This dissertation contains four projects: transforming electronic structure Hamiltonian to approximating Ising-type Hamiltonian to enable electronic structure calculations by quantum annealing, quantum-assisted restricted Boltzmann machine for electronic structure calculations, hybrid quantum classical neural network for calculating ground state energies of molecules and qubit coupled cluster single and double excitations variational quantum eigensolver for electronic structure. In chapter 1 we present a general introduction of quantum computer, including a brief introduction of two quantum computing model: gate model and quantum annealing model. We also give a general review about electronic structure calculations on quantum computer. In chapter 2, we show an approximating mapping between the electronic structure Hamiltonian and the Ising Hamiltonian. The whole mapping is enabled by first enlarging the qubits space to transform the electronic structure Hamiltonian to a diagonal Hamiltonian. Then introduce ancilla qubits to transform the diagonal Hamiltonian to an Ising-type Hamiltonian. We also design an algorithm to use the transformed Hamiltonian to obtain the approximating ground energy of the original Hamiltonian. The numerical simulation results of the transformed Hamiltonian for H2, He2, HeH+, and LiH molecules match the exact numerical calculations of the original Hamiltonian. This demonstrates that one can map the molecular Hamiltonian to an Ising-type Hamiltonian which could easily be implemented on currently available quantum hardware. In chapter 3, we report a hybrid quantum algorithm employing a restricted Boltzmann machine to obtain accurate molecular potential energy surfaces. By exploiting a quantum algorithm to help optimize the underlying objective function, we obtained an efficient procedure for the calculation of the electronic ground state energy for a small molecule system. Our approach achieves high accuracy for the ground state energy for H2, LiH, H2O at a specific location on its potential energy surface with a finite basis set. With the future availability of larger-scale quantum computers, quantum machine learning techniques are set to become powerful tools to obtain accurate values for electronic structures. In chapter 4, we present a hybrid quantum classical neural network that can be trained to perform electronic structure calculation and generate potential energy curves of simple molecules. The method is based on the combination of parameterized quantum circuit and measurements. With unsupervised training, the neural network can generate electronic potential energy curves based on training at certain bond lengths. To demonstrate the power of the proposed new method, we present results of using the quantum-classical hybrid neural network to calculate ground state potential energy curves of simple molecules such as H2, LiH and BeH2. The results are very accurate and the approach could potentially be used to generate complex molecular potential energy surfaces. In chapter 5, we introduce a new variational quantum eigensolver (VQE) ansatz based on the particle preserving exchange gate to achieve qubit excitations. The proposed VQE ansatz has gate complexity up-bounded to O(n4) where n is the number of qubits of the Hamiltonian. Numerical results of simple molecular systems such as BeH2, H2O, N2, H4 and H6 using the proposed VQE ansatz gives very accurate results within errors about 10-3 Hartree.


The progression of breast cancer from the primary tumor setting to the metastatic setting is the critical event defining Stage IV disease, no longer considered curable. The microenvironment at specific organ sites is known to play a key role in influencing the ultimate fate of metastatic cells; yet microenvironmental mediated‐molecular mechanisms underlying organ specific metastasis in breast cancer are not well understood. This review discusses biomimetic strategies employed to recapitulate metastatic organ microenvironments, particularly, bone, liver, lung and brain to elucidate the mechanisms dictating metastatic breast cancer cell homing and colonization. These biomimetic strategies include in vitro techniques such as biomaterial‐based co‐culturing techniques, microfluidics, organ‐mimetic chips, bioreactor technologies, and decellularized matrices as well as cutting edge in vivo techniques to better understand the interactions between metastatic breast cancer cells and the stroma at the metastatic site. The advantages and disadvantages of these systems are discussed. In addition, how creation of biomimetic models will impact breast cancer metastasis research and their broad utility is explored.


Nowadays, consumers could be reached directly, through the rapid development of direct marketing. In order to affect consumers' purchasing decisions, direct marketing method uses specific advertisement tools and distribution channels to establish direct and mutual communication. Alongside the traditional channels, direct marketers have taken advantage of communication tools such as computer, fax, television, smartphones, e-mail and Internet. Thereby direct marketers generally use various direct marketing strategies such as online marketing, face-to-face selling, direct mail marketing, catalog marketing, telemarketing etc. Focusing on three of these direct marketing strategies, namely Social Networking Websites (SNS), Cause-Related Marketing (CRM) and Word of Mouth Marketing (WOM), this research aims at analysing the impacts of SNS, CRM and WOM on consumer's purchasing decisions for Avon cosmetic products in Istanbul, Turkey. The paper utilizes a quantitative survey of 1,421 cosmetics customers in Istanbul to investigate the conceptual relationship between three direct marketing strategies and purchasing decision through nine hypotheses. Data was analysed through T-tests, One-Way Anova and Binary Logistic Regression. Based on the findings of the research, a significant and positive relationship between variables was confirmed. This research provides a contribution to direct marketing literature, since no similar studies have been conducted in cosmetics sector in Turkey.


Introduction For early detection of sepsis, automated systems within the electronic health record have evolved to alert emergency department (ED) personnel to the possibility of sepsis, and in some cases link them to suggested care pathways. We conducted a systematic review of automated sepsis-alert detection systems in the ED. Methods We searched multiple health literature databases from the earliest available dates to August 2018. Articles were screened based on abstract, again via manuscript, and further narrowed with set inclusion criteria: 1) adult patients in the ED diagnosed with sepsis, severe sepsis, or septic shock; 2) an electronic system that alerts a healthcare provider of sepsis in real or near-real time; and 3) measures of diagnostic accuracy or quality of sepsis alerts. The final, detailed review was guided by QUADAS-2 and GRADE criteria. We tracked all articles using an online tool (Covidence), and the review was registered with PROSPERO registry of reviews. A two-author consensus was reached at the article choice stage and final review stage. Due to the variation in alert criteria and methods of sepsis diagnosis confirmation, the data were not combined for meta-analysis. Results We screened 693 articles by title and abstract and 20 by full text; we then selected 10 for the study. The articles were published between 2009–2018. Two studies had algorithm-based alert systems, while eight had rule-based alert systems. All systems used different criteria based on systemic inflammatory response syndrome (SIRS) to define sepsis. Sensitivities ranged from 10–100%, specificities from 78–99%, and positive predictive value from 5.8–54%. Negative predictive value was consistently high at 99–100%. Studies showed some evidence for improved process-of-care markers, including improved time to antibiotics. Length of stay improved in two studies. One low quality study showed improved mortality. Conclusion The limited evidence available suggests that sepsis alerts in the ED setting can be set to high sensitivity. No high-quality studies showed a difference in mortality, but evidence exists for improvements in process of care. Significant further work is needed to understand the consequences of alert fatigue and sensitivity set points.


Consumers tend to have a higher evaluation and purchase intention toward the products with stronger brands. Compared to foreign products, Chinese alternatives usually occupy a weaker brand position. Hence, Chinese manufacturers who want to increase market share commonly adopt a low-price strategy. However, such strategy may greatly weaken the organization's ability to gain profits and undermine its long-term development. Moreover, low price is likely to be used by consumers as a signal of poor quality of the products. Therefore, it is important for Chinese manufacturers with weak brands to adopt new competitive strategies. The purpose of this study was to examine how assortment structure affects consumer's brand choice. The key hypothesis was that the manufacturers with weaker brands, rather than stronger ones, could optimize the assortment structure to affect consumers' brand choice in a retail environment. We conducted three empirical studies to test our hypotheses. In Study 1, we conducted three separated experiments to examine the impact of the assortment structure on consumers' perceived variety of products. In particular, Study 1a explored the main effect of the assortment structure(attribute-based vs. benefit-based) on consumers' perceived variety. Then, studies 1b and 1c composed a Chain-of-Experiments and tested the intermediate mechanism of the construal level in the causal relationship between the assortment structure and consumers' perceived variety: Study 1b examined the impact of assortment structure on consumers' construal level, and Study 1c tested the impact of the construal level on consumers' perceived variety. Study 2 investigated the causal relationship between the assortment structure and consumers' brand choice. Studies 1 and 2 adopted a one-way between-subject design. Study 3 explored the moderating effect of consumers' prior knowledge of brand strength in the causal relationship and used a 2(attribute-based vs. benefit-based assortment structure) × 2(strong vs. weak brand strength) between-subject design. As regards to the findings, compared to the benefit-based assortment structure, the attribute-based assortment structure increased consumers' perceived variety of product, and it was the construal level that mediated this causal relationship. On this basis, the assortment structure of product influenced consumers' brand choice in a retail environment. Meanwhile, a sequential mediation constituted by perceived variety and perceived quality mediated the effect of assortment structure on consumers' brand choice. Finally, consumers' prior knowledge of brand strength moderated the causal relationship between assortment structure and consumers' brand choice. Specifically, the assortment structure affected consumers' brand choice only when consumers initially perceived the brands as weak, rather than strong. In summary, for weak brands, the attribute-based assortment structure increased consumers' perception of the product variety and quality, improving consumers' brand evaluation and purchase intention relative to benefit-based assortment structure. The present research offers some theoretical and managerial implications. Theoretically, our findings suggest that the assortment structure influences consumers' brand choice, and consumers' prior knowledge of brand strength moderates this causal relationship. Managerially, we propose that Chinese manufacturers with weak brands can use the attribute-based assortment structure to increase their sales and market share when competing with strong foreign brands.


A self-instructional approach to the entry-level presentation of urinalysis in a written modular format was used by a class of medical laboratory technician students. The course consisted of 13 modules based upon behavioral objectives. The modules used no audio or visual media but required "hands-on" performance of laboratory procedures. The achievements of a test sample of 12 students were compared with those of a previous class in which the same material was presented in lectures. Evaluation by written tests given to both classes showed no statistical difference. The self-instructed students performed adequately in their practical laboratory work, but the overall learning time was increased by 50 percent when self-pacing was used. A measurement questionnaire revealed that the students preferred instructor-led courses to self-instructional units for a variety of reasons which lead to some further considerations.


The  purpose  of  this  study  was  to  examine  whether  organisation  commitment,  professional commitment and leadership style had influenced toward job satisfaction with motivation as intervening variable.   This research used primary data, auditor on puclic accountant sector in Semarang as population. Using a convenience sampling method, 43 quessioner. The data was analyzed by multiple regression. All data variable meet with validity test, reliability test, normality also classical assumption. The result showed that organization commitment, profesional commitment, leadership style and motivation influenced significantly on job satisfaction. On the other hand organization commitment, profesional  commitment  and  leadership  style  had  influenced  on  job  satisfaction  did  not  through motivation as intevening variable.   Keywords : organization committment, profesional committment, leadership style, motivation, job satisfaction


Martensite phase and its formation are quite attractive and important in industrial steels for reasons of having good properties such as high strength and high hardness. As such, determining the martensite formation start temperature in steel heat treatment operations is extremely important. Some parameters including chemical composition and grain size are effective factors on this temperature. In this investigation, we have made an attempt to determine this temperature with regard to chemical composition of steels. To reach this goal, we have explored the use of feedforward Artificial Neural Network (ANN) with the Back Propagation (BP) learning algorithm. A comparison is made between the Ms temperatures predicted with this model and those from the empirical equation as well as the experimental values obtained from costly and time-consuming tests in scientific and industrial centers for various steels. This comparison indicates that a better agreement exists between the ANN-predicted results and experimental values than the results from the empirical equation and experimental values.


Recently, it was found that IL-13 is involved in allergic inflammation and mucus hypersecretion in in vivo animal models. However, the role of IL-13 in in vitro cellular models has yet to be determined. This study aimed to investigate the direct effect of IL-13 on mucin gene expression and mucin secretion in cultured normal human nasal epithelial cells. After treatment with IL-13, total mucin and MUC5AC mucin levels were measured using an immunoblotting assay. MUC2, MUC5AC and MUC8 mRNA expression were determined using reverse transcription-polymerase chain reaction. Also, immunostaining was performed using a MUC5AC antibody on histologic and cytospin slides. After treatment with S 5 ng/ml IL-13, the level of total mucin and MUC5AC mucin secretion decreased substantially. The expression of MUC2 and MUC8 mRNA increased with higher concentrations of IL-13, but the expression of MUC5AC mRNA decreased. On the 7th day after IL-13 treatment, a significant decrease in the number of MUC5AC-positive cells was confirmed by immunostaining. These findings indicate that IL-13 suppresses MUC5AC mucin gene expression and mucin secretion in cultured normal human nasal epithelial cells in vitro .


Summary:  Successful V(D)J recombination at the T‐cell receptor β (Tcrb) locus is critical for early thymocyte development. The locus is subject to a host of regulatory mechanisms that impart a strict developmental order to Tcrb recombination events and that insure that Tcrb recombination occurs in an allelically excluded fashion. Progress has been made in the understanding of the cis‐acting control of Tcrb locus chromatin structure and the extent to which such accessibility control can account for the developmental regulation of Tcrb recombination. However, recent studies in our laboratory and elsewhere have made it abundantly clear that accessibility control is only part of the story, and multiple additional mechanisms impact both the developmental activation and inactivation of locus recombination events. Here we evaluate our current understanding of developmental regulation at the Tcrb locus. We highlight the many unresolved issues and we discuss how recent concepts emerging from studies of other antigen receptor loci may (or may not) help to resolve these issues.


Abstract Context: Fentanyl analogs are synthetic opioids that bind to mu receptors with high potency. We report two cases where users developed apnea and required naloxone reversal after exposure to small quantities of the fentanyl analogs, furanylfentanyl and ß-hydroxyfentanyl. Case details: A 19 year-old woman reported insufflating a small number of granules of "fentanyl" powder and developed apnea. A 22 year-old woman touched her tongue to powdered "fentanyl" to treat a migraine headache and became apneic. Results: Furanylfentanyl was identified in the first patient's serum (3.6 ng/mL furanylfentanyl), urine (17.6 ng/mL furanylfentanyl) , and in the product (109mg/g powder). ß-hydroxyfentanyl was detected in the second patient's serum (6.5 ng/mL ß-hydroxyfentanyl) and in the product (120 mg/g powder). Discussion: In both cases, furanylfentanyl and ß-hydroxyfentanyl were identified in the serum/plasma and urine. Fentanyl analogs were detected in the product at 109-120mg per gram of powder, which suggests that a 500mcg dose of fentanyl analog is the equivalent to 4.17–4.59mg of powder, or about the mass in 1/500th of a packet of sugar. Unique aspects of these cases are the rarely reported use of furanylfentanyl and ß-hydroxyfentanyl, intentional insufflation of "fentanyl" for therapeutic and recreational use, the small quantities of powder ingested, and the use of non-targeted analysis to identify the fentanyl analogs.


To introduce a novel method of driving robot move. This method is to use the force-line model to drive the limbs of the robot inspired from the skeleton movement driven by muscle. A humanoid robot with the force-line model has been constructed. New software for muscle force estimation has been developed. The solution of the parameters which are the input of the software has been statement. Finally, the input parameters have been obtained by experiment and calculation. The humanoid robot can be driven to imitate human walking by the force which along the force-line. It will provide wide insight in developing new type robot for complex motion and applying the technology of force-line driving model in other filed.


In the anesthetized cat we used laser-Doppler flowmetry to investigate the part played by cervical superior sympathetic trunk (CST) fibers in the control of blood vessels in an orofacial area (the lower lip). The blood flow increase (antidromic vasodilatation) elicited by inferior alveolar nerve (IAN) stimulation was not affected by ongoing repetitive CST stimulation over the frequency range examined (0.2-10 Hz), although reflex parasympathetic vasodilatation was attenuated. The vasoconstrictor responses elicited by IAN stimulation in some preparations were reduced in a frequency-dependent manner (at 0.2-1 Hz) during ongoing CST stimulation (and replaced by vasodilator responses). The vasoconstrictor response evoked directly by brief CST stimulation was attenuated, but not transformed to a vasodilator response, by ongoing CST stimulation. Thus in the cat lower lip 1) sympathetic stimulation attenuated one type of vasodilator response (parasympathetic-mediated vasodilatation), but not another (antidromic vasodilatation), and 2) ongoing sympathetic (CST) stimulation at low frequencies (<1 Hz) prevented further sympathetic-mediated vasoconstriction.


This work assesses how crashes and recoveries affect the performance of a replicated dynamic content web application. RobustStore is the result of retrofitting TPC-W's on-line bookstore with Treplica, a middleware for building dependable applications. Implementations of Paxos and Fast Paxos are at the core of Treplica's efficient and programmer-friendly support for replication and recovery. The TPC-W benchmark, augmented with faultloads and dependability measures, is used to evaluate the behaviour of RobustStore. Experiments apply faultloads that cause sequential and concurrent replica crashes. RobustStore's performance drops by less than 13% during the recovery from two simultaneous replica crashes. When subject to an identical faultload and a shopping workload, a five-replicas RobustStore maintains an accuracy of 99.999%. Our results display not only good performance, total autonomy and uninterrupted availability, they also show that it is simple to develop efficient recovery-oriented applications using Treplica.


This paper develops a novel approach for multitarget tracking, called box-particle probability hypothesis density filter (box-PHD filter). The approach is able to track multiple targets and estimates the unknown number of targets. Furthermore, it is capable to deal with three sources of uncertainty: stochastic, set-theoretic and data association uncertainty. The box-PHD filter reduces the number of particles significantly, which improves the runtime considerably. The small particle number makes this approach attractive for distributed computing. A box-particle is a random sample that occupies a small and controllable rectangular region of non-zero volume. Manipulation of boxes utilizes methods from the field of interval analysis. The theoretical derivation of the box-PHD filter is presented followed by a comparative analysis with a standard sequential Monte Carlo (SMC) version of the PHD filter. To measure the performance objectively three measures are used: inclusion, volume and the optimum subpattern assignment metric. Our studies suggest that the box-PHD filter reaches similar accuracy results, like a SMC-PHD filter but with much considerably less computational costs. Furthermore, we can show that in the presence of strongly biased measurement the box-PHD filter even outperforms the classical SMC-PHD filter.


We have shown previously that caspase-6 activity is lethal to human neurons (LeBlanc et al., 1999; Zhang et al., 2000). Here we find that 17-beta-estradiol but not 17-alpha-estradiol prevents caspase-6-mediated neuronal cell death. 17-beta-estradiol-treated neuronal extracts directly inhibit recombinant active caspase-6, caspase-3, caspase-7, and caspase-8 in vitro. We conclude that 17-beta-estradiol induces a caspase inhibitory factor (CIF) that is preventing neuronal apoptosis. The induction of CIF occurs within 10 min of 17-beta-estradiol exposure to neurons, does not require de novo protein synthesis, and involves mitogen-activated protein kinase activation. The effect is antagonized by the estrogen receptor antagonist tamoxifen. In contrast, 17-beta-estradiol does not induce CIF or prevent caspase-mediated cell death in cultured astrocytes. CIF does not act through oxidation of the caspase active site. CIF activity copurifies with proteins of between 12 and 14 kDa in size. Our results indicate that 17-beta-estradiol induces an inhibitor of active caspases through a receptor-mediated nongenomic pathway and provide an additional mechanism for the neuroprotective action of 17-beta-estradiol that is likely highly relevant to the understanding of the role of estrogen against Alzheimer's disease.


According to the literature, the effect of remittances on income inequality in origin countries of migrants is not clear, whatever empirical approach is used. Aiming at clearing up this ambiguity, some authors took into account the historical, social or economic context of the home countries considered. The underlying idea of most of these studies is actually that the impact of remittances on income inequality depends on whom migrates, i.e. on the location migrants occupy in income distribution in their home country. However, to our knowledge, no macroeconomic study examining the remittances effect on inequality, consider the composition of migratory flows. To reveal at the macroeconomic level the position of migrants in income distribution at origin, we introduce in our equation of inequality non-linearities in the level of development of the recipient countries, in the costs of migration and in the level of brain drain. Using a panel sample of 80 developing countries over the period 1970-2000, and even by factoring in the endogeneity of remittances, this paper provides evidence of some characteristics of countries of origin in which there is an inequality-decreasing effect of remittances on income inequality. It turns out that countries belonging to the Mediterranean Basin have the characteristics revealed.


Cement is one of the key stabilizers for earth constructions since Roman civilization. The invention of cement was one step in the human civilization. However, cement has many issues especially when it comes to the environmental conservation. The production of cement creates a lot of carbon dioxide and destroys the natural setting to some extent due to the high consumption of clay and lime. Therefore, this study was conducted to alter the cement in mud concrete block. The study started with an inventory of alternative stabilizers that can be found in nature as well as in the human production. And then, the chemical patterns of those stabilizers were carefully identified to alter the typical Portland cement. Several mix proportions were tested and developed to alter the cement and found that the following materials can be developed to alter cement. A natural sta bilizer such as tree resins, latex rubber stabilizer, waste ash, rice husk ash and many other ashes can be developed to chemically stabilize the earth blocks. However, out of the invented stabilizers, fly ash and rice husk ash have the high potential to replace cement.


In this paper, a new mechanism is proposed by which aerosols decrease the amount of photosynthetically active radiation (PAR) available to plants for photosynthesis. The mechanism involves the scattering and absorption of PAR by water insoluble aerosol particles (WIA) which deposit on leaves and are not washed off by precipitation. A simple model is developed that predicts the change in the transmittance of PAR, TPAR, for plant leaves due to WIA dry deposition as a function of aerosol chemical, physical, and optical properties. Model estimates for the agricultural Yangtze delta region of China indicate that over a 2‐month period during a growing season, dry deposition of WIA may account for a ∼35% reduction in PAR available for plant photosynthesis. Although, the estimate is sensitive to several factors that are uncertain including aerosol dry deposition velocity, leaf area index, and removal rate of particles by precipitation. Results suggest that impacts on crop yields due to aerosol dry deposition could be considerable in this region and suggest a previously neglected economic incentive for China to mitigate air pollution. Additionally, WIA dry deposition may influence carbon uptake by plants in other locations that experience regional haze.


Straughan, B. 2019. Kama Creek culvert restoration: an assessment of long-term remediation success. 43 pp. The purpose of studying the long term remediation success of Kama Creek, Nipigon Bay, Lake Superior, was to follow up on past remediation research with special attention to emerging concerns and the importance of continued monitoring – particularly on small nursery streams. Monitoring is an important part of ecosystem management that provides decision makers with current conditions and possibly more valuable, historical conditions. In the case of Kama Creek, there have been many alterations to the natural stream from railway and road crossings, channel realignment (1960's), and remediation (October-November 2011). The Kama Creek remediation was initiated because of noted declines in Brook Trout (Savelinus fontinalis) populations throughout Lake Superior and Kama Creek's own reaches. Since being recognized as an area of concern, assessments have been completed to establish pre-remediation conditions (2011), post-remediation conditions (2012), and remediation success (2013, 2014, 2015, and 2018). Individually, the research projects indicate the conditions and health of Kama Creek at one point in time, but combined together the studies directly show the re-establishment of ecological components, stream health over time, and success or failure of the remediation techniques. Indirectly, the continued study of Kama Creek illustrates the importance of monitoring remediation projects, ecosystems, and any ecological element. This habitat assessment of Kama Creek occurred that seven years after the 2011 restoration and continues to demonstrate that the remediation project was successful at increasing the abundance of high quality brook trout habitat. Sediment deposition continues to raise concerns about the long-term changes to the river's morphology and potential impacts on the restored habitat features. However, the current condition of habitat features is maintained and ongoing monitoring s needed to better understand the long-term implications of fluvial geomorphological process on the overall stream habitat quality to decline. The habitat assessment method developed by Kaurin (2015) was an easy-to-follow system encompassing brook trout habitat characteristics and factors influencing such habitat components. This method is susceptible to assessor bias due to the qualitative nature of the assessment and descriptors used for each habitat condition, leaving the accuracy of this method variable between assessors.


Inequalities in educational opportunity are well documented. Regardless of the nature of the disadvantage—low income, underrepresented minority status, or prior achievement—students from backgrounds associated with a given disadvantage have less access to educational opportunities. In this article, we use data from the 2012 National Survey of Science and Mathematics Education to explore how resources are allocated for science instruction specifically. We focus on how three kinds of resources—well-prepared teachers, material resources, and instruction itself—are allocated to classes that are homogeneously grouped by prior achievement level. Regardless of the resource, we find that classes of students with low prior achievement (as perceived by their teachers) have less access. Some of the differences are striking, particularly regarding access to material resources, while others are more subtle. There is also evidence that some policies do not impact teachers equally. For example, time allowed for teacher professional development is perceived differently by teachers in terms of its impact depending on the achievement level of students in the class. The study supports the assertion that what is known about ability grouping in general applies in science instruction specifically. When students with low prior achievement are grouped together, their classes have less access to critical resources for science learning opportunities, potentially widening the gap between them and their higher-achieving peers.


Boronate esters that contain N-donor groups are self-complementary structures, which can assemble by means of dative boron–nitrogen bonds to form macrocycles or polymers. Herein, we describe the synthesis of dioxaborinanes and benzodioxaboroles containing pyridyl side chains. In the solid state, the dioxaborinanes were found to exist predominantly as monomers. Upon crystallization, aggregation into one-dimensional polymers was observed, but only for boronate esters that contained electron-withdrawing groups. The more Lewis acidic benzodioxaboroles, on the other hand, were found to form macrocycles both in solution and in the solid state.


This book examines Zoombombing, the racist harassment and hate speech on Zoom While most accounts refer to Zoombombing as simply a new style or practice of online trolling and harassment in the wake of increased videoconferencing since the outbreak of COVID-19, this volume examines it as a specifically racialized and gendered phenomenon that targets Black people and communities with racialized and gendered harassment Racist Zoombombing brings together histories of online racism and algorithmic warfare with in-depth interviews by Black users on their experiences The book explains how Zoombombing is a form of racial violence, interrogates our ideas about online space and community, and challenges our notions of on and off line distinction between racial harassment of Black people and communities A vital resource for media, culture, and communication students and scholars that are interested in race, gender, digital media, and digital culture © 2021 Lisa Nakamura, Hanah Stiverson and Kyle Lindsey


ABSTRACT The present study aims to cluster five Asia Pacific destinations (Cambodia, Hong Kong, Indonesia, the Philippines, and Singapore) with respect to other countries according to the evolution of the main tourism and economic indicators over the period between 2000 and 2014. By assigning a numerical value to each country corresponding to its position, we summarize all the information into two components ("tourism expenditure and profitability of tourism activity" and "tourism development and economic growth") using different multivariate techniques for dimensionality reduction. By means of perceptual maps, we find that the five Asia Pacific destinations can be clustered into three different groups: Hong Kong and Singapore, which are the most mature markets; Indonesia and the Philippines, with moderate growth rates in most variables; and Cambodia, with top positions in all variables, showing a huge potential in terms of growth and tourism development and the challenges derived therefrom.


Health differences in social mobility are often analysed by income differences or different occupational positions. However, in early adulthood many young people still have very diffuse income situations and are not always fully integrated into the labour market despite many having finished school. This article focusses on the link between intergenerational educational pathways and self-rated health (SRH) among young adults considering their SRH in adolescence. The data source used is the German KiGGS cohort study. The analysis sample comprises 2175 young people at baseline (t0: 2003–2006 age 14–17) and first follow-up (t1: 2009–2012 age 19–24). Combining parent's and young people's highest school degree, the data can trace patterns of intergenerational educational pathways (constant high level of education, upward mobility, downward mobility, constant low level of education). Young people's SRH was recorded at t0 and t1. During adolescence and young adulthood, participants were less likely to report poor SRH if they had a constant high intergenerational education or if they were upwardly mobile. The differences were particularly striking among young adults: average marginal effects (AME) for poor SRH showed much higher risk among downwardly mobile compared to peers with an intergenerational constant high education (AME: 0.175 [0.099; 0.251]), while the upwardly mobile had a significantly lower risk for less than good SRH than peers with an intergenerational constant low level of education (AME: −0.058 [−0.113; −0.004]). In the context of great societal demands and personal developmental needs, educational differences in health tend to increase in young adulthood. Public Health should pay more attention to educational and health inequalities in young adulthood.


Background and Objectives: Historically marginalized religious and cultural groups are at risk for lower quality of care than majority groups. No study to date specifically queries Muslim experiences with the American health care system (AHCS). We performed a thematic analysis of Muslim parents' interactions with the AHCS and how their background informs their approach to care. Methods: This was a qualitative study of Muslim parents of children with life-limiting conditions in the Research Triangle Area from December 2019 to March 2019. We conducted semistructured interviews with parents to assess their experiences with the AHCS. We probed interview transcripts using descriptive content analysis with NVivo10. Results: We interviewed 10 parents in the Research Triangle Area. All patients were female, most were married, most spoke at least one other language in addition to English, and most were not born in the United States. Several themes emerged highlighting open communication with care teams, willingness to share religious affiliations, and the importance of leaning into faith and accepting God's will. Conclusions: A thematic analysis of Muslim parents' interactions with the AHCS describes value in honest communication, mixed concerns about how providers will react to their religious affiliation, and emphasizes the importance of leaning heavily into faith and accepting God's plan. Future studies evaluating needs of Muslim patients, especially those with different diagnoses, language barriers, and a larger sample size will further delineate needs to minimize inequalities in care.


EXCURSIONS TO CULTURAL CENTRES, such as art museums and galleries, can add new and valuable learning opportunities for young children. This paper presents the findings from a large scale national questionnaire that asked early childhood (EC) teachers in New Zealand about their engagement with art museums and galleries for learning experiences, outside of their EC centres. As part of a mixed methods research project, the questionnaire also sought to ascertain the degree to which the EC sector uses art museums and galleries as excursion destinations, and the ways in which they are used (or not). The findings suggest that key factors that both help and hinder visiting art museums and galleries with young children include: the pedagogical approaches EC teachers have in relation to visual art education, the ways in which teachers view successful learning opportunities for young children, and a teacher's own perceptions and fears of art museums and galleries. This study suggests that teachers have mixed views about whether visiting art museums and galleries will provide appropriate experiences for young children.


Cardiovascular diseases are diseases of the heart and blood vessels constituting a major cause of death and disability worldwide. Cardiovascular drug development aims to deliver efficacious drugs to address the public health burden of cardiovascular diseases. However, the high costs associated with cardiovascular drug development, for example due to long-running clinical trials, sometimes including thousands of patients, place a high burden on the development of new efficacious treatments for cardiovascular diseases. Proposals for improving the efficiency of cardiovascular drug development include better disease characterization, more defined target populations, and the use of adaptive clinical trial designs. This dissertation focuses on adaptive clinical trial designs for cardiovascular research.
Adaptive clinical trial designs, commonly referred to as adaptive designs, are clinical trial designs with a preplanned modification of design aspects, under some constraints such as preserving integrity and validity of the trials, based on interim data of the ongoing trial. Design aspects which are commonly modified include the sample size, number of doses or treatments, or endpoints. Adaptive designs offer flexibility compared to traditional clinical trials with a fixed design to accommodate newly gained information. However, with the flexibility comes an increased statistical complexity, as adaptive designs require an increased effort to control the probability that the clinical trial declares efficacy of an inefficacious treatment, that is the type I error rate, and to plan the number of patients required such that an efficacious treatment is detected with a high statistical power.
The focus of this dissertation is on two types of adaptive designs: group sequential designs and designs with a nuisance parameter based sample size re-estimation. In group sequential designs, the efficacy of a treatment is tested repeatedly during the conduct of the trial and the trial is stopped early if efficacy of the treatment can be shown with statistical significance. Thus, an efficacious treatment can be detected early in clinical trials with a group sequential design. In designs with a nuisance parameter based sample size re-estimation, the final sample size is adjusted using estimates of the potentially several nuisance parameters based on interim data. Nuisance parameters are for example the outcome variance in trials with continuous outcomes and the overall event rate in trials with count outcomes. The nuisance parameter based sample size re-estimation aims to assure that a clinical trial achieves the target power independently of the initially planned sample size.
The first objective of this dissertation is to study group sequential designs with recurrent events, motivated by clinical trials with patients suffering from chronic heart failure. In clinical trials with patients suffering from chronic heart failure, a common clinical relevant recurrent event outcome is the number of heart failure hospitalizations, which can also be part of a composite endpoint in combination with cardiovascular death. To model heart failure hospitalizations and the respective composite, a negative binomial model and a more robust semiparametric model have been proposed in the literature. However, group sequential designs have not been studied for these models. Therefore, I propose statistical methods for planning and analyzing group sequential designs for negative binomial models and more robust semiparametric models and study their asymptotic properties. Moreover, I show that the proposed planning and analysis methods result in an appropriate power and type I error rate, respectively, for parameter combinations common in clinical trials with patients suffering from chronic heart failure. I put a particular focus on the longitudinal nature of the recurrent events, i.e., a single subject can experience new events throughout the trial, and its consequential on the group sequential designs. The longitudinal natures of the outcomes distinguishes group sequential designs with recurrent events from group sequential designs for other common models, such a continuous, binary, or survival data.
A second objective of this dissertation is to study nuisance parameter based sample size re-estimation in three-arm trials with normal outcomes; an investigation motivated by clinical trials with patients suffering from hypertension. A common endpoint in these trials modeled as normally distributed is the change of blood pressure between the baseline measurement and the end of the trial. I show that the ideas for nuisance parameter based sample size re-estimation in two-arm trials can be adapted to three-arm trials and highlight that the corresponding approaches do not result in the desired target power. Furthermore, I modify one of the sample size re-estimation procedures such that it results in appropriately powered three-arm clinical trials.
The third objective of this dissertation is to study incorporating prior information on the variance into the nuisance parameter based sample size re-estimation in two-arm trials with normal outcomes. This objective, too, is motivated by clinical trials with patients suffering from hypertension. I propose several ad hoc rules for incorporating prior information into the sample size re-estimation and by means of Monte Carlo simulation studies I show that the incorporation of prior information can reduce the variability of the final sample size when no prior-data conflict is present. However, I illustrate that in the presence of a prior-data conflict, the designs with a sample size re-estimation incorporating prior information do not convey the target power. I also highlight that common approaches of robustifying the prior information cannot completely mitigate the negative effects of a prior-data conflict without also nullifying the benefits of incorporating prior information on the nuisance parameter into the sample size re-estimation.


ABSTRACTInfluences of globalization are getting felt together with the increasing of variety kinds of information providers in the form of press released or unreleased, broadcast or not broadcast, electronic or not electronic information providers, such as, newspaper, magazine, radio television, facsimiles, computer, internet, communication satellite. Improvement of technology of communication and information inclined to influence the condition of social aspect, economic aspect, culture, and also the condition of education. The applications of communication and information are giving the possibility to create global learning condition which is connected to the link that put students in the central of learning process and surrounded by many kinds of electronic learning source. Base on all of that, conventional education should be softer by accepting new style of learning which is completed by improved technology. We really need human beings, who can get along with the improvement of technology, who have knowledge of tools, source and process where knowledge is put as the central of the soul, comprehended and used in their live to increase the quality of work in the purpose of getting better prosperity in their life. The elements of human which are improved in the aspect of technology are power of thinking, power of heart, and physical power.Keywords: globalization, learning, communication and information technology


In the multidisciplinary field of heart research it is of utmost importance, for the description of phenomena such as mechano-electric feedback or heart wall thickening, to accurately identify the biomechanical properties of the myocardium. Hence, this study aims at determining biaxial tensile and triaxial shear properties of the passive human myocardium. This novel combination of biaxial and shear testing, together with the investigation of the myocardial microstructure, yields new innovative and essential information of the material properties to fulfil the short term goals of constructing realistic myocardial models. Through such modeling efforts, capable to capture the biomechanical behaviour of the heart, it is possible to improve some methods of medical treatment, and hence the quality of life for people suffering from heart diseases - at least as a long-term goal.


While having a wide range of applications, automatic speaker verification (ASV) systems are vulnerable to spoofing attacks, in particular, replay attacks that are effective and easy to implement. Most prior work on detecting replay attacks uses audio from a single acoustic microphone only, leading to difficulties in detecting high-end replay attacks close to indistinguishable from live human speech. In this paper, we study the use of a special body-conducted sensor, throat microphone (TM), for combined voice liveness detection (VLD) and ASV in order to improve both robustness and security of ASV against replay attacks. We first investigate the possibility and methods of attacking a TM-based ASV system, followed by a pilot data collection. Second, we study the use of spectral features for VLD using both single-channel and dual-channel ASV systems. We carry out speaker verification experiments using Gaussian mixture model with universal background model (GMM-UBM) and i-vector based systems on a dataset of 38 speakers collected by us. We have achieved considerable improvement in recognition accuracy, with the use of dual-microphone setup. In experiments with noisy test speech, the false acceptance rate (FAR) of the dual-microphone GMM-UBM based system for recorded speech reduces from 69.69% to 18.75%. The FAR of replay condition further drops to 0% when this dual-channel ASV system is integrated with the new dual-channel voice liveness detector.


In many core architectures, clusters with shared memory banks offer a simple and efficient way (high throughput, low latency) to share and communicate data between close cores. Several recent embedded architectures are using such a design e.g. the MPPA chip from Kalray. Nonetheless, especially in the embedded world, as power consumption is an important preoccupation, shared memory is implemented as a set of single-port memory banks managed by a dedicated controller. As a consequence, some serialization is mandatory for concurrent accesses to banks. This means that memory access-time delays can occur on a regular basis, as each cluster is a multicore system by itself. This paper evaluates on a theoretical basis what kind of tradeoff is made by using such a design with regards to memory access-times and real-time performance: it evaluates the mean access-time with the default configuration of the MPPA chip on a probabilistic formalism, and gives a simplified expression of it. It also gives some typical values for use cases, and discuss the relevance of this design and its limitations with regards to the use of dataflow (CSDF) models of computation.


Introduction: Caffeine citrate is widely used for prevention of apnea of prematurity and helps in successful extubation from mechanical ventilation. The optimum caffeine dose in preterm infants with apnea of prematurity has been extensively investigated with varied results. The objective of our study was to compare the efficacy and safety of once versus twice daily maintenance dose of caffeine citrate in premature infants with apnea. Methods: In this study, preterm neonates with gestational age of 28 to 34 weeks, with evidence of apnea of prematurity were included. Both groups received a 20 mg / kg loading dose of caffeine citrate followed by a maintenance dose of 2.5 mg / kg every 12-hour-interval in group 1 and 5 mg / kg every 24-hour-interval in group 2, either orally or by intravenous infusion. Response to treatment, duration to achieve full feeds, possible adverse reactions were evaluated and compared among the two groups. Results: Among two groups, group 1 had early reduction in number of apneic episodes on five consecutive days after loading dose, which was statistically significant. Time taken to establish full feeds following treatment initiation was lower in group 1 compared to group 2 (median: Two vs four days) which was statistically significant. Conclusions : In this study, neonates who received twice daily maintenance dose of caffeine citrate had better outcomes in terms of early reduction in number of apneic episodes and early feed establishment when compared to those receiving once daily maintenance dose of caffeine citrate. Abstract


KRAS-PDEδ protein-protein interaction represents an appealing target for cancer therapy. However, fast release of high-affinity inhibitors from PDEδ hampered drug binding affinity and antiproliferative activity. To overcome the limitations, the first proteolysis-targeting chimeric (PROTAC) small molecules targeting PDEδ were designed. Employing PDEδ inhibitor deltazinone (2) and cereblon ligand pomalidomide (6), a series of potent PROTAC PDEδ degraders were obtained. The most promising compound 17f efficiently induced PDEδ degradation and demonstrated significantly improved antiproliferative potency in KRAS mutant SW480 cells. Compound 17f also achieved significant tumor growth inhibition in the SW480 colorectal cancer xenograft model. This proof-of-concept study provided a new strategy to validate the druggability of KRAS-PDEδ interaction and offered an effective lead compound for the treatment of KRAS mutant cancer.


Abstract The directed preferential attachment model is revisited. A new exact characterization of the limiting in- and out-degree distribution is given by two independent pure birth processes that are observed at a common exponentially distributed time T (thus creating dependence between in- and out-degree). The characterization gives an explicit form for the joint degree distribution, and this confirms previously derived tail probabilities for the two marginal degree distributions. The new characterization is also used to obtain an explicit expression for tail probabilities in which both degrees are large. A new generalized directed preferential attachment model is then defined and analyzed using similar methods. The two extensions, motivated by empirical evidence, are to allow double-directed (i.e. undirected) edges in the network, and to allow the probability of connecting an ingoing (outgoing) edge to a specified node to also depend on the out-degree (in-degree) of that node.


Since the occurrence of the 2008 Wenchuan earthquake ( M s8.0), many researchers have conducted extensive seismological and geophysical observations and investigations and obtained important results about the Longmenshan fault zone. Crustal structure inferred from local tomography shows that seismic velocity exhibits significant changes across the Wenchuan earthquake hypocenter from the south to the north. To the south,obvious low-velocity (low-V) anomalies exist, whereas strong lateral heterogeneities are revealed to the north, which may explain why the aftershocks extend northeastward. The Wenchuan earthquake occurred at the boundary between high-velocity (high-V) and low-V anomalies and a significant low-V zone is revealed below the mainshock hypocenter, suggesting that the nucleation of the Wenchuan earthquake was related to partial melts and/or fluid effects and associated with the reduction of effective normal stress on the fault plane, due to hightemperature and highpressure in the Longmenshan fault zone caused by the India-Asia collision. The upper-mantle structure inferred from teleseismic tomography shows that the Longmenshan fault zone is located in the transition zone from low-V anomalies beneath the Songpan-Ganzi block to high-V anomalies beneath the Sichuan basin. This structural feature extends down to 200−300 km depths. High-V anomalies in the mantle transition zone are connected with those in the upper mantle beneath the Burma arc, indicating that the Wenchuan earthquake could be associated with upwelling of hot and wet materials in the big mantle wedge formed by the deep subduction of the Indian plate. These results suggest that the generation of the Wenchuan earthquake was related to structural heterogeneities in not only the crust but also the upper mantle. In addition,high-poisson's ratio and high-conductivity anomalies are revealed beneath the Wenchuan earthquake source area, which may also reflect lower crustal flow that is compressed and moving eastward. When the eastward flow encountered the strong Sichuan basin block around the Longmenshan fault zone, the flow is further compressed upward along the margin of the Sichuan basin, which could have caused the fault ruptureand generated the Wenchuan earthquake. Some geologists found a vertical co-seismic displacement of 6.5 m in the Longmenshan fault zone, suggesting that there exists an imbricate structure due to the crustal shortening. Such a shortening mechanism could rupture the seismogenic fault leading to the large earthquake. The Zipingpu reservoir is located very close to the Wenchuan earthquake epicenter. It is still debated whether the reservoir triggered the 2008 Wenchuan earthquake or not. Although some simulation results suggest that the Wenchuan earthquake could be triggered by the reservoir, there are large differences in the estimated stress in the hypocentral area due to large uncertainties of the physical parameters adopted in the numerical simulations. Hence, the physical parameters should be determined precisely in future investigations so as to clarify the effect of the reservoir on the seismogenesis. We also discuss the causal mechanism of the 2013 Lushan earthquake ( M s7.0) and future seismic risk in the gap between the aftershock zones of the Wenchuan and Lushan earthquakes.


Granulocyte transfusion is uncommon but essential for some aplastic patients with major infection and those with septic granulomatosis disease and visceral aspergillosis. Compatibility between donor and recipient (ABO, D, Kell blood type, cytomegalovirus) is necessary. Stimulation by dexamethasone, before use of GCSF, permits to obtain approximately 10 x 10(9) white cells per l. Doses of heparin must be calculated to ensure an efficient hypocoagulation without any trouble for the donor immediately after his donation. Sedimentation by hydroxyethylstarch is an unavoidable element to obtain the most efficient separation of granulocytes. Most donations present an amount of white cells between 2 and 4 10 x 10(10). This enables to transfuse efficiently children and adults.


BACKGROUND
To measure and evaluate the legibility of a sample of informative leaflets about common drugs.

METHODS
A descriptive cross-sectional study was performed, using a representative sample of package leaflets corresponding to the 30 most widely consumed drugs in Spain. The Flesch-Szigriszt Index was used as a measuring tool and the INFLESZ score to evaluate the legibility of leaflets of medicinal products. Documents with a Flesch-Szigriszt Index value ≥55 were considered legible.

RESULTS
The mean Flesch-Szigriszt Index value was 52.62 (standard deviation: 4.67). This score is classified as "a bit difficult" on the INFLESZ score. Only 10 of 30 leaflets obtained an acceptable level of legibility. The sections of the leaflets with higher grammatical complexity were "what it is and what it is used for" (indications), "before taking the medication" (contraindications) and "adverse effects".

CONCLUSIONS
The legibility of the package leaflets analyzed could be improved: grammatical structures are usually convoluted, and their comprehension by ordinary citizens belonging to the general public is difficult. The involvement of health care professionals in resolving doubts and giving information to users about the consumption of drugs may be essential for a correct treatment.


Micro-sized spherical Al particles have recently attracted interest for the development of a new concept for coatings based on their capability to form hollow alumina spheres and aluminized diffusion zones in the substrate. For understanding better their oxidation behaviour, spherical µm-Al particles with different sizes were oxidized in air on heating up to 1300°C and under isothermal conditions at 800°C and 850°C. The oxide formation was studied in situ by high temperature X-ray diffraction and the oxidised particles were analysed by scanning electron microscopy. On heating the µm-Al particles begin to form a g-Al2O3 scale before reaching the melting point and the molten Al is kept within the g-Al2O3 shell. On further heating q-Al2O3 is detected, which forms simultaneously with the g-Al2O3. The g-Al2O3 / q-Al2O3 scale is stable and protective under isothermal conditions up to 800°C within the investigated times. On further heating the g-Al2O3 and q-Al2O3 transform simultaneously to a-Al2O3 in a temperature range of 850°C to 1100°C. Under isothermal conditions the g à a-Al2O3 transformation is observed after 160 min at 850°C. During the g à a-Al2O3 transformation shrinkage occurs that leads to formation of pores. A model is proposed describing the mechanism that leads to the formation of the observed whiskers morphologies during the g à a-Al2O3 transformation.


The application of a new technique for sound-scene analysis to the segmentation of complex musical signals is presented. This technique operates by discovering common modulation behavior among groups of frequency subbands in the autocorrelogram domain. The algorithm can be demonstrated to locate perceptual events in time and frequency when it is executed on ecological music examples taken directly from compact disc recordings. It operates within a strict probabilistic framework, which makes it convenient to incorporate into a larger signal-understanding testbed. Only within-channel dynamic signal behavior is used to locate events; therefore, the model stands as a theoretical alternative to methods that use pitch as their primary grouping cue. This segmentation algorithm is one processing element to be included in the construction of music perception systems that understand sound without attempting to separate it into components.


In the grammar of Java is much to be learned include Javanese, Tembung, Ater-atr Seselan Panambangan, Homonin, antonyms, synonyms, Ukara, Proverb Java, Purwakanthi, Song, Gendhing and Karawitan, Fiber, Babad, puppets and much more. At this time only a few children who are familiar with the Java language's grammar. This is usually because the very basis of the delivery of material that is less attractive so that children feel bored quickly. Advances in technology today, perceived benefits in various fields, such as creating a media that can facilitate the child in learning something. In general, media that can be used to learn the language of children, visual media and audio media. Kids learn about the environment and absorbing knowledge through what is seen and heard, so that the sense of sight and hearing is the gateway entrance of science into the child. To more easily learn the Java language, can be made a apliksai to learn the Java language-based multimedia. One of the Java grammar that will be created apliksinya is Macapat song. The purpose of this study was to design and to design an instructional media to learn the song Macapat. This research is expected to facilitate the children in the study of grammar Java one of which is the song Macapat. Keyword : Javanese grammar , song Macapat, Learning Media, Multimed ia.


Vibriosis is an important disease of farmed and wild fish, caused by species of the genus Vibrio. During December 2000, high mortalities were observed in a wild population of big scale sand smelt Atherina boyeri in Limnos, Greece. The microbiological analysis of the moribund fish resulted in the isolation of a pure culture of Vibrio anguillarum. The bacterium was identified by bacteriological procedures and slide agglutination reaction. Focal or more extensive necrosis was found in almost all organs, in all fish examined and the retina of the eyes appeared corrugated. The pathogenicity of the strain for sea bass was confirmed by bath challenge causing mortalities up to 97%. Factors contributing to the outbreak of the disease were considered to be the presence of parasites (Platyhelminthes) in the intestinal tract. No simultaneous infection at a fish farm in the vicinity had been reported. However, since there are disease interactions between wild and cultured fish, infected wild fish, can act as a reservoir of the pathogen.


Ganesh is a popular deity all over India, invoked before all Hindu ceremonies as the Lord of Beginnings and Remover of Obstacles (Vighnaharta). His close association with Mumbai is well attested through the Ganapati Utsav, the Ganesh festival, not least because images of his immersion in the sea against a backdrop of skyscrapers have become a visual cliche about the paradox of the modern and the traditional in today's India. But while this form of Ganesh is a temporary visitor to the city, Ganesh as Siddhivinayak has become perhaps the most visible deity in the city with a large new temple built during the period when the name of the city, Bombay, was changed to the local version of the city's name, said to derive from the goddess Mumba Devi. The article looks at a devotional film about Siddhivinayak, produced in cooperation with the shrine, to see how Ganesh is understood today by the way the shrine tells the story of the deity and his devotees.


Background The goal of virtual elimination of horizontal and mother-to-child HIV transmission in South Africa (SA) has been proposed, but there have been few systematic investigations of which interventions are likely to be most critical to reducing HIV incidence. Objective This study aims to evaluate SA's potential to achieve virtual elimination targets and to identify which interventions will be most critical to achieving HIV incidence reductions. Design A mathematical model was developed to simulate the population-level impact of different HIV interventions in SA. Probability distributions were specified to represent uncertainty around 32 epidemiological parameters that could be influenced by interventions, and correlation coefficients (r) were calculated to assess the sensitivity of the adult HIV incidence rates and mother-to-child transmission rates (2015-2035) to each epidemiological parameter. Results HIV incidence in SA adults (ages 15-49) is expected to decline from 1.4% in 2011-2012 to 0.29% by 2035 (95% CI: 0.10-0.62%). The parameters most strongly correlated with future adult HIV incidence are the rate of viral suppression after initiating antiretroviral treatment (ART) (r=-0.56), the level of condom use in non-marital relationships (r=-0.40), the phase-in of intensified risk-reduction counselling for HIV-positive adults (r=0.29), the uptake of medical male circumcision (r=-0.24) and the phase-in of universal ART eligibility (r=0.22). The paediatric HIV parameters most strongly associated with mother-to-child transmission rates are the relative risk of transmission through breastfeeding when the mother is receiving ART (r=0.70) and the rate of ART initiation during pregnancy (r=-0.16). Conclusions The virtual elimination target of a 0.1% incidence rate in adults will be difficult to achieve. Interventions that address the infectiousness of patients after ART initiation will be particularly critical to achieving long-term HIV incidence declines in South Africa.


We propose a formalisation of spiking neural networks based on timed automata networks. Neurons are modelled as timed automata waiting for inputs on a number of different channels (synapses), for a given amount of time (the accumulation period). When this period is over, the current potential value is computed taking into account the current inputs and the previous decayed potential value. If the current potential overcomes a given threshold, the automaton emits a broadcast signal over its output channel, otherwise it restarts another accumulation period. After each emission, the automaton is constrained to remain inactive for a fixed refractory period. Spiking neural networks are formalised as sets of automata, one for each neuron, running in parallel and sharing channels according to the structure of the network. The model is then validated against some crucial properties defined via proper temporal logic formulae.


Objectives To examine the effectiveness of primary implantable cardioverter defibrillators (ICDs) in elderly patients receiving the device during a hospital admission for exacerbation of heart failure or other acute co-morbidities, with an emphasis on adjustment for early mortality and other factors reflecting healthy candidate bias rather than the effect of the ICD. Design Retrospective cohort study. Setting Linked data from the Centers for Medicare and Medicaid Services and American College of Cardiology-National Cardiovascular Data Registry ICD registry, nationwide heart failure registry, and Medicare claims data 2004-09. Population 23 111 patients aged ≥66 who were admitted to hospital for exacerbation of heart failure or other acute co-morbidities and eligible for primary ICDs. Main outcome measures All cause mortality and sudden cardiac death. Latency analyses with Cox regression were used to derive crude hazard ratios and hazard ratios adjusted for high dimension propensity score for outcomes after 180 days from index implantation or discharge. Results Patients who received an ICD during a hospital admission had lower crude mortality risk than patients who did not receive an ICD (40% v 60% at three years); however, with conditioning on 180 day survival and with adjustment for high dimension propensity score, the apparent benefit with ICD was no longer evident for sudden cardiac death (adjusted hazard ratio 0.95, 95% confidence interval 0.78 to 1.17) and had a diminished impact on total mortality (0.91, 0.82 to 1.00). There were trends towards a benefit with ICD in reducing mortality or sudden cardiac death in patients who had had a myocardial infarction more than 40 days previously, left bundle branch block, or low serum B type natriuretic peptide; however, these trends did not reach significance. Conclusion After adjustment for healthy candidate bias and confounding, the benefits of primary ICD therapy seen in pivotal trials were not apparent in patients aged 66 or over who received ICDs during a hospital admission for exacerbation of heart failure or other acute co-morbidities. Future research is warranted to further identify subgroups of elderly patients who are more likely to benefit from ICDs. Recognition of those patients whose dominant risk factors are from decompensated heart failure and non-cardiac co-morbidities will allow better focus on ICDs in those patients for whom the device offers the most benefit and provides meaningful prolonging of life.


This report describes the reliability, validity, treatment sensitivity, diagnostic performance and normative values for the Short Post-Traumatic Stress Disorder (PTSD) Rating Interview (SPRINT), a brief, global assessment for PTSD. The SPRINT was administered to subjects participating in a clinical trial of PTSD and in a population survey assessing PTSD prevalence. The 8-item SPRINT includes questions assessing the core symptoms of PTSD, as well as related aspects of somatic malaise, stress vulnerability and functional impairment. Validity was assessed against the MINI structured interview, the Davidson Trauma Scale, Treatment Outcome for PTSD Scale, Connor-Davidson Resilience Scale, Sheehan Stress Vulnerability Scale, Sheehan Disability Scale and Clinical Global Impressions of Severity and Improvement Scales. Good test-retest reliability, internal consistency, convergent and divergent validity were obtained. The SPRINT was responsive to symptom change over time and correlated with comparable PTSD symptom measures. In victims of trauma, a score of 14-17 was associated with 96% diagnostic accuracy, whereas in those with PTSD, highest efficiency corresponded to a range of 11-13. The SPRINT demonstrates solid psychometric properties and can serve as a reliable, valid and homogeneous measure of PTSD illness severity and of global improvement.


We examine the relation between the fees paid to auditors for audit and non‐audit services, and the choice of accrual measures for a large sample of firms. Using our pooled sample, we find that the ratio of non‐audit fees to total fees has a positive relation with the absolute value of accruals similar to Frankel, Johnson, and Nelson [2002]. However, using latent class mixture models to identify clusters of firms with a homogenous regression structure reveals that this positive association only occurs for about 8.5% of the sample. In contrast to the fee ratio results, we find consistent evidence of a negative relation between the level of fees (both audit and non‐audit) paid to auditors and accruals (i.e., higher fees are associated with smaller accruals). The latent class analysis also indicates that this negative relation is strongest for client firms with weak governance. Overall, our results are most consistent with auditor behavior being constrained by the reputation effects associated with allowing clients to engage in unusual accrual choices.


Sb2Te3 thin films with thickness of 70, 100, 300, and 600nm were co-evaporated by vacuum evaporation. These films were annealed by 423K, 473K, 523K and 573K, respectively, in the protection of N2 ambient. After that, the film structures were investigated by XRD. Composition of the films was surveyed XRF and XPS. Stoichiometric Sb2Te3 thin films were prepared. Then the Sb2Te3 thin films were applied to CdTe thin film solar cells as back contact layer. The influence of Sb2Te3 thin films thickness on the performances of CdS/CdTe thin film solar cells were surveyed by light I-V characteristics and an efficiency of 12.27%, Voc=808.2mV, Jsc=25.1mA/cm2, FF= 0.6051 was obtained.


By using two ultrarapid freezing techniques, we have captured the structure of rat and rabbit cardiac gap junctions in a condition closer to that existing in vivo than to that previously achieved. Our results, which include those from fully functional hearts frozen in situ in the living animal, show that the junctions characteristically consist of multiple small hexagonal arrays of connexons. In tissue frozen 10 min after animal death, however, unordered arrays are common. Examination of junction structure at intervals up to 40 min after death reveals a variety of configurations including dispersed and close-packed unordered arrays, and hexagonal arrays. By use of an isolated intercalated disk preparation, we show that the configuration of cardiac gap junctions in vitro cannot be altered by factors normally considered to induce functional uncoupling. These experiments demonstrate that, contrary to the conclusions of some earlier studies (Baldwin, K. M., 1979, J. Cell Biol., 82:66-75; Peracchia, C., and L. L. Peracchia, 1980, J. Cell Biol., 87:708-718), the arrangement of gap junction connexons, in cardiac tissue at least, cannot be used as a reliable guide to the functional state of the junctions.


Ultraviolet emission characteristics of cubic (c-) GaN enabled through hexagonal-to-cubic phase transition are reported. Substrate patterning and material growth are shown to affect phase purity and emission characteristics of c-GaN as studied by electron backscatter diffraction, and photo- and cathodoluminescence, respectively. Raman study shows a tensile strain in the c-GaN. Time-resolved photoluminescence reveals c-GaN band edge emission decay time of 11 ps. The ultraviolet emissions from both phases of GaN are linearly polarized in the same direction, which is along the ⟨112̅0⟩ and ⟨110⟩ directions of hexagonal GaN and c-GaN, respectively. Temperature-dependent (5.7 to 280 K) cathodoluminescence studies reveal an internal quantum efficiency of ~29% at room temperature along with intrinsic and extrinsic defect energy levels of ~124 and ~344 meV, respectively, of the phase-transition c-GaN. Using the IQE value and carrier decay lifetime, a radiative lifetime of 38 ps is extracted. Overall, photonic properties of phase-transition c-GaN and their dependence on substrate patterning and material growth are reported.


Contemporary research on 'lesbian families' tends to portray them as progressive examples of non-nuclear parenting that challenge traditional kinship formation. In contrast my data revealed that, in many instances, it remains the 'birth mother' who is figuratively and literally left 'holding the baby', and traditional understandings and experiences of family persist. This article calls into question the representativeness of radical models and addresses the differences between research findings on lesbian parent families. Rather than contest the accuracy of others' research, I argue that the reasons for differences between analyses can be found in the research process. Thus I query the epistemological and methodological foundations of radical research into lesbian parent families.


A comparative study of the girder damage identification of Jintang Cable-stayed Bridge in Zhoushan Island-Land Project using the deflection index, the cable tension index, the beam bottom bending stress index, the modal curvature index and the modal flexibility matrix is introduced. By means of finite element method, a series of damage cases associated with the box girder are analyzed. The result shows that, for different damage types, the best effect of the girder damage identification is the modal curvature index, followed by the cable tension index, the beam bottom bending stress index is nearly of the same effect as the modal flexibility matrix index, and the worst is the deflection index.


A rapidly growing body of research suggests that meditation can change brain and cognitive functioning. Yet little is known about the neurochemical mechanisms underlying meditation-related changes in cognition. Here, we investigated the effects of meditation on spontaneous eyeblink rates (sEBR), a noninvasive peripheral correlate of striatal dopamine activity. Previous studies have shown a relationship between sEBR and cognitive functions such as mind wandering, cognitive flexibility, and attention-functions that are also affected by meditation. We therefore expected that long-term meditation practice would alter eyeblink activity. To test this, we recorded baseline sEBR and intereyeblink intervals (IEBI) in long-term meditators (LTM) and meditation-naive participants (MNP). We found that LTM not only blinked less frequently, but also showed a different eyeblink pattern than MNP. This pattern had good to high degree of consistency over three time points. Moreover, we examined the effects of an 8-week course of mindfulness-based stress reduction on sEBR and IEBI, compared to an active control group and a waitlist control group. No effect of short-term meditation practice was found. Finally, we investigated whether different types of meditation differentially alter eyeblink activity by measuring sEBR and IEBI after a full day of two kinds of meditation practices in the LTM. No effect of meditation type was found. Taken together, these findings may suggest either that individual difference in dopaminergic neurotransmission is a self-selection factor for meditation practice, or that long-term, but not short-term meditation practice induces stable changes in baseline striatal dopaminergic functioning.


The focus of my PhD research was the concept of modularity. In the last 15 years, modularity has become a classic term in different fields of biology. On the conceptual level, a module is a set of interacting elements that remain mostly independent from the elements outside of the module. I used modular analysis techniques to study gene expression evolution in vertebrates. In particular, I identified ``natural'' modules of gene expression in mouse and human, and I showed that expression of organ-specific and system-specific genes tends to be conserved between such distance vertebrates as mammals and fishes. Also with a modular approach, I studied patterns of developmental constraints on transcriptome evolution. I showed that none of the two commonly accepted models of the evolution of embryonic development (``evo-devo'') are exclusively valid. In particular, I found that the conservation of the sequences of regulatory regions is highest during mid-development of zebrafish, and thus it supports the ``hourglass model''. In contrast, events of gene duplication and new gene introduction are most rare in early development, which supports the ``early conservation model''. In addition to the biological insights on transcriptome evolution, I have also discussed in detail the advantages of modular approaches in large-scale data analysis. Moreover, I re-analyzed several studies (published in high-ranking journals), and showed that their conclusions do not hold out under a detailed analysis. This demonstrates that complex analysis of high-throughput data requires a co-operation between biologists, bioinformaticians, and statisticians.


A series of new coordination complexes of CuII, CoII, NiII, ZnII, CdII, and HgII with the Schiff base 3-chloro-N-(1E)-(2-hydroxy quinoline-3-yl]methylene)- 1-benzo(b)thiophene-2-carbohydrazide have been synthesized and characterized by elemental analysis, electrical conductivitymeasurements, IRspectra, electronic spectra, ESRspectra,magnetic susceptibility, TGAandmass spectral data. The Schiff base behaves as tridentate ONO donor ligand and forms the complexes of the type ML stoichiometry.All the complexes are colored and non electrolytes. It is found that CuII, CoII, NiII, ZnII, CdII, and HgII complexes have exhibited octahedral geometry. The ligand and its metal complexes have been screened for their antibacterial activity against E. coli, S. aureus and antifungal activity against, A. niger and C. albicans.


Background Cough variant Asthma (CVA) is defined as chronic cough without wheezing, and may be precursor of typical asthma. Thus, the diagnosis of CVA and early intervention can partly inhibit asthma progression.This study aimed to evaluate the role of spirometry in diagniosis of Cough variant Asthma in Iranian Children. Materials and Methods This descriptive observational study included a total of 73 patients, who were referred to the specialized lung clinic of Tabriz Pediatric Center, Tabriz city, Iran. Patients were divided into two groups with classic asthma (n=37) and cough variant asthma (n=36) and basic spirometry parameters such as FEV1, FVC, FEV1/FVC, FEF 25-75% and PEF were measured, and the spirometry findings of each individual were measured based on the European Respiratory Society (ERS) criteria. Results The mean of FEV1 and FVC in the classic asthma group were 83.45 ± 20.49% and 86.45 ± 21.57%, respectively; and in the cough variant asthma group were 87.44 ± 13.99% and 86.8 ± 14.71%, respectively. There was no significant difference between the two groups for the basic spirometry parameters of FEV1 and FVC (p=0.343, P=0.916; respectively). The average FEV1/FVC parameter in the cough variant asthma group was 89.44±13.07, but it was 72.35±8.47 in the classic asthma group, with a significant difference between the two groups (p<0.05). Conclusion There was a significant difference in the FEV1 / FVC value between two groups of cough and classic asthma. Spirometry of patients with cough variant asthma showed the FEF values (25 -75%) were lower than expected; we suggest using spirometry in the diagnosis of cough variant asthma considering small airways changes.


Driver distraction has been defined in many different ways. The most important difference is whether only visual inattention or also cognitive inattention should be included. Many different methods have been used to assess the prevalence and types of driver distraction that occur, and to describe the consequences in terms of driving performance and crash involvement. There is strong agreement that distraction is detrimental for driving, and that the risk for crashes increases. Drivers rather opt for repeated glances instead of extending one single glance, if the secondary task demands attention for a longer period of time. However, repeated glances have more detrimental effects on driving performance than a single glance of the same duration as one of the repeated glances. Only recently the method of remote eye tracking has emerged, which enables real time identification of visual distraction. So far this method has mostly been used in driving simulators. Different algorithms that diagnose distracted drivers have been tested with promising results. In simulators it is difficult, however, to induce true distraction, due to the short duration of the experiment and the artificial setting. A prolonged field study under naturalistic conditions could provide new insights and validation of simulator studies.


In this paper we extend the notion of multi-unit combinatorial reverse auction by adding a new dimension to the goods at auction. In such a new type of combinatorial auction a buyer can express substitutability relationships among goods: some goods can be substituted with others at a substitution cost. Substitutability relationships allow a buyer to introduce his uncertainty as to whether it is more convenient to buy some goods or others. We introduce such uncertainty in the winner determination problem (WDP) so that not only does the auction help allocate the optimal set of offers ---taking into account substitutability relationships---, but also assesses the substitutability relationships that apply. In this way, the buyer finds out what goods to buy, to whom, and what operations (substitutions) to apply to the acquired goods in order to obtain the initially required ones.


Empirical techniques adapted from ecosystem-resilience theory allow estimation of how public health and public order within the New York Metropolitan Region respond to perturbations driven by changes in policy or economic structure. This approach constitutes a rigorous methodology for health-impact assessment, providing a quantitative measure of the stability of the region. Contrary to entrenched cultural assumption, affluent suburban counties and impoverished central-city neighborhoods remain strongly linked through a probability-of-contact matrix well indexed by the daily journey to work. The public-health ecology of the New York Metropolitan Region is remarkably unstable, greatly amplifying perturbations through mechanisms analogous to positive feedback in mechanical systems, with the single greatest influence being the percentage of the population living in poverty. Given the New York region's overwhelming dominance of national patterns for the hierarchical diffusion of disease and disorder this result has significant policy implication. More explicitly, lowering the rate of poverty in and near New York City would markedly reduce the vulnerability of the United States to emerging infection.


Background: Near-infrared spectroscopy (NIRS) has recognized potential but limited application for non-invasive di- agnostic evaluation. Data analysis methodology that reproducibly distinguishes between the presence or absence of physiologic abnormality could broaden clinical application of this optical technique. Methods: Sample data sets from simultaneous NIRS bladder monitoring and invasive urodynamic pressure-flow studies (UDS) are used to illustrate how a diagnostic algorithm is constructed using classification and regression tree (CART) analysis. Misclassification errors of CART and linear discriminant analysis (LDA) are computed and examples of other urological NIRS data likely amenable to CART analysis presented. Results: CART generated a clinically relevant classification algorithm (error 4%) using 46 data sets of changes in chro- mophore concentration composed of the whole time series without specifying features. LDA did not (error 16%). Using CART NIRS data provided comparable discriminant ability to the UDS diagnostic nomogram for the presence or absence of ob- structive pathology (88% specificity, 84% precision). Pilot data examples from children with and without voiding dysfunction and women with mild or severe pelvic floor muscle dysfunction also show potentially diagnostic differences in chromophore concentration. Conclusions: CART analysis can likely be applied in other NIRS monitoring applications intended to classify patients into those with and without pathology.


An update of the systematic review of evidence on the association between amount of sugars intake and dental caries, as well as on the effect of restricting sugars intake to <10% and <5% energy (E) on caries, was conducted, almost 10 y since the review that informed the World Health Organization (WHO) Guideline on Sugars. The aim was to systematically review epidemiological data published from 2011 to 2020 on the amount of sugars consumption and levels of caries and to report the findings for adults and children. Data sources included MEDLINE, EMBASE, Cochrane Database, Cochrane Central Register of Controlled Trials, Latin American and Caribbean Health Sciences, China National Knowledge Infrastructure, Scopus, and Google Scholar. Eligible studies reported the amount of sugars and caries, measured as prevalence, incidence, or severity. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Risk of bias was assessed using the Office of Health Assessment and Translation tool. Vote counting and harvest plots provided the basis for evidence synthesis. From 488 new papers identified, 23 studies were eligible: 4 cohort, 1 case-controlled, 12 cross-sectional, and 6 ecological. Eleven of 15 studies in children and 6 of 8 studies in adults reported at least 1 positive association between sugars and caries. Six of 7 studies in children and 4 of 4 studies in adults, with data enabling comparison of caries levels with sugars intakes >10%E and <10%E, showed lower caries when sugars intake was <10%E. Amalgamating with original studies yielded 64 of 78 studies showing at least 1 positive association, 20 of 78 a null association, and 3 of 78 a negative association between sugars and caries. GRADE profiles of new and original cohort data confirmed "moderate-quality" evidence that caries is lower when sugars intake is <10%E. Furthermore, new cohort data upgraded the quality of evidence (from "very low" to "low") for lower caries when free sugars are <5%E. The findings support and strengthen original evidence underpinning the WHO recommendations for sugars.


Physical models are invaluable aids for conveying concepts in geometry, particularly concepts about polyhedra. In this paper physical polygons, polygon corners, polygon flat regions, polygon cylinders, polygon nets and polyhedra are all used to show a physical proof that there are five, and only five regular solids. Students from grade school, high school, undergraduate and graduate levels have been presented with this physical proof, and all of them have taken away something worthwhile related to their existing level of knowledge.


Background Multimorbidity receives increasing scientific attention. So does the detrimental health impact of adverse childhood experiences (ACE). Aetiological pathways from ACE to complex disease burdens are under investigation. In this context, the concept of allostatic overload is relevant, denoting the link between chronic detrimental stress, widespread biological perturbations and disease development. This study aimed to explore associations between self-reported childhood quality, biological perturbations and multimorbidity in adulthood. Materials and Methods We included 37 612 participants, 30–69 years, from the Nord-Trøndelag Health Study, HUNT3 (2006–8). Twenty one chronic diseases, twelve biological parameters associated with allostatic load and four behavioural factors were analysed. Participants were categorised according to the self-reported quality of their childhood, as reflected in one question, alternatives ranging from 'very good' to 'very difficult'. The association between childhood quality, behavioural patterns, allostatic load and multimorbidity was compared between groups. Results Overall, 85.4% of participants reported a 'good' or 'very good' childhood; 10.6% average, 3.3% 'difficult' and 0.8% 'very difficult'. Childhood difficulties were reported more often among women, smokers, individuals with sleep problems, less physical activity and lower education. In total, 44.8% of participants with a very good childhood had multimorbidity compared to 77.1% of those with a very difficult childhood (Odds ratio: 5.08; 95% CI: 3.63–7.11). Prevalences of individual diseases also differed significantly according to childhood quality; all but two (cancer and hypertension) showed a significantly higher prevalence (p<0.05) as childhood was categorised as more difficult. Eight of the 12 allostatic parameters differed significantly between childhood groups. Conclusions We found a general, graded association between self-reported childhood difficulties on the one hand and multimorbidity, individual disease burden and biological perturbations on the other. The finding is in accordance with previous research which conceptualises allostatic overload as an important route by which childhood adversities become biologically embodied.


This paper proposes a real-time decentralized control algorithm in multi-area active distribution network relying only on dispersed battery energy storage systems (BESSs). In particular, we propose a zonal control strategy targeting voltage support and line congestion management. The proposed zonal control relies on an accurate dynamic model of BESSs capable to account for their dc active power limits. The communication among different areas is defined using the concept of multi-agents. The effectiveness of the proposed zonal control is assessed and compared to the equivalent centralized control problem using a test case composed by the IEEE 13 nodes distribution test feeders suitably adapted to include stochastic generation and BESSs.


Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA

Prostate Cancer (PCa) is the second leading cause of cancer death in American men.

The inflammatory tumor microenvironment is a fertile niche that releases reactive oxygen species, which accelerates the malignant transformation and appears as a fine tuner of the adhesive behavior of cells. Heme oxygenase 1 (HO-1), the rate-limiting enzyme in heme degradation, represents an essential event in cellular responses to pro-oxidative and pro-inflammatory insults. As we previously reported that HO-1 over-expression impaired tumor growth and angiogenesis in vivo we sought to assess whether HO-1 could regulate the adhesive properties and the morphology of PCa cells. A bioinformatics enrichment analysis using Metacore, GeneMANIA and DAVID was performed; rendering a significant association of the HO-1 regulated genes with several proteins located in the extracellular space and cell membrane; compartments highly correlated with the adhesive behavior of cells. In an effort to understand the molecular mechanisms underlying HO-1's role in cell morphology regulation we used a proteomics approach to identify HO-1 partners. We performed GST-pull-down assays using lysates from PC3 cells transfected with either GST-tagged HO-1 or the empty vector, and the isolated proteins were subjected to MALDI-TOF/TOF analyses.

Our results showed that HO-1 interacts with Muskelin, a nucleocytoplasmic mediator of cellular morphology and adhesiveness. Up-regulation of Muskelin under HO-1 induction in PCa cells was confirmed by confocal microscopy. A high degree of nuclear overlay between HO-1 and Muskelin signals was observed when cells were exposed to hemin, a potent specific inducer of HO-1 or genetically manipulated to over-express HO-1, compared to controls. Interestingly after HO-1 induction, both protein exhibit similar sub-cellular dynamics, relocating from the cell membrane, towards the cell nuclei. Altogether, we have shown for the first time that HO-1 binds and up-regulates Muskelin, a specific factor involved in shaping cellular morphology and adhesive properties, favoring a less aggressive phenotype and further supporting the anti-tumoral function of HO-1in PCa.

Citation Format: Geraldine Gueron, Jimena Giudice, Alejandra Paez, Pia Valacco, Noelia Carabelos, Federico Schuster, Javier Cotignola, Felipe Jaworski, Daiana Leonardi, Maria Binaghi, Marcelo Marti, Nora Navone, Elba Vazquez. Unveiling the molecular significance of HO-1 and muskelin interaction: two masterminds behind the morphology and the adhesive behavior of prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-43. doi:10.1158/1538-7445.AM2014-LB-43


Current large-scale implementations of deep learning and data mining require thousands of processors, massive amounts of off-chip memory, and consume gigajoules of energy. New memory technologies, such as nanoscale two-terminal resistive switching memory devices, offer a compact, scalable, and low-power alternative that permits on-chip colocated processing and memory in fine-grain distributed parallel architecture. Here, we report the first use of resistive memory devices for implementing and training a restricted Boltzmann machine (RBM), a generative probabilistic graphical model as a key component for unsupervised learning in deep networks. We experimentally demonstrate a 45-synapse RBM realized with 90 resistive phase change memory (PCM) elements trained with a bioinspired variant of the contrastive divergence algorithm, implementing Hebbian and anti-Hebbian weight updates. The resistive PCM devices show a twofold to tenfold reduction in error rate in a missing pixel pattern completion task trained over 30 epochs, compared with untrained case. Measured programming energy consumption is 6.1 nJ per epoch with the PCM devices, a factor of ~ 150 times lower than the conventional processor-memory systems. We analyze and discuss the dependence of learning performance on cycle-to-cycle variations and number of gradual levels in the PCM analog memory devices.


The biopharmaceutical industry increasingly demands thorough characterization of protein conformation and conformational dynamics to ensure product quality and consistency. Here, we present a chromatography-based method that is able to characterize protein conformation and conformational dynamics at peptide level resolution in a high-throughput manner. The surface lysine residues of the protein were labeled with a fluorescent dye prior to enzyme digestion. The resulting peptide maps were monitored by fluorescence detection where fluorescence peak area indicates higher solvent accessibility at a specific site. The peptides of reactivity difference and the extent of the difference can be detected by HPLC with fluorescent detector alone, whereas the identity of these peptides can then be determined by mass spectrometry if desired. We first demonstrated this method is suitable for probing protein surface/conformation by studying the effect of deglycosylation on a recombinant mAb, IgG 1. We then applied our method to study the interaction of the mAb with a common excipient, polysorbate-20 (PS-20). The presence of PS-20 increased the fluorescent labeling of several lysine residues on the mAb. This result provides a first insight into PS20-mAb interaction at peptide level resolution.