The first aim of this study was to investigate levels of MMP-2, MMP-9, TIMP-1, TIMP-2 and HIF-1? in placentae throughout pregnancy using various techniques. The study used immunohistochemistry to detect and quantify MMP-2 and MMP 9 expression in placentae from 7-19 and at 40 weeks of gestation. A reduction was found in extravillous trophoblast (EVT) expression of both MMPs as pregnancy progressed. In contrast endothelial expression of both MMPs increased. MMP-2 expression in villous CTB (vCTB) was highest in early pregnancy but decreased with gestation. MMP-9 expression in vCTB was very low throughout pregnancy. Zymography studies revealed a significant decrease in pro-MMP-2 but not pro-MMP-9 activity through gestation although the latter did decrease during the first trimester. The results of the study suggest a role for MMP-2 and MMP-9 not only in early placental development but also in vascular remodelling in the later stages of gestation. Moreover it also suggests that the role of MMP-2, often regarded as less important than MMP-9 in placental development, warrants further study. Immunohistochemical studies on the same placentae showed that TIMP-1 expression in muscle surrounding the villous endothelium and in the villous stroma increased with gestation while vCTB expression did not alter and EVT expression increased during the second trimester. TIMP-2 staining in vCTB decreased with gestation while staining on endothelium, muscle and stroma increased. EVT expression of TIMP-2 was negatively correlated with gestation. Thus TIMP-2 appeared to have a high degree of co-distribution with MMP-2 both spatially and temporally. HIF-1alpha staining on vCTB and EVT decreased with gestation while expression on the endothelium increased. These results suggest both paracrine and autocrine regulation of MMPs may occur early in pregnancy. Furthermore TIMPs and HIF-1alpha may have a role in regulating the processes in which MMPs are involved in later on in pregnancy. Pregnant women living at high altitude are exposed to chronic hypoxia throughout gestation. It has been reported that high altitude pregnancies show physiology intermediate between normal pregnancy and pre-eclampsia and thus may provide a useful in vivo model of the disease. This study compared MMP-9 and MMP-2 expression in placentae from high, moderate and low altitude. Endothelial expression of MMP-9 was lower at high altitude than low altitude while MMP-9 expression in the villous stroma was higher. This may implicate MMP-9 in adaptive responses to hypoxia and villous remodelling in high altitude placentae. There were no differences in MMP-2 expression between high and low altitude placentae supporting previous studies, which have reported that MMP-2 expression may not be subject to regulation by oxygen. Maternal serum markers of endothelial cell activation were measured throughout pregnancy at high and moderate altitude. It was hypothesised that since circulating VCAM-1 and E-Selectin are increased in pre-eclampsia, they might also be elevated in high altitude pregnancy. This hypothesis was not supported and another marker of endothelial activation, ICAM-1, was not found to be increased either. (Abstract shortened by ProQuest.).


Abstract The western escarpment of the Sea of Marmara has recently been recognized as the site of intensive gas emissions escaping from the seafloor. Visual observations with the Nautile submersible indicate that gas escapes from elongated tensile cracks oriented to the northwest in the direction of the maximum principal stress. Here, we report results from a 25-day test in 2007 with four ocean-bottom seismometers (OBSs) showing that this area is also characterized by microseismic activity. A cluster of 13 small-magnitude earthquakes aligned northwest occurred in less than 30 hr at shallow crustal depth below the western slope of the Tekirdag basin. The only two focal mechanisms resolvable using land and sea-bottom data reveal normal faulting with strike-slip components, consistent with the stress field expected in this area. It is suggested that tectonic strain below the western slope of the Tekirdag basin contributes to maintaining a high permeability in fault zones and that the fault network provides conduits for deep-seated fluids to rise up to the seafloor.


Although renal medullary carcinoma (RMC) is a rare subtype of kidney cancer, it is particularly devastating in that it is nearly uniformly lethal. No established guidelines exist for the diagnosis and management of RMC. In April 2016, a panel of experts developed clinical guidelines on the basis of a literature review and consensus statements. The goal was to propose recommendations for standardized diagnostic and management approaches and to establish an international clinical registry and biorepository for RMC. Published data are limited to case reports and small retrospective reviews. The RMC Working Group prepared recommendations to inform providers and patients faced with a low level of medical evidence. The diagnosis of RMC should be considered in all patients younger than 50 years with poorly differentiated carcinoma that arises from the renal medulla. These patients should be tested for sickle cell hemoglobinopathies, and if positive, SMARCB1/INI1 loss should be confirmed by immunohistochemistry. The majority of patients with RMC are diagnosed with metastatic disease. Upfront radical nephrectomy should be considered in patients with good performance status and low metastatic burden or after response to systemic therapy. Currently, cytotoxic, platinum-based chemotherapy provides the best, albeit brief, palliative clinical benefit. Vascular endothelial growth factor-directed therapies and mammalian target of rapamycin inhibitors are ineffective in RMC as monotherapy. Therapeutic trials of novel agents are now available for RMC, and every effort should be made to enroll patients in clinical studies.


Written by an eminent scholar in a style that represents American musicological writing at its communicative best, A History of the Oratorio offers a synthesis and critical appraisal so exhaustive and reliable that the serious student of the oratorio will be compelled to look to these volumes as an indispensable source. No work on the history of the oratorio has yet appeared in the English language that is comparable in scope and treatment with Howard Smither's comprehensive four-volume work. The first part of volume 2 examines in depth the antecedents and origins of the oratorio in Protestant Germany in the seventeenth century. It includes discussions of the Lutheran Historia, sacred dramatic dialogues, and the Lubeck Abendmusiken of Buxtehude. The second part treats the oratorio in Protestant Germany in the early eighteenth century and examines Handel, Reinhard Keiser, and J.S. Bach. The third part considers primarily the English oratorios of Handel. In most sections of A History of the Oratorio, the author has selected for special attention a few oratorios that are representative of each geographical area and period. An exception to this procedure is in the section on Handel in this volume, where all of the composer's English oratorios are treated fully with particular reference to recent specialized Handel studies. Volume 1, The Oratorio in the Baroque Era: Italy, Vienna, Paris, and Volume 3, The Oratorio in the classical Era, expand and continue the study of oratorio history. Although this series was originally announced as a three-volume study, Smither will conclude with a fourth volume. A UNC Press Enduring Edition -- UNC Press Enduring Editions use the latest in digital technology to make available again books from our distinguished backlist that were previously out of print. These editions are published unaltered from the original, and are presented in affordable paperback formats, bringing readers both historical and cultural value.


Hydrological modeling can exploit informative signatures extracted from long time sequences of observed streamflow for parameter calibration and model diagnosis. In this study we explore the diagnostic potential of hydrograph partitioning for model calibration in mountain areas, where meltwater from snow and glaciers is an important source for river runoff (in addition to rainwater). We propose an index-based method to partition the hydrograph according to dominant runoff water sources, and a diagnostic approach to calibrate a mountain hydrological model. First, by accounting for the seasonal variability of precipitation and the altitudinal variability of temperature and snow/glacier coverage, we develop a set of indices to indicate the daily status of runoff generation from each type of water source (i.e., glacier meltwater, snow meltwater, rainwater, and groundwater). Second, these indices are used to partition a hydrograph into four parts associated with four different combinations of dominant water sources (i.e., groundwater, groundwater + snow meltwater, groundwater + snow meltwater + glacier meltwater, and groundwater + snow meltwater + glacier meltwater + rainwater). Third, the hydrological model parameters are grouped by the associated runoff sources, and each group is calibrated to match the corresponding hydrograph partition in a stepwise and iterative manner. Similar to use of the regime curve to diagnose seasonality of streamflow, the hydrograph partitioning curve based on a dominant runoff water source (more briefly called the partitioning curve, not necessarily continuous) can serve as a diagnostic signature that helps relate model performance to model components. The proposed methods are demonstrated via application of a semi-distributed hydrological model (THREW, Tsinghua Representative Elementary Watershed) to the Tailan River basin (TRB) (1324 km 2 ) in the Tianshan Mountains of China. Results show that the proposed calibration approach performed reasonably well. Cross-validation and comparison to an automatic calibration method indicated its robustness.


Who's Who in the Roman World is a wide-ranging biographical survey of one of the greatest civilizations in history. Covering a period from the 5th century BC to AD 364, this is an authoritative and hugely enjoyable guide to an era which continues to fascinate today. The figures included come from all walks of Roman life and include some of history's most famous - not to mention infamous - figures as well as hitherto little-known, but no less fascinating, characters. These include : * the notorious emperors - Caligula; Nero; Elagabalus; Commodus * the great poets, philosophers and historians - Virgil; Tacitus; Seneca; Ovid * the brilliant politicians and soldiers - Hannibal; Scipio; Caesar; Mark Antony; Constantine * noteworthy citizens - Acte, mistress of Nero; Catiline, the revolutionary; Spartacus, champion of the slaves; Gaius Verres, the corrupt governor of Sicily. The inclusion of cross-referencing, a glossary of terms, select bibliographies, maps, genealogies and an author's preface complete what is at once a superb reference resource and an enormously entertaining read.


http://journals.cambridge.org/geo Geological Magazine, established in 1864, is one of the oldest and best-known periodicals in the Earth Sciences. Its worldwide circulation, broad scope and high production values keep the journal at the forefront of the field. It publishes original papers, review articles, rapid communications and discussions about all aspects of the geosciences. It covers petrology, geochemistry, palaeontology, sedimentology, stratigraphy, structural geology, geophysics, and geomorphology, and it includes contributions on volcanology, marine geology, glaciology, palaeoclimatology, palaeoceanography, geochronology, biostratigraphy, geohazards and Earth history, providing a niche for interdisciplinary papers on regional geology and Earth history. To subscribe contact Customer Services


Many scholars have argued that once "basic needs" have been met, higher income is no longer associated with higher in subjective well-being. We assess the validity of this claim in comparisons of both rich and poor countries, and also of rich and poor people within a country. Analyzing multiple datasets, multiple definitions of "basic needs" and multiple questions about well-being, we find no support for this claim. The relationship between well-being and income is roughly linear-log and does not diminish as incomes rise. If there is a satiation point, we are yet to reach it.


Objective, easy to use, easy to comprehend, high face-validity assessment methods for measuring shared awareness in teams are hard to find. This paper describes an experiment where a new measure called Shared Priorities, which is based on ranking of self-generated strategic items, is tested. Trained teams were compared to non-trained teams in a dynamic problem-solving task in terms of performance and shared awareness. The shared priorities measure was used alongside other, well-documented measures of team awareness based on self-rating. The results show that the Shared Priorities measure correlate with performance and could also distinguish between trained and non-trained teams. However, the Shared Priorities measure did not correlate with the other team measures, suggesting that it captures a different quality of team work than the self-rating measures. Further, the shared priorities measure was found to be easily administered and gained a high user acceptance.


Many real-life problems require a partial classification of the data. We use the term "partial classification" to describe the discovery of models that show characteristics of the data classes, but may not cover all classes and all examples of any given class. Complete classification may be infeasible or undesirable when there are a very large number of class attributes, most attributes values are missing, or the class distribution is highly skewed and the user is interested in understanding the low-frequency class. We show how association rules can be used for partial classification in such domains, and present two case studies: reducing telecommunications order failures and detecting redundant medical tests.


The purpose of this Article is to explore whether the United States should amend its international tax rules in ways that might encourage U.S. companies to invest in developing countries. Some scholars, notably Professor Karen Brown, have argued that the current U.S. international tax regime works against the interests of developing countries and should be replaced by one that, she asserts, would benefit developing countries in general and African nations in particular.1 She has proposed that the United States replace its foreign tax credit mechanism with an exemption system for developing countries, at the least for Africa. One of the reasons for the proposal is that, as explained below, the current U.S. system prevents developing countries from offering tax incentives, such as tax holidays, to attract foreign direct investment (FDI) by U.S. multinational corporations (MNCs). Certainly, it is the case that little U.S. FDI finds its way to developing countries. At the end of 2001, total U.S.-owner assets earned abroad totaled $6.2 trillion (valued at cost). But the following shows how little of these assets were in developing countries (in $ billions):2 There is thus a real shortfall in U.S. FDI in developing countries as compared to its FDI in other developed countries. But, proposals such as the one put forward by Professor Brown raise several questions. Is FDI an unqualified good for developing countries? What are the determinants in the location of FDI? Are tax incentives offered by developing countries effective in attracting FDI, even in situations where home country tax rules do not thwart them? Can tax incentives alone attract FDI or are there necessary preconditions a developing country must satisfy before there is FDI at all? Are home country unilateral tax incentives effective in increasing FDI by its MNCs? Is it better for developed countries to assist developing countries by offering tax subsidies to its MNCs or by providing direct financial assistance to developing countries? This paper is an effort to explore these questions to see where the evidence supports clear answers and where it is inconclusive. Part I of this Article provides a broad overview of international tax systems, which countries can adopt, with particular attention to aspects of the system adopted by the United States. Part II examines how, and under what circumstances, the current U.S. system defeats the objectives of developing countries in offering tax holidays to U.S. MNCs. It then proposes a structural solution that would address the problem in the context of the ciirrent system. It is, of course, possible that the proposal would not be acceptable to the U.S. Treasury or to developing countries in general. Thus, the remainder of this Article examines Professor Brown's proposal and others that might be considered in meeting the objectives of increasing the FDI of U.S. MNCs in developing countries. Part III identifies the economic, social, and political factors and forces that adversely affect developing countries. The purpose of this discussion is to lay the groundwork for an assessment of whether particular tax changes by the United States would positively impact these forces and factors. Part III also examines recent reports by the United Nations (U.N.) and the Organization for Economic Cooperation and Development (OECD) that analyze the level and means by which developed countries can aid developing countries. Particular attention will be paid to the role of FDI in these analyses. Part IV reviews the economic evidence on the impact of tax policies on the level and location of FDI. Part V accesses several different changes in the U.S. international tax system in terms of their efficiency and simplicity effects and in terms of their effectiveness in meeting the problems identified in Part III. A concluding section sets forth my own policy conclusions. I. INTERNATIONAL TAX REGIMES: AN OVERVIEW All countries must have some system by which they apply their income tax to cross-border business and investment transitions by their own nationals. …


Rapid technological advances during the last two decades have led to a data-driven revolution in biology opening up a plethora of opportunities to infer informative patterns that could lead to deeper biological understanding. Large volumes of data provided by such technologies, however, are not analyzable using hypothesis-driven significance tests and other cornerstones of orthodox statistics. We present powerful tools in machine learning and statistical inference for extracting biologically informative patterns and clinically predictive models using this data.
Motivated by an existing graph partitioning framework, we first derive relationships between optimizing the regularized min-cut cost function used in spectral clustering and the relevance information as defined in the Information Bottleneck method. For fast-mixing graphs, we show that the regularized min-cut cost functions introduced by Shi and Malik over a decade ago can be well approximated as the rate of loss of predictive information about the location of random walkers on the graph. For graphs drawn from a generative model designed to describe community structure, the optimal information-theoretic partition and the optimal min-cut partition are shown to be the same with high probability.
Next, we formulate the problem of identifying emerging viral pathogens and characterizing their transmission in terms of learning linear models that can predict the host of a virus using its sequence information. Motivated by an existing framework for representing biological sequence information, we learn sparse, tree-structured models, built from decision rules based on subsequences, to predict viral hosts from protein sequence data using multi-class Adaboost, a powerful discriminative machine learning algorithm. Furthermore, the predictive motifs robustly selected by the learning algorithm are found to show strong host-specificity and occur in highly conserved regions of the viral proteome.
We then extend this learning algorithm to the problem of predicting disease risk in humans using single nucleotide polymorphisms (SNP) — single-base pair variations — in their entire genome. While genome-wide association studies usually aim to infer individual SNPs that are strongly associated with disease, we use popular supervised learning algorithms to infer sufficiently complex tree-structured models, built from single-SNP decision rules, that are both highly predictive (for clinical goals) and facilitate biological interpretation (for basic science goals). In addition to high prediction accuracies, the models identify 'hotspots' in the genome that contain putative causal variants for the disease and also suggest combinatorial interactions that are relevant for the disease.
Finally, motivated by the insufficiency of quantifying biological interpretability in terms of model sparsity, we propose a hierarchical Bayesian model that infers hidden structured relationships between features while simultaneously regularizing the classification model using the inferred group structure. The appropriate hidden structure maximizes the log-probability of the observed data, thus regularizing a classifier while increasing its predictive accuracy. We conclude by describing different extensions of this model that can be applied to various biological problems, specifically those described in this thesis, and enumerate promising directions for future research.


The designations employed and the presentation of the material in this work do not imply the expression of any opinion whatsoever on the part of UNAIDS concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimi-tation of its frontiers and boundaries. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by UNAIDS in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. publication of UNAIDS, may be freely reviewed, quoted, reproduced or translated, in part or in full, provided the source is acknowledged. The document may not be sold or used in conjunction with commercial purposes without prior written approval from UNAIDS (Contact: UNAIDS Information Centre). The findings, interpretations and views expressed in this publication do not necessarily reflect official policy, endorsement or positions of the Joint United Nations Programme on HIV/ AIDS (UNAIDS).


The effects of porosity and pore geometry on the fluid saturation and immiscible displacement of greensand reservoir rocks were investigated on eight samples from the North Sea basin. Dynamic Neutron Radiography (DNR) was used to image the front stability during displacement experiments where oil was infiltrating water-saturated samples. The flow characteristics were related to petrography and pore geometry, which may be determined by image analysis of backscattered electron (BSE) micrographs. The fluid saturation observed in each DNR image was modelled in a corresponding BSE image as a means of evaluating the effect of pore geometry on front stability. Piston-like displacement and channelling were observed and these flow patterns were found to reflect variations in pore geometry. The samples with piston-like displacement have homogeneous pore space, whereas the samples with channelling have heterogeneous pore space, with spatial variations in porosity and pore size. The modelled saturation distribution was interpreted using results from petrographic and petrophysical analyses. The results suggest that the micropores of the glauconite grains and clay minerals contain water, whereas the oil is moving through the intergranular pore space during the displacement experiment.


The purpose of this study was to evaluate anew fear of crime scale that accurately reflects the current criminal experiences of older people and test gender differences in fear of crime in a number of items, in the item wording, and in choice response categories. A series of chi-square tests compared the fear of crime scale of older people according to their gender, and then logistic regression models were created and tested between males and females. The finding presents the odds ratios, which suggest that older female odds were 168% higher than older men odds of the item 'Someone forcibly taking your property'. They were 43% lower than older men odds of the item 'Some strangers wandering around your home at midnight' and were 170% higher than older men odds of the item 'Some drag racing adolescents trying to hurt you'. Odds were 141% higher in older women than in older men of the item "Someone trying to abduct you". In conclusion, older women are more afraid of crime than older men. This study suggests that the fear of crime in older women focuses more on bodily injury than in property damage.


Student Voices in Teacher Evaluations Brenda Sue Burr Department of Educational Leadership and Foundations, BYU Doctor of Education In an ever increasingly competitive global marketplace, a concern exists that American students are not being adequately prepared with the skills needed for the 21 century. As a remedy, improving quality of teacher instruction is a current national focus. Stakeholders are questioning current infrequent and inefficient methods of evaluating teacher performance. Many states are looking at using a 360 model of evaluating through multiple perspectives including the students themselves as key stakeholders. One method of accessing student voice and adding another perspective to teacher evaluations would be to include student evaluations in the rating of teacher performance, Student Evaluation of Teaching (SET). While using student evaluations of teacher performance is widespread in higher education, the practice has been limited in public school settings until brought to light by the publication of the recent Gates Foundation MET (Measures of Effective Teaching) Project (2010). Currently, states across the nation are considering adding a student input component to teacher evaluations. With the validity and reliability of student evaluations in the university settings still under debate by professors, public school teachers also fear punitive measures and public judgment based on the verdicts of adolescents. This research examined the archival data from a program study of one high school's student evaluation implementation process, accessing teacher feedback from the initial evaluation process and then an adjusted implementation of student evaluations according to teacher feedback the following year. Based on mixed method design using both qualitative and quantitative methods to analyze teacher questionnaires, focus group open-ended responses and statistical analysis of close-ended agree/disagree statements from teacher questionnaires, this study used triangulation to explore teacher reflections on their anxiety levels created by the student evaluation implementation process, the value they found in student evaluations, and the degree to which student evaluations facilitated change in their teaching instruction. Exploring possibilities through the eyes of teachers to reduce their anxiety and increase their value of student input, this study suggests ways to tap into the potential but underutilized resource in schools that could come from developing a mutually beneficial partnership between students and teachers to improve teacher instruction and increase student learning.


This qualitative study investigates pre-service English Foreign Language (EFL) teacher education in Surakarta, Indonesia. Current literature suggests that producing quality Indonesian EFL teachers is challenging. Transnational agencies and policies have documented Indonesia's low quality education outcomes and have noted evidence of poor EFL teacher competence. Global, national and local institutional level texts include many messages about developing quality education and quality teachers. However, the experiences of pre-service EFL teachers during practice based components of their course are not always consistent with the messages mandated in policy texts. To address this disjunct between policy texts and practice this study examined data from over 20 policy texts across global, national and local institutional levels, 10 group interviews, 34 individual interviews and analysis of several electronic sources, such as blogs and newspapers. Several key findings emerged as a result of a content analysis informed by critical ethnographic methods of inquiry. • Neoliberal ideas through quality discourse have emerged in the global, national and local institutional texts and influenced the formation of quality EFL teachers • The identified subjective and objective dimensions of quality education and quality teachers indicate both agreement and disagreement across policy texts that support and challenge quality education and specifically EFL quality teaching • The differences between and among policies and practice indicate that two research sites still face challenges in achieving globally competitive education outcomes as mandated in global policies. These findings reveal the influence of neoliberal ideas in education systems in general and specifically in English language teaching and the implications for pre-service programs that prepare quality EFL teachers for a globalising world. The flows of ideas about quality are not mutually exclusive. They reinforce and also destabilise messages about the formation of quality teachers. The findings indicate four issues need to be addressed: First, pre-service EFL teacher programs need to generate greater awareness of the global dynamics shaping the formation of education systems and education practice; Second, quality teacher formation includes discussion of the role of subjective and objective dimensions in quality provision; Third, discussion of quality needs to understand the degree to which school infrastructure facilitates and hampers pedagogical implementation; and finally, further investigation is required about the effectiveness of time invested in the practicum.


Turn yourself into a top-notch engineering student and become a successful engineer with the ideas and information in this one-of-akind resource. Get yourself on the path to a challenging, rewarding, and prosperous career as an engineer by getting inside each discipline, learning the differences and making educated choices. Updated and now covering 41 different branches of engineering and engineering technology, Is There an Engineer Inside You? is packed with suggestions and has tremendous advice on thriving in an engineering student environment.


Industrial automation requires hard real-time delivery of data that can be of periodic or sporadic in nature. It is challenging to ensure hard real-time delivery of periodic and sporadic data to a multi-hop away destination in a bandwidth constrained environment, such as wireless sensor networks. In this regard, research has been done for joint scheduling of periodic and sporadic data delivery using the IEEE 802.15.4 standard. However, delivery to a destination that is multiple hops away has not been handled. Moreover, the IEEE 802.15.4 standard compliance is not fully taken care of. This study proposes a novel communication protocol that is IEEE 802.15.4 standard compliant, for real-time delivery of sporadic and periodic data to a destination that is multiple hops away. Implicit decisions at various nodes result in the minimal increase in the control traffic and reduced energy dissipation. The proposed protocol is tested using the OPNET simulator and the correctness is proven through a multitude of simulation results.


This thesis presents a study of stochastic arrays and learning networks. These arrays will be shown to consist of simple elements utilising probabilistic coding techniques which may interact with a random and noisy environment to produce useful results. Such networks have generated considerable interest since it is possible to design large parallel self-organising arrays of these elements which are trained by example rather than explicit instruction. Once the learning process has been completed, they then have the potential ability to form generalisations, perform global optimisation of traditionally difficult problems such as routing and incorporate an associative memory capability which can enable such tasks as image recognition and reconstruction to be performed, even when given a partial or noisy view of the target. Since the method of operation of such elements is thought to emulate the basic properties of the neurons of the brain, these arrays have been termed neural 'networks. The research demonstrates the use of stochastic elements for digital signal processing by presenting a novel systolic array, utilising a simple, replicated cell structure, which is shown to perform the operations of Cyclic Correlation and the Discrete Fourier Transform on inherently random and noisy probabilistic single bit inputs. This work is then extended into the field of stochastic learning automata and to neural networks by examining the Associative Reward-Punish (A(_R-P)) pattern recognising learning automaton. The thesis concludes that all the networks described may potentially be generalised to simple variations of one standard probabilistic element utilising stochastic coding, whose properties resemble those of biological neurons. A novel study is presented which describes how a powerful deterministic algorithm, previously considered to be biologically unviable due to its nature, may be represented in this way. It is expected that combinations of these methods may lead to a series of useful hybrid techniques for training networks. The nature of the element generalisation is particularly important as it reveals the potential for encoding successful algorithms in cheap, simple hardware with single bit interconnections. No claim is made that the particular algorithms described are those actually utilised by the brain, only to demonstrate that those properties observed of biological neurons are capable of endowing collective computational ability and that actual biological algorithms may perhaps then become apparent when viewed in this light.


Physical inactivity has been identified as a leading risk factor for premature mortality globally, and adolescents, in particular, have low physical activity levels. Schools have been identified as a setting to tackle physical inactivity. Economic evidence of school-based physical activity programmes is limited, and the costs of these programmes are not always collected in full. This paper describes a micro-costing and cost-consequence analysis of the 'Girls Active' secondary school-based programme as part of a cluster randomised controlled trial (RCT). Micro-costing and cost-consequence analyses were conducted using bespoke cost diaries and questionnaires to collect programme delivery information. Outcomes for the cost-consequence analysis included health-related quality of life measured by the Child Health Utility-9D (CHU-9D), primary care General Practitioner (GP) and school-based (school nurse and school counsellor) service use as part of a cluster RCT of the 'Girls Active' programme. Overall, 1,752 secondary pupils were recruited and a complete case sample of 997 participants (Intervention n = 570, Control n = 427) was used for the cost-consequence analysis. The micro-costing analysis demonstrated that, depending upon how the programme was delivered, 'Girls Active' costs ranged from £1,054 (£2 per pupil, per school year) to £3,489 (£7 per pupil, per school year). The least costly option was to absorb 'Girls Active' strictly within curriculum hours. The analysis demonstrated no effect for the programme for the three main outcomes of interest (health-related quality of life, physical activity and service use).Micro-costing analyses demonstrated the costs of delivering the 'Girls Active' programme, addressing a gap in the United Kingdom (UK) literature regarding economic evidence from school-based physical activity programmes. This paper provides recommendations for those gathering cost and service use data in school settings to supplement validated and objective measures, furthering economic research in this field. Trial registration: -ISRCTN, ISRCTN10688342. PLOS ONE | https://doi.org/10.1371/journal.pone.0221276 August 16, 2019 1 / 17 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111


A comprehensive study of Na[NixCoyMnz]O2 (x = 1/3, 0.5, 0.6, and 0.8) cathodes is carried out to determine the optimal composition as the electrochemical, structural, and thermal properties of O3-type layered cathodes are strongly dependent on the transition metal composition. Here, the role of each transition metal in [NixCoyMnz]O2 cathodes is identified via electrochemical property characterization, structural analysis, and thermal stability testing. Briefly, an increase of the Ni fraction resulted in an increasingly higher capacity but is accompanied by progressively poor capacity retention. On the other hand, the Co metal played an important role in stabilizing the structure, while the Mn content contributed to enhancing the capacity retention and thermal stability. The present study highlights the importance of appropriately balancing the transition metal composition in a layered Na[NixCoyMnz]O2 cathode. Furthermore, this work provides a design guideline for developing an ideal Na[NixCoyMnz]O2 cathode with both high capacity and optimal cycle retention in addition to thermal stability.


Automated perimetry has made viable a rapid threshold examination of the visual field and has reinforced the role of perimetry in the diagnostic procedure. The aim of this study was twofold: to isolate the influence of certain extraneous factors on the sensitivity gradient, since these might limit the early detection and accurate monitoring of visual field loss and to investigate the efficacy of certain novel combinations of stimulus parameters in the detection of early visual field loss. The work was carried out with particular reference to glaucoma and to ocular hypertension. The effects of media opacities on the visual field were assessed by forward intraocular light scatter (n= 15) and were found to mask diffuse glaucomatous visual field loss and underestimate focal loss. Correction of the visual field indices for the effects of forward intraocular light scatter (n= 26) showed the focal losses to be, in reality, unaffected. Measurements of back scatter underestimated forward intraocular light scatter (n= 60) and the resultant depression of the visual field. Perimetric sensitivity improved with patient learning (n= 25) and exhibited eccentricity- and depth-dependency effects whereby improvements in sensitivity were greatest for peripheral areas of the field and for those areas which initially demonstrated the lowest sensitivity. The effects of practice were retained over several months (n= 16). Perimetric sensitivity decreased during prolonged examination due to fatigue effects (n&61 19); these demonstrated a similar eccentricity-dependency, being greatest for eccentricities beyond 30o. Mean sensitivities over the range of adaptation levels employed obeyed the Weber-Fechner law (n= 10) and, as would be expected, were independent of pupil size. No relationship was found between short-term fluctuation and adaptation level. Detection of diffuse glaucomatous visual field loss was facilitated using a size III stimulus of duration 200msec at an adaptation level of 31.5asb, compared with a size III stimulus of duration 100msec at an adaptation level of 4asb (n= 20). In a pilot study (n= 10), temporal summation was found to be higher in glaucomatous patients compared with age-matched controls, although the difference was not statistically significant.


Efficient and flawless information management plays a key role in successful execution of construction projects, but it has been difficult to implement in the traditional document-based environment. A root cause for waste in construction projects is inaccessible, inadequate or missing information. Necessary information is produced by several parties and it is often fragmented, inconsistent or in an impractical format. A lot of time is wasted - meaning that value is destroyed - in searching information needed for activities on construction site due to the fact that even if the information exists somewhere in the documents, it is not easily available. Visual control systems defined in Lean methodology strive for improving the value added flow. Building Information Modelling (BIM) can facilitate organisation and visualisation of information for specific needs in the process. This paper explores how combining principles of Visual Control and BIM could improve information delivery from information producers to information users to reduce waste in searching and processing the information. The methods of literature study, Value Stream Mapping and Root Cause Analysis are used. Software-based Standardised Model Views (SMVs) and their automated creation from BIM, based on predefined use cases and end-user needs are proposed and illustrated. The use of SMVs facilitates Lean information management, thus reducing rework and time spent on waiting, increasing built-in quality and enhancing flow in production. Evaluated savings in a single subcontractor's work time are at least 10% when SMVs are used.


In this comprehensive history of the Illinois Chapter of the Black Panther Party (ILBPP), Chicago native Jakobi Williams demonstrates that the city's Black Power movement was both a response to and an extension of the city's civil rights movement. Williams focuses on the life and violent death of Fred Hampton, a charismatic leader who served as president of the NAACP Youth Council and continued to pursue a civil rights agenda when he became chairman of the revolutionary Chicago-based Black Panther Party. Framing the story of Hampton and the ILBPP as a social and political history and using, for the first time, sealed secret police files in Chicago and interviews conducted with often reticent former members of the ILBPP, Williams explores how Hampton helped develop racial coalitions between the ILBPP and other local activists and organizations. Williams also recounts the history of the original Rainbow Coalition, created in response to Richard J. Daley's Democratic machine, to show how the Panthers worked to create an antiracist, anticlass coalition to fight urban renewal, political corruption, and police brutality.


This article identifies similarities among three approaches to dealing with rule breaking: the procedural justice model, the restorative justice model, and the study of moral development. Each argues that the long-term goal when dealing with rule breaking is to motivate rule breakers to become more self-regulating in their future conduct. This goal is undermined by punishment-focused models of sanctioning. Sanction-based models, which dominate current thinking about managing criminals, have negative consequences for the individual wrongdoer and for society. It is argued that greater focus needs to be placed on psychological approaches whose goal is to connect with and activate internal values within wrongdoers with the goal of encouraging self-regulatory law-related behavior in the future.


A new SHRIMP U-Pb zircon age of 1091 ± 9 Ma has been acquired for the gneissic, S-type Glenmore Granite from the Margate Terrane of the Natal Metamorphic Province. The Glenmore Granite contains two foliations and mineral textures indicate it underwent two metamorphic episodes separated by a period of retrogression. The presence of a folded S1 foliation in the Glenmore Granite indicates that it was either pre- or syntectonic relative to D1, thus providing a maximum age constraint of 1091 ± 9 Ma on the D1 event in the Margate Terrane. This is ~60 Ma later than the completion of the main tectonism (D1–3) documented from the Tugela Terrane, suggesting diachronous arc accretion. Syntectonic granitoids with ages of ~1090 Ma have also been documented from the Mzumbe terrane, as well as from Western Dronning Maud Land (east Antarctica), and the Cape Meredith Complex in the Falklands, which on reconstruction of Gondwanaland, lie adjacent to the Natal Metamorphic Province.


Tubingen University Library offers a continuously improved next generation bibliographic database for theology and religious studies. The "Index theologicus" database is available worldwide in open access. It is funded by the Deutsche Forschungsgemeinschaft (German Research Foundation) in the funding program "specialised information services" . This paper informs about the background of the project and the steps the Library took in order to transform a legacy online content database system into one of the most important international bibliographies in theology without increasing the number of staff involved.


A document describes a sheet membrane spacesuit water membrane evaporator (SWME), which allows for the use of one common water tank that can supply cooling water to the astronaut and to the evaporator. Test data showed that heat rejection performance dropped only 6 percent after being subjected to highly contaminated water. It also exhibited robustness with respect to freezing and Martian atmospheric simulation testing. Water was allowed to freeze in the water channels during testing that simulated a water loop failure and vapor backpressure valve failure. Upon closing the backpressure valve and energizing the pump, the ice eventually thawed and water began to flow with no apparent damage to the sheet membrane. The membrane evaporator also serves to de-gas the water loop from entrained gases, thereby eliminating the need for special degassing equipment such as is needed by the current spacesuit system. As water flows through the three annular water channels, water evaporates with the vapor flowing across the hydrophobic, porous sheet membrane to the vacuum side of the membrane. The rate at which water evaporates, and therefore, the rate at which the flowing water is cooled, is a function of the difference between the water saturation pressure on the water side of the membrane, and the pressure on the vacuum side of the membrane. The primary theory is that the hydrophobic sheet membrane retains water, but permits vapor pass-through when the vapor side pressure is less than the water saturation pressure. This results in evaporative cooling of the remaining water.


Introduction: the first permanent molar is considered the dental key to occlusion. The presence of caries here is high, hindering the achievement of goals set by various health organizations worldwide in this age group. Objetive: to determine acute dental caries behavior in the first permanent molar within a 12 year-aged population, assisted at The Dental Clinic of Santa Cruz in Goaigoaza Parish. Method: a descriptive cross-sectional study was conducted in The Dental Clinic of Santa Cruz in Goaigoaza Parish, Puerto Cabello, Carabobo, from April 2009 to April 2010. 97 patients (12 year-aged) were selected to form the universe and sample. These patients came to consultation in pain due to the presence of acute dental caries. Variables were recorded such as: age, sex, clinical grade of dental caries, external stimuli causing pain, dental face and the most affected dental arch: the variables were. The information was collected by interview and clinical examination. Results: the males accounted for 63.9 %. 3rd grade dental caries were present in 68.0 %. External stimuli causing pain were cold (75.2 %) and sweet foods (69.1 %) in both genders. The lower right first molar was the more affected (46.4 %) than the left one (36.1 %), as well as the lower dental arch (25.8 %) and the occlusal face (64.9 %). Conclusions: acute 3rd grade dental caries and males patients predominated. Cold and sweet foods were the most frequent external stimuli, The lower right first molar, the occlusal face and lower dental arch were the most affected.


Intensively managed forests in the southeastern United States are a potential source of cellulosic bioenergy and, as conversion technologies improve and demand increases, a greater land area may be required to produce biofuel feedstocks. However, responses of wildlife to forest-based biofuel production are largely unknown. We examined the 4-year response of rodent populations and assemblages to a range of biofuel production regimes, including harvesting residual woody debris and intercropping switchgrass (Panicum virgatum), in an intensively managed loblolly pine (Pinus taeda) forest in eastern North Carolina, USA. We investigated abundance, demography, and community response of rodents in a randomized and replicated field experiment using mark-recapture techniques during 2009–2012. Whereas removal of downed woody biomass did not affect abundance, diversity, or demography of rodents, we detected species-specific effects of incorporating switchgrass. After switchgrass was well established, invasive house mice (Mus musculus) were most abundant in plots with switchgrass. In contrast, white-footed mice (Peromyscus leucopus) were commonly captured in plots without switchgrass and other rodents were not affected by biofuel treatments. Across the study, natural succession exerted greater effects on rodent species and the rodent community than biofuel production regimes. As remaining logs and stumps decay and become limiting, downed wood may become more important to rodents. Our results indicate that intercropping switchgrass and harvesting residual woody material had limited effects on rodents in the Coastal Plain of North Carolina, USA within 4 years of stand establishment.


Energy drives economies and quality of life, yet accessible traditional fuels are increasingly scarce. Federal, state, and local governments have thus determined that renewable energy development is essential and have passed substantial requirements for its use. These lofty goals will fail, however, if policymakers rely upon existing institutions to govern renewable development. Renewable fuels are fugitive resources, and ideal property for renewable technology is defined by the strength of the sunlight or wind that flows over it. When a renewable parcel is identified, a new piece of property is superimposed upon existing boundaries and jurisdictional lines. The entities within these boundaries all possess rights to exclude, and this creates a tragedy with strong anticommons and regulatory commons elements, which hinder renewable development. This Article argues that the many exclusion rights within renewable parcels must be consolidated and governed by a regional agency to address the governance challenges in renewable development, and it analyzes elements of existing regional institutions to suggest the ideal structure of this agency. Once formed, the regional framework should be applied to other areas of energy planning. States and municipalities share oil and gas reservoirs, electricity transmission constraints, and energy generation needs, and collaborative governance in these areas is necessary for a secure future.


Chemically strengthened thin glass (t < 2 mm) is a material that is stronger and due to its small thickness, more flexible than conventional window glass. As such, thin glass offers the possibility for lightweight and flexible glass facades that could change shape depending on external conditions.  This paper explores this concept and presents an MSc study on the use of this material in adaptive facade panels. The behavior of thin glass in this context depends on different factors. The glass thickness and strength define its bending limits, while the desired geometry and movement affect its overall stiffness and visual outcome. In order to integrate these factors, different configurations of panels were analyzed in numerical models. These analyses showed the importance of understanding the desired movement and geometry in order to correctly define the supports and degrees of freedom of the panel, avoiding stress concentration (particularly on the edges) and allowing for an unobstructed movement of the panel. The development of these analyses resulted in the conception of a design example of an adaptive facade panel, taking into consideration the design requirements developed in the research. Finally, as a proof of concept, a mock-up was built simulating the behavior of the design example developed in this research. Although there is still the need for research to be developed so that thin glass can become a building material, this research showed that this is possible and that interesting results, regarding visual effect, ventilation and dead load reduction (in larger scale, an environmental impact reduction is also possible) can be achieved.  Besides that, using thin glass in adaptive panels challenges the concept of glass as a static material, opening new possibilities for its use.


Engaging a century-long debate about the role of race in science In the wake of the sequencing of the human genome in the early 2000s, genome pioneers and social scientists alike called for an end to the use of race as a variable in genetic research (1, 2). Unfortunately, by some measures, the use of race as a biological category has increased in the postgenomic age (3). Although inconsistent definition and use has been a chief problem with the race concept, it has historically been used as a taxonomic categorization based on common hereditary traits (such as skin color) to elucidate the relationship between our ancestry and our genes. We believe the use of biological concepts of race in human genetic research—so disputed and so mired in confusion—is problematic at best and harmful at worst. It is time for biologists to find a better way.


Multiple-input and multiple-output (MIMO) systems formed by multiple transmit and receive antennas can improve performance and increase capacity of wireless communication systems. Diagonal Bell Laboratories Layered Space-Time (D-BLAST) structure offers a low-complexity solution for realizing the attractive capacity of MIMO systems. However, for broadband wireless communications, channel is frequency-selective and orthogonal frequency division multiplexing (OFDM) has to be used with MIMO techniques to reduce system complexity. In this paper, we investigate D-BLAST for MIMO-OFDM systems. We develop a layerwise channel estimation algorithm which is robust to channel variation by exploiting the characteristic of the D-BLAST structure. Further improvement is made by subspace tracking to considerably reduce the error floor. Simulation results show that the layerwise estimators require 1 dB less signal-to-noise ratio (SNR) than the traditional blockwise estimator for a word error rate (WER) of when Doppler frequency is 40 Hz. Among the layerwise estimators, the subspace-tracking estimator provides a 0.8 dB gain for WER with 200 Hz Doppler frequency compared with the DFT-based estimator.


As one of the important step to solve the environment pollution problems, Chinese Government pays much attention to the development of new energy vehicle industries. However, the situation is not satisfied. The paper studied the current situation and efficiency of new energy vehicle in Chinese market. We find that Chinese consumers are not ready to accept the new energy vehicles because of their high price, shortage of infrastructural and supporting policies. On the other hand, the domestic new energy vehicle manufactures still need to improve their new energy vehicles' technical efficiency in order to compete with the other traditional gasoline vehicles.


Objective To determine morbidity, mortality and associated risk factors following patent ductus arteriosus (PDA) ligation in premature infants. Methods Retrospective case note audit of premature infants referred to a national paediatric cardiothoracic surgical service (2001–2007) with univariate and multivariate analysis of potential risk factors for mortality and morbidity. Results 125 infants were enrolled (median gestational age 26 weeks (IQR 25–27 weeks), median birth weight 840 g (IQR 730–1035 g)). Referral characteristics were median LA:Ao 1.8 (IQR 1.5–2.0), 80% ventilated, 18.4% continuous positive airway pressure, 70% diuretics and 58% prior treatment with cyclooxygenase inhibitors (COIs). Median age at PDA ligation was 31 days (IQR 25–41 days). Postoperative characteristics were median time to extubation 5 days (IQR 3–10 days), 36.0% corticosteroids, 46.8% domiciliary oxygen and 4.8% vocal cord palsy. The 30-day and 1-year mortality rates were 4.8% and 12.8%, respectively, with neurodisability in 32% of survivors. All deaths occurred in the ventilated group and were mainly attributable to bronchopulmonary dysplasia (BPD). Gestation and fractional inspired oxygen (FiO2)>60% were significantly associated with 30-day mortality. FiO2, ventilation, lack of prior COIs and postoperative corticosteroids were significantly associated with 1-year mortality. Preoperative FiO2>40% and lack of prior COIs retained independent significance for death at 1 year. Conclusions PDA ligation is well tolerated, with evidence of early benefit. The incidence of neurodisability or death from BPD at 1 year remains high. Increasing preoperative FiO2 and lack of prior treatment with COIs are associated with increased mortality at 1 year.


Researchers often need to gather a comprehensive set of papers relevant to a focused topic, but this is often difficult and time-consuming using existing search methods. For example, keyword searching suffers from difficulties with synonyms and multiple meanings. While some automated research-paper recommender systems exist, these typically depend on either a researcher's entire library or just a single paper, resulting in either a quite broad or a quite narrow search. With these issues in mind, we built a new research-paper recommender system that utilizes both citation information and textual similarity of abstracts to provide a highly focused set of relevant results. The input to this system is a set of one or more related papers, and our system searches for papers that are closely related to the entire set. This framework helps researchers gather a set of papers that are closely related to a particular topic of interest, and allows control over which cross-section of the literature is located. We show the effectiveness of this recommender system by using it to recreate the references of review papers. We also show its utility as a general similarity metric between scientific articles by performing unsupervised clustering on sets of scientific articles. We release an implementation, ExCiteSearch (bitbucket.org/mmmontemore/excitesearch), to allow researchers to apply this framework to locate relevant scientific articles.


Background: Osteoarthritis is a widespread highly painful disabling age-related disease with no known cure. Although novel strategies for ameliorating osteoarthritic damage abound, it is likely that none will be successful over time if the entire spectrum of the disease and the effects of joint biomechanics on joint tissues are not carefully considered. Objectives: 1) To detail the structure of healthy articular cartilage, the key tissue affected by osteoarthritis. 2) To detail what aspects of cartilage damage best characterize osteoarthritis. 3) To consider the role of biomechanical factors in developing solutions to treat osteoarthritic joint damage. Methods: Literature sources from 1980 onwards that have contributed to our knowledge of the topics relevant to this paper were accessed and retrieved. The data were categorized into four predominant themes and conclusions about the state of our knowledge and future directives were formulated. Conclusions: Osteoarthritis prevalence remains high, and a cure appears elusive. A rich body of data has helped us to better understand the key tissue involved, and suggests a repair process might be feasible, if the basic collective information on the role of biomechanics in mediating or moderating articular cartilage integrity and function is forthcoming.


The Board of Overseers of Weill Cornell Medical College in New York City voted to establish the new Ansary Center for Stem Cell Therapeutics. The unique Center will bring together a premier team of scientists to focus on stem cells – the primitive, unspecialized cells thought to have an unrivaled capacity to form all types of cells in the body. As part of Weill Cornell's "Advancing the Clinical Mission" Capital Campaign, the Ansary Center for Stem Cell Therapeutics is being created with a $15 million grant from Shahla and Hushang Ansary, prominent Houston philanthropists. Mr. Ansary is a Vice Chairman of Weill Cornell Medical College's Board of Overseers. Vision of Ansary Center "The Ansary Center will help lead the way into 21st century medicine in this extremely promising area," said Dr. Antonio M. Gotto, Jr., Stephen and Suzanne Weiss Dean of Weill Cornell Medical College in New York City. "Weill Cornell scientists and physicians are already world leaders in stem cell research, and Mr. Ansary's generous gift will help spur the creativity and collaboration of our scientists, as well as help attract the best and brightest young researchers in the field." "We are witnessing the birth of a new field of research that has tremendous potential for relieving human suffering," said Hushang Ansary. It's an exciting time, and we believe this prestigious Center will have a significant impact in the field."Added Dr. David P. Hajjar, Executive Vice Dean for Research at Weill Cornell, "This Center will help position Weill Cornell at the vanguard of stem cell and developmental biology research in this country." Dr. Shahin Rafii, a noted authority in the field and the recently named Arthur Belfer Professor of Genetic Medicine at Weill Cornell, will direct the new Center. Stem Cells: Nature and Potential Stem cells are immature cells that can differentiate into all types of cells in the body, from heart-beat-generating cardiac cells to insulin-producing cells in the pancreas. Embryonic stems cells, or those that exist in the ball of cells that forms shortly after sperm and egg meet, are thought to have enormous potential when it comes to developing into different types of cells. Adult stem cells – which can be found in umbilical cord blood, bone marrow, blood, and other parts of the body – have tremendous potential as well. The Ansary Center will take a synergistic approach to stem cell research and bring together scientists from different areas of biomedical research to solve complex problems. They hope to discover the wellspring of adult stem cells in the body and ways to manipulate stem cells to treat human illness. In particular, the researchers hope to understand the regulation of cells that give rise to blood vessels, to insulin-producing cells in the pancreas (which are damaged in diabetics), and to neurons of the brain and nervous system. "Stem cells have long been known to reside in the blood and bone marrow, and are responsible for churning out the massive number of red blood cells and infection-fighting white blood cells the body needs," said Dr. Rafii, who is also Professor of Medicine in the Division of Hematology-Oncology at Weill Cornell. "Now scientists are starting to find organ-specific stem cells nearly everywhere, which opens up novel strategies to regenerate adult organs." Stem Cell Innovations at Weill Cornell Dr. Rafii has made a number of advances in stem cell research, including the discovery of vascular stem cells that are present in the adult bone marrow and can contribute to wound healing and tumor revascularization. In addition, his group has found that stem cells in bone marrow must move from one location to another before they can mature and begin regenerating new cells. He and his team also identified the growth factors that facilitate this movement, which could help cancer patients recovering from the severe blood- and immune-suppressing effects of chemotherapy. In other innovative research on stem cells at the Medical College, Dr. Neeta Roy, Assistant Professor of Neuroscience, recently isolated neural progenitor cells from fetal spinal cord tissue, which could one day be used to treat damaged nerves and brain tissue. And Dr. Jay Edelberg, Assistant Professor of Medicine in the Greenberg Division of Cardiology and in Cell and Developmental Biology, is studying the potential use of bone-marrow precursor cells to mend damaged and aging hearts. From Bench to Bedside "It is hoped that stem cells can one day be used to replace cells that are dead or damaged by illness – including for heart attack, stroke, diabetes, and Alzheimer's disease," said Dr. Rafii. While researchers at the Ansary Center will focus on many types of stem cell research, they particularly hope to find ways to boost the growth of adult stem cells. For example, for decades it was nearly etched in stone that certain organs – including the brain, heart, and ovaries – had a finite number of cells. If damaged or used up, it was thought these organs had no way of generating new cells. In recent years, tantalizing new evidence has suggested that hibernating stem cells may be lurking inside these and other organs. "If we can find a way to stimulate these cells, either in the laboratory or in the body, we could deliver large amounts of a patient's own stem cells as a treatment," said Dr. Rafii. "Such cells could be used to enhance brain recovery after stroke, accelerate wound healing in diabetics, and regenerate heart muscle after a heart attack." Adult stem cells could also have the potential to be used in gene therapy. "Such cells could be genetically altered to carry therapeutic 'payloads' that might destroy the blood vessels supplying tumors," said Dr. Ronald Crystal, a pioneer in gene therapy and Chairman of the Department of Genetic Medicine at Weill Cornell. "Such genetically altered cells might also be used to reverse tissue injury in heart attack, stroke, liver damage, or heart disease-damaged arteries." The Ansary Center will also create a rigorous environment where scientists from various disciplines will collaborate on finding tissue-specific cell signals that help regulate and promote the survival of adult stem cells. This information could be used to find or design drugs that could boost stem cell growth or differentiation. The Center will function in accordance with all Federal regulations regarding the use of adult, fetal, and embryonic stem cells. Hushang Ansary Iranian-born Hushang Ansary is a prominent Houston philanthropist, active in business and civic affairs. He is Chairman of Parman Capital Group, a privately held global investment enterprise. Mr. Ansary is a trustee of the George Bush Presidential Library Foundation and a founding member of the James A. Baker III Institute for Public Policy at Rice University. Mr. Ansary has been a member of Weill Cornell's Board of Overseers since 1998. He was elected a Vice Chairman in 2004. Hushang Ansary is a recipient of the Woodrow Wilson International Center for Scholars' Award for Corporate Citizenship and of the Ellis Island Medal of Honor. Mr. Ansary is a former Iranian Finance and Economic Minister, Chairman/CEO of National Iranian Oil Company, and Ambassador to the United States. Contact: Jonathan Weil: firstname.lastname@example.com, Phone:212-821-0566


With the capability of localizing optical energy via surface plasmon resonance (SPR), plasmonic Au nanostructures hold great promise for enhancing the solar water splitting of semiconductor photocatalysts. While the content of Au plays a critical role in mediating interfacial charge transfer, its quantitative influence on the efficiency of plasmon-assisted water splitting is still not fully understood. This work aimed to explore the correlations among plasmonic metal content, SPR-mediated charge transfer and electromagnetic response, and the resultant photoactivity enhancement toward photoelectrochemical (PEC) water splitting. The PEC system was constructed by employing Au particle-decorated ZnO nanocrystals (ZnO–Au) as the plasmonic photoanode. Time-resolved photoluminescence spectroscopy and finite-difference time-domain simulations were utilized to evaluate the optimal Au content which attained effective charge separation and imposed a significant SPR effect for achieving the largest photoactivity enhancement. The charge transfer at the photoanode/electrolyte interface and its dependence on the Au content were examined with electrochemical impedance analysis, which manifested the effectiveness of the optimal Au content in facilitating the hole transfer kinetics. The present study reports a technical advance in the realization of the quantitative effect of Au for designing sophisticated plasmonic PEC systems that enabled efficient solar-to-fuel energy conversion.


Dynamic behavior of a program can be assessed through examination of events emitted by the program during execution. Temporal properties define the order of occurrence and timing constraints on event occurrence. Such specifications are important for safety-critical real-time systems for which a delayed response to an emitted event may lead to a fault in the system. Since temporal properties are rarely specified for programs and due to the complexity of the formalisms, it is desirable to suggest properties by extracting them from traces of program execution for testing, verification, anomaly detection, and debugging purposes. We propose a framework for automatically mining properties that are in the form of timed regular expressions (TREs) from system traces. Using an abstract structure of the property, the framework constructs a finite state machine to serve as an acceptor. As part of the framework, we propose two novel algorithms optimized for mining general TREs and a fragment without negation. The framework is evaluated on industrial strength safety-critical real-time applications (a deployed autonomous hexacopter system and a commercial vehicle in operation) using traces with more than 1 Million entries. Our framework is open source and available online:https://bitbucket.org/sfischme/tre-mining


This thesis will present the results of an investigation into arable crops and farming systems of Bronze Age Ireland. Earlier studies have suggested that barley - particularly the naked variety - was the predominant crop of this period, with wheat playing a very minor role in farming economies. These studies relied heavily upon evidence from plant impressions on ceramic vessels. The research presented here will explore the production and consumption of crops in Bronze Age Ireland through the examination of an alternative dataset – the evidence from charred plant macro-remains recovered from archaeological excavations.

Investigations are focused upon evidence from the Middle and Late Bronze Age in Ireland, due to a relative dearth of Early Bronze Age material. The collation and analysis of mainly unpublished data from more twenty sites provide a strong contrast to the evidence from the seed impressions record. Clear differences can also be observed when comparing data from the Middle and Late Bronze Age periods. Investigation of the types of contexts in which these remains were recorded has revealed new insights into deposition processes and activities at this time. Analysis of the arable weeds accompanying the cereals has also enabled an exploration of cultivation, harvesting and crop-processing activities.

Investigation of the scale of agricultural production suggests the mobilisation of communities for agricultural work, as well as the accumulation of agricultural surpluses. The record from Bronze Age Ireland does, however, indicate that a variety of agricultural strategies could have been deployed, and a progressive or 'evolutionary' trend towards agricultural intensification is unlikely to have occurred in all areas.


Chimeric anti-CD4 monoclonal antibody was administered intravenously as a single dose to eight patients with mycosis fungoides. The dose was escalated throughout the study between patients groups, and individual patients received 50, 100, or 200 mg per dose. Seven of eight patients responded to treatment with an average freedom from progression of 25 weeks (range, 6 to 52 weeks). The treatment was well tolerated, and there was no clinical evidence of immunosuppression. Following treatment, there was significant suppression of peripheral blood CD4 counts in all patients for 1 to 22+ weeks. Only one patient made a very low titer human antichimeric antibody response. All but two patients made primary antibody and T-cell proliferative responses to a foreign antigen administered 24 hours after antibody infusion. However, there was generally marked, but temporary suppression of T-cell proliferative responses in vitro to phytohemagglutinin (PHA), tetanus toxoid, and normal donor lymphocytes. We conclude that at the dose levels studied, this antibody (1) had clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) decreased T-cell proliferative responses in vitro, and (5) did not induce tolerance to a foreign antigen.


Context: Ectopic pregnancy is a life threatening gynaecological emergency; it is a significant cause of maternal morbidity and mortality, thus poses various anaesthetic challenges. Aims: To determine the profile of women that present with ectopic gestation, their mode of presentation, the anaesthetic technique used, complications and outcome. Settings and Design: This was a retrospective review of ectopic pregnancy at the University of Ilorin teaching hospital from 1st January 2015 to 31st December 2018. Materials and Methods: Data were obtained from operating theatre records, anaesthetic records regarding modes of anaesthesia, complications and outcomes were extracted. Statistical analysis used: Analysis was done IBM SPSS version 22. Results: There were 89 cases of ectopic pregnancies that were managed during the period of review. The incidence of ectopic pregnancy in this study was 0.9% of all deliveries. A total of 69 (77.5%) of the case file were available and were retrieved and analysed. The age range was 25–29 years, with mean age of 27.5 ± 5.4 years. Most of the patients presented with ruptured ectopic 57 (82.6%). All the patients had general anaesthesia, and ketamine 47 (68.2%) was the predominant induction agent (P = 0.007). The most common surgical intervention performed was open laparotomy with unilateral salpingectomy 60 (87%). Fifty three (76.8%) of the patients required intra operative blood transfusion. All patients with the American Society of Aanesthesiologists (ASA) IVE had ruptured ectopic, while 88% of patients with ASA IIIE presented with ruptured ectopic. Ninety per cent of the patient that were ASA IVE had an immediate post operative complication. While the least complication was seen in patients with ASA IE 3 (37.5%). No patient required intensive care admission, and no mortality was recorded. Conclusion: The most common form of presentation of ectopic pregnancy in this study was ruptured unilateral ectopic, and general anaesthesia for laparotomy was the most common intervention.


The localization of the city of Liège, in the Meuse (Maas) valley, later the development of its
industries and its port, were all conditioned by the natural geography of its site. Yet today the
site itself and its natural characteristics are seldom perceptible from within the city. The large
scale destructions in the city fabric during the last two centuries broke up its historical siteresponsive
urban morphology. The disappearing industry left the landscape scarred with now
meaningless traces, and no strong alternative vision for its future. While the region is waiting for
"the" solution, for the definitive project that will give it new impulse and identity, the abandoned
industrial sites and many of their surroundings are turning into "non-sites".
To gain a new vision specific to the valley, one must read todays' landscape as a palimpsest left
by rural uses and urban developments, including industrial artifacts, overlaid on its original
geomorphology. A "project" approach, such as that proposed by many landscape architects at
different scales, from garden to forest and larger urban development, offers a way of observing
and interpreting the landscape, eventually leading to iterative, local interventions, ("landscape
acupuncture"). Inspired by the site-responsive agricultural past of the valley, the interventions
should lead to a new spatial language of urban agriculture and forestry. Each of these
interventions can turn into a "landscape laboratory", involving local stakeholders, whose aim is
to articulate small scale landscape elements with long-term place and time-contextual
investment, and thus redefine its identity.


Members of Zygophylloideae are shrubs, shrublets and herbs of arid and semiarid areas of almost all continents, and many of the species are major components of the vegetation in their areas of distribution. A phylogenetic analysis of Zygophylloideae based on noncoding trnL plastid DNA sequences and morphological data, indicates that the currently recognised genera Augea, Tetraena, and Fagonia, are embedded in Zygophyllum. A new generic classification based on six monophyletic and morphologically distinctive entities is proposed here: Augea, Fagonia, Melocarpum, Roepera, Tetraena and Zygophyllum. The taxonomy of the genus Fagonia is revised in detail. A key to the 34 species recognised is presented, as well as descriptions and distribution maps for each species. Five new species are described and illustrated, F. densispina, F. gypsophila and F. latistipulata from Somalia, and F. hadramautica and F. mahrana from the southern part of the Arabian peninsula. Of the accepted species, 26 are restricted to the Old World and eight to the New World. The names of all four species of Fagonia currently on the IUCN Red List of Threatened Plants are put into synonymy. Instead, eight other species are proposed for this list.Relationships within Fagonia are inferred from analysis of plastid trnL intron and nuclear ribosomal ITS sequences. The phylogenetic analysis is performed using parsimony and Bayesian model averaging. All species of Fagonia in the Old World, except F. cretica, form a weakly supported clade, and all Fagonia species of the New World, except F. scoparia, form a second, well supported clade, sister to the Old World clade. Fagonia scoparia, endemic to northeastern Mexico, is sister to all other Fagonia species. Vicariance-dispersal analysis indicated that the occurrences of Fagonia in South America and southern Africa are due to dispersals, and that the ancestor of Fagonia had a distribution in agreement with the boreotropics hypothesis.


Background and Objective : Percutaneous Coronary Intervention (PCI) is a common procedure in treatment of coronary artery diseases. Anxiety is a common psychological reaction to cardiovascular interventions. Anxiety can affect physiological responses and cause blood pressure increase, cardiac output decrease, cardiac o2 demand increase, and finally ischemic pain. The aim of this study was to assess the effect of aromatherapy massage on anxiety of patients undergone the PCI. Materials and Methods : In this semi-experimental study, 76 patients undergone elective PCI who had met the inclusion criteria for the study were recruited using convenience sampling method and were randomly divided into two control and experimental groups. The patients in the control group received routine care with eight hours bed rest after the PCI. The patients in the experimental group underwent aromatherapy massage with a solution composed of mint, celery and lavender essences in sweet almond oil (%1 concentration). The intensity of anxiety was measured using the Spilberger state anxiety inventory in three stages (prior to the intervention, immediately after the intervention, and two hours after the intervention) .The incidence of bleeding was observed before and after the intervention. The incidence of hematoma was observed 24 hours after the intervention. Results : The intensity of anxiety had significantly decreased after aromatherapy massage in the experimental group in comparison with the control group (P< 0.0005). The effect was stable up to two hours after the intervention (P< 0.0005). In the experimental group, anxiety decreased significantly after the intervention (P< 0.0005). None of the patients in the study had bleeding. Moreover, 92.1% of patients were satisfied from the intervention procedure. Conclusion : The results showed that the aromatherapy massage was a safe, non-expensive, and effective method in decreasing anxiety of patients undergone the PCI.


Abstract. The Gimballed Limb Observer for Radiance Imaging of the Atmosphere (GLORIA) is a prototype of an imaging Fourier Transform Spectrometer (FTS) for PREMIER, a former candidate mission for ESA's Earth Explorer 7. GLORIA is deployed on board various research aircraft such as the Russian M55 Geophysica or the German HALO. The instrument provides detailed infrared images of the Upper Troposphere/Lower Stratosphere (UTLS) region, which plays a crucial role in the climate system. GLORIA uses a two-dimensional detector array for infrared limb observations in emission and therefore needs large-area blackbody radiation sources (126 mm × 126 mm) for calibration. In order to meet the highly demanding uncertainty requirements for the scientific objectives of the GLORIA missions and due to the sophisticated tomographic evaluation scheme, the spatial distribution of the radiance temperature of the blackbody calibration sources has to be determined with an uncertainty of about 0.1 K. Since GLORIA is exposed to the hostile environment of the UTLS with mutable low temperature and pressure, an in-flight calibration system has to be carefully designed to cope with those adverse circumstances. The GLORIA in-flight calibration system consists of two identical weight-optimised high-precision blackbody radiation sources, which are independently stabilised at two different temperatures. The two point calibration is in the range of the observed atmospheric infrared radiance emissions with 10 K below and 30 K above ambient temperature, respectively. Thermo-Electric Coolers are used to control the temperature of the blackbody radiation sources offering the advantage of avoiding cryogens and mechanical coolers. The design and performance of the GLORIA in-flight calibration system is presented. The blackbody calibration sources have been comprehensively characterised for their spatially (full aperture) and spectrally (7 to 13 μm) resolved radiation properties in terms of radiance temperatures traceable to the International Temperature Scale (ITS-90) at the Physikalisch-Technische Bundesanstalt (PTB), the national metrology institute of Germany.


Deep generative adversarial networks (GANs) have gained growing popularity in numerous scenarios, while usually suffer from high parameter complexities for resource-constrained real-world applications. However, the compression of GANs has less been explored. A few works show that heuristically applying compression techniques normally leads to unsatisfactory results, due to the notorious training instability of GANs. In parallel, the lottery ticket hypothesis shows prevailing success on discriminative models, in locating sparse matching subnetworks capable of training in isolation to full model performance. In this work, we for the first time study the existence of such trainable matching subnetworks in deep GANs. For a range of GANs, we certainly find matching subnetworks at 67%-74% sparsity. We observe that with or without pruning discriminator has a minor effect on the existence and quality of matching subnetworks, while the initialization weights used in the discriminator play a significant role. We then show the powerful transferability of these subnetworks to unseen tasks. Furthermore, extensive experimental results demonstrate that our found subnetworks substantially outperform previous state-of-the-art GAN compression approaches in both image generation (e.g. SNGAN) and image-to-image translation GANs (e.g. CycleGAN). Codes available at https://github.com/VITA-Group/GAN-LTH.


This paper investigates the seasonal characteristics of ETFs return, risk, tracking error and volume and reveals the existence of a strong November effect in performance. The paper also demonstrates the inexistence of any persistent and univocal January effect in ETFs performance. Considering the volatility and the tracking error of ETFs, the paper demonstrates that a semi-strong seasonality in risk of ETFs exists during November and that ETFs achieve their best replication performance in November too. The combination of high average performance and low average risk and tracking error signals an opportunity for investors to gain sufficient returns by exposing themselves in modest or low volatility and tracking failure. Also, a straightforward relationship among risk and tracking error is demonstrated by the paper. Finally, the study indicates that there is no a specific and stead monthly effect in ETFs trading activity but there is some evidence for the direct conjuncture among risk and volume. This positive connection is basically interpreted in selling of ETF shares when investors perceive that their investments are over risky.


Endoscopy is a routine imaging technique used for both diagnosis and minimally invasive surgical treatment. While the endoscopy video contains a wealth of information, tools to capture this information for the purpose of clinical reporting are rather poor. In date, endoscopists do not have any access to tools that enable them to browse the video data in an efficient and user friendly manner. Fast and reliable video retrieval methods could for example, allow them to review data from previous exams and therefore improve their ability to monitor disease progression. Deep learning provides new avenues of compressing and indexing video in an extremely efficient manner. In this study, we propose to use an autoencoder for efficient video compression and fast retrieval of video images. To boost the accuracy of video image retrieval and to address data variability like multi-modality and view-point changes, we propose the integration of a Siamese network. We demonstrate that our approach is competitive in retrieving images from 3 large scale videos of 3 different patients obtained against the query samples of their previous diagnosis. Quantitative validation shows that the combined approach yield an overall improvement of 5% and 8% over classical and variational autoencoders, respectively.


Summary
The protective properties of various second-stage larval and egg preparations of Ascaris suum were evaluated in mice. Groups of mice were injected by several "immunization" schedules with (1) lyophilized and live embryonated eggs, (2) lyophilized and live hatched second-stage larvae, (3) supernate of ground embryonated eggs, (4) live embryonated eggs per os and (5) excretions and secretions of second-stage larvae. Immunization also was attempted by planting diffusion chambers containing live second-stage larvae intraperitoneally in mice.
The criterion of immunity was a significantly lower number of larvae in the lungs of mice 8 days after a challenge infection by embryonated eggs by mouth. The results show that under the conditions of the experiment, a marked protective immunity was produced when live larvae were used for the immunization. Immunization with excretions and secretions of second-stage larvae resulted in a significant immunity, as did implanting diffusion chambers containing second-stage larvae. However, the degree of resistance produced by these latter two methods was not as high as that produced by actual infection.


Along with steadily increasing interest in biopharmaceuticals such as peptides, proteins, or nucleic acids, development of strategies for their effective cytosolic delivery gained comparable attention. Indeed, being very potent in frames of bioactivity, these macromolecules do not readily enter the cytosol. Therefore, their application field is often restricted to extracellular targets. To overcome this limitation, and to achieve the ability to address intracellular targets, different approaches have been done aiming at improved cellular uptake. Beside strategies based on delivery of macromolecules with liposomes,[28-29] polymersomes,[30] nanoparticles,[32] or pore-forming proteins,[35-36] cell-penetrating peptides have emerged as a versatile tool for intracellular delivery of different cargoes. In particular, arginine-rich CPPs and their even more potent cyclic versions have numerously been reported as efficient delivery vehicles.[50, 52]
In the frame of the present work, a system for efficient cytosolic delivery of biomolecular cargo was developed, based on CPP-bearing dextran hybrids. The initial study was focused on two arginine-free peptides. The 13 amino acid antimicrobial peptide aurein1.2 has been reported[68] to enhance cytoplasmic delivery by mediating endosomal escape of endocytosed proteins. The cationic amphiphilic 25 amino acid peptide L17E, a variant of haemolytic M lycotoxin with diminished cytotoxicity, was reported[56] to promote cytosolic uptake of different functional proteins up to full-length antibodies. So far, L17E-mediated cargo delivery was induced upon co-incubation with the peptide merely, and no efforts have been made to introduce a covalent linkage between both components, peptide and cargo. In the present study, both aurein1.2 and L17E were not able to promote cellular uptake when covalently linked to model conjugate in single unit. Hence, it remained to be investigated, whether an uptake-increasing multivalency effect could be generated by linkage of the respective peptide on a suitable scaffold in multiple copies.
Comprising α-(1-6) glycosidic bonds between D-glucose repeating units, biocompatible dextran polysaccharide has already been reported as a suitable hydrophilic scaffold for the generation of high-DAR antibody-drug conjugates[76] or multivalent platform for DR5-induced apoptosis.[78] The hydroxy groups of the glucose repeating units as well as the polysaccharide reducing end offered possibilities for multivalent functionalization of dextran.[61, 76, 78] Therefore, 10 kDa dextran was chosen as platform for covalent oligomerization of cell-penetrating peptides aurein1.2 and L17E. To this end, amine functionality was introduced to the polysaccharide reducing end via reductive amination and the hydroxy groups of the glucose repeating units were modified via carboxyethylation. Subsequent conversion of the introduced carboxyl moieties into either maleimide- or azide-functionalities enabled peptide and/or cargo conjugation via maleimide-thiol addition or Cu(I)-catalyzed azide-alkyne cycloaddition.
Decoration of maleimide-functionalized dextran polysaccharide with multiple copies of aurein1.2, respectively L17E, and a fluorescent label gave peptide-dextran hybrids, whose intracellular distribution was analyzed upon uptake in HeLa cells. L17E-dextran hybrid showed considerable superior uptake compared to the aurein1.2 variant. HeLa cells treated with TAMRA-labeled and L17E-decorated dextran module 37 at low micromolar concentration showed effective uptake of the macromolecule with fluorescence signals spread all over the cytosol and even nucleus (Figure 37, Figure 92). Furthermore, TAMRA-labeled dextran 37, covalently decorated with on average 3.8 L17E units, showed increased uptake compared to a TAMRA-labeled dextran co-incubated with solitary L17E peptide, as reported in the literature.[56] These encouraging findings led to development of a strategy for intracellular delivery of various cargo beyond fluorophore molecules, applying L17E-dextran hybrid as delivery module.
A possible cytotoxic effect of L17E-dextran module was assessed, applying dextran 42, decorated with on average 4.8 L17E peptide units. In the taken cell line, an IC50 value of approximately 10 µM (Figure 41) was determined, which was rather low and in an acceptable range when taken into consideration that L17E was derived from naturally haemotoxic lycotoxin.
L17E-dextran mediated cytosolic and nuclear delivery of peptide nucleic acid (PNA) was validated by mis-splicing correction assay in appropriate HeLa cells, stably transfected with enhanced green-fluorescent protein (eGFP) gene. Therefore dextran 43 was equipped with multiple copies of both L17E and PNA. The L17E-dextran module was able to deliver bioactive PNA into the nucleus of HeLa cells, whereupon the cargo PNA induced mis-splicing correction, leading to enhanced GFP fluorescence (Figure 45). This validated not only cytosolic, but even nuclear translocation of L17E-dextran module. Furthermore, the potential of dextran, equipped with multiple L17E peptides, was demonstrated to mediate intracellular uptake of PNA, that in general lacks cellular permeability and is not efficiently taken up by cells.
Finally, L17E-dextran module showed its ability to promote intracellular delivery of covalently conjugated protein cargo. To this end, a construct was designed, combining eGFP as model protein with L17E-decorated dextran serving as cytosolic uptake-promoting module. Synthesis was performed via iEDDA conjugation of a norbornene-functionalized dextran, bearing multiple orthogonal azide moieties, to a methyltetrazine-modified eGFP protein, followed by CuAAC "click" with alkyne-modified L17E peptide. At low micromolar concentration, yielded L17E-dextran-eGFP 44 was efficiently taken up by HeLa cells, visualized by widely spread and homogenic eGFP fluorescence inside the cytosol (Figure 52).
In conclusion, decoration of dextran polysaccharide with multiple copies of L17E peptides resulted in peptide-dextran hybrid, acting as a versatile uptake-mediating module. L17E-dextran promoted cytoplasmic delivery of covalently conjugated biomolecular cargo at low micromolar concentration without largely compromising cell viability. L17E has already been reported to promote cytosolic uptake of proteins, up to full-length antibodies, upon simple coincubation of solitary L17E peptide with the cargo.[56] However, uptake-mediating ability was improved via combining the oligomerization of L17E peptide on polysaccharide scaffold with the introduction of covalent connections between all counterparts: peptide, cargo, and dextran. In this way, a modular delivery system was established, which enabled intracellular delivery of various cargo, from PNA to proteins. Dependent on type and nature of the cargo, the multifunctionalized dextran backbone could be decorated following two strategies (Figure 59): One possibility included decoration of glucose repeating units with multiple copies of L17E and with multiple copies of cargo molecules simultaneously, while a further conjugation site at the reducing end remained accessible for conjugation of a potential second type of cargo. This option seemed to be beneficial for delivery of cargo such as peptides or PNA. The second possibility was based on decoration of the glucose repeating units with multiple L17E only, while the cargo was conjugated to the polysaccharide reducing end. The latter option seemed to be most suitable for more bulky cargo, such as proteins.
In addition to the encouraging results of this proof-of-concept studies, several issues remain to be investigated. For solitary L17E co-incubation-mediated cytoplasmic cargo delivery an uptake mechanism was proposed based on transient membrane permeabilization. L17E was thought to induce actin rearrangement upon interaction with the cell membrane, leading to membrane ruffling followed by macropinocytosis. Before macropinosome formation was accomplished, L17E assumedly ruptured the ruffled membrane, thus paving the way of direct cargo entry into the cytoplasm.[70] It remains to be ascertained, whether the same mechanism is appropriate for L17E in its dextran-conjugated state.
Moreover, regarding L17E-dextran mediated delivery of covalently conjugated protein cargo, it remains to substitute eGFP model protein with a functional biomolecule of interest. A broad range of intracellular targets exist, whose specific binding or functional blocking could be of interest in a therapeutic context. Single-domain antibodies, also called nanobodies, could be ideal candidates for addressing intracellular targets. Therefore, cytosolic delivery of these macromolecules would be of great importance and in the future, potentially could be realized via site-specific conjugation to L17E-dextran delivery module.


Caching is an approach to smoothen the variability of traffic over time. Recently it has been proved that the local memories at the users can be exploited for reducing the peak traffic in a much more efficient way than previously believed. In this work we improve upon the existing results and introduce a novel caching strategy that takes advantage of simultaneous coded placement and coded delivery in order to decrease the worst case achievable rate with 2 files and K users. We will show that for any cache size 1/K <; M <; 1 our scheme outperforms the state of the art.


In the last twenty years, a consensus has developed among courts and scholars that customary international law has the status of federal common law. We label this consensus the "modern position." Courts have endorsed the modern position primarily to support their conclusion that international human rights lawsuits between aliens "arise under" the laws of the United States for purposes of Article III of the Constitution. Scholars have pushed the consequences of the modern position further by arguing that customary international law preempts inconsistent state law under the Supremacy Clause, binds the President under the Take Care Clause, and even supersedes prior inconsistent federal legislation. In this Article, we question the modern position's historical validity, and show that its recent rise to orthodoxy has been accompanied by little critical scrutiny. We then question contemporary arguments for the modern position and show how these arguments depart form basic understandings about American representative democracy, federal common law, separation of powers, and federalism. We conclude that, in the absence of authorization by the federal political branches, customary international law should not have the status of federal law. This conclusion requires less change in judicial practice than might commonly be thought. Nonetheless, the story of the modern position's rise and continued influence presents cautionary lessons for a democratic society increasingly governed by international law.