectable effect on total opioid prescriptions, which points to substantial opioid substitution among chronic users of prescription opioids. We found no effects of regulatory changes on opioid-related hospitalizations. These results suggest that restrictions on pharmaceutical formularies can reduce fills of targeted opioids with the additional benefit of altering treatment of opioid-naive and other patients differently. Canadian policy makers may wish to extend such regulations to more provincial formularies and private insurers, and policy makers in the US and elsewhere could fruitfully follow suit.


Stabilizing greenhouse gas (GHG) concentrations at any level will require deep reductions in GHG emissions. Net global CO2 emissions, in particular, must eventually be brought to or below zero. Emissions reductions of this magnitude will require large-scale transformations in human societies, from the way that we produce and consume energy to how we use the land surface. The more ambitious the stabilization goal, the more rapid this transformation must occur. A natural question in this context is what will be the transformation pathway toward stabilization; that is, how do we get from here to there?

The topic of this chapter is transformation pathways. The chapter is motivated primarily by three questions. First, what are the near-term and future choices that define transformation pathways including, for example, the goal itself, the emissions pathway to the goal, the technologies used for and sectors contributing to mitigation, the nature of international coordination, and mitigation policies? Second, what are the key decision making outcomes of different transformation pathways, including the magnitude and international distribution of economic costs and the implications for other policy objectives such as those associated with sustainable development? Third, how will actions taken today influence the options that might be available in the future?

Two concepts are particularly important for framing any answers to these questions. The first is that there is no single pathway to stabilization of GHG concentrations at any level. Instead, the literature elucidates a wide range of transformation pathways. Choices will govern which pathway is followed. These choices include, among other things, the long-term stabilization goal, the emissions pathway to meet that goal, the degree to which concentrations might temporarily overshoot the goal, the technologies that will be deployed to reduce emissions, the degree to which mitigation is coordinated across countries, the policy approaches used to achieve these goals within and across countries, the treatment of land use, and the manner in which mitigation is meshed with other policy objectives such as sustainable development.

The second concept is that transformation pathways can be distinguished from one another in important ways. Weighing the characteristics of different pathways is the way in which deliberative decisions about transformation pathways would be made. Although measures of aggregate economic implications have often been put forward as key deliberative decision making factors, these are far from the only characteristics that matter for making good decisions. Transformation pathways inherently involve a range of tradeoffs that link to other national and policy objectives such as energy and food security, the distribution of economic costs, local air pollution, other environmental factors associated with different technology solutions (e.g., nuclear power, coal-fired carbon dioxide capture and storage (CCS)), and economic competitiveness. Many of these fall under the umbrella of sustainable development.

A question that is often raised about particular stabilization goals and transformation pathways to those goals is whether the goals or pathways are "feasible". In many circumstances, there are clear physical constraints that can render particular long-term goals physically impossible. For example, if additinional mitigation beyond that of today is delayed to a large enough degree and carbon dioxide removal (CDR) options are not available (see Section 6.9), a goal of reaching 450 ppm CO2eq by the end of the 21st century can be physically impossible. However, in many cases, statements about feasibility are bound up in subjective assessments of the degree to which other characteristics of particular transformation pathways might influence the ability or desire of human societies to follow them. Important characteristics include economic implications, social acceptance of new technologies that underpin particular transformation pathways, the rapidity at which social and technological systems would need to change to follow particular pathways, political feasibility, and linkages to other national objectives. A primary goal of this chapter is to illuminate these characteristics of transformation pathways.


We present the design of an integrated multiplexer and a dc clamp for the input analog interface of a high-speed video digitizer in the 1.1-V 65-nm complementary metal-oxide-semiconductor process. The ac-coupled video signal is dc restored using a novel all-digital current-mode charge pump. An eight-input multiplexer is realized with T-switches, each containing two series-connected bootstrapped switches. A T-switch's grounding branch is merged with the pull-down end of the clamping charge pump. An adaptive digital feedback loop encompassing a video analog-to-digital converter (ADC) controls the clamp charge pump. The bootstrapped switches have been adapted to suit the video environment, allowing on-the-fly recharging. The varying on-resistance of the conventional bootstrapped switch is utilized to linearize the multiplexer response by canceling the effect of the nonlinear load capacitance contributed by the clamp transistors. Under worst case conditions, the multiplexer maintains a 62-85-dB spurious-free dynamic range over a range of known input video frequencies, and it reduces the second-order harmonic component upon optimization. The dc clamp provides 12-bit precision over the full range of the video ADC and can set the dc at the target level for at most 194 video lines.


Abstract:Rachilde (1860–1953) and Jean Lorrain (1855–1906) co-opted the titillating appeal of taboos surrounding gender and sexuality for the means of self-promotion. Their approach constitutes a particularly productive yet ambivalent form of fin-desiècle literary complicity, integral to avant-garde sociability. This article analyzes their media-savvy contributions to a polemical debate surrounding the bas bleu figure, in a review called Le Zig-Zag. In these exchanges, their adoption of sexually ambiguous media personae was fundamentally ambivalent, acting simultaneously as collaborative performance and self-defense mechanism. By orchestrating the revelation of risqué biographical anecdotes, the pair wagered their reputations and friendships in exchange for infamy. They were enabled and abetted in their construction of subversive solidarity by structures and techniques specific to periodical culture. As exemplary "partners in crime," Rachilde and Lorrain manipulated the appeal of the illicit alongside avant-garde forms of mediatized sociability, demonstrating the potential gain and risk involved in the process.


In February 2016, the External Reporting Board (XRB) introduced the New Zealand version of IFRS 16 named the New Zealand Equivalent to International Financing Reporting Standard 16 Leases (NZ IFRS 16). Effective 1 January 2019, adoption of this accounting standard is compulsory for Tier 1 and Tier 2 for-profit entities (NZ IFRS 16, par. NZ 2.1). A review of existing academic and professional publications indicated the impact of capitalization of operating leases varies significantly depending on country and industry. Therefore, the study's problem was linked to the impact of the NZ version of IFRS 16 (NZ IFRS 16) on the financial statements of the NZX listed firms. NZ IFRS 16 (Leases) requires companies to initially recognise right-of-use assets at cost and lease liabilities at present value (NZ IFRS 16, par. 22, 23 and 26). This study capitalizes the operating leases for a sample of 76 New Zealand listed firms using data obtained from the reported financial statements of these companies for 2017. The accounting treatment of the off-balance sheet operating leases is largely based on Constructive Capitalization by Imhoff, Lipe & Wright (1991), with several modifications based on the literature review. The findings are described by descriptive statistics and are tested with parametric and non-parametric statistical tools. Application of NZ IFRS 16 will produce a statistically significant effect on the metrics and ratios depicting the financial position and financial performance of the sampled firms, except for EBITDA and Interest cover. In addition, based on quantitative benchmarks of materiality identified by Eilifsen & Messier (2015), the impact of NZ IFRS 16 is material for the Profit before tax and Total assets metrics of the sampled listed companies. The study provides specific New Zealand evidence on the impact of implementation of NZ IFRS 16. The results can be used by stakeholders interested in information about the lease-related assets and obligations of firms operating in the New Zealand economy. Some findings about the impact of capitalization of operating leases are useful to management and/or the decision-makers of New Zealand listed firms.


Extending prior research on the third-person effect, which has focused on perceived media effects on adults, the present study examined parents' beliefs about the effects of televised violence on their own and other children, and how these perceptions are related to two different behavioral responses: parental mediation of television and support for censorship. Respondents were parents of children aged 3 to 18 (N = 70), who were contacted as part of a random sample for a larger study. Via telephone interviews, parents rated their perceptions of three effects of televised violence: (1) viewing the world as a dangerous place; (2) approving of aggression; and (3) behaving aggressively. As predicted, third-person perceptions were observed for all three types of influence, but were larger for the more socially undesirable aggression - related effects. Both parental mediation and support for censorship were associated with the perceived effects of televised violence. Evidence suggested that parents' behavioral responses were motivated by concern about both their own and other children, but that the pattern of responses varied for the three different effects of viewed violence.


Abstract Background Sarcoma are a heterogeneous group of tumor which can be split into two subgroups with distinct genetics. Half of sarcoma presents an important genomic reorganization correlated to tumor aggressiveness. At this stage, the origin of this instability is still unknown. Cell fusion is a physiological mechanism involved in several processes including myoblast differentiation and already described to be involved in aneuploidy generation and genomic instability. We thus hypothesized that cell fusion could participate to sarcoma oncogenesis by generating genomic instability. Methods We established cell line of hybrids from spontaneous fusion of immortalized myoblasts. Tumor and metastasis development were evaluated upon grafting and whole genome and transcriptome sequencing with in-vitro mechanistic studies were performed to decipher phenotypes acquired by hybrids upon fusion. Results In vitro hybrid cell lines show a more aggressive phenotype than parental cell lines by increasing proliferation and clonogenic capacities. Only hybrids form tumors upon grafting and may develop also metastasis. Aneuploidy triggered by cell fusion induces genome reorganization and in vivo tumor genome show alterations corresponding to those observed in human rhabdomyosarcoma. Indeed, 85% of hybrid tumors harbor DMD deletions as observed in sarcoma with myogenic origin. The study of this protein reveals that tumors lose the expression of Dp427 isoform which is the one reported as a tumor suppressor. This malignant transformation of hybrids is associated to transcriptomic remodeling toward a decrease of the expression of genes involved in muscle differentiation. Conclusions To our knowledge, this is the first model able to reproduce the complex genomic of sarcoma. The detection of those hybrid cells in sarcoma tumor allowed us to push forward they are involved in sarcoma development and progression and their quantification in tumors or in circulating cells could thus establish an early prognostic marker. Finally, specific therapeutic targeting of this hybrids could represent new approach. Legal entity responsible for the study Frederic Chibon. Funding Association pour la Recherche contre le Cancer (ARC) Fondation pour la Recherche Medicale (FRM). Disclosure All authors have declared no conflicts of interest.


Many linguists define classification systems in terms of semantic profiling. The classifier profiles a semantic trait common to all the classified items. This paper rejects semantic profiling in favor of a combinatorial definition of classification and evaluates verb classification in five languages of the Sinitic, Tai-Kadai, Miao-Yao and Tibeto-Burman families. Only sortal verb classifiers in Sinitic, Tai-Kadai, Miao-Yao (not Tibeto-Burman) are classificatory in the combinatorial sense. Sortal verb classifiers stand for a lexical classification technique in which the classifiers are derived from adjunct noun phrases. Cross-linguistically, the technique contrasts with other techniques such as the classification of verbs by incorporated core arguments found in Native American languages. This paper also evaluates mensural verb classifiers and auto-classifiers which are generally not classificatory in the combinatorial sense.


Solo exhibition of collaborative works by Ross Birrell and David Harding. New installation of video, light and sound works which were first exhibited together in Winter Line, Kunsthalle Basel, Jan-Mar 2014.

Taking its title from Rainer Maria Rilke's poem 'To Music', Where language ends (Talbot Rice Gallery (2015) is an exhibition of works produced over a 10-year collaboration with the artist David Harding, former Head of Sculpture and Environmental Art and GSA.

The exhibition features site-specific films, sculptural objects, sound work, prints and coloured window installations. Through video and installations we weave complex layers of history into poetic acts of translation and transposition. As with Winter Line, in Where language ends music plays a central role.

For the occasion of the exhibition, I composed a work for piano, violin and cello,also titled, Where language ends, and performed in the gallery by the DaVinci Trio.


Introduction: Bilateral hydronephrosis on prenatal ultrasound can be managed expectantly or with surgical intervention. The treatment strategies and outcomes are not clearly defined. Methods: We conducted a retrospectively audit of outcomes of management of prenatally detected severe bilateral ureteropelvic junction obstruction (UPJO) in our institution.Patients with bilateral Grade 3–4 hydronephrosis were included. Those with complications like rupture, underwent bilateral intervention within 4 weeks; in the remaining, unilateral pyeloplasty was performed at 4–12 weeks. The contralateral renal unit was re-evaluated at a later date for further improvement or deterioration. All the patients were followed up with ultrasonography and renogram at 3 months, 6 months, and 1-year post operatively. The case records were analyzed for the resolution of antero-posterior diameter (APD) or the improvement in single-kidney glomerular filtration rate (s-GFR) in the operated units. Results: Over 15 years, 28 patients (56 renal units) had bilateral UPJO (male-to-female ratio = 13:1). Twelve units underwent neonatal intervention to tackle the complications (6 bilateral pyeloplasty), 17 units underwent early pyeloplasty, and 15 underwent late pyeloplasty. Twelve of the twenty-two (54%) contralateral units, which were stented/observed, resolved spontaneously. Receiver operating characteristics analysis revealed that those with initial APD <25 mm and initial s-GFR >35 ml/m were more likely to improve during the observation. Ten of the forty-four operated units (22%) failed to show an improvement. Units with initial s-GFR <10 ml/m had poor chance of postoperative functional recovery. Conclusions: In neonates with bilateral UPJO, the worse affected kidney is operated first, as it still has the potential to recover. The contralateral milder UPJO unit is known to recover spontaneously following unilateral pyeloplasty. In those with bilateral Grade 4 UPJO and mass, bilateral pyeloplasty is feasible. Alternatively, unilateral pyeloplasty + contralateral cystoscopic retrograde stenting may prevent rupture or functional deterioration in the opposite kidney.


This paper tackles unpaired image enhancement, a task of learning a mapping function which transforms input images into enhanced images in the absence of input-output image pairs. Our method is based on generative adversarial networks (GANs), but instead of simply generating images with a neural network, we enhance images utilizing image editing software such as Adobe® Photoshop® for the following three benefits: enhanced images have no artifacts, the same enhancement can be applied to larger images, and the enhancement is interpretable. To incorporate image editing software into a GAN, we propose a reinforcement learning framework where the generator works as the agent that selects the software's parameters and is rewarded when it fools the discriminator. Our framework can use high-quality non-differentiable filters present in image editing software, which enables image enhancement with high performance. We apply the proposed method to two unpaired image enhancement tasks: photo enhancement and face beautification. Our experimental results demonstrate that the proposed method achieves better performance, compared to the performances of the state-of-the-art methods based on unpaired learning.


We present a moderate-deviations principle around non-degenerate attractors of the empirical measure of random variables distributed according to a mean-field Gibbs measure. We state a result for a large class of densities of the Gibbs measure. This result is an application of a rank-dependent moderatedeviations principle for a collection of U-empirical measures. The results are applied to diffusion processes with mean-field interaction leading to a McKean-Vlasov limit, and to the Curie-Weiss model.


Current Inflammatory bowel disease (IBD) treatments focus on inhibition of excessive inflammation, and clinical remission rates have reached a plateau. There is a clear unmet need for agents that directly repair and regenerate the intestinal epithelial barrier as mucosal healing has been associated with reduced hospitalizations and long-term remission. Wnt/β-catenin signaling promotes intestinal stem cell renewal and is crucial for intestinal epithelial homeostasis and regeneration. Fzd5, a Wnt receptor, is highly expressed in intestinal epithelium. We have engineered a FZD5,8 and LRP6 bi-specific IgG1 antibody, SZN-1326, which potently induced Wnt signaling in a Super Top Flash (STF) Luciferase reporter assay, stimulated intestinal organoid growth, increased Wnt target gene Axin2 expression in the colon tissue and ameliorated Dextran Sulfate Sodium (DSS)-induced colitis in mice. The objective of the current studies was to compare the efficacy of SZN-1326, a Wnt signal activator, to Cyclosporine A, which has been shown to have activity in an acute DSS-induced colitis mouse model.

 To induce acute colitis, 7- to 8-week-old female C57BL/6 mice were given drinking water containing 4.0% (w/v) DSS for 7 days followed by 1.0% DSS for 3 days. Groups of mice were treated either with an isotype control antibody (anti-GFP), one intraperitoneal (IP) injection of SZN-1326 at 2, 6, 20 mg/kg on day 4 or two injections of SZN-1326 at 1, 3, 10 mg/kg on days 4 and 7, or treated daily with Cyclosporine A by oral gavage at 80 mg/kg on days 0–9, and the mice were taken down on day 10.

 Mice subjected to DSS developed severe colitis characterized by profound and sustained weight loss and bloody diarrhea, resulting in the increase of disease activity index (DAI). SZN-1326 treatments improved body weight, decreased fecal score, and reduced DAI much more effectively than Cyclosporine A. Histological evaluation showed SZN-1326 treatments repaired the damaged colon epithelium, decreased colon histology scores of inflammation, mucosal erosion, and goblet cell loss, at doses as low as 1 mg/kg dosed twice or a single dose of 2 mg/kg. In addition, SZN-1326 treatments significantly decreased serum levels of inflammatory cytokines, Lipocalin-2, IL-6 and IL-8, while Cyclosporine A treatment led only to a reduction of Lipocalin-2.

 In an acute mouse IBD model, SZN-1326 at various dosing regimen stimulated intestinal epithelial regeneration, induced mucosal healing and restored the epithelial barrier resulting in reduced inflammation, improved body weight and reduced disease activity. In contrast, Cyclosporine A showed only a mild effect on reducing DAI and lipocalin-2.


White clover (Trifolium repens L.) is at a disadvantage to perennial ryegrass (Lolium perenne L.; PRG) due to its limited cold tolerance and low growth rates at colder temperatures, which can affect subsequent spring herbage dry matter (DM) availability. The effect of PRG ploidy on white clover morphology and growth over winter, and its subsequent recovery in spring and the following growing season, is poorly understood. The objective of this study was to compare the effect of white clover inclusion and PRG ploidy on sward structure, plant morphology and growth of PRG–white clover swards over winter. Four swards (diploid PRG only, tetraploid PRG only, diploid PRG–white clover and tetraploid PRG–white clover) were evaluated over a full winter period (November–February) at a farmlet scale. The PRG ploidy had no effect on herbage DM production, white clover content or tissue turnover (P > 0.05) over winter. However, white clover inclusion caused a significant decrease in herbage DM production (P < 0.001; −254 kg DM/ha) and tiller density (P < 0.001; −1,953 tillers/m2) over winter. Stolon mass was not affected by PRG ploidy (P > 0.05); however, stolon length and number of leaves per stolon were affected by PRG ploidy (P < 0.05). Including white clover in PRG swards can alter winter sward dynamics, potentially causing difficulties in subsequent spring management and performance due to the reduced over-winter growth rate when compared with PRG.


A characteristic of the Nordic states is their ambition to provide their citizens with a variety of good quality welfare services. A significant part of the responsibility for arranging reliable local solutions is devoted to the municipal level irrespective of the size of the municipality. This means a great variation in local capacity to meet different types of requirements. Especially small municipalities, which also face depopulation and an ageing population, are increasingly challenged to find renewal strategies and action plans to secure both municipal service obligations at reasonable cost per capita and competent staff. Besides rearranged internal steering, organizational frameworks, and working instructions, new solutions may be launched based on resource mobilization and a striving for improved performance in a wider spatial context. This paper explores how three municipalities in the north of Sweden have developed a voluntary intermunicipal collaboration and how it relates to alternative collaborative options in the regional context. The strengths and weaknesses of the chosen approach and its outcome are discussed based on interviews with the local government commissioners and their executive civil servants in different positions. The strength of the achieved collaborative profile is that it meets needs for higher cost efficiency and competence among staff within some municipal sectors. Further is noted that the chosen collaborative profile is not challenging the democratic accountability in each municipality. However, a weakness is that the collaborative results achieved after ten years of collaborative intentions are of marginal importance for all involved municipalities. These experiences are reflected upon with advantages and disadvantages of a merge alternative in mind.


ABSTRACT This review article is concerned with the construction of identity in academic discourse. It examines recent journal articles and monographs in applied linguistics and considers various perspectives on the issue. After a brief introduction and review of the theoretical background relating to identity, followed by a characterization of academic discourse and how it relates to identity theory, the article explores the following topics: linguistic resources for audience engagement; voice and academic identity; disciplinary identity; identity in peripheral academic genres; academic identity development over time; academic identity and English as a lingua franca; power, ideology, and critical language awareness in academic identity construction; language reuse, intertextuality, and academic identity; pedagogically oriented studies and academic identity construction; and methodological diversity and innovation in the study of academic identity. The article concludes with suggestions for future work in the field of academic identity research.


The in-core neutron flux mapping system in a pressurized water reactor yields information on the neutron flux distribution in the reactor core at selected core locations by means of movable detectors. The detector cables run through guide tubes (thimbles). For reactor operation, the thimbles are inserted into nuclear fuel assemblies through conduits connected from the bottom of the reactor vessel to a seal table. During the plant refueling outage period, the thimbles are withdrawn up to 4 meters from the seal table, the height of fuel assemblies. Thimble handling work has been performed by maintenance personnel. Manual handling efficiency is low due to narrow and high-radiation working environment around the seal table. Besides, manual force exerted on the thimbles is not unidirectional, which may cause serious damage to the thimbles. To overcome these difficulties and maintain the thimbles safely, an automatic thimble handling system that is composed of a thimble handling machine system, a control system, a thimble tensioner and so on, has been developed. The user-friendliness of a control system and the robustness of thimble handling machine are particularly emphasized to guarantee minimum radiation exposure to maintenance personnel and efficient thimble maintenance.


A new learning way for neural network (NN) in which its weights can be optimized by using the ant colony algorithm is presented in this paper. The learning of neural network belongs to continuous optimization. The ant colony algorithm is initially developed for hard combinatorial optimization. A kind of ant colony optimization (ACO) for continuous optimization, which includes global searching, local searching and definite searching, is developed based on the basic ant colony algorithm. A three-layer neural network, as an example, is trained to express nonlinear function. The efficiency of the new algorithm is examinated. It is found that the new developed method has the merits of both ant colony algorithm and neural network.


Bordetella pertussis cells express multiple virulence-associated surface proteins, including adenylate cyclase, agglutinogens 2 and 3, filamentous hemagglutinin, pertussis toxin, and outer-membrane protein (Omp) 30/32 and Omp91. Surface proteins that are not virulence-associated include three peptidoglycan-associated Omps of apparent molecular weights 40,000, 25,000, and 18,000. Omp40 is an anion-selective porin and is the most abundant surface protein of virulent and avirulent cells. Three independent approaches--immunomicroscopy, surface radioiodination, and isolation of Triton X-100-insoluble envelope proteins--suggest that the Triton-insoluble fraction of the B. pertussis cell envelope is the outer membrane. Agglutinogens 2 and 3 and filamentous hemagglutinin lie outside the outer membrane, the first two as fimbriae and the last as a microcapsule. Adenylate cyclase and pertussis toxin are present in the outer membrane but may be present transiently or present in small amounts.


The importance of nutrient management plans (NMPs) in mitigating the impact of farm-based nutrient applications on the environment is widely acknowledged. However, despite years of promotion by agencies, most farmers still have not developed a NMP. Those plans that have been developed vary in quality and in the degree to which they are actually implemented. Although effective tools have emerged to aid plan development, the planning process remains time and resource intensive. In addition, information about NMPs and actual nutrient application rates generally is not available to resource managers who address water quality issues. This study examines changes in nutrient management behaviors and perceptions among 259 farmers, who participated in a multisession educational workshop series focused on understanding and developing NMPs. Based on structured interviews with farmers before and again one to three years after the workshops, the study finds that farmers are developing NMPs, understanding their plans, and also changing nutrient application rates (both increasing and decreasing). After implementing their NMPs, a strong majority (69%) of the participants believe that their plan has saved them money with no negative effect on yield. Three main findings hold implications for broader water quality and land conservation programs: (1) NMP education courses can lead to changes in farmer nutrient management behaviors, not always toward reducing nutrients; (2) farmers acknowledge challenges in fully implementing their plans, yet a high percentage (82%) indicate that they follow their plan on most (>76%) of their land; and (3) there is a need for accessible approaches to measure and track nutrient management behaviors separate from NMPs and in cases where they do not exist.


A grid differs from traditional high performance computing systems in the heterogeneity of the computing nodes as well as the communication links that connect the different nodes together. In grids there exist users and service providers. The service providers provide the service for jobs that the users generate. Typically the amount of jobs generated by all the users are more than any single provider can handle alone with any acceptable quality of service (QoS). As such, the service providers need to cooperate and allocate jobs among them so that each is providing an acceptable QoS to their customers. QoS is of particular concerns to service providers as it directly affects customers' satisfaction and loyalty. In this paper, we propose a game theoretic solution to the QoS sensitive, grid job allocation problem. We model the QoS based, grid job allocation problem as a cooperative game and present the structure of the Nash Bargaining Solution. The proposed algorithm is fair to all users and represents a Pareto optimal solution to the QoS objective. One advantage of our scheme is the relatively low overhead and robust performance against inaccuracies in performance prediction information.


A centralized optical burst switching (OBS)-based grid architecture is proposed. Three scheduling strategies, for the resources on the grid level, the network level, and the OBS network level, respectively, are presented and analyzed. The overall grid performance and the network performance under different scheduling strategies are analyzed and compared by simulation.


Despite the recent explosion of scholarly interest in "star studies," Brazilian film has received comparatively little attention. As this volume demonstrates, however, the richness of Brazilian stardom extends well beyond the ubiquitous Carmen Miranda. Among the studies assembled here are fascinating explorations of figures such as Eliane Lage (the star attraction of Sao Paulo's Vera Cruz studios), cult horror movie auteur Coffin Joe, and Lazaro Ramos, the most visible Afro-Brazilian actor today. At the same time, contributors interrogate the inner workings of the star system in Brazil, from the pioneering efforts of silent-era actresses to the recent advent of the non-professional movie star.


The interaction between vacancies and Sn and Cu solute atoms in an Al-1.7at.%Cu- 0.01at.%Sn alloy was investigated by exploring the effect of incorporating natural ageing into conventional age hardening treatment. It was found that provided the artificial ageing temperature does not exceed a critical value between 160°C and 200°C, a narrow window of natural ageing (3-100 h) will result in a significant acceleration of the age hardening response and no decrease in peak hardness. Transmission electron microscopy showed that this effect reflects a large and rapid increase in number density of Cu GP(I) zones, and, to a lesser extent, of θ". The distribution and number density of θ' are essentially unaffected. Three-dimensional atom probe provided strong evidence that refinement of GP(I) zone distribution is not due to clustering of Cu atoms onto pre-existing Sn clusters. Instead it appears to be caused by a subtle interaction between vacancies, Sn and Cu atoms.


In response to external oxidative stress/DNA damaging agents, mammalian cells may choose one of the following pathways to avoid propagation of the damaged cells: repair the DNA and proceed with the normal cell cycle; trigger apoptosis; or undergo senescence to block cell division. If these safeguard mechanisms fail, cells containing damaged/mutated DNA will continue to propagate leading to cancer. Working with Human Diploid Fibroblasts, we have observed that young quiescent fibroblasts, unlike dividing fibroblasts, do not undergo apoptosis when subjected to high dose of external oxidative stress. Interestingly, when those quiescent fibroblasts are sub-cultured following H2O2 treatment, they display all the features of the senescent cell phenotype. Our results have indicated that p21 and MnSOD over-expression in quiescent cells is highly correlated to resistance to oxidative stress and may induce senescence. Moreover, there was no observable DNA damage in quiescent fibroblasts after 500 μM H2O2 treatment even though oxidative damage to lipids and proteins was detected both before and after treatment. Most importantly, the mitochondrial membrane potential in quiescent cells remained unchanged even after exposure to a high dose of external oxidative stress. In dividing cells, Bcl-2 expression was down-regulated whereas Bax expression was up-regulated following oxidative stress. On the other hand, Bcl-2 levels remained high and Bax was down-regulated in quiescent cells under identical treatment. Our results reveal that the over-expression of p21 and Mn-SOD and the down-regulation of Bax in quiescent cells could be responsible for their resistance against external oxidative stress and onset of senescence.


ABSTRACT The contribution of homologous exchange (recombination) of core genes in the adaptive evolution of bacterial pathogens is not well understood. To investigate this, we analyzed fully assembled genomes of two Escherichia coli strains from sequence type 131 (ST131), a clonal group that is both the leading cause of extraintestinal E. coli infections and the main source of fluoroquinolone-resistant E. coli. Although the sequences of each of the seven multilocus sequence typing genes were identical in the two ST131 isolates, the strains diverged from one another by homologous recombination that affected at least 9% of core genes. This was on a par with the contribution to genomic diversity of horizontal gene transfer and point gene mutation. The genomic positions of recombinant and mobile genetic regions were partially linked, suggesting their concurrent occurrence. One of the genes affected by homologous recombination was fimH, which encodes mannose-specific type 1 fimbrial adhesin, resulting in functionally distinct copies of the gene in ST131 strains. One strain, a uropathogenic isolate, had a pathoadaptive variant of fimH that was acquired by homologous replacement into the commensal strain background. Close examination of FimH structure and function in additional ST131 isolates revealed that recombination led to acquisition of several functionally distinct variants that, upon homologous exchange, were targeted by a variety of pathoadaptive mutations under strong positive selection. Different recombinant fimH strains also showed a strong clonal association with ST131 isolates that had distinct fluoroquinolone resistance profiles. Thus, homologous recombination of core genes plays a significant role in adaptive diversification of bacterial pathogens, especially at the level of clonally related groups of isolates.


Aging is a central notion in various domains, including biomedicine. There is an urgent need for a unified and interdisciplinary framework for articulating the multifaceted character of aging. To take initial steps towards such a framework, we provide an ontological analysis of the six defining features of aging based on Basic Formal Ontology (BFO): functional decline, structural damage, reserve depletion, cellular senescence, phenotypic change, and the increase in the probability of death or disease. Our proposal leverages the BFO dispositional account of function as well as a BFO-compliant theory of dispositions and dispositional approach to causation. We also briefly discuss premature aging, disease, health, and homeostasis in relation with aging.


Early bearing, self-pollinating and medium-to-big-seeded Philippine makapuno hybrid VMAC5 is propagated through in vitro embryo culture. This yields one plantlet per embryo in at least six months. To evaluate the potential of mass producing planting materials in vitro, a protocol developed by the Philippine Coconut Authority was used to initiate somatic embryogenesis in whole and cut plumule explants from VMAC5 nuts. Calloid initiation was obtained 8 to 12 days from initial culture in semi-solid medium under dark incubation at 8% in cut and 5% in whole plumules. White translucent structures characteristic of embryogenic calloids formed on the cut plumules one month after initial culture. At 60 days old, distinct ear-shaped pre-embryogenic structures and white shiny globular pre-somatic embryos developed in whole explants. Hard, friable, and whitish to yellowish calloids with pre-embryogenic masses were also observed in cut plumule explants. At 90 days after the initial culture, more distinct pre-somatic and globular somatic embryos developed in both explants.


We argue that social welfare programs are linked with the destruction of social capital, as measured by interpersonal trust in laboratory games. To test for this, we employ experimental data for representative samples of individuals in six Latin American capital cities (Bogota, Buenos Aires, Caracas, Lima, Montevideo, and San Jose). In fact, we find that participation in welfare programs damages trust, a result that is robust to the inclusion of individual risk measures and a broad array of controls. Whereas we argue that endogeneity is not a critical issue, we also control for it using an instrumental variables approach. Our findings also support the notion that low take up rates may be due to stigma linked to trust and social capital, rather than to transaction costs. JEL Classification Code: D01, O12, O10


Coffee leaf rust (CLR) is a pandemic and a serious threat for coffee sustainability in many coffee producing countries. To overcome this CLR, the world's consensus is to use of resistant cultivars which can be created through coffee breeding program. This research aimed to study genotypic and phenotypic correlations between CLR symptoms of seven arabica coffee (Coffea arabica L.) genotypes that were selected from different districts of North Sumatra Province, Indonesia. This experimental research using a randomized complete block design with three replications was conducted at the experimental garden of the Faculty of Agriculture, Universitas HKBP Nommensen in Medan. The result of this study indicate that leaf rust severity (LRS) had a genotypic component variance of 86.8% which indicated that LRS was controlled more dominantly by plant genetics than other unknown factors. Severity indicated by LRS showed no genotypic and phenotypic correlation with dispersal indicated by branch rust incidence (BRI) and leaf rust incidence (LRI). BRI genotypically correlated with LRI. The results of this study could contribute to resistance coffee breeding for CLR.