An expert opinion elicitation has been used to evaluate phenomena that could affect releases of radionuclides during accidents at sodium-cooled fast reactors. The intent was to identify research needed to develop a mechanistic model of radionuclide release for licensing and risk assessment purposes. Experts from the USA, France, the European Union, and Japan identified phenomena that could affect the release of radionuclides under hypothesized accident conditions. They qualitatively evaluated the importance of these phenomena and the need for additional experimental research. The experts identified seven phenomena that are of high importance and have a high need for additional experimental research: High temperature release of radionuclides from fuel during an energetic eventEnergetic interactions between molten reactor fuel and sodium coolant and associated transfer of radionuclides from the fuel to the coolantEntrainment of fuel and sodium bond material during the depressurization of a fuel rod with breached claddingRates of radionuclide leaching from fuel by liquid sodiumSurface enrichment of sodium pools by dissolved and suspended radionuclidesThermal decomposition of sodium iodide in the containment atmosphereReactions of iodine species in the containment to form volatile organic iodides. Other issues of high importance were identified that might merit further research as development of the mechanistic modelmore » of radionuclide release progressed.« less


Yazd, a desert city located in the center of Iran has very long and fantastic history of coordination with nature to cope with very harsh climate of the region. Two, three or four sided traditional courtyard houses considered as the best prototype of sustainable architecture, which few follow logically. This paper presents traditional concepts using a passive solar house designed and built by present author in 2001. The research evaluated the family reactions, positive and negative aspects and performance features of the house under the concept of "post occupancy evaluation". The results indicated that family likes and dislikes are about the negative feeling of the cool draft in the sitting area, good lighting and views, some acoustical problems and positive feeling of cool air from the cold sunken courtyard. In general, the positive reflections of the family were much more than negative aspects.


ABSTRACT Beta interferon (IFN-β) gene expression in response to virus infection relies on the dynamic assembly of a multiprotein enhanceosome complex that is initiated by the activation of two inducible transcription factors, interferon regulatory factor 3 (IRF3) and NF-κB. Virus or double-stranded RNA-induced activation of IFN-β gene expression is prevented by the addition of protein deacetylase inhibitors. The isolated IRF-responsive positive regulatory domain was found to require deacetylation for its activity, but IRF3 protein activation leading to its nuclear translocation and DNA binding was not impaired by deacetylase inhibition. In contrast, NF-κB activity was not affected by deacetylase inhibitors. RNA interference indicated that several deacetylase enzymes, including histone deacetylase 1 (HDAC1), HDAC8, and HDAC6, influence IFN-β gene expression with opposing effects. While HDAC1 and HDAC8 repress IFN-β expression, HDAC6 acts as a coactivator essential for enhancer activity. Virus replication is enhanced in HDAC6-depleted cells, demonstrating HDAC6 is an essential component of innate antiviral immunity.


The characteristics of the intra-cavity loss modulation laser diode (ICLM-LD) proposed in this paper were numerically and experimentally evaluated. A lower modulation sensitivity degradation rate (MSDR) of −0.30 dB/GHz and a wider 3 dB bandwidth of 49 GHz compared to those of direct modulation lasers (−0.49 dB/Hz, 16 GHz) were numerically confirmed. In addition, an MSDR of −0.29 dB/GHz and a 3 dB bandwidth wider than 30 GHz were experimentally confirmed using the fabricated ICLM-LD. The ICLM-LD will thus become a key part of ultrahigh-speed direct modulation lasers with external cavities whose modulation sensitivity is enhanced by the photon–photon resonance effect.


This paper presents a first-order scaling-friendly VCO-based closed-loop ΔΣ ADC. It uses the VCO as both quantizer and integrator, and thus, obviates the need for power-hungry scaling-unfriendly OTAs and precision comparators. It arranges two VCOs in a differential manner, which cancels out even-order distortions. Most importantly, it has an inherit mismatch shaping capability that automatically addresses the DAC mismatches. The prototype ΔΣ ADC in 130 nm CMOS occupies a small area of only 0.03 mm2 and achieves 66.5 dB SNDR over 2 MHz BW while sampling at 300 MHz and consuming 1.8 mW from a 1.2 V power supply. It can also operate with a low analog supply of 0.7 V and achieves 65.8 dB SNDR while consuming 1.1 mW.


We study a variant of the classical bootstrap percolation process on Erdős Rényi random graphs. The graphs we consider have inhibitory vertices obstructing the diffusion of activity and excitatory vertices facilitating it. We study both a synchronous and an asynchronous version of the process. Both begin with a small initial set of active vertices, and the activation spreads to all vertices for which the number of excitatory active neighbors exceeds the number of inhibitory active neighbors by a certain amount. We show that in the synchronous process, inhibitory vertices may cause unstable behavior: tiny changes in the size of the starting set can dramatically influence the size of the final active set. We further show that in the asynchronous model the process becomes stable and stops with an active set containing a nontrivial deterministic constant fraction of all vertices. Moreover, we show that percolation occurs significantly faster asynchronously than synchronously.


In this paper, analytical solutions of period-1 motions in a time-delayed Duffing oscillator with a periodic excitation are investigated through the Fourier series, and the stability and bifurcation of such periodic motions are discussed by eigenvalue analysis. The symmetric and asymmetric period-1 motions in such time-delayed Duffing oscillator are obtained analytically, and the frequency-amplitude characteristics of period-1 motions in such a time-delayed Duffing oscillator are investigated. Numerical illustrations of period-1 motions are given by numerical and analytical solutions.Copyright © 2014 by ASME


The simulation of random correlation matrices is an important procedure in different research areas. This study presents a method called Custom Matrix generator, which generates correlation matrices that always fulfill the appropriate mathematical conditions. In addition, we present an algorithm based on this method which can generate customized correlation matrices for different applications used in several studies. The method is efficient in terms of computational time and it minimizes errors in the process of generating customized correlation matrices.


The present investigation is on bioethanol and biohydrogen production from oxalate-rich rhubarb leaves which are an underutilized residue of rhubarb cultivation. Rhubarb leaves can be the feedstock for bioethanol and biohydrogen production using thermophilic, anaerobic bacteria. The fermentation of second-generation biomass to biofuels by Thermoanaerobacter has already been reported as well as their high ethanol and hydrogen yields although rhubarb biomass has not been examined for this purpose. Thermoanaerobacter thermohydrosulfuricus strain AK91 was characterized (temperature and pH optima, substrate utilization spectrum) which demonstrates that the strain can utilize most carbohydrates found in lignocellulosic biomass. Additionally, the influence of specific culture conditions, namely the partial pressure of hydrogen and initial glucose concentration, were investigated in batch culture and reveals that the strain is inhibited. Additionally, batch experiments containing common inhibitory compounds, namely carboxylic acids and aldehydes, some of which are present in high concentrations in rhubarb. Strain AK91 is not affected by alkanoic carboxylic acids and oxalate up to at least 100 mM although the strain was inhibited by 40 mM of malate. Interestingly, strain AK91 demonstrated the ability to reduce alkanoic carboxylic acids to their primary alcohols; more detailed studies with propionate as a model compound demonstrated that AK91's growth is not severally impacted by high propionate loadings although 1-propanol titers did not exceed 8.5 mM. Additionally, ethanol and hydrogen production from grass and rhubarb leaf hydrolysates was investigated in batch culture for which AK91 produced 7.0 and 6.3 mM g−1, respectively.


Internet-of-Things (IoT) and cyber-physical systems (CPSs) may consist of thousands of devices connected in a complex network topology. The diversity and complexity of these components present an enormous attack surface, allowing an adversary to exploit security vulnerabilities of different devices to execute a potent attack. Though significant efforts have been made to improve the security of individual devices in these systems, little attention has been paid to security at the aggregate level. In this article, we describe a comprehensive risk management system, called GRAVITAS, for IoT/CPS that can identify undiscovered attack vectors and optimize the placement of defenses within the system for optimal performance and cost. While existing risk management systems consider only known attacks, our model employs a machine learning approach to extrapolate undiscovered exploits, enabling us to identify attacks overlooked by manual penetration testing (pen-testing). The model is flexible enough to analyze practically any IoT/CPS and provide the system administrator with a concrete list of suggested defenses that can reduce system vulnerability at optimal cost. GRAVITAS can be employed by governments, companies, and system administrators to design secure IoT/CPS at scale, providing a quantitative measure of security and efficiency in a world where IoT/CPS devices will soon be ubiquitous.


Robert E. Duffy Robert E. Duffy is an Associate Professor of aeronautical engineering and astronautics at Rensselaer Polytechnic Institute. Dr. Duffy received his degrees form Rensselaer. He has worked as an aeronautical engineer at Wright-Patterson Air Force Base, as a research engineer at Grumman Aerospace Corporation, and as a consultant to numerous corporations. He is currently the technical director of Panaflight Corporation. His professional society affiliations include membership in the American Helicopter Society, the American Society of Mechanical Engineers, and the AIAA, in which he is an Associate Fellow. An author of over 45 articles and papers, Professor Duffy is currently investigating nonsteady flow effects on the aerodynamic characteristics of rotorcraft as a member of the ARO Rotorcraft Center of Excellence at Rensselaer.


Increasing evidence indicates that hypertension and hypertensive end organ damage are not only mediated by haemodynamic injury but that inflammation also plays an important role. The complement system protects the host from a hostile microbial environment and maintains tissue and cell integrity through the elimination of altered or dead cells. As an important effector arm of innate immunity, it plays also central roles in the regulation of adaptive immunity. Thus, complement activation may drive the pathology of hypertension through its effects on innate and adaptive immune responses, aside from direct effects on the vasculature. Recent experimental data strongly support a role for complement in all stages of arterial hypertension. The remarkably similar clinical and histopathological features of malignant nephrosclerosis and atypical haemolytic uraemic syndrome suggest also a role for complement in the development of malignant nephrosclerosis. Here, we review the role of complement in hypertension and hypertensive end organ damage.


The analysis of mechanobiology of arterial tissues remains an important topic of research for cardiovascular pathologies evaluation. In the current state of the art, the gold standard to characterize the tissue mechanical behavior is represented by experimental tests, requiring the harvesting of ex-vivo specimens. In recent years though, image-based techniques for the in vivo estimation of arterial tissue stiffness were presented. The aim of this study is to define a new approach to provide local distribution of arterial stiffness, estimated as the linearized Young's Modulus, based on the knowledge of in vivo patient-specific imaging data. In particular, the strain and stress are estimated with sectional contour length ratios and a Laplace hypothesis/inverse engineering approach, respectively, and then used to calculate the Young's Modulus. After describing the method, this was validated by using a set of Finite Element simulations as input. In particular, idealized cylinder and elbow shapes plus a single patient-specific geometry were simulated. Different stiffness distributions were tested for the simulated patient-specific case. After the validation from Finite Element data, the method was then applied to patient-specific ECG-gated Computed Tomography data by also introducing a mesh morphing approach to map the aortic surface along the cardiac phases. The validation process revealed satisfactory results. In the simulated patient-specific case, root mean square percentage errors below 10% for the homogeneous distribution and below 20% for proximal/distal distribution of stiffness. The method was then successfully used on the three ECG-gated patient-specific cases. The resulting distributions of stiffness exhibited significant heterogeneity, nevertheless the resulting Young's moduli were always contained within the 1–3 MPa range, which is in line with literature.


This article aims to present a methodological proposal for conceiving degree projects in the higher education system. These projects integrate regulatory framework aspects of Ecuador and conceptual elements that consider new paradigms of knowledge. The methodology used consisted of participatory action research that began with an exploratory research design and academic dialogue led by a team of researchers. The methodology allowed establishing the relationship between the elements that integrate career projects with the use of hermeneutics as a method and the analysis of content as a technique for reviewing legal and conceptual documents published by the Ecuadorian Higher Education Council (CES). The next phase consisted of a process of orientation and accompaniment to work teams; while in the final phase, the result was the generation of this methodological proposal and the presentation of the projects for redesigning the agricultural and communication careers at the Pontifical Catholic University of Ecuador, in Ibarra (PUCE-SI). The projects were approved and are currently offered, so that the methodology is considered validated satisfactorily. This work is very useful for the academic departments of higher education institutions because, based on legal and conceptual elements, it formulates pragmatic orientations in the identification of key aspects that allow conceiving and articulating the curriculum of career projects.


We present PrinType, a fingerprint recognition based typing technique for virtual reality. Different regions of fingers covered by friction ridges are assigned to different keys (i.e. letters, numbers, punctuation, or functions). Once the thumb-worn fingerprint sensor touches a finger, the contact region (and its key) is recognized by matching the current image with registered templates. Using only a small sensor, PrinType turns each segment of all fingers into a touchable key. We designed keyboard layouts corresponding to three interaction sub-spaces: whole finger keyboard, fingertip keyboard, and single-handed keyboard. A 12-person user study was conducted to evaluate the performance of different strategies. Our user evaluation showed that participants achieved an average of 29.56, 32.38, and 34.22 WPM with 0.79%, 0.20%, and 0.21% not corrected error rate in the three strategies. In addition, we provided a detailed analysis of various micro metrics to further understand user performance and technical characteristics. Overall, PrinType is favored by users for its usability, efficiency, and novelty.


Transgender identities are still considered a psychiatric pathology in many countries according to the prevailing biomedical model. However, in recent years, this pathologizing vision has begun to shift towards a perspective that focuses on the diversity of transgender peoples' experiences. However, some transgender people still face denial of services, discrimination, harassment, and even violence by healthcare professionals, causing them to avoid seeking ongoing or preventive healthcare. This article describes the health experiences of transgender people in Barcelona regarding their access and use of non-specialized health services. Semi-structured interviews were conducted using a descriptive phenomenological approach with sixteen transgender people between December 2018 and July 2019. The data were analyzed descriptively and thematically following the method proposed by Colaizzi with the help of the Atlas.ti8 software. Transgender people care experiences were divided into three categories: overcoming obstacles, training queries, and coping strategies. Participants identified negative experiences and difficulties with the health system due to healthcare providers' lack of competence. Discriminatory, authoritarian, and paternalist behaviors are still present and hinder the therapeutic relationship, care, and access to healthcare services. There is a fundamental need for the depathologization of transgender reality and training for healthcare professionals in the field of sexual diversity. Training in sexual and gender diversity must be included in the curricula of university courses in the health sciences.


N-Methyl-d-aspartate (NMDA) receptor overactivation has been proposed to induce excitotoxic neuronal death by enhancing membrane phospholipid degradation. In previous studies, we have shown that NMDA releases choline and reduces membrane phosphatidylcholine in vivo. We now observed that glutamate and NMDA induce choline release in primary neuronal cortical cell cultures. This effect is Ca2+-dependent and is blocked by MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate). In cortical neurons, the NMDA receptor-mediated choline release precedes excitotoxic cell death but not neuronal death induced by either osmotic lysis or serum deprivation. Glutamate, at concentrations that release arachidonic acid, does not release choline in cerebellar granule cells, unless these cells are rendered susceptible to excitotoxic death by energy deprivation. The NMDA-evoked release of choline is not mediated by phospholipases A2 or C. Moreover, NMDA does not activate phospholipase D in cortical cells. However, NMDA inhibits incorporation of [methyl-3H]choline into both membrane phosphatidylcholine and sphingomyelin. These results show that the increase in extracellular choline induced by NMDA receptor activation is directly related with excitotoxic cell death and indicate that choline release is an early event of the excitotoxic process produced by inhibition of phosphatidylcholine synthesis and not by activation of membrane phospholipid degradation.


. Telework is the application of information technology to enable workers to perform their jobs from home or other locations to avoid commuting through congested rush hour traffic. Successful telework solutions will provide the organization as well as the teleworker with the means to perform their job, potentially more efficiently than before, while achieving increased employee satisfaction, reducing facility costs for the employer, and reducing traffic congestion, fuel consumption, and green-house gasses. This paper describes the concept of telework and outlines a systems engineering approach to implementation of telework solutions that extend beyond casual ad-hoc instances.


Removing the barriers of space and time, whilst still enabling individuals to converse in groups, promises to transform our practices and understanding of social dialogue. Technologies have evolved sufficiently to make these aspirations a reality, and educational technologists and researchers alike are actively seeking to identify the implications of such changes for society. Both are interested in identifying the unique feature sets and characteristics of particular technologies to identify what added value they represent for the learning experience. Nowhere is this more apparent, at the present time, than in respect to Web 2.0 technologies (McLoughlin & Lee, 2007;Mejias, 2005). There is a need to explore further the processes of identifying and measuring the added value that might be represented by the technological opportunities or affordances of specific technologies. The intention of this chapter is to explore, through the examination of a specific Web 2.0 application (VoiceThread), the opportunities for evaluating systematically the execuTive summary


The relationship between the structures of reduced, protonated diiron compounds relevant to the diiron subsite of the Fe-hydrogenase H cluster, [2Fe]H, and the rate of electrocatalytic proton reduction is explored by a combination of experimental and computational approaches. Analysis of the X-ray absorption fine structure (XAFS) of the two-electron, two-proton product of [Fe(CO)3]2(μ-PPh2)2 (DP) shows distortions of the primary coordination environment of the Fe centre that result from the trans influence of the terminally bound hydrido ligand. The difference in Fe–C(O) bond lengths for the CO groups cis and trans to the hydrido ligand is similarly predicted by density functional theory, although there is relatively poor agreement between the magnitude of the difference obtained by XAFS and DFT methods. The calculated energies of the cis and trans stereoisomers of DP-H2 with both hydrido ligands normal to the FeP2 plane (axial:axial) are within 0.5 kcal mol–1 of each other and lower, by approximately 4.5 kcal mol–1, than those of the axial:equatorial isomer. Similar trends in the relative energies are found for the hydrido forms of [Fe(CO)3]2[μ-PhP(CH2)3PPh] (3P). The rates of dihydrogen elimination from 3P-H2 and analogues with ethanedithiolate and propanedithiolate bridging ligands (2S-H2 and 3S-H2) have been re-evaluated by using recent DFT calculations of equilibrium constants and reduction potentials. The rate constants 4–8, 2–7 and 1.5–4 s–1 for dihydrogen elimination from the two-electron, two-proton analogues of 2S, 3S and 3P, respectively, for reactions conducted with p-toluenesulfonic acid fall within a narrow range and are consistent with reactions following a similar path but inconsistent with the different transition states proposed for dihydrogen elimination from 2S-H2 and 3S-H2.


On the sixth centenary commemoration (2006) of Ibn Khaldun, the focus in this essay is on the forgotten concept of 'human nature' in the studies of those who have dealt with his 'new social science' (ilmu al-umrani al-bashari). Though the concept is essential for the study of Ibn Khaldun's interdisciplinary thought; it has hardly been studied by those who have focused their scholarly work on the author of the Muqaddimmah's thought heritage. This essay attempts to shed light on Ibn Khaldun's concept of human nature. Here, three different types of the latter are identified in Ibn Khaldun's vision of humans. These types of human nature do not only affect the behaviours of single members of human societies, but they do also influence the rise and fall of the entire human societies and civilisations.


Introduction: This study aimed to investigate the distribution of ethmoid roof variation and symmetry according to Keros classification. Materials and Methods: This cross-sectional study assessed the paranasal CT scans of 600 patients over 18 years of age with no history of surgery, trauma, or localized fracture in the ethmoid, nose, and anterior skull base. The lateral lamella of the cribriform plate (LLCP) sizes were measured and classified as Keros type I (1-3 mm), II (4-7mm), and III (8-16mm). Moreover, the symmetry was surveyed in accordance with the LLCP measurements on both sides of the ethmoid roof. These variations were analyzed regarding gender and age. Results: In total, 600 patients participated in this study out of whom 311 cases were male. According to the results, the mean age of the participants was 37.50±16.63 years. Furthermore, the mean values of the LLCP height for the right and left sides were 4.17±1.69 and 4.93±1.97 mm, respectively. Moreover, the asymmetry was observed in 38.3% of the cases, and they were classified as 36.7% Keros type I, 50.5% Keros type II, and 12.8% Keros type III. Conclusion: Keros type II and symmetry were the most common variations in this study. In addition, these variations were independent of age and gender.


The aim of this study was to evaluate the effect of product market competition on the management of discretionary accruals, the accruals-based management and real earnings management of listed companies on the Stock Exchange in Tehran. The sample consisted of 145 company during the period 1389 till 1393 the companies listed on stock selection and test hypotheses using panel data with the help of generalized least squares method, has been done. The results of the study hypothesis, suggests that product market competition has a positive impact on positive discretionary accruals (increase of profit), but the impact of competition on the negative discretionary accruals as well as the absolute value of discretionary accruals not confirmed. The results also show a positive impact on the overall accrual is competition. The effects of competition in the management of real profits, the results suggest that competition for discretionary spending unusually negative effect on cash flow unusual and abnormal production costs had a positive effect.


The emergence of the Internet has changed the way we teach and learn. This paper provides a general overview of the state of the quality of virtual education environments. First of all, some problems with the quality criteria applied in this field and the need to develop quality seals are presented. Likewise, the dimensions and subdimensions of an empirical instrument to improve and assess the quality of online education are examined. This tool has already been applied to several educational contexts; though not definitive, it aims to improve not only specific areas, but also the whole educational approach as a system.


The shelf seas account for only 9% of the surface area of the global ocean, yet are estimated to be responsible for 16% of global primary productivity and 47% of global annual carbon export. While the importance of these seas in the marine carbon cycle is well-recognised, the relationship between the physical environment and the magnitude and fate of biological production is still largely undetermined. Using a range of approaches, this project examined the relationship between physical processes and biological carbon flow over various time and space scales in a temperate shelf sea. Autonomous high-resolution sensor surveys in Liverpool Bay and the Irish Sea reveal that this region is net autotrophic on an annual scale with estimates of regional net community production rates based on oxygen mass balance ranging from 1.3 to 4.2 mol C m-2 y-1. The highest NCP rates were measured in a Region Of Freshwater Influence (Liverpool Bay). Ship-based sampling in the Celtic Sea illustrated the influence of water column structure on rates of primary and bacterial production and community structure. The highest rates of primary production were observed in the fully mixed water column (55.1 mmol C m-2 d-1). However, bacterial production rates were lowest at the mixed site (6.8 mmol C m-2 d-1). In contrast, primary production and bacterial production at the seasonally stratified sites and shelf break were comparable (34.8 mmol C m-2 d-1 and 37.2 mmol C m-2 d-1 respectively, and 12.9 and 12.9 mmol C m-2 d-1 respectively). The phytoplankton community was dominated by diatoms at the mixed site and dinoflagellates at the seasonally stratified sites, with both diatoms and dinoflagellates occurring at the shelf edge. Bacterial carbon demand at each site was estimated using published empirical relationships. However, at three out of the four sites examined, the estimated daily rate of total primary production was insufficient to meet the daily bacterial carbon demands, implying that either an external source of carbon was required or that the assumptions used during estimates of bacterial processing of carbon were incorrect. Finally, the definition of export production in shelf seas is examined in relation to the potential pathways of carbon flow on daily and seasonal timescales in shelf seas.


BA, Kagey-Sobotka A, Lichtenstein LM. Discontinuing venom immunotherapy: extended observations. J Allergy Clin Immunol 1998;101:298–305. 4. Light WC. Insect sting fatality 9 years after venom treatment. J Allergy Clin Immunol 2001;107:925. 5. Haeberli G, Bronnimann M, Hunziker T, Muller U. Elevated basal serum tryptase and hymenoptera venom allergy: relation to severity of sting reactions and to safety and efficacy of venom immunotherapy. Clin Exp Allergy 2003;33:1216–1220. 6. Golden DB. Fatal insect allergy after discontinuation of venom immunotherapy. J Allergy Clin Immunol 2001;107:925–926.


Policymakers are under intense pressure to respond effectively to the ongoing COVID-19 situation. Epidemiological models, which have been helpful in many previous infectious diseases' epidemics, have been inconsistent and often incorrect in predicting burden of COVID-19 outbreak. Modelers are struggling to identify and capture appropriate drivers of the current outbreak giving conflicting conclusions. COVID-19 is not only exerting unprecedented social pressure on the vulnerable population but also its patterns are getting impacted by existing and aggravating social problems. The present article stresses the role of this dual nature of the impact of COVID-19 and suggests modelers to incorporate challenges at the interface of COVID-19 preparedness and social epidemics such as homelessness and opioid use. There is an urgent need to encourage social distancing policies to protect people and prevent the spread of the virus, while ensuring that other social crises and vulnerable populations are not ignored.


Efficient verification of computation, also known as delegation of computation, is one of the most fundamental notions in computer science, and in particular it lies at the heart of the P vs. NP question. This article contains a high level overview of the evolution of proofs in computer science, and shows how this evolution is instrumental to solving the problem of delegating computation. We highlight a curious connection between the problem of delegating computation and the notion of no-signaling strategies from quantum physics.


CD4+CD25+ regulatory T cells (TRegs) are critical for the acquisition of peripheral allograft tolerance. However, it is unclear whether TRegs are capable of mediating alloantigen-specific suppressive effects and, hence, contributing to the specificity of the tolerant state. In the current report we have used the ABM TCR transgenic (Tg) system, a C57BL/6-derived strain in which CD4+ T cells directly recognize the allogeneic MHC-II molecule I-Abm12, to assess the capacity of TRegs to mediate allospecific effects. In these mice, 5–6% of Tg CD4+ T cells exhibit conventional markers of the TReg phenotype. ABM TRegs are more effective than wild-type polyclonal TRegs at suppressing effector immune responses directed against I-Abm12 alloantigen both in vitro and in vivo. In contrast, they are incapable of suppressing responses directed against third-party alloantigens unless these are expressed in the same allograft as I-Abm12. Taken together, our results indicate that in transplantation, TReg function is dependent on TCR stimulation, providing definitive evidence for their specificity in the regulation of alloimmune responses.


Polymer nanospheres were synthesized through polymerization of resorcinol/formaldehyde (RF) in the presence of a basic amino acid, l-lysine, as a catalyst. The diameters of the RF polymer nanospheres can be tuned in the range of 30−650 nm by adjusting the molar ratios of l-lysine/H2O and resorcinol/H2O in the precursor solutions. The pH of l-lysine solution was reduced from 9.3 to 7.0 just after it was mixed with the RF solution, indicating that l-lysine molecules in the solution were consumed by interacting with resorcinol. As a result, particle growth rate extremely reduces. Thus, the particle size of the RF polymer was not much dependent with synthesis time. Thus, the use of l-lysine facilitates precise control of the size of the RF polymer nanospheres compared to the synthesis using an ammonia solution as a catalyst. Carbonized particles showed the same size as the RF polymer nanospheres. The resulting carbon nanospheres had mesopores and macropores with a surface area of 330−400 m2/g.


In recent years, the digitalization and media convergence has increased, which has made the market for public service- medias more competitive. Perhaps this is why public service has chosen to communicate with recipients outside their own channels.The purpose of this quantitative study is to find out how students attitudes looks towards the fact that public service are performing marketing communication. To find out, we conducted a survey, as 256 students of Linnaeus University in Kalmar answered. Together with the study we have used different theoretical references in order to analyse the responses from the survey, and obtain our conclusions.By analysing the empirical material we came to the conclusion that the majority are in favour of public service performing communication outside its own channels. But we also noticed that the communication needs to be in a certain way for the students to be positive. It needs to be informative and ideally distributed through the Internet.


PURPOSE
To describe the prevalence of refractive error (RE) and its association with other environmental and health factors among population aged ≥50 years who lived in Gilan, Iran in 2014.

METHODS
In this population-based cross-sectional study, 3281 individuals aged ≥50 years living in Gilan for at least 6 months were enrolled. The prevalence of different types of REs including myopia (spherical equivalent (SE)≤-0.50D), high myopia (SE ≤ -6.00D), hyperopia (SE≥ + 0.50D), high hyperopia (SE≥ + 3.00D), astigmatism (cylinder < -0.50D) and high astigmatism (cylinder < -2.25D) were determined. Anisometropia was defined as the SE difference of ≥1.00D between the two eyes. Associated factors including age, body mass index (BMI) and education were also studied.

RESULTS
2587 eligible individuals (58% female subjects) with the mean age of 62.6 ± 8.8 years participated (87.6% response rate). The prevalence of myopia, hyperopia and astigmatism was 19.2%, 48.6% and 57.4%, respectively. 3.6% high hyperopia, 0.5% high myopia and 4.5% high astigmatism were identified. The positive simultaneous effects3 of older age (Odds Ratio (OR) = 3.14), nuclear (OR = 1.71) and posterior subcapsular (OR = 1.61) cataracts as well as the negative effects of higher levels of education (OR = 0.28) were obtained on myopia. Higher BMI was found as a risk factor for hyperopia (OR = 1.67), while older patients were less likely to be hyperopic (OR = 0.31).

CONCLUSION
Higher incidence of myopia and astigmatism was found in patients aged over 70 years. It was also found that patients at older ages who suffered with cataracts were at a higher risk of myopia, while elderly people with greater BMI were at a higher risk of hyperopia.


Abstract Although there is a common belief that more footballers are representing countries other than their native ones in recent World Cup editions, a historical overview on migrant footballers representing national teams is lacking. To fill this gap, a database consisting of 10,137 football players who participated in the World Cup (1930–2018) was created. To count the number of migrant footballers in national teams over time, we critically reflect on the term migrant and the commonly used foreign-born proxies in mainstream migration research. A foreign-born approach to migrants overlooks historical-geopolitical changes like the redrawing of international boundaries and colonial relationships, and tends to shy away from citizenship complexities, leading to an overestimation of the number of migrant footballers in a database. Therefore, we offer an alternative approach that through historical contextualization with an emphasis on citizenship, results in more accurate data on migrant footballers – contextual-nationality approach. By comparing outcomes, a foreign-born approach seems to indicate an increase in the volume of migrant footballers since the mid-1990s, while the contextual-nationality approach illustrates that the presence of migrant footballers is primarily a reflection of trends in international migration.


The Drosophila auditory system consists of four large basal segments: the arista, the funiculus, the pedicel, and the scape. When an acoustic stimulus is applied to the arista and the funiculus their mechanical vibrations are transmitted to chordotonal neurons in Johnston's organ where mechanoelectric transduction arises. We study the mechanotransduction mechanism in the Drosophila auditory system by using a laser Doppler vibrometer (LDV) and extracellular electrophysiology. We find that large and small peaks appear alternatively and that the antenna vibration is asymmetric depending on whether the pedicel and the scape are fixed. Interestingly, we find that this asymmetric vibration accompanies the alternating neural peak structure. Here, we propose a mathematical model to explain the alternating peak structure by using a model consisting of two opposing neurons that are modeled as strings. Generally, strings have tension only when they are elongated. This property allows the alternating neural peaks for asymmetric antenna motion.


Tumorous heterotopic (ectopic, aberrant) gastric mucosa in the small bowel, other than in the Meckel's diverticulum or other congenitally anomalous bowel, is exceedingly rare. Fourteen cases have been recorded in the literature (Table). Two recent experiences at the Mary Hitchcock Memorial Hospital with tumors of the small intestine due to heterotopic gastric mucosa are reported below, followed by a review of the literature on this subject. Report of Cases Case1.—A 25-year-old man had been healthy until three weeks prior to admission when he experienced recurring intermittent midabdominal crampy pain and two-hour postprandial vomiting. There was no hematemesis or rectal bleeding. Physical examination results were unremarkable, except for slight tenderness over the right periumbilical area without rebound or spasm. Radiographic examination of the upper gastrointestinal tract showed a slightly dilated proximal jejunum with an intussuscepting pedunculated polypoid tumor in this segment of bowel (Fig 1). At operation intussusception was not


Consumer perceptions of brand motives related to corporate environmental responsibility affect the decisions of both corporations and consumers. Yet prior literature has typically viewed these firm motives as dichotomous, either solely intrinsic or solely extrinsic. The authors argue for a novel approach to positioning sustainability motives, where the brand communicates both intrinsic and extrinsic benefits together, as a joint motive. With a joint motive, a brand can highlight how an effort can benefit both planet and business with a "doing well by doing good" approach. Across five experiments, including a field study on Facebook, this research investigates the positive impact of the joint motive and its ability to enhance the credibility of sustainable initiatives via heightened perceptions of trustworthiness and expertise. Results provide converging evidence for the benefits of presenting a joint motive for sustainability efforts with implications for policy and practice.


The Internet provides an immense source of data. Its ubiquity, general availability and ease of use make it potentially an ultimate tool to search for information. However, the availability of data does not directly imply the availability of information. Web search engines, sophisticated tools designed to retrieve information from the Internet, could be rather unsatisfactory when dealing with todays size, complexity and dynamic of the Web. A series of advanced techniques has been proposed to leverage search services in order to increase the user satisfaction. Collaborative search is an innovative search paradigm based on implicit collaboration and knowledge exchange between inquirers. In this paper, we focus on comparison of several query similarity measures for the use in collaborative search environment.


A fully-differential folded-cascode op amp design is presented which achieves both high dc gain and high unity-gain frequency. The high dc gain is attained using an active cascode circuit to increase the output resistance of the amplifier. In contrast to previous work, the gain-enhancement is implemented using only two fully-differential op amps instead of four single-ended amplifiers. Implementation of common mode feedback for these internal amplifiers is achieved with a single device made possible due to the local unity-gain feedback around the amplifiers. Simulation results indicate that the fully-differential technique results in superior performance over the conventional technique in terms of area, power, and settling behavior. >


New geochemical data including Sm/Nd isotopic data show evidence for an early Paleozoic arc/back-arc complex in the Nashoba terrane of southeastern New England. The Nashoba terrane lies between rocks of Ganderian affinity to the northwest and Avalonian affinity to the southeast. It consists of early Paleozoic mafic to felsic metavolcanic and metasedimentary rocks that were intruded by intermediate to felsic plutons and metamorphosed to upper amphibolite facies conditions in the mid-Paleozoic. Major and trace element geochemical data indicate that the early Paleozoic igneous rocks contain a mix of arc, MORB, and alkaline signatures, and that the terrane formed as a primitive volcanic arc/back-arc complex built on thinned continental crust. Amphibolites have +4 to +7.5εNd(500) values consistent with formation in a primitive volcanic arc with minimal crustal contamination. Intermediate and felsic gneisses have εNd(500) values between +1.2 and –0.75 indicating a mixture of juvenile arc magmas and an evolved (likely basement) source. Depleted mantle model ages of 1.2 to 1.6 Ga point to a Mesoproterozoic or older age for this source. Metasedimentary rocks yielded –6 to –8.3 εNd(500) values and 1.6 to 1.8 Ga model ages, indicating an isotopically evolved source (or sources) that included Paleoproterozoic or older material. The εNd(500) values and model ages of the intermediate and felsic and metasedimentary rocks indicate that the basement to the Nashoba terrane is Ganderian rather than Avalonian. The Nashoba terrane therefore represents a Ganderian arc/back-arc complex similar to the Cambrian Penobscot arc/back-arc seen in Maritime Canada and Newfoundland, and particularly in the Annidale and New River terranes of southern New Brunswick. This correlation has not previously been recognized in southeastern New England. The Ganderian affinity of the Nashoba terrane also extends Ganderia farther SE in New England than previously established and indicates that the Nashoba terrane did not originate as a separate oceanic arc/back-arc complex or microcontinent.


Neuromyelitis optica (NMO) is an inflammatory disorder of the CNS that preferentially affects the optic nerve and spinal cord, causing optic neuritis and transverse myelitis, the latter typically being associated with longitudinally extensive signal change on MRI. It is estimated to affect about 1–3 individuals per 100,000 in the general world population, but is overrepresented in nonwhite populations (particularly Asians and those of Afro-Caribbean descent) as a major proportion of CNS demyelinating disease.1–5 It follows a relapsing course in the majority of individuals, and most patients have early disability due to severe relapses; within 5 years of disease onset, over 50% of patients with relapsing NMO are blind in one eye or both eyes or require ambulatory support.6,7


The exhaustive nature of fossil fuels and environmental concerns associated with greenhouse gases are the major causes of the paradigm shift from conventional vehicles to electric vehicles (EVs). The electrification of the transportation sector and the increasing popularity of the EVs have driven scientists and researchers to delve into charging stations. Underdeveloped charging infrastructure, optimal placement of charging stations, and charge scheduling in the charging stations are the major concerns for the large‐scale deployment of EVs. Even few questions related to EVs, such as the vehicle price and driving range, can be partially solved with a well‐developed charging infrastructure. Existing old infrastructure may bring severe limitations in the realization of the optimal placement of charging stations as EVs have not existed when the road and grid infrastructure have been developed. For the past few years, the studies associated with the optimal placement and sizing of EV charging stations have drawn the consideration of the researchers. The researchers have used different approaches, objective functions, and applied different optimization algorithms while dealing with the problem of charging station placement. The complex and dynamic nature of the problem has led researchers to apply different optimization algorithms for the solution of the problem. In this particular review study, the research works bearing on the charging infrastructure planning for the EVs are considered. Thus, this review work will endow the research community with the latest developments and research findings in the paradigm of charging infrastructure planning for EVs.


Deceased SARS patients displayed severe acute lung injury (ALI) with exuberant inflammatory responses yet faster neutralizing IgG development. The mechanism underlying this discrepancy remains elusive. Here, we combine vaccination and passive immunization strategies to determine whether anti-spike (S) IgG modulates SARS-CoV-mediated lung injury in Chinese rhesus macaques. We found that macaques pre-vaccinated with MVA-S displayed more severe lung injury compared with MVA-vaccinated controls after SARS-CoV challenge. Moreover, passive immunization of purified anti-spike IgG but not control IgG resulted dose-dependently in enhanced lung infection and severer lung injury, associated with prolonged responses of pro-inflammatory alveolar MAC387+ and CD163+TGF-b− macrophages, IL-6 production and delayed wound-healing CD163+TGF-b+ macrophages response. Consistently, accumulated pro-inflammatory CD163+TGF-b− macrophages were found in lungs of deceased SARS patients. Our results demonstrated that anti-spike IgG exacerbates lung injury likely by enhancing infection and skewed alveolar monocyte-macrophage responses, which may have significant implications to CoV-mediated pathogenesis and immunotherapy.


In this paper we use the Kohonen neural network based Self Organizing Map (SOM) algorithm for Urdu Character Recognition. Kohenen NN have more efficient in terms of performance as compare to other approaches. Classification is used to recognize hand written Urdu character. The number of possible unknown character is reducing by pre-classification with respect to subset of the total character set. So the proposed algorithm is attempt to group similar character .Members of pre-classified group are further analyzed using a statistical classifier for final recognition. A recognition rate of around 79.9% was achieved for the first choice and more than 98.5% for the top three choices. The result of this paper shows that the proposed Kohonen SOM algorithm yields promising output and feasible with other existing techniques.


WHO, for the first time in its history, asked in 2003, all Member States to sign and enforce a Framework Convention on Tobacco Control (FCTC). Ten years later, it seems important to describe the achievements made in Belgium. The main legislative measures that are taken to control the major avoidable risk factor for health, are recalled. The present status of Belgium activity in this field is described, with an emphasis on the role of health professionals to help smokers quit. The difficult challenge of curing chronic tobacco dependence disease is underlined. Regarding the fight to render tobacco products less attractive, some breakthroughs are occurring in specific countries, and some are maybe coming soon in Europe.


This is a very nicely produced dictionary covering a wide range of mathematical concepts, most of which are illustrated with informative examples. The dictionary has clearly been written (and is written clearly) for readers with a range of mathematical abilities, and the author tries to ensure that the readability of each article matches the level of difficulty of the topic being described. So, for example, he spends three pages (yes, three pages) defining absolute value, and about the same amount of space discussing maximum and minimum problems involving calculus. For those readers who already have some mathematical background this approach may often become a little irritating (does explaining the multiplication of whole numbers really have to occupy two pages?). But on the whole the author has succeeded in writing a dictionary of mathematics which should be extremely helpful to all types of students (apart perhaps from mathematics specialists) particularly those taking say quantitative method courses in the social sciences and having a rather sketchy mathematical background. And even the odd ageing statistician may find the dictionary helpful to remind themselves that sin sin 1⁄4 1 2 cos ÿ ð Þ ÿ cos þ ð Þ 1⁄2 Š for example, although the number of statistical concepts included is small, and their definitions sometimes a little hard to take. But overall, highly recommended for students and others needing to recall how to calculate a percentage, or use a table of logarithms.


Purpose To evaluate the long-term outcome (up to 7 years) of presumed ocular tuberculosis (TB) when the therapeutic decision was based on WHO guidelines. Methods Twelve out of 654 new uveitic patients (1998-2004) presented with choroiditis and positive tuberculosis skin test (TST) (skin lesion diameter >15 mm). Therapy was administered according to WHO recommendations after ophthalmic and systemic investigation. The area size of ocular lesions at presentation and after therapy, measured on fluorescein and indocyanine green angiographies, was considered the primary outcome. Relapse of choroiditis was considered a secondary outcome. The T-SPOT TB test was performed when it became available. Results Visual acuity significantly improved after therapy (p=0.0357). The mean total surface of fluorescein lesions at entry was 44.8±20.9 (arbitrary units) and decreased to 32.5±16.9 after therapy (p=0.0165). The mean total surface of indocyanine green lesions at entry was 24.5±13.3 and decreased to 10.8±5.4 after therapy (p=0.0631). The T-SPOT TB revealed 2 false TST-positive results. The mean follow-up was 4.5±1.5 years. Two relapses out of 10 confirmed ocular TB was observed after complete lesion healing, 2.5 years and 4.5 years after therapy, respectively. Conclusions A decrease of ocular lesion mean size and a mean improvement of VA were observed after antituberculous therapy. Our long-term follow-up of chorioretinal lesions demonstrated relapse of ocular tuberculosis in 10% of patients with confirmed ocular TB, despite complete initial retinal scarring.


Land use/land cover change analysis is one of the most particular techniques to understand how land was used in the past, what types of changes are to be expected in the future, as well as the forces and processes behind the changes. Thus, the objective of this study was to investigate the land use land cover changes and its driving forces in Mago National Park, southern Ethiopia. Satellite image of Landsat5 TM (1988, 1998 and 2008) and Landsat8 OLI/TIRS (2018) years were employed. In addition, social survey was conducted to study the drivers of land use/land cover changes. QGIS 3.2 and SPSS software's were used for satellite image processing, accuracy assessment, map preparation and descriptively analyze the driving forces of LULCC respectively. Supervised classification with maximum likelihood algorithm was conducted for satellite image analysis and generation of information using Quantum GIS 3.2. In the first period (1988-1998), woodland, riverine forest, water body and bare land decreased by 6.76%, 37.98%, 22.37% and 70.14% respectively, while grass land, and degraded land increased by 16.11% and 85.67% respectively. In the second period, (1998 2008), woodland, riverine forest and degraded land were decreased by 5.44%, 4.61% and 80.74% respectively, while grass land, water body and bare land is increased by 14.74%, 3.76% and 52.58% respectively. From 2008-2018 riverine forest, grassland, water body and bare land decreased by 1.33%, 15.16% and 4.82% and 25.02% respectively, while woodland increased by 11.84%, and degraded land increased by 85.49% respectively. Riverine forest, water body, grass land and bare land showed decrement and that of woodland, degraded land indicated increment during study period. From 1988-2018, woodland, riverine forest, water body and bare land indicated decrement and the remaining grass land and bare land cover types indicated increment during study period. The result of social survey indicated that expansion of agriculture, human induced fire, overgrazing and hunting are proximate driving forces of the change in Mago National Park. Population pressure, poverty, decreased farmlands productivity, education, weak law enforcement and cultural factors are the major underlying causes of the observed changes. Therefore, proper land use planning, legal support, and strong law enforcement are the key recommendations to sustain natural resources of the study area.


Lung cancer is the leading cause of cancer death in both men and women. Although novel therapies are emerging, we are interested in boosting tumor-specific immune responses in infiltrating lymphocytes. In a flow cytometric analysis of the immune infiltrate in non-small cell lung cancer (NSCLC) tumors (n=25), we found that the total number of infiltrating B cells (TIL-Bs) in the tumor versus the matched tumor-adjacent tissue was increased compared to other immune subsets, specifically T cells. Most NSCLC TIL-Bs were activated (CD69+ and CD86+) and had a memory phenotype (CD27+). Proliferation, antigen presentation, and antibody production studies were done to assess the range of function in TIL-Bs. Positively isolated TIL-Bs that were stimulated for three days through the antigen receptor had varied proliferation when compared to B cells from the tumor adjacent tissue, which suggests a spectrum of function in TIL-Bs at the site of the tumor. For antigen presentation, TIL-Bs stimulated CD4 tumor infiltrating lymphocytes (CD4 TILs) to proliferate without the addition of tumor lysate compared to the negative and positive controls (T cells alone and T cells activated through the T cell receptor, respectively). This suggests that TIL-Bs can present endogenous tumor antigens to CD4 TILs; however, antigen presentation is not as robust with TIL-Bs from other patient tumors, which is another example of a spectrum in TIL-B function. Finally, we assayed total antibody production (IgG) by TIL-Bs to determine if this is a function at the site of the tumor. Tumor and tumor adjacent B cells produce antibody in comparison to B cells from the periphery of a normal donor; this function is uniform unlike proliferation and antigen presentation. We predict that TIL-Bs have a range of function in their response against tumors. Our overall hypothesis is that tumor immunity in NSCLC is influenced by the molecular signature of TIL-Bs, which directs proliferation, presentation of tumor antigens to T cells, and production of anti-tumor antibodies. We are determining if proliferation, antigen presentation, and antibody production are tumor antigen-specific, particularly for the lung cancer-testis antigen XAGE-1b. This antigen was the most highly expressed in our patient tumor cells when analyzed by real time PCR and has been shown to play a role in NSCLC. We are performing experiments with TIL-Bs to test XAGE-1b specific proliferation and antigen presentation. Further, we generated a XAGE-1b ELISA to test the specificity of the antibodies generated by the TIL-Bs. Three out of twelve patient sera were positive for XAGE-1b-specific antibodies indicating that the XAGE-1b ELISA is working for the detection of XAGE-1b antibodies. Further, we are isolating cells from tumor, tumor adjacent, and normal (cancer-free) lung tissue to analyze the molecular signature of TIL-Bs to identify a pathway upstream of B cell signaling that may be altered and influencing TIL-B function. Results from this study will advance the understanding of the function of TIL-Bs in solid tumors, and which functions can be targeted. Ultimately, this project will provide a platform for a therapeutic vaccine for lung cancer patients, and more importantly, will help us understand why some patients do not respond well to immunotherapy. Such results may lead to the development of a prognostic tool to screen patients that will respond to vaccine. Citation Format: Tullia C. Bruno, Daniel Munson, Brandon Moore, Katherine Waugh, Jeffrey Kern, Jill E. Slansky. The function of B cells in non-small cell lung cancer patients. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A11.


Dihydrolipoamide dehydrogenase (E3) belongs to the pyridine nucleotide-disulfide oxidoreductase family including glutathione reductase and thioredoxin reductase. It catalyzes the reoxidation of dihydrolipoyl moiety of the acyltransferase components of three alpha-keto acid dehydrogenase complexes and of the hydrogen-carrier protein of the glycine cleavage system. Isoleucine-51 of human E3, located near the active disulfide center Cys residues, is highly conserved in most E3s from several sources. To examine the importance of this highly conserved Ile-51 in human E3 function, it was substituted with Ala using site-directed mutagenesis. The mutant was expressed in Escherichia coli and highly purified using an affinity column. Its E3 activity was decreased about 100-fold, indicating that the conservation of the Ile-51 residue in human E3 was very important to the efficient catalytic function of the enzyme. Its altered spectroscopic properties implied that conformational changes could occur in the mutant.


Background: Percutaneous Coronary Intervention (PCI) is the preferred method of revascularization in Acute ST Elevation Myocardial Infarction (STEMI). Aim: Our aim was to study the clinical profile and outcomes of patients who underwent PCI for STEMI at tertiary cardiac centre of Bangladesh. Methods: It is a retrospective, single centre study, performed at Bangabandu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. All patients who underwent PCI for STEMI from November 2017 to July 2019 were enrolled in this study. All the data were collected from hospital registry and cath lab records. Results: The Study showed that out of 232 patients who presented with STEMI, 74.5% were male with average age of 57.39 years. The mean time of presentation after onset of symptom/s was 17.5 hours. About 66% patients presented in less than 12 hours of symptoms onset, 21% presented at 12-24 hours of symptoms onset and 13% patients presented late. Primary PCI was done in 87% of patients. Almost all patients (98.2%) underwent coronary artery stenting with drug eluting stents. Multivessel PCI during index procedure was done in 7 patients. TIMI III flow following PCI was achieved in 97% cases. Average LVEF at discharge was 44.73%. There were 8 deaths, all after Primary PCI. In-hospital mortality rates for patients presenting with and without cardiogenic shock were 38.46% and 1.59% respectively. The overall mortality rate was 3.98%. Conclusion: This study has reemphasized that PCI is effective in the management of STEMI cases in Bangladesh with improving mortality rates and decreasing complications. Minimizing the delayed presentation after the onset of symptoms should be one of the prime focuses for effective management of STEMI.


As Dr Runyon correctly points out, trials of albumin for the prevention of post-paracentesis circulatory dysfunction (PCD) have not demonstrated any survival advantage compared with large-volume paracentesis (LVP) without albumin. However, in our view, we consider that survival in this setting should not be the only factor that justifies the use of albumin after LVP. The development of renal failure and hyponatraemia in patients with cirrhosis either after paracentesis or from another cause are important complications of the disease. In fact, both parameters that define these complications (serum creatinine and serum sodium) are independent prognostic factors of survival in cirrhosis and are included in the MELD and UKELD score for organ allocation (1, 2). Additionally, in patients who are listed for liver transplantation, the presence of renal failure and hyponatraemia are indicators of poor post-transplantation outcome (3, 4). Thus, prevention of these complications is of critical importance in clinical hepatology. As mentioned in our article, a trial that can demonstrate a superior survival advantage of albumin needs a large number of patients. Furthermore, such a trial should include patients who undergo LVP4 6–8 L (as they have a higher risk of developing PCD) with an adequate sample size that could detect significant differences in survival during follow-up. This hypothetical study is very difficult to perform because, according to the previous subgroup analysis from our unit [reference (8) above], where we found survival differences for LVP4 8 L, the difference in survival obtained would require a very high number of patients in order to obtain significant results (5). Another point we would like to address is the argument against the use of LVP plus albumin in patients with large/tense ascites without prior use of diuretics. Dr Runyon implies that diuretic-sensitive patients should receive diuretics and that these patients are not good candidates for LVP with albumin infusion. This leaves LVP as a therapeutic method only for patients with refractory ascites. We disagree with this statement, as several studies indicate that the general population of patients with cirrhosis and large/tense ascites have less complications (i.e. renal failure, hyponatraemia and encephalopathy) when treated with LVP plus albumin as compared with those treated with diuretics (6–8). Thus, current recommendations state that large/tense ascites (regardless of patients being resistant or not to diuretics) should be treated with LVP plus albumin, followed by diuretics [references (4) and (5) above]. In conclusion, the currently available data indicate that PCD after LVP should be prevented because it is potentially harmful to patients with cirrhosis. We therefore recommend the use of albumin as the plasma expander of choice after LVP when 4 5 L of ascites is removed. Preventing PCD not only provides better care for patients but it also avoids the appearance of deleterious complications (dilutional hyponatraemia and hepatorenal syndrome) that are well known to be associated with a poor survival in patients with advanced cirrhosis. Therefore, the protective effect of albumin on the circulatory system favours its use in this setting.


A novel Gram-stain-positive, non-endospore-forming, coccoid actinobacterium, designated strain D3-40(T), was isolated from the soil of a natural cave and characterized by means of a polyphasic taxonomic analysis. 16S rRNA gene sequence analysis showed that strain D3-40(T) is a member of the suborder Micrococcineae and forms a distinct branch at the base of a Brevibacteriaceae cluster. Its closest relative is the type strain of Brevibacterium samyangense (95.7 % sequence similarity). The chemotaxonomic characteristics were as follows: the cell-wall peptidoglycan contained meso-diaminopimelic acid as the diagnostic diamino acid; the major menaquinone was MK-9(H2); the polar lipids consisted of phosphatidylglycerol, phosphatidylinositol, an unknown glycolipid and an unknown phospholipid; the major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0, iso-C15 : 0, C16 : 0 and cyclohexyl-C17 : 0; mycolic acids were absent. The G+C content of the DNA was 64.3 mol%. On the basis of morphological, chemotaxonomic and phylogenetic data, it is suggested that the organism represents a novel species of a new genus within the family Brevibacteriaceae, for which the name Spelaeicoccus albus gen. nov., sp. nov. is proposed. The type strain of the type species is D3-40(T) ( = KCTC 29141(T) = DSM 26341(T)).


Determination of organophosphorus fire retardants and plasticizers at trace levels in wastewater is described. In this work, microwave assisted extraction (MAE) and solid-phase microextraction (SPME) are used for sample preparation to extract and preconcentrate the analytes, followed by analysis by gas chromatography coupled to inductively coupled plasma mass spectrometry (GC-ICP-MS) for phosphorus-specific detection. Gas chromatography coupled to time of flight mass spectrometry (GC-TOF-MS) was used to confirm the organphosphorus fire retardants in wastewater. The detection limits of organophosphorus fire retardants (OPFRs) were 29 ng L(-1) for tri-n-butyl phosphate (TnBP), 45 ng for L(-1) for tris(2-butoxyethyl)phosphate (TBEP), and 50 ng L(-1) for tris(2-ethylhexyl)phosphate (TEHP). Optimized extraction conditions were performed at 65 degrees C for 30 min and with 10% NaCl. Application of MAE during the sample preparation prior to the SPME allowed the detection of tris(2-ethylhexyl) phosphate, which has been difficult to determine in previous work. Application of the method to wastewater samples resulted in detecting 3.1 microg L(-1) P from TnBP, 5.0 microg L(-1) P from TBEP, and 4.0 microg L(-1) P from TEHP. The presence of these compounds were also confirmed by SPME-GC-TOF-MS.


In this study, the properties of ring, rotor, and vortex spun yarns produced in different counts from cotton, viscose rayon, and 50/50 cotton-modal blended fibers were investigated. Yarn samples were converted into knitted fabrics in a single jersey circular knitting machine and dyed with reactive dyestuff to determine the physical performances of the yarns in knitted form. The results revealed that vortex spun yarns have lower hairiness and better pilling resistance over ring and open-end rotor spun yarns. Furthermore, viscose rayon yielded more satisfactory results in the vortex spinning system in terms of yarn strength, particularly in coarser yarn counts and hairiness.


Introduction: Leishmaniasis is a parasitic disease which caused by a protozoan belong to the genus, Leishmania. IL-2 is an important cytokine that progresses lymphocytes from G1 to S phase, leading to T cells growth and proliferation. IL-2 is produced by activated CD4+ T cells and stimulates T and B lymphocytes, monocytes and natural killer cells. The present study was designed to determine and define the leishmania major-induced suppression of IL-2Rα expression in the peripheral human T-lymphocytes in vitro condition. Materials & Methods: Leishmania major standard strain (MRHO/IR/75/EK) was cultured in the NNN medium and proliferated in RPMI medium. Human peripheral T lymphocytes were also cultured in RPMI medium. Phytohemaglutinin-stimulated lymphocytes, in the present and/or absent of leishmania major promastigotes, were sampled at the incubation times, 12, 24, 36, 48h, stained with FITC-labelled anti-CD25 (IL-2Rα chain MAb) and PE-labelled antiCD4 (CD4 MAb) and then, analyzed by flowcytometry. Data were analyzed by using the WIN MDI software and statistical tests. Findings: Results of this study showed that leishmania major suppressed the expression of IL-2R in the activated T cells and inhibited the proliferation of lymphocytes. We found the expression of IL-2R by human peripheral T Lymphocytes. These T cells that co-cultured with leishmania major and stimulated with Phytohemagglutinin, were significantly suppressed 6h after culture initiation. However, the suppressed effect was seen to be moderate. The magnitude of this effect further increased when greater numbers of promastigotes were added. Discussion & Conclusion: Inhibition of IL2R expression by the leishmania parasite may play a role in the suppressive effects associated with leishmaniasis disease. Molecular and biochemical characterization of the leishmania immuno suppressive factors can be useful for vaccine development and also for drug related studies.


In this study, Michael Hundley explores the diverse deities of ancient Near Eastern and biblical literature, from deified doors and diseases to the masters of the universe. Using data from Mesopotamia, Hittite Anatolia, Egypt, the Levant, and non-priestly Genesis and Exodus, Hundley explains their context-specific approach to deity, which produces complex and seemingly contradictory portraits. He suggests that ancient deities gained prominence primarily by co-opting the attributes of other deities, rather than by denying their existence or inventing new powers. He demonstrates that the primary difference between biblical and ancient Near Eastern presentations lies in their rhetorical goals, not their conceptions of gods. While others promote divine supremacy, Genesis and Exodus promote exclusive worship. Hundley argues that this monolatry redefined the biblical divine sphere and paved the way for the later development of monotheism and monotheistic explanations of evil.


AIMS
The aim is to make a systematic review of the literature to assess the effect of lipid-lowering drugs on venous thromboembolism (VTE) occurrence.

METHODS AND RESULTS
MEDLINE and EMBASE databases were searched to identify studies that evaluated the effect of lipid-lowering drugs, in particular statins and fibrates, on VTE risk until April 2009. A scoring system was used to divide studies into two quality categories. Odds ratios (ORs) and 95% confidence intervals (CIs) were then calculated and pooled using a fixed and a random-effects model. Statistical heterogeneity was evaluated through the use of I(2) statistics. Three randomized controlled trials (RCTs), three cohort, and eight case-control studies were included in our systematic review, for a total of 863 805 patients. Statins use significantly reduced VTE risk [OR, 0.81; 95% CI, 0.66-0.99, random-effect model)]. There was a very high heterogeneity among the studies (I(2) > 80%). The use of fibrates was associated with a significant increase in the risk of VTE (OR, 1.58; 95% CI, 1.23-2.02), without heterogeneity (I(2) = 0%). Data on other lipid-lowering drugs were lacking.

CONCLUSION
This meta-analysis of available literature suggests that statins may lower the risk of VTE, whereas fibrates may increase this risk. Due to several methodological limitations, this conclusion should be considered with caution, and additional, specifically designed RCTs are warranted.


In this paper we revisit the classical fluctuation-dissipation theorem with derivations and interpretations based on quantum electrodynamics (QED). As a starting point we take the widely cited semiclassical expression of the theorem connecting the absorption coefficient with the correlation spectra of a radiating molecular dipole. The literature is suggesting how this connection can be derived in terms of quantum mechanical statistical averages, but the corresponding results in terms of QED seems to be very difficult to trace in detail. The problem is therefore addressed here based on first principles. Interestingly, it turns out that the QED approach applied to the aforementioned statistical averages does not only prove the validity of the fluctuation-dissipation theorem, but it also provides a derivation and a quantum mechanical interpretation of Schwarzschild's equation for radiative transfer. In particular, it is found that the classical Beer-Bouguer-Lambert law is due to absorption as well as of stimulated emission, and furthermore that the source term in Schwarzschild's equation (Kirchhoff's law) is due solely to spontaneous emission. The significance of the fluctuation-dissipation theorem is finally elaborated on in terms of the appropriate scaling of line strength parameters (including line mixing) which is relevant in far infrared and millimeter wave broadband applications.


The increased number of reports in the literature dealing with sporotrichosis has served to focus the attention of clinicians on the variety of clinical pictures produced by this disease. These articles have repeatedly called attention to the fact that sporotrichosis closely simulates tuberculosis, syphilis' and a number of other cutaneous disorders, and, as a result of this, cases of sporotrichosis are being recognized with increasing frequency. The case reported here shows how necessary it is to employ every possible aid in confirming or eliminating a diagnosis of this condition. This case had all the clinical characteristics of sporotrichosis, but in our attempt to confirm this diagnosis we found that we were dealing with a case of inoculation tuberculosis of sporotrichoid type. REPORT OF CASE M. W., a white man, aged 44, came to the clinic in January, 1926, with lesions as shown in figure 1. The following history was obtained:


Model‐reduction techniques aim to reduce the computational complexity of simulating dynamical systems by applying a (Petrov–)Galerkin projection process that enforces the dynamics to evolve in a low‐dimensional subspace of the original state space. Frequently, the resulting reduced‐order model (ROM) violates intrinsic physical properties of the original full‐order model (e.g., global conservation, Lagrangian structure, state‐variable bounds) because the projection process does not generally ensure preservation of these properties. However, in many applications, ensuring the ROM preserves such intrinsic properties can enable the ROM to retain physical meaning and lead to improved accuracy and stability properties. In this work, we present a general constrained‐optimization formulation for projection‐based model reduction that can be used as a template to enforce the ROM to satisfy specific properties on the kinematics and dynamics. We introduce constrained‐optimization formulations at both the time‐continuous (i.e., ODE) level, which leads to a constrained Galerkin projection, and at the time‐discrete level, which leads to a least‐squares Petrov–Galerkin projection, in the context of linear multistep schemes. We demonstrate the ability of the proposed formulations to equip ROMs with desired properties such as global energy conservation and bounds on the total variation.


An Analysis of Primary Medical Care an International Study. W J Stephen pp 414 £12.50 Cambridge University Press 1979 The prospect of reading any book titled 'An Analysis ... an International Study' normally enthralls me not, and I noted with cynicism Sir George Godber's prefatory encomium: 'This is an achievement in a class of its own'. Furthermore, come page 362, Dr Stephen permits himself the obligatory swipe at academic practice: that it has 'become tainted with one of the modern status symbols ... increasing attendances at meetings and conferences, both nationally and internationally . . . there is little evidence that they are of much value'. Did Dr Stephen remember that his book is itself based on exactly such international contact? Nevertheless, this analysis is worthwhile, wellwritten and thought-provoking, and Sir George's preliminary words are amply justified. The following nuggets exemplify: from Scandinavia, 'There was excellent continuity of supervision for a number of diseases, but virtually no continuity of care for people and their families'; from Japan, 'there are over 20,000 different payments for different medicaments'; and from Australia, New Zealand and Canada, 'the fee structures emphasise the rewards for technical and surgical procedures rather than consultation, communication and general care'. He notes the danger of separating 'private' specialists outside hospital from those within, as in Germany, and of fully-fledged deputizing services as an alternative system of medicine, as in Denmark. He sees ideas fermenting overseas which have also developed here: that all doctors should spend some time in training in primary care units; that consultants should see patients and teach in surgeries and health centres; and that postgraduate work should enable higher fees to be charged (19% in the example cited). Dr Stephen's material includes some very individual assessments, and the freedom he gives himself to judge is most helpful in making the reader draw his own conclusions; for example, one wonders whether the 'medical school' can only turn out doctors in its own image, and whether indeed the hospital doctor and the primary health care doctor are not different animals linked only by the accident of their medical education a help in one case, and a handicap in the other?


The study examined changes in lysine decarboxylase (LDC), ornithine decarboxylase (ODC) and tyrosine decarboxylase (TyDC) activity in tissues of pea (Pisum sativum L.) infested by the pea aphid (Acyrthosiphon pisum Harris). The aphid induced increased ODC activity after one day and at two weeks. The effect was clearly systemic. TyDC activity increased after one day and at one week at feeding sites (aerial parts), while LDC activity increased only after one day of infestation and then decreased. Attack by aphids also affected enzyme activity in root tissues not directly damaged by the herbivores. The mechanisms of the response induced by pea aphid infestation in pea are discussed.


With fast development and wide applications of next generation sequencing (NGS), genomic sequence information is within reach to various research fields. Three benchtop NGS instruments are now available. The 454 GS Junior (Roche), Ion PGM (Life Technologies) and MiSeq (Illumina) are laser-printer sized and offer modest set-up and running costs. By reviewing 2 studies that compared the performance of these instruments, the major characteristics of each benchtop platforms are compared to enable direct comparisons. The 454 GS Junior generated the longest reads and most contiguous assemblies but had the lowest throughput. The Ion Torrent PGM had the highest throughput and fastest run time. The MiSeq had the highest throughput per run and lowest error rates. The Ion Torrent PGM and 454 GS Junior both produced homopolymer-associated indel errors. Although all the platforms allow multiplexing of samples, details of experimental design, library preparation and data analysis may constrain the options. The features of the platforms provide opportunities both to conduct groundbreaking studies and to waste money. Thus, careful considerations should be made before purchasing or using any of them.


Recent advances in cutting tool materials and PVD surface coatings are making highspeed dry machiningan increasingly viable machining operation in commercial manufacturing sectors. In this investigation, the performance of cathodic arc TiN and TiAlN coatings was assessed on HSS twist drills used to machine 1015 and 2080 workpiece materials under aggressive machining conditions. 17.6-26.4 m/min cutting speeds and 0.10-0.15 mm/rev feed rates were used as cutting parametersand all the experiments conducted under dryconditions. Number of holes drilled by TiN, TiAlNcoated and uncoated tools observed and TiN coating was found to be superiour than the others. The drill wear was observed using scanning electron microscopy (SEM) and also macroscopy, and comparative wear properties were discussed.


In 2023, Listeria monocytogenes persistence remains a problem in the food business. A profound understanding of how this pathogen persists may lead to better aimed intervention/prevention strategies. The lack of a uniform definition of persistence makes the comparison between studies complex. Harborage sites offer protection against adverse environmental conditions and form the ideal habitat for the formation of biofilms, one of the major persistence strategies. A retarded growth rate, disinfectant resistance/tolerance, desiccation resistance/tolerance, and protozoan protection complete the list of persistence strategies for Listeria monocytogenes and can occur on themselves or in combination with biofilms. Based on the discussed persistence strategies, intervention strategies are proposed. By enhancing the focus on four precaution principles (cleaning and disinfection, infrastructure/hygienic design, technical maintenance, and work methodology) as mentioned in Regulation (EC) No. 852/2004, the risk of persistence can be decreased. All of the intervention strategies result in obtaining and maintaining a good general hygiene status throughout the establishment at all levels ranging from separate equipment to the entire building.


In previous communications from this laboratory a method of examining the rates of reaction of gases after collision with electrons has been described; and in particular the use of a triode of special construction and dimensions for determining the critical potentials at which the reaction takes place has been noted. This method has now been applied to the combustion of nitrogen, which has been shown to depend upon ionisation of the nitrogen, activation or ionisation of oxygen apparently playing no part. This conclusion is supported by the measurements of critical potentials, by the chemical examination of the reaction products in the experiments to be described, and to some extent by measurements of the efficiency of the process.


Electric power quality, which is a current interest to several power utilities all over the world, is often severely affected by harmonics and transient disturbances. There is no unique model which can assess the power quality problem and to identify and classify them properly. Existing automatic recognition methods need improvement in terms of their versatility, reliability, and accuracy. The FUZZY LOGIC based tools have been applied for the PQ classification. This paper addresses Power quality problem classification by wavelet and fuzzy expert system. Major Key issues and challenges related to these advanced techniques in automatic classification of PQ problems are highlighted. New intelligent system technologies using DSP, expert systems, AI and machine learning provide some unique advantages in intelligent classification of PQ distortions.


Objectives: The cell cycle regulator p21Waf1/Cip1 belongs to the family of cyclin-dependent kinase inhibitors (CDKIs). Depending on the cellular condition, p21Waf1/Cip1 can either, inhibit the cell cycle or promote proliferation, prohibit or induce apoptosis and increase or decrease cell differentiation. The contradictory nature of p21Waf1/Cip1 encouraged us to investigate the effects of this CDKI on the expression of chromatin modifying enzymes in colorectal tumor cells. Methods: Three different HCT116 cell lines were used for our studies. HCT116 WT, HCT116 p21-/- and HCT116 p53-/-. The isolated RNA was analyzed via Epigenetic Chromatin Modification Enzymes RT2 Profiler PCR Arrays from Qiagen. Western Blot analysis was performed to verify the results of the PCR arrays. In addition, immunohistochemical staining of different chromatin modifiers was performed on tissue microarrays of colon cancer patients. The protein structure of p21Waf1/Cip1 was generated by computational modelling techniques to investigate possible interactions between p21Waf1/Cip1 and chromatin modifying enzymes. Ex vivo crypt organoids from WT and p21 -/- mice were studied for chromatin signature. Results: The PCR arrays provided us with astonishing results. Compared to the wild type HCT116 cells, we could see a clear deregulation of a high number of different chromatin modifying enzymes in the two knock out cell lines. SETD1B was up-regulated 1,8 times in p21-/- and HDAC1, which is a known interaction partner of p21Waf1/Cip1, was down regulated about 2 times compared to the WT cells. This could also be proven by Western Blot and immunohistochemical analysis. The data was further processed and analyzed using an R package termed as HTqPCR and it was observed that ATF2 was up-regulated, while AURKB, different HDACs, and DNMT3B genes were down-regulated in p21-/- cells compared to the WT cells. The interaction between p21Waf1/Cip1 and HDAC1 could be analyzed on an atomic scale by molecular dynamics simulations. Conclusion: Our data strongly suggests that p21Waf1/Cip1 is very important for chromatin regulation in colon cancer cells and that its loss induces an active histone code. Interestingly most p21-dependent effects were independent of p53. These exciting and new findings have to be further investigated. Citation Format: Pablo Lennert, Katharina Erlenbach-Wuensch, Carsten Kroeger, Sara Steinmann, Kerstin Huebner, Sushmita Paul, Felix Rausch, Arndt Hartmann, Regine Schneider-Stock. p21Waf1/Cip1 dependent chromatin modifications in colorectal tumor cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2194. doi:10.1158/1538-7445.AM2015-2194


We have used a murine renal adenocarcinoma of spontaneous origin (Renca) inplanted in the peritoneal cavity to study the therapeutic potential of biological response modifiers (BRMs) used alone or in conjunction with chemotherapy. This tumor model is therapeutically challenging since following intraperitoneal (i.p.) injection, the tumor grows progressively with hemorrhagic ascites, abdominal metastases to lymph nodes, liver, spleen, most serous membranes, and, in some animals, metastases to extra-abdominal sites (lungs). In the absence of therapy, death invariably occurs within 36 +/- 2 days. The tumor is efficiently lysed in 4 hours by peritoneal cells isolated from mice treated with BRMs. Both MVE-2 and rIL-2 significantly increased the survival time of tumor-bearing mice, but only treatment with MVE-2 led to definite cures of i.p. Renca. A single i.p. injection of MVE-2 cured 20% of the tumor-bearing mice, while repeated i.p. administration of this drug at 12 day intervals cured 70% of i.p. Renca-bearing mice. Combined therapy with doxorubicin hydrochloride and a single dose of MVE-2 cured 90% of tumor-bearing animals. The superior therapeutic efficiency of MVE-2 compared to that of the rIL-2 may be due to its ability, after i.p. inoculation, to generate and maintain high levels of cytotoxic effector cell activity for an elevated period of time within the peritoneal cell population. Additionally, MVE-2 augments effector cell activity in the liver, lungs, spleen, and blood and may therefore more efficiently interfere with metastasis formation in those compartments. The additive effects of MVE-2 and the chemotherapeutic agent suggest that more effective therapy may be achieved by the combination of immunotherapy with BRMs with chemotherapeutic drugs.


Angola is a diamond rich country. It is also a country that, after decades of war, desperately needs to bring itself out of poverty. In order to do this, Angola now has sought and obtained positive trade relations with all of the BRICS countries of Brazil, Russia, India, China and South Africa. This paper investigates the BRICS countries historical and diplomatic involvement in the Angolan diamond sector. In a broader sense, this paper examines Angola's collaboration with BRICS and argues that diamonds in Angola have helped foster better co-ordination and cooperation between the BRICS countries. Moreover, BRICS countries should and do have a role in the development of Angola, and the developing African country needs to learn valuable lessons from its developmental experiences if it is continue on its accelerated growth path.


The main disadvantage of applying the IRT method is presence of plenty false indications in thermograms. A simple use of IRT equipment with better temperature resolution would not help in distinguishing the mines, since noise comes not from a camera, but from soil surface. Recognizing the role of moisture and density of sand and possibilities to express it quantitatively plays an important role. In our model of thermal properties of the soil the volumetric unit of the soil consists of mineral and organic particles, as well as water and air. All needed parameters can be calculated. Calculations of thermal signatures of the underground objects were made basing on 3D-heat equation for the sinus type heating of 3D model and cooling by convection. Measurements were made for field and laboratory stand-ups, using methodologies typical for "single-shot" measurements as well as analyses of transient processes based on sequence of thermograms. Results of simulations and measurements confirm expectation tha that high level of "radiant noises" is caused mainly by differences in the moisture and sand density levels.


Patrick K. Kimes: New Statistical Learning Approaches with Applications to RNA-seq Data (Under the direction of Yufeng Liu, J. S. Marron, D. Neil Hayes) This dissertation examines statistical learning problems in both the supervised and unsupervised settings. The dissertation is composed of three major parts. In the first two, we address the important question of significance of clustering, and in the third, we describe a novel framework for unifying hard and soft classification through a spectrum of binary learning problems. In the unsupervised task of clustering, determining whether the identified clusters represent important underlying structure, or are artifacts of natural sampling variation, has been a critical and challenging question. In this dissertation, we introduce two new methods for addressing this question using statistical significance. In the first part of the dissertation, we describe SigFuge, an approach for identifying genomic loci exhibiting differential transcription patterns across many RNA-seq samples. In the second part of this dissertation, we describe statistical Significance of Hierarchical Clustering (SHC), a Monte Carlo based approach for testing significance in hierarchical clustering, and demonstrate the power of the method to identify significant clustering using two cancer gene expression datasets. Both methods were implemented and made available as open source packages in R. In the final part of this dissertation, we propose a spectrum of supervised learning problems which spans the hard and soft classification tasks based on fitting multiple decision rules to a dataset. By doing so, we reveal a novel collection of binary supervised learning problems. We study the problems using the framework of large-margin classification and a class of piecewise linear surrogate losses, for which we derive statistical properties. We evaluate our approach using simulations and a magnetic resonance imaging (MRI) dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study.


Background/Objectives: Pancreatic cancer is an exceptional aggressive cancer, and acquired drug resistance in this type of cancer is common. Reactive oxygen species (ROS) play an essential role in cell apoptosis, which is a key mechanism by which radio- or chemotherapy induces cell killing. Mitochondria are the major source of ROS in cells. Thus, alterations in the expression of mitochondrial proteins involved in ROS production or scavenging may be closely linked to the resistance of cancer cells to radio- or chemotherapy. The objective of this study was to use a comparative proteomic method to screen the mitochondrial proteins that confer the resistance of pancreatic cancer cells to ROS-inducing anticancer compounds. Methodology/Principal Findings: In order to eliminate the complications caused by genetic background variations, we generated a pancreatic cancer isogenic stable cell line that differs in sensitivity to 2-methoxyestradiol (2-ME), a ROS-inducing anticancer compound. The isogenic stable cell line was generated by exposing the pancreatic cancer MIA PaCa-2 cells (an undifferentiated pancreatic cancer cell line) to increasing concentrations of 2-ME (0.5-2.5 µM) over a three month period. One clone that survived from the long-term exposure to 2-ME showed strong 2-ME resistance, which was gauged by both cell apoptotic assay and the long-term clonogenic survival assay. We measured cellular ROS levels with flow cytometry using a fluorescent probe DCFH-DA, and it was shown that the resistant cells contained an elevated level of ROS, almost 3-fold that of the parental cells. We then used a two-dimensional gel electrophoresis based comparative proteomics method to compare the expressions of mitochondrial proteins between the parental and the resistant cells, followed by mass spectrometry analysis of the differentially expressed proteins. One protein identified to be upregulated in the resistant cells was manganese superoxide dismutase (SOD2), a mitochondrial protein that converts superoxide radicals to hydrogen peroxides (H 2 O 2 ). To examine whether the upregulated SOD2 was related to the 2-ME resistance of the resistant cells, we silenced or ectopically overexpressed SOD2 gene in the cells. The results demonstrated that silencing of SOD2 with small hairpin RNA resensitized the resistant cells to 2-ME, and stable overexpression of SOD2 led the parental cells to 2-ME resistance. In addition, the 2-ME-resistant cells also demonstrated resistance to gamma-ray radiation, suggesting the acquired 2-ME resistance of pancreatic cancer cells is not restricted to ROS-inducing compound 2-ME but is also linked to the radio-resistance of the cells. Because H 2 O 2 , the product of SOD2, is also toxic to cells, we examined the expression or activity of several important mitochondrial proteins that are involved in detoxifying H 2 O 2 in the mitochondria. The results demonstrated that the expression or activity of those proteins was not enhanced, suggesting they may not positively contribute to the enhanced 2-ME-resistance of the resistant cells. Conclusions: Our results suggest that pancreatic cancer cells acquire resistance to ROS-inducing anticancer agents through increasing the threshold of ROS tolerance of the cells (hence, the resistance to the oxidative agent-mediated cell killing and apoptosis). Upregulation of SOD2 expression in the mitochondria plays a key role in this enhanced tolerance to ROS-inducing anticancer drugs, and potentially also to ionizing radiation. Citation Format: Jianhong Zhou, Yuchun Du. Acquired resistance of pancreatic cancer cells to 2-methoxyestradiol is associated with the upregulation of manganese superoxide dismutase in the mitochondria. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B76.


In this paper, we propose a defect analysis system, which automatically aligns a digitized copy of a printed output to a reference electronic original and subsequently illustrates potential image quality artifacts. We focus on image defects or artifacts caused by shortfalls in mechanical or electrophotographic processes. In this method, log-polar transform and mutual information techniques are used for image registration. A confidence map is then calculated by comparing the contrast and entropy of the neighborhood for each pixel in both images. This confidence map results in a qualitative difference between printed documents and electronic originals. The algorithm was demonstrated successfully on a database of 94 images with 95.7% accuracy.


Background: This study assesses the expressions of estrogen and progesterone receptors in endometrioid carcinomas of the endometrium and their association with established clinicopathological prognostic parameters. Methods: We reviewed the pathology and medical records from 45 cases of endometrioid endometrial carcinomas that were seen from 2006 to 2011 for relevant clinical and histological parameters. Grade I and stage IA tumors were analyzed and compared with higher grades and stages IB- IV. Estrogen and progesterone immunostained slides were analyzed. Results: Patients' age ranged from 32 to 77 years (mean: 58.13 years). Postmenopausal bleeding was the most common presenting complaint seen in 75.6% of cases. Associated co-morbidities such as diabetes, hypertension and other malignancies were seen in 88% of cases. Myometrial invasion of less than 50% of myometrial thickness was seen in 70.5% cases. There were 40% of tumors classified as FIGO grade 1 and 65.85% were FIGO stage IA. Estrogen and progesterone expressions were seen in 40 (90%) cases, predominantly in FIGO stage I disease. However there was no statistically significant association of estrogen and progesterone expression with any of the clinicopathological prognostic factors. In 23 of the 30 cases that had follow up data, there was no evidence of disease. Of these, only one case was negative for both hormone receptors. Progesterone positivity alone was seen in 87% of cases with no evidence of disease. Conclusions: Nuclear immunostaining with estrogen and progesterone was seen in the majority of cases (90%). Although we have observed a linear increase in progesterone receptor positivity with disease-free survival, this finding needs to be confirmed with additional, larger studies.