bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative splicing expands the prognostic impact of KRAS in microsatellite stable primary colorectal cancer
Authors: Eilertsen Ina A. , Sveen Anita , Strømme Jonas M. , Skotheim Rolf I. , Nesbakken Arild , Lothe Ragnhild A.
Published: August 2018

KRAS mutation is a well‐known marker for poor response to targeted treatment and patient prognosis in microsatellite stable (MSS) colorectal cancer (CRC). However, variation in clinical outcomes among patients wild‐type for KRAS underlines that this is not a homogeneous population. Here, we evaluated the prognostic impact of KRAS alternative splicing in relation to mutation status in a single‐hospital series of primary MSS CRCs (N = 258). Using splicing‐sensitive microarrays and RNA sequencing, the relative expression of KRAS‐4A versus KRAS‐4B transcript variants was confirmed to be down‐regulated in CRC compared to normal colonic mucosa (N = 41; p ≤ 0.001). This was independent of mutation status, however, gene set enrichment analysis revealed that the effect of splicing on KRAS signaling was specific to the KRAS wild‐type subgroup, in which low relative KRAS‐4A expression was associated with a higher level of KRAS signaling (p = 0.005). In concordance, the prognostic value of KRAS splicing was also dependent on mutation status, and for patients with Stage I–III KRAS wild‐type MSS CRC, low relative KRAS‐4A expression was associated with inferior overall survival (HR: 2.36, 95% CI: 1.07–5.18, p = 0.033), a result not found in mutant cases (pinteraction = 0.026). The prognostic association in the wild‐type subgroup was independent of clinicopathological factors, including cancer stage in multivariable analysis (HR: 2.68, 95% CI: 1.18–6.09, p = 0.018). This suggests that KRAS has prognostic value beyond mutation status in MSS CRC, and highlights the importance of molecular heterogeneity in the clinically relevant KRAS wild‐type subgroup.
Insights from multidimensional analyses of the pan‐cancer DNA methylome heterogeneity and the uncanonical CpG–gene associations
Authors: Liu Yang , Huang Rongyao , Liu Yu , Song Wanlu , Wang Yuting , Yang Yang , Dong Shengcheng , Yang Xuerui
Published: August 2018

Although the DNA methylome profiles have been available in large cancer cohorts such as The Cancer Genome Atlas (TCGA), integrative analysis of the DNA methylome architectures in a pan‐cancer manner remains limited. In the present study, we aimed to systematically dissect the insightful features related to the inter‐tumoral DNA methylome heterogeneity in a pan‐cancer context of 21 cancers in TCGA. First, pan‐cancer clustering of the DNA methylomes revealed convergence of cancers and, meanwhile, new classifications of cancer subtypes, which are often associated to prognostic differences. Next, within each type of cancer, we showed that the transcription factor (TF) genes tend to bear more dynamic promoter DNA methylation profiles than the other genes, which serves as a potential source of the transcriptome heterogeneity in cancers. Finally, we found unanticipated significant numbers of the non‐canonical promoter CpG sites that are positively correlated with the gene expression. Distribution patterns of these CpG sites in the CpG islands, ChIP‐seq, DNaseI‐seq, PMD regions and histone modification landscapes suggested against a pervasive mechanism of transcriptional activation due to mCpG‐dependent binding of TFs, which is not in complete agreement with previous hypothesis. In summary, our deep mining of the highly heterogeneous DNA methylome data in a pan‐cancer context generated novel insights into the architecture of cancer epigenetics and provided a series of resources for further investigations in the related fields of cancer genomics and epigenetics.
Determination of the origin of oral squamous cell carcinoma by microarray analysis: Squamous epithelium or minor salivary gland?
Authors: Kinouchi Makoto , Izumi Sayaka , Nakashiro Koh‐ichi , Haruyama Yasuo , Kobashi Gen , Uchida Daisuke , Hasegawa Tomonori , Kawamata Hitoshi
Published: August 2018

More than 90% of oral cancers are histopathologically squamous cell carcinomas (SCCs). According to clinical behavior and histopathological features, we hypothesize that oral SCC can originate from either oral squamous epithelium or minor salivary glands. Here, we examined whether some oral SCCs originate from minor salivary glands, and investigated whether these tumors show particularly aggressive biological behavior. The mRNA expression profiles of samples obtained from six patients with oral floor SCC (five men, one woman; mean age, 62.7 years) were analyzed using a microarray containing 32,878 probes. The six samples were divided into two groups by clustering of expression levels of 845 probes differentially expressed in normal oral squamous epithelium and normal salivary glands. The expression profile in four cases was similar to that of normal oral squamous epithelium, and in two cases was similar to that of normal salivary glands. Furthermore, we identified nine genes that reveal the origin of the oral SCC. Subsequently, we examined the expression levels of these nine marker genes by reverse transcriptase‐polymerase chain reaction to determine the origin of 66 oral SCCs. Twelve of the 66 oral SCCs were considered to originate from minor salivary glands, and these tumors showed high metastatic potential (p = 0.044, Chi‐square test). Furthermore, SCC derived from minor salivary glands showed a poor event‐free survival rate (p = 0.017, Kaplan–Meier analysis). In conclusion, determination of the origin of oral SCC is helpful in planning treatment for patients with oral SCC.
Microenvironmental control of glucose metabolism in tumors by regulation of pyruvate dehydrogenase
Authors: Golias Tereza , Kery Martin , Radenkovic Silvia , Papandreou Ioanna
Published: August 2018

During malignant progression cancer cells undergo a series of changes, which promote their survival, invasiveness and metastatic process. One of them is a change in glucose metabolism. Unlike normal cells, which mostly rely on the tricarboxylic acid cycle (TCA), many cancer types rely on glycolysis. Pyruvate dehydrogenase complex (PDC) is the gatekeeper enzyme between these two pathways and is responsible for converting pyruvate to acetyl‐CoA, which can then be processed further in the TCA cycle. Its activity is regulated by PDP (pyruvate dehydrogenase phosphatases) and PDHK (pyruvate dehydrogenase kinases). Pyruvate dehydrogenase kinase exists in 4 tissue specific isoforms (PDHK1–4), the activities of which are regulated by different factors, including hormones, hypoxia and nutrients. PDHK1 and PDHK3 are active in the hypoxic tumor microenvironment and inhibit PDC, resulting in a decrease of mitochondrial function and activation of the glycolytic pathway. High PDHK1/3 expression is associated with worse prognosis in patients, which makes them a promising target for cancer therapy. However, a better understanding of PDC's enzymatic regulation in vivo and of the mechanisms of PDHK‐mediated malignant progression is necessary for the design of better PDHK inhibitors and the selection of patients most likely to benefit from such inhibitors.
Impact of clinicopathological characteristics on survival in patients treated with immune checkpoint inhibitors for metastatic melanoma
Authors: Zhao Bin , Zhao Hong , Zhao Jiaxin
Published: August 2018

Immune checkpoint inhibitors (ICIs) have unprecedented effects on the treatment of metastatic melanoma. However, little is known about the prognostic values of various clinicopathological characteristics. Here, PubMed, Embase and Cochrane database were searched from inception to April 2018 for random controlled trials (RCTs) that compared ICIs with controls. The hazard ratios (HRs) for overall survival (OS) according to gender, age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), lactate dehydrogenase (LDH) level and metastasis stage were extracted. Four phase III RCTs involving 1,598 patients with metastatic melanoma were included in this study. Compared with conventional agents, ICIs were associated with prolonged OS (HR, 0.67; 95% CI, 0.50–0.88; p = 0.005). The pooled OS HR was 0.60 (95% CI, 0.42–0.84; p = 0.003) in men; 0.84 (95% CI, 0.69–1.01; p = 0.07) in women. The difference in efficacy between men and women was significant (pinteraction = 0.03). The OS HR was 0.59 (95% CI, 0.41–0.83; p = 0.003) in patients >65 years old; 0.74 (95% CI, 0.55–1.01; p = 0.054) in patients <65 years old. The OS HR was 0.75 (95% CI, 0.60–0.94; p = 0.01) in patients with ECOG PS = 1; 0.64 (95% CI, 0.38–1.06; p = 0.08) in patients with ECOG PS = 0. Additionally, the long‐term benefits were independent of metastasis stage and LDH level. In summary, although immunotherapy significantly prolongs OS in metastatic melanoma, the long‐term benefits in women, younger patients (<65 years old) and patients with ECOG PS = 0 were marginal. These results may assist in treatment decision‐making, design and interpretation of clinical trials and economic analyses.
Toll‐like receptors: Important immune checkpoints in the regression of cervical intra‐epithelial neoplasia 2
Authors: Halec Gordana , Scott Mark E. , Farhat Sepideh , Darragh Teresa M. , Moscicki Anna‐Barbara
Published: August 2018

Toll‐like receptors (TLRs) are innate immune defenders thought to be critical for the clearance of human papillomavirus (HPV) infections hence preventing the development of HPV‐associated high‐grade cervical intra‐epithelial neoplasia (CIN2 or 3), a potential cervical cancer precursor. However, the role of TLRs in the regression of established cervical lesions, such as CIN2, is hindered by a lack of prospective design studies. Using SYBR green real‐time PCR assays, we have examined the gene expression of TLR2, TLR3, TLR7, TLR8 and TLR9, in cytobrush collected endocervical cells of 63 women diagnosed with CIN2 at study entry (baseline) and followed over a 3‐year period. Wilcoxon rank‐sum test was used to examine the association between TLR expression levels, measured at baseline, and CIN2 outcome (regression vs. persistence/progression) over time. HPV genotyping was performed using Roche Linear Array Assay detecting 37 HPV types. Women with CIN2 regression showed significantly higher baseline levels of TLR2 (p = 0.006) and TLR7 (p = 0.007), as well as a non‐significant trend for a higher TLR8 expression (p = 0.053) compared to women with CIN2 persistence/progression. Six women with CIN2 regression, who presented with an HR‐HPV DNA‐negative CIN2 lesion at study entry, had significantly higher baseline levels of TLR2 (p = 0.005), TLR7 (p = 0.013) and TLR8 (p = 0.012), compared to women with CIN2 persistence/progression, suggesting their role in clearance of HPV prior to clearance of the lesion. Our results confirm a key role of TLRs in regression of CIN2 and support the potential use of TLR‐agonists for treatment of these lesions.
LRRK1 regulation of actin assembly in osteoclasts involves serine 5 phosphorylation of L‐plastin
Authors: Si Mingjue , Goodluck Helen , Zeng Canjun , Pan Songqin , Todd Elizabeth M. , Morley Sharon Celeste , Qin Xuezhong , Mohan Subburaman , Xing Weirong
Published: August 2018

Mice with disruption of Lrrk1 and patients with nonfunctional mutant Lrrk1 exhibit severe osteopetrosis phenotypes because of osteoclast cytoskeletal dysfunction. To understand how Lrrk1 regulates osteoclast function by modulating cytoskeleton rearrangement, we examined the proteins that are differentially phosphorylated in wild‐type mice and Lrrk1‐deficient osteoclasts by metal affinity purification coupled liquid chromatography/mass spectrometry (LC/MS) analyses. One of the candidates that we identified by LC/MS is L‐plastin, an actin bundling protein. We found that phosphorylation of L‐plastin at serine (Ser) residues 5 was present in wild‐type osteoclasts but not in Lrrk1‐deficient cells. Western blot analyses with antibodies specific for Ser5 phosphorylated L‐plastin confirmed the reduced L‐plastin Ser5 phosphorylation in Lrrk1 knockout (KO) osteoclasts. micro computed tomography (Micro‐CT) analyses revealed that the trabecular bone volume of the distal femur was increased by 27% in the 16 to 21‐week‐old L‐plastin KO females as compared with the wild‐type control mice. The ratio of bone volume to tissue volume and connectivity density were increased by 44% and 47% (both P < 0.05), respectively, in L‐plastin KO mice. Our data suggest that targeted disruption of L‐plastin increases trabecular bone volume, and phosphorylation of Ser5 in L‐plastin in the Lrrk1 signaling pathway may in part contribute to actin assembly in mature osteoclasts.
Experiences of First‐Year Engineering Students Working on Ill‐Structured Problems in Teams
Authors: Dringenberg Emily , Purzer Şenay
Published: August 2018

Background

As engineers solve problems that are ill‐structured and require collaboration, a common goal of engineering programs is to develop students' competencies for solving such problems in teams, often using cornerstone design experiences.

Purpose

With the goal of designing effective learning environments, this study identifies qualitatively different ways that engineering students experienced ill‐structured problems while working in teams.

Design/Method

This phenomenographic study employs interview data from 27 first‐year engineering students. Iterative data analysis resulted in categories of student experiences and their logical relationships.

Results

Seven categories describing collaborative, ill‐structured problem‐solving experiences emerged: completion, transition, iteration, organization, collaboration, reasoning, and growth. These categories are organized in an outcome space along dimensions we call reaction to ambiguity and use of multiple perspectives that can be used to frame students' perspectives from less comprehensive to more comprehensive.

Conclusions

First‐year engineering students experience team‐based, ill‐structured problem solving in a variety of ways. The resulting outcome space is of practical use to educators who teach courses involving collaborative, ill‐structured problem solving.
Clinical features and seasonal variations in the prevalence of macrolide‐resistant Mycoplasma pneumoniae
Authors: Akashi Yusaku , Hayashi Daisuke , Suzuki Hiromichi , Shiigai Masanari , Kanemoto Koji , Notake Shigeyuki , Ishiodori Takumi , Ishikawa Hiroichi , Imai Hironori
Published: August 2018

Background

Mycoplasma pneumoniae is a common pathogen causing pneumonia; macrolide‐resistant strains are rapidly spreading across Japan. However, the clinical features of macrolide‐resistant M. pneumoniae pneumonia have not been well established. Here, we evaluated the clinical characteristics and seasonal variations in the prevalence of M. pneumoniae with macrolide‐resistant mutations (MRM).

Methods

The monthly prevalence of MRM in M. pneumoniae strains isolated from May 2016 to April 2017 was retrospectively analyzed, and the clinical characteristics of pneumonia cases with MRM were compared to those of cases without MRM. The M. pneumoniae isolates and point mutations at site 2063 or 2064 in domain V of 23S rRNA were evaluated by the GENECUBE system and GENECUBE Mycoplasma detection kit.

Results

Mycoplasma pneumoniae infection was identified in 383 cases, including 221 cases of MRM (57.7%). The MRM prevalence was 86.3% (44/51) between May and July 2016, demonstrating an apparent decrease in September 2016, subsequently reaching 43.0% (34/79) in November 2016. Mycoplasma pneumoniae pneumonia was diagnosed in 275 cases, including 222 pediatric and 53 adult cases. Macrolide use preceding evaluation was found to be the only feature of MRM pneumonia cases both in children (odds ratio [OR] 3.86, 95% confidence interval [CI]:1.72–8.66) and in adults (OR 7.43, 95% CI: 1.67–33.1).

Conclusions

The determination rate of MRM varied widely throughout the year, and our study demonstrated the challenges in predicting M. pneumoniae with MRM based on clinical features at diagnosis. Therefore, continuous monitoring of the prevalence of MRM is warranted, which may help in selecting an effective treatment.
Risk factors for postoperative infection after gastrointestinal surgery among adult patients with inflammatory bowel disease: Findings from a large observational US cohort study
Authors: Liang Huifang , Jiang Baoguo , Manne Sudhakar , Lissoos Trevor , Bennett Dimitri , Dolin Paul
Published: August 2018

Background and Aim

Postoperative infection (POI) is a major source of morbidity and prolongation of hospitalization in inflammatory bowel disease (IBD) patients. This large observational study was conducted to further describe risk factors and to quantify the proportion of POIs that are preventable.

Methods

We conducted a retrospective cohort analysis of the Optum US health insurance claims database. The study population included adults with ulcerative colitis (UC) or Crohn's disease (CD) who underwent lower gastrointestinal (GI) surgery of small intestine, colon, rectum, or anus during September 2014 to September 2016. Multiple logistic regression was used to identify and quantify risk factors and determine the proportion of infections that are preventable.

Results

A total of 3360 adult IBD patients with lower GI surgery were included in the study. Their mean age was 51 years, 52.5% were women, and 59.5% had CD. The 30‐day POI incidence was 15.1% (95% confidence interval: 14.0–16.4%). We identified the following nonmodifiable or procedural risk factors: history of POI, open procedure, red blood cell transfusion within 6 months, preoperative hospital stay of at least 4 days, lower GI ostomy surgery, lower GI resection surgery, and a history of chronic obstructive pulmonary disease. Modifiable risk factors included corticosteroid use and anemia prior to surgery, but few infections were attributable to these modifiable factors.

Conclusions

This large, observational, real‐world evidence study from the US found that the majority of the observed risk factors were nonmodifiable or procedure‐related. Corticosteroid use and anemia before surgery were identified as modifiable risk factors.
Health care risk managers' consensus on the management of inappropriate behaviors among hospital staff
Authors: Zadeh Sahar Ebrahim , Haussmann Robert , Barton Craig D.
Published: August 2018

Medical errors are the third‐leading cause of death in the United States. One of the problems is timely recognition and management of inappropriate health care worker behaviors that lead to intimidation and loss of staff focus, eventually leading to errors. The purpose of this qualitative modified Delphi study was to seek consensus among a panel of experts in hospital risk management practices on the practical methods for early detection of inappropriate behaviors among hospital staff, which may be used by hospital managers to considerably mitigate the risk of medical mishaps. High reliability theory guided the research process, utilizing the conceptual framework of the fair and just culture patient safety model. A single research question asked what level of consensus exists among hospital risk management experts as to the practical methods for early detection of inappropriate behavior among hospital staff, which managers may use to ultimately mitigate the risk of preventable medical mishaps. This study included nonprobability purposive sampling (n = 34) and three rounds of questionnaires. Consensus was reached on 8 factors: setting expectations, developing a culture of respect, holding staff accountable, enforcing a zero‐tolerance policy, confidentiality of reporting, communicating expected behavior, open communication, and investigating inappropriate behaviors.
Single‐step purification and characterization of antifreeze proteins from leaf and berry of a freeze‐tolerant shrub seabuckthorn (Hippophae rhamnoides)
Authors: Sharma Bhavana , Sahoo Dinabandhu , Deswal Renu
Published: August 2018

Seabuckthorn is a freeze‐tolerant Himalayan shrub, capable of withstanding temperatures below −40°C. Antifreeze proteins prevent freezing associated damage by restricting ice crystals growth. In the present study, homogenous purification of two antifreeze proteins (41 and 39 kDa) from Hippophae rhamnoides leaf and one (41 kDa) from berry was performed using ice‐affinity chromatography. MS identification and Basic Local Alignment Search Tool search showed homology of berry antifreeze proteins with disease resistance protein while leaf antifreeze proteins showed similarity with transmembrane protein (39 kDa) and low temperature induced protein (41 kDa) suggesting their role in cold stress signalling. Hexagon shaped ice crystals (Nanoliter osmometer) and ice recrystallization inhibition assay (Splat assay) confirmed higher ice recrystallization inhibition activity of purified leaf (2.5 fold decrease in mean ice crystal size) and berry (2.1 fold decrease) antifreeze proteins. String interactome analysis showed interaction of antifreeze proteins with cold stress modulated targets including pathogenesis related proteins. This probably is the first report of antifreeze proteins purification from naturally growing seabuckthorn. Further validation of these targets may open gates for commercial utilization of this plant growing abundantly in Himalayan regions of India, for crop improvement of freeze susceptible crops or biomedical applications like cryopreservation of tissues and cells.
A simple, sensitive, and straightforward LC–MS approach for rapid analysis of three potential genotoxic impurities in rabeprazole formulations
Authors: Yenugu Veera Manohara Reddy , Ambavaram Vijaya Bhaskar Reddy , Moniruzzaman Muhammad , Madhavi Gajulapalle
Published: August 2018

In the present study, a sensitive and fully validated liquid chromatography with mass spectrometry method was developed for the quantification of three potential genotoxic impurities in rabeprazole drug substance. The separation was achieved on Symmetry C18 column (100 × 4.6 mm, 3.5 μm) using 0.1% formic acid in water as mobile phase A and acetonitrile as mobile phase B in gradient elution mode at 0.5 mL/min flow rate. Triple quadrupole mass detection with electrospray ionization was operated in selected ion recording mode for the quantification of impurities. The calibration curves were demonstrated good linearity over the concentration range of 1.0–4.5 ppm for O‐phenylenediamine, 1.8–4.5 ppm for 4‐nitrolutidine‐N‐oxide and 1.0–4.5 ppm for benzyltriethylammonium chloride with respect to 10 mg/mL of rabeprazole. The correlation coefficient obtained in each case was >0.998. The recoveries were found satisfactory over the range between 94.22 and 106.84% for all selected impurities. The method validation was carried out following International Conference on Harmonization guidelines, from which the developed method was able to quantitate the impurities at 1.0 ppm for O‐phenylenediamine, 1.8 ppm for 4‐nitrolutidine‐N‐oxide and 1.0 ppm for benzyltriethylammonium chloride. Furthermore, the proposed method was successfully evaluated for the determination of selected impurities from bulk drug and formulation samples of rabeprazole within the acceptable limits.
Placental Pulsatility: Quantitative Assessment of Placental Bed Vasculature by 2‐Dimensional Doppler Cine Imaging
Authors: Schwartz Nadav , Siegal Julia , Rourke Aaron , Sehgal Chandra M.
Published: August 2018

Objectives

Vascular resistance is known to be one of the determinants of pulsatile flow. This study aimed to investigate whether quantitative 2‐dimensional Doppler ultrasound can capture and evaluate the pulsatility within the placental bed vasculature.

Methods

The placental bed vasculature was imaged by directional power Doppler ultrasound. Ten‐second cine clips were recorded by using standardized machine settings. A region of interest with a prominent Doppler signal in the uteroplacental interface was analyzed for the percentage of vascularity to generate a time‐vascularity waveform. A vascular pulsatility index representing variation over the cardiac cycle was calculated by the ratio of the systolic‐diastolic difference in vascularity to the mean vascularity. The acquisitions were repeated with 6 different pulse repetition frequencies (PRFs) and 3 wall motion filter (WMF) settings to evaluate their impact on the Doppler measurements.

Results

Ten sets of cine clips were analyzed for this study. The pulsatile nature of the vascularity was readily apparent in each cine clip. The measured time‐vascularity waveforms showed uniform cyclic variation in vascularity over the cardiac cycle, with systolic vascularity significantly higher than diastolic vascularity at each combination of PRF and WMF (P < .05). A gradual increase in the vascular pulsatility index was observed with an increasing PRF or WMF. Normalization of systolic‐to‐diastolic measurement provided a stable vascular assessment across the range of PRFs.

Conclusions

Doppler cine clips provide a dynamic representation of the placental bed vasculature and a novel analytic approach to quantitatively evaluating the pulsatility of this critical vascular network. Further work is warranted to explore the reproducibility and clinical potential of this approach.
CLEAR: A Novel Approach to Ultrasound Equipment Homeostasis
Authors: Prats Michael I. , Nelson Bret P. , Gold Delia L. , Branditz Lauren D. , Boulger Creagh T. , Bahner David P.
Published: August 2018

Protocols for the sanitation and maintenance of point‐of‐care ultrasound (US) equipment are lacking. This study introduces the CLEAR protocol (clean, locate, energize, augment supplies, and remove patient identifiers) as a tool to improve the readiness of US equipment, termed US equipment homeostasis. The state of US equipment homeostasis in the emergency department of a single academic center was investigated before and after implementing this protocol, with an improvement in outcomes. These findings demonstrate that the CLEAR protocol can improve US homeostasis. CLEAR can function as a teaching tool to promote homeostasis as well as a checklist to assess compliance.
Experimental evidence reveals impact of drought periods on dissolved organic matter quality and ecosystem metabolism in subalpine streams
Authors: Harjung Astrid , Ejarque Elisabet , Battin Tom , Butturini Andrea , Sabater Francesc , Stadler Masumi , Schelker Jakob
Published: August 2018

Subalpine streams are predicted to experience lower summer discharge following climate change and water extractions. In this study, we aimed to understand how drought periods impact dissolved organic matter (DOM) processing and ecosystem metabolism of subalpine streams. We mimicked a gradient of drought conditions in stream‐side flumes and evaluated implications of drought on DOM composition, gross primary production, and ecosystem respiration. Our experiment demonstrated a production and release of DOM from biofilms and leaf litter decomposition at low discharges, increasing dissolved organic carbon concentrations in stream water by up to 50%. Absorbance and fluorescence properties suggested that the released DOM was labile for microbial degradation. Dissolved organic carbon mass balances revealed a high contribution of internal processes to the carbon budget during low flow conditions. The flumes with low discharge were transient sinks of atmospheric CO2 during the first 2 weeks of drought. After this autotrophic phase, the metabolic balance of these flumes turned heterotrophic, suggesting a nutrient limitation for primary production, while respiration remained high. Overall our experimental findings suggest that droughts in subalpine streams will enhance internal carbon cycling by transiently increasing primary production and more permanently respiration as the drought persists. We propose that the duration of a drought period combined with inorganic nutrient availability are key variables that determine if more carbon is respired in situ or exported downstream.
Enhancement of Out‐of‐Plane Hole Mobility in Poly(3‐Hexylthiophene)‐b‐Poly(styrene) Film
Authors: Tomita Eri , Kim Kyusun , Minegishi Kazushi , Nakamura Akitaka , Kanehashi Shinji , Ogino Kenji
Published: August 2018

Two or three orders of higher magnitude out‐of‐plane hole mobilities are observed in the films of poly(3‐hexylthiophene)‐b‐poly(styrene) (P3HT‐b‐PSt) compared with those of P3HT fabricated with the same conditions in a diode geometry. From grazing incidence wide angle X‐ray diffraction analysis, it is found that there is a trend that PSt domains hinder the growth of alkyl stacking, and promote that of the π–π stacking. Differential scanning calorimetry thermogram of P3HT‐b‐PSt exhibits distinct double endothermic peaks, and double glass transitions. The larger change of heat capacity in glass transition at higher temperature indicates that the larger content of rigid amorphous region exists compared with P3HT. It is considered that the higher content of rigid amorphous domain (short‐range ordered packing) interconnects the crystallites (long‐range ordered packing) leading to the extraordinary higher mobility in P3HT‐b‐PSt film.
Dual innervation may occur in a partially denervated muscle
Authors: Obongo Rais , Bon‐Mardion Nicolas , Duclos Celia , Strunski Vladimir , Guerout Nicolas , Marie Jean‐Paul
Published: August 2018

Introduction: With a view to simplifying surgical techniques for selective laryngeal reinnervation, we addressed the question of whether it is feasible to receive additional innervation by a partially denervated muscle using an infrahyoid muscle model. Methods: In 90 rats (6 groups of 15), phrenic nerve transfer was used to reinnervate the sternothyroid muscle. In some cases, residual innervation by the original nerve was present. Three months later we performed electromyographic studies, contraction strength measurements, histologic assessment, and retrograde labeling. Results: Muscles reinnervated by the phrenic nerve had a greater “dual‐response” rate (in terms of nerve latency, contraction strength, and retrograde labeling) than muscles in the control groups. Discussion: The phrenic nerve can impart its inspiratory properties to an initially denervated strap muscle—even when residual innervation is present. The preservation of contractile potential confirmed the feasibility of dual innervation in a previously injured muscle. Muscle Nerve 59:108–115, 2019
Size and shape analysis of Trioza erytreae Del Guercio (Hemiptera: Triozidae), vector of citrus huanglongbing disease
Authors: Aidoo Owusu F , Tanga Chrysantus M , Paris Thomson M , Allan Sandra A , Mohamed Samira A , Khamis Fathiya M , Sétamou Mamoudou , Borgemeister Christian , Ekesi Sunday
Published: August 2018

BACKGROUND

The African citrus triozid (ACT) Trioza erytreae Del Guercio (Hemiptera: Triozidae) is one of the most devastating pests of citrus with a well‐known role as a vector of the phloem‐limited bacteria (Candidatus Liberibacter africanus) associated with huanglongbing (citrus greening disease), currently considered the world's most serious disease of citrus. Although the pest can successfully develop and reproduce on non‐citrus host plants, there is no documented information on the geometric morphometry of ACT. We determine the effect of host plants on ACT morphometry under controlled laboratory conditions using traditional and geometric analysis.

RESULTS

ACT reared on C. limon and Citroncirus spp. was significantly larger than when reared on the other host plant species. ACT reared on C. anisata and C. tangelo was consistently smaller than that reared on M. koenigii and C. sinensis. Based on warped outline drawings, ACT reared on Citroncirus spp. and Murraya koenigii had narrower wings than when reared on C. anisata, C. limon, and C. sinensis with slightly broader wing patterns.

CONCLUSION

This study clearly demonstrates that host plant species affect morphometric variation in ACT, which might have a direct impact on fitness parameters of the pest as well as its potential for dispersion. Wing shape and size appear to be useful in separating populations of ACT into different groups. © 2018 Society of Chemical Industry
Phytotherapic use of the Crocus sativus L. (Saffron) and its potential applications: A brief overview
Authors: Leone Sheila , Recinella Lucia , Chiavaroli Annalisa , Orlando Giustino , Ferrante Claudio , Leporini Lidia , Brunetti Luigi , Menghini Luigi
Published: August 2018

Crocus sativus L. (Saffron) has long been known for multiple target therapeutic uses. The plant metabolism is well investigated and the main metabolites related to saffron organoleptic qualities are crocin, crocetin, picrocrocin, and safranal. Particularly, the most abundant of them, such as crocin and safranal, are investigated for their multiple biological activities and known as potential drugs. We aimed to review the constituent features of the plant, along with its potential therapeutic effects in depression, neurodegenerative diseases, diabetes mellitus, atherosclerosis, cancer, and sexual dysfunction. A systematic literature search was conducted in PubMed, Medline, Scopus, and EMBASE, with particular attention to preclinical and clinical studies. Although saffron and its components showed potential clinical applications, further investigations are necessary to confirm the effective use of “Red Gold” and its real applications in clinical practice.
Multichannel Singular Spectrum Analysis in the Estimates of Common Environmental Effects Affecting GPS Observations
Authors: Gruszczynska Marta , Rosat Severine , Klos Anna , Gruszczynski Maciej , Bogusz Janusz
Published: August 2018

We described a spatio-temporal analysis of environmental loading models: atmospheric, continental hydrology, and non-tidal ocean changes, based on multichannel singular spectrum analysis (MSSA). We extracted the common annual signal for 16 different sections related to climate zones: equatorial, arid, warm, snow, polar and continents. We used the loading models estimated for a set of 229 ITRF2014 (International Terrestrial Reference Frame) International GNSS Service (IGS) stations and discussed the amount of variance explained by individual modes, proving that the common annual signal accounts for 16, 24 and 68% of the total variance of non-tidal ocean, atmospheric and hydrological loading models, respectively. Having removed the common environmental MSSA seasonal curve from the corresponding GPS position time series, we found that the residual station-specific annual curve modelled with the least-squares estimation has the amplitude of maximum 2 mm. This means that the environmental loading models underestimate the seasonalities observed by the GPS system. The remaining signal present in the seasonal frequency band arises from the systematic errors which are not of common environmental or geophysical origin. Using common mode error (CME) estimates, we showed that the direct removal of environmental loading models from the GPS series causes an artificial loss in the CME power spectra between 10 and 80 cycles per year. When environmental effect is removed from GPS series with MSSA curves, no influence on the character of spectra of CME estimates was noticed.
$$ \mathcal{N}=2 $$ moduli of AdS4 vacua: a fine-print study
Authors: Bachas Constantin , Bianchi Massimo , Hanany Amihay
Published: August 2018

Abstract

We analyze the moduli spaces near

$$ \mathcal{N}=4 $$

N
=
4

supersymmetric AdS4 vacua of string theory by combining and comparing various approaches: (a) the known exact solutions of Type IIB string theory with localized 5-brane sourcees; (b) the holographically dual 3d quiver gauge theories; (c) gauged supergravity; and (d) the representations of the superconformal algebra

$$ \mathfrak{o}\mathfrak{s}\mathfrak{p}\left(4\left|4\right|\right) $$

o
s
p

4

4

. Short multiplets containing the marginal

$$ \mathcal{N}=2 $$

N
=
2

deformations transform in the (2; 0), (0; 2) or (1; 1) representations of the R-symmetry group SU(2)
H

× SU(2)
C
. The first two are classified by the chiral rings of the Higgs and Coulomb branches, while the latter contain mixed-branch operators. We identify the origin of these moduli in string theory, matching in particular the operators of the chiral rings with open strings on the magnetized 5-brane sources. Our results provide new evidence for the underlying holographic duality. The existence of a large number of bound-state moduli highlights the limitations of effective supergravity.
Soft-drop thrust
Authors: Baron Jeremy , Marzani Simone , Theeuwes Vincent
Published: August 2018

Abstract

Soft drop, a technique originally developed in the context of jet physics in proton-proton collisions in order to reduce the contamination from non-perturbative effects, is applied to event shapes in electron-positron annihilation. In particular, we study the thrust distribution at the Z pole and show that the region where non-perturbative corrections due to the hadronisation process are small is considerably extended if soft drop is applied. Therefore, we argue that the use of soft drop to reduce hadronisation effects is potentially of great benefit in the context of strong coupling determination using event shapes, which would be otherwise characterised by a strong correlation between α

s
and non-perturbative parameters. However, reduced sensitivity to hadronisation corrections is only one of the aspects that need to be considered. In this context, we show that perturbative calculability, especially away from the soft and collinear region of the event-shape spectrum, has a nontrivial interplay with the soft-drop observable of choice. To this purpose, besides thrust, we investigate the behaviour of the hemisphere mass as well as the jet mass. We find that the latter shows the most promising behaviour in the intermediate region of the spectrum, especially if small jet radii are considered.
Geroch group description of bubbling geometries
Authors: Roy Pratik , Virmani Amitabh
Published: August 2018

Abstract

The Riemann-Hilbert approach to studying solutions of supergravity theories allows us to associate spacetime independent monodromy matrices (matrices in the Geroch group) with solutions that effectively only depend on two spacetime coordinates. This offers insights into symmetries of supergravity theories, and in the classification of their solutions. In this paper, we initiate a systematic study of monodromy matrices for multi- center solutions of five-dimensional U(1)3 supergravity. We obtain monodromy matrices for a class of collinear Bena-Warner bubbling geometries. We show that for this class of solutions, monodromy matrices in the vector representation of SO(4,4) have only simple poles with residues of rank two and nilpotency degree two. These properties strongly suggest that an inverse scattering construction along the lines of [arXiv:1311.7018 [hep-th]] can be given for this class of solutions, though it is not attempted in this work. Along the way, we clarify a technical point in the existing literature: we show that the so-called “spectral flow transformations” of Bena, Bobev, and Warner are precisely a class of Harrison transformations when restricted to the situation of two commuting Killing symmetries in five-dimensions.
Improvement of butanol production in Clostridium acetobutylicum through enhancement of NAD(P)H availability
Authors: Qi Feng , Thakker Chandresh , Zhu Fayin , Pena Matthew , San Ka-Yiu , Bennett George N
Published: August 2018

Clostridium acetobutylicum is a natural producer of butanol, butyrate, acetone and ethanol. The pattern of metabolites reflects the partitioning of redox equivalents between hydrogen and carbon metabolites. Here the exogenous genes of ferredoxin-NAD(P)+ oxidoreductase (FdNR) and trans-enoyl-coenzyme reductase (TER) are introduced to three different Clostridium acetobutylicum strains to investigate the distribution of redox equivalents and butanol productivity. The FdNR improves NAD(P)H availability by capturing reducing power from ferredoxin. A butanol production of 9.01 g/L (36.9% higher than the control), and the highest ratios of butanol/acetate (7.02) and C4/C2 (3.17) derived metabolites were obtained in the C acetobutylicum buk- strain expressing FdNR. While the TER functions as an NAD(P)H oxidase, butanol production was decreased in the C. acetobutylicum strains containing TER. The results illustrate that metabolic flux can be significantly changed and directed into butanol or butyrate due to enhancement of NAD(P)H availability by controlling electron flow through the ferredoxin node.
Multifunctional Proteins: Involvement in Human Diseases and Targets of Current Drugs
Authors: Franco-Serrano Luis , Huerta Mario , Hernández Sergio , Cedano Juan , Perez-Pons JosepAntoni , Piñol Jaume , Mozo-Villarias Angel , Amela Isaac , Querol Enrique
Published: August 2018

Multifunctionality or multitasking is the capability of some proteins to execute two or more biochemical functions. The objective of this work is to explore the relationship between multifunctional proteins, human diseases and drug targeting. The analysis of the proportion of multitasking proteins from the MultitaskProtDB-II database shows that 78% of the proteins analyzed are involved in human diseases. This percentage is much higher than the 17.9% found in human proteins in general. A similar analysis using drug target databases shows that 48% of these analyzed human multitasking proteins are targets of current drugs, while only 9.8% of the human proteins present in UniProt are specified as drug targets. In almost 50% of these proteins, both the canonical and moonlighting functions are related to the molecular basis of the disease. A procedure to identify multifunctional proteins from disease databases and a method to structurally map the canonical and moonlighting functions of the protein have also been proposed here. Both of the previous percentages suggest that multitasking is not a rare phenomenon in proteins causing human diseases, and that their detailed study might explain some collateral drug effects.
Re-engaging with Sustainability in the Anthropocene Era
Authors: Hoffman Andrew J. , Jennings P. Devereaux
Published: August 2018

Re-engaging with Sustainability in the Anthropocene Era applies organization theory to a grand challenge: our entry into the Anthropocene era, a period marked not only by human impact on climate change, but on chemical waste, habitat destruction, and despeciation. It focuses on institutional theory, modified by political readings of organizations, as one approach that can help us navigate a new course. Besides offering mechanisms, such as institutional entrepreneurship, social movements, and policy shifts, the institutional-political variant developed here helps analysts understand the framing of scientific facts, the counter-mobilization of skeptics, and the creation of archetypes as new social orders.
IS TRUE BELIEF REALLY A FUNDAMENTAL EPISTEMIC VALUE?
Authors: Aschliman Lance K.
Published: August 2018

In this paper, I question the orthodox position that true belief is a fundamental epistemic value. I begin by raising a particularly epistemic version of the so-called “value problem of knowledge” in order to set up the basic explanandum and to motivate some of the claims to follow. In the second section, I take aim at what I call “bottom-up approaches” to this value problem, views that attempt to explain the added epistemic value of knowledge in terms of its relation to a more fundamental value of true belief. The final section is a presentation of a value-theoretic alternative, one that explains the value problem presented in the first section while also doing justice to intuitions that may cause us to worry about bottom-up approaches. In short,knowledgeand not mere true belief is a fundamental epistemic value as it is the constitutive goal of propositional inquiry.
Particle-in-cell simulations of laser–plasma interactions at solid densities and relativistic intensities: the role of atomic processes
Authors: Wu D. , He X. T. , Yu W. , Fritzsche S.
Published: August 2018

Direct numerical simulation of intense laser–solid interactions is still of great challenges, because of the many coupled atomic and plasma processes, such as ionization dynamics, collision among charged particles and collective electromagnetic fields, to name just a few. Here, we develop a new particle-in-cell (PIC) simulation code, which enables us to calculate laser–solid interactions in a more realistic way. This code is able to cover almost ‘all’ the coupled physical processes. As an application of the new code, the generation and transport of energetic electrons in front of and within the solid target when irradiated by intense laser beams are studied. For the considered case, in which laser intensity is$10^{20}~\text{W}\cdot \text{cm}^{-2}$and pre-plasma scale length in front of the solid is$10~\unicode[STIX]{x03BC}\text{m}$, several quantitative conclusions are drawn: (i) the collisional damping (although it is very weak) can significantly affect the energetic electrons generation in front of the target, (ii) the Bremsstrahlung radiation will be enhanced by 2–3 times when the solid is dramatically heated and ionized, (iii) the ‘cut-off’ electron energy is lowered by an amount of 25% when both collision damping and Bremsstrahlung radiations are included, and (iv) the resistive electromagnetic fields due to Ohmic heating play nonignorable roles and must be taken into account in such interactions.
A study of cascading failures in real and synthetic power grid topologies
Authors: SPIEWAK RUSSELL , SOLTAN SALEH , FORMAN YAKIR , BULDYREV SERGEY V. , ZUSSMAN GIL
Published: August 2018

Using the direct current power flow model, we study cascading failures and their spatial and temporal properties in the U.S. Western Interconnection (USWI) power grid. We show that yield (the fraction of demand satisfied after the cascade) has a bimodal distribution typical of a first-order transition. The single line failure leads either to an insignificant power loss or to a cascade which causes a major blackout with yield less than 0.8. The former occurs with high probability if line tolerance α (the ratio of the maximal load a line can carry to its initial load) is greater than 2, while a major blackout occurs with high probability in a broad range of 1 < α < 2. We also show that major blackouts begin with a latent period (with duration proportional to α) during which few lines overload and yield remains high. The existence of the latent period suggests that intervention during early stages of a cascade can significantly reduce the risk of a major blackout. Finally, we introduce the preferential Degree And Distance Attachment model to generate random networks with similar degree, resistance, and flow distributions to the USWI. Moreover, we show that the Degree And Distance Attachment model behaves similarly to the USWI against failures.
When Do the Advantaged See the Disadvantages of Others? A Quasi-Experimental Study of National Service
Authors: MO CECILIA HYUNJUNG , CONN KATHARINE M.
Published: August 2018

Are there mechanisms by which the advantaged can see the perspectives of the disadvantaged? If advantaged individuals have prolonged engagement with disadvantaged populations and confront issues of inequality through national service, do they see the world more through the lens of the poor? We explore this question by examining Teach For America (TFA), as TFA is a prominent national service program that integrates top college graduates into low-income communities for two years and employs a selection model that allows for causal inference. A regression discontinuity approach, utilizing an original survey of over 32,000 TFA applicants and TFA’s selection data for the 2007–2015 application cycles, reveals that extended intergroup contact in a service context causes advantaged Americans to adopt beliefs that are closer to those of disadvantaged Americans. These findings have broad implications for our understanding of the impact of intergroup contact on perceptions of social justice and prejudice reduction.