bluuebunny/crossref_metadata_2025 huggingface dataset:
Manufactura digital: reconsideraciones teóricas y operativas en torno al ejercicio proyectual contemporáneo.
Authors: Corvalán Tapia Felipe Andrés
Published: November 2017

La integración de las fases de diseño, representación y fabricación que la tecnología digital permite, abre nuevas posibilidades al proyecto, reemplazando un proceso secuencial por otro simultáneo. Una simultaneidad que se vincula con una concepción artesanal y pre-moderna de la arquitectura. Los sistemas CAD/CAM establecen un puente de conexión interactivo entre la mente y la mano, entre creación y producción, posibilitando un desarrollo colaborativo del proyecto, desafiando la tradicional noción de autoría. Los puntos de contacto entre el trabajo artesanal y estas innovadoras tecnologías, permiten pensar a estas últimas como una suerte de manufactura digital, capaz de re-significar el vínculo entre conocimiento (software) y materialización (hardware), entre teoría y práctica . En este contexto, la presente investigación plantea una reflexión sobre las implicancias –teóricas y operativas– que esta incorporación tecnológica tiene o puede tener sobre la arquitectura y su desarrollo disciplinar, considerando además los desafíos planteados por la realidad contemporánea. 

The integration between design, representation and fabrication that digital technology allows, opens up new possibilities for the project. Thus simultaneous processes

replace the traditionally sequential processes. This simultaneity can be linked to a pre-modern architectural conception. The CAD/CAM systems connect mind and

hand, creation and production. This allows a collaborative working within the project, reshaping the author’s concept.

The connection between craftwork and these new technologies permits to think of these technologies as a kind of digital manufacturing; capable of re-signifying the link between knowledge (software) and materialization

(hardware), between theory and practice. In this context, the following research proposes a theoretical and operational discussion about the technological implications on architecture and its disciplinary development, considering

also the challenges of contemporary reality.
Entrevista a Juan Herreros
Authors: Herreros Juan , Peñín Llobell Alberto
Published: November 2017

Entrevista a Juan Herreros
Concurso Internacional Museo del Prado
Authors: - Foster and Partners , - Rubio Arquitectura
Published: November 2017

Foster + Partners y Rubio Arquitectura han ganado

el concurso internacional para la revitalización y

remodelación del histórico Salón de Reinos, que

se incorporará al Campus Prado en Madrid.

El diseño aspira a crear un nuevo foco urbano donde

todos los edificios que constituyen el Campus

Prado quedarán reunidos y enlazados mediante espacios

públicos y uniones subterráneas.

El Salón de Reinos es uno de los fragmentos

supervivientes del que fuera el Palacio del Buen Retiro,

del s. XVII, y ha sido objeto de numerosos cambios y

adiciones, acumulando varios estratos de historia

a lo largo de los siglos.

Las intervenciones que se plantean devolverán la vida a

los magníficos interiores del pasado y

añadirán novedosas salas de exposiciones y espacios

públicos. La propuesta se remonta cuatro siglos

F atrás para redescubrir la fachada original en tres niveles, y constituye la base sobre la cual alojar un

nuevo y espectacular espacio. Los muros exteriores han

sido delicadamente ampliados para introducir

la luz y establecer un vínculo con la nueva plaza cívica.

Foster + Partners and Rubio Arquitectura have won the international competition to revitalise and refurbish the historic Hall of Realms (Salón de Reinos) as a new addition to the Museo del Prado campus in Madrid.

The vision is to create a new public focus for the city by bringing together the various buildings that comprise the Prado with public spaces and underground links.

The Hall of Realms is a noble structure and one of the very few that have survived from the former Palacio del Buen Retiro of the seventeenth century. It has been the

subject of changes and expansion, gathering many layers of history over the centuries.

The interventions will bring fresh life to the magnificent interiors from the past as well as adding new state-of-the-art galleries and public spaces. The proposal goes back four centuries to re-discover the original three

storey southern façade. This becomes the backdrop for a spectacular new space within the building. The existing outer walls have been delicately opened up to bring light

and views in from the new civic plaza.
Editorial
Authors: Obiol Cordon Cecilia
Published: November 2017

Editorial Palimpsesto 16
Congres Arquitectura 2016
Authors: Comeron Graupera Lluis Xavier
Published: November 2017

Congres Arquitectura 2016
Efecto de la acción posterior a la recepción sobre la amortiguación de los saltos verticales.
Authors: Gutiérrez-Dávila M. , Olivares J. , Pancorbo D. , Rojas F.J.
Published: November 2017

El principal objetivo de este estudio ha sido comprobar el efecto que tienen tres acciones posteriores al aterrizaje del salto vertical (aterrizaje discreto (AD), aterrizaje preparatorio al salto (APS), aterrizaje preparatorio a la carrera (APC)) sobre los factores mecánicos que determinan la amortiguación. Han participado 29 estudiantes con experiencia en deportes donde el salto vertical constituye una habilidad básica. Se ha utilizado una plataforma de fuerza operando a 500 Hz, sincronizada con una cámara de vídeo que registraba a 210 Hz el plano sagital del movimiento. En la situación AD, debían dejarse caer a una plataforma desde una altura de 0.5 m partiendo de una posición erguida con los brazos por encima de la cabeza y permitiendo su participación libre durante la fase de impacto (FI). En la condición APS, se procede igual pero, a continuación, se realiza un salto vertical máximo y, en la condición APC, el aterrizaje se acompaña con un desplazamiento horizontal. Los resultados indican que el 2-PMF (pico máximo de fuerza) es mayor para AD, alcanzándose antes que en APS y APC. Al inicio de la recepción el centro de gravedad está más adelantado en APC debido a la carrera posterior. En el 2-PMF, el desplazamiento horizontal del CG (SxCG) y la velocidad horizontal del CG (VxCG) se han incrementado con la carrera posterior con respecto a las otras dos situaciones, una tendencia cinemática que se mantiene hasta el final de FI. Con la carrera posterior, la mayor contribución a la amortiguación la realizan las piernas en su desplazamiento hacia delante, mientras que en las otras dos situaciones se compensa con el desplazamiento hacia atrás de los muslos.
Worldwide Frequency of Commonly Detected EGFR Mutations
Authors: Graham Rondell P. , Treece Amanda L. , Lindeman Neal I. , Vasalos Patricia , Shan, Mu , Jennings Lawrence J. , Rimm David L.
Published: November 2017

Context.—

Recurrent epidermal growth factor receptor (EGFR) mutations are seen in a subset of pulmonary adenocarcinomas. These mutations are targeted by EGFR inhibitors and are a biomarker for response to EGFR inhibitor therapies. Initial data have indicated an increased frequency of activating EGFR mutations in nonsmoking Asian females. However, there are very few studies of global scope that address the question of mutation distribution across the population of lung cancer.

Objective.—

To determine the frequency of EGFR mutations in exons 18 through 21 detected in clinical laboratories participating in the College of American Pathologists proficiency testing program for EGFR in calendar year 2013.

Design.—

We reviewed the surveys from 170 clinical laboratories from 20 countries that participated in the College of American Pathologists EGFR proficiency testing program. The proficiency testing includes questions regarding the total numbers of tests performed at each common mutation site, including both activating and resistance mutations, and their frequency. Countries were grouped into regional groups in order to assess frequency of mutation by type, and to indirectly assess ethnic differences in mutation frequencies.

Results.—

Among the treatment-sensitive activating mutations, the most common are exon 19 mutations (n = 10 802 of 136 533 cases; 7.9% of total cases tested) and the exon 21 L858R mutation (n = 10 351 of 136 533 cases; 7.6% of total cases tested) and the least common are exon 20 mutations (n = 466 of 136 533 cases; 0.3% of total cases tested). The T790M mutation in exon 20 is the more common resistance mutation (n = 1010 of 136 533 cases; 0.7% of all cases tested). The highest activating mutation frequency is seen in southern Asia (n = 4260 of 9337 cases; 46%) and the lowest activating mutation frequencies are in South and North America (n = 113 of 1439 cases and 7926 of 86 654 cases; 8% and 9%, respectively).

Conclusions.—

Our data confirm that activating EGFR mutations are more common in southern Asia and that the distribution of activating EGFR mutations varies significantly across the regions. Similarly, the frequency and distribution of resistance mutations also show significant variation when comparing southern Asia with other regions.
The cost of a combination Anti-Retroviral Therapy (cART) optimization pathway as maintenance therapy in HIV-1 infected patients
Authors: Ravasio Roberto , Rigo Fabio , Lattuada Emanuela , Concia Ercole , Lanzafame Massimiliano
Published: November 2017

BACKGROUND: In order to reduce/prevent combination Anti-Retroviral Therapy (cART)-related toxicity, while maintaining its therapeutic effectiveness over time, the optimization of the antiretroviral therapy could be performed.AIM: To estimate the economic impact on the Italian National Health Service (NHS) of a cART optimization pathway as maintenance therapy in HIV-1 infected patients over one-year period.METHODS: Patient data were retrieved from the electronic medical record system in use (year 2015) in a reference HIV Center in Northern Italy. The analysis considered naïve patients and non-naïve patients. To estimate the actual ART expenditure charged to the Center we calculated the cost of cART received during 12 months for each patient. Subsequently, referring to the same patients, a "potential" cART expenditure was estimated. This potential expenditure was estimated taking in consideration the adoption of a specific optimization pathway aimed at maintaining over the time the cART efficacy. Lastly, to assess the sustainability of the optimization pathway, we compared the actual cART expenditure with the potential one. We considered only drug costs (ex-factory prices, included all discounts and VAT) from the perspective of the Italian NHS.RESULTS: In the 2015, the total expenditure for 564 enrolled HIV-1 patients treated with cART was € 4,042,983. The mean treatment cost per patient was € 7,168. If the Center adopted a specific optimization pathway, the total expenditure would be € 3,914,855 (€ -128,128).CONCLUSIONS: From the Italian NHS’s perspective, the adoption of a specific cART optimization pathway represents a cost-saving option as maintenance antiretroviral therapy in HIV-1 infected patients.
Reducing Bidirectional Pedestrian Conflict Based on Lane Formation Phenomenon in Subway Corridors
Authors: Qiao Jing , Sun Lishan , Qiu Shi , Rong Jian , Liu Xiaoming
Published: November 2017

With the rapid increase of the subway passenger volume, the conflict among passengers emerges as a significant issue which affects subway serviceability, especially in the bidirectional flow. The aim of this study is to explore the characteristics of the bidirectional flow of pedestrians in a subway corridor. Pedestrian experiments were conducted to investigate microscopic characteristics of the pedestrian flow. It was found that the microscopic characteristics, including the walking speed and turning angle, were time-dependent and had a generalized trend with time. It was also found that different pedestrian volumes affected the microscopic characteristics. Based on the trend of the microscopic characteristics, the lane formation phenomenon was observed and quantitatively studied, identifying three phases: conflict phase, lane formation phase, and steady lane phase. To alleviate the bidirectional pedestrian conflict, additional pedestrian experiments for the countermeasure of adding separating strap in the corridor, which was based on the lane formation analysis, was conducted. The effectiveness of the countermeasure was demonstrated through a before-and-after comparison. The results showed that adding the separation between the adjacent lanes had the best performance in reducing the conflicts. The results would provide a rationale for subway managers in optimizing the corridor bidirectional pedestrian flow.
Investigating the Applicability of Upstream Detection Strategy at Pedestrian Signalised Crossings
Authors: Hassan Sitti A , Hounsell Nick B , Shrestha Birendra P
Published: November 2017

In the UK, the Puffin crossing has provision to extend pedestrian green time for those who take longer to cross. However, even at such a pedestrian friendly facility, the traffic signal control is usually designed to minimise vehicle delay while providing the crossing facility. This situation is rather contrary to the current policies to encourage walking. It is this inequity that has prompted the need to re-examine the traffic control of signalised crossings to provide more benefit to both pedestrians and vehicles. In this context, this paper explores the possibility of implementing an Upstream Detection strategy at a Puffin crossing to provide a user friendly crossing. The study has been carried out by simulating a mid-block Puffin crossing for various detector distances and a number of combinations of pedestrian and traffic flows. This paper presents the simulation results and recommends the situations at which Upstream Detection would be suitable.
Container Throughput Forecasting Using Dynamic Factor Analysis and ARIMAX Model
Authors: Intihar Marko , Kramberger Tomaž , Dragan Dejan
Published: November 2017

The paper examines the impact of integration of macroeconomic indicators on the accuracy of container throughput time series forecasting model. For this purpose, a Dynamic factor analysis and AutoRegressive Integrated Moving-Average model with eXogenous inputs (ARIMAX) are used. Both methodologies are integrated into a novel four-stage heuristic procedure. Firstly, dynamic factors are extracted from external macroeconomic indicators influencing the observed throughput. Secondly, the family of ARIMAX models of different orders is generated based on the derived factors. In the third stage, the diagnostic and goodness-of-fit testing is applied, which includes statistical criteria such as fit performance, information criteria, and parsimony. Finally, the best model is heuristically selected and tested on the real data of the Port of Koper. The results show that by applying macroeconomic indicators into the forecasting model, more accurate future throughput forecasts can be achieved. The model is also used to produce future forecasts for the next four years indicating a more oscillatory behaviour in (2018-2020). Hence, care must be taken concerning any bigger investment decisions initiated from the management side. It is believed that the proposed model might be a useful reinforcement of the existing forecasting module in the observed port.
Collision Avoidance via Adaptive Trajectory Control in Case of a Sudden Decrease in the Maximum Road Friction Coefficient
Authors: Şahin Hasan
Published: November 2017

This study analyses an Adaptive Trajectory Control (ATC) system in case of a sudden change in μ-max (maximum tyreroad friction coefficient) during an emergency lane change manoeuvre in order to maintain the driving safety. Autonomous front wheel steering (FWS) systems have been developed for emergency steering situations. The trajectory design is also a part of these systems. Moreover, in this study ATC has been designed by sensing μ-max to complete the emergency steering manoeuvre successfully. Therefore, the originality of this paper arises from the necessity of a trajectory change in case of a sudden change in μ-max to minimize the distance between the desired and the actual path. Suitable cases were designed by using a two-track model in IPG/CarMaker (MATLAB/Simulink). Results show that ATC could be used during an emergency steering manoeuvre in case of a sudden decrease in μ-max as it can be advantageous in certain critical traffic situations. Therefore, ATC could beused as an alternative system instead of Electronic Stability Program.
Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments
Authors: Spira Felix , Cuylen-Haering Sara , Mehta Shalin , Samwer Matthias , Reversat Anne , Verma Amitabh , Oldenbourg Rudolf , Sixt Michael , Gerlich Daniel W
Published: November 2017

The actomyosin ring generates force to ingress the cytokinetic cleavage furrow in animal cells, yet its filament organization and the mechanism of contractility is not well understood. We quantified actin filament order in human cells using fluorescence polarization microscopy and found that cleavage furrow ingression initiates by contraction of an equatorial actin network with randomly oriented filaments. The network subsequently gradually reoriented actin filaments along the cell equator. This strictly depended on myosin II activity, suggesting local network reorganization by mechanical forces. Cortical laser microsurgery revealed that during cytokinesis progression, mechanical tension increased substantially along the direction of the cell equator, while the network contracted laterally along the pole-to-pole axis without a detectable increase in tension. Our data suggest that an asymmetric increase in cortical tension promotes filament reorientation along the cytokinetic cleavage furrow, which might have implications for diverse other biological processes involving actomyosin rings.
Amount of sediment drained into the Pacific coast in northwestern Baja California, Mexico
Authors: Pou-Alberú S , Pozos-Salazar G
Published: November 2017

The amount of sediment drained into the Pacific coast due to the orographic system of northern Baja California was estimated by indirect methods. Langbein and Schumm’s (1958) equation was used to relate the erosive action of the rain and the protective action of the vegetation. Statistics on pluvial precipitation for 1950 to 1983 of 21 stations of the Secretaría de Agricultura y Recursos Hidráulicos were used. Furthermore, topographical data of 44 charts of the Instituto Nacional de Estadística, Geografía e Informática (INEGI), corresponding to the northern area of Baja California, were digitized on a PRIME 750 computer and processed with a program (TOPOGRAFIC) developed at the Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE). Two drainage basins were identified as maximum potential sources of sediment: the Tijuana River basin (S = 809649.88 tons/year) and the Guadalupe River basin (S = 834889.13 tons/year). According to the model, these are not maximum values. Higher values can be expected with greater rainfall and we therefore consider this area to be one of high geological risk.
Zooplankton biomass of the northernmost Gulf of California
Authors: Farfán C , Álvarez-Borrego S
Published: November 2017

To assess the spatial and temporal fluctuations of zooplankton biomass, as dry organic weight per cubic meter (B), in the northernmost Gulf of California, twelve oceanographic cruises were carried out during the period October 1972-October 1973. There was no clear seasonal cycle. However, there are some persistent characteristics. The highest B values (as high as 154 mg m–3) were always found in the channels around Montague Island (at the Colorado River delta). In general, B values increased westward or northwestward. In the period May-October 1973, there were more uniform gradients, with values at the southeast one order of magnitude smaller than those at the northwest. In general, calanoid copepods were the most abundant taxonomic group, both numerically and in terms of biomass. Without considering B the values found around Montague Island, minimum values were found in October (1-4 mg m–3) and maximum values in August (25-150 mg m–3). A principal component analysis shows that the B variance was partly explained by a component whose structure is associated to the bathymetry. The linkage may be S‰. Highest salinities in the Montague Island area indicate higher residence time of water, because they are due to the greater accumulated effect of evaporation in comparison with the more southern areas. Greater residence time may also be related to higher zooplancton biomass in the north. There was a weak ENSO (El Niño-Southern Oscillation) event in the years 1972-73. However, strong local dynamics, mainly upwelling and mixing phenomena associated with tides, maintain sufficiently high nutrient concentrations for primary productivity not to have been significantly affected by ENSO events in the central and northern Gulf (tidal amplitude may be as high as 9 m at the Colorado River delta). Thus, our B data may not reflect any effect of the “El Niño” event in 1972-73.
Estimation of the reproductive biomass of the pacific mackerel (Scomber japonicus Houttuyn, 1782) In The Gulf Of California (January-February 1987)
Authors: Green-Ruiz YA , Aguirre-Medina G
Published: November 2017

Thee distribution and abundance of the Pacific mackerel (Scomber juponicus Houttuyn, 1782), derived from the analysis of 5.5 oblique tows made in the Gulf of California in January-February 1987, are presented. The reproductive biomass was estimated at 165,908 metric tons (MT), with a maximum sustainable yield of 16,518 MT if mortality (z) is 0.497.
Nitrogen effect on growth and carrageenan content in Gigartina canaliculata Harv. (Rhodophyta, Gigartinales), in outdoor tank cultures
Authors: González-Gómez MA , Zertuche-González JA , Pacheco-Ruíz I
Published: November 2017

Gigartina canaliculata was cultivated under different nutrient conditions in 100-l tanks, to study the effect on growth and yield and quality of carrageenan. The cultures were under four frequencies of pulse fertilization: every 2, 4, 7 and 14 days, for seven weeks. The doses for each fertilization consisted of 100:00 µM of NO3–:PO4–2 for three hours. An inverse relationship was observed between growth and carrageenan yield: the highest growth was observed in the more fertilized culture (5.5% day–2), whereas the highest carrageenan yield was observed in the less fertilized culture (49%). Maximum gel strengh was 41 g cm–2 for the more fertilized cultures (two and three times a week). However, there were no significant differences in the sulfate content among the treatments (22%). The different nutrient doses resulted in a difference in carrageen a yield of approximately 5% among the highest and the lowest fertilized culture. The production of biomass, however, was 1.8 times higher for the more fertilized culture. Thus, carrageenan yield production per tank was much higher for the more fertilized culture.
Effect of the microalga Pavlova lutheri (Droop) Hibberd cultured with agricultural fertilizers on the growth and survival of larvae and postlarvae of the mussel Mytilus edulis (L.)
Authors: McAnally-Salas LS , Ocampo-Aranda FJ , García-Pámanes LE
Published: November 2017

An evaluation was made of the growth and survival of Mytilus edulis larvae to metamorphosis, fed on Pavlova lutheri cultured with three nitrogen sources: two agricultural fertilizers (urea and ammonium sulphate) and laboratory-grade nitrate (medium f/2). In the larval stage, survival between trials was greater than 92.0%, whereas total survival was greater than 87.0% and there were no significant differences between the three treatments. Growth of larvae fed Pavlova lutheri cultured with ammonium sulphate and f/2 was the same during the first 20 days of larval development, except on days 6 and 10. Lesser growth occurred in the treatment with urea and there were significant differences relative to the other two treatments, except on day 20 when growth was the same as in the treatment with ammonium sulphate. Seed survival was better in the two treatments with agricultural fertilizers, with no differences between the two, than in the f/2 treatment, with significant differences relative to urea and ammonium sulphate. Better seed growth was obtained in the treatment with ammonium sulphate, whereas growth in the urea and f/2 treatments was similar and there were no significant differences between the two. The results indicate that urea and ammonium sulphate, especially the latter, can be considered good alternatives for use in the laboratory production of microalgae, reducing costs by 98.81% relative to f/2.
Assimilation and growth efficiencies of postlarvae and juveniles of the Malaysian prawn, Macrobrachium rosenbergii (De Man), fed two balanced diets
Authors: Díaz-Herrera F , Pérez-Cruz E , Juárez-Castro G , Bückle-Ramírez LF
Published: November 2017

Assimilation efficiency was determined in postlarvae and juveniles of the freshwater prawn, Macrobrachium rosenbergii, fed Purina Trout Chow and Bovilac Prawn diets. Assimilation, which depends on the assimilation efficiency as well as on the amount of food intake, was 43% higher for the postlarvae and 60% higher for the juveniles fed Purina than for those fed Bovilac (P < 0.05). The assimilation efficiency values were calculated by the Condrey et al. (1972) modified method, which considers the assimilated food in dry weight from the consumed material. The results show that postlarvae and juveniles fed Purina had an assimilation efficiency of 13 and 43.5% higher (P < 0.05) than the ones fed Bovilac. The indices of utilization of consumed or assimilated energy for growth, K1 and K2, were significantly higher (P < 0.05) for the prawns fed Purina than for those fed Bovilac.
Comment on “Radiative Transfer in CO2‐Rich Atmospheres: 1. Collisional Line Mixing Implies a Colder Early Mars”
Authors: Turbet M. , Tran H.
Published: November 2017

Ozak et al. (2016) claimed that explicitly including the effect of CO2 collisional line mixing in their radiative transfer calculations yield CO2 atmospheres that are more transparent to infrared radiation than when spectra calculations are made using sub‐Lorentzian line shapes. This would in particular imply significantly colder surface temperatures (up to 15 K) for early Mars than estimated in previous studies. Here we show that the relative cooling that Ozak et al. (2016) associated to the effect of collisional line mixing is in fact due to a wrong choice of broadening species (air instead of CO2). We then calculated line‐by‐line spectra of pure CO2 atmospheres using a line‐mixing model developed for self‐broadened CO2. Using the LMD Generic model (in 1‐D radiative‐convective mode), we find that calculations made with the proper collisional line mixing model and with sub‐Lorentzian line shapes lead to differences between early Mars surface temperatures smaller than 2 K only.
Assessment and Construction of Designed Experiments
Authors: Anderson‐Cook Christine M. , Lu Lu
Published: November 2017

Collecting data as part of a designed experiment involves choices between different candidate designs. The criteria for choosing between these designs involve many competing objectives that frequently force us to make trade‐offs based on which of these ideal characteristics of the design we think are most important. Optimality criteria are single‐number summaries for the “goodness” of the design, which typically focus on the quality of estimation or prediction. In addition to these measures, the robustness of the design to model misspecification, problems with data collection during the experiment, or erroneous data are also important. A number of the characteristics of good designs are outlined and compared, and some graphical methods for better understanding the performance of a design are shown. Simultaneously, considering multiple criteria is helpful to maximize the gain of information from the experiment. Given the trade‐offs between different aspects of design performance including the size of the experiment, using a structured approach for guiding the evaluation and comparison can help facilitate discussion for making an informed and tailored decision that matches the goals of a particular experiment.
K
ullback–
L
eibler Information
Authors: Claeskens Gerda
Published: November 2017

The Kullback–Leibler information number, , determined for two probability measures defined on the same measurable space, often serves as a type of “distance” between the two measures. Projections (‐projections) defined in terms of minimizing the Kullback–Leibler information number over appropriate sets of probability measures are often useful for finding desirable estimators. Kullback–Leibler information numbers also play a useful role in hypothesis testing problems, and they are the basis for several information criteria used for model selection.
Targeted Minimum Loss‐Based Estimation
Authors: van der Laan Mark J. , Benkeser David , Sofrygin Oleg
Published: November 2017

Statistical models that accurately reflect scientific knowledge are often, by necessity, infinite‐dimensional. Estimation of smooth parameters using standard estimation techniques in such models is problematic. For example, maximum likelihood estimators often behave poorly in large models due to the fact that such estimators trade off bias and variance with respect to estimation of the density of the observed data, while the target parameter is a low‐dimensional summary measure of this density. To obtain valid estimators in these situations, we must tailor the estimation procedure to the parameter of interest. Targeted minimum loss‐based estimation (TMLE) provides a template for constructing well‐behaved estimators of smooth parameters in infinite‐dimensional models. TMLE estimators are not only asymptotically consistent and normally distributed but also are designed to exhibit robust finite‐sample performance. The remainder of this article provides an introduction to the TMLE procedure and discusses recent advances in the field of targeted learning.
Proteomic Analysis of Post‐Translational Modifications by Mass Spectrometry
Authors: Gruhler Albrecht , Jensen Ole N.
Published: November 2017

The sections in this article are

Introduction

Considerations for the Experimental Design ofPTMAnalysis by Proteomics

Analysis ofPTMsby Proteomic Approaches

Conclusions and Perspectives

Acknowledgements
Proteomics of Disulphide and Cysteine Oxidoreduction
Authors: Maeda Kenji , Hägglund Per , Finnie Christine , Svensson Birte
Published: November 2017

The sections in this article are

Introduction

Control of Cellular Redox Status

Proteomics Techniques for Analysis of Cysteine Modifications

Conclusions and Perspectives

Acknowledgements
Cereal Proteomics
Authors: Komatsu Setsuko
Published: November 2017

The sections in this article are

Introduction

Comprehensive Analysis and Cataloguing of Cereal Proteins

Functional Analysis of Cereal Using Differential Proteomics

Future Prospects of Cereal Proteomics
Surveying the Plant Cell Wall Proteome, or Secretome
Authors: Isaacson Tal , Rose Jocelyn K.C.
Published: November 2017

The sections in this article are

Introduction

The Multifunctional Cell Wall

Technical and Conceptual Challenges in Defining the Cell Wall Proteome, or Secretome

Approaches for Plant Cell Wall Protein Extraction and Identification

Computational Prediction of the Plant Secretome

Functional Screens for Extracellular Proteins

Contamination and Validation of the Cell Wall Proteome

Conclusions
General Transcription Factors and the Core Promoter: Ancient Roots
Authors: Gurley William B. , O'Grady Kevin , Czarnecka‐Verner Eva , Lawit Shai J.
Published: November 2017

The sections in this article are

Introduction

Origins of the Eukaryotic Promoter

Organization of the Eukaryotic Promoter

Transcription FactorIID

Role ofTFIIDin Development

Mediator

Transcription FactorIIB
Matrix Attachment Regions and Transcriptional Gene Silencing
Authors: Thompson William F. , Spiker Steven , Allen George C.
Published: November 2017

The sections in this article are

Introduction

Costs and Consequences of Transgene Expression Variation

Position Effects

Gene Silencing

Matrix Attachment Regions

MARsand Transgene Expression

MAREffects inArabidopsis

Conclusions
Combinatorial Control of Floral Organ Identity by
MADS
‐Domain Transcription Factors
Authors: Theißen Günter , Melzer Rainer
Published: November 2017

The sections in this article are

Introduction

ABC
: Early Genetic Models of Floral Organ Identity

From the
ABC
to the
ABCDE
Model

Elective Affinities of Homeotic Proteins: The Floral Quartet Model

Beyond the Floral Quartets
Sensu Stricto
: Multimeric Complexes of Other
MIKC
‐Type Proteins

Outlook: The Devil is Always in the Details – What We Still Don't Know about Floral Quartets

Acknowledgments
Outgrowing the laboratory diagnosis of type 1 von Willebrand disease: A two decade study
Authors: Abou‐Ismail Mouhamed Yazan , Ogunbayo Gbolahan O. , Secic Michelle , Kouides Peter A.
Published: November 2017

Von Willebrand Factor (VWF) levels are known to increase with age in the general population, but that effect is unclear in von Willebrand disease (VWD) patients. Thus, it is important to assess the trends of VWF levels with age, and the extent and rate of their normalization in patients with VWD. In a retrospective cohort study, we reviewed the medical records of 126 patients between 1996 and 2016 who met the NHLBI diagnostic criteria for type 1 VWD or “Low VWF” (LVWF). We followed all their historically documented VWF antigen (VWF:Ag), VWF activity (VWF:RCo), and Factor VIII (FVIII) levels longitudinally over time, correlating data with clinical setting at time of testing. The average duration of follow‐up was 10.5 ± 3.7 years (SD). Out of the total study population, 27.8% achieved the primary outcome of complete normalization (CN) of both VWF:Ag and VWF:RCo levels, including 19.6% and 32.5% of those with VWD and LVWF, respectively. Linear regression demonstrated statistically significant positive trends of VWF:Ag, VWF:RCo, FVIII with time, calculated at 2.4, 1.4, and 1.4 U dL‐1/year, respectively (P < .001 each). In the largest study population of VWD patients to date whose levels were followed longitudinally, there is a statistically significant rise in VWF:Ag, VWF:RCo, and FVIII levels observed with time. CN of both VWF:Ag and VWF:RCo levels was observed in almost a third of patients with VWD or LVWF, over an average of 10 years. Whether the bleeding phenotype also improves is unclear and requires further study.
Solvent‐free, l‐Leucine‐Catalyzed Direct Dehydrative Esterification of Carboxylic Acids with Alcohols: Direct Synthesis of 3‐Alkoxy 1(3 H)‐isobenzofuranone
Authors: Kumar Manoranjan , Thakur Krishna , Sharma Sushila , Nayal Onkar S. , Kumar Neeraj , Singh Bikram , Sharma Upendra
Published: November 2017

A l‐leucine‐catalyzed mild and efficient method has been developed for the synthesis of open‐chain as well as cyclic esters. A wide range of alcohols, including primary, secondary, and tertiary with aliphatic and aromatic side chains, were successfully tolerated. In the case of 2‐carboxybenzaldehydes with different alcohols, 3‐alkoxy‐1‐(3 H)‐isobenzofuranones were obtained in good yields. Alcohols from natural origin have also been reacted with various acids successfully to get the corresponding esters. The reaction proceeded under neat conditions and there is no need for any acid, base, or removal of water during the reaction.
Synthesis of Chiral Acyclic Pyrimidine Nucleosides with a Sulfur‐Containing Side Chain via Enantioselective Tandem Conjugate Addition/Protonation
Authors: Li Jian‐Ping , Tuo Hao‐Ran , Xie Ming‐Sheng , Kang Bo , Qu Gui‐Rong , Guo Hai‐Ming
Published: November 2017

A direct route to chiral pyrimidine acyclic nucleoside analogues with a sulfur‐containing side chain is reported via enantioselective tandem conjugated addition‐protonation reactions of thioacetic acid to α‐pyrimidine substituted acrylates. In the presence of a quinine‐derived thiourea catalyst, diverse chiral sulfur‐containing pyrimidine acyclic nucleoside analogues could be obtained in excellent yields (95–99 %) and with moderate to excellent enantioselectivity values (up to 99 % ee).
Efficient Encapsulation of Fluorinated Drugs in the Confined Space of Water‐Dispersible Fluorous Supraparticles
Authors: Pigliacelli Claudia , Maiolo Daniele , Nonappa  , Haataja Johannes S. , Amenitsch Heinz , Michelet Claire , Sánchez Moreno Paola , Tirotta Ilaria , Metrangolo Pierangelo , Baldelli Bombelli Francesca
Published: November 2017

Fluorophobic‐driven assemblies of gold nanomaterials were stabilized into water‐dispersible fluorous supraparticles by the film‐forming protein hydrophobin II. The strategy makes use of fluorous nanomaterials of different dimensions to engineer size and inner functionalization of the resulting confined space. The inner fluorous compartments allow efficient encapsulation and transport of high loadings of partially fluorinated drug molecules in water.
Atom‐Specific Mutagenesis Reveals Structural and Catalytic Roles for an Active‐Site Adenosine and Hydrated Mg2+ in Pistol Ribozymes
Authors: Neuner Sandro , Falschlunger Christoph , Fuchs Elisabeth , Himmelstoss Maximilian , Ren Aiming , Patel Dinshaw J. , Micura Ronald
Published: November 2017

The pistol RNA motif represents a new class of self‐cleaving ribozymes of yet unknown biological function. Our recent crystal structure of a pre‐catalytic state of this RNA shows guanosine G40 and adenosine A32 close to the G53–U54 cleavage site. While the N1 of G40 is within 3.4 Å of the modeled G53 2′‐OH group that attacks the scissile phosphate, thus suggesting a direct role in general acid–base catalysis, the function of A32 is less clear. We present evidence from atom‐specific mutagenesis that neither the N1 nor N3 base positions of A32 are involved in catalysis. By contrast, the ribose 2′‐OH of A32 seems crucial for the proper positioning of G40 through a H‐bond network that involves G42 as a bridging unit between A32 and G40. We also found that disruption of the inner‐sphere coordination of the active‐site Mg2+ cation to N7 of G33 makes the ribozyme drastically slower. A mechanistic proposal is suggested, with A32 playing a structural role and hydrated Mg2+ playing a catalytic role in cleavage.
Ligand‐Directed Divergent Synthesis of Carbo‐ and Heterocyclic Ring Systems
Authors: Lee Yen‐Chun , Kumar Kamal , Waldmann Herbert
Published: November 2017

Chemical tools that enable a catalytic reaction to selectively and efficiently yield different products will allow charting of wider chemical space. In ligand‐directed divergent synthesis, a common mode of catalysis is modulated by employing different ligands for catalytic organometallic complexes to transform either common substrates or common reactive intermediates into distinct molecular scaffolds. The strategy has the potential to create important and diverse scaffolds and to unveil novel modes of catalytic transformations for wider synthetic applications. This strategy is described and recent efforts in this emerging field of catalysis, focusing on transition‐metal catalysis for the synthesis of carbo‐ and heterocyclic ring systems, are reviewed.
Synthesis, spectral characterization, thermal studies and biological activity of (Z)‐5‐((1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)diazenyl)‐6‐hydroxy‐2‐mercaptopyrimidin‐4(3H)‐one and its metal complexes
Authors: Emam Sanaa M. , Abouel‐Enein Saeyda A. , Abouzayed Fatma I.
Published: November 2017

(Z)‐5‐((1,5‐Dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)diazenyl)‐6‐hydroxy‐2‐mercaptopyrimidin‐4(3H)‐one (H3L) was exploited as a ligand for the synthesis of a series of metal complexes, where the metal was Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Pd(II), Cr(III) and Ru(III). The structural features of the ligand and the synthesized complexes were characterized using various analytical, spectral and thermal measurements. Infrared spectra showed that the ligand coordinates to all metal ions in a neutral keto–enol–thiol manner. It behaves in a tetradentate fashion in all binuclear complexes except the Cr(III) complex, where it is hexadentate, and in a tridentate fashion in mononuclear complexes. The azo group participates in chelation only in the case of binuclear complexes. All complexes exhibit octahedral geometry except Pd(II) and Cu(II) acetate which are square planar and square pyramidal, respectively. Kinetic parameters were computed from thermal decomposition data. Axial electron spin resonance spectra were obtained for Cu(II) complexes indicating ()1as a ground state with smallg||values affording strong interaction between the ligand and metal ions. The biological measurements reveal that the ligand has antioxidant activity relative to the metal complexes, while the metal complexes have cytotoxicity in comparison to the free ligand.
Effect of adding a reactive plasticizer on the mechanical, thermal, and morphology properties of nylon toughened wheat gluten materials
Authors: Langstraat Thomas , Van Puyvelde Peter , Delcour Jan , Verpoest Ignaas , Goderis Bart
Published: November 2017

Blends of wheat gluten (WG) with up to 30% aliphatic nylon were prepared by mixing in 70% aqueous ethanol solution at 110 °C in a sealed reactor. After solvent removal and mechanical milling, rigid plaques were compression molded from the powdered blends. The microstructure of the molded plaques was studied via scanning electron microscopy. All compositions showed a phase separated morphology with seemingly poor compatibility between the two components. Up to 10% addition, the nylon was dispersed within the gluten matrix as discrete particles with an average diameter >10 μm. At higher nylon volume fractions there was evidence for the presence of gluten sub‐inclusions within the nylon phases. The dispersion of particles in a blend containing 10% nylon was improved and the particle size was decreased to roughly 5 μm by addition of an epoxy functionalized ethylene glycol oligomer. The additive simultaneously lowered the modulus of the WG matrix and appeared to improve the interfacial bonding between the gluten and the nylon. In cross‐sections of the ternary blends, fine filaments were observed spanning the gluten/nylon phases at the phase boundary. The compression molded plaques continued to exhibit brittle failure in mechanical bending tests characteristic of glassy gluten materials, however, the mechanical toughness was boosted to almost three times that of reference gluten plaques by the combined addition of the nylon and reactive plasticizer. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45931.
Evolution of morphology, ferroelectric, and mechanical properties in poly(vinylidene fluoride)–poly(vinylidene fluoride‐trifluoroethylene) blends
Authors: Suresh G. , Mallikarjunachari G. , Jatav Sanjay , Thirmal Ch. , Ramachandra Rao M. S. , Satapathy Dillip K.
Published: November 2017

Considering the complementary properties of poly(vinylidene fluoride) (PVDF) and poly(vinylidene fluoride‐trifluoroethylene) [P(VDF‐TrFE)], it appears that their blends have the potential to be promising candidates for device applications. We report the evolution of morphology, ferroelectric, and mechanical properties (modulus and hardness) and their dependence on preparation temperature for PVDF–P(VDF‐TrFE) blends. From ferroelectric hysteresis measurements it was found that P(VDF‐TrFE) rich blends treated at higher temperature show significant values of remanent polarization. Remanent polarization values show a fourfold increase in these P(VDF‐TrFE) rich blends treated at higher temperature. Interestingly, blends prepared from high temperature showed greater value of remanent polarization even though they were found to consist of smaller amount of electroactive phase as compared to their low temperature treated counterpart. Nanoindentation experiments revealed that high temperature treatment improves the modulus of blends by at least 100%. This report attempts to tie these findings to the morphology and crystallinity of these blends. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45955.
Genetic Variants inERAP1andERAP2Associated With Immune‐Mediated Diseases Influence Protein Expression and the Isoform Profile
Authors: Hanson Aimee L. , Cuddihy Thomas , Haynes Katelin , Loo Dorothy , Morton Craig J. , Oppermann Udo , Leo Paul , Thomas Gethin P. , Lê Cao Kim‐Anh , Kenna Tony J. , Brown Matthew A.
Published: November 2017

Objective

Endoplasmic reticulum aminopeptidase 1 (ERAP‐1) andERAP‐2,encoded on chromosome 5q15, trim endogenous peptides forHLA‐mediated presentation to the immune system. Polymorphisms inERAP1and/orERAP2are strongly associated with several immune‐mediated diseases with specificHLAbackgrounds, implicating altered peptide handling and presentation as prerequisites for autoreactivity against an arthritogenic peptide. Given the thorough characterization of disease risk–associated polymorphisms that alterERAPactivity, this study aimed instead to interrogate the expression effect of chromosome 5q15 polymorphisms to determine their effect onERAPisoform and protein expression.

Methods

RNAsequencing and genotyping across chromosome 5q15 were performed to detect genetic variants inERAP1andERAP2associated with altered total gene and isoform‐specific expression. The functional implication of a putative messengerRNAsplice‐altering variant onERAP‐1 protein levels was validated using mass spectrometry.

Results

Polymorphisms associated with ankylosing spondylitis (AS) significantly influenced the transcript and protein expression of ERAP‐1 and ERAP‐2. Disease risk–associated polymorphisms in and around both genes were also associated with increased gene expression. Furthermore, key risk‐associatedERAP1variants were associated with altered transcript splicing, leading to allele‐dependent alternate expression of 2 distinct isoforms and significant differences in the type ofERAP‐1 protein produced.

Conclusion

In accordance with studies demonstrating that polymorphisms that increase aminopeptidase activity predispose to immune disease, the increased risk also attributed to increased expression ofERAP1andERAP2supports the notion of using aminopeptidase inhibition to treatASand otherERAP‐associated conditions.
Semi‐Global Robust Output Regulation for A Class of Singular Nonlinear Systems with Unknown Algebraic Equations
Authors: Huang Bomin , Lan Weiyao
Published: November 2017

This paper considers semi‐global robust output regulation problem for a class of singular nonlinear systems whose algebraic equations are not precisely known. Since the algebraic equations are not known, the output regulation problem of singular nonlinear systems cannot be solved by directly reducing the singular nonlinear system into a normal nonlinear system. Based on internal model principle, we convert the robust output regulation problem of singular nonlinear systems into a robust stabilization problem of an augmented singular nonlinear system. The augmented singular nonlinear system is also with unknown algebraic equations. However, without transforming the singular nonlinear system into a normal nonlinear system, it is shown that the augmented singular nonlinear system can be semi‐globally stabilized by a high gain output feedback control law under some reasonable assumptions. Moreover, the semi‐global stabilization control law of the augmented singular nonlinear systems also solves the semi‐global robust output regulation problem of the original singular nonlinear system.