bluuebunny/crossref_metadata_2025 huggingface dataset:
Magneto-thermoelectric effects in rectangular quantum wire with an infinitely high potential in the presence of electromagnetic wave (electron - acoustic phonon interaction)
Authors: Hung Tran Hai , Quang Doan Minh , Bau Nguyen Quang , Nhan Nguyen Vu
Published: July 2019

Based on the quantum kinetic equation for electrons, we have theoretically studied the influence of a Strong Electromagnetic Wave on the Ettingshausen Effect (EC) in a rectangular quantum wire with an infinite potential (RQWIP). We obtain the analytic expressions for the kinetic tensor as well as the Ettingshausen coefficient in the rectangular quantum wire with an infinite potential with the dependence on B and Ω…… The results are numerically evaluated and graphed for GaAs/GaAs:Al quantum wire. We survey the electrical and thermal conductivity tensor depend on Electromagnetic Wave frequency and temperature. The results give us appearance of the Shubnikov–de Haas oscillations when we survey the dependence of Ettingshausen coefficient on the magnetic field. Then, we realize that as the temperature increases, the Ettingshausen coefficient decreases. This shows that the Electromagnetic Wave have a clear impact on the effects. These are latest results which have been studied in terms of Ettingshausen effect in rectangular quantum wire.
Effects of temperature and dopant concentration on oxygen vacancy diffusion coefficient of yttria-stabilized zirconia
Authors: Lam Le Thu , Hung Vu Van
Published: July 2019

Oxygen vacancy diffusion coefficient in yttria-stabilized zirconia (YSZ) is investigated by statistical moment method. Vacancy-dopant association energy, vacancy migration energy are calculated as a function of temperature and dopant concentration. Oxygen vacancy diffusion coefficient increases with the increasing temperature but decreases with the dopant concentration. This degradation of the diffusion coefficient arises from the limitation for oxygen vacancy migration across cation barriers with the increasing dopant concentration. Calculated results are in good agreement with other theoretical and experimental results.
Theoretical predictions of two-dimensional covalent organic frameworks (COF) with triangular topologies
Authors: Thao Nguyen Thi , Tuoc Vu Ngoc , Phuong Trinh Thi
Published: July 2019

In the last decades, covalent organic frameworks (COFs) – the class of highly ordered organic crystalline porous, have attracted huge research interest because of their unique structures and potential applications in gas separation/storage, catalysis, energy storage and optoelectronic materials device. In this works, we proposed several series of triangular topologies to study the applicability of the formation of two-dimensional (2D) COFs from various pre-defined individual building blocks using Density Functional based tight-binding (DFTB) method. Different high-symmetry stacking, e.g. AA and AB stacking sequence are also designed and investigated. The designed series band gaps are found to be ranging from 0 eV to 2.93 eV. Furthermore, the COF series, revealing a variety of promising mechanical and electronic properties, which can potentially find future realistic applications.
Nonlinear optically detected electrophonon resonance full width at half maximum in a parabolic GaAs quantum well with different phonon models
Authors: Hien Nguyen Dinh , Dung Nguyen Trung , Dinh Le , Phong Tran Cong
Published: July 2019

The effect of different phonon models (confined and bulk phonons) on the linear optically detected electrophonon resonance (LODEPR), nonlinear optically detected electron-phonon resonance (NLODEPR) effect and full-width at half-maximum (FWHM) of the LODEPR and NLODEPR peaks via both one and two photon absorption processes in a parabolic GaAs quantum well by using the state-dependent operator projection is theoretically studied. The obtained numerical result for the parabolic GaAs/AlAs quantum well shows that the FWHM of the LODEPR and NLODEPR peaks increase with increasing well’s confinement frequency and temperature for the above both models of the phonon. Besides, the FWHM of the LODEPR and NLODEPR peaks for the confined phonon case varies faster and have a larger value than it does for the bulk phonon case. Furthermore, the FWHM of the NLODEPR peaks is about one order of value smaller than the linear one for the above both models of the phonon; in the large range of the confinement frequency (ωz
/ωLO
< 0.2), the effect of phonon confinement on the FWHM of the LODEPR and NLODEPR peaks becomes important and cannot be neglected in considering.
Stakeholder perceptions of smart infusion pumps and drug library updates: A multisite, interdisciplinary study
Authors: DeLaurentis Poching , Walroth Todd A , Fritschle Andrew C , Yu Denny , Hong Jee Eun , Yih Yuehwern , Fuller James
Published: July 2019

Purpose

Results of a questionnaire-based study to evaluate smart infusion pump end users’ perceptions and understanding of the drug library update process are reported.

Methods

The Indianapolis Coalition for Patient Safety, Inc., in partnership with the Regenstrief Center for Healthcare Engineering, conducted a 33-item electronic, cross-sectional survey across 5 Indiana health systems from May through November 2017. Interdisciplinary participants identified for survey distribution included nurses, pharmacists, biomedical engineers, administrators, and medication safety officers. The survey assessed the following domains: patient safety, the drug library update process, knowledge of drug libraries and the update process, and end-user perceptions.

Results

A total of 778 submitted surveys were included in the data analysis, with a large majority of responses (90.2%) provided by nurses. The use of drug libraries for ensuring patient safety was deemed extremely important or important by 88% of respondents, but 36% indicated that they were unsure of whether drug libraries are updated on a routine basis in their health system. Approximately two-thirds agreed that the current update process improves quality of care (65.0%) and patient safety (68.1%). Moreover, 53.3% agreed that the current drug library update process was effective. However, less than 10% responded correctly when asked about the steps required to update the drug library. Furthermore, only 18% correctly indicated that when a pump is on it may not necessarily contain the most up-to-date version of the drug library.

Conclusion

A survey of 5 health systems in Indianapolis identified several end-user knowledge gaps related to smart pump drug library updates. The results suggest that these gaps were most likely due to a combination of the 2-step update process and the fact that the current drug library version is not easy to find and/or user-friendly and it is unclear when an update is pending.
50 years on: legacies of the Apollo programme
Authors: Pernet-Fisher John F , McDonald Francesca E , Zeigler Ryan A , Joy Katherine H
Published: July 2019

On the 50th anniversary since humans first set foot on the Moon, John Pernet-Fisher, Francesca McDonald, Ryan Zeigler and Katherine Joy take a look back at the legacies of the Apollo programme.
Constitution-making and International Relations Theories
Authors: Lerner Hanna , Lupovici Amir
Published: July 2019

Constitution-making has become an intrinsic component of international politics, nevertheless, international relations scholars largely refrain from theorizing it tending to view formal constitutional drafting as a domestic project. The article proposes an understanding of constitution-making as an international (in addition to national) political phenomenon. We develop a new and comprehensive classification of international influences on constitution-making. We also demonstrate how the empirical study of constitution-making can illuminate overlooked areas of research and challenge existing international relations theories. Our focus here is on the study of international norms. We present three theoretical insights concerning the emergence of international norms, their dissemination, and the role of epistemic communities in facilitating their expansion. We conclude by highlighting how the interaction between international and domestic factors in the crafting of constitutions further challenges the disciplinary distinction between domestic and international politics.
Effect of divergence in residual feed intake on expression of lipid metabolism-related genes in the liver of meat-type ducks1
Authors: Jin Sihua , Yang Lei , Fan Xinfeng , Wu Minghui , Xu Yuan , Chen Xianzen , Lin Zhiqiang , Geng Zhaoyu
Published: July 2019

Lipid metabolism is considered one of the important factors affecting residual feed intake (RFI). However, the relationship between RFI and expression of lipid metabolism-related genes is unknown in meat-type ducks. To address this issue, a total of 1,000 male meat-type ducks with similar body weight were randomly selected to measure body weight gain and feed intake from 21 to 42 d of age to estimate RFI. The 8 greatest- (high RFI [HRFI]) and lowest- (low RFI [LRFI]) ranking birds were then selected for the present study. Relative expressions of key genes, namely sirtuin 1 (Sirt1), forkhead box O1 (Foxo1), peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding transcription factor 1c (SREBP-1c), fas cell surface death receptor (FAS), acetyl-CoA carboxylase alpha (ACC), carnitine palmitoyltransferase 1A (CPT1A), and acyl-CoA oxidase 1 (ACOX1), were then determined in the HRFI and LRFI ducks by quantitative PCR. The results showed that RFI, feed conversion ratio (FCR), and average daily feed intake (ADFI) were significantly lower (P < 0.05) in LRFI ducks than in HRFI ducks. In addition, expression of Sirt1, Foxo1, CPT1A, and ACOX1 were significantly higher in LRFI ducks than in HRFI ducks (P < 0.05), whereas PPARγ and FAS expression levels were significantly lower in LRFI ducks than in HRFI ducks (P < 0.01). Correlation analysis showed that Sirt1, CPT1A, and ACOX1 expressions were significantly negatively correlated with FCR (r = −0.81 to −0.93; P < 0.01), whereas PPARγ and FAS expressions were significantly positively correlated with FCR (r = 0.74 to 0.87; P < 0.01). PPARγ expression was significantly positively correlated with RFI (r = 0.83; P < 0.01), whereas CPT1A and ACOX1 expressions were significantly negatively correlated with RFI (r = −0.84 to −0.89; P < 0.01). Sirt1 mRNA expression was positively correlated with Foxo1, CPT1A, and ACOX1 mRNA expression (r = 0.78 to 0.92; P < 0.01). Association of Foxo1 with CPT1A and ACOX1 was positive (r = 0.88 to 0.96; P < 0.01). These results suggest that genes related to fatty acid oxidation are upregulated in the liver of ducks with high feed efficiency, while genes associated with lipid synthesis are downregulated. Furthermore, the inclusion of lipid metabolism-related genes in future breeding programs might be beneficial for selecting ducks with greater feed efficiency phenotype.
Effects of abomasally infused amylase and increasing amounts of corn starch on fecal excretion of starch, total and microbial nitrogen, and volatile fatty acids in heifers1
Authors: Robbers Kristina , Westreicher-Kristen Edwin , Troescher Arnulf , Susenbeth Andreas
Published: July 2019

The aim of the present study was to study the effect of exogenous amylase on postruminal disappearance of increasing amounts of corn starch being infused into the abomasum of heifers, and to detect a possible limitation of starch digestion in the small intestine. Four rumen-fistulated heifers (2 German Black Pied and 2 Jersey × German Black Pied) with an initial BW of 565 ± 6 kg were fed 5.6 kg DM/d of a diet targeted to contain only a negligible amount of starch. Animals were assigned randomly to a crossover trial with 2 experimental periods lasting 35 d each with 10 d of diet adaption followed by 25 d of sample collection. During the sampling period, each animal was abomasally infused with native corn starch at 5 levels (953, 1,213, 1,425, 1,733, and 1,993 g DM/d) each for a 5-d period with and without exogenous amylase, respectively. At days 6 to 10 the heifers received an abomasal infusion of starch in amounts of 724 g/d. Feces were sampled 4 times a day during the collection periods. Titanium dioxide was ruminally administered (10 g/d) to estimate fecal excretion. Purine bases in feces were determined and used as a marker for microbial N excretion. Fecal excretion of microbial N increased linearly with increasing level of starch infusion (P < 0.001), indicating a constant proportion of the infused starch being fermented in the hindgut. In contrast, the apparent digestibility of starch from the total postruminal tract decreased linearly from 90% to 80% (P < 0.001) when the intestinal starch supply increased from 1 to 2 kg/d. There is strong evidence based on the increasing starch excretion with feces and the indication of a constant proportion of infused starch being fermented in the hindgut for a decreasing efficiency of starch digestion in the small intestine with increasing intestinal supply. Amylase administration increased fecal excretion of butyrate (P = 0.04) and tended to increase isovalerate excretion (P = 0.06). However, amylase did not affect fecal excretion of microbial N or starch, suggesting that pancreatic amylase activity may not be the primarily limiting factor of postruminal starch digestion in heifers when corn starch is abomasally infused in amounts up to 2 kg/d.
Effect of prior ipsilateral lower extremity surgery on 2-year outcomes following hip arthroscopy for femoroacetabular impingement syndrome
Authors: Kunze Kyle N , Beck Edward C , Okoroha Kelechi R , Chahla Jorge , Suppauksorn Sunikom , Bush-Joseph Charles A , Katakam Akhil , Nho Shane J
Published: July 2019

The purpose of this study was to determine the influence of prior lower extremity surgery on patient reported outcomes following hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Consecutive patients who underwent hip arthroscopy for FAIS and a prior history of ipsilateral lower extremity surgery were identified and matched 2:1 by age, gender, and body mass index (BMI) to controls without a history of lower extremity surgery. The minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) were calculated for HOS–ADL, HOS–SS, and mHHS. Preoperative and 2-year postoperative patient reported outcomes of both groups were compared, and logistic regression was performed to determine whether lower extremity surgery influenced achieving MCID and PASS. A total of 102 patients (24.94%) with prior history of ipsilateral lower extremity surgery were identified. Ipsilateral orthopaedic knee surgery accounted for more than half (53.92%) of all prior surgeries. Patients with a history of ipsilateral lower extremity surgery had significant lower 2-year PROs, satisfaction, and greater pain when compared to patients without lower extremity surgery (P < 0.001 all). A history of ipsilateral lower extremity surgery was a negative predictor of achieving MCID for HOS–ADL and HOS–SS, as well as PASS for HOS–ADL, HOS–SS, and mHHS (P < 0.001 all).

In conclusion, patients with prior lower extremity surgery were found to have inferior outcome scores and a lower likelihood of achieving clinically significant outcome improvement compared to patients without a history of lower extremity surgery at two years postoperatively.
The effect of arthroscopic capsulotomy and repair on native resting hip joint forces using a non-destructive extra-articular method
Authors: Schaffer Joseph C , Vasconcellos Daniel , Kelly Meghan , Kaplan Nathan B , Maqsoodi Noorullah , Olles Mark , Elfar John C , Giordano Brian D
Published: July 2019

Previous methods for measuring intra-articular forces require significant soft tissue dissection and intra-articular insertion of sensory instruments. This study demonstrates a minimally invasive method of measuring native resting hip joint force without disrupting the soft tissue envelope. This method is then utilized to determine the effect of capsulotomy and repair on these forces. Twenty fresh-frozen human cadaver hemipelves were percutaneously instrumented with an iliac crest locking plate and retrograde femoral nail to allow for testing using a distracting force. Force–displacement curves were generated in the native state, and after joint venting, an anterior hip approach, capsulotomy, capsular repair and soft tissue dissections. Mean native resting hip joint force was 110.5 N (SD 54.3 N). Capsular venting resulted in a significant decrease in hip joint force compared with the native state (100.2 N, SD 45.2 N, P = 0.026). A further decrease in hip joint force was observed with a T-capsulotomy (79.9 N, SD 40.1 N, P < 0.001 compared with anterior hip approach), with restoration of these forces after capsular repair (84.8 N, SD 40.5, P = 0.014 versus T-capsulotomy and P = 0.67 versus anterior hip approach). Soft tissue dissection resulted in a large decrease in hip joint force compared with the hip’s native state (59.7 N, SD 28.4 N, P = 0.002). Taken together, the findings suggest that this method is effective in measuring hip joint force and may be more accurate than those requiring significant soft tissue dissection. Furthermore, the data suggest that capsular repair likely plays an important role in the restoration of biomechanical forces in the hip after capsulotomy.
RNA-guided piggyBac transposition in human cells
Authors: Hew Brian E , Sato Ryuei , Mauro Damiano , Stoytchev Ilko , Owens Jesse B
Published: July 2019

Safer and more efficient methods for directing therapeutic genes to specific sequences could increase the repertoire of treatable conditions. Many current approaches act passively, first initiating a double-stranded break, then relying on host repair to uptake donor DNA. Alternatively, we delivered an actively integrating transposase to the target sequence to initiate gene insertion. We fused the hyperactive piggyBac transposase to the highly specific, catalytically dead SpCas9-HF1 (dCas9) and designed guide RNAs (gRNAs) to the CCR5 safe harbor sequence. We introduced mutations to the native DNA-binding domain of piggyBac to reduce non-specific binding of the transposase and cause the fusion protein to favor binding by dCas9. This strategy enabled us, for the first time, to direct transposition to the genome using RNA. We showed that increasing the number of gRNAs improved targeting efficiency. Interestingly, over half of the recovered insertions were found at a single TTAA hotspot. We also found that the fusion increased the error rate at the genome-transposon junction. We isolated clonal cell lines containing a single insertion at CCR5 and demonstrated long-term expression from this locus. These vectors expand the utility of the piggyBac system for applications in targeted gene addition for biomedical research and gene therapy.
Resonant Doppler effect in systems with variable delay
Authors: Müller-Bender D. , Otto A. , Radons G.
Published: July 2019

We demonstrate that a time-varying delay in nonlinear systems leads to a rich variety of dynamical behaviour, which cannot be observed in systems with constant delay. We show that the effect of the delay variation is similar to the Doppler effect with self-feedback. We distinguish between the non-resonant and the resonant Doppler effect corresponding to the dichotomy between conservative delays and dissipative delays. The non-resonant Doppler effect leads to a quasi-periodic frequency modulation of the signal, but the qualitative properties of the solution are the same as for constant delays. By contrast, the resonant Doppler effect leads to fundamentally different solutions characterized by low- and high-frequency phases with a clear separation between them. This is equivalent to time-multiplexed dynamics and can be used to design systems with well-defined multistable solutions or temporal switching between different chaotic and periodic dynamics. We systematically study chaotic dynamics in systems with large dissipative delay, which we call generalized laminar chaos. We derive a criterion for the occurrence of different orders of generalized laminar chaos, where the order is related to the dimension of the chaotic attractor. The recently found laminar chaos with constant plateaus in the low-frequency phases is the zeroth-order case with a very low dimension compared to the known high dimension of turbulent chaos in systems with conservative delay.

This article is part of the theme issue ‘Nonlinear dynamics of delay systems’.
Class-C semiconductor lasers with time-delayed optical feedback
Authors: Lingnau Benjamin , Turnwald Jonas , Lüdge Kathy
Published: July 2019

We perform a linear stability analysis and numerical bifurcation diagrams of a class-C laser with time-delayed optical feedback. We employ a rate equation system based on the Maxwell–Bloch equations, and study the influence of the dephasing time on the laser dynamics. We find a stabilizing effect of an intermediate dephasing time, i.e. when moving from a class-B to a class-C laser. At long dephasing times, a destabilization of the laser solution occurs by a feedback-induced unlocking of Rabi oscillations at the second laser threshold. We predict an optimum resistance to time-delayed optical feedback for dephasing times close to the photon cavity lifetime.

This article is part of the theme issue ‘Nonlinear dynamics of delay systems’.
Experimental observations on unsafe zones in milling processes
Authors: Dombovari Zoltan , Iglesias Alex , Molnar Tamas G. , Habib Giuseppe , Munoa Jokin , Kuske Rachel , Stepan Gabor
Published: July 2019

The unsafe zone in machining is a region of the parameter space where steady-state cutting operations may switch to regenerative chatter for certain perturbations, and vice versa. In the case of milling processes, this phenomenon is related to the existence of an unstable quasi-periodic oscillation, the in-sets of which limit the basin of attraction of the stable periodic motion that corresponds to the chatter-free cutting process. The mathematical model is a system of time-periodic nonlinear delay differential equations. It is studied by means of a nonlinear extension of the semidiscretization method, which enables the estimation of the parameter ranges where the unsafe (also called bistable) zones appear. The theoretical results are checked with thorough experimental work: first, step-by-step parameter variations are adapted to identify hysteresis loops, then harmonic burst excitations are used to estimate the extents of the unsafe zones. The hysteresis loops are accurately distinguished from the dynamic bifurcation phenomenon that is related to the dynamic effect of slowly varying parameters. The experimental results confirm the existence of the bistable parameter regions.

This article is part of the theme issue ‘Nonlinear dynamics of delay systems’.
Modified Long-Axis In-Plane Ultrasound Technique Versus Conventional Palpation Technique For Radial Arterial Cannulation: A Prospective Randomized Controlled Trial
Authors: Wang Jiebo , Lai Zhongmeng , Weng Xianfeng , Lin Yong , Wu Guohua , Su Jiansheng , Huang Qijian , Zeng Jian , Liu Junle , Zhao Zisong , Yan Ting , Zhang Liangcheng , Zhou Linying
Published: July 2019

Background

A low first-pass success rate of radial artery cannulation was obtained when using the conventional palpation technique(C-PT) or ultrasound-guided techniques, we therefore evaluate the effect of a modified long-axis in-plane ultrasound technique (M-LAINUT) in guiding radial artery cannulation in adults.

Methods

We conducted a prospective, randomized and controlled clinical trial of 288 patients undergoing radial artery cannulation. Patients were randomized 1:1 to M-LAINUT or C-PT group at fujian medical university union hospital between 2017 and 2018. Radial artery cannulation was performed by three anesthesiologists with different experience. The outcome was the first and total radial artery cannulation success rates, the number of attempts and the cannulation time.

Results

285 patients were statistically analyzed. The success rate of first attempt was 91.6% in the M-LAINUT group (n=143) and 57.7% in the C-PT group (n=142; P<0.001) (odds ratio, 7.9; 95% confidence interval, 4.0-15.7). The total success rate (≤5 min and ≤3 attempts) in the M-LAINUT group was 97.9%, compared to 84.5% in the palpation group (p <0.001) (odds ratio, 8.5; 95% confidence interval, 2.5-29.2). The total cannulation time was shorter and the number of attempts was fewer in the M-LAINUT group than that in the C-PT group (p <0. 05).

Conclusion

Modified long-axis in-plane ultrasound-guided radial artery cannulation can increase the first and total radial artery cannulation success rates, reduce the number of attempts and shorten the total cannulation time in adults.
Bias correction methods for test-negative designs in the presence of misclassification
Authors: Endo Akira , Funk Sebastian , Kucharski Adam J.
Published: July 2019

Abstract

The test-negative design has become a standard approach for vaccine effectiveness studies. However, previous studies suggested that it may be more sensitive than other designs to misclassification of disease outcome caused by imperfect diagnostic tests. This could be a particular limitation in vaccine effectiveness studies where simple tests (e.g. rapid influenza diagnostic tests) are used for logistical convenience. To address this issue, we derived a mathematical representation of the test-negative design with imperfect tests, then developed a bias correction framework for possible misclassification. Test-negative design studies usually include multiple covariates other than vaccine history to adjust potential confounders; our methods can also address multivariate analyses and be easily coupled with existing estimation tools. We validated the performance of these methods using simulations of common scenarios for vaccine efficacy and were able to obtain unbiased estimates in a variety of parameter settings.
An efficient genome editing strategy to generate putative null mutants inCaenorhabditis elegansusing CRISPR/Cas9
Authors: Wang Han , Park Heenam , Liu Jonathan , Sternberg Paul W.
Published: July 2019

Null mutants are essential for analyzing gene function. Here, we describe a simple and efficient method to generateCaenorhabditis elegansnull mutants using CRISPR/Cas9 and short single stranded DNA oligo repair templates to insert a universal 43-nucleotide-long stop knock-in (STOP-IN) cassette into the early exons of target genes. This cassette has stop codons in all three reading frames and leads to frameshifts, which will generate putative null mutations regardless of the reading frame of the insertion position in exons. The STOP-IN cassette also contains an exogenous Cas9 target site that allows further genome editing and provides a unique sequence that simplifies the identification of successful insertion events via PCR. As a proof of concept, we inserted the STOP-IN cassette right at a Cas9 target site inaex-2to generate new putative null alleles by injecting preassembled Cas9 ribonucleoprotein and a short synthetic single stranded DNA repair template containing the STOP-IN cassette and two 35-nucleotide-long homology arms identical to the sequences flanking the Cas9 cut site. We showed that these newaex-2alleles phenocopied an existing loss-of-function allele ofaex-2. We further showed that the newaex-2null alleles could be reverted back to the wild-type sequence by targeting exogenous Cas9 cut site included in the STOP-IN cassette and providing a single stranded wild-type DNA repair oligo. We applied our STOP-IN method to generate new putative null mutants for additional 20 genes, including three pharyngeal muscle-specific genes (clik-1, clik-2, andclik-3), and reported a high insertion rate (46%) based on the animals we screened. We showed that null mutations ofclik-2cause recessive lethality with a severe pumping defect andclik-3null mutants have a mild pumping defect, whileclik-1is dispensable for pumping. We expect that the knock-in method using the STOP-IN cassette will facilitate the generation of new null mutants to understand gene function inC. elegansand other genetic model organisms.

We report a simple and efficient CRISPR/Cas9 genome editing strategy to generate putative nullC. elegansmutants by inserting a small universal stop knock-in (STOP-IN) cassette with stop codons in three frames and frameshifts. The strategy is cloning-free, with the mixture consisting of preassembled Cas9 ribonucleoprotein and single stranded repair DNA oligos directly injected into gonads of adultC. elegans. The universal STOP-IN cassette also contains a unique sequence that simplifies detection of successful knock-in events via PCR and an exogenous Cas9 target sequence that allows further genome editing.
PI16 is a non-neuronal regulator of neuropathic pain
Authors: Singhmar Pooja , Trinh Ronnie The Phong , Ma Jiacheng , Huo XiaoJiao , Peng Bo , Heijnen Cobi J , Kavelaars Annemieke
Published: July 2019

Chronic pain is a major clinical problem of which the mechanisms are incompletely understood. Here we describe the concept that PI16, a protein of unknown function mainly produced by fibroblasts, controls neuropathic pain. The spared nerve injury model of neuropathic pain increases PI16 protein levels in fibroblasts in DRG meninges and in the epi/perineurium of the sciatic nerve. We did not detect PI16 expression in neurons or glia in spinal cord, DRG and nerve. Mice deficient in PI16 are protected against neuropathic pain. In vitro, PI16 promotes trans-endothelial leukocyte migration. In vivo, PI16−/− mice show reduced endothelial barrier permeability, lower leukocyte infiltration and reduced activation of the endothelial barrier regulator MLCK and reduced phosphorylation of its substrate MLC2 in response to SNI. In summary, our findings support a model in which PI16 promotes neuropathic pain by mediating a cross talk between fibroblasts and the endothelial barrier leading to barrier opening, cellular influx and increased pain. Its key role in pain and its limited cellular and tissue distribution makes PI16 an attractive target for pain management.

Graphical Abstract
Prescription Opioid Distribution After the Legalization of Recreational Marijuana in Colorado, 2007-2017
Authors: Kropp Amalie K. , Nichols Stephanie D. , Chung Daniel Y. , McCall Kenneth L. , Piper Brian J.
Published: July 2019

Importance

Opioid related overdoses and overprescribing continue to be an ongoing issue within the United States. Further consideration of nonopioid alternatives as a substitute to treat chronic noncancer pain and in the treatment of opioid use disorders (OUD) is warranted.

Objective

To examine the association between the legalization of Colorado’s recreational marijuana and prescription opioid distribution trends. Two states that have not legalized recreational marijuana were selected for comparison.

Methods

The United States Drug Enforcement Administration’s Automation of Report and Consolidated Orders System (ARCOS) was used to examine nine pain medications: oxycodone, fentanyl, morphine, hydrocodone, hydromorphone, oxymorphone, tapentadol, codeine, meperidine and two OUD medications: methadone and buprenorphine from 2007-2017 in Colorado, Utah, and Maryland. The drug weights were extracted, examined, and graphed. Medications were converted to their oral morphine milligram equivalents (MME) using standard conversion factors.

Results

Colorado reached a peak of pain MME weight in 2012 and had an −11.66% reduction from 2007 to 2017. During the same interval, Utah had a +9.64% increase in pain medication distribution and Maryland, a −6.02% reduction. As for medications used for OUD, Colorado, Utah, and Maryland had +19.42% increase, −31.45% reduction, and +66.56% increase, respectively. Analysis of the interval pre (2007-2009) versus post (2013-2017) marijuana legalization was completed. Statistically significant changes were observed for Colorado (P=0.033) and Maryland (P=0.007), but not Utah (P=0.659) for pain medications. Analysis of the OUD medications identified significant changes for Colorado (P=0.0003) and Maryland (P=0.0001), but not Utah (P=0.0935). Over the decade, Colorado’s opioid distribution was predominantly (72.49%) for pain with one-quarter (27.51%) for an OUD. Utah distributed 61.00% for pain and 39.00% for OUD. However, Maryland was one-third (37.89%) for pain but over-three-fifths (62.11%) for an OUD.

Conclusion

There has been a significant decrease in the prescription opioid distribution after the legalization of marijuana in Colorado. This finding was particularly notable for opioids indicated predominantly for analgesia such as hydrocodone, morphine and fentanyl. Colorado had a larger decrease in opioid distribution after 2012 than Utah or Maryland. Therefore, marijuana could be considered as an alternative treatment for chronic pain and reducing use of opioids. Also, when combined with other novel research, it may also reduce the overdose death rate. Additional research with more comparison states is ongoing.
A novel lineage of candidate pheromone receptors for sex communication in moths
Authors: Bastin-Héline Lucie , Fouchier Arthur de , Cao Song , Koutroumpa Fotini , Caballero-Vidal Gabriela , Robakiewicz Stefania , Monsempes Christelle , François Marie-Christine , Ribeyre Tatiana , Cian Anne de , Walker William B. , Wang Guirong , Jacquin-Joly Emmanuelle , Montagné Nicolas
Published: July 2019

Sex pheromone receptors (PRs) are key players in chemical communication between mating partners in insects. In the highly diversified insect order Lepidoptera, male PRs tuned to female-emitted type I pheromones (which make up the vast majority of pheromones identified) form a dedicated subfamily of odorant receptors (ORs). Here, using a combination of heterologous expression and in vivo genome editing methods, we bring functional evidence that at least one moth PR does not belong to this subfamily but to a distantly related OR lineage. This PR, identified in the cotton leafworm Spodoptera littoralis, is over-expressed in male antennae and is specifically tuned to the major sex pheromone component emitted by females. Together with a comprehensive phylogenetic analysis of moth ORs, our functional data suggest two independent apparitions of PRs tuned to type I pheromones in Lepidoptera, opening up a new path for studying the evolution of moth pheromone communication.
Non-apoptotic caspase-dependent regulation of enteroblast quiescence in Drosophila
Authors: Arthurton Lewis , Nahotko Dominik Antoni , Alonso Jana , Baena-Lopez Luis Alberto
Published: July 2019

Caspase malfunction in stem cells often instigates the appearance and progression of multiple types of cancer, including human colorectal cancer. However, the caspase-dependent regulation of intestinal stem cell properties remains poorly understood. Here, we demonstrate that Dronc, the Drosophila ortholog of caspase-9/2 in mammals, limits the proliferation of intestinal progenitor cells and prevents the premature differentiation of enteroblasts into enterocytes. Strikingly, these unexpected roles of Dronc are non-apoptotic and have been uncovered under experimental conditions without basal epithelial turnover. A novel set of genetic tools have also allowed us to correlate these Dronc functions with its specific accumulation and transient activation in enteroblasts. Finally, we establish that the Dronc-dependent regulation of enteroblast quiescence, largely relies on the fine-tuning of the Notch and Insulin-TOR signalling pathways. Together, this data provides novel insights into the caspase-dependent but non-apoptotic modulation of enteroblast differentiation in non-regenerative conditions. These findings could improve our understanding regarding the origin of caspase-related intestinal malignancies, and the efficacy of therapeutic interventions based on caspase-modulating molecules.
Probabilistic Assessment of Nerve Regeneration with Diffusion MRI: Validation in Rat Models of Peripheral Nerve Trauma
Authors: Manzanera Esteve Isaac V. , Farinas Angel F. , Pollins Alonda C. , Nussenbaum Marlieke E. , Cardwell Nancy L. , Kang Hakmook , Does Mark D. , Thayer Wesley P. , Dortch Richard D.
Published: July 2019

Nerve regeneration after injury must occur in a timely fashion to restore function. Unfortunately, current methods (e.g., electrophysiology) provide limited information following trauma, resulting in delayed management and suboptimal outcomes. Herein, we evaluated the ability of diffusion MRI to monitor nerve regeneration after injury/repair. Sprague-Dawley rats were divided into three treatment groups (sham=21, crush=23, cut/repair=19) and ex vivo diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) was performed 1-12 weeks post-surgery. Behavioral data showed a distinction between crush and cut/repair nerves at 4 weeks. This was consistent with DTI, which found that thresholds based on the ratio of radial and axial diffusivities (RD/AD=0.40±0.02) and fractional anisotropy (FA=0.53±0.01) differentiated crush from cut/repair injuries. By the 12th week, cut/repair nerves whose behavioral data indicated a partial recovery were below the RD/AD threshold (and above the FA threshold), while nerves that did not recover were on the opposite side of each threshold. Additional morphometric analysis indicated that DTI-derived normalized scalar indices report on axon density (RD/AD: r=−0.54, p<1e-3; FA: r=0.56, p<1e-3). Interestingly, higher-order DKI analyses did not improve our ability classify recovery. These findings suggest that DTI can distinguish successful/unsuccessful nerve repairs and potentially identify cases that require reoperation.
Determinants of anemia among pregnant women in northern Ghana
Authors: Adokiya Martin N. , Aryeetey Richmond , Yost Monica , Jones Andrew D. , Wilson Mark L.
Published: July 2019

Anemia is a global public health issue affecting half of all pregnant women in developing countries. In 2014, 42% of Ghanaian pregnant women aged 15-49 years were anemic (<11.0g/dl) but information on the determinants of anemia, particularly dietary diversity during the critical third trimester of pregnancy is limited. We assessed the association between determinants and anemia among pregnant women in northern Ghana.

We employed a cross-sectional design involving 624 pregnant women (≥20 weeks of gestation) attending four antenatal care (ANC) health facilities ~25 kilometres north of Tamale, Ghana between July and August 2017. Hemoglobin concentration (measured using Hemocue HB 301) was classified as severe, moderate, or mild. Other data included socio-demographic characteristics, malaria prevention, deworming, and iron/folate tablet use. The FAO Minimum Dietary Diversity (MDD-W) metric was used to categorize women into “inadequate” (MDD-W <5 food groups) and “adequate” (MDD-W ≥5). Logistic regression models were used to determine the association between moderate/severe anemia (Hb<9.0g/dl) and mild anemia (9.0-10.9g/dl), or with ‘no anemia’ (≥11.0g/dl) using STATA 14 software.

Of 624 women sampled, hemoglobin data were available for 601. The mean age was 27.81±0.25 years, gestational age was 31.93±0.13 weeks, ANC attendance was 3.89±0.07; Hb concentration was 9.73g/dl±0.07, and MDD-W index for ten food groups was 5.33±0.04. Anemia (Hb<11.0g/dl) was observed in 74.8% of women (moderate/severe anemia=33.4% and mild anemia=41.4%). Using adjusted logistic regression, women who received deworming medication had lesser odds of being moderate/severe anemic (aOR=0.51, P=0.021). While women who were engaged in other occupation (herdsmen) and no previous parity had higher odds of being moderate/severe anemic (aOR=2.90, P=0.042) and (aOR=2.13, P=0.004) respectively. Moderate/severe anemia was not statistically associated with MDD-W, nor with socioeconomic status/wealth index. Conclusion, anemia in pregnancy was nearly twice that of Ghana as a whole. Deworming medication was found to be protective intervention for anemia during pregnancy.
Lung Tumour Cell-derived Exosomes Promote the Expansion of MDSC Through miR-21a/PDCD4/IL-6/STAT3 Pathway
Authors: Zhang Xingju , Li Fei , Zhang Jiale , Tang Ying , Xiao Bin , Wan Ying , Jiang Shan
Published: July 2019

The percentage of MDSC population in peripheral blood is significantly increased in lung cancer patients. The accumulation of MDSC contributes to the development of a tumour-associated immune suppressive environment. But the mechanism mediating MDSC accumulation in lung cancer patients is elusive. We found that exosomes from Lewis lung cancer cells (LLC-Exo) can be taken up by the mice bone marrow cells and then promote MDSC expansion, which enhance tumour growth. Mechanistically, during the induction of MDSC from the bone marrow cells, miR-21a from LLC-Exo can stimulate BM cells to produce more IL-6 by inhibitingpdcd4expression post-transcriptionally. Autocrine IL-6 induces tyrosine 705(Y705) of STAT3 to be phosphorylated during MDSC expansion. LLC-Exo with miR-21a deletion lost its ability to stimulate IL-6 production, STAT3 activation and MDSC expansion. These results demonstrate that lung cancer cell-derived exosomes promote functional MDSC expansion through activation of miR-21a/PDCD4/IL-6/STAT3 pathway.
A high-content RNAi screen reveals multiple roles for long noncoding RNAs in cell division
Authors: Stojic Lovorka , Lun Aaron T L , Mascalchi Patrice , Ernst Christina , Redmond Aisling M , Mangei Jasmin , Barr Alexis R , Bousgouni Vicky , Bakal Chris , Marioni John C , Odom Duncan T , Gergely Fanni
Published: July 2019

Genome stability relies on proper coordination of mitosis and cytokinesis, where dynamic microtubules capture and faithfully segregate chromosomes into daughter cells. The role of long noncoding RNAs (lncRNAs) in controlling these processes however remains largely unexplored. To identify lncRNAs with mitotic functions, we performed a high-content RNAi imaging screen targeting more than 2,000 human lncRNAs. By investigating major hallmarks of cell division such as chromosome segregation, mitotic duration and cytokinesis, we discovered numerous lncRNAs with functions in each of these processes. The chromatin-associated lncRNA,linc00899,was selected for in-depth studies due to the robust mitotic delay observed upon its depletion. Transcriptome analysis oflinc00899-depleted cells together with gain-of-function and rescue experiments across multiple cell types identified the neuronal microtubule-binding protein,TPPP/p25,as a target oflinc00899.Linc00899binds the genomic locus ofTPPP/p25and suppresses its transcription through acis-acting mechanism. In cells depleted oflinc00899,the consequent upregulation ofTPPP/p25alters microtubule dynamics and is necessary and sufficient to delay mitosis. Overall, our comprehensive screen identified several lncRNAs with roles in genome stability and revealed a new lncRNA that controls microtubule behaviour with functional implications beyond cell division.
Climate change alters beneficial crop-microbe-invertebrate interactions
Authors: Zytynska Sharon E. , Eicher Moritz , Rothballer Michael , Weisser Wolfgang W.
Published: July 2019

Increasing levels of CO2 and tropospheric ozone (O3) due to climate change are contributing to reduced plant health and unstable crop yield production1. The inoculation of plant roots with beneficial fungi or bacteria can increase plant health2. However, this is often studied under very controlled conditions and it is unknown how climate change or interactions with other species can alter the resulting benefits. Here we show that the rhizosphere bacterium Acidovorax radicis N35 can increase plant growth and reduce insect growth – with increased impact in a high-stress elevated O3 environment, but reduced impact under elevated CO2. In a fully-factorial climate chamber experiment we disentangled the impacts of climate factors (elevated CO2 and elevated O3) and biotic interactions (plant cultivar, sap-feeding insects and earthworms) on cereal growth and insect suppression mediated by A. radicis N35. Earthworms promoted plant aboveground growth, whereas A. radicis N35 promoted root growth, and overall plant growth was higher when both species were present. However, earthworms also promoted insect growth and therefore increased plant damage through herbivory. While A. radicis N35 inoculation was able to mitigate these negative effects to some extent under an ambient environment this was lost under climate change conditions. Our results show that knowledge-based solutions for sustainable agriculture should include biotic interactions and must be tested across variable climate change scenarios in order to build resilient cropping systems.
NBR1-mediated p62-liquid droplets enhance the Keap1-Nrf2 system
Authors: Sánchez-Martín Pablo , Sou Yu-shin , Kageyama Shun , Komatsu Masaaki
Published: July 2019

p62/SQSTM1 is a multivalent protein that has an ability to cause a liquid-liquid phase separation and serves as a receptor protein that participates in cargo isolation during selective autophagy. This protein is also involved in the non-canonical activation of the Keap1-Nrf2 system, a major oxidative stress response pathway. Here we show a role of Neighbor of BRCA1 gene 1 (NBR1), an autophagy receptor structurally similar to p62/SQSTM1, in the p62-liquid droplet formation and the Keap1-Nrf2 pathway. The overexpression of NBR1 blocked selective degradation of p62/SQSTM1 through autophagy and promoted the accumulation and phosphorylation of p62/SQSTM1 in liquid-like bodies, which is required for the activation of Nrf2. NBR1 was induced in response to oxidative stress, and then the p62-mediated Nrf2 activation was up-regulated. Conversely, loss of Nbr1 suppresses not only the formation of p62/SQSTM1-liquid droplets but also p62-dependent Nrf2 activation during oxidative stress. Taken together, our results show that NBR1 mediates p62/SQSTM1-liquid droplet formation to activate the Keap1-Nrf2 pathway.