bluuebunny/crossref_metadata_2025 huggingface dataset:
Multilocus approaches for the measurement of selection on correlated genetic loci
Authors: Gompert Zachariah , Egan Scott P. , Barrett Rowan D. H. , Feder Jeffrey L. , Nosil Patrik
Published: October 2016

The study of ecological speciation is inherently linked to the study of selection. Methods for estimating phenotypic selection within a generation based on associations between trait values and fitness (e.g. survival) of individuals are established. These methods attempt to disentangle selection acting directly on a trait from indirect selection caused by correlations with other traits via multivariate statistical approaches (i.e. inference of selection gradients). The estimation of selection on genotypic or genomic variation could also benefit from disentangling direct and indirect selection on genetic loci. However, achieving this goal is difficult with genomic data because the number of potentially correlated genetic loci (p) is very large relative to the number of individuals sampled (n). In other words, the number of model parameters exceeds the number of observations (p ≫ n). We present simulations examining the utility of whole‐genome regression approaches (i.e. Bayesian sparse linear mixed models) for quantifying direct selection in cases where p ≫ n. Such models have been used for genome‐wide association mapping and are common in artificial breeding. Our results show they hold promise for studies of natural selection in the wild and thus of ecological speciation. But we also demonstrate important limitations to the approach and discuss study designs required for more robust inferences.
The Dialogue of Faith and Cultures: From Paul VI to Benedict XVI
Authors: Phillips Peter
Published: October 2016

Vatican II's documents Gaudium et Spes and Ad gentes reveal two interrelated dialogues: a dialogue between Church and other religious traditions, and a more general dialogue between faith and particular societies. The theme takes its cue form Paul VI's first encyclical, Ecclesiam Suam (1964) and, in the last fifty years, has flowered into a rich body of teaching expressed in various documents. It became central to the teaching of John Paul II with his passionate concern for the dignity of the human person. Benedict XVI in a series of speeches delivered both before and after becoming Pope introduced a note of caution to such cultural dialogue. While accepting that he offered an impressive case against the positivism, which he considered to be undermining contemporary culture, we should be hesitant in following his more cautious approach.
Muscle layer histopathology and manometry pattern of primary esophageal motility disorders including achalasia
Authors: Nakajima N. , Sato H. , Takahashi K. , Hasegawa G. , Mizuno K. , Hashimoto S. , Sato Y. , Terai S.
Published: October 2016

Background

Histopathology of muscularis externa in primary esophageal motility disorders has been characterized previously. We aimed to correlate the results of high‐resolution manometry with those of histopathology.

Methods

During peroral endoscopic myotomy, peroral esophageal muscle biopsy was performed in patients with primary esophageal motility disorders. Immunohistochemical staining for c‐kit was performed to assess the interstitial cells of Cajal (ICCs). Hematoxylin Eosin and Azan‐Mallory staining were used to detect muscle atrophy, inflammation, and fibrosis, respectively.

Key Results

Slides from 30 patients with the following motility disorders were analyzed: achalasia (type I: 14, type II: 5, type III: 3), one diffuse esophageal spasm (DES), two outflow obstruction (OO), four jackhammer esophagus (JE), and one nutcracker esophagus (NE). ICCs were preserved in high numbers in type III achalasia (n=9.4±1.2 cells/high power field [HPF]), compared to types I (n=3.7±0.3 cells/HPF) and II (n=3.5±1.0 cells/HPF). Moreover, severe fibrosis was only observed in type I achalasia and not in other types of achalasia, OO, or DES. Four of five patients with JE and NE had severe inflammation with eosinophilic infiltration of the esophageal muscle layer (73.8±50.3 eosinophils/HPF) with no epithelial eosinophils. One patient with JE showed a visceral myopathy pattern.

Conclusions & Inferences

Compared to types I and II, type III achalasia showed preserved ICCs, with variable data regarding DES and OO. In disorders considered as primary esophageal motility disorders, a disease category exists, which shows eosinophilic infiltration in the esophageal muscle layer with no eosinophils in the epithelium.
Genetic consequences of Quaternary climatic oscillations in the Himalayas: Primula tibetica as a case study based on restriction site‐associated DNA sequencing
Authors: Ren Guangpeng , Mateo Rubén G. , Liu Jianquan , Suchan Tomasz , Alvarez Nadir , Guisan Antoine , Conti Elena , Salamin Nicolas
Published: October 2016

The effects of Quaternary climatic oscillations on the demography of organisms vary across regions and continents. In taxa distributed in Europe and North America, several paradigms regarding the distribution of refugia have been identified. By contrast, less is known about the processes that shaped the species’ spatial genetic structure in areas such as the Himalayas, which is considered a biodiversity hotspot. Here, we investigated the phylogeographic structure and population dynamics of Primula tibetica by combining genomic phylogeography and species distribution models (SDMs).

Genomic data were obtained for 293 samples of P. tibetica using restriction site‐associated DNA sequencing (RADseq). Ensemble SDMs were carried out to predict potential present and past distribution ranges.

Four distinct lineages were identified. Approximate Bayesian computation analyses showed that each of them have experienced both expansions and bottlenecks since their divergence, which occurred during or across the Quaternary glacial cycles. The two lineages at both edges of the distribution were found to be more vulnerable and responded in different ways to past climatic changes.

These results illustrate how past climatic changes affected the demographic history of Himalayan organisms. Our findings highlight the significance of combining genomic approaches with environmental data when evaluating the effects of past climatic changes.
Sonifying science: listening to cancer
Authors: Ihde Don
Published: October 2016

As a long‐time scholar of science and art practices, I look particularly at the role of tools and instruments which make these practices possible. I note that science, historically, has favoured visualist imaging, but art, particularly in performance modes, often uses acoustic imaging. Early modern science was dominantly optical in instrumentation, but uses of optics often preceded science use in early modern times. In late modern times, much more complex instrumentation often originated in the sciences, but artists frequently adapted to acoustic practices. Sonifying science, from imaging space phenomena to medical phenomena, is traced here, focusing upon medical sonification in detecting cancers.
Postcanine microstructure in Cricodon metabolus, a Middle Triassic gomphodont cynodont from south‐eastern Africa
Authors: Hendrickx Christophe , Abdala Fernando , Choiniere Jonah
Published: October 2016

Cricodon metabolus is a trirachodontid cynodont from the Anisian (Middle Triassic) of eastern and southern Africa. It has labiolingually expanded (gomphodont) postcanines but also a sectorial tooth in the last postcanine locus. In this paper, we examine the crown microstructure of isolated sectorial and gomphodont postcanines belonging to the holotype specimen of this taxon using scanning electron microscopy. The enamel of both teeth is prismless and composed of discontinuous columnar divergence units, supporting the consistent presence of synapsid columnar enamel in cynognathians. Abundant tubules and numerous irregularly spaced incremental lines are also visible in the enamel and dentine layers in each tooth. This study reveals that the enamel thickness varies along the tooth row in Cricodon as the enamel layer of the gomphodont postcanines is 11.5 times thicker than that of the sectorial crown. It is likely that this difference reflects occlusal stresses and fewer replacements in gomphodont postcanines relative to sectorial teeth. Approximately 100 incremental growth lines of von Ebner are present in the dentine layer, indicating that the deposition of the dentine by odontoblasts occurred for three months before the animal's death.
What The Tortoise Has To Say About Diachronic Rationality
Authors: Valaris Markos
Published: October 2016

Even if you believe just what you rationally ought to believe, you may be open to rational criticism if you do so ‘for the wrong reasons’, as we say. Some have thought that this familiar observation supports the idea that there are diachronic norms of epistemic rationality – namely, norms of good reasoning. Partly drawing upon Carroll's story of Achilles and the Tortoise, this article criticises this line of thought on the grounds that it rests on a mistaken conception of inference.
Genotyping‐by‐sequencing approaches to characterize crop genomes: choosing the right tool for the right application
Authors: Scheben Armin , Batley Jacqueline , Edwards David
Published: October 2016

In the last decade, the revolution in sequencing technologies has deeply impacted crop genotyping practice. New methods allowing rapid, high‐throughput genotyping of entire crop populations have proliferated and opened the door to wider use of molecular tools in plant breeding. These new genotyping‐by‐sequencing (GBS) methods include over a dozen reduced‐representation sequencing (RRS) approaches and at least four whole‐genome resequencing (WGR) approaches. The diversity of methods available, each often producing different types of data at different cost, can make selection of the best‐suited method seem a daunting task. We review the most common genotyping methods used today and compare their suitability for linkage mapping, genomewide association studies (GWAS), marker‐assisted and genomic selection and genome assembly and improvement in crops with various genome sizes and complexity. Furthermore, we give an outline of bioinformatics tools for analysis of genotyping data. WGR is well suited to genotyping biparental cross populations with complex, small‐ to moderate‐sized genomes and provides the lowest cost per marker data point. RRS approaches differ in their suitability for various tasks, but demonstrate similar costs per marker data point. These approaches are generally better suited for de novo applications and more cost‐effective when genotyping populations with large genomes or high heterozygosity. We expect that although RRS approaches will remain the most cost‐effective for some time, WGR will become more widespread for crop genotyping as sequencing costs continue to decrease.
Border Fences and their Impacts on Large Carnivores, Large Herbivores and Biodiversity: An International Wildlife Law Perspective
Authors: Trouwborst Arie , Fleurke Floor , Dubrulle Jennifer
Published: October 2016

Fences, walls and other barriers are proliferating along international borders on a global scale. These border fences not only affect people, but can also have unintended but important consequences for wildlife, inter alia by curtailing migrations and other movements, by fragmenting populations and by causing direct mortality, for instance through entanglement. Large carnivores and large herbivores are especially vulnerable to these impacts. This article analyses the various impacts of border fences on wildlife around the world from a law and policy perspective, focusing on international wildlife law in particular. Relevant provisions from a range of global and regional legal instruments are identified and analysed, with special attention for the Bonn Convention on Migratory Species and the European Union Habitats Directive.
Orbital pacing of the Early Jurassic carbon cycle, black‐shale formation and seabed methane seepage
Authors: Xu Weimu , Ruhl Micha , Hesselbo Stephen P. , Riding James B. , Jenkyns Hugh C.
Published: October 2016

The Early Jurassic (ca 201 to 174 Ma) was marked by a series of rapid perturbations in climate, the environment and global geochemical cycles, which have been linked to volcanic outgassing and the release of biogenic or thermogenic methane into the ocean–atmosphere system. The state of the global carbon cycle and prevailing climatic and environmental conditions that existed at this time are, however, poorly constrained. Here, mudrocks of the Lower Sinemurian Arietites bucklandi ammonite Biozone at coastal exposures at Kilve, Somerset, UK, have been studied. This succession includes laminated organic‐rich black shales, which are present throughout the Bristol Channel Basin, and coincides with a 2 to 3‰ negative carbon‐isotope excursion, distinct changes in inferred land vegetation and abundant marine prasinophytes (green algae). The event itself does not represent a single perturbation of the regional environment, but follows in a sequence of eccentricity‐modulated, precession‐paced perturbations that occur throughout the preceding Hettangian stage, with the periodic formation of organic‐rich laminated black shales in the Bristol Channel Basin. However, the Early Sinemurian event studied herein is more extreme in nature, with sedimentary total organic carbon values of 5 to 11% persisting over about 2 m, representing ca 100 kyr, possibly in phase with short (ca 100 kyr) and long (ca 405 kyr) eccentricity forcing. The formation of methane‐seep carbonate‐cemented mounds took place relatively soon after the deposition of laminated black shales. Biogenic methane probably formed in response to microbial methanogenesis in the organic‐rich black shale, which was subsequently channelled to the sediment–water interface approximately 5 m above the source bed, and ca 200 kyr after cessation of formation of the black shale.
Three‐dimensional seismic characterization of a complex sediment drift in the South China Sea: Evidence for unsteady flow regime
Authors: Sun Qiliang , Cartwright Joe , Lüdmann Thomas , Wu Shiguo , Yao Genshun
Published: October 2016

This study describes a previously unobserved reflection seismic configuration comprising a honeycomb planform and a repeated erosion/infill cross‐section, based on high‐resolution three‐dimensional/two‐dimensional seismic data and bathymetric data. The honeycomb structures cover an area of more than 5000 km2 and are developed within the Late Miocene to recent deep‐water sediments of the north‐western South China Sea. Linear erosional troughs up to 10 km long and 1 km wide are widely developed in this area, are intimately related to the particular seismic configuration and interpreted to represent a new type of sediment drift that is caused by unsteady bottom current regimes operating since the Late Miocene. The unsteady bottom current regimes are suggested to be triggered by irregular seabed morphologies. Considerable sea‐floor topography was generated as a direct result of tectonic movements in the area since the Late Miocene, and this topography then influenced the pathways of strong bottom currents. This study highlights that: (i) an unsteady bottom current regime can be laterally extensive and persist for millions of years; (ii) structurally controlled sea‐floor relief plays an important role in controlling the depositional pattern; and (iii) the bottom currents were active since the Late Miocene, flowing from the south‐east through the Xisha–Guangle Gateway and crossing the honeycomb structure zone. This study documents a new style of drift and will help to improve current knowledge of palaeoceanography and understanding of the South China Sea deep‐water circulation which is at present still poorly understood.
Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis
Authors: Trotter Patrick B. , Robb Matthew , Hulme William , Summers Dominic M. , Watson Christopher J. E. , Bradley J. Andrew , Neuberger James
Published: October 2016

Background

Deceased organ donors, where the cause of death is meningitis or encephalitis, are a potential concern because of the risks of transmission of a potentially fatal infection to recipients.

Methods

Using the UK Transplant Registry, a retrospective cohort analysis of deceased organ donors in the UK was undertaken to better understand the extent to which organs from deceased donors with meningitis and/or encephalitis (M/E) (of both known and unknown cause) have been used for transplantation, and to determine the associated recipient outcomes.

Results

Between 2003 and 2015, 258 deceased donors with M/E were identified and the causative agent was known in 188 (72.9%). These donors provided 899 solid organs for transplantation (455 kidneys and 444 other organs). The only recorded case of disease transmission was from a donor with encephalitis of unknown cause at time of transplantation who transmitted a fatal nematode infection to 2 kidney transplant recipients. A further 3 patients (2 liver and 1 heart recipient) died within 30 days of transplantation from a neurological cause (cerebrovascular accident) with no suggestion of disease transmission. Overall, patient and graft survival in recipients of organs from donors with M/E were similar to those for all other types of deceased organ donor.

Conclusion

Donors dying with M/E represent a valuable source of organs for transplantation. The risk of disease transmission is low but, where the causative agent is unknown, caution is required.
Norovirus infection in solid organ transplant recipients: a single‐center retrospective study
Authors: Lee Lauren Y. , Ladner Daniela P. , Ison Michael G.
Published: October 2016

Background

Norovirus (NoV) is gaining recognition as an important cause of diarrhea among solid organ transplant (SOT) recipients, but existing studies have been limited by a small sample size.

Methods

We conducted a retrospective study of all adult SOT recipients diagnosed with NoV between 2006 and 2013 and compared their data to that of adult SOT recipients with diarrhea who tested negative for NoV during that time.

Results

A total of 192 patients with diarrhea had stool NoV testing as part of their work‐up during the study period; of these patients, 35% (67) tested positive for NoV. Of patients with diarrhea without NoV, Clostridium difficile (25%) and cytomegalovirus (12%) were the most commonly identified infectious cause of diarrhea. Diarrheal duration was significantly protracted in NoV patients, with an average of 241 days vs 75 days in the control group (P=.0007). One patient death and 2 graft failures were related to the NoV illness within the first month after the onset of diarrhea, and 30% of NoV patients had a ≥20% increase in creatinine within 1 year of diagnosis. These outcomes did not differ significantly from those of SOT patients with diarrhea in the non‐NoV group.

Conclusions

NoV is a common cause of diarrhea among SOT recipients at our institution and is responsible for a very prolonged course of chronic diarrhea.
Combined analysis of cross‐reacting antibodies anti‐β1AR and anti‐B13 in advanced stages of Chagas heart disease
Authors: Rodeles Luz M. , Vicco Miguel H. , Bontempi Iván A. , Siano Alvaro , Tonarelli Georgina , Bottasso Oscar A. , Arias Pablo , Marcipar Iván S.
Published: October 2016

Objective

Autoantibodies cross‐reacting with the β1 adrenergic receptor (anti‐β1AR and anti‐p2β) and cardiac myosin antigens (anti‐B13) have been related to the pathogenesis of chronic Chagas heart disease (CCHD). Studies exploring their levels in different stages are scarce. We aimed to evaluate the relationship of these autoantibodies with the clinical profile of chronic patients, especially regarding their classificatory accuracy in severe presentation with heart failure.

Methods and results

We conducted a cross‐sectional study of 155 T. cruzi‐seropositive patients and 26 age‐ and gender‐matched healthy controls. They were categorised in three stages of CCHD. Serum antibodies were measured by specific immunoassays. Symptomatic individuals showed increased levels of anti‐β1AR and anti‐B13, while anti‐p2β antibodies were similar between groups. A composite logistic regression model including anti‐B13, anti‐β1AR antibody levels and age was able to predict systolic heart failure yielding an area under the curve of 83% (sensitivity of 67% and specificity of 89%).

Conclusions

In our study, anti‐β1AR and anti‐B13 antibodies were higher in individuals with chronic Chagas heart disease stage III, mainly in those with dilated cardiomyopathy associated with systolic heart failure. Logistic regression analysis showed that both antibodies were good predictors of severe CCHD. As well as being involved in disease progression, anti‐β1AR and anti‐B13 antibodies may be used as a serum marker of poor prognosis in terms of heart compromise.
IMAGING DIAGNOSIS—ULTRASONOGRAPHIC APPEARANCE OF SKELETAL MUSCLE METASTASES IN A DOG WITH HEMANGIOSARCOMA
Authors: Fabbi Martina , Di Palma Stefano , Manfredi Sabrina , Gnudi Giacomo , Miduri Francesca , Daga Eleonora , Melis Gabriele Costantino , Bianchi Ezio , Voccia Simone , Volta Antonella
Published: October 2016

A 13‐year‐old spayed female German shepherd dog was presented for acute onset of lethargy, anorexia, and disseminated erythematous skin lesions. Thoracic radiographs and abdominal ultrasonographic findings were consistent with metastatic hemangiosarcoma. Multiple, ill‐defined, irregularly shaped hypoechoic nodules were also detected within the thoracic and abdominal wall. Hemangiosarcoma metastases to the skeletal muscle were confirmed based on histopathological examination. Multivisceral involvement was also confirmed by necropsy. Metastatic neoplasia should be considered as a differential diagnosis for dogs with ill‐defined, irregular, hypoechoic, intramuscular nodules.
Plasticity in mitochondrial cristae density allows metabolic capacity modulation in human skeletal muscle
Authors: Nielsen Joachim , Gejl Kasper D. , Hey‐Mogensen Martin , Holmberg Hans‐Christer , Suetta Charlotte , Krustrup Peter , Elemans Coen P. H. , Ørtenblad Niels
Published: October 2016

Key points

In human skeletal muscles, the current view is that the capacity for mitochondrial energy production, and thus endurance capacity, is set by the mitochondria volume.

However, increasing the mitochondrial inner membrane surface comprises an alternative mechanism for increasing the energy production capacity.

In the present study, we show that mitochondrial inner membranes in leg muscles of endurance‐trained athletes have an increased ratio of surface per mitochondrial volume.

We show a positive correlation between this ratio and whole body oxygen uptake and muscle fibre mitochondrial content.

The results obtained in the present study help us to understand modulation of mitochondrial function, as well as how mitochondria can increase their oxidative capacity with increased demand.

Mitochondrial energy production involves the movement of protons down a large electrochemical gradient via ATP synthase located on the folded inner membrane, known as cristae. In mammalian skeletal muscle, the density of cristae in mitochondria is assumed to be constant. However, recent experimental studies have shown that respiration per mitochondria varies. Modelling studies have hypothesized that this variation in respiration per mitochondria depends on plasticity in cristae density, although current evidence for such a mechanism is lacking. In the present study, we confirm this hypothesis by showing that, in human skeletal muscle, and in contrast to the current view, the mitochondrial cristae density is not constant but, instead, exhibits plasticity with long‐term endurance training. Furthermore, we show that frequently recruited mitochondria‐enriched fibres have significantly increased cristae density and that, at the whole‐body level, muscle mitochondrial cristae density is a better predictor of maximal oxygen uptake rate than muscle mitochondrial volume. Our findings establish an elevating mitochondrial cristae density as a regulatory mechanism for increasing metabolic power in human skeletal muscle. We propose that this mechanism allows evasion of the trade‐off between cell occupancy by mitochondria and other cellular constituents, as well as improved metabolic capacity and fuel catabolism during prolonged elevated energy requirements.
Financial Viability of Energy Conservation Using Natural Light in an Academic Building in Temperate Zone
Authors: Sharma Pooja , Rakshit Dibakar
Published: October 2016

The environment of a regularly occupied space can be extensively improved by maximum utilization of natural light/daylight, which is available in abundance. In Indian climate, availability of sufficient day light in both direct and diffused form of radiation can lead to reduction in dependency on artificial lighting thus, decreasing energy demand for artificial lighting system. In this study, an institutional building in New Delhi, India is analyzed for its daylighting characteristics. The academic block of a building comprising all categories of regularly spaces is modeled and simulated using Integrated environmental solutions - virtual environment (IES VE). The objective is to analyze the extent of penetration of natural light into these spaces of the building for reducing energy requirement for artificial lighting by studying a room, which performs the worst as per present case parameters. The conclusion puts forth the optimal solutions for utilizing maximum day light in a work space, complying with standards set forth by building construction council by utilizing the principles for increasing luminous flux level through visual light transmittance, window-to-wall ratio, and controlled usage of artificial lighting. Considering all these factors in the analysis, energy savings and carbon mitigation due to these savings in regularly occupied spaces are finally evaluated.
Review on Percolating and Neck-Based Underfills for Three-Dimensional Chip Stacks
Authors: Brunschwiler Thomas , Zürcher Jonas , Del Carro Luca , Schlottig Gerd , Burg Brian , Zimmermann Severin , Zschenderlein Uwe , Wunderle Bernhard , Schindler-Saefkow Florian , Stässle Rahel
Published: October 2016

Heat dissipation from three-dimensional (3D) chip stacks can cause large thermal gradients due to the accumulation of dissipated heat and thermal interfaces from each integrated die. To reduce the overall thermal resistance and thereby the thermal gradients, this publication will provide an overview of several studies on the formation of sequential thermal underfills that result in percolation and quasi-areal thermal contacts between the filler particles in the composite material. The quasi-areal contacts are formed from nanoparticles self-assembled by capillary bridging, so-called necks. Thermal conductivities of up to 2.5 W/m K and 2.8 W/m K were demonstrated experimentally for the percolating and the neck-based underfills, respectively. This is a substantial improvement with respect to a state-of-the-art capillary thermal underfill (0.7 W/m K). Critical parameters in the formation of sequential thermal underfills will be discussed, such as the material choice and refinement, as well as the characteristics and limitations of the individual process steps. Guidelines are provided on dry versus wet filling of filler particles, the optimal bimodal nanosuspension formulation and matrix material feed, and the over-pressure cure to mitigate voids in the underfill during backfilling. Finally, the sequential filling process is successfully applied on microprocessor demonstrator modules, without any detectable sign of degradation after 1500 thermal cycles, as well as to a two-die chip stack. The morphology and performance of the novel underfills are further discussed, ranging from particle arrangements in the filler particle bed, to cracks formed in the necks. The thermal and mechanical performance is benchmarked with respect to the capillary thermal and mechanical underfills. Finally, the thermal improvements within a chip stack are discussed. An 8 - or 16-die chip stack can dissipate 46% and 65% more power with the optimized neck-based thermal underfill than with a state-of-the-artcapillary thermal underfill.
Toward a Generalized Energy Prediction Model for Machine Tools
Authors: Bhinge Raunak , Park Jinkyoo , Law Kincho H. , Dornfeld David A. , Helu Moneer , Rachuri Sudarsan
Published: October 2016

Energy prediction of machine tools can deliver many advantages to a manufacturing enterprise, ranging from energy-efficient process planning to machine tool monitoring. Physics-based energy prediction models have been proposed in the past to understand the energy usage pattern of a machine tool. However, uncertainties in both the machine and the operating environment make it difficult to predict the energy consumption of the target machine reliably. Taking advantage of the opportunity to collect extensive, contextual, energy-consumption data, we discuss a data-driven approach to develop an energy prediction model of a machine tool in this paper. First, we present a methodology that can efficiently and effectively collect and process data extracted from a machine tool and its sensors. We then present a data-driven model that can be used to predict the energy consumption of the machine tool for machining a generic part. Specifically, we use Gaussian process (GP) regression, a nonparametric machine-learning technique, to develop the prediction model. The energy prediction model is then generalized over multiple process parameters and operations. Finally, we apply this generalized model with a method to assess uncertainty intervals to predict the energy consumed by any part of the machine using a Mori Seiki NVD1500 machine tool. Furthermore, the same model can be used during process planning to optimize the energy-efficiency of a machining process.
Laser Metal Deposition Additive Manufacturing of TiC Reinforced Inconel 625 Composites: Influence of the Additive TiC Particle and Its Starting Size
Authors: Gu Dongdong , Cao Sainan , Lin Kaijie
Published: October 2016

In this study, laser metal deposition (LMD) additive manufacturing was used to deposit the pure Inconel 625 alloy and the TiC/Inconel 625 composites with different starting sizes of TiC particles, respectively. The influence of the additive TiC particle and its original size on the constitutional phases, microstructural features, and mechanical properties of the LMD-processed parts was studied. The incorporation of TiC particles significantly changed the prominent texture of Ni–Cr matrix phase from (200) to (100). The bottom and side parts of each deposited track showed mostly the columnar dendrites, while the cellular dendrites were prevailing in the microstructure of the central zone of the deposited track. As the nano-TiC particles were added, more columnar dendrites were observed in the solidified molten pool. The incorporation of nano-TiC particles induced the formation of the significantly refined columnar dendrites with the secondary dendrite arms developed considerably well. With the micro-TiC particles added, the columnar dendrites were relatively coarsened and highly degenerated, with the secondary dendrite growth being entirely suppressed. The cellular dendrites were obviously refined by the additive TiC particles. When the nano-TiC particles were added to reinforce the Inconel 625, the significantly improved microhardness, tensile property, and wear property were obtained without sacrificing the ductility of the composites.
Energy-Efficient Robot Configuration for Assembly
Authors: Mohammed Abdullah , Schmidt Bernard , Wang Lihui
Published: October 2016

Optimizing the energy consumption of robot movements has been one of the main focuses for most of today's robotic simulation software. This optimization is based on minimizing a robot's joint movements. In many cases, it does not take into consideration the dynamic features. Therefore, reducing energy consumption is still a challenging task and it involves studying the robot's kinematic and dynamic models together with application requirements. This research aims to minimize the robot energy consumption during assembly. Given a trajectory and based on the inverse kinematics and dynamics of a robot, a set of attainable configurations for the robot can be determined, perused by calculating the suitable forces and torques on the joints and links of the robot. The energy consumption is then calculated for each configuration and based on the assigned trajectory. The ones with the lowest energy consumption are selected. Given that the energy-efficient robot configurations lead to reduced overall energy consumption, this approach becomes instrumental and can be embedded in energy-efficient robotic assembly.
Temperature-Dependent Thermal Boundary Conductance at Metal/Indium-Based III–V Semiconductor Interfaces
Authors: Larkin LeighAnn S. , Redding MacKenzie R. , Le Nam Q. , Norris Pamela M.
Published: October 2016

At the microscale length and smaller, solid–solid interfaces pose a significant contribution to resistance, resulting in a build-up of energy carriers, in turn leading to extreme temperature gradients within a single electronic component. These localized temperature gradients, or “hot spots,” are known to promote degradation, thus reducing device longevity and performance. To mitigate thermal management issues, it is crucial to both measure and understand conductance at interfaces in technologically relevant thin film systems. Recent trends in photonic devices have been pushing the consumption of indium in the U.S. to grow exponentially each year. Thus, we report on the temperature-dependent thermal boundary conductances at a series of metal/In-based III–V semiconductor interfaces. These measurements were made using time-domain thermoreflectance (TDTR) from 80 to 350 K. The high-temperature thermal boundary conductance results indicate, for these interfaces, that interfacial transport is dominated by elastic transmission, despite varying levels of acoustic mismatch. There is a strong direct correlation between the interfacial bond strength, approximated by the picosecond acoustics, and the thermal boundary conductance values. Both the interfacial bond strength and the overlap in the phonon density of states (PDOS) play significant roles in the magnitude of the thermal boundary conductance values. Measurements are compared against two separate predictive models, one for a perfect interface and one which accounts for disorder, such as interfacial mixing and finite grain sizes.
Transient Performance Analysis of an Industrial Gas Turbine Operating on Low-Calorific Fuels
Authors: Singh Vrishika , Axelsson Lars-Uno , Visser W.P.J.
Published: October 2016

The demand for more environmentally friendly and economic power production has led to an increasing interest to utilize alternative fuels. In the past, several investigations focusing on the effect of low-calorific fuels on the combustion process and steady-state performance have been published. However, it is also important to consider the transient behavior of the gas turbine when operating on nonconventional fuels. The alternative fuels contain very often a large amount of dilutants resulting in a low energy density. Therefore, a higher fuel flow rate is required, which can impact the dynamic behavior of the gas turbine. This paper will present an investigation of the transient behavior of the all-radial OP16 gas turbine. The OP16 is an industrial gas turbine rated at 1.9 MW, which has the capability to burn a wide range of fuels including ultra-low-calorific gaseous fuels. The transient behavior is simulated using the commercial software GSP including the recently added thermal network modeling functionality. The steady-state and transient performance model is thoroughly validated using real engine test data. The developed model is used to simulate and analyze the physical behavior of the gas turbine when performing load sheds. From the simulations, it is found that the energy density of the fuel has a noticeable effect on the rotor over-speed and must be considered when designing the fuel control.
Inverse characterization of the frequency-dependent acoustic and elastic parameters of porous materials by surface-normal impedance method
Authors: Liu Yaoguang
Published: October 2016

A method for characterizing the frequency-dependent acoustic and elastic parameters of porous materials is proposed and validated in the paper, based on the Biot theory. The parameters include the characteristic impedance, propagation coefficient (also denoted as complex wave number), and longitudinal modulus. The first two are the macroscopic acoustic properties of pore fluid, while the last one is the elastic property of frame. A system related to the three parameters is constructed through the normal surface impedance of three samples with different thickness, based on the transfer matrix theory. With the measured surface impedance and appropriate initial values, an iterative procedure based on the Newton–Raphson method is used to solve the system. The three parameters are identified simultaneously, and then validated by two experimental methods, respectively, i.e., a modified two cavity method for the acoustic parameters and a quasi-static mechanical method for the elastic parameter. The parameters identified from the proposed method are consistent with the results of the two methods except for the imaginary part of the longitudinal modulus. It is shown that the proposed method would have a better performance if the discrepancy of frame displacements among different samples is moderate, corresponding to a reasonable selection of the thickness.
Erratum: Modeling sound-source localization in sagittal planes for human listeners [J. Acoust. Soc. Am. 136, 791–802 (2014)]
Authors: Baumgartner Robert , Majdak Piotr , Laback Bernhard
Published: October 2016

This erratum concerns Eq. (4) of the original article, which defines the distance metric of the comparison process of the sagittal-plane sound localization model. The distance metric was actually implemented as a mean absolute difference but was erroneously described as a L1-norm difference.
Paper of note in
Science Translational Medicine
Authors: Ferrarelli Leslie K.
Published: October 2016

This week’s article highlights the involvement of epithelial cells and smooth muscle in allergy-induced asthma.
Pressure-induced oxidative activation of PKG enables vasoregulation by Ca
2+
sparks and BK channels
Authors: Khavandi Kaivan , Baylie Rachael L. , Sugden Sarah A. , Ahmed Majid , Csato Viktoria , Eaton Philip , Hill-Eubanks David C. , Bonev Adrian D. , Nelson Mark T. , Greenstein Adam S.
Published: October 2016

Constriction of small-diameter arteries triggers a signaling pathway that causes their dilation.
Impaired coordination between signaling pathways is revealed in human colorectal cancer using single-cell mass cytometry of archival tissue blocks
Authors: Simmons Alan J. , Scurrah Cherié R. , McKinley Eliot T. , Herring Charles A. , Irish Jonathan M. , Washington M. Kay , Coffey Robert J. , Lau Ken S.
Published: October 2016

A single-cell analytical approach in the clinic may lead to more effective treatment strategies for cancer patients.
Oxidant signaling underlies PKGIα modulation of Ca
2+
sparks and BK
Ca
in myogenically active arterioles
Authors: Hill Michael A. , Braun Andrew P.
Published: October 2016

Small arteries react to constriction by producing reactive oxygen species that alter Ca
2+
signaling (Khavandi
et al
., in 11 October 2016 issue).
Defining the daughter swarmer cell
Authors: Mushegian Alexandra A.
Published: October 2016

A DNA-binding protein may organize DNA to enable
Caulobacter
to divide into morphologically different daughter cells.
Multiple paths spread toxic α-synuclein aggregates
Authors: VanHook Annalisa M.
Published: October 2016

Oligomeric α-synuclein can enter cells through receptor-mediated endocytosis and can be transferred between cells through nanotubes.
New connections: Detecting tumor-specific signaling
Authors: Gough Nancy R.
Published: October 2016

Technology development enables researchers to help clinicians optimize treatment by understanding tumor cell–specific changes in signaling pathways.
A Novel Fluorescence Resonance Energy Transfer-Based Screen in High-Throughput Format To Identify Inhibitors of Malarial and Human Glucose Transporters
Authors: Kraft Thomas E. , Heitmeier Monique R. , Putanko Marina , Edwards Rachel L. , Ilagan Ma Xenia G. , Payne Maria A. , Autry Joseph M. , Thomas David D. , Odom Audrey R. , Hruz Paul W.
Published: October 2016

The glucose transporter PfHT is essential to the survival of the malaria parasite
Plasmodium falciparum
and has been shown to be a druggable target with high potential for pharmacological intervention. Identification of compounds against novel drug targets is crucial to combating resistance against current therapeutics. Here, we describe the development of a cell-based assay system readily adaptable to high-throughput screening that directly measures compound effects on PfHT-mediated glucose transport. Intracellular glucose concentrations are detected using a genetically encoded fluorescence resonance energy transfer (FRET)-based glucose sensor. This allows assessment of the ability of small molecules to inhibit glucose uptake with high accuracy (Z′ factor of >0.8), thereby eliminating the need for radiolabeled substrates. Furthermore, we have adapted this assay to counterscreen PfHT hits against the human orthologues GLUT1, -2, -3, and -4. We report the identification of several hits after screening the Medicines for Malaria Venture (MMV) Malaria Box, a library of 400 compounds known to inhibit erythrocytic development of
P. falciparum
. Hit compounds were characterized by determining the half-maximal inhibitory concentration (IC
50
) for the uptake of radiolabeled glucose into isolated
P. falciparum
parasites. One of our hits, compound MMV009085, shows high potency and orthologue selectivity, thereby successfully validating our assay for antimalarial screening.
Randomized, Open-Label Study of the Pharmacokinetics and Safety of Oral and Intravenous Administration of Omadacycline to Healthy Subjects
Authors: Sun Haiying , Ting Lillian , Machineni Surendra , Praestgaard Jens , Kuemmell Andreas , Stein Daniel S. , Sunkara Gangadhar , Kovacs Steven J. , Villano Stephen , Tanaka S. Ken
Published: October 2016

Omadacycline is a first-in-class aminomethylcycline antibiotic with microbiological activity against Gram-positive and Gram-negative aerobes and anaerobes and atypical bacteria that is being developed for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). The bioavailability of a phase 3 tablet formulation relative to that obtained via intravenous (i.v.) administration (and of other oral formulations relative to that of the phase 3 tablet) was investigated in an open-label, randomized, four-period, crossover study with healthy subjects age 18 to 50 years. Subjects received omadacycline at 100 mg i.v., 300 mg orally as two different tablet formulations with different dissolution profiles, and 300 mg as an oral solution. Plasma omadacycline concentrations were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Twenty of 24 subjects completed all treatment periods. The two tablet formulations produced equivalent total exposures. The phase 3 tablet produced an exposure equivalent to that of the 100-mg i.v. dose, with a geometric mean ratio (90% confidence intervals [CI]) for area under the concentration-time curve from 0 h to infinity [AUC
∞
]) of 1.00 (0.93, 1.07). The absolute bioavailability of the tablets was approximately 34.5%. Intersubject variability was consistent among the oral formulations (∼20 to 25%). Single oral and i.v. doses of omadacycline were well tolerated; three subjects experienced mild adverse events (dizziness, nausea, and vomiting) that resolved without intervention. A 300-mg dose of the tablet formulation of omadacycline intended for use in phase 3 studies produced a total exposure equivalent to that of a 100-mg i.v. dose.
Siderophore Cephalosporin Cefiderocol Utilizes Ferric Iron Transporter Systems for Antibacterial Activity against Pseudomonas aeruginosa
Authors: Ito Akinobu , Nishikawa Toru , Matsumoto Shuhei , Yoshizawa Hidenori , Sato Takafumi , Nakamura Rio , Tsuji Masakatsu , Yamano Yoshinori
Published: October 2016

Cefiderocol (S-649266) is a novel parenteral siderophore cephalosporin conjugated with a catechol moiety at the third-position side chain. The
in vitro
activity of cefiderocol against
Pseudomonas aeruginosa
was enhanced under iron-depleted conditions, whereas that of ceftazidime was not affected. The monitoring of [thiazole-
14
C]cefiderocol revealed the increased intracellular accumulation of cefiderocol in
P. aeruginosa
cells incubated under iron-depleted conditions compared with those incubated under iron-sufficient conditions. Cefiderocol was shown to have potent chelating activity with ferric iron, and extracellular iron was efficiently transported into
P. aeruginosa
cells in the presence of cefiderocol as well as siderophores, while enhanced transport of extracellular ferric iron was not observed when one of the hydroxyl groups of the catechol moiety of cefiderocol was replaced with a methoxy group. We conclude that cefiderocol forms a chelating complex with iron, which is actively transported into
P. aeruginosa
cells via iron transporters, resulting in potent antibacterial activity of cefiderocol against
P. aeruginosa
.
Design and Validation of Novel Chikungunya Virus Protease Inhibitors
Authors: Das Pratyush Kumar , Puusepp Laura , Varghese Finny S. , Utt Age , Ahola Tero , Kananovich Dzmitry G. , Lopp Margus , Merits Andres , Karelson Mati
Published: October 2016

Chikungunya virus (CHIKV; genus
Alphavirus
) is the causative agent of chikungunya fever. CHIKV replication can be inhibited by some broad-spectrum antiviral compounds; in contrast, there is very little information about compounds specifically inhibiting the enzymatic activities of CHIKV replication proteins. These proteins are translated in the form of a nonstructural (ns) P1234 polyprotein precursor from the CHIKV positive-strand RNA genome. Active forms of replicase enzymes are generated using the autoproteolytic activity of nsP2. The available three-dimensional (3D) structure of nsP2 protease has made it a target for
in silico
drug design; however, there is thus far little evidence that the designed compounds indeed inhibit the protease activity of nsP2 and/or suppress CHIKV replication. In this study, a set of 12 compounds, predicted to interact with the active center of nsP2 protease, was designed using target-based modeling. The majority of these compounds were shown to inhibit the ability of nsP2 to process recombinant protein and synthetic peptide substrates. Furthermore, all compounds found to be active in these cell-free assays also suppressed CHIKV replication in cell culture, the 50% effective concentration (EC
50
) of the most potent inhibitor being ∼1.5 μM. Analysis of stereoisomers of one compound revealed that inhibition of both the nsP2 protease activity and CHIKV replication depended on the conformation of the inhibitor. Combining the data obtained from different assays also indicates that some of the analyzed compounds may suppress CHIKV replication using more than one mechanism.