bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonspecific Interstitial Pneumonia
Authors: Javidan-Nejad Cylen
Published: August 2019

Nonspecific interstitial pneumonia (NSIP) represents a less common idiopathic interstitial pneumonia than usual interstitial pneumonia (UIP) with a much better prognosis. Most cases of NSIP are secondary to collagen vascular disease, hypersensitivity or drug toxicity. These secondary forms of NSIP help to explain why it is more often seen on CT than UIP. Unlike UIP, NSIP is characterized by a paucity of honeycombing on CT and greater ground-glass opacity and reticulation. Subpleural sparing when present may suggest the diagnosis. Unlike UIP, NSIP tends to exhibit histologic spatial and temporal homogeneity. When extensive bronchiectasis is seen in association with an NSIP pattern, collagen vascular disease must be considered. When air trapping is encountered, hypersensitivity pneumonitis must be excluded. Biopsy is usually reserved for those patients with an NSIP pattern who do not have a known underlying condition. If the diagnosis of NSIP can be made, immunotherapy may prevent progression and may even reverse some CT findings.
Mediastinal Lymphadenopathy
Authors: Carter Brett W.
Published: August 2019

Lymphadenopathy represents the pathologic enlargement of lymph nodes. Within the chest, the mediastinum is the most commonly affected region. Mediastinal lymphadenopathy may result in loss of normal mediastinal contours or thickening of lines and stripes. On computed tomography (CT), lymph nodes measuring greater than 1 cm in short-axis dimension are typically considered enlarged. Although many disease process may result in mediastinal lymphadenopathy, including lymphoma, metastatic disease, infections, and sarcoidosis, specific characteristics such as attenuation, enhancement, and calcification help narrow the differential diagnosis. PET/CT demonstrates the metabolic activity of structures such as lymph nodes and may help in identifying pathologic lymphadenopathy. However, PET/CT cannot reliably differentiate between lymphadenopathy due to active malignancy and certain benign processes such as active infection or sarcoidosis.
Vascular Lesions of the Mediastinum
Authors: Carter Brett W.
Published: August 2019

Vascular lesions represent approximately 10% of mediastinal masses detected on chest radiography. The most common lesions include abnormalities of the systemic arteries and veins, pulmonary arteries and veins, and thoracic aorta. Benign neoplasms such as hemangiomas and lymphangiomas are rare. Vascular abnormalities may be congenital or acquired, and the former may be associated with congenital heart disease in the pediatric population. Most acquired lesions are degenerative, post-traumatic, or neoplastic. Vascular lesions of the mediastinum may be detected on chest radiography as loss of normal mediastinal contours, focal opacities, or thickening of lines and stripes. These abnormalities are best evaluated with cross-sectional imaging such as contrast-enhanced computed tomography (CT) or CT angiography (CTA).
Chest Wall Abnormalities
Authors: Jokerst Clinton E. , Cummings Kristopher W. , Bierhals Andrew J.
Published: August 2019

The chest wall constitutes a relatively conspicuous space made up primarily of bones, muscles and fat. The chest wall also contains specialized tissues such as nerves, lymph nodes, blood vessels, and breast tissue. Abnormalities that lead to either masses or absence of these tissues are usually obvious upon visual inspection but occasionally imaging is required for evaluation. Differential diagnoses are very much based on the age, the symptoms and the tissue of origin. CT and MR are often both used as a result of their complementary nature. Congenital variations of the chest wall such as Poland syndrome, and Pectus Excavitum/carinatum must be understood to avoid confusion with pathology. Certain tumors are typical of the chest wall (Desmoid tumors and elastofibroma dorsi) and the thoracic radiologist should be familiar with their CT and MR appearances.
Hyperluminous starburst gives up its secrets
Authors: Ivison R J , Page M J , Cirasuolo M , Harrison C M , Mainieri V , Arumugam V , Dudzevičiūtė U
Published: August 2019

HATLAS J084933.4 + 021443 was identified as a dusty starburst via its rest-frame far-infrared (far-IR) emission. Multifrequency imaging and spectroscopy revealed a cluster of four dusty galaxies at z = 2.41, covering 80 kpc. Here, we use Atacama Large Millimetre Array to confirm a more distant, fifth protocluster member, and present X-ray and rest-frame optical imaging spectroscopy of the brightest, an unlensed hyperluminous IR galaxy (HyLIRG). The data reveal broad Hα and bright [N ii] lines, and bright X-ray emission, characteristics that betray a Type-1 active galactic nucleus (AGN), strengthening evidence that AGN are ubiquitous amongst HyLIRGs. The accreting black hole is supermassive, Mbh ≈ 2 × 109 M⊙, with little intrinsic absorption, NH ≈ 5 × 1021 cm−2. The X-ray properties suggest the accretion luminosity rivals that of the starburst, yet it is not obvious where this emerges in its panchromatic spectral energy distribution. We outline three scenarios that could give rise to the observed characteristics, and how we might distinguish between them. In the first, we see the AGN through the host galaxy because of the cavity it excavates. In the others, the AGN is not cospatial with the starburst, having been ejected via asymmetric gravitational radiation, or having evolved towards the naked quasar phase in an unseen companion.
The Lyman-α forest as a diagnostic of the nature of the dark matter
Authors: Garzilli Antonella , Magalich Andrii , Theuns Tom , Frenk Carlos S , Weniger Christoph , Ruchayskiy Oleg , Boyarsky Alexey
Published: August 2019

The observed Lyman-α flux power spectrum (FPS) is suppressed on scales below ${\sim} ~ 30\, {\rm km\, s}^{-1}$. This cut-off could be due to the high temperature, T0, and pressure, p0, of the absorbing gas or, alternatively, it could reflect the free streaming of dark matter particles in the early universe. We perform a set of very high resolution cosmological hydrodynamic simulations in which we vary T0, p0, and the amplitude of the dark matter free streaming, and compare the FPS of mock spectra to the data. We show that the location of the dark matter free-streaming cut-off scales differently with redshift than the cut-off produced by thermal effects and is more pronounced at higher redshift. We, therefore, focus on a comparison to the observed FPS at z > 5. We demonstrate that the FPS cut-off can be fit assuming cold dark matter, but it can be equally well fit assuming that the dark matter consists of ∼7 keV sterile neutrinos in which case the cut-off is due primarily to the dark matter free streaming.
A sceptical analysis of quantized inertia
Authors: Renda Michele
Published: August 2019

We perform an analysis of the derivation of quantized inertia (QI) theory, formerly known with the acronym MiHsC, as presented by McCulloch. Two major flaws were found in the original derivation. We derive a discrete blackbody radiation spectrum, deriving a different formulation for F(a) than the one presented in the original theory. We present a numerical result of the new solution which is compared against the original prediction.
New evidence for weak magnetic fields in Herbig Ae/Be stars
Authors: Järvinen S P , Carroll T A , Hubrig S , Ilyin I , Schöller M
Published: August 2019

In recent years Herbig Ae/Be stars receive considerable attention as their disks are believed to be the sites of on-going planet formation. Confirming the presence of magnetic fields in these stars is critical for understanding the transport of angular momentum during the protostellar phase. Furthermore, magnetic fields set the conditions for strongly anisotropic accretion. In this study we present the results of our recent observing campaigns of a sample of Herbig Ae/Be stars aimed at measurements of their magnetic fields applying the Singular Value Decomposition method to high resolution spectropolarimetric observations. The strongest longitudinal magnetic field of 209 G is detected in the Herbig Be star HD 58647, whereas the weakest field of 17 G is measured in the Herbig Ae star HD 190073. A change of polarity is detected for HD 58647 and in the Herbig Be star HD 98922. The obtained results provide further evidence that Herbig Ae/Be stars possess much weaker magnetic fields than their lower mass counterpart T Tauri stars with magnetic fields of kG order.
Multiplanet systems in inviscid discs can avoid forming resonant chains
Authors: McNally Colin P , Nelson Richard P , Paardekooper Sijme-Jan
Published: August 2019

Convergent migration involving multiple planets embedded in a viscous protoplanetary disc is expected to produce a chain of planets in mean motion resonances (MMRs), but the multiplanet systems observed by the Kepler spacecraft are generally not in resonance. We demonstrate that under equivalent conditions, where in a viscous disc convergent migration will form a long-term stable system of planets in a chain of MMRs, migration in an inviscid disc often produces a system which is highly dynamically unstable. In particular, if planets are massive enough to significantly perturb the disc surface density and drive vortex formation, the smooth capture of planets into MMRs is disrupted. As planets pile up in close orbits, not protected by resonances, close encounters increase the probability of planet–planet collisions, even while the gas disc is still present. While inviscid discs often produce unstable non-resonant systems, stable, closely packed, non-resonant systems can also be formed. Thus, when examining the expectation for planet migration to produce planetary systems in MMRs, the effective turbulent viscosity of the protoplanetary disc is a key parameter.
iDamage: a method to integrate modified DNA into the yeast genome
Authors: Masłowska Katarzyna H , Laureti Luisa , Pagès Vincent
Published: August 2019

In order to explore the mechanisms employed by living cells to deal with DNA alterations, we have developed a method by which we insert a modified DNA into a specific site of the yeast genome. This is achieved by the site-specific integration of a modified plasmid at a chosen locus of the genome of Saccharomyces cerevisiae, through the use of the Cre/lox recombination system. In the present work, we have used our method to insert a single UV lesion into the yeast genome, and studied how the balance between error-free and error-prone lesion bypass is regulated. We show that the inhibition of homologous recombination, either directly (by the inactivation of Rad51 recombinase) or through its control by preventing the polyubiquitination of PCNA (ubc13 mutant), leads to a strong increase in the use of Trans Lesion Synthesis (TLS). Such regulatory aspects of DNA damage tolerance could not have been observed with previous strategies using plasmid or randomly distributed DNA lesions, which shows the advantage of our new method. The very robust and precise integration of any modified DNA at any chosen locus of the yeast genome that we describe here is a powerful tool that will enable the exploration of many biological processes related to replication and repair of modified DNA.
Customizing an Electronic Medical Record to Automate the Workflow and Tracking of an Antimicrobial Stewardship Program
Authors: Katzman Michael , Kim Jihye , Lesher Mark D , Hale Cory M , McSherry George D , Loser Matthew F , Ward Michael A , Glasser Frendy D
Published: August 2019

Background

Documenting the actions and effects of an antimicrobial stewardship program (ASP) is essential for quality improvement and support by hospital leadership. Thus, our ASP tallies the number of charts reviewed, types of recommendations, how and to whom they were communicated, whether they were followed, and any effects on antimicrobial days of therapy. Here we describe how we customized the electronic medical record at our institution to facilitate our workflow and data analysis, while highlighting principles that should be adaptable to other ASPs.

Methods

The documentation system involves the creation of a novel and intuitive ASP form in each chart reviewed and 2 mutually exclusive tracking systems: 1 for active forms to facilitate the daily ASP workflow and 1 for finalized forms to generate cumulative reports. The ASP form is created by the ASP pharmacist, edited by the ASP physician, reopened by the pharmacist to assess whether the recommendation was followed and to quantify any antimicrobial days avoided or added, then reviewed and finalized by the ASP physician. Active forms are visible on a real-time “MPage,” whereas all finalized forms are compiled nightly into 65 informative tables and associated graphs.

Results and Conclusions

This system and its underlying principles have automated much of the documentation, facilitated follow-up of interventions, improved the completeness and validity of recorded data and analysis, enabled our ASP to expand its activities, and been associated with decreased antimicrobial usage, drug resistance, and Clostridioides difficile infections.
The role of ultrasound and magnetic resonance imaging for treat to target in rheumatoid arthritis and psoriatic arthritis
Authors: Mandl Peter , Aletaha Daniel
Published: August 2019

The treat-to-target (T2T) approach has revolutionized the way we treat patients with rheumatic and musculoskeletal diseases. Recent attention has focused on imaging techniques, in particular musculoskeletal ultrasound and MRI as a focus for T2T strategies. Recently, a number of randomized clinical trials have been performed that compared tight clinical control vs control augmented by imaging techniques. While the three published trials have concluded that imaging does not add to tight clinical care, implementing imaging into the T2T strategy has actual advantages, such as the detection of subclinical involvement, and information on joint involvement/pathology and may possess potential advantages as evidenced by certain secondary endpoints. This review examines the findings of these studies and discusses the advantages and disadvantages of incorporating imaging into the T2T strategy.
Immunocrit, colostrum intake, and preweaning body weight gain in piglets after split suckling based on birth weight or birth order1
Authors: Morton Jodi M , Langemeier Austin J , Rathbun Theresa J , Davis Duane L
Published: August 2019

Preweaning survival and growth are compromised in litters with larger numbers of piglets. We evaluated two approaches for altering initial nursing with the goal to improve access to colostrum by groups of piglets that are known to have reduced access to colostrum. Therefore, we temporarily (1.5 h) removed either the heaviest six piglets in the litter (WT) or the first half of the piglets born (ORD) to provide a short period of nursing with reduced competition for the remaining piglets. We found that WT piglets were heavier (P ≤ 0.05) at 7 d after farrowing and gained more body weight (BW) from farrowing to day 7 than control (CON) piglets which were raised in litters with ad libitum nursing during the same period. Further, we found that the heaviest piglets consumed more (P < 0.001) colostrum and gained more (P < 0.001) BW during the preweaning period but did not have (P > 0.10) greater immunocrits. Although ORD piglets had similar colostrum intake, immunocrits, and preweaning weights as controls, we found that overall the piglets born in the first half of litters had greater (P < 0.01) immunocrits than piglets born in the last half of the litter. Therefore, both birth weight and birth order have effects on traits that are important for prenatal growth and survival, but they differ in that birth weight is more closely related to colostrum intake and birth order affects immunocrit.
Increased Bone Marrow-Specific Adipogenesis by Clofazimine Causes Impaired Fracture Healing, Osteopenia, and Osteonecrosis Without Extraskeletal Effects in Rats
Authors: Porwal Konica , Pal Subhashis , Tewari Deepshikha , Pal China Shyamsundar , Singh Priya , Chandra Tewari Mahesh , Prajapati Gurudayal , Singh Pragati , Cheruvu Srikanth , Khan Yasir A , Sanyal Sabyasachi , Gayen Jiaur R , Ampapathi Ravishankar , Mridha Asit R , Chattopadhyay Naibedya
Published: August 2019

Mycobacterium leprae infection causes bone lesions and osteoporosis, however, the effect of antileprosy drugs on the bone is unknown. We, therefore, set out to address it by investigating osteogenic differentiation from bone marrow (BM)-derived mesenchymal stem cells (MSCs). Out of 7 antileprosy drugs, only clofazimine (CFZ) reduced MSCs viability (IC50 ∼ 1 μM) and their osteogenic differentiation but increased adipogenic differentiation on a par with rosiglitazone, and this effect was blocked by a peroxisome proliferator-activated receptor gamma antagonist, GW9662. CFZ also decreased osteoblast viability and resulted in impaired bone regeneration in a rat femur osteotomy model at one-third human drug dose owing to increased callus adipogenesis as GW9662 prevented this effect. CFZ treatment decreased BM MSC population and homing of MSC to osteotomy site despite drug levels in BM being much less than its in vitro IC50 value. In adult rats, CFZ caused osteopenia in long bones marked by suppressed osteoblast function due to enhanced adipogenesis and increased osteoclast functions. A robust increase in marrow adipose tissue (MAT) by CFZ did not alter the hematologic parameters but likely reduced BM vascular bed leading to osteonecrosis (ON) characterized by empty osteocyte lacunae. However, CFZ had no effect on visceral fat content and was not associated with any metabolic and hematologic changes. Levels of unsaturated fatty acids in MAT were higher than saturated fatty acids and CFZ further increased the former. From these data, we conclude that CFZ has adverse skeletal effects and could be used for creating a rodent ON model devoid of extraskeletal effects.
A Genomic Approach to Develop a New qPCR Test Enabling Detection of the Pyricularia oryzae Lineage Causing Wheat Blast
Authors: Thierry Maud , Gladieux Pierre , Fournier Elisabeth , Tharreau Didier , Ioos Renaud
Published: August 2019

Rapid detection is key to managing emerging diseases because it allows their spread around the world to be monitored and limited. The first major wheat blast epidemics were reported in 1985 in the Brazilian state of Paraná. Following this outbreak, the disease quickly spread to neighboring regions and countries and, in 2016, the first report of wheat blast disease outside South America was released. This Asian outbreak was due to the trade of infected South American seed, demonstrating the importance of detection tests in order to avoid importing contaminated biological material into regions free from the pathogen. Genomic analysis has revealed that one particular lineage within the fungal species Pyricularia oryzae is associated with this disease: the Triticum lineage. A comparison of 81 Pyricularia genomes highlighted polymorphisms specific to the Triticum lineage, and this study developed a real-time PCR test targeting one of these polymorphisms. The test’s performance was then evaluated in order to measure its analytical specificity, analytical sensitivity, and robustness. The C17 quantitative PCR test detected isolates belonging to the Triticum lineage with high sensitivity, down to 13 plasmid copies or 1 pg of genomic DNA per reaction tube. The blast-based approach developed here to study P. oryzae can be transposed to other emerging diseases.
Quantification of gastric emptying caused by impaired coordination of pyloric closure with antral contraction: a simulation study
Authors: Ishida Shunichi , Miyagawa Taimei , O'Grady Gregory , Cheng Leo K. , Imai Yohsuke
Published: August 2019

Proper coordination of gastric motor functions is required for healthy gastric emptying. However, pyloric function may be impaired by functional disorders or surgical procedures. Here, we show how coordination between pyloric closure and antral contraction affects the emptying of liquid contents. We numerically simulated fluid dynamics using an anatomically realistic gastrointestinal geometry. Peristaltic contractions in the proximal stomach resulted in gastric emptying at a rate of 3–8 ml min
−1
. When the pylorus was unable to close, the emptying rate increased to 10–30 ml min
−1
, and instantaneous retrograde flow from the duodenum to the antrum occurred during antral relaxation. Rapid emptying occurred if the pylorus began to open during the terminal antral contraction, and the emptying rate was negative if the pylorus only opened during the antral relaxation phase. Our results showed that impaired coordination between antral contraction and pyloric closure can result in delayed gastric emptying, rapid gastric emptying and bile reflux.
Incorporating household structure and demography into models of endemic disease
Authors: Hilton Joe , Keeling Matt J.
Published: August 2019

The spread of infectious diseases is intimately linked with the strength and type of contact between individuals. Multiple observational and modelling studies have highlighted the importance of two forms of social mixing: age structure, where the likelihood of interaction between two individuals is determined by their ages; and household structure, which recognizes the much stronger contacts and hence transmission potential within the family setting. Age structure has been ubiquitous in predictive models of both endemic and epidemic infections, in part due to the ease of assessing someone’s age. By contrast, although household structure is potentially the dominant heterogeneity, it has received less attention, in part due to an absence of the necessary methodology. Here, we develop the modelling framework necessary to predict the behaviour of endemic infections (which necessitates capturing demographic processes) in populations that possess both household and age structure. We compare two childhood infections, with measles-like and mumps-like parameters, and two populations with UK-like and Kenya-like characteristics, which allows us to disentangle the impact of epidemiology and demography. For this high-dimensional model, we predict complex nonlinear dynamics, where the dynamics of within-household outbreaks are tempered by historical waves of infection and the immunity of older individuals.
Simultaneous normal form transformation and model-order reduction for systems of coupled nonlinear oscillators
Authors: Liu X. , Wagg D. J.
Published: August 2019

In this paper, we describe a direct normal form decomposition for systems of coupled nonlinear oscillators. We demonstrate how the order of the system can be reduced during this type of normal form transformation process. Two specific examples are considered to demonstrate particular challenges that can occur in this type of analysis. The first is a 2 d.f. system with both quadratic and cubic nonlinearities, where there is no internal resonance, but the nonlinear terms are not necessarilyε1-order small. To obtain an accurate solution, the direct normal form expansion is extended toε2-order to capture the nonlinear dynamic behaviour, while simultaneously reducing the order of the system from 2 to 1 d.f. The second example is a thin plate with nonlinearities that areε1-order small, but with an internal resonance in the set of ordinary differential equations used to model the low-frequency vibration response of the system. In this case, we show how a direct normal form transformation can be applied to further reduce the order of the system while simultaneously obtaining the normal form, which is used as a model for the internal resonance. The results are verified by comparison with numerically computed results using a continuation software.
Periodic Schwarz–Christoffel mappings with multiple boundaries per period
Authors: Baddoo Peter J. , Crowdy Darren G.
Published: August 2019

We present an extension to the theory of Schwarz–Christoffel (S–C) mappings by permitting the target domain to be a single period window of a periodic configuration having multiple polygonal (straight-line) boundaries per period. Taking the arrangements to be periodic in the
x
-direction in an (
x
, 
y
)-plane, three cases are considered; these differ in whether the period window extends off to infinity as
y
 →  ± ∞, or extends off to infinity in only one direction (
y
 →  + ∞ or
y
 →  − ∞), or is bounded. The preimage domain is taken to be a multiply connected circular domain. The new S–C mapping formulae are shown to be expressible in terms of the Schottky–Klein prime function associated with the circular preimage domains. As usual for an S–C map, the formulae are explicit but depend on a finite set of accessory parameters. The solution of this parameter problem is discussed in detail, and illustrative examples are presented to highlight the essentially constructive nature of the results.
A methodology for identifying optimum vibration absorbers with a reaction mass
Authors: Ying Zhang Sara , Li Yi-Yuan , Jiang Jason Zheng , Neild Simon A. , Macdonald John H. G.
Published: August 2019

Tuned mass dampers (TMDs), in which a reaction mass is attached to a structural system via a spring–parallel–damper connection, are commonly used in a wide range of applications to suppress deleterious vibrations. Recently, a mass-included absorber layout with an inerter element, termed the tuned mass damper inerter (TMDI), was introduced, showing significant performance benefits on vibration suppression. However, there are countless mass-included absorber layouts with springs, dampers and inerters, which could potentially provide more preferred dynamic properties. Currently, because there is no systematic methodology for accessing them, only an extremely limited number of mass-included absorber layouts have been investigated. This paper proposes an approach to identify optimum vibration absorbers with a reaction mass. Using this approach, a full class of absorber layouts with a reaction mass and a pre-determined number of inerters, dampers and springs connected in series and parallel, can be systematically investigated using generic Immittance-Function-Networks. The advan- tages of the proposed approach are demonstrated via a 3 d.f. structure example.
New ways to acquire resistance: imperfect convergence in insect adaptations to a potent plant toxin
Authors: Dobler Susanne , Wagschal Vera , Pietsch Niels , Dahdouli Nadja , Meinzer Fee , Romey-Glüsing Renja , Schütte Kai
Published: August 2019

Evolution of insensitivity to the toxic effects of cardiac glycosides has become a model in the study of convergent evolution, as five taxonomic orders of insects use the same few similar amino acid substitutions in the otherwise highly conserved Na,K-ATPase α. We show here that insensitivity in pyrgomorphid grasshoppers evolved along a slightly divergent path. As in other lineages, duplication of the Na,K-ATPase α gene paved the way for subfunctionalization: one copy maintains the ancestral, sensitive state, while the other copy is resistant. Nonetheless, in contrast with all other investigated insects, the grasshoppers' resistant copy shows length variation by two amino acids in the first extracellular loop, the main part of the cardiac glycoside-binding pocket. RT-qPCR analyses confirmed that this copy is predominantly expressed in tissues exposed to the toxins, while the ancestral copy predominates in the nervous tissue. Functional tests with genetically engineered
Drosophila
Na,K-ATPases bearing the first extracellular loop of the pyrgomorphid genes showed the derived form to be highly resistant, while the ancestral state is sensitive. Thus, we report convergence in gene duplication and in the gene targets for toxin insensitivity; however, the means to the phenotypic end have been novel in pyrgomorphid grasshoppers.
Pathogen spillover from
Apis mellifera
to a stingless bee
Authors: Purkiss Terence , Lach Lori
Published: August 2019

Pathogen spillover from managed bees is increasingly considered as a possible cause of pollinator decline. Though spillover has been frequently documented, evidence of the pathogen's virulence in the new host or mechanism of transmission is rare. Stingless bees (Apocrita: Meliponini) are crucial pollinators pan-tropically and overlap with managed honeybees (
Apis mellifera
) in much of their range.
Nosema ceranae
is the most prevalent disease of adult
A. mellifera.
We used laboratory experiments and field surveys to investigate the susceptibility of stingless bees (
Tetragonula hockingsi
) to
N. ceranae
, infection prevalence and transmissibility via flowers. We found that 67% of
T. hockingsi
fed sucrose with
N. ceranae
had detectable spores in their ventriculus, and they died at 2.96 times the rate of sucrose-only fed bees. Five of six field hives harboured bees with
N. ceranae
present at least once during our five-month survey, with prevalence up to 20%. In our floral transmission experiment, 67% of inflorescences exposed to infected
A. mellifera
yielded
N. ceranae
spores, and all resulted in
T. hockingsi
with
N. ceranae
spores in their guts. We conclude that
N. ceranae
is virulent in
T. hockingsi
under laboratory conditions, is common in the local
T. hockingsi
population and is transmissible via flowers.
A new QRS detector stress test combining temporal jitter and F-score (JF) reveals significant performance differences amongst popular detectors
Authors: Porr Bernd , Macfarlane Peter W
Published: August 2019

QRS detection within an electrocardiogram (ECG) is the basis of virtually any further processing and any error caused by this detection will propagate to further processing stages. However, standard benchmarking procedures of QRS detectors are seriously flawed because they report almost always close to 100% accuracy for any QRS detection algorithm. This is due to the use of large temporal error margins and noise-free ECG databases which grossly overestimate their performance. The use of a large fixed error margin masks temporal jitter between detection and ground truth measurements. Here, we present a new performance measure (JF) which combines temporal jitter with the F-score, and also an ECG database with decreasing levels of signal to noise ratios based on noise generated from different tasks. Our new performance measure JF fully encompasses all the types of errors that can occur, equally weights them and provides a percentage value which allows direct comparison between QRS detection algorithms. In combination with the new noisy ECG database, the JF performance measure now varies between 50% and 100% for different detectors and signal to noise conditions thereby making it possible to find the best detector for an application.
Choice-selective sequences dominate in cortical relative to thalamic inputs to nucleus accumbens, providing a potential substrate for credit assignment
Authors: Parker Nathan F. , Baidya Avinash , Cox Julia , Haetzel Laura , Zhukovskaya Anna , Murugan Malavika , Engelhard Ben , Goldman Mark S. , Witten Ilana B.
Published: August 2019

How are actions linked with subsequent outcomes to guide choices? The nucleus accumbens, which is implicated in this process, receives glutamatergic inputs from the prelimbic cortex and midline regions of the thalamus. However, little is known about whether and how representations differ across these input pathways. By comparing these inputs during a reinforcement learning task in mice, we discovered that prelimbic cortical inputs preferentially represent actions and choices, whereas midline thalamic inputs preferentially represent cues. Choice-selective activity in the prelimbic cortical inputs is organized in sequences that persist beyond the outcome. Through computational modeling, we demonstrate that these sequences can support the neural implementation of reinforcement learning algorithms, both in a circuit model based on synaptic plasticity, and one based on neural dynamics. Finally, we test and confirm predictions of our circuit models by direct manipulation of nucleus accumbens input neurons. Thus, we integrate experiment and modeling to suggest neural solutions for credit assignment.
Multi-omic analysis of medium-chain fatty acid synthesis byCandidatusWeimerbacter bifidus, gen. nov., sp. nov., andCandidatusPseudoramibacter fermentans, sp. nov.
Authors: Scarborough Matthew J. , Myers Kevin S. , Donohue Timothy J. , Noguera Daniel R.
Published: August 2019

Chain elongation is emerging as a bioprocess to produce valuable medium-chain fatty acids (MCFA; 6 to 8 carbons in length) from organic waste streams by harnessing the metabolism of anaerobic microbiomes. Although our understanding of chain elongation physiology is still evolving, the reverse β-oxidation pathway has been identified as a key metabolic function to elongate the intermediate products of fermentation to MCFA. Here, we describe two chain-elongating microorganisms that were enriched in an anaerobic microbiome transforming the residues from a lignocellulosic biorefining process to short- and medium-chain fatty acids. Based on a multi-omic analysis of this microbiome, we predict thatCandidatusWeimerbacter bifidus, gen. nov., sp. nov. used xylose to produce MCFA, whereasCandidatusPseudoramibacter fermentans, sp. nov., used glycerol and lactate as substrates for chain elongation. Both organisms are predicted to use an energy conserving hydrogenase to improve the overall bioenergetics of MCFA production.

IMPORTANCE

Microbiomes are vital to human health, agriculture, environmental processes, and are receiving attention as biological catalysts for production of renewable industrial chemicals. Chain elongation by MCFA-producing microbiomes offer an opportunity to produce valuable chemicals from organic streams that otherwise would be considered waste. However, the physiology and energetics of chain elongation is only beginning to be studied, and we are analyzing MCFA production by self-assembled communities to complement the knowledge that has been acquired from pure culture studies. Through a multi-omic analysis of an MCFA-producing microbiome, we characterized metabolic functions of two chain elongating bacteria and predict previously unreported features of this process.
Zinc-α2-Glycoprotein Is An Inhibitor Of Amine Oxidase Copper-Containing 3
Authors: Romauch Matthias
Published: August 2019

Zinc-alpha2-glycoprotein (ZAG) is a major plasma protein whose levels increase in chronic energy-demanding diseases and thus serves as an important clinical biomarker in the diagnosis and prognosis of the development of cachexia. Current knowledge suggests that ZAG mediates progressive weight loss through β-adrenergic signaling in adipocytes, resulting in the activation of lipolysis and fat mobilization. Here, through crosslinking experiments, amine oxidase copper-containing 3 (AOC3) is identified as a novel ZAG binding partner. AOC3 – also known as vascular adhesion protein 1 (VAP-1) and semicarbazide sensitive amine oxidase (SSAO) – deaminates primary amines, thereby generating the corresponding aldehyde, H2O2and HN3. It is an ectoenzyme largely expressed by adipocytes and induced in endothelial cells during inflammation. Extravasation of immune cells depends on amine oxidase activity and AOC3-derived H2O2has an insulinogenic effect. The observations described here suggest that ZAG acts as an allosteric inhibitor of AOC3 and interferes with the associated pro-inflammatory and anti-lipolytic functions. Thus, inhibition of the deamination of lipolytic hormone octopamine by AOC3 represents a novel mechanism by which ZAG might stimulate lipolysis. Furthermore, experiments involving overexpression of recombinant ZAG reveal that its glycosylation is co-regulated by oxygen availability and that the pattern of glycosylation affects its inhibitory potential. The newly identified protein interaction between AOC3 and ZAG highlights a previously unknown functional relationship, which may be relevant to inflammation, energy metabolism and the development of cachexia.
GATA3 controls mitochondrial biogenesis in primary human CD4+T cells during DNA damage
Authors: Callender Lauren A. , Schroth Johannes , Carroll Elizabeth C. , Romano Lisa E.L. , Hendy Eleanor , Kelly Audrey , Lavender Paul , Akbar Arne N. , Chapple J. Paul , Henson Sian M.
Published: August 2019

Introductory paragraph

GATA binding protein 3 (GATA3) has traditionally been regarded as a lineage-specific transcription factor that drives the differentiation of CD4+T helper (Th) 2 cells. However, increasing evidence shows that GATA3 is involved in a myriad of processes such as immune regulation, proliferation and maintenance in other T cell and non-T cell lineages. We show here a previously unknown mechanism utilized by CD4+T cells to increase mitochondrial mass in response to DNA damage through the binding of GATA3, AMP-activated protein kinase (AMPK), peroxisome-proliferator-activated receptor γ co-activator-1α (PGC1α), nuclear factor erythroid 2-related factor 2 (NRF2) and superoxide dismutase 3 (SOD3) to the DNA damage repair (DDR) component ATR. These findings extend the pleotropic nature of GATA3 and highlight the potential for GATA3-targeted cell manipulation for clinical interventions.
Deficiency in the endocytic adaptor protein PHETA1/2 impairs renal and craniofacial development
Authors: Ates Kristin M. , Wang Tong , Moreland Trevor , Veeranan-Karmegam Rajalakshmi , Anand Priya , Wenzel Wolfgang , Kim Hyung-Goo , Wolfe Lynne A. , Stephen Joshi , Adams David R. , Markello Thomas , Tifft Cynthia J. , Gahl William A. , Gonsalvez Graydon B. , Malicdan May Christine , Flanagan-Steet Heather , Pan Y. Albert
Published: August 2019

A critical barrier in the treatment of endosomal and lysosomal diseases is the lack of understanding of thein vivofunctions of the putative causative genes. We addressed this by investigating a key pair of endocytic adaptor proteins, PH domain containing endocytic trafficking adaptor 1 and 2 (PHETA1/2, also known as FAM109A/B, Ses1/2, IPIP27A/B), which interact with the protein product ofOCRL, the causative gene for Lowe syndrome. Here we conducted the first study of PHETA1/2in vivo, utilizing the zebrafish system. We found that impairment of both zebrafish orthologs,pheta1andpheta2, disrupted endocytosis and ciliogenesis. In addition,pheta1/2mutant animals exhibited reduced jaw size and delayed chondrocyte maturation, indicating a role in craniofacial development. Deficiency ofpheta1/2resulted in dysregulation of cathepsin K, which led to an increased abundance of type II collagen in craniofacial cartilages. The abnormal renal and craniofacial phenotypes in thepheta1/2mutant animals were consistent with the clinical presentations of a patient with ade novoarginine (R) to cysteine (C) variant (R6C) of PHETA1. Expressing the patient-specific variant in zebrafish exacerbated craniofacial deficits, suggesting that the R6C allele acts in a dominant-negative manner. Together, these results provide insights into thein vivoroles of PHETA1/2 and suggest that the R6C variant is contributory to the pathogenesis of disease in the patient.
Context-dependent dynamics lead to the assembly of functionally distinct pitcher-plant microbiomes
Authors: Bittleston Leonora S. , Gralka Matti , Leventhal Gabriel E. , Mizrahi Itzhak , Cordero Otto X.
Published: August 2019

Niche construction through interspecific interactions can condition future community states on past ones. However, the extent to which such history dependency can steer communities towards functionally different states remains a subject of active debate. Using bacterial communities collected from wild pitchers of the carnivorous pitcher plant,Sarracenia purpurea, we tested the effects of history on composition and function across communities assembled in synthetic pitcher plant microcosms. We found that the diversity of assembled communities was determined by the diversity of the system at early, pre-assembly stages. Species composition was also contingent on early community states, not only because of differences in the species pool, but also because the same species had different dynamics in different community contexts. Importantly, compositional differences were proportional to differences in function, as profiles of resource use were strongly correlated with composition, despite convergence in respiration rates. Early differences in community structure can thus propagate to mature communities, conditioning their functional repertoire.
Structural genomic applied on the rust fungus Melampsora larici-populina reveals two candidate effector proteins adopting cystine-knot and nuclear transport factor 2-like protein folds
Authors: de Guillen Karine , Lorrain Cécile , Tsan Pascale , Barthe Philippe , Petre Benjamin , Saveleva Natalya , Rouhier Nicolas , Duplessis Sébastien , Padilla André , Hecker Arnaud
Published: August 2019

Rust fungi are plant pathogens that secrete an arsenal of effector proteins interfering with plant functions and promoting parasitic infection. Effectors are often species-specific, evolve rapidly, and display low sequence similarities with known proteins or domains. How rust fungal effectors function in host cells remains elusive, and biochemical and structural approaches have been scarcely used to tackle this question. In this study, we used a strategy based on recombinant protein production in Escherichia coli to study eleven candidate effectors of the leaf rust fungus Melampsora larici-populina. We successfully purified and solved the three-dimensional structure of two proteins, MLP124266 and MLP124017, using NMR spectroscopy. Although both proteins show no sequence similarity with known proteins, they exhibit structural similarities to knottin and nuclear transport factor 2-like proteins, respectively. Altogether, our findings show that sequence-unrelated effectors can adopt folds similar to known proteins, and encourage the use of biochemical and structural approaches to functionally characterize rust effector candidates.
Developmental Characterization ofZswim5Expression in the Progenitor Domains and Tangential Migration Pathways of Cortical Interneurons in the Mouse Forebrain
Authors: Chang Chuan-Chie , Kuo Hsiao-Ying , Chen Shih-Yun , Lu Kuan-Ming , Fong Weng Lam , Wu Hsiao-Lin , Saito Tetsuichiro , Liu Fu-Chin
Published: August 2019

GABAergic interneurons play an essential role in modulating cortical networks. The progenitor domains of cortical interneurons are localized in developing ventral forebrain, including the medial ganglionic eminence (MGE), caudal ganglionic eminence (CGE), preoptic area (POA) and preoptic hypothalamic border domain (POH). Here, we characterized the expression pattern ofZswim5, an MGE-enriched gene in the mouse forebrain. At E11.5 to E13.5, prominentZswim5expression was detected in the subventricular zone (SVZ) of MGE, CGE, POA and POH of ventral telencephalon in which progenitors of cortical interneurons resided. At E15.5 and E17.5,Zswim5remained detectable in the SVZ of pallidal primordium (MGE).Zswim5mRNA was markedly decreased after birth and was absent in the adult forebrain. Interestingly,Zswim5expression pattern resembled the tangential migration pathways of cortical interneurons.Zswim5-positive cells in the MGE appeared to migrate from the MGE through the SVZ of LGE to overlying neocortex. Indeed,Zswim5was co-localized with Nkx2.1 and Lhx6, markers of progenitos and migratory cortical interneurons. Double labeling showed that Mash1/Ascl1-positive cells did not expressZswim5.Zswim5expressing cells showed none or at most low levels of Ki67 but co-expressed Tuj1 in the SVZ of MGE. These results suggest thatZswim5is immediately upregulated as progenitors exiting cell cycle to become postmitotic. Given that recent studies have elucidated that the cell fate of cortical interneurons is determined shortly after postmitotic, the timing ofZswim5expression in early postmitotic cortical interneurons suggests a potential role ofZswim5in regulation of neurogenesis and tangential migration of cortical interneurons.
XANES and EXAFS of dilute solutions of transition metals at XFELs
Authors: Chatterjee Ruchira , Weninger Clemens , Loukianov Anton , Gul Sheraz , Fuller Franklin D. , Cheah Mun Hon , Fransson Thomas , Pham Cindy C. , Nelson Silke , Song Sanghoon , Britz Alexander , Messinger Johannes , Bergmann Uwe , Alonso-Mori Roberto , Yachandra Vittal K. , Kern Jan , Yano Junko
Published: August 2019

This work has demonstrated that X-ray absorption spectroscopy (XAS), both Mn XANES and EXAFS, of solutions with millimolar concentrations of metal is possible using the femtosecond X-ray pulses from XFELs. Mn XAS data were collected using two different sample delivery methods, a Rayleigh jet and a drop-on-demand setup, with varying concentrations of Mn. Here, a new method for normalization of XAS spectra based on solvent scattering that is compatible with data collection from a highly variable pulsed source is described. The measured XANES and EXAFS spectra of such dilute solution samples are in good agreement with data collected at synchrotron sources using traditional scanning protocols. The procedures described here will enable XFEL-based XAS on dilute biological samples, especially metalloproteins, with low sample consumption. Details of the experimental setup and data analysis methods used in this XANES and EXAFS study are presented. This method will also benefit XAS performed at high-repetition-rate XFELs such as the European XFEL, LCLS-II and LCLS-II-HE.
Finite-element analysis of turbine generator using homogenization method taking account of magnetic anisotropy
Authors: Minehisa Ryoko , Takahashi Yasuhito , Fujiwara Koji , Takahashi Norio , Fujita Masafumi , Tsujikawa Kazuma , Nagakura Ken
Published: August 2019

Purpose

This paper aims to propose a homogenization method considering magnetic anisotropy for a magnetic field analysis of a turbine generator. To verify the validity of the proposed method, the effects of magnetic anisotropy and a space factor on a no-load saturation curve and no-load iron loss of the turbine generator are discussed.

Design/methodology/approach

The proposed method was derived from the combination of the homogenization of microscopic fields in a laminated iron core with the modelling of two-dimensional magnetic properties based on free energy. To verify the validity, the proposed method was applied to a finite-element analysis of a simple ring core model. Finally, a no-load saturation curve and iron loss of the turbine generator was investigated by using the proposed method.

Findings

The computational accuracy of the homogenization method considering magnetic anisotropy is almost the same as that of the detailed modelling of the laminated structure in the magnetic field analysis of the laminated iron core. Furthermore, it is clarified that magnetic anisotropy does not have a large influence on the no-load saturation curve of the turbine generator because of the large air gap. On the other hand, the space factor affects the shape of the no-load saturation curve.

Originality/value

This paper verifies the validity of the homogenization method considering magnetic anisotropy method and elucidates the effects of magnetic anisotropy and a space factor on no-load characteristics of the turbine generator.