bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism behind dry etching of Si assisted by pulsed visible laser
Authors: Peck Jason A. , Ruzic David N.
Published: November 2017

Poly-Si films were etched using a 13.56 MHz capacitively coupled plasma source while simultaneously being exposed to a pulsed Nd:YAG laser using 266 and 532 nm lines, with Gaussian pulse durations of 100 Hz and 7 ns. For a fluorocarbon etch recipe of 50:8 sccm Ar:C4F8 with varying O2, a minimum laser intensity for the etch onset was necessary to overcome CFx polymer deposition. This etch onset occurred at 6 ± 1 mJ/cm2/pulse; beyond this onset, the etch rate increased linearly with laser intensity. Null results of laser etch enhancement using continuous wave diode sources demonstrated the necessity of the instantaneous application of the pulsed Nd:YAG source. To determine the mechanism of laser etch enhancement at 532 nm, highly doped Si samples were tested, with varying optical absorption depths while keeping the photon energy constant. It was shown that at phosphorus contents of 1019 cm−3 and 1021 cm−3, 532 nm etch enhancement trends were 1.7× and 3.7× higher than those on intrinsic Si, showing that instantaneous surface heating was key in desorbing involatile etch products. Further investigation of the surface fluorine content via X-ray photon spectroscopy showed that distinct desorption stages occurred for increasing pulse energy—trends which aligned very well with SiFx desorption promoted by steady-state wafer heating. Gas arrival/surface saturation experiments with varying pressures and pulse rates showed that, in straightforward etching discharges such as Ar/SF6, laser removal per pulse plateaus when the pulse rate is lower than the rate of surface saturation, while in fluorocarbon-rich etch chemistries such as Ar/C4F8/O2 mixtures, a minimum pulse rate must be maintained to overcome the CFx polymer layer being deposited.
Modeling the perturbation growth in an acoustically excited plane jet
Authors: Nagy Péter Tamás , Paál György
Published: November 2017

Four methods of varying complexity to investigate jet instability were tested on a plane jet and compared with CFD results. A unified treatment that includes the acoustic excitation in an incompressible simulation was developed. It turned out that the more sophisticated methods have no real advantage over the well-established Orr-Sommerfeld and Rayleigh equations. A new mode with extremely high growth rates in the vicinity of the nozzle exit was discovered.
Saturation of the photoneutralization of a H− beam in continuous operation
Authors: Bresteau D. , Blondel C. , Drag C.
Published: November 2017

An unprecedented, greater than 50%, photodetachment rate is obtained on a H− beam in the continuous regime. The key element of the experimental setup is a medium-finesse optical cavity, suspended around the anion beam, which makes it possible to recycle the photon flux in the interaction region, at the crossing between the anion and laser beams. The cavity is injected by a narrow-linewidth ytterbium-doped fibre laser, at the wavelength 1064 nm. The light power stored in the cavity is about 14 kW for 24 W of input light power. Similar greater-than-50% photo-neutralization efficiencies can be contemplated for beams with kinetic energies much larger than 1.2 keV of the presently used H− beam, given the fact that the stored light power can be increased, for larger beam diameters, by several orders of magnitude. The technique can thus be relied on to design novel D0 injectors, for fusion reactors, with a much better efficiency than the molecular-collision based injectors presently developed for ITER. It can also be applied to the production of neutral beams of any species that can be conveniently prepared in the form of an anion beam, provided that efficient light power storage can be achieved for the corresponding photodetachment wavelength.
Energy distributions of electrons emitted by a biased laser-produced plasma at 1013 W cm−2
Authors: Raymond Xavier , Versteegen Maud , Gobet Franck , Hannachi Fazia , Henares Jose Luis , Tarisien Medhi
Published: November 2017

In this paper, we present the electron bunches extracted from a dense plasma produced by the interaction of a ns laser at an intensity of 1013 W cm−2 with a solid target, when this plasma expands in an electric field. The plasma expansion dynamics measured in the previous works [M. Comet et al., J. Appl. Phys. 119, 013301 (2016)] is used to determine the electron charge density profile at different instants after the laser shot. When applying the electric field, a few 1013 electrons are extracted with continuous energy distributions. Particle-In-Cell simulations are run to understand the extraction process and reproduce the measured energy distributions, with the electron charge density profiles used as inputs. These simulations show that the electron extraction proceeds from the plasma front edge throughout the plasma expansion.
Coercivity enhancement in VO2/Ni bilayers due to interfacial stress
Authors: Lauzier J. , Sutton L. , de la Venta J.
Published: November 2017

We studied the temperature dependence of the magnetic properties of VO2/Ni bilayers deposited on three different substrates. The temperature induced VO2 transformation from a monoclinic to a rutile structure induces strain in the Ni film. Due to an inverse magnetostrictive effect, the coercivity of the Ni films is strongly modified. The morphology of the films is influenced by the substrate choice and has a strong impact on the magnetic properties. Ni films grown on top of rutile VO2 show a reversible change in the coercivity and a strong enhancement of the coercivity near the transition temperature. The coercivity enhancement of Ni is associated with the phase coexistence observed in the VO2 first order phase transition.
Communication: The Al + CO2 → AlO + CO reaction: Experiment vs. theory
Authors: Sun Zhi , Moore Kevin B. , Schaefer Henry F.
Published: November 2017

Based on their highly sophisticated crossed-beam experimental studies of the Al + CO2 → AlO + CO reaction, Honma and Hirata have directly challenged the results of earlier theoretical studies of this system. We report high level theoretical studies of this system. It is shown that, consistent with Honma-Hirata experimental conclusions, the previous theoretical prediction of a substantial barrier height for this reaction was incorrect. However, for the structures of the possible intermediates, in agreement with the 1992 theoretical study of Sakai, we find striking disagreement with the experimental conclusion that the O–C–O moiety is nearly linear. The energies of the three entrance channel intermediates lie 14.4, 15.2, and 16.4 kcal mol−1 below separated Al + CO2.
Hybrid simulation of electron energy distributions and plasma characteristics in pulsed RF CCP sustained in Ar and SiH4/Ar discharges
Authors: Wang Xi-Feng , Jia Wen-Zhu , Song Yuan-Hong , Zhang Ying-Ying , Dai Zhong-Ling , Wang You-Nian
Published: November 2017

Pulsed-discharge plasmas offer great advantages in deposition of silicon-based films due to the fact that they can suppress cluster agglomeration, moderate the energy of bombarding ions, and prolong the species' diffusion time on the substrate. In this work, a one-dimensional fluid/Monte-Carlo hybrid model is applied to study pulse modulated radio-frequency (RF) plasmas sustained in capacitively coupled Ar and SiH4/Ar discharges. First, the electron energy distributions in pulsed Ar and SiH4/Ar plasmas have been investigated and compared under identical discharge-circuit conditions. The electron energy distribution function (EEDF) in Ar discharge exhibits a familiar bi-Maxwellian shape during the power-on phase of the pulse, while a more complex (resembling a multi-Maxwellian) distribution with extra inflection points at lower energies is observed in the case of the SiH4/Ar mixture. These features become more prominent with the increasing fraction of SiH4 in the gas mixture. The difference in the shape of the EEDF (which is pronounced inside the plasma but not in the RF sheath where electron heating occurs) is mainly attributed to the electron-impact excitations of SiH4. During the power-off phase of the pulse, the EEDFs in both Ar and SiH4/Ar discharges evolve into bi-Maxwellian shapes, with shrinking high energy tails. Furthermore, the parameter of ion species in the case of SiH4/Ar discharge is strongly modulated by pulsing. For positive ions, such as SiH3+ and Si2H4+, the particle fluxes overshoot at the beginning of the power-on interval. Meanwhile, for negative ions such as SiH2− and SiH3−, density profiles observed between the electrodes are saddle-shaped due to the repulsion by the self-bias electric field as it builds up. During the power-off phase, the wall fluxes of SiH2− and SiH3− gradually increase, leading to a significant decrease in the net surface charge density on the driven electrode. Compared with ions, the density of SiH3 is poorly modulated by pulsed power and is nearly constant over the entire modulation period, but the density of SiH2 shows a detectable decline in the afterglow. However, because of a much smaller content of SiH2, the deposition rate hardly shows any variation under the selected waveform of the pulse.
Factors associated with unplanned readmissions in a major Australian health service
Authors: Considine Julie , Fox Karen , Plunkett David , Mecner Melissa , O'Reilly Mary , Darzins Peteris
Published: November 2017

Objective
The aim of the present study was to gain an understanding of the factors associated with unplanned hospital readmission within 28 days of acute care discharge from a major Australian health service.

Methods
A retrospective study of 20575 acute care discharges from 1 August to 31 December 2015 was conducted using administrative databases. Patient, index admission and readmission characteristics were evaluated for their association with unplanned readmission in ≤28 days.

Results
The unplanned readmission rate was 7.4% (n=1528) and 11.1% of readmitted patients were returned within 1 day. The factors associated with increased risk of unplanned readmission in ≤28 days for all patients were age ≥65 years (odds ratio (OR) 1.3), emergency index admission (OR 1.6), Charlson comorbidity index >1 (OR 1.1–1.9), the presence of chronic disease (OR 1.4) or complications (OR 1.8) during the index admission, index admission length of stay (LOS) >2 days (OR 1.4–1.8), hospital admission(s) (OR 1.7–10.86) or emergency department (ED) attendance(s) (OR 1.8–5.2) in the 6 months preceding the index admission and health service site (OR 1.2–1.6). However, the factors associated with increased risk of unplanned readmission ≤28 days changed with each patient group (adult medical, adult surgical, obstetric and paediatric).

Conclusions
There were specific patient and index admission characteristics associated with increased risk of unplanned readmission in ≤28 days; however, these characteristics varied between patient groups, highlighting the need for tailored interventions.

What is known about the topic?
Unplanned hospital readmissions within 28 days of hospital discharge are considered an indicator of quality and safety of health care.

What does this paper add?
The factors associated with increased risk of unplanned readmission in ≤28 days varied between patient groups, so a ‘one size fits all approach’ to reducing unplanned readmissions may not be effective. Older adult medical patients had the highest rate of unplanned readmissions and those with Charlson comorbidity index ≥4, an index admission LOS >2 days, left against advice and hospital admission(s) or ED attendance(s) in the 6 months preceding index admission and discharge from larger sites within the health service were at highest risk of unplanned readmission.

What are the implications for practitioners?
One in seven discharges resulted in an unplanned readmission in ≤28 days and one in 10 unplanned readmissions occurred within 1 day of discharge. Although some patient and hospital characteristics were associated with increased risk of unplanned readmission in ≤28 days, statistical modelling shows there are other factors affecting the risk of readmission that remain unknown and need further investigation. Future work related to preventing unplanned readmissions in ≤28 days should consider inclusion of health professional, system and social factors in risk assessments.
Tracking and tracing central Queensland’s Macroderma – determining the size of the Mount Etna ghost bat population and potential threats
Authors: Augusteyn John , Hughes Jane , Armstrong Graeme , Real Kathryn , Pacioni Carlo
Published: November 2017

The ghost bat, Macroderma gigas, colony at Mount Etna was at the centre of Australia’s longest-running conservation campaign. To protect the colony the Queensland Government removed recreational facilities and gated caves. The size and genetic diversity of the Mount Etna M. gigas population were estimated using cave searches, direct captures and molecular analysis to determine whether these actions have benefitted the species. In addition, telemetry was undertaken and red fox, Vulpes vulpes, scats analysed to identify possible threats. Results suggest that the population has declined by 79% since the late 1990s, has low microsatellite diversity, low effective population size (Ne) and is undergoing a population bottleneck. VHF- and GPS-collared animals were found to forage over agricultural land up to 11.8 km from their daytime roost, suggesting that poor land management and barbed-wire fences could be potential threats. No ghost bat remains were found in fox scats. We recommend that compliance be increased around Johansen’s Cave to reduce disturbance during the maternity season and landholders be encouraged to undertake management that is sympathetic to ghost bats.
Effects of nitrogen addition on soil oxidisable organic carbon fractions in the rhizospheric and bulk soils of Chinese pines in north-western China
Authors: Liu Hongfei , Xue Sha , Wang Guoliang , Liu Guobin
Published: November 2017

Increased atmospheric nitrogen (N) deposition caused by human activities has potentially important effects on ecosystem carbon (C) dynamics and different effects on C fractions with different stabilities and chemical compositions. A better understanding of the responses of different C fractions to N addition is vital for maintaining soil quality and protecting vegetation. In order to investigate the differential effects of N addition on total soil organic carbon (SOC) and four SOC fractions with increasing degrees of oxidisability in Pinus tabuliformis rhizospheric and bulk soils, a 6-year pot experiment was performed testing the effects of the addition of N at rates of 2.8, 5.6, 11.2, 22.4 and 44.8 g m–2 year–1 compared with a control (CK) group (no N addition). Addition of N addition had significant (P < 0.05) effects on SOC fractions of very labile C (C1) and recalcitrant C (C4), but negligible effects on total SOC (TOC) and SOC fractions of labile C (C2) and less labile C (C3). The C1 content and ratio of C1 to TOC in rhizospheres decreased following the addition of low levels (N2.8–N5.6) of N, but increased after the addition of high levels (N11.2–N44.8) of N, with minimum values obtained after the addition of 11.2 N g m–2 year–1. Low rates (N2.8–N5.6) of N addition considerably increased C4 and the ratio of C4 to TOC in the rhizosphere, whereas addition of high rates (N11.2–N44.8) of N decreased these parameters. The responses of C1 and C4 in the bulk soil to N addition were opposite. The SOC fraction was significantly higher in the rhizosphere than in the bulk soil, indicating large rhizospheric effects. However, increased N addition weakened these effects. These findings suggest that low rates (N2.8–N5.6) of N addition stabilise SOC against chemical and biological degradation, whereas increased rates of N addition increase the lability of SOC in the bulk soil. Thus, the rhizosphere plays a vital role in soil carbon stability and sequestration in response to N addition.
How to rewire the host cell: A home improvement guide for intracellular bacteria
Authors: Cornejo Elias , Schlaermann Philipp , Mukherjee Shaeri
Published: November 2017

Intracellular bacterial pathogens have developed versatile strategies to generate niches inside the eukaryotic cells that allow them to survive and proliferate. Making a home inside the host offers many advantages; however, intracellular bacteria must also overcome many challenges, such as disarming innate immune signaling and accessing host nutrient supplies. Gaining entry into the cell and avoiding degradation is only the beginning of a successful intracellular lifestyle. To establish these replicative niches, intracellular pathogens secrete various virulence proteins, called effectors, to manipulate host cell signaling pathways and subvert host defense mechanisms. Many effectors mimic host enzymes, whereas others perform entirely novel enzymatic functions. A large volume of work has been done to understand how intracellular bacteria manipulate membrane trafficking pathways. In this review, we focus on how intracellular bacterial pathogens target innate immune signaling, the unfolded protein response, autophagy, and cellular metabolism and exploit these pathways to their advantage. We also discuss how bacterial pathogens can alter host gene expression by directly modifying histones or hijacking the ubiquitination machinery to take control of several host signaling pathways.
Costs of a Practice‐based Air Quality Regulation: Dairy Farms in the San Joaquin Valley
Authors: Zhang Wei
Published: November 2017

Facing the difficulty of accurately measuring pollution from agriculture, economists have recommended regulatory approaches using proxies such as management practices to reduce agricultural pollution. Using farm‐level cost data on a panel of dairy farms, I estimate the effects of a practice‐based air quality regulation for dairy farms in the San Joaquin Valley in California. As opposed to ex ante analyses, my econometric results indicate that the air quality regulation has not significantly affected the total costs of milk production. Estimates also suggest that the regulation might have differential effects on different elements of costs. I support the econometric findings with evidence on how dairy farms comply with the regulation. Calculated adoption rates of different pollution‐mitigation practices using administrative data reveal that dairy farms have mainly adopted labor‐intensive practices to comply with the regulation.
Acute Systemic Complications of Convulsive Status Epilepticus—A Systematic Review
Authors: Sutter Raoul , Dittrich Tolga , Semmlack Saskia , Rüegg Stephan , Marsch Stephan , Kaplan Peter W.
Published: November 2017

Objectives:

Status epilepticus is a neurologic emergency with high morbidity and mortality requiring neurointensive care and treatment of systemic complications. This systematic review compiles the current literature on acute systemic complications of generalized convulsive status epilepticus in adults and their immediate clinical impact along with recommendations for optimal neurointensive care.

Data Sources:

We searched PubMed, Medline, Embase, and the Cochrane library for articles published between 1960 and 2016 and reporting on systemic complications of convulsive status epilepticus.

Study Selection:

All identified studies were screened for eligibility by two independent reviewers.

Data Extraction:

Key data were extracted using standardized data collection forms.

Data Synthesis:

Thirty-two of 3,046 screened articles were included. Acute manifestations and complications reported in association with generalized convulsive status epilepticus can affect all organ systems fueling complex cascades and multiple organ interactions. Most reported complications result from generalized excessive muscle contractions that increase body temperature and serum potassium levels and may interfere with proper and coordinated function of respiratory muscles followed by hypoxia and respiratory acidosis. Increased plasma catecholamines can cause a decay of skeletal muscle cells and cardiac function, including stress cardiomyopathy. Systemic complications are often underestimated or misinterpreted as they may mimic underlying causes of generalized convulsive status epilepticus or treatment-related adverse events.

Conclusions:

Management of generalized convulsive status epilepticus should center on the administration of antiseizure drugs, treatment of the underlying causes, and the attendant systemic consequences to prevent secondary seizure-related injuries. Heightened awareness, systematic clinical assessment, and diagnostic workup and management based on the proposed algorithm are advocated as they are keys to optimal outcome.
Trunk Exercises Improve Gait Symmetry in Parkinson Disease
Authors: Hubble Ryan P. , Naughton Geraldine , Silburn Peter A. , Cole Michael H.
Published: November 2017

Objective

Deficits in step-to-step symmetry and trunk muscle activations have been linked to falls in Parkinson disease. Given such symptoms are poorly managed with anti-parkinsonian medications, alternate therapies are needed. This blind phase II randomized controlled trial sought to establish whether exercise can improve step-to-step symmetry in Parkinson disease.

Design

Twenty-four Parkinson disease patients with a falls history completed baseline assessments of symptom severity, balance confidence, mobility, and quality of life. Step-to-step symmetry was assessed by deriving harmonic ratios from three-dimensional accelerations collected for the head and trunk. Patients were randomly assigned to either 12 wks of exercise and falls prevention education or falls prevention education only. Both groups repeated the baseline tests 12 and 24 wks after the initial assessment. The Australian and New Zealand Clinical Trials Registry number is ACTRN12613001175763.

Results

At 12 wks, the exercise group had statistically significant and clinically relevant improvements in anterior-posterior step-to-step trunk symmetry. In contrast, the education group recorded statistically significant and clinically meaningful reductions in medial-lateral and vertical step-to-step trunk symmetry at 12 wks.

Conclusions

Given that step-to-step symmetry improved for the exercise group and declined for the education group after intervention, active interventions seem more suited to increasing independence and quality of life for people with Parkinson disease.

To Claim CME Credits

Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME

CME Objectives

Upon completion of this article, the reader should be able to do the following: (1) Describe the effect deficits in trunk muscle function have on gait in individuals with Parkinson disease; (2) Identify the benefits of targeted trunk exercises on step-to-step symmetry; and (3) Discuss the benefits of improving step-to-step symmetry in individuals with Parkinson disease.

Level

Advanced

Accreditation

The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Avian thermoregulation in the heat: phylogenetic variation among avian orders in evaporative cooling capacity and heat tolerance
Authors: Smit Ben , Whitfield Maxine C. , Talbot William A. , Gerson Alexander R. , McKechnie Andrew E. , Wolf Blair O.
Published: November 2017

Little is known about the phylogenetic variation of avian evaporative cooling efficiency and heat tolerance in hot environments. We quantified thermoregulatory responses to high air temperature (Ta) in ~100-g representatives of three orders: African cuckoo (Cuculus gularis, Cuculiformes), lilac-breasted roller (Coracias caudatus, Coraciiformes), and Burchell’s starling (Lamprotornis australis, Passeriformes). All three species initiated respiratory mechanisms to increase evaporative heat dissipation when body temperature (Tb) approached 41.5°C in response to increasingTa, with gular flutter observed in cuckoos and panting in rollers and starlings. Resting metabolic rate (RMR) and evaporative water loss (EWL) increased by quantitatively similar magnitudes in all three species, although maximum rates of EWL were proportionately lower in starlings. Evaporative cooling efficiency [defined as the ratio of evaporative heat loss (EHL) to metabolic heat production (MHP)] generally remained below 2.0 in cuckoos and starlings, but reached a maximum of ~3.5 in rollers. The high value for rollers reveals a very efficient evaporative cooling mechanism, and is similar to EHL/MHP maxima for similarly sized columbids which very effectively dissipate heat via cutaneous evaporation. This unexpected phylogenetic variation among the orders tested in the physiological mechanisms of heat dissipation is an important step toward determining the evolution of heat tolerance traits in desert birds.

Summary statement

We show that avian evaporative cooling efficiency and heat tolerance display substantial taxonomic variation that are, unexpectedly, not systematically related to the use of panting versus gular flutter processes.
Histone Deacetylase 11 is an ε-N-Myristoyllysine Hydrolase
Authors: Moreno-Yruela Carlos , Galleano Iacopo , Madsen Andreas S. , Olsen Christian A.
Published: November 2017

Histone deacetylase (HDAC) enzymes are important regulators of diverse biological function, including gene expression, rendering them potential targets for intervention in a number of diseases, with a handful of compounds approved for treatment of certain hematologic cancers. Among the human zinc-dependent HDACs, the most recently discovered member, HDAC11, is the only member assigned to subclass IV, the smallest protein, and the least well understood with regards to biological function. Here we show that HDAC11 cleaves long chain acyl modifications on lysine side chains with remarkable efficiency compared to acetyl groups. We further show that several common types of HDAC inhibitors, including the approved drugs romidepsin and vorinostat, do not inhibit this enzymatic activity. Macrocyclic hydroxamic acid-containing peptides, on the other hand, potently inhibit HDAC11 demyristoylation activity. These findings should be taken carefully into consideration in future investigations of the biological function of HDAC11 and will serve as a foundation for the development of selective chemical probes targeting HDAC11.
Development of real-time polymerase chain reaction assays allowing molecular detection ofEchinococcus felidis, Echinococcus granulosussensu stricto, andEchinococcus canadensisin carnivore feces samples, animal and human hydatid cyst material from Uganda and Kenya
Authors: Kopp Katharina
Published: November 2017

First evaluations on field samples, including carnivore feces, animal and human hydatid cyst material from Uganda and Kenya, showed specific amplification of two target regions of the mitochondrial genome ofEchinococcusspecies according to melt and high-resolution melt curve analyses of the developed real-time PCR assays. Consecutive sequencing of PCR products revealed that, apart fromEchinococcus felidis, sequences of two other tapeworm species,Echinococcus granulosussensu stricto andEchinococcus canadensis, which are also endemic in East Africa, were detected by the developed real-time PCR assays.
Impact of sequence variant detection and bacterial DNA extraction methods on the measurement of microbial community composition in human stool
Authors: Hughes Riley , Alkan Zeynep , Keim Nancy L. , Kable Mary E.
Published: November 2017

Background

The human gut microbiome has been widely studied in the context of human health and metabolism, however the question of how to analyze this community remains contentious. This study compares new and previously well established methods aimed at reducing bias in bioinformatics analysis (QIIME 1 and DADA2) and bacterial DNA extraction of human fecal samples in 16S rRNA marker gene surveys.

Results

Analysis of a mock DNA community using DADA2 identified more chimeras (QIIME 1: 0.70% of total reads vs DADA2: 1.96%), fewer sequence variants, (QIIME 1: 1297.4 + 98.88 vs. DADA2: 136.27 + 11.35, mean + SD) and correct taxa at a higher resolution of classification (i.e. genus-level) than open reference OTU picking in QIIME 1. Additionally, the extraction of whole cell mock community bacterial DNA using four commercially available kits resulted in varying DNA yield, quality and bacterial community composition. Of the four kits compared, ZymoBIOMICS DNA Miniprep Kit provided the greatest yield, with a slight enrichment of Enterococcus. However, QIAamp Fast DNA Stool Mini Kit resulted in the highest DNA quality. Mo Bio PowerFecal DNA Kit had the most dramatic effect on the mock community composition, resulting in an increased proportion of members of the family Enterobacteriaceae and genus Eshcerichia as well as members of genera Lactobacillus and Pseudomonas. The presence of a sterile fecal matrix had a slight, but inconsistent effect on the yield, quality and taxa identified after extraction with all four DNA extraction kits. Extraction of bacterial DNA from native stool samples revealed a distinct effect of the DNA stabilization reagent DNA/RNA Shield on community composition, causing an increase in the detected abundance of members of orders Bifidobacteriales, Bacteroidales, Turicibacterales, Clostridiales and Enterobacteriales.

Conclusion

These results confirm that the DADA2 algorithm is superior to sequence clustering by similarity to determine microbial community structure. Additionally, commercially available kits used for bacterial DNA extraction from fecal samples have some effect on the proportion of high abundance members detected in a microbial community, but it is less significant than the effect of using DNA stabilization reagent, DNA/RNA Shield.
Detection of cytosolicShigella flexnerivia a C-terminal triple-arginine motif of GBP1 inhibits actin-based motility
Authors: Piro Anthony S. , Hernandez Dulcemaria , Luoma Sarah , Feeley Eric. M. , Finethy Ryan , Yirga Azeb , Frickel Eva M. , Lesser Cammie F. , Coers Jörn
Published: November 2017

Dynamin-like guanylate binding proteins (GBPs) are gamma interferon (IFNγ)-inducible host defense proteins that can associate with cytosol-invading bacterial pathogens. Mouse GBPs promote the lytic destruction of targeted bacteria in the host cell cytosol but the antimicrobial function of human GBPs and the mechanism by which these proteins associate with cytosolic bacteria are poorly understood. Here, we demonstrate that human GBP1 is unique amongst the seven human GBP paralogs in its ability to associate with at least two cytosolic Gram-negative bacteria,Burkholderia thailandensisandShigella flexneri.Rough lipopolysaccharide (LPS) mutants ofS. flexnerico-localize with GBP1 less frequently than wildtypeS. flexneri, suggesting that host recognition of O-antigen promotes GBP1 targeting to Gram-negative bacteria. The targeting of GBP1 to cytosolic bacteria, via a unique triple-arginine motif present in its C-terminus, promotes the co-recruitment of four additional GBP paralogs (GBP2, GBP3, GBP4 and GBP6). GBP1-decoratedShigellareplicate but fail to form actin tails leading to their intracellular aggregation. Consequentially, wildtype but not the triple-arginine GBP1 mutant restrictsS. flexnericell-to-cell spread. Furthermore, human-adaptedS. flexneri,through the action of one its secreted effectors, IpaH9.8, is more resistant to GBP1 targeting than the non-human-adapted bacillusB. thailandensis. These studies reveal that human GBP1 uniquely functions as an intracellular ‘glue trap’ inhibiting the cytosolic movement of normally actin-propelled Gram-negative bacteria. In response to this powerful human defense programS. flexnerihas evolved an effective counter-defense to restrict GBP1 recruitment.

Importance

Several pathogenic bacterial species evolved to invade, reside and replicate inside the cytosol of their host cells. One adaptation common to most cytosolic bacterial pathogens is the ability to co-opt the host’s actin polymerization machinery, in order to generate force for intracellular movement. This actin-based motility enables Gram-negative bacteria such asShigellato propel themselves into neighboring cells thereby spreading from host cell to host cell without exiting the intracellular environment. Here, we show that the human protein GBP1 acts as a cytosolic ‘glue trap’ capturing cytosolic Gram-negative bacteria through a unique protein motif and preventing disseminated infections in cell culture models. To escape from this GBP1-mediated host defense,Shigellaemploys a virulence factor that prevents or dislodges the association of GBP1 with cytosolic bacteria. Thus, therapeutic strategies to restore GBP1 binding toShigellamay lead to novel treatment options for shigellosis in the future.
Intermittent Ca2+signals mediated by Orai1 regulate basal T cell motility
Authors: Dong Tobias X. , Othy Shivashankar , Greenberg Milton L. , Jairaman Amit , Akunwafo Chijioke , Leverrier Sabrina , Yu Ying , Parker Ian , Dynes Joseph L. , Cahalan Michael D.
Published: November 2017

Ca2+influx through Orai1 channels is crucial for several T cell functions, but a role in regulating basal cellular motility has not been described. Here we show that inhibition of Orai1 channel activity increases average cell velocities by reducing the frequency of pauses in human T cells migrating through confined spaces, even in the absence of extrinsic cell contacts or antigen recognition. Utilizing a novel ratiometric genetically encoded cytosolic Ca2+indicator, Salsa6f, which permits real-time monitoring of cytosolic Ca2+along with cell motility, we show that spontaneous pauses during T cell motility in vitro and in vivo coincide with episodes of cytosolic Ca2+signaling. Furthermore, lymph node T cells exhibited two types of spontaneous Ca2+transients: short-duration “sparkles” and longer duration global signals. Our results demonstrate that spontaneous and self-peptide MHC-dependent activation of Orai1 ensures random walk behavior in T cells to optimize immune surveillance.
Identification of Tumor-Reactive B Cells and Systemic IgG in Breast Cancer Based on Clonal Frequency in the Sentinel Lymph Node
Authors: McDaniel Jonathan R. , Pero Stephanie C. , Voss William N. , Shukla Girja S. , Sun Yujing , Schaetzle Sebastian , Lee Chang-Han , Horton Andrew P. , Harlow Seth , Gollihar Jimmy , Ellefson Jared W. , Krag Christopher C. , Tanno Yuri , Sidiropoulos Nikoletta , Georgiou George , Ippolito Gregory C. , Krag David N.
Published: November 2017

A better understanding of antitumor immune responses is key to advancing the field of cancer immunotherapy. Endogenous immunity in cancer patients, such as circulating anticancer antibodies or tumor-reactive B cells, has been historically yet incompletely described. Here, we demonstrate that tumor-draining (sentinel) lymph node (SN) is a rich source for tumor-reactive B cells that give rise to systemic IgG anticancer antibodies circulating in the bloodstream of breast cancer patients. Using a synergistic combination of high-throughput B-cell sequencing and quantitative immunoproteomics, we describe the prospective identification of tumor-reactive SN B cells (based on clonal frequency) and also demonstrate an unequivocal link between affinity-matured expanded B-cell clones in the SN and antitumor IgG in the blood. This technology could facilitate the discovery of antitumor antibody therapeutics and conceivably identify novel tumor antigens. Lastly, these findings highlight the unique and specialized niche the SN can fill in the advancement of cancer immunotherapy.

SIGNIFICANCE

Using high-throughput molecular cloning and antibody proteomics to study coordinated antitumor immunity in breast cancer patients, we simultaneously demonstrate that the sentinel lymph node is a localized source of expanded antitumor B cells undergoing affinity maturation and that their secreted antibodies are abundant as systemic IgG circulating in blood.
Morphological constraints on cerebellar granule cell combinatorial diversity
Authors: Gilmer Jesse I. , Person Abigail L.
Published: November 2017

Combinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar granule cell layer and examined how GCL architecture contributes to granule cell (GrC) combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fibers clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing.

Significance Statement

Cerebellar granule cells are among the simplest neurons, with tiny somata and on average just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer (GCL) as a combinatorial expander, where each granule cell represents a unique combination of inputs. Despite the centrality of these theories to cerebellar physiology, the degree of expansion supported by anatomically realistic patterns of inputs is unknown. Using modeling and anatomy, we show that realistic input patterns constrain combinatorial diversity by producing redundant combinations, which nevertheless could support temporal diversification of like-combinations, suitable for learned timing. Our study suggests a neural substrate for producing high levels of both combinatorial and temporal diversity in the GCL.
Functional Connectomics from Data: Probabilistic Graphical Models for Neuronal Network of C. elegans
Authors: Liu Hexuan , Kim Jimin , Shlizerman Eli
Published: November 2017

We propose a data-driven approach to represent neuronal network dynamics as a Probabilistic Graphical Model (PGM). Our approach learns the PGM structure by employing dimension reduction to network response dynamics evoked by stimuli applied to each neuron separately. The outcome model captures how stimuli propagate through the network and thus represents functional dependencies between neurons, i.e., functional connectome. The benefit of using a PGM as the functional connectome is that posterior inference can be done efficiently and circumvent the complexities in direct inference of response pathways in dynamic neuronal networks. In particular, posterior inference reveals the relations between known stimuli and downstream neurons or allows to query which stimuli are associated with downstream neurons. For validation and as an example for our approach we apply our methodology to a model ofCaenorhabiditis elegansnervous system which structure and dynamics are well-studied. From its dynamical model we collect time series of the network response and use singular value decomposition to obtain a low-dimensional projection of the time series data. We then extract dominant patterns in each data matrix to get pairwise dependency information and create a graphical model for the full somatic nervous system. The PGM enables us to obtain and verify underlying neuronal pathways dominant for known behavioral scenarios and to detect possible pathways for novel scenarios.
Processive movement of Actin by Biased Polymerization: A new paradigm of Axonal Transport
Authors: Chakrabarty Nilaj , Dubey Pankaj , Tang Yong , Ganguly Archan , Ladt Kelsey , Leterrier Christophe , Jung Peter , Roy Subhojit
Published: November 2017

Classic pulse-chase studies have shown that actin is conveyed in slow axonal transport, but the mechanistic basis for this movement is unknown. Recently, we reported that axonal actin was surprisingly dynamic, with focal assembly/dis-assembly events (“hotspots”) and elongating polymers along the axon-shaft (“trails”). Using a combination of live imaging, super-resolution microscopy, and modeling, here we explore how these axonal actin dynamics can lead to processive transport. We found abundant actin nucleation, along with a slow, anterogradely-biased flow of actin in axon-shafts. Starting with first principles of monomer/filament assembly – and incorporating imaging data – we generated a quantitative model simulating axonal hotspots and trails. Our simulations predict that the axonal actin dynamics indeed lead to an anterogradely-biased flow of the population, at rates consistent with slow transport. Collectively, the data point to a surprising scenario where local assembly and biased polymerization generate the slow axonal transport of actin. This mechanism is distinct from polymer-sliding, and seems well suited to convey highly dynamic cytoskeletal cargoes.

Acknowledgements

This work was supported by an NIH grant to SR (R01NS075233). The authors thank Stephanie Gupton (UNC) for the Mena/Vasp constructs.
REMAP: An online remote sensing application for land cover classification and monitoring
Authors: Murray Nicholas J. , Keith David A. , Simpson Daniel , Wilshire John H. , Lucas Richard M.
Published: November 2017

Recent assessments of progress towards global conservation targets have revealed a paucity of indicators suitable for assessing the changing state of ecosystems. Moreover, land managers and planners are often unable to gain timely access to maps they need to support their routine decision-making. This deficiency is partly due to a lack of suitable data on ecosystem change, driven mostly by the considerable technical expertise needed to make ecosystem maps from remote sensing data.

We have developed a free and open-access online remote sensing and environmental modelling application, REMAP (the remote ecosystem monitoring and assessment pipeline;https://remap-app.org) that enables volunteers, managers, and scientists with little or no experience in remote sensing to develop high-resolution classified maps of land cover and land use change over time.

REMAP utilizes the geospatial data storage and analysis capacity of the Google Earth Engine, and requires only spatially resolved training data that define map classes of interest (e.g., ecosystem types). The training data, which can be uploaded or annotated interactively within REMAP, are used in a random forest classification of up to 13 publicly available predictor datasets to assign all pixels in a focal region to map classes. Predictor datasets available in REMAP represent topographic (e.g. slope, elevation), spectral (Landsat Archive image composites) and climatic variables (precipitation, temperature) that can inform on the distribution of ecosystems and land cover classes.

The ability of REMAP to develop and export high-quality classified maps in a very short (<10 minute) time frame represents a considerable advance towards globally accessible and free application of remote sensing technology. By enabling access to data and simplifying remote sensing classifications, REMAP can catalyse the monitoring of land use and change to support environmental conservation, including developing inventories of biodiversity, identifying hotspots of ecosystem diversity, ecosystem-based spatial conservation planning, mapping ecosystem loss at local scales, and supporting environmental education initiatives.
Prediction of Epileptic Seizures based on Mean Phase Coherence
Authors: Aggarwal Gorish , Gandhi Tapan K.
Published: November 2017

Around 1-2 % of the world's population suffers from epilepsy and 20 % of that vulnerable mass can't be cured through surgery or medicine. Epileptic seizures often occur unpredictably and may cause serious damage to the patient in adverse situations, for e.g. getting a seizure while driving or crossing a road can be fatal. In such a scenario, a reliable mechanism to predict the onset of seizure beforehand is much desirable. In this study, A reliable real-time technique for prediction of epileptic seizures is presented. Mean Phase Coherence (MPC), as a measure of phase synchronization, is used to predict impending seizures in a multi-channel EEG data. It was found that during the pre-ictal stages, MPC values and thus phase synchronization between various channels was found to drop significantly below the level in a non-ictal EEG signal. The range of the prediction horizon for seizures varied from 4-10 mins and prediction of impending seizure attack is possible for 8 out of 10 test cases.
Evaluation of TRPM8 and TRPA1 participation in dental pulp sensitivity to cold stimulation
Authors: Michot Benoit , Lee Caroline , Podborits Eugene , Gibbs Jennifer L.
Published: November 2017

Sensory neurons innervating the dental pulp have unique morphological and functional characteristics compared to neurons innervating other tissues. Stimulation of dental pulp afferents whatever the modality or intensity of the stimulus, even light mechanical stimulation that would not activate nociceptors in other tissues, produces an intense pain. These specific sensory characteristics could involve receptors of the Transient Receptor Potential channels (TRP) family. In this study, we evaluated 1) the expression of TRPA1 and TRPM8 receptors in trigeminal ganglion neurons innervating the dental pulp compared to sensory neurons innervating the oral mucosa or the skin of the face, and 2) the involvement of these receptors in dental pulp sensitivity to cold stimulation. We showed a similar expression of TRPM8 and CGRP in sensory neurons innervating the dental pulp, the skin or the buccal mucosa. On the contrary, TRPA1 was expressed in a higher proportion of neurons innervating the mucosa (43%) than in neurons innervating the dental pulp (19%) or the skin (24%). Moreover, neurons innervating the dental pulp had a higher proportion of large neurons (24%) compared to neurons innervating the skin (8%) or the mucosa (10%). The evaluation of trigeminal ganglion neuron sensitivity to TRPM8 agonist, TRPA1 agonist and cold stimulation, showed that a significant proportion of neurons innervating the skin (10%) or the mucosa (37%) were sensitive to cold stimulation but insensitive to TRPM8 and TRPA1 activation. Similarly, the application of a cold stimulation on the tooth induced an overexpression of cFos in the trigeminal nucleus that was not prevented by administration of a TRPA1 antagonist or the genetic deletion of TRPM8. However, the pretreatment with the local anesthetic carbocaine abolish the cold-induced cFos overexpression. In conclusion, the unique sensory characteristics of the dental pulp would be independent to TRPA1 and TRPM8 expression and functionality.