This paper proposes a new end-to-end trainable model for lossy image compression, which includes several novel components. The method incorporates 1) an adequate perceptual similarity metric; 2) saliency in the images; 3) a hierarchical auto-regressive model. This paper demonstrates that the popularly used evaluations metrics such as MS-SSIM and PSNR are inadequate for judging the performance of image compression techniques as they do not align with the human perception of similarity. Alternatively, a new metric is proposed, which is learned on perceptual similarity data specific to image compression. The proposed compression model incorporates the salient regions and optimizes on the proposed perceptual similarity metric. The model not only generates images which are visually better but also gives superior performance for subsequent computer vision tasks such as object detection and segmentation when compared to existing engineered or learned compression techniques.


Hypertension or prehypertension are the diseases which affect entire body. Many times there would have been organ damage even before the diagnosis of hypertension. So it becomes very essential to diagnose hypertension or ra ther prehypertension at an early stage so that the preventive measures can be employed. Heart rate variability (HRV) proves to be the best tool to diagnose prehypertension at early stage. The aim of this study was to record HRV in offsprings of hypertensive parents and offsprings of normotensive parents and compare the results between the two groups. A cross sectional study was done in I MBBS students (2011-2012) of S.Nijalingappa Medical college, Bagalkot, Karnataka, India. 20 cases were obtained and were matched with 20 controls, HRV was recorded in both the groups using polyrite and analysed for time and fr equency domain parameters. Statistical analysis was done by Unpaired t test using EPI-i nfo software. The time domain parameters were found to be decreased in cases but were not statistically significant. Low frequency domain (LF) was higher and high frequency domain (HF) was lower in cases when compared to controls and the difference was statistically significant. The LF/HF ratio was also higher in cases and was statistically sign ificant. There is increased sympathetic drive and decreased parasympathetic drive in cases when compared to controls indicating autonomic imbalance in the predisposed group. So if detected earlier, preventive measures can be undertaken to prevent prehypertension and subsequently hypertension in them.


The 1981 and 1990 European Values Surveys showed a decline for almost all religious
variables, a decline even sharper among young people, except for belief in an afterlife. The
younger the respondents, the less religious they were likely to be. These results confirmed
the thesis of increasing secularization in Europe and the West. However, the most recent,
1999 survey shows this downward trend to be counterbalanced by two other tendencies:
internal Christian renewal and increased "believing without belonging", both phenomena
that are clearly more developed among young people. The respective strengths of these three
developments vary by country surveyed. The same phenomena are even more pronounced in
Eastern European (former communist bloc) countries and in Russia, once again particularly
among young people. The changes may be interpreted as a turning point after the break with
religiosity that characterized the 1960s and 70s.


Memory corruption, reading uninitialized memory, using freed memory, and other memory-related errors are among the most difficult programming bugs to identify and fix due to the delay and non-determinism linking the error to an observable symptom. Dedicated memory checking tools are invaluable for finding these errors. However, such tools are difficult to build, and because they must monitor all memory accesses by the application, they incur significant overhead. Accuracy is another challenge: memory errors are not always straightforward to identify, and numerous false positive error reports can make a tool unusable. A third obstacle to creating such a tool is that it depends on low-level operating system and architectural details, making it difficult to port to other platforms and difficult to target proprietary systems like Windows. This paper presents Dr. Memory, a memory checking tool that operates on both Windows and Linux applications. Dr. Memory handles the complex and not fully documented Windows environment, and avoids reporting false positive memory leaks that plague traditional leak locating algorithms. Dr. Memory employs efficient instrumentation techniques; a direct comparison with the state-of-the-art Valgrind Memcheck tool reveals that Dr. Memory is twice as fast as Memcheck on average and up to four times faster on individual benchmarks.


The baffled cavity flow—the first representative of a class of chaotic flows produced by time-dependent changes of geometries—is introduced and extensions to spatially-periodic systems proposed. Both experimental and computational results are reported. The goal of the study is to put into evidence some of the steps and considerations when designing a new mixing flow; a related objective is to demonstrate the use of an efficient and accurate numerical technique (BIEM) suitable for mixing studies in time-dependent geometries. Several parameters that affect the degree of mixing are studied: the mixing protocol—how the baffles are alternated and how many baffles are used in the flow during each piecewise motion; baffle sizes and shapes; geometrical and flow parameters, such as the wall displacement per period; and details of the baffle's motions.


We would like to introduce the Happiness studio, [SHED, Spatial Happiness and Environmental Design] where we will start to establish a base for research and active projects that seek to understand spatial happiness.

At the moment there are no scholarly definitions of Spatial Happiness and we are on the threshold of a new spatial philosophy that we can genuinely contribute to and be a part of this burgeoning thinking. Our inaugural project focuses on Workspace, a place that has been under rigorous rethinking throughout the 21st century. New technology and more flexible working practices have reshaped our office environment; however has the well-being of the staff been considered thoroughly enough? and has this best practice been disseminated to all businesses in the UK?

What measures should we work towards as on the one hand the workplace is where we spend the majority of our daylight hours, where we share our creativity and future thinking. Would businesses both attract the best thinkers if their well-being and environment was considered more highly and would they start to outperform their expectations because of the improved conditions?

The idea of 24 hour workspaces is well established but have employers taken our circadian rhythms into account? The statistics show eventual poorer health of those that work through the hours of darkness. Mobile technology now enables us to select different environments to work in, but do these environments establish good posture and adversely if you did remain at the workstation, how you encourage movement and posture realignment, does this mean that we can do away with the office chair, should we test other seating solutions where you encounter discomfort encouraging timely movement? Should employees been given a nutritional programme to ensure better energy levels throughout the day, aiding constant concentration and therefore facilitating a more productive output perhaps more importantly the workforce would concede less errors. Better food would engender better moods and overall satisfaction and very possibly have a zero on costs.

We are not in favour of over regulation and box ticking and individual requirements are specific and choice is integral to the field of well being but some of these measures should be adopted as the norm, why would you accept anything less than healthy practice?


Once upon a time a man and a woman had a child who lived. Then they had another child and it died, and then another child and that child also died. The first child was a little girl, the second and third were boys. The children were named Katherine, Benjamin, and Robert, but their names were mostly shortened to Kathy, Ben, and Rob. After the death of the third child, the man and the woman chose not to have another child but instead to have a dog that their young daughter christened Lady. The man took pictures of his wife, his daughter, and his dog and then asked his wife to take a picture of himself. The photos were developed and put in the photo album. "Finally, we are four!" the woman wrote beside it, but barely three years later, she left the man and thus, indirectly, her daughter and dog as well.


The anthropometric tables today used in biomechanics are not individualized and are inadequate for precise measurement and calculations. Series of individualized anthropometric measurement methods are preformed lately, which use expensive commercial computer vision systems or clinical devices. Computer vision systems with laser light or structured light showed to be the best solution when fast and individualized measurement of anthropometric parameters are required, which can be proven by numerous commercial systems today available for aiding designers to create individualized garment. These devices offer resolutions and details of a 3D body model far beyond real requirements of simple anthropometric calculations, and cannot fully utilize expensive equipment. Goal of our work was to create simple body-surface scanner using only consumer electronic components; digital camera, office LPD projector and a PC. Technique used in our system inherits best features of a laser and structured light scanners, while robust light coding enables us to measure in virtual any conditions.


Seven different tree species (coniferous and broad leaved) were selected for small scale pelletizing tests: birch (Betula sp.), aspen (Populus tremula L.), grey alder (Alnus incana L.), poplar (Populus sp.), European larch (Larix decidua Miil.), pine (Pinus sylvestris) and lodgepole pine (Pinus contorta). Tree species were mixed in different combinations and proportions. Wood mixture from one tree specie (several tree species were tested as base material during study) was used as base material with volume share in the mix at least 70% and mixtures from other tree species were used as additives. In total 49 different tree mixes were tested in pellet production where mechanical durability and water absorption was later measured for each sample. Mechanical durability where grey alder was mixed with pine was 98.8% (fulfils ENplus quality class). Poplar also showed high results and in some mixes meet the criteria for mechanical durability with best result 99% in mixes with European larch and lodgepole pine (proportions 80:10:10). From 9 different poplar mixes 7 of them showed mechanical durability higher than 97.5%. In tests where no additives was added (100% poplar), poplar pellets mechanical durability was 98.8%. Other mixes with birch, aspen and grey alder when they were taken as base material for pellet production (base material wood volume share in the mixture at least 70%, where remaining 30% consists of other tree specie mixtures) didn't meet the mechanical durability limit for ENplus quality classes and it was lower than 97.5%. Also in samples where birch and grey alder were used without adding other tree species durability was under 97.5%. European larch was the only one from coniferous trees was tested as base material and the best results in mechanical durability showed in mixes with lodgepole pine (proportion 70:30). From 9 different European larch mixes 7 of them showed mechanical durability higher than 97.5%, which is suitable for ENplus certification. Water absorption in pellets with different tree species composition does not change significantly and ranges from 0.70 to 0.73 ml g-1 when in commercially available litter material it is 0.75–0.8 ml g-1. Water absorption tests leads to a conclusion that if pellets mechanical durability is not sufficient to sell it as combustion material in could be sold as litter material for animals.


I shall presuppose as undefended background to what follows a position of scientific realism, a doctrine to the effect (i) that the world exists and (ii) that through the working out of ever more sophisticated theories our scientific picture of reality will approximate ever more closely to the world as it really is. Against this background consider, now, the following question: 1. Do the empirical theories with the help of which we seek to approximate a good or true picture of reality rest on any non-empirical presuppositions? One can answer this question with either a 'yes' or a 'no'. 'No' is the preferred answer of most contemporary methodologists -- Murray Rothbard is one distinguished counterexample to this trend -- who maintain that empirical theories are completely free of non-empirical ('a priori') admixtures and who see science as a matter of the gathering of pure 'data' obtained through simple observation. From such data scientific propositions are then supposed to be somehow capable of being established.


Received: September 2011, Accepted: October 2011 Background: Genital injuries are important because of their association with injuries to major organs and vasculature of pelvis. Both degolving of genitalia skin and amputation of penile glans and testis are rare conditions. Although genital injury is rarely life threatening, it can result in serious sexual, psychological and physiological consequences. This study aimed to introduce few very rare cases with genital injuries among pistachio farmers in Rafsanjan, Iran. Materials and Methods: This study is a case series conducted from 2000 up to 2009 in Moradi hospital of Rafsanjan city, Iran. Patients data were gathered during 10 years and analyzed using SPSS software version 16. Results: Among 9 victims of genital injuries, caused by accident with tractor during spraying pistachio farms, 7 had suffered from partial or total scrotal or penile degolving, one suffered from testis amputation and one from penile glans amputation. Mean age of victims was 28.6 ± 3.57 years, and they were unemployed for 3.1 ± 0.78 weeks on average. Conclusion: In order to reduce genitalia injuries caused by agricultural machinery, tractors safety should be given more attention and also pistachio farm workers should become aware of these occupational risks.


The aim of this work is to demonstrate how Dai vernacular architecture in South China developed within the context of an integrated traditional cultural system, despite the absorption of neighbouring cultural influences from Southeast Asia and the Han, and thereby contribute to an improved understanding of vernacular architecture. Besides considering the physical determinants, climatic constraints, and aesthetic meanings of the Dai vernacular architecture in South China, I try to demonstrate how "the house", "social structure", "kinship and marriage", "politics", "economics" and "religion" are ideologically integrated just as they are also inextricably bound together in concrete behaviour.
In the work, four related sections form the primary discussion of the Dai house. The first addresses Dai religious cosmology, which is a mixture of largely Theravada Buddhism and "animism". By examining concepts of time, space and classification of spirits in the Dai cosmology, this part reveals how a traditional Dai house is constructed as part of an idealised order. In the second part, historical influences are taken into account to show how Dai houses in Sipsong Panna and Dehong, sharing identical social and climatic backgrounds, finally evolved into two different forms. The third part deals with the Dai social categorisation, which was largely reflected in the spatial arrangements of the houses. The social categorisation considered in this section includes both asymmetrical relationships within the household within a house, and the hierarchical relationship between the lower domestic unit, the village, and the higher level, the state. The final part considers the effects of modernisation on Dai houses. This section aims to show the tension between respect for local customs and calls for the abandonment of "old and backward ways" reflected in the Dai houses. At the same time, it is argued that the modern Dai house shares more common features in its spatial arrangement and structural system with Han vernacular houses than the houses of other Tai groups in Southeast Asia do.
It is argued that Dai vernacular architecture in these pre-industrial societies cannot be reduced to static, timeless object, but is varied and has been both cumulative and changing over time. This point addresses the more basic issue of the preservation of traditions within the modern world. In addition, the cultural and material constraints in pre-industrial societies must be understood in terms of the cultural logic of these societies, and not interpreted according to ideas which emerged from entirely different kinds of society.
This work has tried to provide comprehensive material about the houses of Dai people of South China and the bordering countries of Southeast Asia. This contribution is considered to be valuable because too little is known about the history of this architecture, and also because the fieldwork for this work has been conducted at a strategic time, when the Dai people are encountering the forces of modernisation, and are at the cross-roads of the confrontation of modernisation with their traditional culture, which is leading to new formulations and affirmations of their ethnic identity.
The framework and conceptual tools for the analysis of the house in this work derive from many anthropologists and architects. One contribution of this work may be to complement studies of the relationship between houses and societies in Southeast Asia.


Objective:To assess associations between abacavir (ABC) use and systemic inflammation. Design:Nested case–control study. Methods:The Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) cohort participants who initiated ABC were matched, using propensity score methods, to ABC-unexposed persons. Levels of high-sensitivity C-reactive protein (hsCRP) (μg/ml), interleukin-6 (IL-6) (pg/ml), and D-dimer (μg/ml) were measured from pre-HAART and on-HAART plasma. Random-effects models compared markers by ABC exposure and by changes from pre-HAART levels. Results:Biomarkers were measured in N = 508 matched pairs (328 women; 180 men). Pre-HAART levels did not differ by exposure group except that hsCRP levels were higher among WIHS women who subsequently used ABC (P = 0.04). Regardless of ABC use, mean hsCRP increases and D-dimer reductions were seen when comparing pre-HAART to on-HAART levels, in the overall group (28 and −27%), for MACS men (28 and −31%) and for WIHS women [29 and −24%, P < 0.01 for all]; IL-6 levels declined in MACS men (P = 0.02). No adjusted biomarker level differences existed by ABC exposure at the on-HAART visit. HIV RNA reductions correlated with D-dimer (r = 0.14, P < 0.01) and IL-6 (r = 0.12, P < 0.01) reductions. Associations between ABC use and mean biomarker levels were modified by pre-HAART antiretroviral therapy experience. Renal dysfunction was equally likely among non-ABC and ABC recipients. Discussion:ABC use was not associated with plasma elevations in hsCRP, IL-6, and D-dimer. Mechanisms other than increased systemic inflammation may account for ABC's reported association with increased cardiovascular disease. HAART-associated reductions in D-dimer and IL-6 were apparent regardless of ABC use and were correlated with HIV RNA reductions.


Objective: To investigate the profiles of inhaled allergens of Allergic Rhinitis (AR) patients and to study its correlation with local airborne pollen distribution under the environment of grassland in northern China.
Method: 353 AR patients were recruited in this study. 131 were male and 221 were female. All subjects received Skin Prick Test (SPT) for 16 allergens. Meanwhile, Durham sampler was applied to acquire the pollen distribution data from local site in 2015.
Result: 317 of 353 patients (89.8%) were positive to at least one allergen. The most common allergens were: Artemisia (75.0%), Humulus (61.9%), Chenopodium (58.5%), Ragweed (56.3%), Ulmus (47.2%). Artemisia tended to be the severest allergens tested with a rate of severe sensitization of 59.1%. The positive rate of grass/weed pollen was significant higher than tree pollen (83.3% vs. 62.9%, P<0.001). The allergic sensitization rate decreased along with age increasing (P=0.005). 9.4% of AR patients was mono-sensitized, 3.97% was double-sensitized, 7.7% was triple-sensitized while 68.8% was polysensitized (χ2=584.80, P<0.001). The peak pollen season was July to August in Xilingol grassland. The pollen monitoring showed the main airborne pollen in local region were Artemisia and Chenopodiaceae, with a portion of 54.2% and 30.7% of the total pollen grains in 2015, respectively.
Conclusion: Artemisia was the predominant allergens for AR patients in grassland region both in allergic sensitization and air distribution indicating environmental impact on AR. Grass/weed pollen had a higher sensitization rate than tree pollen and poly-sensitization was the main sensitization type evoked the challenge of precise immunotherapy for those AR patients.


Building on Bill's Arnold's thesis that the presence of Aramaic in Ezra presents a shift in perspective to an external point of view, Joshua Berman has theorized that Ezra 4:8—6:18 presents a narrator who is speaking from a gentile point of view as opposed to a Judean voice for the Hebrew that precedes and follows this Aramaic section. However, Berman's thesis does not account for all of the narration in this Aramaic text. The narrative verses that link the individual letters in this section indicate that the controlling voice for the overall narration is pro-Judean. These verses employ the Judeo-centric language and demonstrate that the author had a Judean source for much of the information he presents. Moreover, the narrative that connects the letters demonstrates the narrator's knowledge of the Judean prophets, their names, patronymics and office as prophets (5:1; 6:14), revealing his Judean perspective. Ultimately, this narrator reveals his viewpoint by placing the command of God next to the decrees of Persian kings (6:14). Thus, Ezra 4:8—6:18 is a single literary creation, a document that is the result of an archival search and is designed to persuade the reader that the Judeans ought to be allowed to build in Jerusalem. The inclusion of this Aramaic document in Ezra is the author/editor's way of demonstrating that even under foreign dominance, the Judeans will ultimately prosper because their God controls the events of the narrative and speaks through pro-Judean narrators even in a foreign tongue.


A model to predict the temperature rise in the reacted zone of discharging electrochemical devices has been developed. The model assumes that electrode kinetics are fast and concentration gradients are negligible. In the model, the temperature rise is predicted using the one-dimensional heat diffusion equation for a porous medium. The instantaneous power per unit area dissipated in the reacted zone is used as a source term in the heat diffusion equation. With fixed parameters such as discharge current density, charge capacity per unit volume, electrode electrical conductivity, electrode porosity, and thermophysical properties of the pore-space fluid and electrode, the transient temperature distribution in the reacted zone is calculated as a function of time. An analytical solution is derived for the transient temperature distribution in the reacted zone. Subsequently, the maximum electrode temperature is readily obtained, and the maximum electrode temperature at complete discharge is derived.


Background and Aim: Lack of formal training and assessment in communication skills in India combined with suboptimal doctor-patient ratio leave them with little time, and therefore, patients dissatisfied with doctor's therapeutic communication and often lead to violence against doctors. There is thus an urgent need for health-care providers and their trainers to be formally and systematically trained and assessed. Materials and Methods: Descriptive study (describing the process of training module development using ADDIE Framework) and an educational intervention study (using the Kirkpatrick model for measuring effectiveness of the training). Module's contents were identified through the literature search followed by content, context, and construct validation by communication and subject experts. Modular 8 hour training was implemented for 50 participants in two batches on two different days. Results: In the immediate postintervention feedback, all participants agreed that the training will be beneficial to them in real life and they expressed confidence in teaching communication skills to their students, particularly in breaking bad news and resolving doctor-patient conflicts in the real life. Effectiveness of intervention is reflected by gain in knowledge scores from 6.84 (at pretraining) to 10.76 (immediate posttraining) and sustained at 10.8 (at 3 months posttraining). The impact of the training on their communication skills is also demonstrated by the skill scores showing incremental increase from 12.4 (at pretraining) to 19.16 (immediate posttraining) and then 21.8 (at 3 months posttraining) which is statistically significant (P < 0.05). Conclusion: The training was effective, accepted well by trainees and has been institutionalised.


In 2000 I was awarded a Nuffield Farming Scholarship to study the impact of biotechnology, in particular genetically modified crops, on international agricultural research, production and marketing. I studied this topic in 2001 in Canada, USA and United Kingdom in an attempt to gain an insight into the issues with GM crops and how this may impact on our decision to grow them in Western Australia. I was impressed by the technology available that opened up a range of opportunities for vast improvements in production traits, quality of food, food safety and environmental and human health benefits. I also gained an understanding of the challenges faced by Canada and the US in production, identity preservation, testing and marketing of GM crops. In contrast the UK gave me a valuable appreciation of the influence of the marketplace in determining the future of GM research and production. Since my return I have had an opportunity to reflect on what I learnt and assess the impact this has on our decision to grow GM crops in WA in an environment of growing public concern and debate. The technology provides us with a valuable tool for more efficient production and market segmentation and we must take advantage of it to remain competitive in the world market. However, we need to learn from the mistakes made by other countries producing GM crops and commit resources to very good testing and identity preservation systems backed by strong regulatory, research, development and production processes to minimise the risk of making the same mistakes.


There is no subject at the interface oflaw, psychiatry and medical ethics which is more controversial than psychosurgery. The divergent views ofthe treatment begin with its definition. The World Health Organisation' and others2 define psychosurgery as the selective surgical removal or destruction of nerve pathways or normal brain tissue with a view to influencing behaviour. However, proponents of psychosurgery demur on the basis that the 'modern' treatment is concerned predominantly with emotional illness, without any specific effect upon behaviour. The alternative definition offered is 'the surgical treatment of certain psychiatric illnesses by means of localised lesions placed in specific cerebral sites.3 It is difficult entirely to accept this definition because, as examined below, scientific psychiatry is notyet in a position to directly treat psychiatric illness solely through surgical intervention. There is no reliable theoretical relationship between particular cerebral sites (which are normal and healthy) and an identifiable psychiatric illness or symptomatology. Given this state ofpsychiatric understanding, it is misleading to suggest fine distinctions between generalised alteration of behaviour or mood and treatment of an illness. Highly divergent practices and theories (relating to the multiplicity of conditions treated, surgical methods adopted and areas of the brain operated upon) further undermine exaggerated claims that psychosurgery can scientifically 'treat' specific illness through precise surgical intervention. Nonetheless, contemporary psychosurgery does not contain quite the same 'broadbrush' approach of its ancestors and it can lay some legitimate claim as an effective empirical treatment in narrowly limited circumstances. Major ethical problems still, however, arise and these will be discussed in this article.


This research examines the implications of consumers' belief in karma—the belief that the universe bestows rewards for doing right and exacts punishments for doing wrong—in the context of prosocial behavior. Although intuitively, believing in karma should result in greater intentions to do right by supporting a charity, karmic beliefs are found to facilitate prosocial behavior only in contexts not associated with self-gains. A series of experiments shows that those with strong (vs. weak) beliefs in karma actually respond less favorably to charitable appeals that rely on common marketing tools meant to enhance consumer responses but that also cue self-gains by offering incentives or by highlighting self-benefits. However, these effects are only obtained for donations of time, which represent a means to enhance social connections, but not for donations of money. Consistent with the proposition that prosocial behaviors motivated by self-gains do not engender karmic rewards, lower intentions to do right among those with strong karmic beliefs are driven by a shift from other-focused to self-focused attention following appeals that cue self-gains, as compared to appeals that do not. Results imply that marketers need to take into account consumers' karmic beliefs when seeking to incentivize prosocial behavior.


This study applied conversation analysis for the first time to episodes in which children express pain and bodily sensations in the everyday setting of family mealtimes. It focuses on the components of children s expressions, the character of parents responses, and how the sequence is resolved.

Three families who had a child with a long term health condition were recruited through voluntary support groups and agreed to film 15-17 mealtimes. In total 47 mealtimes were recorded totalling 23 hours of data. Each family had two children aged 15 months to nine years and included a heterosexual married couple. This data was supplemented by archives in the Discourse and Rhetoric Group: a further nine hours of mealtime recordings by two families each with two children aged three to seven years.

The analysis describes four key components of children s expressions of bodily sensation and pain: lexical formulations; prosodic features; pain cries and embodied actions, revealing the way in which they can be built together to display different aspects of the experience. The results highlight the nature of these expressions as initiating actions designed in and for interaction. An examination of the sequence that follows demonstrates the negotiated character of pain. Descriptions of the nature of the child s pain and its authenticity are produced, amended, resisted or accepted in the turns that follow. During these sequences participant orientations reveal the pervasive relevance of eating related tasks that characterises mealtime interaction.

The discussion concludes by describing the unique insights into the negotiated rather than private nature of a child s pain demonstrated by this study, and the way in which pain can be understood as produced and dealt with as part of the colourful tapestry of everyday family life in which everyday tasks are achieved, knowledge and authority is claimed and participants are positioned in terms of their relationship to one another.


ABSTRACT HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. IMPORTANCE Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF279, is due to the blocking of virus interactions with both the CXCR4 and CCR5 coreceptors. The ability of NF279 to abrogate cellular calcium signaling induced by the respective chemokines showed that this compound acts as a dual-coreceptor antagonist. P2X1 receptor antagonists could thus represent a new class of dual-coreceptor inhibitors with a structure and a mechanism of action that are distinct from those of known HIV-1 coreceptor antagonists.


Many everyday Islamic spaces in the "West" are almost undetectable. In Montreal, zoning regulations, economic restrictions, and the recurring debate surrounding religious accommodations significantly impact how and where Muslim communities establish their places of worship. These buildings are present, yet often hidden in the physical urban fabric - which is deemed "secular" - that surrounds us. This thesis explores questions of visibility / invisibility, and secular / sacred space: what is it that we call the secular public space? How does it compare to religious space, and how permeable is it to the non-secular? Where does the sacredness of a place rest? How do the different places of worship in a city connect together? This research investigates this theological landscape as a vernacular that is repurposed into a religious space and place of a community, and studies ways to make these religious spaces visible, to reveal another landscape within Montreal.


The application of high pressure advanced fuel injection equipment allows for better control of spray mixing, which ultimately can lead to a more favourable trade-off in noise, soot and NOx formation across the engine operating map. The new Diesel research facility at the University of Brighton has been specifically designed to enable the study of Diesel sprays at realistic automotive in-cylinder conditions while simultaneously providing excellent optical access for both qualitative and quantitative measurements of the combusting/non-combusting spray. The rig is constructed around a single cylinder two-stroke Diesel engine with a specially designed optical chamber incorporated between the cylinder and head. Spray cone angle and penetration data extracted from photographic and high-speed video studies undertaken in the test rig are presented. Injection pressures of 160 MPa and in-cylinder pressures of 10 MPa were achieved.


Novel [15]crown-5 and [18]crown-6 o-terphenyls differing in number and position of sulfur in the side chains and their corresponding triphenylene analogues were synthesized via a nucleophilic aromatic displacement of fluoride as the key step. Except for one short chain derivative all other compounds showed enantiotropic columnar mesophases which were studied by DSC, POM and XRD (WAXS, SAXS). The presence of sulfur induced broad room temperature columnar mesophases. This effect was more pronounced for bend [15]crown-5 derivatives than for linear [18]crown-6 derivatives. Redox properties were mostly governed by the triphenylene moieties, showing stepwise oxidation of the individual triphenylene units.


I entered the bacterial chromosome field in 2004 as a fresh Ph.D. trained in theoretical physics. Ten years is not long enough for one to gain the depth and breadth of a scientific discipline of long history, certainly not for an early career scientist to write an essay of the status of A Mathematician's Apology (Hardy 1940). Nevertheless, I agreed to write this perspective as a physicist who entered biology, because my colleagues are often curious to know what drives physicists to become (physical) biologists, and makes them stay in biology despite many challenges. I also wanted to share several lessons I have learned because, while some of them are personal and specific to my field, I have a good reason to believe that they might resonate with many future travelers. This perspective is for them.


The aim of this study is to evaluate the effect of different feeding rates and frequencies on angelfish (Pterophyllum scalare) and severum (Heros severus) larvae. For this purpose, two similar experiments were conducted in parallel. For each experiment, a total of 360 larvae were distributed in 36-1 L aquariums. The experiments were done using a factorial 3x3 completely randomized design, with four replicates. The feeding rates of 50, 100 and 150 artemia nauplii larvae-1 and the feeding frequencies of one, two and four meals day-1 were tested. Parameters of growth performance, uniformity of the batch and survival rate were determined at the end of both experimental periods. No interaction was observed between feed rates and frequencies in angelfish for all parameters evaluated; growth performance was higher in fish fed with 150 nauplii larvae-1, which were divided in two and four meals day-1. The severum larvae presented interaction between feeding rates and feeding frequencies; growth performance was higher in fish fed with two and four meals day-1. Thus, in order to facilitate feed management and reduce manpower costs during ornamental angelfish and severum larvae production, it is recommended to supply 150 artemia nauplii larvae-1 divided in two meals day-1 to fish.

 Key words: Angelfish, feeding practices, ornamental fish farming, severum.


Firms and NGOs often collaborate to establish new supply chains. With a formal model, we analyze how NGOs can alleviate market failures and improve supplier economic inclusion while strategically interacting with firms. We account for the specific goals of the NGO and the need to induce collaboration between firms and their suppliers. The analysis reveals a "valley of disappointment", when NGO efforts benefit all actors but only marginally the firm. We also show that more powerful firms might prefer to internalize NGO functions, while firms with lower bargaining power and higher investment requirements are better off collaborating with NGOs. Finally, we study NGOs-firms matching patterns and find that firms with higher bargaining power match with NGOs holding stronger capabilities.


We develop a dynamic network model whose links are governed by banks' optimizing decisions and by an endogenous tâtonnement market adjustment. Banks in our model can default and engage in firesales: risk is trasmitted through direct and cascading counterparty defaults as well as through indirect pecuniary externalities triggered by firesales. We use the model to assess the evolution of the network configuration under various prudential policy regimes, to measure banks' contribution to systemic risk (through Shapley values) in response to shocks and to analyze the effects of systemic risk charges. We complement the analysis by introducing the possibility of central bank liquidity provision.


PT. Indonesia Telecommunications ( Persero) Tbk., is a BUMN [of] which
is on year 1995 have succeeded to come into the both competitive national market
and also global through the program privatization by selling some of its share to
society ( Go-Public). PT. Telkom Policy of privatization is meant to muster the
society fund that can obtain a fresh fund to fulfilling PT. Telkom defrayal of
investment and working capital. In the year 2001 PT. Telkom have run the second
phase of privatization to be more improve the company performance.
This research aim to analyze the performance of PT. Telkom financial work
after the implementation of the second phase privatization in the year 2001, by
using measurement of finance ratio, for example: Liquidity Ratio, Activity Ratio,
Solvency Ratio, Profitability Ratio and Return of stockholder Investment Ratio.
This measurement [is] conducted to see the storey; level of efficiency and
effectivity PT. Telkom after doing the second phase of privatization in the year
2001. The Analysis method used are descriptive analyze by using 11 finance ratio
which is pursuant to data of financial statement PT. Telkom which have been
processed from year 2000 up to year 2005, got from corner of BEJ UNDIP.
From all analyzed ratio, obtained result that in generally PT.TELKOM
second phase of privatization performance in the year 2001 can be told good
either due PT. Telkom have succeeded to improve the performance of company in
the second phase of privatization. This matter can be seen from the number of
better ratio storey; level after the second phase of privatization if it compared to
the implementation before the second phase of privatization in the year 2001. But
in the case of taking care of storey; level of company advantage, company
management have to be more care about the consistency growth level of company
advantage by improving efficiency and effectivity to reduce the company cost
which must be accounted on and maximize the management of company asset,
especially in its circulating assets.
Therefore the writer give suggest to the company to conduct effective asset
management by using the asset ( investment) to be more improve the earnings,
without overruling circulating assets owned. Besides PT. Telkom require to do the
better evaluation to its long-range projects as a whole, including program of
product development of telecommunications service assessed by less efficient that
able to harm company.


Integrin-mediated leukocyte adhesion is a critical aspect of leukocyte function that is tightly regulated by diverse stimuli, including chemokines, antigen receptors, and adhesion receptors. How cellular signals from CD31 and other adhesion amplifiers are integrated with those from classical mitogenic stimuli to regulate leukocyte function remains poorly understood. Here, we show that the cytoplasmic tail of CD31, an important integrin adhesion amplifier, propagates signals that induce T cell adhesion via β1 (VLA-4) and β2 (LFA-1) integrins. We identify the small GTPase, Rap1, as a critical mediator of this effect. Importantly, CD31 selectively activated the small Ras-related GTPase, Rap1, but not Ras, R-Ras, or Rap2. An activated Rap1 mutant stimulated T lymphocyte adhesion to intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM), as did the Rap1 guanine nucleotide exchange factor C3G and a catalytically inactive mutant of RapGAP. Conversely, negative regulators of Rap1 signaling blocked CD31-dependent adhesion. These findings identify a novel important role for Rap1 in regulating ligand-induced cell adhesion and suggest that Rap1 may play a more general role in coordinating adhesion-dependent signals during leukocyte migration and extravasation. Our findings also suggest an alternative mechanism, distinct from interference with Ras-proximal signaling, by which Rap1 might mediate transformation reversion.


Knowledge on anatomical, physical and mechanical properties of wood is
necessary in assessing the potential utilisation of wood. The main objectives of this
study are to determine the cellular composition and anatomical variations of juvenile
rubberwood (Hevea brasiliensis) and their extent in the selected clones and age
groups. Another objective is to determine the structure of juvenile wood in relation to
physical and mechanical properties. Three different clones, PB 359, PB 3 66 and
RRIM 600 from two age groups, namely 10 and 22 years old were selected from
Golden Hope Plantation Bhd. Three trees were felled for each clone and age group.
Each tree was divided into three portions along the height namely, stump (S₁), trunk (S₃) and branch (S₅). Outer and inner samples along the radial position were chosen for
comparative studies on the anatomical, physical and mechanical properties. All
samples for each test were prepared in accordance with the British Standard (BS 373:1957) specifications.


Expression of the rutabaga-encoded type I adenylyl cyclase in Drosophila mushroom bodies can rescue the short-term memory defect in rutabaga mutant flies. In order to differentiate between a potential developmental role of the adenylyl cyclase from its acute function in memory formation, McGuire et al. developed a system to control both temporal and spatial expression of a transgene in Drosophila. Using this system, rutabaga expression in the mushroom bodies during adulthood allowed for normal memory acquisition by otherwise mutant rutabaga animals. This technique will be useful more generally to study when and where gene products are needed during the lifetime of an organism. S. E. McGuire, P. T. Le, A. J. Osborn, K. Matsumoto, R. L. Davis, Spatiotemporal rescue of memory dysfunction in Drosophila. Science 302, 1765-1768 (2003). [Abstract] [Full Text]


The importance of irritability, as measured among the symptoms of oppositional defiant disorder (ODD), has dramatically come to the fore in recent years. New diagnostic categories rely on the distinct clinical utility of irritability, and models of psychopathology suggest it plays a key role in explaining developmental pathways within and between disorders into adulthood. However, only a few studies have tested multidimensional models of ODD, and the results have been conflicting. Further, consensus has not been reached regarding which symptoms best identify irritability. The present analyses use 5 large community data sets with 5 different measures of parent-reported ODD, comprising 16,280 youth in total, to help resolve these questions. Across the samples, ages ranged from 5 to 18, and included both boys and girls. Confirmatory factor analyses demonstrated that a modified bifactor model showed the best fit in each data set. The structure of the model included 2 correlated specific factors (irritability and oppositional behavior) in addition to a general ODD factor. In 4 models, the best fit was obtained using the items "being touchy," "angry," and "often losing temper" as indicators of irritability. Given the structure of the models and the generally high correlation between the specific dimensions, the results suggest that irritability may not be sufficiently distinct from oppositional behavior to support an entirely independent diagnosis. Rather, irritability may be better understood as a dimension of psychopathology that can be distinguished within ODD, and which may be related to particular forms of psychopathology apart from ODD.


Should laws about sex and pornography be based on social conventions about what is disgusting? Should felons be required to display bumper stickers or wear T-shirts that announce their crimes? This powerful and elegantly written book, by one of America's most influential philosophers, presents a critique of the role that shame and disgust play in our individual and social lives and, in particular, in the law. Martha Nussbaum argues that we should be wary of these emotions because they are associated in troubling ways with a desire to hide from our humanity, embodying an unrealistic and sometimes pathological wish to be invulnerable. Nussbaum argues that the thought-content of disgust embodies "magical ideas of contamination, and impossible aspirations to purity that are just not in line with human life as we know it." She argues that disgust should never be the basis for criminalizing an act, or play either the aggravating or the mitigating role in criminal law it currently does. She writes that we should be similarly suspicious of what she calls "primitive shame," a shame "at the very fact of human imperfection," and she is harshly critical of the role that such shame plays in certain punishments. Drawing on an extraordinarily rich variety of philosophical, psychological, and historical references--from Aristotle and Freud to Nazi ideas about purity--and on legal examples as diverse as the trials of Oscar Wilde and the Martha Stewart insider trading case, this is a major work of legal and moral philosophy.


Here, we report sub-diffraction resolution in two-photon excitation (TPE) fluorescence microscopy achieved by merging this technique with continuous-wave (CW) stimulated-emission depletion (STED). We show an easy-to- implement and promising laser combination based on Ti:Sapphire ultrafast laser source for two-photon excitation and a commercial Leica TCS STED-CW microscope for resolution enhancement. Images of fluorescent nanoparticles produce comparative similar resolution to the one photon excitation. Two-photon excitation STED microscopy achieves approximately 3-4 fold improvement in resolution in the radial direction over conventional 2PELSM. Further improvements in resolution are theoretically achievable, suggesting that 2PE STED microscopy will permit nanoscale imaging, for instance, of neuronal structures located in relatively intact brain tissue.


This comprehensive history traces the development of mathematical ideas and the careers of the men responsible for them. Volume 1 looks at the discipline's origins in Babylon and Egypt, the creation of geometry and trigonometry by the Greeks, and the role of mathematics in the medieval and early modern periods. Volume 2 focuses on calculus, the rise of analysis in the nineteenth century, and the number theories of Dedekind and Dirichlet. The concluding volume covers the revival of projective geometry, the emergence of abstract algebra, the beginnings of topology, and the influence of Godel on recent mathematical study.


We present results from testing of parallel versions of algorithms for derivativefree optimization. Such algorithms are required when an analytical expression for the objective function is not available, which often happens in simulator-driven product development. Since the objective function is unavailable, we cannot use the common algorithms that require gradient and Hessian information. Instead special algorithms for derivative-free optimization are used. Such algorithms are typically sequential, and here we present the rst test results of parallelization of such algorithms. The parallel extensions include using several start points, generating several points from each start point in each iteration, alternative model building, and more. We also investigate whether we can generate synergy between the di erent start points through information sharing. Examples of this include using several models to predict the objective function value of a point in order to prioritize the order in which points are sent for evaluation. We also present results for higher-level control of the optimization algorithms.


In this study, we show that Au-Cu2-xSe heterogeneous nanocrystals have great promise for use in photothermal therapy (PTT). Ligand-stabilized heterogeneous gold-copper selenide (Au-Cu2-xSe) hybrid nanocrystals were synthesized by a colloidal gold seed-mediated method. The nanocrystals exhibit broad localized surface plasmon resonance (LSPR) across visible and near-infrared (NIR) wavelengths, arising from interactions between the two nanocrystal domains. After a ligand-exchange process, the NCs readily disperse in water while retaining their LSPR absorbance. Upon illumination with a 980 nm laser, the Au-Cu2-xSe nanocrystals produced significant photothermal heating with a photothermal transduction efficiency comparable to that of larger gold nanostructures that have been widely studied for PTT. In vitro photothermal heating of Au-Cu2-xSe nanocrystals in the presence of human cervical cancer cells caused cell ablation after 10 min laser irradiation. Cell viability assays demonstrated that the hybrid nanocrystals are biocompatible at doses needed for photothermal therapy. Overall, these heterogeneous nanocrystals provide the NIR PTT efficacy of larger gold nanorods in a much smaller overall nanostructure that may have advantages with respect to biodistribution and clearance.


The main purpose of this book is to study the relation between the personal, religious visions and auditions of the internationally known Swedish artist Violet Tengberg (born 1920) and her artistic creations. In the descriptive part of the study the artist's "outer" activity in the form of artistic creation, development of motives, and exhibitions is presented. Complementary to this presentation, the artist's "inner" world, consisting of religious visions, is described. These experiences supply us with a key to understanding the symbolism in Violet Tengberg's art. After this descriptive part a theoretical part follows, in which the author along with a critical discussion of the psychology of creativity and mental imagery, presents and criticizes religio-psychological studies of religious visions. The innovation in the present study consists of an integrated model of analysis, based on the psychology of creativity and mental imagery. This model is applied to the study of religious visions. An important result is that Violet Tengberg's symbolism and visionary experiences mutually reinforce each other. Her paintings are an expression of creative mysticism. (Less)


This research addresses the use of dual-polarimetric descriptors for automatic large-scale ship detection and characterization from synthetic aperture radar (SAR) data. Ship detection is usually performed independently on each polarization channel and the detection results are merged subsequently. In this study, we propose to make use of the complex coherence between the two polarization channels of Sentinel-1 and to perform vessel detection in this domain. Therefore, an automatic algorithm, based on the dual-polarization coherence, and applicable to entire large scale SAR scenes in a timely manner, is developed. Automatic identification system (AIS) data are used for an extensive and also large scale cross-comparison with the SAR-based detections. The comparative assessment allows us to evaluate the added-value of the dual-polarization complex coherence, with respect to SAR intensity images in ship detection, as well as the SAR detection performances depending on a vessel's size. The proposed methodology is justified statistically and tested on Sentinel-1 data acquired over two different and contrasting, in terms of traffic conditions, areas: the English Channel the and Pacific coastline of Mexico. The results indicate a very high SAR detection rate, i.e., >80%, for vessels larger than 60 m and a decrease of detection rate up to 40 % for smaller size vessels. In addition, the analysis highlights many SAR detections without corresponding AIS positions, indicating the complementarity of SAR with respect to cooperative sources for detecting dark vessels.


1. The concentrations of electrolytes and free amino acids in plasma and the quadriceps femoris muscle were studied in ten apparently healthy elderly men, 52–77 years of age. The results were compared with those previously recorded for men 20–36 years old. 2. The two groups of subjects did not differ with regard to serum electrolytes and intracellular water content but the extracellular water in the older subjects exceeded that of the younger group by about 50%. The muscle specimens of the elderly men were also characterized by a 40% elevation of their total contents of Na+ and Cl − , whereas the content of K + and Mg 2+ was almost identical in both groups. 3. The means recorded for the plasma concentrations of most amino acids tended to be higher in the elderly men. The differences reached statistical significance for tyrosine, histidine, valine, lysine and total essential amino acids. In keeping with the findings in plasma, the amino acid concentrations in the muscle of the older group tended to exceed those of the younger ones. The difference reached statistical significance with regard to total amino acids, essential and non-essential amino acids, aspartate, alanine, citrulline, histidine, arginine, leucine and lysine. The various mechanisms that may contribute to these findings are discussed.


The problem of transmit beamforming to multiple cochannel multicast groups is considered, when the channel state is known at the transmitter and from two viewpoints: minimizing total transmission power while guaranteeing a prescribed minimum signal-to-interference-plus-noise ratio (SINR) at each receiver; and a "fair" approach maximizing the overall minimum SINR under a total power budget. The core problem is a multicast generalization of the multiuser downlink beamforming problem; the difference is that each transmitted stream is directed to multiple receivers, each with its own channel. Such generalization is relevant and timely, e.g., in the context of the emerging WiMAX and UMTS-LTE wireless networks. The joint problem also contains single-group multicast beamforming as a special case. The latter (and therefore also the former) is NP-hard. This motivates the pursuit of computationally efficient quasi-optimal solutions. It is shown that Lagrangian relaxation coupled with suitable randomization/cochannel multicast power control yield computationally efficient high-quality approximate solutions. For a significant fraction of problem instances, the solutions generated this way are exactly optimal. Extensive numerical results using both simulated and measured wireless channels are presented to corroborate our main findings.


IMS Learning Design (IMS LD, 2003) is a pedagogically expressive specification to model Units of Learning (UoL). IMS LD's generality implies that it should also be capable of modelling computer-based educational games. Issues on synchronization, grouping, multirole playing, timing, collaborative working, dynamic feedback, adaptive learning and more are implicit or explicit in educational gaming and can be approached with it. Also, a framework must be defined to describe what is considered as an educational game. Many games, both commercial and free, are described as educational ones yet the educational character of a game depends on the objectives, the context and the moment when it is run. In order to support this definition, we will establish a classification of educational games that we will use to define their relationship with IMS LD, as well. Furthermore, this article will provide some answers to general questions about IMS LD coming from a broad study of a concrete field, as educational games is.


Our study sets out to discuss the religious policy of Emperor Heraclius ( 610-641) in regards to Hebrews. Before the relic of the Holy Cross was reinstalled in Jerusalem (31 March 630), Emperor Heraclius's relations with the Hebrews do not seem to be tense. Starting with 630, Heraclius  retaliates against the Hebrews as a punishment for their collaboration with the Persians, as well as for their involvement in the massacre of Christians when Jerusalem was conquered by the Persians (614). The Emperor issued an edict for the forced conversion of Hebrews to Christianity. The scope of this edict covered the entire Byzantine Empire, but it was only enforced in Cartagena (May 31, 632). Saint Maximus the Confessor condemns Heraclius's decision to forcibly convert Cartagena Hebrews to Christianity. Heraclius's decree was contested among the Hebrews. Their forced christening caused their migration to Persia. Also, Heraclius's anti-Hebrew policy determined them to facilitate the Arab expansion in Byzantine territories.
Keywords: religious policy, emperor Heraclius, Hebrews, conversion, baptism


GenOpt is an optimization program for the minimization of a cost function that is evaluated by an external simulation program. It has been developed for optimization problems where the cost function is computationally expensive and its derivatives are not available or may not even exist. GenOpt can be coupled to any simulation program that reads its input from text files and writes its output to text files. The independent variables can be continuous variables (possibly with lower and upper bounds), discrete variables, or both, continuous and discrete variables. Constraints on dependent variables can be implemented using penalty or barrier functions. GenOpt uses parallel computing to evaluate the simulations. GenOpt has a library with local and global multi-dimensional and one-dimensional optimization algorithms, and algorithms for doing parametric runs. An algorithm interface allows adding new minimization algorithms without knowing the details of the program structure. GenOpt is written in Java so that it is platform independent. The platform independence and the general interface make GenOpt applicable to a wide range of optimization problems. GenOpt has not been designed for linear programming problems, quadratic programming problems, and problems where the gradient of the cost function is available. For such problems, as well as for other problems, special tailored software exists that is more efficient.


Since the first edition of Modern Constitutional Law was published nearly thirty years ago, it has continued to be one of the best sellers in a very competitive market. Over the years, many law professors have adopted this user-friendly casebook-which is no surprise, given the rave reviews this book has enjoyed. Professor Thomas E. Baker stated that he has "been so loyal to the Rotunda brand name over the years," because the book is compact without being superficial. It "remarkabl[y]" manages "to include all the important cases yet preserves a fuller set of opinions to guarantee 'thoughtful classroom discussion. This new edition incorporates the many changes in Constitutional law, such as the Second Amendment and the recent decisions dealing with National Security and holding detainees captured in the War on Terror. Moreover, this book manages to accomplish this goal while retaining its compact size.


The relation between age and amino-acid epimer ratios (alloisoleucine/isoleucine, A/I) of Holocene land snails was quantitatively evaluated through 14 C and amino-acid analysis of 33 samples from fluvial and colluvial sediments and rodent middens in the Northern Negev Desert of Israel. A/I is strongly correlated with 14 C ages in fluvial and rodent midden deposits ( r = 0.95 and 0.94, respectively), permitting age estimates from A/I ratios with precisions of ±700 and ±660 yr. The correlation is weaker in colluvial deposits ( r = 0.74), and age estimates from A/I ratios are correspondingly less precise (±1580 yr). This probably results from delayed burial, which exposes the shells to intense radiation on the desert surface. Because of the generally strong relation between age and A/I, amino-acid epimerization analysis of individual shells can be used to identify mixed-age deposits and to reconstruct species chronologies from mixed-age deposits.


It is well known that Russia is heavily dependent on its energy sector, from both an economic and a political perspective. As a result, the fall in the oil price over the past two years and the dramatic changes taking place in the global gas market are having signifi cant consequences for both the Kremlin and Russia's domestic energy companies. However, instead of reviewing the increased risks for Russia from the change in global energy markets, this edition of the Oxford Energy Forum discusses how Russia has started to adapt its policies and commercial strategies in a number of different areas. Some of the new strategies appear very positive, while others carry inherent risks, but all show how the world's largest producer of hydrocarbons is being forced to respond politically and commercially to the shock of lower commodity prices.


In early 2003, a young Wall Street investment banker named Bo Parfet set out to accomplish something very few had done before--climbing the highest mountain on every continent. He was not a professional climber, but what began as a casual interest would soon become a lifelong passion and in just over four years, Bo would overcome the odds and conquer all of the mountains--Kilimanjaro, Aconcagua, Denali, Vinson Massif, Elbrus, Carstenz Pyramid, Kosciusko, and Everest--with courage, unbridled passion, and determination. Combining the gripping narrative of "Into Thin Air" with the adrenaline-fueled drama of "Vertical Limit," "Die Trying" is the incredible story of one man's battle against his own limitations. From dodging avalanches to crossing a ladder over a seemingly bottomless crevasse, to making his way through the Khumbu Icefall and burying a dead teammate at 27, 000 feet, we experience all of the author's exhilarating, often terrifying climbs first-hand. We travel with him during his near-death experiences when falling into a crevasse in New Zealand and nearly-drowning in crocodile-infested rapids during a canoe race in Belize. And we share the terror of his confrontations with corrupt army officials, cannibalistic tribesmen, and local militia groups. Harrowing and uplifting, "Die Trying" is a riveting memoir that will inspire all of us to defy the odds and fulfill our dreams.


Recently, nucleic acid-based RNA and DNA vaccines have represented a better solution to avoid infectious diseases than "traditional" live and non-live vaccines. Synthetic RNA and DNA molecules allow scalable, rapid, and cell-free production of vaccines in response to an emerging disease such as the current COVID-19 pandemic. The development process begins with laboratory transcription of sequences encoding antigens, which are then formulated for delivery. The various potent of RNA over live and inactivated viruses are proven by advances in delivery approaches. These vaccines contain no infectious elements nor the risk of stable integration with the host cell genome compared to conventional vaccines. Conventional mRNA-based vaccines transfer genes of interest (GOI) of attenuated mRNA viruses to individual host cells. Synthetic mRNA in liposomes forms a modern, refined sample, resulting in a safer version of live attenuated RNA viruses. Self-amplifying RNA (saRNA) is a replicating version of mRNA-based vaccines that encode both (GOI) and viral replication machinery. saRNA is required at lower doses than conventional mRNA, which may improve immunization. Here we provide an overview of current mRNA vaccine approaches, summarize highlight challenges and recent successes, and offer perspectives on the future of mRNA vaccines.


On March 11, 2008, the Judicial Conference of the United States, the administrative policy-making body of the federal judiciary, approved the first set of nationally binding rules for dealing with accusations of misconduct by federal judges. The new rules implement recommendations made by a committee chaired by Supreme Court Justice Stephen Breyer. The Breyer Committee found that although the judiciary has been doing a very good overall job in handling complaints against judges, the error rate in high-visibility cases is far too high. The new regulatory regime comes into existence at a time when federal judges have been accused of ethical transgressions that span the spectrum of actionable misbehavior. Indeed, at least three judges face the possibility of impeachment proceedings. This article examines the newly adopted misconduct rules against the background of these recent controversies. The underlying question is the same one that Congress grappled with when it established the current statutory framework in 1980: can federal judges be trusted to investigate and impose appropriate discipline for misconduct in their ranks? The article begins with a brief account of the history that led to the promulgation of the new rules. Next, the article outlines the procedures established by Congress and the judiciary for handling allegations of misconduct by federal judges. The remainder of the article addresses the major issues raised by the new rules: the move toward greater centralization in the administration of the disciplinary system; the definition of misconduct; the possible need for greater procedural formality; the nature and timing of public disclosure; and efforts to make the process more visible.


Rule of law (RoL) promotion has become a go-to-tool in the complex process of stabilizing and rebuilding (post-)conflict States. The process is driven by a heterogeneous group of national, foreign, and international actors who define and prescribe RoL norms and standards, who programme, finance, implement, and eventually monitor RoL reforms. While the legitimacy and effectiveness of RoL promotion has undergone scrutiny, particularly within the overall context of international development assistance, an aspect that has so far received little attention is the legality of RoL promotion. This concerns both the mandate of the various actors and the execution of RoL activities on the ground. Since 2001, the international community has intensely supported the RoL in Afghanistan rendering it a veritable testing ground for RoL promotion. The article explores the legal framework for actors in RoL promotion in Afghanistan from 2001 up to the present day, with a focus on the German Government, its development cooperation agencies, and private non-governmental organizations (NGOs). The article shows that while detailed rules bind the monitoring and evaluation of RoL activities in line with the existing international frameworks for development assistance, few laws and principles guide the programming and implementation of RoL promotion. The existing standards are generally too abstract to guide specific RoL promotion activities. Further concretization and harmonization is necessary in the interest of the sustainability of RoL promotion in Afghanistan – and elsewhere. 173 The Law Behind Rule of Law Promotion in Fragile States


The present paper explores the effects of different risk incidents on a Transportation Model developed for HazMat (Hazardous Materials) shipments. The particular objective of this study is to elucidate the effects of occurrence probabilities of the different risk events on the transportation model featuring total transportation cost. First, the present research study addresses the problem of identifying and evaluating various risk factors that influence the HazMat transportation network. Next, a modeling framework for HazMat transportation is proposed as a special case of the traditional transportation network in the presence of risk-informed safety constraints that need to be satisfied. A comprehensive characterization of the underlying risk profile that is probabilistically realized through appropriately conducted Monte Carlo simulations that capture the effect of underlying irreducible uncertainties associated with the main risk-drivers is followed by the proposed solution approach to the corresponding minimum cost flow network problem while reducing risks at the desired levels. In order to examine the impact of the occurrence possibilities of different risk events on the transportation model, appropriate parameterized simulation work is carried out, resulting in identifying release probability zones and safe network configurations that correspond to certain low-risk levels and degrees of risk-related uncertainties. These simulation studies help making informed decisions on optimal transportation configurations for ensuring safety in hazardous material shipments. Finally, the presented methodological framework demonstrates its potential usefulness in making risk-informed decisions while transporting goods and classes of materials that can be potentially proven dangerous to public health and ecosystem functions.


The empirical finding that democracies do not fight each other has long suggested that regime type influences international behavior. In the research reported here, we demonstrate that the democratic peace is only the most visible manifestation of the impact of domestic political structure on international relations. We consider the complete range of cooperative and conflictual interaction of each state in the international system with every dyadic partner in its politically relevant international environment between 1953 and 1978. We demonstrate a strong and consistent relationship between regime type and foreign policy behavior, both at the monadic and the dyadic level. States with more democratic characteristics tend to behave more cooperatively and less conflictually in the international system; these tendencies intensify when democratic states interact with other democracies. Meanwhile, non-democracies tend to treat democracies with more conflictual and less cooperative behavior. The influence of the internal institutional structures of states on their external behavior extends well beyond decisions to go to war. The empirical findings reported herein suggest that future research will benefit from increased attention to the relationships among state structure, leaders' incentives, foreign policy behavior, and international outcomes.


One of the most memorable moments of the 2014 Academy Awards was Ellen DeGeneres's famous selfie taken with Bradley Cooper, Meryl Streep, and other famous friends. This so -called "Oscar Selfie" has been estimated to be worth millions of advertising dollars for the event's sponsor, Samsung. DeGeneres' use of selfies as a promotional tool was novel method of documenting Hollywood's greatest night which proved an undeniable successful. However, the fact that Bradley Cooper actually captured the Oscar Selfie raises a number of important questions about how user-generated content distributed through social media fits into existing intellectual property law. At the heart of this investigation is the question of authorship, specifically who has the right to exploit a work posted to social media, and how the circumstances under which the work was created may affect the rights attached to it. I used the Oscar Selfie as an example in order to explore issues in rights management and the potential outcome of controversies arising out of content shared over social media with ambiguous authorship. Examining these issues through the lens of a series of hypothetical suits, this article concludes that existing copyright laws provide a finding of co-authorship, implied-license, and the applicability of fair use defenses to permit many forms of expression distributed through social media. Legal practitioners need to understand how intellectual property and creative expression are used in this arena and how the law is best applied if they are to keep pace with the wellspring of creativity and controversy that is social media. In general, it is better to respect the intentions of the parties when the distributed work was created and to ensure that the fluid exchange of ideas over social media is maintained. Superimposing restrictions which may favor one party over the other when there is not a clear case of infringement is largely incompatible with the common use social media platforms and contradicts the bulk of existing intellectual property law. Copyright © 2015 The John Marshall Law School Cite as Michael Reed, Who Owns Ellen's Oscar Selfie? Deciphering Rights of Attribution Concerning User Generated Content on Social Media , 14 J. MARSHALL REV. INTELL. PROP. L. 564 (2015).


The interest in embryology, the science of the development of a zygote into a completely developed foetus, has increased greatly in recent years due to a number of studies involving embryonic and induced pluripotent stem cells. In addition, the development of techniques such as cloning has aided to understand the critical events that occur during embryonic development. In this study, we describe the morphology of two sheep embryos and one foetus using macroscopic and microscopic techniques. We investigated sheep without defined breed on days 24, 32, and 50 of gestation (estimated by crown-rump length [CR]). Macroscopically, we observed the development of E1 (24 days), with visible optic vesicle, but without retinal pigmentation and the forelimbs bud in development. In the E2 (32 days), we noticed the presence of optic retinal pigmentation and forelimbs more developed in comparison with E1. As expected, F1 revealed an eyeball already covered and the forelimbs developed. Meanwhile, microscopic analysis revealed somite, ventricle, atrium, and oral cavity in development in E1. However, in F1 we were able to identify more complex structures, such as ossification in the spine, ventricle, atrium, intraventricular septum, pericardial sac, and oral cavity with tongue. This work brings more precise and detailed data on the morphological characteristics of the major organ systems (nervous, circulatory, respiratory, digestive, and urinary) at each embryonic and foetal stage analysed.


The Living and Dying gallery opened at the British Museum five years ago. Praised by critics, this award-winning exhibition is one of the most well attended exhibitions at the Museum. A visit to the gallery makes it apparent that it is the contemporary art installation, Cradle to Grave, that is particularly attractive to the visitors. The aim of this article is to explore why this installation is so effective. However, rather than evaluating visitor responses to the installation, this article analyses the fundamental premises that make it so successful. Using three different theories of 'proximity', 'presence' and 'flow of materials' I thereby attempt a deeper understanding of the installation's particular intensity. Thus, this article presents a type of exhibition analysis that tries to incorporate the 'meaning production' potential of an exhibition, i.e., what an exhibition tells, along with the exhibition's capability to produce 'presence' and 'material grounding', i.e., what it does.


The membrane attack complex (MAC) of complement was extracted from the membranes of cells lysed by human complement and its properties were compared with those of the fluid phase complex SC5b-9. Upon sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunochemical analysis, the two isolated complexes had identical subunit compositions, except that the MAC lacked the S-protein. The sedimentation coefficient and molecular weight of the extracted and isolated MAC were, respectively, 33.5 S and 1.7 x 10(6) daltons, compared to 23 S and 1.0 x 10(6) dalton for SC5b-9. Because the molecular weight of the MAC is approximately two times greater than that of C5b-0 (800,000 daltons), the MAC is considered the dimer of C5b- 9. Under specified conditions, the 33.5 S dimer could be converted to the 23 S monomer without dissociation of subunits. The MAC had the electron microscopic appearance and dimensions that are characteristic for the complement produced ultrastructural membrane lesions. SC5b-9 had a different ultrastructure that is dissimilar to the morphology of the lesions. The isolated MAC could be reincorporated into phospholipid bilayers and assumed on the surface of the resultant lipid vesicles the orientation and appearance of typical complement lesions.


Characterization of the Group B Streptococcus Hemolysin and its Role in Intrauterine Infection Christopher-Mychael Whidbey Chair of the Supervisory Committee: Lakshmi Rajagopal, Ph.D. Pathobiology Program, Department of Global Health Intrauterine infection and inflammation are a major cause of perinatal morbidity, including preterm birth. A pathogen associated with intrauterine infection, preterm birth, and perinatal disease is Streptococcus agalactiae, or Group B streptococcus (GBS). Despite its importance to public health, little is known about the immune response during intrauterine GBS infection and the role of specific GBS virulence factors in this process. One major GBS virulence factor is the β-hemolysin which allows GBS to lyse host cells; however, the hemolysin had never been purified and its molecular nature was undefined. Additionally, the mechanism of hemolysinmediated cytotoxicity, the host cellular immune response to the hemolysin, and the role of the hemolysin during intrauterine infection were unknown. Gaining insight into the molecular nature of the β-hemolysin and the role it plays in GBS pathogenesis is important to develop new therapeutic strategies for GBS associated disease. This dissertation describes our efforts to purify and characterize the GBS hemolysin, understand the mechanisms of pigment-mediated host cell lysis, and establish the role of this toxin during intrauterine infection that lead to fetal injury. The molecule responsible for GBS hemolytic activity had not been identified at the onset of this project. Using genetic and biochemical approaches, we demonstrated that the GBS hemolysin is not a protein toxin, but rather an ornithine rhamnolipid pigment produced by the bacterial cyl operon. The GBS pigment is toxic to both red blood cells and amniotic epithelial cells. Overproduction of this pigment allows GBS to traverse human placental membranes. Hyperpigmented GBS strains were identified among clinical isolates from women in preterm birth, supporting the hypothesis that the pigment is important during intrauterine infection. With purification of this major virulence factor, we were able to investigate how the GBS pigment causes membrane disruption and identify the immune pathways it activates. We found that the GBS pigment induces membrane perturbations in lipid membranes, which leads to ion flux. In red blood cells, this ion flux results in colloidal-osmotic lysis. In macrophages, membrane disruption triggers activation of the NLRP3 inflammasome, leading to activation of caspase 1. Caspase 1 activation by both whole cell GBS and the purified pigment is NLRP3 dependent, and results in secretion of IL-1β and the programmed, proinflammatory cell death known as pyroptosis. We developed a murine model of intrauterine infection to test the role of the GBS pigment in vivo. Infection with hyperpigmented/hyperhemolytic bacteria resulted in intrauterine fetal injury and preterm birth. Intrauterine fetal death in NLRP3 deficient mice was decreased compared to wild-type mice, demonstrating a role for pigment-mediated activation of NLRP3 during intrauterine infection. Interestingly, even in NLRP3-deficient mice, hyperpigmented GBS caused more fetal death that nonpigmented GBS. These results suggest that both NLRP3 dependent and NLRP3-independent pathways contribute to pathogenesis during intrauterine infection. Together, these data demonstrate that the GBS hemolysin, an ornithine rhamnolipid toxin, plays a key role during intrauterine infection.


A longitudinal analysis of data from the Swiss Household Panel shows that satisfaction with the division of household tasks decreases when children aged 0-17 are present in the household, subsequently increases, and then drops again after retirement. This W-shaped pattern over time varies across individuals, however, as the sense of satisfaction is a construct that is gendered and generational, individual and interactional. Although the effect is small, men's satisfaction is more influenced by the number of hours spent on housework than that of women, so despite large inequalities, women often report being satisfied with household organization. Women's satisfaction depends on a larger number of factors, notably increasing expectations of equality over the generations. It is correlated above all with their partner's practical and emotional involvement. Overall, men's and women's satisfaction with the division of household tasks depends primarily on their perception of a number of aspects of common life which go beyond the domestic sphere, such as their partner's feelings. Thus, to fully capture the sense of satisfaction, an analysis must include not only the type of household tasks concerned, as is often the case, but also the context within which they are divided and the individuals involved.


This paper explores how political actors, processes, debates and institutions influence the reduction and reproduction of chronic poverty in Uganda. Uganda provides a particularly appropriate case study for such work, as the country's recent success in poverty reduction has been significantly related to 'getting the politics right'. However, findings here suggest that politics in contemporary Uganda holds as many threats as opportunities for reducing long-term poverty. The policy processes, debates and interventions that might challenge chronic poverty are steadily moving from the margins of the poverty agenda towards the mainstream. For example, the current review of the Poverty Eradication Action Plan (Uganda's home-grown PRSP) has identified social protection - likely to be a key policy response to chronic poverty - as one of the key cross-cutting themes. However, arguments for targeting the poorest groups and regions currently lack political persuasiveness, as such programmes have tended to become highly politicised and subject to both national clientelism and local elite capture. There is a 'politics of inclusion' in Uganda that stretches to most groups of the chronically poor, although this has yet to be transformed into a 'politics of justice', in part because the institutional representatives of Uganda's chronically poor are currently marginal in terms of command over resources and policy influence. On a broader note, little effort has been made amongst development actors in Uganda to articulate the type of 'pro-poor' or redistributive growth that is likely to be required to alleviate chronic poverty. It might be argued that this reflects a 'global' politics of staying poor in Uganda, with the neo-liberal policy hegemony playing an important role in shaping the possibility of reducing chronic poverty. Many amongst the political elite perceive the rising inequality in Uganda as a potential threat to them, although only over the long-run. Many also see the poverty reduction agenda as externally imposed and profligate with resources, suggesting that if poverty reduction is to stay on the political agenda in Uganda for long enough to impact on chronic poverty, national ownership of the poverty agenda must be broadened and deepened beyond the current 'champions'. Ongoing political conflict in northern Uganda and the perennial threat of regional instability remains the greatest threat to both the chronically poor and the poverty reduction agenda. In addition, the debate over presidential succession and the potential move towards multi-partyism appears to have triggered an intensification of neo-patrimonial political practice, posing a significant threat to the poverty reduction agenda. However, the paper also finds that the policies and programmes likely to challenge chronic poverty can be usefully aligned with the most progressive aspects of political actors and policies in Uganda. These include certain civil society actors, participatory poverty assessments, the local government development programme and social sector ministries. Finally, it is proposed that a number of shifts are required within the ways in which politics is understood within poverty analysis. One example, is that we might need to reconceptualise the long term politics of commitment to poverty reduction in terms of a 'contract' rather than in terms of 'ownership'.


The Neutron Scattering Society of America (NSSA) established the Clifford G. Shull Prize in Neutron Science to recognize outstanding research in neutron science and leadership promoting the North American neutron scattering community. The prize is named in honor of Prof. Clifford G. Shull, who received the Nobel Prize in 1994 with Prof. Bertram Brockhouse for seminal developments in the field of neutron science. The establishment of the prize was announced at the inaugural American Conference on Neutron Scattering (ACNS) in 2002.


Building on Carter and Jennings' (2002a,b, 2004) seminal works on socially responsible purchasing and logistics, this multinational study investigates the extent to which socially responsible supplier selection (SRSS) is associated with customer firms' financial performance in three key world economic regions. We collect and utilize a unique dataset consisting of a total of 479 manufacturing, retail, and service provider firms operating in three distinct national cultures: China, the United Arab Emirates, and the United States of America. Based on an exploratory empirical analysis, we observe evidence that, overall, firms that consider social responsibility aspects during the supplier selection process enjoy financial performance advantages versus rivals. However, model comparisons across the studied countries reveal differential outcomes of SRSS by region. Our findings aid supply chain managers by linking SRSS to commonly expected outcomes within these important national settings.


Increased flooding, urban diffuse pollution and habitat fragmentation are predicted as the climate changes and urbanisation increases; all will affect human and wildlife well-being negatively. Sustainable drainage systems (SuDS) have the potential to mitigate these effects and also provide additional amenity and biodiversity benefits. However, the current SuDS approach is site-specific and technically focused, hence, failing to generate anticipated amenity and biodiversity benefits. Therefore, a new SuDS approach is required.

A critical evaluation of the SuDS approach, the Ecosystem Approach, ecosystem services and disservices enabled an innovative SuDS Communication and Planning Framework to be created. The framework highlights key amenity and biodiversity related ecosystem services and disservices produced by vegetated SuDS systems, coupled with drivers affecting the production of these services and disservices.

This framework was validated by examining 49 representative sites within Greater Manchester using two ecosystem services and disservices variables assessment methods (vegetation structure cover-abundance and cultural ecosystem services and disservices appraisals). Resultant scores for five ecosystem services were calculated, where habitat for species and recreation ecosystem services were found to be synergistically linked to each other in a positive correlation. The result also enabled recommendations to be made that future vegetated SuDS development would benefit from involving local communities.

Overall the research produced practical Ecosystem Approach methods for SuDS development decision making, and the SuDS Communication and Planning Framework provides an innovative, easy to use tool to implement Ecosystem Approach compliant solutions for key SuDS stakeholders (planners, developers, designers, researchers and policy makers). Finally, the SuDS Communication and Planning Framework can now be found in the second part of the UK National Ecosystem Approach, UK NEA follow-on, as part of a series of Ecosystem Approach toolkits incorporated into the decision making processes for managing the urban environment in a sustainable way.


In this study, the values of the wealth and productive services capital stocks in Finland between 1900 and 2009 are estimated. Several modifications to the prevailing conventions of measurement are suggested. First, the sudden death (one hoss shay) deterioration of the asset is the justifiable deterioration pattern in this context. Renovation investments that preserve the e±ciency of the asset must explicitly be attached to the fundamental equation determining the asset price but they must not any more be included as separate investments in the estimate. With these modifications the wealth capital stock of highways obtains the value of 43 billion euros in 2009, the "official" figure being only 15 billion euros. Secondly, the competitive market hypothesis in the case of infrastructure investments is questioned. Using a typical cost-benefit rule and parameter values applied in project appraisals to estimate the value of the expected benefits of a typical highway project, the wealth capital stock of highways obtains the value of 170 billion euros in 2009. Thirdly, new road investments have a positive external effect on previous investments in improving the performance of the whole network. Using a spatial accessibility index and its changes to estimate the intensity of the external effects, the wealth capital stock of highways reaches the value of 200 billion euros in 2009.


Argumentation in Actual Practice contains a collection of topical studies about argumentative discourse in context written by argumentation scholars from a diversity of academic backgrounds. Some contributions provide general perspectives, other contributions deal with specific issues, particular types of argumentative discourse or individual argumentative speech events. The contexts in which argumentation is examined vary from politics and the media to medical, juridical, educational, commercial or military contexts, a specific academic discipline, a special issue or pertain to all kinds of contextualised argumentative discourse. The issues discussed include the interpretation and analysis of argumentation, strategic manoeuvring, argument schemes, the stock issues, the fallacies, the principle of charity and the persuasiveness of argumentative discourse. A common feature is that they are all empirically-oriented and that virtually all of them are strongly concerned with an adequate understanding of contextualised argumentative discourse and the factors that may increase or decrease its reasonableness and effectiveness.


BACKGROUND
In clinical trials, HCV salvage treatment with Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of >95% in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort.

METHODS
We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE).

FINDINGS
Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n=46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n=82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n=18/18, GT1b n=2/4), 89% in GT3 (n=59/66) and 100% in GT6 (n=3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were four serious AEs including one death and three hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12.

CONCLUSION
This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most however serious AEs can occur in those with advanced liver disease.


Ten years ago Lowell, Massachusetts was a high-tech success story. After several decades of stagnation, the Lowell area had emerged as a thriving center for high-technology employment. The Lowell story was viewed as a "model for reindustrialization" for older cities throughout the world. In recent years Lowell has once again become the focus of international attention, this time as an example of a failed economic development strategy. Widespread layoffs and plant closings within its computer industry, particularly the collapse of Wang Laboratories, have dealt a crushing blow to the local economy. This article analyzes the boom and bust periods the Lowell economy experienced with high-technology employment, identifying what went wrong and what might have been done to mitigate the impacts of economic and industrial change.