. Safety operation of important civil structures such as bridges can be estimated by using fracture analysis. Since the analytical methods are not capable of solving many compli-cated engineering problems, numerical methods have been increasingly adopted. In this paper, a part of isotropic material which contains a crack is considered as a partial model and the proposed model quality is evaluated. EXtended IsoGeometric Analysis (XIGA) is a new developed numerical approach [1, 2] which benefits from advantages of its origins: eXtended Finite Element Method (XFEM) and IsoGeometric Analysis (IGA). It is capable of simulating crack propagation problems with no remeshing necessity and capturing singular field at the crack tip by using the crack tip enrichment functions. Also, exact representation of geometry is possi-ble using only few elements. XIGA has also been successfully applied for fracture analysis of cracked orthotropic bodies [3] and for simulation of curved cracks [4]. XIGA applies NURBS functions for both geometry description and solution field approximation. The drawback of NURBS functions is that local refinement cannot be defined regarding that it is based on tensor-product constructs unless multiple patches are used which has also some limitations. In this contribution, the XIGA is further developed to make the local refinement feasible by using T-spline basis functions. Adopting a recovery based error estimator in the proposed approach for evaluation of the model quality and performing


The breeding programmes of many crops use diallel analyses because of the genetic information they offer to breeders. Six morphological and agronomic traits of Snap bean (Phaseolus vulgaris L.) were studied to investigate their gene action, and to estimate the general combining abilities (GCA) and specific combining abilities (SCA) of parents and crosses. Three snap bean varieties Amy, Monel and Morlane and two dry bean varieties GLP 20 and GLPX 92 were used as parents in a complete diallel cross. The experiment was laid out in a randomized complete block design in a greenhouse. Significant (p < 0.01) additive and dominance effects were observed for days to flowering, plant height at flowering, number of pods per plant, pod weight per plant, pod length and pod diameter. Additive gene effects were predominant for all traits apart from pod weight. Significant (p < 0.01) maternal and non-maternal reciprocal effects were detected on plant height and days to flowering. Estimates of GCA, SCA and reciprocal effects suggested that Amy, Morlane and GLP 20 were generally the best combiners for incorporation into snap bean breeding programmes. This basic information is valuable for snap bean breeding programmes.


Multipass differential synthetic aperture radar (SAR) interferometry (DInSAR), with its capability to accurately monitor ground displacements, has dramatically pushed the applications of imaging radars in many fields, particularly in the area of environmental risk monitoring and security. Advanced DInSAR techniques operating at reduced resolution allow monitoring very wide areas whereas persistent scatterers interferometry (PSI) and more recently SAR tomography for very high resolution sensors, have shown to be powerful methods for providing 3-D point clouds representing buildings and infrastructures as well as in the monitoring of their possible slow temporal deformations. In this chapter, a detailed description of these techniques is provided, starting on the basic principles of the SAR interferometry and highlighting the relationship between interferometric and tomographic approaches.


Protein folding is crucial for most proteins to achieve their correct three-dimensional conformations and function properly. Defects in protein folding frequently caused by mutations lead to a range of protein misfolding diseases, including Alzheimer's disease, Parkinson's disease, cystic fibrosis, amyloidosis, Gaucher disease, etc. One approach to treat these devastating diseases would be to use pharmacological chaperones, which are small-molecules that bind to and stabilize misfolded proteins, thereby correcting their pathogenic misfolding and rescuing their functions. As such, pharmacological chaperone therapy holds great promise for the treatment of numerous protein misfolding diseases. In this review, we highlight recent strategies for identifying small-molecules that act as pharmacological chaperones and revert protein misfolding diseases, with a focus on reports within the last five years.


Proton conduction in nanopores is important for applications in fuel cells, chemical sensors and information processing devices inspired by nature. Here, we present a nanoporous material, a metal–organic framework (MOF) thin film, allowing photomodulation of the aqueous and alcoholic proton conduction of the guests by almost two orders of magnitude. The MOF film possesses spiropyran groups which undergo reversible UV-light induced isomerization to the merocyanine form, a highly polar, zwitterionic molecule, where the strong binding of the guests to the merocyanine isomer efficiently suppresses the proton conduction. Such materials with photomodulated ionic conduction contribute to the development of advanced, remote-controllable chemical sensors and to switchable devices interfacing with biological systems.


From her humble beginnings to her time in the spotlight as the first female Republican Vice Presidential candidate, Sarah Palin has led an extraordinary life. "Going Rogue" will recount her political experiences, her time as Mayor of Wasilla and as the first female governor of Alaska, as well as her rapid rise on the national stage during the 2008 campaign. Additionally, she'll share insights into the personal challenges she's faced including balancing her time as a working mother, recognising the war's impact with her son serving combat in Iraq, having a child with a disability and supporting her teenage daughter through an unplanned pregnancy. Palin has received much attention through the media, but never before has her complete story been told in her own words. The memoir will be both a personal and political chronicle of her life.


This research programme was a practice-led investigation into the interrelationship between composition, digital technology and intermedia performance. Within the first year
of this investigation Superfield [Mumbai] (2009) expanded on the intellectual ideas surrounding the notion of a Theatre of Sound and developed Sound Theatre: an experimental intermedia performance concept combining field recordings and live computer music; the mental 'seeing' evoked from sound and a theatre performance environment.
One specific element developed through this piece was the collaboration between computer-performer and human-performer, augmenting the composition-performance relationship and leading to the theoretical concepts of wholeness, dimensionality and embeddedness. These ideas were interrogated through The Cape Jeremy Affair (2010),
which investigated the meaning of the laptop as an autonomous performer alongside human musicians, and incorporated a 'phenomenology' of listening as it relates to music and performance embodiment.
Over a period of many months these concepts were developed and became the core
philosophical and theoretical argument of this programme. Each new insight was embedded into the compositional process with questions of phenomenology, performance
environment, and audience engagement becoming of primary importance. Towards the end of this investigation it became apparent that this programme might be heading into areas that would traditionally be described as "opera", but without containing any of the elements one might associate with the traditional 'recipe'. The final project X\ Sentimental Journey (2011) addressed this issue, expanded on all the previous concepts, enlarged the ensemble, engaged with networking computer systems and focussed on a Total compositional/ experiential paradigm.


Evidence is accumulating that drug resistance in Mycobacterium tuberculosis is by no means a homogeneous biological entity. This perception implies limitations of current procedures for in vitro drug susceptibility testing, based on unique but often poorly understood techniques in diagnostic mycobacteriology. The aim of this paper is to briefly review the molecular mechanisms of mycobacterial drug resistance, to critically reflect the principles involved in drug susceptibility testing of M. tuberculosis in the diagnostic laboratory and to discuss possible implications for therapy.


Depositors in authorised deposit-taking institutions (ADIs) in Australia benefit from a number of layers of protection designed to ensure that their funds are safe. At the broadest level, Australia has a strong system of prudential regulation and supervision which, together with sound management at individual institutions, has meant that problems in ADIs have been rare. In addition, depositors benefit from strong protections in the unlikely event that an ADI fails. They have a priority claim on the assets of a failed ADI ahead of other unsecured creditors, known as 'depositor preference'. Depositor protection arrangements were further strengthened in 2008 with the introduction of the Financial Claims Scheme (FCS), under which the Australian Government guarantees the timely repayment of deposits up to a predefined cap. This cap was temporarily set at $1 million per person per ADI when the FCS was introduced and is scheduled to be set on a permanent basis at $250 000 per person per ADI from 1 February 2012.


Evolving business needs call for customizing choreographed interactions. However, conventional choreography description languages provide only a partial view of the interaction. Business goals of each participant and organizational dependencies motivating the interaction are not captured in the specification of messaging. Absence of this critical business knowledge makes it hard to reason if a particular customization satisfies the goals of participants. Furthermore, there is no systematic means to assess the impact of change in one participant's process (local view) on the choreography (global view) as well as on other participants' processes. To this end, we argue for the benefits of representing choreography at the level of requirements motivating the interaction. We propose a framework that allows participants to collaborate on customizing choreographed interactions, while reconciling their competing business needs. To bridge the worlds of messaging and requirements, we employ an automated technique for deriving a choreography description from the customized requirements.


In Germany, the productivity of professional services, a sector dominated by micro and small firms, declined by 40 percent between 1995 and 2014. This productivity decline also holds true for professional services in other European countries. Using a German firm-level dataset of 700,000 observations between 2003 and 2017, we analyze this largely uncovered phenomenon among professional services, the 4th largest sector in the EU15 business economy, which provide important intermediate services for the rest of the economy. We show that changes in the value chain explain about half of the decline and the increase in part-time employment is a further minor part of the decline. In contrast to expectations, the entry of micro and small firms, despite their lower productivity levels, is not responsible for the decline. We also cannot confirm the conjecture that weakening competition allows unproductive firms to remain in the market.


The study of environmental impacts of seafood production as a result of ecolabelling and certification is a young yet rapidly growing discipline that lacks theoretical models. Pieces of the model have been suggested in the literature, and these pieces are formalized here realizing the current operating parameters of the global seafood industry. The derived pull-threshold model assumes that if producers exceed the threshold, there is no incentive to improve while if too far below, improvement is most likely beyond technical or financial means. Thus, a single certification is only a marginal solution to the larger picture. Those producers immediately below the certification threshold are within range or 'pull' of the threshold to improve as a result of certification. Results from a single threshold model applied to compliance data indicated that a maximum improvement of 12.5%, achieved when the pull was the greatest and the threshold was at the lower end of the impact distribution. When impacts were continuous (e.g. escapes in aquaculture), greater improvement was observed with thresholds targeting the producers at the higher end of the impact distribution. In all cases, improvement was maximized with a triple threshold model, indicating that single threshold scenario will not drive the greatest movement towards environmental improvement throughout the industry. Innovation is potentially more important in reducing environmental impacts of seafood production and needs to be accounted for as the seafood certification or ecolabelling continues to mature.


Selenocysteine incorporation at UGA codons requires cis‐acting mRNA secondary structures and several specialized trans‐acting factors. The latter include a selenocysteine‐specific tRNA, an elongation factor specific for this tRNA and a SECIS‐binding protein, SBP2, which recruits the elongation factor to the selenoprotein mRNA. Overexpression of selenoprotein mRNAs in transfected cells results in inefficient selenocysteine incorporation due to limitation of one or more of these factors. Using a transfection‐based competition assay employing overexpression of selenoprotein mRNAs to compete for selenoprotein synthesis, we investigated the ability of the trans‐acting factors to overcome competition and restore selenocysteine incorporation. We report that co‐expression of SBP2 overcomes the limitation produced by selenoprotein mRNA overexpression, whereas selenocysteyl‐tRNA and the selenocysteine‐specific elongation factor do not. Competition studies indicate that once bound to SECIS elements, SBP2 does not readily exchange between them. Finally, we show that SBP2 preferentially stimulates incorporation directed by the seleno protein P and phospholipid hydroperoxide glutathione peroxidase SECIS elements over those of other selenoproteins. The mechanistic implications of these findings for the hierarchy of selenoprotein synthesis and nonsense‐mediated decay are discussed.


Abstract Cover is an important trout habitat component resulting from the geomorphologic characteristics of a stream channel, the stream-bank interface with the riparian community, and the stream flow. By means of regression analysis, this study quantitatively describes the relative importance of three cover parameters (overhead bank cover, rubble-boulder-aquatic vegetation areas, and deepwater areas) and two cover models as indicators of trout standing stock in eight small streams in southeast Wyoming. Results indicated that overhead bank cover, provided primarily by riparian vegetation, is the cover parameter that explains the greatest amount of variation in trout population size.


Dying declarations have taken on increased importance since the Supreme Court indicated that even if testimonial, they may present a unique exception to its new confrontation jurisprudence. Starting with Crawford v. Washington in 2004, the Court has developed strict rules concerning the use of testimonial statements made by unavailable declarants. Generally, testimonial statements (those made with the expectation that they will be used to prosecute the accused) may be admitted only if they were previously subject to cross examination. The only exceptions appear to be dying declarations and forfeiture by wrongdoing if the accused intentionally rendered the declarant unavailable. This Article argues that the dying declaration merits examination for two important reasons. First, its status as an exception to the Court's new confrontation rules seriously undermines the Court's dramatic new interpretation of the Confrontation Clause and demonstrates the internal contradictions of the Court's originalist approach. Second, the dying declaration exception presents one of the few remaining ways in which testimonial statements by absent victims of domestic violence can be heard. Remarking on the prominence of women both in the Court's recent confrontation jurisprudence and in the dying declaration caselaw, this Article examines the role of women's voices and the means by which those voices are either excluded from or invited into the courtroom. The Article also explores the policy issues stemming from the admission of unconfronted statements by victims of femicide. It attempts to balance respect and justice for victims with fairness to the accused, and argues that dying declarations by victims of domestic violence possess unique qualities that justify a limited exception to the confrontation right.


Abstract. Two quantitative retrieval techniques were evaluated to estimate methane (CH4) enhancement in concentrated plumes using high spatial and moderate spectral resolution data from the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS). An iterative maximum a posteriori differential optical absorption spectroscopy (IMAP-DOAS) algorithm performed well for an ocean scene containing natural CH4 emissions from the Coal Oil Point (COP) seep field near Santa Barbara, California. IMAP-DOAS retrieval precision errors are expected to equal between 0.31 to 0.61 ppm CH4 over the lowest atmospheric layer (height up to 1.04 km), corresponding to about a 30 to 60 ppm error for a 10 m thick plume. However, IMAP-DOAS results for a terrestrial scene were adversely influenced by the underlying land cover. A hybrid approach using singular value decomposition (SVD) was particularly effective for terrestrial surfaces because it could better account for spectral variability in surface reflectance. Using this approach, a CH4 plume was observed extending 0.1 km downwind of two hydrocarbon storage tanks at the Inglewood Oil Field in Los Angeles, California (USA) with a maximum near surface enhancement of 8.45 ppm above background. At COP, the distinct plume had a maximum enhancement of 2.85 ppm CH4 above background, and extended more than 1 km downwind of known seep locations. A sensitivity analysis also indicates CH4 sensitivity should be more than doubled for the next generation AVIRIS sensor (AVIRISng) due to improved spectral resolution and sampling. AVIRIS-like sensors offer the potential to better constrain emissions on local and regional scales, including sources of increasing concern like industrial point source emissions and fugitive CH4 from the oil and gas industry.


In the modern financial architecture, financial services and products increasingly are provided outside of the traditional banking system — and thus without the need for bank intermediation between capital markets and the users of funds. Most corporate financing, for example, no longer is dependent on bank loans but raised through special-purpose entities, money-market mutual funds, securities lenders, hedge funds, and investment banks. This shift, referred to as "disintermediation" and described as creating a "shadow banking" system, is so radically transforming finance that regulatory scholars need to rethink their assumptions. Two of the fundamental market failures underlying shadow banking — information failure and agency failure — were also prevalent in the bank-intermediated financial system. By amplifying systemic risk, however, disintermediation greatly increases the importance of what scholars long have viewed as a third market-failure category: externalities. Viewing externalities as a distinct category of market failure is misleading, though: externalities are fundamentally consequences, not causes, of failures; and all market failures can result in externalities. Focusing on externalities also obscures who should be responsible for causing the externalities. This article argues that the third market-failure category should be reconceptualized as a "responsibility failure": a firm's ability to externalize a significant portion of the costs of taking a risky action. That not only would more precisely describe the market failure but also would help to illuminate that sometimes the government itself, not merely individual firms, should bear responsibility for causing externalities, and that exercising this responsibility may require the government to enact laws that require firms to internalize those costs.


Abstract I present a Stackelberg model of conflict, in which contestants have limited endowments to be put in two separate sectors, thus incorporating salient features of many conflicts. The model is applied to the case of conflict over natural resources. Consistent with amounting empirical evidence regarding a so-called "resource curse," I find that the relation between conflict intensity and resource rents is non-monotonous, and that the economy's income growth rate may be negatively affected by resource abundance.


BACKGROUND AND OBJECTIVES
We carried out a prospective, randomized trial to test whether a computer-based decision support system to initiate and maintain oral anticoagulant (OA) treatment can improve the laboratory quality of therapy.

DESIGN AND METHODS
Two separate sets of patients on oral anticoagulants, in five Italian anticoagulant clinics, were studied: 335 patients in the first three months of treatment (stabilization phase), 916 patients (775 patient-years) beyond the third month of treatment (maintenance phase). Patients were randomized to a computerized system, which included algorithms able to suggest OA dosing and to schedule appointments (computer-aided dosing) or to an arm in which OA were prescribed by the same teams of expert physicians without such algorithms (control group). Primary outcomes were: A) the percentage of patients reaching a stable state of anticoagulation during each of the first three months of treatment; B) the percentage of time individuals spent within the aimed therapeutic range (maintenance phase).

RESULTS
Patients in the computer-aided dosing group achieved a stable state significantly faster (p<0.01) and they spent more time within the therapeutic range during maintenance (p<0.001) than controls. The favorable effect of computer-aided dosing was mainly due to a reduction of the time spent below the therapeutic range and was associated with an increase of mean INR value, of anticoagulant drug dosage, and with a reduction of the number of appointments per patient (all changes significant: p<0.001).

INTERPRETATION AND CONCLUSIONS
The computer decision-aided support improves the laboratory quality of anticoagulant treatment, both during long-term maintenance and in the early, highly unstable phase of treatment, and it also significantly reduces the number of scheduled laboratory controls.


The granules commonly yielded by spray drying procedures exhibit a hard shell and an irregular, dimpled shape, which is often described as donut-like morphology. Sintered parts produced from such granules suffer from microstructural defects and reduced mechanical properties resulting from these disadvantageous granule properties.
Using the example of alumina, zirconia and zirconia-toughened alumina (ZTA) batches, this paper shows that the morphology of the granules can be tuned by adjusting slurry stability. High zeta potential is essential to optimally disperse the particles. But to achieve spherical and soft granules the electrostatic repulsion forces between the particles should be reduced before spray granulation. Electrostatic repulsion forces were changed with the addition of nitric acid. Measurements of zeta potential and viscosity, as well as sedimentation investigations with an optical centrifuge were used for precise slurry assessment as a major precondition for optimal and reproducible adjustment of slurries before spray drying. Sedimentation analysis using an optical centrifuge was performed to investigate different influences like that of additive composition, solids content or pH-value on the sedimentation behavior. Adequately flocculated slurries lead to homogeneous, soft granules that can be easily deformed and pressed. The fraction of donut-shaped particles and the rigidity of granules were reduced. Consequently, the sintered parts produced from these granulates show improvements regarding porosity, pore size distribution, sintered density and biaxial strength.


Thomas Nipperdey offers readers insights into the history and the culture of German nationalism, bringing to light much-needed information on the immediate prenational period of transition. A subject of passionate debates, the beginnings of German nationalism here receive a thorough-going exploration, from the dissolution of the Holy Roman Empire to Bismarck's division of the German-speaking world into three parts: an enlarged Prussian state north of the Main, an isolated Austria-Hungary in the south, and a group of Catholic states in between. This altering of power structures, Nipperdey maintains, was the crucial action on which the future of the German state hinged. He traces the failure of German liberalism amidst the rise of nationalism, turning it from a story of inevitable catastrophe toward a series of episodes filled with contingency and choice.The book opens with the seismic effect of Napoleon on the German "ancien-regime." Napoleon's modernizing hegemony is shown to have led to the gradual emergence of a civil society based on the liberal bourgeoisie. Nipperdey examines the fate of this society from the revolutions of 1848-49 through the rise of Bismarck. Into this story he weaves insights concerning family life, working conditions, agriculture, industrialization, and demography as well as religion, learning, and the arts.Originally published in 1996.The Princeton Legacy Library uses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These paperback editions preserve the original texts of these important books while presenting them in durable paperback editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905."


Background : Quality of life is an indicator of health. Quality of life is used to evaluate the physical and psychosocial effects of an illness suffered by a person, including a person's knowledge and perception of the illness. In order to achieve optimal quality of life, patients with hypertension were reported frequent use defense mechanisms to repress emotions or regulate emotions. Objective : The aim of this study was to investigate the effect of emotion regulation training to improve the quality of life among patients with hypertension. The hypothesis of this study stated that there was an influence of emotion regulation training to quality of life among patients with hypertension. Methods : The quality of life was measured by using quality of life scale based on aspect from WHOQOL-BREF (1998). An experimental method used was a pre and post-test control group design. Data were analysed by using Mann Whitney U. Results : The researchers found that there was no difference in the level of quality of life between the experimental group and the control group were not given training. However, the results of this study indicate that the quality of life scores in the experimental group increased during follow-up (p=0,002 (p<0,05). This suggest that quality of life among experimental group has increased compared to the control group, and consequently it accepted the hypothesis. Conclusion : Emotion regulation strategies can helped a person to cope the life stress that can be associated with psychological distress and quality of life.


The following problem is considered in this paper: Suppose k strings of unit length are to be distributed amongst x hats. If cuts in the strings are allowed, how should the string (parts) be distributed amongst the hats so that, if the shortest string is removed from each hat, the remaining (combined) string length in the hat with the most string is as small as possible? We solve this problem for a number of special cases (i.e. for certain values of x and k) and provide good bounds on the solution for the remaining cases.


Objective: To evaluate the clinical and cost effectiveness of two training strategies to promote the use of research evidence in speech and language therapy (SLT) management of poststroke dysphagia. Design: Pragmatic, cluster randomized trial. Setting: Seventeen SLT departments in north-west England. Participants: Two SLTs from each department received training and cascaded information across their department. Process of care was measured from the notes of 708 patients with acute poststroke dysphagia across eight departments allocated to training strategy A, and 762 patients across nine departments in strategy B. Interventions: Strategy A: training on the critical appraisal of published research papers and practice guidelines. Strategy B: strategy A plus training on management of change in clinical practice. Main outcome measures: Pre-and post-training adherence to practice guidelines in poststroke dysphagia management, based on a review of case notes. Incremental cost of increased adherence to clinical guidelines. Results: Departments' practice differed in adherence to guidelines. Departments changed following training (F=2.22, df 16, 1436, p=0.004). The effect of training strategy on clinical practice was not significant. Strategy B departments engaged in more activities relating to research use following training than strategy A. Total costs of training averaged £2001, t2892, $3886 (SD £502, t726, $975) for strategy A and £3366, t4866, $6537 (SD £2121, t3066, $4119) for strategy B. Conclusions: Training in research implementation in addition to critical appraisal and guideline introduction is associated with increased dissemination activities and awareness of research information, but not with changes in clinical practice within six months of training. The department in which SLTs work influences their use of research. The process of poststroke dysphagia management can be measured using a tool developed from practice guidelines.


MicroRNAs, central players of numerous cellular processes, regulate mRNA stability or translational efficiency. Although these molecular events are established, the mechanisms regulating microRNA function and expression remain largely unknown. The microRNA let-7i regulates Toll-like receptor 4 expression. Here, we identify a novel transcriptional mechanism induced by the protozoan parasite Cryptosporidium parvum and Gram(−) bacteria-derived lipopolysaccharide (LPS) mediating let-7i promoter silencing in human biliary epithelial cells (cholangiocytes). Using cultured cholangiocytes, we show that microbial stimulus decreased let-7i expression, and promoter activity. Analysis of the mechanism revealed that microbial infection promotes the formation of a NFκB p50-C/EBPβ silencer complex in the regulatory sequence. Chromatin immunoprecipitation assays (ChIP) demonstrated that the repressor complex binds to the let-7i promoter following microbial stimulus and promotes histone-H3 deacetylation. Our results provide a novel mechanism of transcriptional regulation of cholangiocyte let-7i expression following microbial insult, a process with potential implications for epithelial innate immune responses in general.


Five mixed-breed dogs underwent splenic sequestration scintigraphy following intravenous injection of 647.5 to 740 MBq (17.5–20 mCi) of 99mTechnetium labeled autologous red blood cells (RBCs) that had been chemically denatured using two μg of stannous chloride. Left lateral dynamic images were obtained for 20 minutes after injection. Regions of interest (ROI) were drawn around the splenic body and ventral extremity, ventral liver and caudal abdominal great vessels and time activity curves created. Count density information was obtained and uptake ratios were calculated for the spleen ROI/vessel ROI, liver ROI/vessel ROI and spleen ROI/liver ROI at 1, 2.5, 5, 10, 15 and 20 minutes after injection. Two additional studies using different RBC denaturing procedures were done in four of the five dogs. In the second study, the stannous chloride level was doubled to 4.0 μg, while in the third study, the RBCs were denatured by addition of 2.0 μg of stannous chloride and heating at 49°C for 15 minutes. Progressive splenic uptake of denatured RBCs was seen in all dogs during the first 15 to 20 minutes of each study, no matter which denaturing technique was utilized. Significant increases in the spleen ROI:/vessel ROI and spleen ROI:liver ROI ratios were obtained at 5, 10, 15 and 20 minutes when compared to the 1 minute values for each of the labeling techniques. A significant difference was not identified between the three ratios at 15 minutes between the three labeling techniques. There was a trend of increasing values for each ratio where 2.0 μg of stannous chloride technique being the lowest, 4.0 μg of stannous chloride having an intermediate value and the heated technique had the highest values. The heating technique resulted in higher liver activity and increased variability of the mean liver ROI/vessel ROI ratios at all times (1, 2.5, 5,10, and 15 minutes). Using a non-linear least squares regression analysis, a double exponential equation fit the spleen ROI/vessel ROI and spleen ROI/liver ROI ratios for all three labeling techniques. Imaging of the spleen using all three techniques was acceptable, and a persistent blood pool image would allow for vascular imaging and cardiac gated studies 30 minutes after injection of the denatured, labeled autologous red blood cells. Veterinary Radiology & Ultrasound, Vol. 36, No. I, 1995, pp 57–63.


This paper addresses the need for an objective and accessible system that assists academics in the quality review of their teaching and curricula. This is achieved via the Quality Review Instrument (QRI), which was trialled in a postgraduate research proposal course. The QRI provides a scaffold that can guide academics in the development and redevelopment of their courses, and facilitates reflection in and on the teaching process by teacher, peers and learners. At the same time, the QRI provides a robust and objective approach to evaluation of teaching for quality assurance. The comprehensive approach to review of teaching described in this paper facilitates a process that leads to the reshaping of academic and institutional practice in ways that can support and enhance the quality of teaching, learning and the student experience. The review template was constructed by the instructor and reviews of the course were completed by the instructor and two independent reviewers. Students completed the Student Evaluation of Teaching instrument (SET) and the Course Evaluation Instrument (CEI). Responses from the SET and the CEI were compared with the results of the QRI. The results demonstrated that the QRI has a high degree of reliability, even when used by reviewers with different backgrounds and different levels of experience. The instructor also rated the course in a very similar way to the two independent reviewers. The strong relationship between the student responses and the reviewers lends validity to the QRI.


Concepts and implications of altruism bias and pathological altruism The profound benefits of altruism in modern society are self-evident. However, the potential hurtful aspects of altruism have gone largely unrecognized in scientific inquiry. This is despite the fact that virtually all forms of altruism are associated with tradeoffs—some of enormous importance and sensitivity—and notwithstanding that examples of pathologies of altruism abound. Presented here are the mechanistic bases and potential ramifications of pathological altruism, that is, altruism in which attempts to promote the welfare of others instead result in unanticipated harm. A basic conceptual approach toward the quantification of altruism bias is presented. Guardian systems and their over arching importance in the evolution of cooperation are also discussed. Concepts of pathological altruism, altruism bias, and guardian systems may help open many new, potentially useful lines of inquiry and provide a framework to begin moving toward a more mature, scientifically informed understanding of altruism and cooperative behavior.  Key words: Cooperation, empathy, codependency, narcissism, philantrophy.


Why does the relationship between income and partisanship vary across U.S. regions? Some answers to this question have focused on economic context (in poorer environments, economics is more salient), whereas others have focused on racial context (in racially diverse areas, richer voters oppose the party favoring redistribution). Using 73 million geocoded registration records and 185,000 geocoded precinct returns, we examine income-based voting across local areas. We show that the political geography of income-based voting is inextricably tied to racial context, and only marginally explained by economic context. Within homogeneously nonblack localities, contextual income has minimal bearing on the income-party relationship. The correlation between income and partisanship is strong in heavily black areas of the Old South and other areas with a history of racialized poverty, but weaker elsewhere, including in urbanized areas of the South. The results demonstrate that the geography of income-based voting is inseparable from racial context.


Aims: To investigate the contribution of vascular risk factors (VRFs), vascular diseases (VDs) and white matter lesions (WMLs) to the progression of mild cognitive impairment (MCI) to dementia and Alzheimer's disease (AD). Methods: Two hundred forty-five consecutive subjects with MCI (age 74.09 ± 6.92 years) were followed for an average of 2.4 years. The Hachinski Ischemic Score and the Framingham Stroke Risk Profile were used to summarize VRFs and VDs. WMLs were graded using the Age-Related White Matter Changes Scale. Results: One hundred twenty-nine (52.6%) out of 245 subjects at risk converted to dementia, including 87 cases of AD. When hypertension occurred in MCI with deep WMLs, a 1.8-fold increased risk of dementia was observed (95% CI = 1.0–3.4). When deep WMLs occurred in MCI with high scores (≥4) on the Hachinski scale, a 3.5-fold (95% CI = 1.6–7.4) and 3.8-fold (95% CI = 1.2–11.5) risk of progression to dementia and AD was observed, respectively. Analogously, the joint effect of WMLs and high scores (≥14) on the Framingham scale nearly doubled the risk of dementia (hazard ratio = 1.9, 95% CI = 1.1–3.3). Conclusions: Accelerated progression of MCI to dementia and AD is to be expected when VRFs and VDs occur together with WMLs.


Phylogenetic reconstruction of the evolutionary relationships among 61 of the 70 species of the parrotfish genera Chlorurus and Scarus (Family Labridae) based on mitochondrial and nuclear gene sequences retrieved 15 well-supported clades with mid Pliocene/Pleistocene diversification. Twenty-two reciprocally monophyletic sister-species pairs were identified: 64% were allopatric, and the remainder were sympatric. Age of divergence was similar for allopatric and sympatric species pairs. Sympatric sister pairs displayed greater divergence in morphology, ecology, and sexually dimorphic colour patterns than did allopatric pairs, suggesting that both genetic drift in allopatric species pairs and ecologically adaptive divergence between members of sympatric pairs have played a role in diversification. Basal species typically have small geographical ranges and are restricted to geographically and ecologically peripheral reef habitats. We found little evidence that a single dominant process has driven diversification, nor did we detect a pattern of discrete, sequential stages of diversification in relation to habitat, ecology, and reproductive biology. The evolution of Chlorurus and Scarus has been complex, involving a number of speciation processes.


State-of-the-art federated learning methods can perform far worse than their centralized counterparts when clients have dissimilar data distributions. For neural networks, even when centralized SGD easily finds a solution that is simultaneously performant for all clients, current federated optimization methods fail to converge to a comparable solution. We show that this performance disparity can largely be attributed to optimization challenges presented by nonconvexity. Specifically, we find that the early layers of the network do learn useful features, but the final layers fail to make use of them. That is, federated optimization applied to this non-convex problem distorts the learning of the final layers. Leveraging this observation, we propose a Train-Convexify-Train (TCT) procedure to sidestep this issue: first, learn features using off-the-shelf methods (e.g., FedAvg); then, optimize a convexified problem obtained from the network's empirical neural tangent kernel approximation. Our technique yields accuracy improvements of up to +36% on FMNIST and +37% on CIFAR10 when clients have dissimilar data.


The 1.5 generation (Ilchom ose) refers to Koreans who immigrated to the United States as children. Unlike their first-generation parents and second-generation children born in the United States, 1.5ers have been socialized in both Korean and American cultures and express the cultural values and beliefs of each. In this first extended look at the 1.5 generation in Hawaii, Mary Yu Danico attempts to fill a void in the research by addressing the social process through which Korean children are transformed from immigrants into 1.5ers. Dozens of informal, in-depth interviews and case studies provide rich data on how family, community, and economic and political factors influence and shape Korean and Korean American identity in Hawaii. Danico examines the history of Koreans in Hawaii, their social characteristics, and current demographics. Her close consideration of socio-cultural influences firmly establishes the 1.5 generation in the mainstream discussion of identity formation and race relations.


Pharming NV and Esteve are developing Rhucin, a recombinant human C1 esterase inhibitor. Rhucin is currently undergoing phase III clinical trials in North America and is awaiting regulatory approval in Western Europe for the treatment of prophylactic and acute hereditary angioedema. Pharming is also investigating Rhucin for the potential treatment of cerebral ischemic injury.


The Black Sea consists of two oceanic basins separated by the mid-Black Sea ridge. The east-west-oriented west Black Sea basin opened as a back-arc rift in the Cretaceous by tearing a Hercynian continental sliver, the Istanbul zone, from the present-day Odessa shelf. The Istanbul zone, which was initially contiguous with the Moesian platform in the west, moved south during the Late Cretaceous-Paleocene with respect to the Odessa shelf along two transform faults: the dextral west Black Sea and the sinistral west Crimean faults. It collided in the early Eocene with a Cimmeride zone in the south, thereby ending the extension in the western Black Sea and deactivating both the west Black Sea and the west Crimean faults as strike-slip faults. The east Black Sea basin opened as a result of the counterclockwise rotation of an east Black Sea block around a rotation pole located north of the Crimea. This block was bounded by the west Crimean fault, the southern margin of the eastern Black Sea, and the southern frontal thrusts of the Greater Caucasus. The rotation of the east Black Sea block was contemporaneous with the rifting of the west Black Sea basin but lasted until the Miocene, resulting in continuous compression along the Greater Caucasus.


Abstract Objectives: We sought to define the prevalence of tuberculin skin test (TST) positivity in a group of newly hospitalized patients, to identify risk factors for positive tests, and to examine the impact of testing on infection control practices. Design: Unblinded cohort study over 5 days in July 1992. Setting: A 1,000-bed university-affiliated hospital. Patients: All patients admitted (excluding obstetric patients and newborns) were interviewed. Patients without a history of tuberculosis (TB) or a positive TST were offered a TST with Candida and tetanus controls. Results: Of 346 patients offered the test, 21 (6%) had a prior history of TB or a positive TST, and 36 (10%) declined to participate; 279 of the remaining 289 completed the study. Anergy was demonstrated in 94 (33.7%) of 279 patients. New positive TSTs were identified in 19 (10.3%) of 185 nonanergic patients. Of the 19 TST-positive patients, 6 (32%) had infiltrates on chest radiographs and were evaluated for active TB. One patient was treated empirically for active TB, and five received isoniazid prophylaxis. Risk factors for a new positive TST included age (odds ratio [OR], 1.56 per decade of life; P=.021), African American race (OR, 4.81; P=.008), alcohol abuse (OR, 5.53; P=.005), and peptic ulcer disease (OR, 4.53; P=.017). Risk factors for anergy included admission to a surgical service (OR, 2.1; P=.006), current use of steroids (OR, 2.65; P=.005), and human immunodeficiency virus (HIV) infection (OR, undefined; P=.034). Conclusions: Despite a high rate of anergy, routine tuberculin skin testing identified a substantial number of patients with TB infection who might otherwise have gone unrecognized.


The annotated draft typescript contains commentary and explanatory notes on "Declaration of the Rights of the Child" adopted by the Social Commission of the United Nations in April 1950, and various children related topics, such as children's clubs (Sunday Schools, boy scouts, girl guides, community centres, Youth Centres, Young Farmer's Clubs, Junior Eureka League), Youth Lead Activities (drawing from the experiences of the Junior Eureka League it is possible to learn from the past and build a children's organisation which is lead by young people based on the project method of work giving children a sense of membership in their own independent organisation), the adult protection (highlighting the roles of the labour movement, women's movement, parents auxiliaries and advisory committees), and the task of studying. The "Two Tasks in Defence of Children" chapter debates on the future of Australia and what it would be like when our own children are grown up, questioning the provision of basic human needs in future such as food, clothing, shelter and education. In the 122 pages that are provided, Ruth discusses children of the 10 – 16 age group and problems peculiar to them if they are to be understood well enough to be offered effective guidance for their development.


This paper considers a non-consequentialist argument raised by opponents of alternative litigation financing (sometimes called third-party litigation financing). The objection is that, apart from any effect that this method of funding might have on litigation rates, settlement incentives, or the lawyer-client relationship, something is intrinsically wrong with allowing a third party (not a litigant, the lawyer, or a liability insurer) to invest in a litigated claim. Somehow the participation of third-party funders transforms a non-market good into a commodity. This is a familiar form of argument, made familiar in legal scholarship by the work of Margaret Radin, and recently advanced by Michael Sandel in his critique of market modes of valuing various human goods. My argument here is that, first of all, opponents of third-party funding have not made the commodification objection with any real rigor and, second, if they were to make it rigorously, the most promising way to flesh it out would be using an expressive account of values. On an expressive approach, the argument would be that alternative litigation finance somehow manifests an inappropriate attitude toward the civil justice system. An expressivist might contend, for example, that in a tort lawsuit there is an intrinsically relational quality to a cause of action, which gives rise to agent-relative reasons which create obligations for wrongdoers to rectify harms. Allowing third parties to invest in these claims manifests the wrong type of attitude toward rights-based, relational values, by implying that the victim's rights are fungible with money. The trouble with that argument, however, is that the tort system includes practices such as insurance and settlement which depart from a strictly agent-relative understanding of the normative basis of tort liability. Other tort doctrines, such as the recoverability of damages for emotional distress and the enforceability of advance contractual waivers of liability, similarly exhibit the commodifying tendency to which opponents of alternative litigation finance object. Moreover, the anti-commodification is only an argument that works with a corrective justice approach; most opponents of alternative litigation finance are probably not committed corrective justice (or civil recourse) theorists. On a welfarist or consequentialist account of the tort system, third-party funding seems acceptable from the get-go, since all doctrines are evaluated in terms of their efficiency. While this paper does not endorse the anti-commodification critique of alternative litigation finance, it aims to show what a non-strategic anti-commodification argument would look like.


We have used three-dimensional particle dynamics simulations, coupled with volume-averaged gas phase hydrodynamics, to study vertically vibrated gas-fluidized beds of fine, cohesive powders. The volume-averaged interstitial gas flow is restricted to be one-dimensional (1D). This simplified model captures the spontaneous development of 1D traveling waves, which corresponds to bubble formation in real fluidized beds. We have used this model to probe the manner in which vibration and gas flow combine to influence the dynamics of cohesive particles. We have found that, as the gas flow rate increases, cyclic pressure pulsation produced by vibration becomes more and more significant than direct impact, and in a fully fluidized bed, this pulsation is virtually the only relevant mechanism. We demonstrate that vibration assists fluidization by creating large tensile stresses during transient periods, which helps break up the cohesive assembly into agglomerates.


ABSTRACT The biology of soft tissue sarcomas and locally aggressive connective tissue tumors evolves rapidly. At least seven molecular subgroups of connective tissue tumors may be distinguished: 1) sarcoma with specific translocations generating fusion transcription factors or growth factors; 2) sarcomas with mutated activated kinases (KIT in GIST); 3) sarcomas with deletion of tumor suppressor genes such as NF1 sarcomas; 4) Sarcomas with simple genetic alterations (MDM2/CDK4 gene amplification in WD/DD liposarcomas;); 5) Tumors with alterations of the intercellular adhesion pathways (aggressive fibromatosis with APC deletion or beta catenin mutations); 6) tumors with histone protein mutations such as giant cell tumor of the bone; 5) Finally, sarcomas with gross genetic alterations (e.g. leiomyosarcomas, UPS) represent a mixed bag for which the CINSARC expression profile distinguishes subgroups with very different prognosis This biological classification is therefore rapidly evolving and guides in real time the development of novel treatment. The identification of the "driver" mutation paved the way for the selection of efficient targeted therapies, following the paradigm of KIT and PDGFRA kinase mutations in GIST. Other examples are currently identified, in DFSP, a PDGF driven tumor and in PVNS, an M-CSF driven tumor. For this later group, 2 novel MCSFR inhibitors have been shown to have an outstanding clinical activity in phase I in ASC O 2014. This concept has therefore been fruitful, but now shows limitations, as observed with IGF1R Ab, or may be associated with a less dramatic activity in some pathways such as MDM2 inhibitors or CDK4 inhibitors. In addition, tumor heterogeneity, in the primary tumor, in the metastases, and following exposure to a TKI are now frequently observed, calling for innovative strategies to overcome this common phenomenon. During this presentation, we will review how the understanding of the driver molecular alterations of these tumors paved the way for the development of targeted treatment inhibiting driver mutations, and discuss the next steps to be explored. Disclosure: JY Blay: Research support and honoraria from Novartis, Roche, Bayer, Pharmamar and GSK.


We describe the velocity distribution function of a granular gas of electrically charged particles by means of a Sonine polynomial expansion and study the decay of its granular temperature. We find a dependence of the first non-trivial Sonine coefficient, a2, on time through the value of temperature. In particular, we find a sudden drop of a2 when temperature approaches a characteristic value, T*, describing the electrostatic interaction. For lower values of T, the velocity distribution function becomes Maxwellian. The theoretical calculations agree well with numerical direct simulation Monte Carlo to validate our theory.


Gang members from elsewhere congregated on lawns, on sidewalks, and in front of apartment complexes at all hours. They displayed a casual contempt for notions of law, order, and decency -- openly drinking, smoking dope, sniffing toluene, and even snorting cocaine laid out in neat lines on the hoods of residents' cars. San Jose prosecutors responded by obtaining and enforcing a broad injunction against the gangs and their members, based on the finding that the gangs' activities constituted a public nuisance. California prosecutors have sought such anti-gang public nuisance injunctions since 1987. Their constitutionality was in doubt for ten years until People ex rel. Gallo v. Acuna, in which the California Supreme Court upheld this injunction as a lawful and important means to hold the gang members accountable and restore community to Rocksprings.This Article critiques anti-gang public nuisance injunctions through the lens of restorative justice principles. The rhetorical justification for anti-gang injunctions is strikingly similar to the rhetoric of the restorative justice movement. Restorative justice rests on the tenets that any crime is injurious, and that the best response is one that heals the injuries caused to the victim, the community, and the offender. The anti-gang public nuisance injunctions share significant similarities with typical restorative justice programs: both are deviations from traditional criminal court (or even juvenile court) models; both privilege participation of affected communities; both re-conceive lawbreaking as injury; and both, at least in theory, are based on notions of redress of those injuries. Further, both provoke serious opposition from civil libertarians. Fundamentally, though, the anti-gang public nuisance injunctions undermine the promise of restorative justice as deeply as they weaken traditional rights-based protections, and the betrayal of the goals of restorative justice may be of even greater consequence.


Droplet evaporation-based cooling techniques, such as the spray cooling, give high heat transfer rates by utilizing latent energy and are usually preferred in thermal applications. However, with the significant rise in heat dissipation levels for high heat flux devices, these devices cannot be thermally managed due to the limited cooling capacity of existing thermal fluids. In this paper, we report the evaporation of the Cu–Al2O3 hybrid nanofluid (HNF) droplet on a copper surface as well as its own residue surface, developed from the evaporation of the first Cu–Al2O3 HNF droplet. As the main novelty, we identify the critical residue size and investigate the residue size effect, above and below the critical residue size, on evaporation rate of the succeeding Cu–Al2O3 HNF droplet resting over a residue surface. We also develop a new analytical model to estimate the Cu–Al2O3 HNF droplet evaporation rate and compare our results with other existing models. The results show that the Cu–Al2O3 HNF droplet gives 17% higher evaporation rate than a water droplet on a copper surface. Also, the evaporation rate of the Cu–Al2O3 HNF droplet on a residue surface sharply increases by 106% with increasing residue size up to the critical residue size. However, further increasing the residue size above its critical value has a negligible effect on the droplet evaporation rate. Moreover, the evaporation rate of the Cu–Al2O3 HNF droplet on its residue surface is enhanced up to 104% when compared to a copper surface.


Thermoelectrics have emerged as a strategy for solar‐to‐electricity conversion, as they can complement photovoltaic devices as IR harvesters or operate as stand‐alone systems often under strong light and heat concentration. Inspired by the recent success of inorganic‐based solar thermoelectric generators (STEGs), in this manuscript, the potential of benchmark organic thermoelectric materials for solar harvesting is evaluated. It is shown that the inherent properties of organic semiconductors allow the possibility of fabricating organic STEGs (SOTEGs) of extraordinary simplicity. The broadband light absorption exhibited by most organic thermoelectrics combined with their low thermal conductivities results in a significant temperature rise upon illumination as seen by IR thermography. Under 2 sun illumination, a temperature difference of 50 K establishes between the illuminated and the non‐illuminated sides of a poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) film, and ≈40 K for a carbon nanotube/cellulose composite. Moreover, when using light as a heat source, the Seebeck coefficient remains unaffected, while a small photoconductivity effect is observed in PEDOT:PSS and carbon nanotubes. Then, the effect of several geometrical factors on the power output of a solar organic thermoelectric generator is investigated, enabling us to propose simple SOTEG geometries that capitalize on the planar geometry typical of solution‐processable materials. Finally, a proof‐of‐concept SOTEG is demonstrated, generating 180 nW under 2 suns.


Evoking his early personal experiences, computer art pioneer Paul Brown wrote in the mid-1990s that to work with computers was akin to a 'kiss of death'. According to him, as a result of sheer prejudice, the majority of people in the art world did not acknowledge such artworks as interesting, valid or important. Although recurrent in the literature concerned with such art, Brown's claims must be confronted with the relative success of artistic practices interchangeably labelled as computer, new media, cybernetic, electronic or simply digital art. However, as attested by this proliferation of labels as well as by the development of numerous dedicated awards, degrees, galleries, museums, awards and publications, the success of such practices cannot be explained by artistic merit alone. Since many in the art world do not accept these artworks, as Brown and others suggest, how can we explain the works' success in securing and developing their own space over the course of fifty years? This thesis investigates the emergence, development and institutionalisation of the field termed here as 'art, science and technology' (AST) between 1965 and the mid-1970s in Europe and North America. Also recognised by the aforementioned labels (among others), AST is an umbrella term that arguably designates the artistic practices interested in the adoption, theorisation and dissemination of post-war technologies and, particularly, information technology. Yet, despite this shared interest, here I argue that it is the particular institutional arrangement of AST that best distinguishes it from other artistic practices. A direct consequence of its rejection, AST's emergence as a separate field is here explained via a revision of its initial social and cultural contexts. Arising from the technophile cultural climate of the long 1950s, and alongside the massive investments in technology made by Western governments in the same period, early AST developed not within traditional artistic spaces but within industries and universities. In the late 1960s, however, with the rise of economic, political and social uncertainties alongside escalating international conflicts, it became increasingly difficult to justify an art produced with the tools and support of the military– industrial complex. If on the one hand artists such as Brown understood these new artworks as central to art and its history, a normative development of a new technological era, on the other hand opponents located at the centre of contemporary art lambasted these new artworks for their supposedly scientific, commercial and aesthetic pretensions. Differently from previous attempts aimed at justifying the artistic worthiness of art produced with post-war technology, this thesis presents the history of such practices from the point of view of its own struggle – that is, its fight for survival. Ultimately, here I explain and describe how AST became detached from art while claiming its status. This is an effort not interested in the merits of these practices per se but, instead, concerned with AST's development as an autonomous and prosperous field.


In 155 cats, both with and without clinical signs of hyperthyroidism, total thyroxine (TT4) concentrations were compared to a sensitive, semi-quantitative thyroid palpation technique. On the basis of TT4 concentrations, 23 of the 155 cats were classified as hyperthyroid. The size of individual thyroid glands was scored between '0' (non-palpable) and a maximum of '6'. One or more enlarged thyroid glands (score >0) were palpated in 22 of the 23 hyperthyroid cats and in 78 of the 132 euthyroid cats. However, none of the 132 euthyroid cats had a thyroid lobe score of greater than '3' whereas 18 of the 23 hyperthyroid cats had a thyroid lobe score of '4' or greater, and in two of the five that had scores below '4' there was evidence of intrathoracic functional thyroid tissue on scintigraphy.


Duchenne Muscular Dystrophy (DMD) is a severe and progressive skeletal muscle wasting disease characterised by [Ca2+]-induced hyper-catabolism, and subsequently, a higher demand for energy production to modulate intracellular Ca2+ homeostasis, and protein degradation and synthesis pathways. The broad aim of this thesis was to elucidate potential defects in metabolism of the C57BL/10 mdx mouse model of DMD, and to determine the role of Ca2+ in any such defects. In particular, this thesis has examined the efficacy of the nutritional supplements creatine (Cr) and to a lesser extent, isolated whey protein (WP), in improving intracellular Ca2+ regulation, energy and protein balance and tissue architecture, thus alleviating a degree of the dystrophic pathology. 1. Whether the ATP-producing capacity of dystrophic mitochondria is defective remains largely contentious, and no study to date has directly quantified and contrasted ATP-production rate under the major macronutrient pathways feeding the mitochondria in either mdx hind limb or the more human DMD phenotype-like diaphragm. Chapter Three has demonstrated severely depressed mitochondrial ATP production rate (MAPR) of mdx diaphragm across all macronutrient substrate pathways, but to a lesser extent under protein metabolism, and in tibialis anterior (TA) across the sum of all macronutrient substrate pathways. Function of the electron transport chain complex II was not impaired in dystrophic diaphragm, but was notably depressed in TA. Citrate synthase activity was comparable to controls in both muscles, as was mitochondrial protein content. However, the susceptibility of dystrophic mitochondrial to mechanical damage during the mitochondria isolation process was significantly greater in mdx compared to controls, and in diaphragm compared to TA. It is postulated that mdx skeletal muscle has an intrinsic inability to utilise macronutrient substrates leading to substrate "back-up" and inhibition/down-regulation of key Krebs' cycle enzymes, thus creating an intracellular "starvation" scenario. That protein metabolism was less affected than the other macronutrient substrate pathways suggests that a portion of the muscle hyper-catabolism observed in DMD may occur due to autophagy to increase amino acid funnelling to mitochondria for ATP production. 2. Supplementation of the high-energy storage nutrient Cr is demonstrably beneficial in maintaining muscle function, energy status and cell survival rate in human DMD and dystrophic mdx skeletal muscle. Long-term chronic dose supplementation regimes, however, have been associated with down-regulation of creatine transporter (CreaT) expression thus making such regimes futile in maintaining consistently high intramuscular PCr stores. Chapter Four has demonstrated successful prevention of CreaT mRNA down-regulation by a chronic dose in utero and life-long Cr supplementation protocol, and subsequently persistently elevated [PCr] compared to unsupplemented mdx skeletal muscle. This was associated with a drastically reduced amount of muscle damage as depicted by Evan's blue dye (EBD) uptake into myofibres, and a lesser degree of damage to those fibres that were permeant to EBD. This unequivocally demonstrates that muscle wasting occurs secondary to metabolic compromise and failure to maintain ATP supply to intracellular mechanisms that promote cell survival. 3. Effective intracellular Ca2+ regulation by the sarcoplasmic reticulum (SR) is integral to muscle function and becomes of paramount importance to the maintenance of cell survival in conditions of increasing [Ca2+]i such as that evident in DMD. Chapter Five details an optimised method for the fluorometric quantitation of SR Ca2+ flux kinetics currently utilised by our laboratory. It was demonstrated that the SR Ca2+ ATPase (SERCA) preferentially utilises ATP produced by a linked creatine kinase (CK) system over both exogenously administered ATP and ATP produced by SR-linked glycolytic enzymes, and as such, SR Ca2+ uptake rate was considerably faster under these conditions. It was also demonstrated that high [ADP] proximal to the SR vesicles impairs the binding of Ca2+ to Fura-2 and that the presence of 25mM PCr and low [ADP] drastically reduces passive Ca2+ leak from the SR. Thus, this study provides sound rationale for the use of Cr supplementation to improve intracellular Ca2+ handling by the SR subsequent to increasing PCr stores and the buffering of rising [ADP] during metabolic compromise. 4. It has been suggested that the beneficial effects observed in human DMD and dystrophic mdx skeletal muscle following Cr supplementation result from an improved capacity for intracellular Ca2+ handling by the SR and, therefore, delayed degenerative progression. Chapter Six has demonstrated no direct modulatory effect for Cr supplementation on SERCA or RyR function such to increase/decrease SR Ca2+ uptake, leak or release rates, but postulates that the benefit imparted by Cr supplementation is in maintaining maximum uptake (and subsequently release) velocity secondary to buffering rising [ADP] and collapse of the ATP:ADP ratio proximal to the SR. This study has also investigated the effects of supplementation with WP and a Cr+WP combination. As with Cr supplementation, WP induced no direct modulation of SR Ca2+ flux kinetics. Both supplements were shown to modulate differential expression of specific intracellular protein pools, although not necessarily net protein accretion. It is speculated that modification of expressed intracellular protein pools permits the "switching" of dystrophic mdx skeletal muscle from a "functional" phenotype to a "cell survival" phenotype, and that this is inhibited in unsupplemented muscle by a lack of amino acid and energy resources. It was also apparent that Cr and WP supplementation exerted different effects on tissue architecture maintenance. Cr supplementation increased the proportional area of functional muscle tissue and decreased non-muscle "gap" areas thus suggesting a role in muscle hypertrophy, where as Cr+WP combined increased active/recent degeneration and regeneration and the proportion of centrally-nucleated previously damaged fibres compared to peripherally-nucleated undamaged fibres in functional muscle tissue, thus indicating a potentially damaging effect. Collectively, the studies comprising this thesis indicate that the progressive skeletal muscle wasting evident in DMD is closely related to dissipating energy stores, and that the primary disease pathology may, therefore, be an intrinsic metabolic defect caused by the DMD genotype that subsequently induces Ca2+ dys-regulation. Cr supplementation was shown to provide several benefits to dystrophic mdx skeletal muscle architecture, including reduced severity of degenerative cycles, maintenance of muscle tissue and reduced proportional area of non-muscle tissue secondary to increased intramuscular [PCr]. The findings of Chapter Five suggest that Cr supplementation modulates its effect by maintaining normal [PCr] and a high ATP:ADP and PCr:Cr proximal to the SR, such to maintain maximum Ca2+ uptake velocity and reduce passive Ca2+ leak. Both Cr and WP supplementation also seem to modulate intracellular protein synthesis such to increase the capacity for myofibre survival. Thus, these supplements could be of benefit in the adjunct treatment of DMD, and warrant further investigation as to their long-term and mechanistic efficacy.


A comprehensive overview of investment banking for professionals and students

 The investment banking industry has changed dramatically since the 2008 financial crisis. Three of the top five investment banks in the United States have disappeared, while Goldman Sachs and Morgan Stanley have converted to commercial banking charters. This Third Edition of The Business of Investment Banking explains the changes and discusses new opportunities for students and professionals seeking to advance their careers in this intensely competitive field.

 The recent financial regulation overhaul, including the Dodd-Frank legislation, is changing what investment banks do and how they do it, while the Volcker rule has shaken up trading desks everywhere.

 This new edition updates investment banking industry shifts in practices, trends, regulations, and statistics

 Includes new chapters on investment banking in BRIC countries, as Brazil, Russia, India, and China now account for a quarter of the global economy

 Explains the shift in the listing of securities away from New York to various financial centers around the world, and how major exchanges compete for the same business

 This new edition, reflecting the current state of the investment banking industry, arrives in time to better serve professionals wanting to advance their careers and students just beginning theirs.


Some bat species, including eastern red bats (Lasiurus borealis), roost for short periods beneath leaf litter on the forest floor during winter in the south-eastern USA, a region subjected to frequent fire. The variability in fuel consumption, the heterogeneous nature of burns, and the effects of litter and duff moisture on forest-floor temperatures during winter burning could influence potential survival for bats beneath the leaf litter if they are unable to escape on-coming flames. We measured temperatures below leaf litter in 64 south-slope plots during nine controlled burns in the Ouachita Mountains of Arkansas to determine the probability of survival. Maximum temperature recorded under leaf litter at each plot averaged 292°C (±20 s.e.) and ranged from 10 to 717°C. Only three (5%) of the plots experienced temperatures that were deemed survivable (<60°C sustained for 60 s) during burns on warmer winter days (air temperatures 15.0–26.1°C). Temperatures below the leaf litter measured just before the arrival of fire (average = 19.6°C) suggested that if bats were roosting in plots they would have been in shallow torpor, which would have enabled faster escape from approaching flames. Burning during the warmer periods of winter (e.g. ≥15°C) and during afternoons could potentially improve survival by bats roosting under leaf litter by reducing arousal and escape times.


SUMMARY We employ adjoint methods in a series of synthetic seismic tomography experiments to recover surface wave phase-speed models of southern California. Our approach involves computing the Frechet derivative for tomographic inversions via the interaction between a forward wavefield, propagating from the source to the receivers, and an 'adjoint' wavefield, propagating from the receivers back to the source. The forward wavefield is computed using a 2-D spectral- element method (SEM) and a phase-speed model for southern California. A 'target' phase- speed model is used to generate the 'data' at the receivers. We specify an objective or misfit function that defines a measure of misfit between data and synthetics. For a given receiver, the remaining differences between data and synthetics are time-reversed and used as the source of the adjoint wavefield. For each earthquake, the interaction between the regular and adjoint wavefields is used to construct finite-frequency sensitivity kernels, which we call event kernels. An event kernel may be thought of as a weighted sum of phase-specific (e.g. P) banana- doughnut kernels, with weights determined by the measurements. The overall sensitivity is simply the sum of event kernels, which defines the misfit kernel. The misfit kernel is multiplied by convenient orthonormal basis functions that are embedded in the SEM code, resulting in the gradient of the misfit function, that is, the Frechet derivative. A non-linear conjugate gradient algorithm is used to iteratively improve the model while reducing the misfit function. We illustrate the construction of the gradient and the minimization algorithm, and consider various tomographic experiments, including source inversions, structural inversions and joint source-structure inversions. Finally, we draw connections between classical Hessian-based tomography and gradient-based adjoint tomography.


Protein–protein interactions (PPIs) are at the heart of signal transduction and are central to the function of protein machine in biology. The highly specific protein–protein binding is quantitatively characterized by the binding free energy whose accurate calculation from first principle is a grand challenge in computational biology. Accurate prediction of critical residues along with their specific and quantitative contributions to protein–protein binding free energy is extremely helpful to reveal binding mechanisms and identify drug‐like molecules that alter PPIs. In this overview, we describe an interaction entropy (IE) approach combined with the MM/GBSA method for solvation to compute residue‐specific protein–protein binding free energy. In this approach, the entropic contribution to binding free energy of individual residue is explicitly computed by using the IE method from a single MD trajectory. Studies for an extensive set of realistic protein–protein interaction systems demonstrated that by including the entropic contribution, the agreement between the computed residue‐specific binding free energies and the corresponding experimental data is systematically improved. We also show application of the current approach to the important major histocompatibility complex (MHC)‐antigen binding to provide important information on hot spots with potential application for use in cancer vaccine. WIREs Comput Mol Sci 2018, 8:e1342. doi: 10.1002/wcms.1342


We demonstrate ultralong-range swept-source optical coherence tomography (OCT) imaging using vertical cavity surface emitting laser technology. The ability to adjust laser parameters and high-speed acquisition enables imaging ranges from a few centimeters up to meters using the same instrument. We discuss the challenges of long-range OCT imaging. In vivo human-eye imaging and optical component characterization are presented. The precision and accuracy of OCT-based measurements are assessed and are important for ocular biometry and reproducible intraocular distance measurement before cataract surgery. Additionally, meter-range measurement of fiber length and multicentimeter-range imaging are reported. 3D visualization supports a class of industrial imaging applications of OCT.


Purpose: We sought to investigate the clinical response to MET inhibition in patients diagnosed with structural MET alterations and to characterize their functional relevance in cellular models. Experimental Design: Patients were selected for treatment with crizotinib upon results of hybrid capture–based next-generation sequencing. To confirm the clinical observations, we analyzed cellular models that express these MET kinase alterations. Results: Three individual patients were identified to harbor alterations within the MET receptor. Two patients showed genomic rearrangements, leading to a gene fusion of KIF5B or STARD3NL and MET. One patient diagnosed with an EML4-ALK rearrangement developed a MET kinase domain duplication as a resistance mechanism to ceritinib. All 3 patients showed a partial response to crizotinib that effectively inhibits MET and ALK among other kinases. The results were further confirmed using orthogonal cellular models. Conclusions: Crizotinib leads to a clinical response in patients with MET rearrangements. Our functional analyses together with the clinical data suggest that these structural alterations may represent actionable targets in lung cancer patients. Clin Cancer Res; 24(6); 1337–43. ©2017 AACR.


Correspondence analysis (CA) is a popular method that can be used to analyse relationships between categorical variables. Like principal component analysis, CA solutions can be rotated both orthogonally and obliquely to simple structure without affecting the total amount of explained inertia. We describe a MATLAB package for computing CA. The package includes orthogonal and oblique rotation of axes. It is designed not only for advanced users of MATLAB but also for beginners. Analysis can be done using a user-friendly interface, or by using command lines. We illustrate the use of CAR with one example.


The paper offers an analysis of an urban agriculture case in Plovdiv, the second largest city in Bulgaria, where the municipality is clearing more than 2 hectares of allotments that have been tolerated on public land for more than 30 years in order to extend the neighbouring park, without involving the evicted allotment users in a discussion about the future of urban agriculture. At the same time, a number of non-governmental organizations are promoting urban agriculture practices as a social innovation that can alleviate pressing urban problems such as poverty and social exclusion. Using two theoretical viewpoints, the text presents this case as an example of the barriers that hinder a social practice that displays all the prerequisites to fully empower its members and be implemented as a meaningful social innovation. The first viewpoint is based on the writings of Moulaert and co-authors, and explores the factors that make social innovations capable of changing social relations in regard to governance, thus enabling satisfaction of the needs and increasing the level of participation of deprived groups in society by boosting the civic capability to access required resources (Moulaert et al, 2005). The second viewpoint gives grounds for analysing public space as a common good that exists in three interrelated but distinct forms: perceived, conceived and lived space (Lefebvre, 1991; 1996). Borrowing from Lefebvre's model, the paper analyses the social processes that characterise the development of urban agriculture practices as a manifestation of "the right to the city" in the sense of civic engagement in the creation of urban space and its physical use.


In order to understand the behavior of individual cells, single cell analyses have attracted attention since most cell-based assays provide data with values averaged across a large number of cells. Techniques for the manipulation and analysis of single cells are crucial for understanding the behavior of individual cells. In the present study, we have developed single cell culture arrays using magnetic force and a pin holder, which enables the allocation of the magnetically labeled cells on arrays, and have analyzed their dynamics. The pin holder was made from magnetic soft iron and contained more than 6000 pillars on its surface. The pin holder was placed on a magnet to concentrate the magnetic flux density above the pillars. NIH/3T3 fibroblasts that were labeled with magnetite cationic liposomes (MCLs) were seeded into a culture dish, and the dish was placed over the pin holder with the magnet. The magnetically labeled cells were guided on the surface where the pillars were positioned and allocated on the arrays with a high resolution. Single-cell patterning was achieved by adjusting the number of cells seeded, and the target cell was collected by a micromanipulator after removing the pin holder with the magnet. Furthermore, change in the morphology of magnetically patterned cells was analyzed by microscopic observation, and cell spreading on the array was observed with time duration. Magnetic force-based cell patterning on cell culture arrays would be a suitable technique for the analysis of cell behavior in studies of cell-cell variation and cell-cell interactions.


Conventional gravimetric (weight loss) calibration of jet nebulizers overestimates their aerosol output by up to 80% due to unaccounted evaporative loss. We examined two methods of measuring true aerosol output from jet nebulizers. A new adaptation of a widely available clinical assay for lithium (determined by flame photometry, LiCl method) was compared to an existing electrochemical method based on fluoride detection (NaF method). The agreement between the two methods and the repeatability of each method were examined. Ten Mefar jet nebulizers were studied using a Mefar MK3 inhalation dosimeter. There was no significant difference between the two methods (p=0.76) with mean aerosol output of the 10 nebulizers being 7.40 mg x s(-1) (SD 1.06; range 5.86-9.36 mg x s(-1)) for the NaF method and 7.27 mg x s(-1) (SD 0.82; range 5.52-8.26 mg x s(-1)) for the LiCl method. The LiCl method had a coefficient of repeatability of 13 mg x s(-1) compared with 3.7 mg x s(-1) for the NaF method. The LiCl method accurately measured true aerosol output and was considerably easier to use. It was also more repeatable, and hence more precise, than the NaF method. Because the LiCl method uses an assay that is routinely available from hospital biochemistry laboratories, it is easy to use and, thus, can readily be adopted by busy respiratory function departments.


Based on oxygen (O2), pH, calcium (Ca2+), and carbonate (CO32‐) sediment pore‐water concentration profiles, we compare the benthic dissolution of autochthonous calcite in oligotrophic Lake Lucerne and eutrophic Lake Sempach. Despite their difference in trophic state, the two lakes have similar benthic O2 regimes because L. Sempach is artificially oxygenated. This peculiarity enabled the study of the direct effect of trophic state on benthic calcite dissolution. Although areal benthic O2 fluxes did not differ, O2 penetrated deeper into the sediment of the oligotrophic L. Lucerne, where most organic matter (OM, 96%) was degraded aerobically, whereas in L. Sempach, aerobic and anaerobic decomposition contributed about equal amounts to the biogenic carbon dioxide production. Release rates of bicarbonate from L. Sempach sediments exceeded those of L. Lucerne nearly twofold. The HCO3− : Ca2+ ratio of benthic fluxes was 3.7 in L. Lucerne compared to 10.3 in L. Sempach, suggesting that in L. Sempach most of the released HCO3− did not originate from calcite dissolution. Furthermore, benthic calcite dissolution in L. Lucerne exceeded that in L. Sempach by two‐fold, despite lower pH values in the pore water of L. Sempach. Differences in benthic microbial decomposition of OM and redissolution of calcite crystals are explained by the longer residence time of OM and calcite in the oxic sediment layer of the oligotrophic lake and the larger weight‐specific surface area of its smaller autochthonous calcite crystals. We suggest that trophic state and O2 supply to the sediment are key parameters controlling the cycling of calcite and organic carbon in lakes.


Purpose: The incidence of hepatocellular carcinoma is increasing in the United States, and liver cancer is the second leading cause of cancer-related mortality worldwide. Nonalcoholic steatohepatitis (NASH) is becoming an important risk for hepatocellular carcinoma, and most patients with hepatocellular carcinoma have underlying liver cirrhosis and compromised liver function, which limit treatment options. Thus, novel therapeutic strategies to prevent or treat hepatocellular carcinoma in the context of NASH and cirrhosis are urgently needed. Experimental Design: Constitutive activation of STAT3 is frequently detected in hepatocellular carcinoma tumors. STAT3 signaling plays a pivotal role in hepatocellular carcinoma survival, growth, angiogenesis, and metastasis. We identified C188-9, a novel small-molecule STAT3 inhibitor using computer-aided rational drug design. In this study, we evaluated the therapeutic potential of C188-9 for hepatocellular carcinoma treatment and prevention. Results: C188-9 showed antitumor activity in vitro in three hepatocellular carcinoma cell lines. In mice with hepatocyte-specific deletion of Pten (HepPten− mice), C188-9 treatment blocked hepatocellular carcinoma tumor growth, reduced tumor development, and reduced liver steatosis, inflammation, and bile ductular reactions, resulting in improvement of the pathological lesions of NASH. Remarkably, C188-9 also greatly reduced liver injury in these mice as measured by serum aspartate aminotransferase and alanine transaminase levels. Analysis of gene expression showed that C188-9 treatment of HepPten− mice resulted in inhibition of signaling pathways downstream of STAT3, STAT1, TREM-1, and Toll-like receptors. In contrast, C188-9 treatment increased liver specification and differentiation gene pathways. Conclusions: Our results suggest that C188-9 should be evaluated further for the treatment and/or prevention of hepatocellular carcinoma. Clin Cancer Res; 23(18); 5537–46. ©2017 AACR.


This paper proposes a methodology to estimate the correlation model between a pair of images that are given under the form of linear measurements. We consider an image pair whose common objects are relatively displaced due to the positioning of vision sensors. In such scenarios the correlation model that relates the displacement between the objects is effectively represented by a disparity image. We consider a framework where each image is directly acquired and compressed by projecting onto a random basis of lower dimension. Given the linear measurements computed from the images we propose to estimate the underlying correlation model directly in the compressed domain without reconstructing the images that is usually a costly solution. We first show that the correlated images can be efficiently related using a linear operator. Using this linear relationship between the images we derive the relationship between the corresponding measurements in the compressed domain. The underlying correlation model is then built by solving a regularized energy minimization problem. Experimental results show that the proposed scheme estimates an accurate correlation model between the images. Also we show by experiments that the proposed scheme performs competitively with the scheme that estimates the correlation model from the reconstructed images.


The increase of human population every year results in increasing of water usage and demand. This phenomenon affects the overall water quality and change the flow of river ecosystems. Various residential and commercial building were built along Dondang river basin in Pulau Pinang. Irresponsible residents and factory manager treat the river as sites for illegal garbage dumping and waste disposal. As an effort to monitor river water quality in Malaysia, Alam Sekitar Malaysia (ASMA) collaborated with Department of Environment (DOE) Malaysia to measure water quality parameters every month. The data used for Dondang River was dated from January 1998 until December 2007 at three stations at different sites. Different variables in this model include Dissolve Oxygen (DO), Biological Oxygen Demand (BOD), Suspended Solid (SS), pH, ammonia (NH 3 ), temperature, nitrate (NO 3 ), total solid (TS) and phosphate (PO4).were used as inputs while the prediction is made for Chemical Oxygen Demand (COD). The number of hidden layer, processing elements, the value of learning rule and transfer were adjusted to achieve the minimum error and highest prediction accuracy. The prediction of COD were divided into training, cross validation and testing data. The best possible model estimation was choose from the model with higher generalization, less minimum square error and high r squared value. The model estimation then tested with Mean Sensitivity test to check the validity of the model and to determine the factors that affect the value of COD the most.. Sensitivity analysis showed that BOD is the most important variable that determine COD, followed by phosphate concentration, DO, susupended solids and temperature. The results are consistent with the effects of land use on the river water quality as Dondang River flows through mainly housing area and factories or industrial area.


To couple two or more subsystem solvers in time domain, co-simulation methods are used in many fields of application. In the framework of mechanical systems, there exist mainly two ways to couple different subsystems, namely coupling either by constitutive laws or by algebraic constraint equations.
In this work, the numerical stability and the convergence behavior of co-simulation methods is analyzed. For the stability analysis, a test model has to be defined. Following the stability definition for numerical time integration schemes, namely Dahlquist's stability theory, a linear test model is used. The co-simulation test model applied here is a two-mass oscillator, where the two masses are connected by a spring-damper element or by a rigid link. Discretizing the test model with a co-simulation method, recurrence equations can be derived, which describe the time discrete co-simulation solution.
Applying an applied-force coupling approach, the stability behavior of the linear two-mass oscillator is characterized by 7 independent parameters. In order to compare different co-simulation approaches, 2D stability plots are convenient. Therefore, 5 of the 7 parameters are fixed so that the spectral radius can be depicted as a function of the remaining 2 parameters. The results presented show that implicit coupling schemes exhibit a significantly better numerical stability behavior than explicit schemes. Furthermore, enhanced stability behavior can be achieved by extending the coupling conditions, i.e., by taking into account derivatives and integrals of the constitutive equations. Especially, a very good stability behavior may be obtained with the D-extended force/force-coupling approach in combination with quadratic approximation functions.
The analysis of the numerical stability of co-simulation methods with algebraic constraints is the second subject of this work. 5 independent parameters have to be introduced for the corresponding test model. The dimensionless real and imaginary part of the eigenvalue of subsystem 1 are used as axes in 2D stability plots; the other 3 parameters are held constant. Three classical methods for constraint stabilization, namely the Baumgarte stabilization technique, the weighted multiplier approach and the projection technique, are discussed for different approximation orders. Alternatively, co-simulation approaches on index-2 and on index-1 level are discussed, where the Lagrange multiplier is discretized between the macro-time points (extended multiplier approach). As a result, the coupling conditions and their time derivatives can simultaneously be fulfilled at the macro-time points. Different multibody models are used in order to demonstrate the application of the above mentioned co-simulation techniques.


The intermolecular cross-benzoin and acyloin condensation reactions are powerful approaches to α-hydroxy carbonyls in a single step. However, their potentiality suffers from the occurrence of side reactions including self-condensation and the formation of the undesired cross-acyloin. The broad range of azolium salt precatalysts available confers high tunability to NHC mediated benzoin condensation, assuring a good level of selectivity to the direct coupling between two non-equivalent aldehydes. Many efforts have also been devoted to the design of strategies that expand the range of suitable reaction partners beyond the traditional aldehydes and to the discovery of novel umpolung catalytic systems. The synthesis of both racemic and enantiomerically enriched acyloins is reviewed.


The Power of Plagues is now available on Wiley.comMembers, use the code ASM20 at check out to receive your 20% discount.
How pathogenic microorganisms have shaped human civilization
The Power of Plagues presents a rogues' gallery of epidemic-causing microorganisms placed in the context of world history. Author Irwin W. Sherman introduces the microbes that caused these epidemics and the people who sought (and still seek) to understand how diseases and epidemics are managed. What makes this book especially fascinating are the many threads that Sherman weaves together as he explains how plagues past and present have shaped the outcome of wars and altered the course of medicine, religion, education, feudalism, and science. Cholera gave birth to the field of epidemiology. The bubonic plague epidemic that began in 1346 led to the formation of universities in cities far from the major centers of learning (and hot spots of the Black Death) at that time. And the Anopheles mosquito and malaria aided General George Washington during the American Revolution. Sadly, when microbes have inflicted death and suffering, people have sometimes responded by invoking discrimination, scapegoating, and quarantine, often unfairly, against races or classes of people presumed to be the cause of the epidemic.
Pathogens are not the only stars of this book. Many scientists and physicians who toiled to understand, treat, and prevent these plagues are also featured. Sherman tells engaging tales of the development of vaccines, anesthesia, antiseptics, and antibiotics. This arsenal has dramatically reduced the suffering and death caused by infectious diseases, but these plague protectors are imperfect, due to their side effects or attenuation and because microbes almost invariably develop resistance to antimicrobial drugs.
The Power of Plagues provides a sobering reminder that plagues are not a thing of the past. Along with the persistence of tuberculosis, malaria, river blindness, and AIDS, emerging and remerging epidemics continue to confound global and national public health efforts. West Nile virus, Lyme disease, and Ebola and Zika viruses are just some of the newest rogues to plague humans.
The argument that civilization has been shaped to a significant degree by the power of plagues is compelling, and The Power of Plagues makes the case in an engaging and informative way that will be satisfying to scientists and non-scientists alike.
Paperback, 494 pages, full-color illustrations.