bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of latanoprost‐induced diffuse facial skin hyperpigmentation
Authors: Kim Ho Young , Lee Soo Kyung , Lee Jae Ho , Suh Joong Heon , Kim Myoung Shin , Lee Un Ha
Published: March 2019

Introduction

Latanoprost is a prostaglandin F2α analogue, which has been used as a first‐line drug for open‐angle glaucoma. Common side effects of latanoprost include hyperpigmentation. While it usually occurs on irides or periocular skin, diffuse facial hyperpigmentation is rarely reported.

Case presentation

A 71‐year‐old woman was presented with diffuse gray‐brown colored maculopatches on her face. The symptom appeared 1 week after she started to use latanoprost eye drops for glaucoma. Biopsy specimen revealed vacuolar degeneration of dermo‐epidermal junction and pigment incontinence in dermis.

Objective

The aim of this paper is to introduce a rare adverse effect of latanoprost and effective way of treatment.

Methods

We stopped her from using latanoprost. She was also treated with 532‐nm potassium titanyl phosphate laser and low‐fluence 1064‐nm Q‐switched Nd:YAG laser, while using topical agents.

Result

After 10 weeks, we observed hyperpigmentation of her face was effectively and safely treated. The patient was satisfied with the result.

Conclusion

Diffuse facial pigmentation could be one of the latanoprost‐induced adverse effects and the laser treatments with topical agents we used can make it improve faster.
755 nm picosecond laser for facial atrophic scar—Case reports of long‐term clinical efficacy following up
Authors: Huang Ching‐Hsin , Hsieh Fu‐Sen , Chang Hung‐Chia , Peng Jui‐Hui , Peng Hsien‐Li Peter
Published: March 2019

Introduction

Acne vulgaris is one of the most common dermatological problems in Asia. While the disease itself is self‐limited and temporary, the dystrophic texture changes after the inflammatory process are often a serious aesthetic concern. Many energy‐based devices have seen good results in treating atrophic acne scars, and the picosecond laser with specific lens is one of the newer options, and lack reports on its long‐term efficacy.

Materials and Methods

We report three Taiwanese cases who, to our knowledge, consist of the longest clinical follow‐up times for atrophic scar treatment with the 755 nm diffractive lens picosecond laser. Photographs were compared on a by‐session basis by two blinded dermatologists independent of the primary treating physician and given an improvement range of <25%, 25%‐50%, 50%‐75%, and >75%.

Results

While there are minor (<25%) improvements in all cases after the first four treatment sessions, all three cases saw the greatest improvement in skin texture (>75% in two cases, 50%‐75% in one) when they were followed up 6, 13.5, and 28 months post‐last treatment.

Conclusion

Our results demonstrate excellent, long‐onset, and long‐term efficacy of the picosecond laser with diffractive lens in the treatment of acne atrophic scars. It also demonstrates the safe use of the device on Asian skins without symptoms of postinflammatory hyperpigmentation.
Serious complication as a result of lip augmentation with vitamin E
Authors: Ehsani Amir Hooshang , Ansari Mahshid Sadat , Ghanadan Alireza , Mehdizade Rayeni Neda , Noormohammad Poor Pedram , Ansari Mahsa
Published: March 2019

Nowadays lip augmentation with FDA‐approved fillers is becoming popular. However, because of financial concerns many patients seek for unregistered materials. Here, we report two cases who use vitamin E for lip augmentation. They experience severe infiltration and discharge less than one month after injection. Biopsy revealed lipogranuloma formation. They were treated with incision and drainage, antibiotic, and corticosteroids. Although these complications are usually difficult to treat, the patients had good clinical response and no recurrence in 5‐month follow‐up.
Performance is in the eye of the beholder
Authors: Tannenbaum Evan R , Tavares Walter , Kuper Ayelet
Published: March 2019

The authors argue that the time has come to explore solutions to gender bias by considering the extensive literature outlining its mechanisms and manifestations rather than engaging in further study of its existence.
H3K4 trimethylation by CclA regulates pathogenicity and the production of three families of terpenoid secondary metabolites in Colletotrichum higginsianum
Authors: Dallery Jean‐Félix , Adelin Émilie , Le Goff Géraldine , Pigné Sandrine , Auger Annie , Ouazzani Jamal , O'Connell Richard J.
Published: March 2019

The role of histone 3 lysine 4 (H3K4) methylation is poorly understood in plant pathogenic fungi. Here, we analysed the function of CclA, a subunit of the COMPASS complex mediating H3K4 methylation, in the brassica anthracnose pathogen Colletotrichum higginsianum. We show that CclA is required for full genome‐wide H3K4 trimethylation. The deletion of cclA strongly reduced mycelial growth, asexual sporulation and spore germination but did not impair the morphogenesis of specialized infection structures (appressoria and biotrophic hyphae). Virulence of the ΔcclA mutant on plants was strongly attenuated, associated with a marked reduction in appressorial penetration ability on both plants and inert cellophane membranes. The secondary metabolite profile of the ΔcclA mutant was greatly enriched compared to that of the wild type, with three different families of terpenoid compounds being overproduced by the mutant, namely the colletochlorins, higginsianins and sclerosporide. These included five novel molecules that were produced exclusively by the ΔcclA mutant: colletorin D, colletorin D acid, higginsianin C, 13‐epi‐higginsianin C and sclerosporide. Taken together, our findings indicate that H3K4 trimethylation plays a critical role in regulating fungal growth, development, pathogenicity and secondary metabolism in C. higginsianum.
Temporary heat stress suppresses PAMP‐triggered immunity and resistance to bacteria in Arabidopsis thaliana
Authors: Janda Martin , Lamparová Lucie , Zubíková Alžběta , Burketová Lenka , Martinec Jan , Krčková Zuzana
Published: March 2019

Recognition of pathogen‐associated molecular patterns (PAMPs) is crucial for plant defence against pathogen attack. The best characterized PAMP is flg22, a 22 amino acid conserved peptide from flagellin protein. In Arabidopsis thaliana, flg22 is recognized by the flagellin sensing 2 (FLS2) receptor. In this study, we focused on biotic stress responses triggered by flg22 after exposure to temporary heat stress (HS). It is important to study the reactions of plants to multiple stress conditions because plants are often exposed simultaneously to a combination of both abiotic and biotic stresses. Transient early production of reactive oxygen species (ROS) is a well‐characterized response to PAMP recognition. We demonstrate the strong reduction of flg22‐induced ROS production in A. thaliana after HS treatment. In addition, a decrease in FLS2 transcription and a decrease of the FLS2 presence at the plasma membrane are shown after HS. In summary, our data show the strong inhibitory effect of HS on flg22‐triggered events in A. thaliana. Subsequently, temporary HS strongly decreases the resistance of A. thaliana to Pseudomonas syringae. We propose that short exposure to high temperature is a crucial abiotic stress factor that suppresses PAMP‐triggered immunity, which subsequently leads to the higher susceptibility of plants to pathogens.
Involvement of glutathione metabolism in Eichhornia crassipes tolerance to arsenic
Authors: de Souza Reis I. N. R , Alves de Oliveira J. , Ventrella M. C. , Otoni W. C. , Marinato C. S. , Paiva de Matos L.
Published: March 2019

Aquatic macrophytes are potentially useful for phytoremediation programmes in environments contaminated by arsenic (As). Biochemical and physiological modification analyses in different plant parts are important to understand As tolerance mechanisms.

The objective was to evaluate glutathione metabolism in leaves and roots of Eichhornia crassipes (Mart.) Solms treated to As. Specimens of E. crassipes were cultured for 3 days in Clark's nutrient solution containing 7 μm As. The enzymes ATP sulphurylase (ATPS), glutathione reductase (GR), glutathione peroxidase (GSH‐Px), glutathione sulphotransferase (GST) and γ‐glutamylcysteine synthetase (γ‐ECS) activity, glutathione content, total protein and non‐protein thiols were evaluated.

The ATPS activity increased in roots. GR activity in leaves and GSH‐Px in roots were lower. GST activity was higher in roots and lower in leaves, and γ‐ECS activity was higher in leaves. Glutathione levels were lower, total thiol levels were higher and non‐protein levels did not change in E. crassipes leaves and roots. Exposure to As increased enzyme activity involved with sulphur metabolism, such as ATPS. Higher GR activity and lower GSH‐Px indicate increased glutathione conjugation to As due to increased GSH availability. The higher GST activity indicates its participation in As detoxification and accumulation through As GSH conjugation. Changes in glutathione and thiol levels suggest high phytochelatin synthesis.

In conclusion, the increments in ATPS, GR, GST and γ‐ECS activity indicate that these enzymes are involved in GSH metabolism and are part of the E. crassipes As detoxification mechanism.
New insights into the distribution of alien cyanobacterium Chrysosporum bergii (Nostocales, Cyanobacteria)
Authors: Kokociński Mikołaj , Soininen Janne
Published: March 2019

Invasive and alien cyanobacteria are considered as a serious threat to aquatic ecosystems due to their ability to produce cyanotoxins and outcompeting native species. Among cyanobacteria, Nostocales is a group with strong competitive advantages including the production of resting cells, ability to fix nitrogen or high affinity to phosphorus. A species Chrysosporum bergii has broadened its original distribution from brackish and seawater habitats of Caspian and Aral Seas to northern regions of Europe. The aim of our study was to expand the knowledge on the distribution of C. bergii, its preferred habitats in the invaded areas and examine whether the biomass of C. bergii is related with biomass of other alien or native cyanobacteria. We examined the phytoplankton community composition and the abiotic factors in randomly selected lakes of western Poland. For the first time, we showed that it occurs widely in lakes of this region. However, it occurred in one third of the investigated lakes and its contribution to total phytoplankton biomass was low. It occurred more frequently in shallow lakes with low conductivity and dissolved phosphorus, yet with higher total phosphorus concentration. The most remarkable finding was a negative relationship of C. bergii biomass with the biomass of native A. gracile, but a positive relationship with an invasive cyanobacterium C. raciborskii. This result suggests that these alien species occur under similar environmental conditions in Polish lakes. Moreover, the morphological features of C. bergii in Poland were similar to those of Anabaena bergii var. limnetica Couté et Preisig from Lithuania and Anabaena bergii from Czech Republic.
Shade delays flowering in Medicago sativa
Authors: Lorenzo Christian D. , Alonso Iserte Javier , Sanchez Lamas Maximiliano , Antonietti Mariana Sofia , Garcia Gagliardi Pedro , Hernando Carlos E. , Dezar Carlos Alberto A. , Vazquez Martin , Casal Jorge J. , Yanovsky Marcelo J. , Cerdán Pablo D.
Published: March 2019

Shade‐intolerant plants respond to the decrease in the red (R) to far‐red (FR) light ratio (R:FR) occurring under shade by elongating stems and petioles and by re‐positioning leaves, in a race to outcompete neighbors for the sunlight resource. In some annual species, the shade avoidance syndrome (SAS) is accompanied by the early induction of flowering. Anticipated flowering is viewed as a strategy to set seeds before the resources become severely limiting. Little is known about the molecular mechanisms of SAS in perennial forage crops like alfalfa (Medicago sativa). To study SAS in alfalfa, we exposed alfalfa plants to simulated shade by supplementing with FR light. Low R:FR light produced a classical SAS, with increased internode and petiole lengths, but unexpectedly also with delayed flowering. To understand the molecular mechanisms involved in uncoupling SAS from early flowering, we used a transcriptomic approach. The SAS is likely to be mediated by increased expression of msPIF3 and msHB2 in low R:FR light. Constitutive expression of these genes in Arabidopsis led to SAS, including early flowering, strongly suggesting that their roles are conserved. Delayed flowering was likely to be mediated by the downregulation of msSPL3, which promotes flowering in both Arabidopsis and alfalfa. Shade‐delayed flowering in alfalfa may be important to extend the vegetative phase under suboptimal light conditions, and thus assure the accumulation of reserves necessary to resume growth after the next season.
Can furosemide prevent transfusion‐associated circulatory overload? Results of a pilot, double‐blind, randomized controlled trial
Authors: Pendergrast Jacob , Armali Chantal , Cserti‐Gazdewich Christine , Hansen Mark , Kiss Alex , Lieberman Lani , Parmar Nagina , Scales Damon , Skeate Robert , Callum Jeannie , Lin Yulia
Published: March 2019

BACKGROUND

Transfusion‐associated circulatory overload (TACO) is a leading cause of transfusion‐attributable morbidity. It is unclear whether diuretics are safe and effective in preventing this reaction.

MATERIALS AND METHODS

In a pilot controlled feasibility trial, inpatients 65 years or older ordered a single unit of red blood cells were randomized to pre‐transfusion furosemide 20 mg or placebo intravenously. Primary outcome was the ability to enroll 80 patients within a 2‐month time period. Secondary feasibility outcomes included proportion of RBC transfusions meeting eligibility criteria, proportion of eligible patients enrolled, and compliance to study protocol. Clinical outcomes included the incidence of TACO and associated complications.

RESULTS

Nine months of enrollment were required for 80 patients to complete the study, due primarily to fewer transfusions than expected meeting eligibility criteria and lower than anticipated consent rates. Protocol compliance was below target due to missing chart documentation of patient fluid balance, and transfusion infusion time. Blinding was maintained throughout the study and treatment arms were well‐balanced. A single case of TACO occurred in each arm, for an overall incidence of 2.5%. No differences in peri‐transfusion vital signs, B‐natriuretic peptide, or signs of furosemide toxicity were observed.

CONCLUSION

The study protocol was not feasible as designed, primarily due to challenges in patient enrollment. Modifications to trial design to improve feasibility in future studies have been identified.
Peripheral localization of the epithelial sodium channel in the apical membrane of bronchial epithelial cells
Authors: Musante Ilaria , Scudieri Paolo , Venturini Arianna , Guidone Daniela , Caci Emanuela , Castellani Stefano , Conese Massimo , Galietta Luis J.V.
Published: March 2019

New Findings

What is the central question of this study?

What is the precise subcellular localization of the epithelial sodium channel (ENaC) in human airway epithelium?

What is the main finding and its importance?

ENaC protein has an unexpected localization in the peripheral region of the apical membrane of bronchial epithelial cells, very close to tight junctions. This may be important for the mechanism of Na+ absorption

The epithelial sodium channel (ENaC) has a key role in absorbing fluid across the human airway epithelium. Altered activity of ENaC may perturb the process of mucociliary clearance, thus impairing the innate defence mechanisms against microbial agents. The proteins forming ENaC are present on the apical membrane of the epithelium. However, their precise localization is unknown. In the present study, we used two antibodies recognizing the α and β ENaC subunits. Both antibodies revealed a restricted localization of ENaC in the peripheral region of the apical membrane of cultured bronchial epithelial cells, close to but not overlapping with tight junctions. In contrast, the cystic fibrosis transmembrane conductance regulator chloride channel was more diffusely expressed on the whole apical membrane. Modulation of ENaC activity by aprotinin or elastase resulted in a decrease or increase in the peripheral localization, respectively. Our results suggest that sodium absorption is mainly occurring close to tight junctions where this cation may be rapidly expelled by the Na+/K+ pump present in lateral membranes. This arrangement of channels and pumps may limit Na+ build‐up in other regions of the cells.
Multimodal Tuning of an Axisymmetric Resonator
Authors: Behbahani Amir H. , M'Closkey Robert T.
Published: March 2019

This paper reports an approach for the simultaneous elimination of the modal frequency differences within two pairs of modes in an axisymmetric resonator. Fabricated devices exhibit frequency detuning, which can be eliminated by strategically mass loading the resonator. Each pair of modes responds to the mass loading differently so models are developed to predict the postloading frequency differences. The models are incorporated into a search procedure to select deposition sites that simultaneously reduce the modal frequency difference within each pair. The proposed approach is successfully implemented on a resonator whose modal frequency differences are reduced below 200 mHz from an initial frequency difference of 23.5 Hz for a pair of modes at 13.8 kHz, and a 2.4 Hz difference for another pair of modes at 24.3 kHz.
Diesel Engine Acoustic Emission Airflow Clogging Diagnostics With Machine Learning
Authors: Cowart Jim , Moore Patrick , Yosten Harrison , Hamilton Leonard , Prak Dianne Luning
Published: March 2019

A diesel engine electrical generator set (“gen-set”) was instrumented with in-cylinder indicating sensors as well as acoustic emission microphones near the engine. Air filter clogging was emulated by progressive restriction of the engine's inlet air flow path during which comprehensive engine and acoustic data were collected. Fast Fourier transforms (FFTs) were analyzed on the acoustic data. Dominant FFT peaks were then applied to supervised machine learning neural network analysis with matlab-based tools. The progressive detection of the air path clogging was audibly determined with correlation coefficients greater than 95% on test data sets for various FFT minimum intensity thresholds. Further, unsupervised machine learning self-organizing maps (SOMs) were produced during normal-baseline operation of the engine. The degrading air flow engine sound data were then applied to the normal-baseline operation SOM. The quantization error (QE) of the degraded engine data showed clear statistical differentiation from the normal operation data map. This unsupervised SOM-based approach does not know the engine degradation behavior in advance, yet shows clear promise as a method to monitor and detect changing engine operation. Companion in-cylinder combustion data additionally shows the degrading nature of the engine's combustion with progressive airflow restriction (richer and lower density combustion).
Dynamic Behavior of a Solid Oxide Steam Electrolyzer System Using Transient Photovoltaic Generated Power for Renewable Hydrogen Production
Authors: Saeedmanesh Alireza , Colombo Paolo , McLarty Dustin , Brouwer Jack
Published: March 2019

This study investigates the dynamic behavior of a solid oxide steam electrolyzer (SOSE) system without an external heat source that uses transient photovoltaic (PV) generated power as an input to produce compressed (to 3 MPa) renewable hydrogen to be injected directly into the natural gas network. A cathode-supported crossflow planar solid oxide electrolysis (SOE) cell is modeled in a quasi-three-dimensional thermo-electrochemical model that spatially and temporally simulates the performance of a unit cell operating dynamically. The stack is composed of 2500 unit cells that are assumed to be assembled into identically operating stacks, creating a 300 kW electrolyzer stack module. For the designed 300 kW SOSE stack (thermoneutral voltage achieved at design steady-state conditions), powered by the dynamic 0–450 kW output of PV systems, thermal management and balancing of all heat supply and cooling demands is required based upon the operating voltage to enable efficient operation and prevent degradation of the SOSE stacks. Dynamic system simulation results show that the SOSE system is capable of following the dynamic PV generated power for a sunny day (maximum PV generated power) and a cloudy day (highly dynamic PV generated power) while the SOSE stack temperature gradient is always maintained below a maximum set point along the stack for both days. The system efficiency based upon lower heating value of the generated hydrogen is between 0–75% and 0–78% with daily hydrogen production of 94 kg and 55 kg for sunny and cloudy days, respectively.
Inverse identification of a higher order viscous parameter of rigid porous media in the high frequency domain
Authors: Roncen R. , Fellah Z. E. A. , Piot E. , Simon F. , Ogam E. , Fellah M. , Depollier C.
Published: March 2019

In this paper, a modeling extension for the description of wave propagation in rigid porous media at high frequencies is used. To better characterize the visco-inertial and thermal interactions between the fluid and the structure in this regime, two additional characteristic viscous and thermal surfaces Σ and Σ′ are taken into account, as initially introduced in Kergomard, Lafarge, and Gilbert [Acta Acust. Acust. 99(4), 557–571 (2013)]. This extends the modeling order of the dynamic tortuosity and compressibility. A sensitivity analysis is performed on the additional parameters, showing that only the viscous surface Σ has an influence on transmitted waves in the high frequency regime, for materials having a low viscous characteristic length. A general Bayesian inference is then conducted to infer simultaneously the posterior probability densities of the parameters associated with the visco-inertial effects, i.e., the porosity, tortuosity, the viscous characteristic length, and the viscous characteristic surface. The proposed method is based on the measurement of waves transmitted by a slab of rigid porous material in the time domain. Bayesian inference results obtained on three different porous materials are presented.
Evidence of pair-density wave in spin-valley locked systems
Authors: Venderley Jordan , Kim Eun-Ah
Published: March 2019

DMRG simulation predicts spatially modulated superconductivity in a triangular system with spin-valley locking for the first time.
Optical pulling at macroscopic distances
Authors: Li Xiao , Chen Jun , Lin Zhifang , Ng Jack
Published: March 2019

A cocktail of independent yet compatible mechanisms pull an object from far with light.
Intermolecular dialkylation of alkenes with two distinct C(sp
3
)─H bonds enabled by synergistic photoredox catalysis and iron catalysis
Authors: Ouyang Xuan-Hui , Li Yang , Song Ren-Jie , Hu Ming , Luo Shenglian , Li Jin-Heng
Published: March 2019

An intermolecular dialkylation of alkenes via a radical process with two distinct C(sp
3
)─H bonds is described.
That’s the Way You Do It
Authors: Roop R. Martin
Published: March 2019

About one-third of the proteins encoded by the bacterial genomes that have been sequenced to date are proteins of “unknown function.” Studies aimed at defining the biological functions of these proteins represent an important frontier in prokaryotic biology. The study presented by J.
Cas4 Nucleases Can Effect Specific Integration of CRISPR Spacers
Authors: Zhang Zhufeng , Pan Saifu , Liu Tao , Li Yingjun , Peng Nan
Published: March 2019

The Cas4 family endonuclease is an essential component of the adaptation module in many variants of CRISPR-Cas adaptive immunity systems. The
Crenarchaeota
Sulfolobus islandicus
REY15A carries two
cas4
genes (
cas4
and
csa1
) linked to the CRISPR arrays. Here, we demonstrate that Cas4 and Csa1 are essential to CRISPR spacer acquisition in this organism. Both proteins specify the upstream and downstream conserved nucleotide motifs of the protospacers and define the spacer length and orientation in the acquisition process. Conserved amino acid residues, in addition to those recently reported, were identified to be important for these functions. More importantly, overexpression of the
Sulfolobus
viral Cas4 abolished spacer acquisition, providing support for an anti-CRISPR role for virus-encoded Cas4 proteins that inhibit spacer acquisition.
Introducing an AKI predictive tool for patients undergoing orthopaedic surgery
Authors: Baird David Paul , Rae Fraser , Beecroft Christina , Gallagher Katherine , Sim Stephanie , Vaessen Robert , Wright Emily , Bell Samira
Published: March 2019

Patients undergoing surgery are at increased risk of acute kidney injury (AKI). AKI is associated with adverse outcomes such as increased mortality and future risk of developing chronic kidney disease. We have developed a validated preoperative scoring tool to predict postoperative AKI in patients undergoing orthopaedic surgery using seven readily available parameters. The aim of this project was to establish the use of this scoring tool with a target compliance of 80% in patients undergoing orthopaedic surgery requiring an overnight stay at Perth Royal Infirmary, a district general hospital in NHS Tayside. We created an intervention bundle for patients at high risk of AKI, which we defined as greater than 10%. An electronic tool available on smartphones and desktop computers was developed that can be used to calculate the score. The interventions were incorporated into the electronic tool and posters outlining the intervention were placed in clinical areas. Patients undergoing elective procedures were scored in the preassessment clinic while emergency patients were scored by the admitting doctors. The score was introduced using four PDSA cycles. This confirmed that the scoring tool functioned well and was being used accurately. Compliance for patients undergoing elective surgery was reasonable at 19/24 (79%) in the third and fourth PDSA cycles but was poorer for emergency admissions with compliance of only 3/7 (43%). There was excellent compliance with the suggested medication changes and postoperative blood test monitoring as advised by our intervention bundle for those at high risk of AKI. Fluid balance monitoring was advised for all patients but the outcome was similar following our intervention at 27/41 (66%) compared with 23/37 (62%) in the baseline data collection. Compliance with fluid balance monitoring was higher in patients at high risk of AKI (9/12, 75%).
Sildenafil does not reliably improve exercise performance in hypoxia: a systematic review
Authors: Carter Eric Alexander , Lohse Keith , Sheel William , Koehle Michael
Published: March 2019

Objective

Sildenafil is a pulmonary vasodilator that may reduce the decrement in endurance performance in moderate hypoxia. We assessed the efficacy of sildenafil to improve performance in hypoxia.

Data sources/eligibility Criteria

We systematically searched electronic databases (until August 2018) for randomised trials comparing sildenafil with placebo. We also examined the effect of sildenafil on pulmonary artery pressure (PAP), cardiac output (CO) and pulse oxygen saturation (SPO2) compared with placebo in hypoxia. Fourteen studies were included; 210 subjects received sildenafil 40, 50 or 100 mg/day.

Results

Sildenafil showed a large effect for decreasing PAP during exercise and at rest, a small effect for increasing CO during exercise and a moderate effect at rest, a moderate effect for increasing SPO2and a small effect for improving performance. In a subgroup analysis, there was no statistically significant difference between 100 and 50 mg sildenafil dose on SPO2. Sildenafil had a moderate effect on increasing SPO2and performance at terrestrial hypobaric altitude but only a small effect on both in normobaric hypoxia. Regression analysis showed that hypoxic dose (PO2) and metabolic rate do not account for a significant portion of the variance in effect size for sildenafil on PAP, CO, SPO2and performance.

Conclusion

This meta-analysis indicates that sildenafil reduces PAP, has a moderate to small effect on CO and SPO2, and no effect on performance.
The Origins of the Park Jung-hee Syndrome in South Korea
Authors: CHOI EUNJUNG , WOO JONGSEOK
Published: March 2019

In the past few decades, post-democratization politics in South Korea have witnessed an upsurge in authoritarian nostalgia, called the “Park Jung-hee syndrome.” This paper examines the origins of public nostalgia for the authoritarian dictator by putting two theoretical arguments, i.e., the socialization thesis and the system output thesis, to an empirical test. This paper utilizes the 2010 Korea Democracy Barometer from the Korea Barometer and the 2010 and the 2015 Korean National Identity Survey from the East Asia Institute. The empirical analysis of the South Korean case strongly supports the political socialization argument, suggesting that citizens’ yearning for Park Jung-hee is not merely an outcome of the negative evaluations of the democratic governments’ performances. Rather, their authoritarian nostalgia is in large part an outcome of their political socialization during the Park dictatorship. The analysis implies that, although a resurgence of the Park Jung-hee syndrome in post-democratization South Korea is not expected to derail the country’s route to democratic deepening, it may continue to be a main source of political division in partisan and electoral politics in the future.
Augmenting Operating Systems with OpenCL Accelerators
Authors: Tu Chia-Heng , Lin Te-Sheng
Published: March 2019

Heterogeneous computing leverages more than one kind of processors to boost the performance of user-space applications with the heterogeneous programming languages, e.g., OpenCL. While some works have been done to accelerate the computations required by Linux kernel software, they are either application-specific solutions or tightly coupled with the certain computing platforms and are not able to support the general-purpose in-kernel accelerations using different types of processors. In this article, the general-purpose software framework called Kernel acceleration with OpenCL (KOCL), is proposed to tackle the problem. KOCL exposes a set of the high-level programming interfaces for the Linux kernel module developers to offload compute-intensive tasks on different hardware accelerators without managing and coordinating the platform-specific computing and memory resources. The simplified programming efforts are achieved by the developed platform management and memory models, which provide a systematic means of managing the heterogeneous hardware resources. In addition, the one- and zero-copy data-buffering schemes are offered by KOCL, so that the offloaded tasks deliver high performance on the platforms with different memory architectures. We have developed the prototype system to accelerate the Network-Attached Storage server applications. Significant performance improvements are achieved with the three different types of accelerators, i.e., the multicore processor, the integrated GPU, and the discrete GPU, respectively. We believe that KOCL is useful for the design of embedded appliances to evaluate the performance of design alternatives.
Genome-wide association study identifies the PLAG1-OXR1 region on BTA14 for carcass meat yield in cattle
Authors: Zhang Rui , Miao Jian , Song Yuxin , Zhang Wengang , Xu Lingyang , Chen Yan , Zhang Lupei , Gao Huijiang , Zhu Bo , Li Junya , Gao Xue
Published: March 2019

Carcass meat yield is an important carcass trait that contributes to the production efficiency and economic benefits in beef cattle. It is therefore critical to identify quantitative trait loci associated with carcass traits to enable selection. Our previous studies have identified several causal variants within the pleomorphic adenoma gene 1 ( PLAG1) and coiled-coil-helix-coiled-coil-helix domain-containing 7 ( CHCHD7) genes on BTA14 for carcass traits in Chinese Simmental. In the current study, we carried out a genome-wide association study for carcass meat yield in 472 Wagyu cattle with Bovine HD SNP array. Our results showed that 27 single nucleotide polymorphisms (SNPs) were identified for tenderloin weight (TDW), striploin weight (SPW), chuck roll weight (CRW), bicep weight (BPW), knuckle weight (KCW), and flank steak weight (FSW) in Wagyu cattle. Of these SNPs, 10 distinct SNPs were detected within the oxidation resistance 1 ( OXR1), fatty acid binding protein 5 ( FABP5), TNF receptor superfamily member 11b ( TNFRSF11B), and zinc finger CCCH-type containing 3 ( ZC3H3) genes on BTA14. Notably, three significant SNPs, BovineHD1400016738, BovineHD1400016743, and BovineHD1400016665 within OXR1, were shown strong linkage disequilibrium (r2 > 0.8) and significantly associated with CRW ( P = 1.37 × 10−8 ~ 1.94 × 10−8). Moreover, Ingenuity Pathway Analysis showed that OXR1, FABP5, and CAP1A genes were involved in a single network and FABP5 may regulate the expression of OXR1 gene via node gene, peroxisome proliferator-activated receptor gamma ( PPARG). Overall, this study suggests that OXR1 and FABP5 are candidate genes affecting carcass traits in Wagyu and the PLAG1-OXR1 region on BTA14 as a putative susceptibility locus for carcass meat yield for both Chinese Simmental and Wagyu.
Profiling expression changes of genes associated with temperature and sex during high temperature-induced masculinization in the Nile tilapia brain
Authors: Zhao Yan , Mei Yuan , Chen Hong Ju , Zhang Li Tao , Wang Hui , Ji Xiang Shan
Published: March 2019

Fish sex-determining mechanisms can be classified as genotypic (GSD), temperature (TSD), or genotypic plus temperature effects (GSD+TE). Previous studies have shown that culturing water temperature during thermosensitive periods (TSP) could affect the expression of many genes in the gonad in some fish. However, few studies have focused on gene expression changes in the brain after temperature treatment during TSP in fish species. In this study, three families were developed by crossing XX neomales with XX females and one of them was used for transcriptome analysis. The results showed that a total of 105, 3164 and 4666 DEGs were respectively obtained in FC (female control) vs. FT (high temperature-treated females at TSP), FC vs. MC (male control), and MC vs. FT comparison groups. By profiling analysis, we show that the mRNA expression levels of 16 differentially expressed genes (DEGs) exhibited significant downregulation or upregulation after high temperature treatment and reached a similar level as that in MC. Among the 16 DEGs, LOC100699848 (lysine specific demethylase 6A) and Jarid2 contained JmjC domain, showing the possible important role of JmjC domain in response to temperature treatment in Nile tilapia. Kdm6b (lysine demethylase 6B) and Jarid2 have been shown to play important roles in reptile TSD, showing the relative conservation of underlying regulation mechanisms between TSD in reptile and TSD or GSD+TE in fish species. Finally, the transcriptome profiling was validated by quantitative real-time PCR in nine selected genes. These results provide a direction for investigating the GSD+TE molecular mechanism in fish species.
Functional Analysis of Somatic Mutations Affecting Receptor Tyrosine Kinase Family in Metastatic Colorectal Cancer
Authors: Duplaquet Leslie , Figeac Martin , Leprêtre Frédéric , Frandemiche Charline , Villenet Céline , Sebda Shéhérazade , Sarafan-Vasseur Nasrin , Bénozène Mélanie , Vinchent Audrey , Goormachtigh Gautier , Wicquart Laurence , Rousseau Nathalie , Beaussire Ludivine , Truant Stéphanie , Michel Pierre , Sabourin Jean-Christophe , Galateau-Sallé Françoise , Copin Marie-Christine , Zalcman Gérard , De Launoit Yvan , Fafeur Véronique , Tulasne David
Published: March 2019

Besides the detection of somatic receptor tyrosine kinases (RTK) mutations in tumor samples, the current challenge is to interpret their biological relevance to give patients effective targeted treatment. By high-throughput sequencing of the 58 RTK exons of healthy tissues, colorectal tumors, and hepatic metastases from 30 patients, 38 different somatic mutations in RTKs were identified. The mutations in the kinase domains and present in both tumors and metastases were reconstituted to perform an unbiased functional study. Among eight variants found in seven RTKs (EPHA4-Met726Ile, EPHB2-Val621Ile, ERBB4-Thr731Met, FGFR4-Ala585Thr, VEGFR3-Leu1014Phe, KIT-Pro875Leu, TRKB-Leu584Val, and NTRK2-Lys618Thr), none displayed significantly increased tyrosine kinase activity. Consistently, none of them induced transformation of NIH3T3 fibroblasts. On the contrary, two RTK variants (FGFR4-Ala585Thr and FLT4-Leu1014Phe) caused drastic inhibition of their kinase activity. These findings indicate that these RTK variants are not suitable targets and highlight the importance of functional studies to validate RTK mutations as potential therapeutic targets.
Enhancing Therapeutic Efficacy of Oncolytic Herpes Simplex Virus-1 with Integrin β1 Blocking Antibody OS2966
Authors: Lee Tae Jin , Nair Mitra , Banasavadi-Siddegowda Yeshavanth , Liu Joseph , Nallanagulagari Tejaswini , Jaime-Ramirez Alena Cristina , Guo Jeffrey Yunhua , Quadri Haroon , Zhang Jianying , Bockhorst Kurt H. , Aghi Manish K. , Carbonell W. Shawn , Kaur Balveen , Yoo Ji Young
Published: March 2019

Integrin β1 receptor, expressed on the surface of tumor cells and macrophages in the tumor microenvironment (TME), has been implicated in both tumor progression and resistance to multiple modalities of therapy. OS2966 is the first clinical-ready humanized monoclonal antibody to block integrin β1 and was recently orphan designated by the FDA Office of Orphan Products Development. Here, we tested therapeutic potential of OS2966-mediated integrin β1 blockade to enhance the efficacy of oncolytic herpes simplex virus-1 (oHSV) through evaluation of virus replication, tumor cell killing efficiency, effect on the antiviral signaling pathway, co-culture assays of oHSV-infected cells with macrophages, and in vivo bioluminescence imaging on mammary fat pad triple-negative breast cancer xenograft and subcutaneous and intracranial glioma xenografts. OS2966 treatment decreased interferon signaling and proinflammatory cytokine induction in oHSV-treated tumor cells and inhibited migration of macrophages, resulting in enhanced oHSV replication and cytotoxicity. OS2966 treatment also significantly enhanced oHSV replication and oHSV-mediated antitumor efficacy in orthotopic xenograft models, including triple-negative breast cancer and glioblastoma. The results demonstrated the synergistic potential of the combinatory treatment approach with OS2966 to improve antitumor efficacy of conventional oHSV therapy.
RAC1b Overexpression Confers Resistance to Chemotherapy Treatment in Colorectal Cancer
Authors: Goka Erik T. , Chaturvedi Pallavi , Lopez Dayrelis T. Mesa , Garza Adriana De La , Lippman Marc E.
Published: March 2019

Resistance to chemotherapy represents a major limitation in the treatment of colorectal cancer. Novel strategies to circumvent resistance are critical to prolonging patient survival. Rac1b, a constitutively activated isoform of the small GTPase Rac1, is upregulated with disease progression and promotes cell proliferation and inhibits apoptosis by activation of NF-κB signaling. Here, we show that Rac1b overexpression correlates with cancer stage and confirmed Rac1b expression is associated with increased growth through enhancing NF-κB activity. Rac1b knockdown reduced cellular proliferation and reduced NF-κB activity. Surprisingly, Rac1b expression and NF-κB activity were upregulated in cells treated with chemotherapeutics, suggesting that Rac1b facilitates chemo-resistance through activation of NF-κB signaling. Knockdown of Rac1b or Rac inhibition increases the sensitivity of the cells to oxaliplatin. When used in combination, inhibition of Rac prevents the increase in NF-κB activity associated with chemotherapy treatment and increases the sensitivity of the cells to oxaliplatin. Although Rac inhibition or oxaliplatin treatment alone reduces the growth of colorectal cancer in vivo, combination therapy results in improved outcomes compared with single agents alone. We provide the first evidence that Rac1b expression confers resistance to chemotherapy in colorectal cancer. Additionally, we show that the use of a Rac inhibitor prevents chemoresistance by blocking activation of chemotherapy induced NF-κB signaling, providing a novel strategy to overcome resistance to chemotherapy in colorectal cancer.
Preclinical Investigation of 212Pb-DOTAMTATE for Peptide Receptor Radionuclide Therapy in a Neuroendocrine Tumor Model
Authors: Stallons Tania A. Rozgaja , Saidi Amal , Tworowska Izabela , Delpassand Ebrahim S. , Torgue Julien J.
Published: March 2019

Somatostatin analogues have been examined as a treatment for somatostatin receptor overexpressing tumors for years; specifically, octreotate (TATE) and octreotide (TOC). Several versions of these analogues coupled to beta or gamma nuclides are currently used as imaging agents, as treatments with peptide receptor radionuclide therapy (PRRT) for patients with neuroendocrine tumors or are being explored in preclinical and clinical settings. Our study describes the use of 212Pb-DOTAMTATE, the octreotate analogue, in combination with 212Pb, the parent of an alpha emitter. Preclinical studies demonstrated tumor targeting of 212Pb-DOTAMTATE of >20% ID/g up to 24 hours post drug injection. The addition of kidney protection agents, including l-lysine and l-arginine decreases drug accumulation in the kidneys and the addition of ascorbic acid to the chelation mixture reduces oxidation of the drug product. 212Pb-DOTAMTATE displays a favorable toxicity profile with single-dose injections of 20 μCi showing 100% survival and with nontoxic cumulative doses up to 45 μCi, when fractionated into three smaller doses of 15 μCi. In an initial efficacy study, a single 10 μCi injection of 212Pb-DOTAMTATE extended the mean survival 2.4-fold. Efficacy was enhanced by giving three treatment cycles of 212Pb-DOTAMTATE and reducing the time between injections to two weeks. Efficacy was optimized further by the addition of a chemo-sensitizing agent, 5-fluorouracil, given in combination with three cycles of 10 μCi 212Pb-DOTAMTATE. These conditions led to 79% of the animals being tumor free at the end of the 31-week study suggesting that 212Pb-DOTAMTATE alone or in combination with a chemotherapeutic may have positive clinical implications.
Prospective Clinical Sequencing of Adult Glioma
Authors: Zheng Siyuan , Alfaro-Munoz Kristin , Wei Wei , Wang Xiaojing , Wang Fang , Eterovic Agda Karina , Shaw Kenna R. Mills , Meric-Bernstam Funda , Fuller Gregory N. , Chen Ken , Verhaak Roel G. , Mills Gordon B. , Yung W.K. Alfred , Weathers Shiao-Pei , de Groot John F.
Published: March 2019

Malignant gliomas are a group of intracranial cancers associated with disproportionately high mortality and morbidity. Here, we report ultradeep targeted sequencing of a prospective cohort of 237 tumors from 234 patients consisting of both glioblastoma (GBM) and lower-grade glioma (LGG) using our customized gene panels. We identified 2,485 somatic mutations, including single-nucleotide substitutions and small indels, using a validated in-house protocol. Sixty-one percent of the mutations were contributed by 12 hypermutators. The hypermutators were enriched for recurrent tumors and had comparable outcome, and most were associated with temozolomide exposure. TP53 was the most frequently mutated gene in our cohort, followed by IDH1 and EGFR. We detected at least one EGFR mutation in 23% of LGGs, which was significantly higher than 6% seen in The Cancer Genome Atlas, a pattern that can be partially explained by the different patient composition and sequencing depth. IDH hotspot mutations were found with higher frequencies in LGG (83%) and secondary GBM (77%) than primary GBM (9%). Multivariate analyses controlling for age, histology, and tumor grade confirm the prognostic value of IDH mutation. We predicted 1p/19q status using the panel sequencing data and received only modest performance by benchmarking the prediction to FISH results of 50 tumors. Targeted therapy based on the sequencing data resulted in three responders out of 14 participants. In conclusion, our study suggests ultradeep targeted sequencing can recapitulate previous findings and can be a useful approach in the clinical setting.
Lúcio Costa e os Jesuítas nas Revistas do SPHAN (1937-1945)
Authors: Entringer Rogério
Published: March 2019

Este artigo demonstra como os jesuítas e sua arquitetura (1549-1759), junto ao nome de Lúcio Costa, são recorrentes nos artigos das revistas do SPHAN entre 1937 e 1945. Defendemos a tese de que o SPHAN e seus intelectuais, entre eles Costa, por meio dessas revistas, utilizaram os signos dos jesuítas, tal como sua importância histórica na formação do Brasil e o valor patrimonial de sua arte e arquitetura, para permitir à sociedade estado-novista representar a si mesma, fundar uma identidade nacional pelo movimento moderno e delinear a ideia de uma República justificada pela história.
Novas dinâmicas urbanas para a resolução de problemas das cidades: um olhar sobre a Porto Alegre online/offline de hoje.
Authors: Gallina Gabriel , Tarouco Fabricio
Published: March 2019

A efetividade no trato dos problemas urbanos e sociais não acompanhou a rápida urbanização das grandes cidades. Novas dinâmicas vêm emergindo de uma sociedade que age criativamente, coletivamente e de forma colaborativa, implementando novos canais para resolução de problemas que não dependam exclusivamente do poder público. O artigo se propõe a analisar novos modelos de engajamento popular e divisão de responsabilidades que vem se impondo nas cidades contemporâneas, observando dinâmicas online, offline ou mistas da participação social representadas pelo codesign. Como cenário para discussão, se definiu como recorte o contexto da mobilidade urbana em Porto Alegre durante a última década.
Fetal and maternal factors are associated with mortality due to circulatory system disorders in children
Authors: Salim Thais Rocha , Soares Gabriel Porto , Klein Carlos Henrique , Oliveira Gláucia Maria Moraes
Published: March 2019

OBJECTIVE: To analyze the association of characteristics recorded at the time of birth, including weight, occurrence of asphyxia, gestation duration, maternal age and education level, with death from diseases or malformations of the circulatory system in children under 18 years of age. METHODS: The Brazilian Information System on Live Births and Information System on Mortality databases were linked and evaluated following a longitudinal cohort analysis strategy. The following independent variables were evaluated: characteristics recorded at the time of birth, including weight, occurrence of asphyxia, gestation duration, maternal age and education level. Dependent variables were death from diseases or malformations of the circulatory system in children under 18 years of age. Crude relative risks were estimated and relative risks were adjusted for the variables. RESULTS: 6,380 deaths were linked to 4,282,260 birth records, yielding 5,062 pairs considered as true. Low birth weight (RR = 2.26), asphyxia at 1 (RR = 1.72) and 5 minutes (RR = 1.51), prematurity (RR = 1.50), maternal age ≥ 40 years (RR = 2.06), and low maternal education level (RR = 1.45) increased the probability of death caused by circulatory system diseases. In the association with death by malformations of the circulatory system, the predictive variables showed the same association profile, but with greater intensity. CONCLUSIONS: Fetal and maternal factors are associated with increased mortality due to diseases and malformations of the circulatory system. Measures to control these factors and improve access to their diagnosis and treatment would contribute to reducing the number of deaths caused by diseases and malformations of the circulatory system. However, the identification of environmental influences during gestation and birth on the risk of death should be carefully considered due to being influenced by genetic factors.