bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of Mn, Li2O and LiF in the JSI TRIGA reactor to study potential tritium production monitors for fusion applications
Authors: Kodeli I. , Radulović V. , Veniger G. , Kavšek D. , Kuc T. , Ciechanowski M. , Pohorecki W.
Published: May 2019

Two series of measurements were performed in the JSI TRIGA research reactor in 2014 and 2017 to validate the 55Mn(n,γ)56Mn cross-sections and experimentally investigate the relationship between the 55Mn(n,γ)56Mn reaction and the rate of tritium production through the 6Li(n,t)4He reaction. Indeed, previously observed similarities between the sensitivity profiles of the neutron reaction of tritium production on lithium, 6Li(n,t)4He, and those of the 55Mn(n,γ)56Mn reaction in tritium breeder modules indicated that the latter reaction could be used as an effective monitor of tritium production, at least for short-term monitoring (the half-life of 56Mn being 2.579 h). However, experimental verification, improvements and validation of the 55Mn(n,γ)56Mn cross-sections are needed in order to meet the required accuracy. Foils of certified reference material Al–1%Mn, as well as LiF thermoluminescent detectors and Li2O samples were irradiated, both bare and under cadmium, to study the potential use of the 55Mn(n,γ)56Mn reaction for monitoring tritium production in fusion devices. Additionally, Al–0.1%Au was also irradiated for comparison, the 197Au(n,γ)198Au reaction cross-section being a standard. In order to obtain complementary information for data validation purposes, the irradiations were performed in positions within the JSI TRIGA reactor with different neutron spectra, i.e. in the central channel, the pneumatic tube and the F19 position, both in the outer ‘F’ ring of the reactor core and in the IC-40 irradiation channel located in the graphite reflector surrounding the reactor core. Bare and cadmium-covered irradiations were needed to subtract the contribution of epithermal neutrons to the 55Mn(n,γ)56Mn reaction. Calculations of the reaction rates were performed using the Monte Carlo code MCNP6.1 with a detailed model of the JSI TRIGA reactor, with the samples, the irradiation capsules and covers being modelled explicitly. The uncertainties involved in the measurements and the calculations were carefully evaluated. The principal objective was to study the energy response and correlations between the 55Mn(n,γ)56Mn reaction in irradiated Al–1%Mn and the 6Li(n,t)4He reaction in irradiated LiF and Li2O. Good consistency between the measured and calculated 55Mn(n,γ)56Mn and 197Au(n,γ)198Au reaction rates, in most cases within the uncertainty bars, was observed.
Anomalous optical saturation of low-energy Dirac states in graphene and its implication for nonlinear optics
Authors: Semnani Behrooz , Jago Roland , Safavi-Naeini Safieddin , Majedi Hamed , Malic Ermin , Tassin Philippe
Published: May 2019

We reveal that optical saturation of the low-energy states takes place in graphene for arbitrarily weak electromagnetic fields. This effect originates from the diverging field-induced interband coupling at the Dirac point. Using semiconductor Bloch equations to model the electronic dynamics of graphene, we argue that the charge carriers undergo ultrafast Rabi oscillations leading to the anomalous saturation effect. The theory is complemented by a many-body study of the carrier relaxations dynamics in graphene. It will be demonstrated that the carrier relaxation dynamics is slow around the Dirac point, which in turn leads to a more pronounced saturation. The implications of this effect for the nonlinear optics of graphene are then discussed. Our analysis shows that the conventional perturbative treatment of the nonlinear optics, i.e. expanding the polarization field in a Taylor series of the electric field, is problematic for graphene, in particular at small Fermi levels and large field amplitudes.
Risk Factors for Bites and Diseases Associated With Black-Legged Ticks: A Meta-Analysis
Authors: Fischhoff Ilya R , Keesing Felicia , Ostfeld Richard S
Published: May 2019

The emergence and spread of Lyme disease and other infections associated with black-legged ticks is causing a public health crisis. No human vaccines are currently available, and both diagnosis and treatment are sometimes ineffectual, leading to advocacy for self-directed preventative measures. These recommendations are widely communicated to the public, but there is limited evidence for their efficacy. We undertook a systematic review and mixed-effects meta-regression analysis of factors purported to increase or decrease risk of black-legged tick bites and tick-borne disease. Published articles used in the study spanned the years 1984–2018. Variables associated with increased probability of tick-borne disease, with odds ratios significantly greater than 1, included deer abundance, high density of nymph-stage black-legged ticks, landscapes with interspersed herbaceous and forested habitat, low human population density, gardens, cat ownership, and race. Contrary to recommendations, use of landscape-related tick control measures, such as clearing brush, trimming branches, and having a dry barrier between lawn and woods, tended to increase risk. Pet ownership increased bite risk. Bite risk was highest for children aged 5 years or less, with a secondary peak in persons aged 50–70 years. Although some widely disseminated recommendations are supported by the research analyzed, others require further evaluation. Additional research is also needed to understand the mechanisms underlying significant relationships.
Pharmacy students’ attitudes and perceptions toward pharmacogenomics education
Authors: Coriolan Shanice , Arikawe Nimota , Moscati Arden , Zhou Lisheng , Dym Stephanie , Donmez Seda , Garba Adinoyi , Falbaum Sasha , Loewy Zvi , Lull Melinda , Saad Maha , Shtaynberg Jane , Obeng Aniwaa Owusu
Published: May 2019

Purpose

To evaluate final-year pharmacy students’ perceptions toward pharmacogenomics education, their attitudes on its clinical relevance, and their readiness to use such knowledge in practice.

Methods

A 19-question survey was developed and modified from prior studies and was pretested on a small group of pharmacogenomics faculty and pharmacy students. The final survey was administered to 978 final-year pharmacy students in 8 school/colleges of pharmacy in New York and New Jersey between January and May 2017. The survey targeted 3 main themes: perceptions toward pharmacogenomics education, attitudes toward the clinical relevance of this education, and the students’ readiness to use knowledge of pharmacogenomics in practice.

Results

With a 35% response rate, the majority (81%) of the 339 student participants believed that pharmacogenomics was a useful clinical tool for pharmacists, yet only 40% felt that it had been a relevant part of their training. Almost half (46%) received only 1–3 lectures on pharmacogenomics and the majority were not ready to use it in practice. Survey results pointed toward practice-based trainings such as pharmacogenomics rotations as the most helpful in preparing students for practice.

Conclusions

Final-year student pharmacists reported varying exposure to pharmacogenomics content in their pharmacy training and had positive attitudes toward the clinical relevance of the discipline, yet they expressed low confidence in their readiness to use this information in practice.
The US Supreme Court does Kompetenz-Kompetenz
Authors: Samuel Adam
Published: May 2019

In Henry Schein and New Prime, the US Supreme Court reached two unanimous decisions on arbitration. Both cases in quite different ways gave rise to questions about the original German doctrine or version of Kompetenz-Kompetenz, the ability of the parties to submit by agreement their jurisdictional disputes to arbitration. Each decision, though, contains so much more. In Henry Schein, the court rejected the view that the court could effectively terminate an arbitration by concluding that the right to arbitrate was clearly not there. It required a proper enquiry including an investigation as to whether the AAA Commercial Rules constitute a Kompetenz-Kompetenz agreement. The facts presented suggested a more complex enquiry than that about the arbitrator's jurisdiction and powers. In New Prime, the Court applied the exclusion from the Federal Arbitration Act for employees engaged in interstate commerce to a self-employed lorry driver. It refused to save the clause on the basis on a Kompetenz-Kompetenz agreement or an inherent jurisdiction.
The relationship of body condition, superoxide dismutase, and superoxide with sperm performance
Authors: Friesen Christopher R , de Graaf Simon P , Olsson Mats
Published: May 2019

Sperm competition theory predicts a negative correlation between somatic investment and traits that aid in pre- and postcopulatory sexual selection. Sperm performance is critical for postcopulatory success but sperm are susceptible to damage by free radicals such as superoxide radicals generated during mitochondrial respiration (mtSOx). Males can ameliorate damage to spermatozoa by investing in the production of antioxidants, like superoxide dismutase (SOD), which may act as a mechanistic link to pre- and postcopulatory trade-offs. Some male Australian, color-polymorphic painted dragon lizards (Ctenophorus pictus) possess a yellow throat patch (bib) that females prefer over nonbibbed males and are also more likely to win male–male contests indicating that males with bibs may be better at monopolizing females. We tested whether the sperm performance in nonbibbed males was superior to that of bibbed males. We show that overall sperm performance was not different between the bib-morphs, however, higher mtSOx levels were negatively correlated with sperm performance in bibbed males, but not of nonbibbed males. Blood cell mtSOx levels are negatively correlated with SOD activity in the plasma in all males early in the breeding season but SOD was lower in bibbed males. Nonbibbed males maintain a positive correlation between body condition and SOD activity over time while bibbed males do not. Together, these data suggest physiological associations between body condition, SOD activity, and sperm performance are linked to the expression of a yellow gular patch, which may be related to intrinsic differences in the metabolism of bibbed versus nonbibbed males.
A critical review of five machine learning-based algorithms for predicting protein stability changes upon mutation
Authors: Fang Jianwen
Published: May 2019

A number of machine learning (ML)-based algorithms have been proposed for predicting mutation-induced stability changes in proteins. In this critical review, we used hypothetical reverse mutations to evaluate the performance of five representative algorithms and found all of them suffer from the problem of overfitting. This approach is based on the fact that if a wild-type protein is more stable than a mutant protein, then the same mutant is less stable than the wild-type protein. We analyzed the underlying issues and suggest that the main causes of the overfitting problem include that the numbers of training cases were too small, and the features used in the models were not sufficiently informative for the task. We make recommendations on how to avoid overfitting in this important research area and improve the reliability and robustness of ML-based algorithms in general.
Mutations in C1orf194, encoding a calcium regulator, cause dominant Charcot-Marie-Tooth disease
Authors: Sun Shun-Chang , Ma Di , Li Mei-Yi , Zhang Ru-Xu , Huang Cheng , Huang Hua-Jie , Xie Yong-zhi , Wang Zhong-Ju , Liu Jun , Cai De-Cheng , Liu Cui-Xian , Yang Qi , Bao Fei-Xiang , Gong Xiao-Li , Li Jie-Ru , Hui Zheng , Wei Xiao-feng , Zhong Jian-Mei , Zhou Wan-jun , Shang Xuan , Zhang Cheng , Liu Xing-Guo , Tang Bei-Sha , Xiong Fu , Xu Xiang-Min
Published: May 2019

Charcot-Marie-Tooth disease is a hereditary motor and sensory neuropathy exhibiting great clinical and genetic heterogeneity. Here, the identification of two heterozygous missense mutations in the C1orf194 gene at 1p21.2-p13.2 with Charcot-Marie-Tooth disease are reported. Specifically, the p.I122N mutation was the cause of an intermediate form of Charcot-Marie-Tooth disease, and the p.K28I missense mutation predominately led to the demyelinating form. Functional studies demonstrated that the p.K28I variant significantly reduced expression of the protein, but the p.I122N variant increased. In addition, the p.I122N mutant protein exhibited the aggregation in neuroblastoma cell lines and the patient’s peroneal nerve. Either gain-of-function or partial loss-of-function mutations to C1ORF194 can specify different causal mechanisms responsible for Charcot-Marie-Tooth disease with a wide range of clinical severity. Moreover, a knock-in mouse model confirmed that the C1orf194 missense mutation p.I121N led to impairments in motor and neuromuscular functions, and aberrant myelination and axonal phenotypes. The loss of normal C1ORF194 protein altered intracellular Ca2+ homeostasis and upregulated Ca2+ handling regulatory proteins. These findings describe a novel protein with vital functions in peripheral nervous systems and broaden the causes of Charcot-Marie-Tooth disease, which open new avenues for the diagnosis and treatment of related neuropathies.
Behavioral and Neural Responses to Vitamin C Solution in Vitamin C-deficient Osteogenic Disorder Shionogi/Shi Jcl-od/od Rats
Authors: Yasuo Toshiaki , Suwabe Takeshi , Sako Noritaka
Published: May 2019

To investigate the appetite for vitamin C (VC), we conducted behavioral and neural experiments using osteogenic disorder Shionogi/Shi Jcl-od/od (od/od) rats, which lack the ability to synthesize VC, and their wild-type controls osteogenic disorder Shionogi/Shi Jcl- +/+ (+/+) rats. In the behavioral study, rats were deprived of VC for 25 days and then received two-bottle preference tests with a choice between water and 10 mM VC. The preference for 10 mM VC solution of od/od rats was significantly greater than that of +/+ rats. In the neural study, the relative magnitudes of the whole chorda tympani nerve (CTN) responses to 100–1000 mM VC, 3–10 mM HCl, 100–1000 mM NaCl, and 20 mM quinine▪HCl in the VC-deficient rats were significantly smaller than those in the nondeficient ones. Further, we conducted additional behavioral experiments to investigate the appetite for sour and salty taste solutions of VC-deficient od/od rats. Preference scores for 3 mM citric acid increased in od/od rats after VC removal, compared with before, whereas preference scores for 100 and 150 mM NaCl were decreased in VC-deficient od/od rats. The preference for 300 mM NaCl was not changed. Hence, our results suggest that the reduction of the aversive taste of VC during VC deficiency may have involved the reduction of CTN responses to acids. Overall, our results indicate that VC-deficient rats ingest sufficient VC to relieve their deficiency and that VC deficiency causes changes in peripheral sensitivity to acids, but nongustatory factors may also affect VC intake and choice.
Domestic River Water Use and Risk of Typhoid Fever: Results From a Case-control Study in Blantyre, Malawi
Authors: Gauld Jillian S , Olgemoeller Franziska , Nkhata Rose , Li Chao , Chirambo Angeziwa , Morse Tracy , Gordon Melita A , Read Jonathan M , Heyderman Robert S , Kennedy Neil , Diggle Peter J , Feasey Nicholas A
Published: May 2019

Background

Typhoid fever remains a major cause of morbidity and mortality in low- and middle-income settings. In the last 10 years, several reports have described the reemergence of typhoid fever in southern and eastern Africa, associated with multidrug-resistant H58 Salmonella Typhi. Here, we identify risk factors for pediatric typhoid fever in a large epidemic in Blantyre, Malawi.

Methods

A case-control study was conducted between April 2015 and November 2016. Cases were recruited at a large teaching hospital, and controls were recruited from the community, matched by residential ward. Stepwise variable selection and likelihood ratio testing were used to select candidate risk factors for a final logistic regression model.

Results

Use of river water for cooking and cleaning was highly associated with risk of typhoid fever (odds ratio [OR], 4.6 [95% confidence interval {CI}, 1.7–12.5]). Additional risk factors included protective effects of soap in the household (OR, 0.6 [95% CI, .4–.98]) and >1 water source used in the previous 3 weeks (OR, 3.2 [95% CI, 1.6–6.2]). Attendance at school or other daycare was also identified as a risk factor (OR, 2.7 [95% CI, 1.4–5.3]) and was associated with the highest attributable risk (51.3%).

Conclusions

These results highlight diverse risk factors for typhoid fever in Malawi, with implications for control in addition to the provision of safe drinking water. There is an urgent need to improve our understanding of transmission pathways of typhoid fever, both to develop tools for detecting S. Typhi in the environment and to inform water, sanitation, and hygiene interventions.
Prognostic Accuracy of Soluble Triggering Receptor Expressed on Myeloid Cells (sTREM-1)-based Algorithms in Febrile Adults Presenting to Tanzanian Outpatient Clinics
Authors: Richard-Greenblatt Melissa , Boillat-Blanco Noémie , Zhong Kathleen , Mbarack Zainab , Samaka Josephine , Mlaganile Tarsis , Kazimoto Thekla , D’acremont Valerie , Kain Kevin C
Published: May 2019

Background

The inability to identify individuals with acute fever at risk of death is a barrier to effective triage and management of severe infections, especially in low-resource settings. Since endothelial and immune activation contribute to the pathogenesis of various distinct life-threatening infections, we hypothesized that measuring mediators of these pathways at clinical presentation would identify febrile adults at risk of death.

Methods

Plasma concentrations of markers of endothelial (angiopoetin-1/2, soluble fms-like tyrosine kinase-1, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1) and immune (soluble triggering receptor expressed on myeloid cells [sTREM-1], interleukin-6, interleukin-8, chitinase-3-like protein-1, soluble tumor necrosis factor receptor-1, procalcitonin [PCT], C-reactive protein [CRP]) activation pathways were determined in consecutive adults with acute fever (≥38°C) at presentation to outpatient clinics in Dar es Salaam, Tanzania. We evaluated the accuracy of these mediators in predicting all-cause mortality and examined whether markers could improve the prognostic accuracy of clinical scoring systems, including the quick sequential organ failure assessment (qSOFA) and Glasgow coma scale (GCS).

Results

Of 507 febrile adults, 32 died (6.3%) within 28 days of presentation. We found that sTREM-1 was the best prognostic marker for 28-day mortality (area under the receiver operating characteristic [AUROC] 0.87, 95% confidence interval [CI] 0.81–0.92) and was significantly better than CRP (P < .0001) and PCT (P = .0001). The prognostic accuracy of qSOFA and the GCS were significantly enhanced when sTREM-1 was added (0.80 [95% CI 0.76–0.83] to 0.91 [95% CI 0.88–0.94; P < .05] and 0.72 [95% CI 0.63–0.80] to 0.94 [95% CI 0.91–0.97; P < .05], respectively).

Conclusions

Measuring sTREM-1 at clinical presentation can identify febrile individuals at risk of all-cause febrile mortality. Adding severity markers such as sTREM-1 to simple clinical scores could improve the recognition and triage of patients with life-threatening infections in resource-limited settings.
Video Hashing with DCT and NMF
Authors: Tang Zhenjun , Chen Lv , Yao Heng , Zhang Xianquan , Yu Chunqiang
Published: May 2019

Video hashing is a novel technique of multimedia processing and finds applications in video retrieval, video copy detection, anti-piracy search and video authentication. In this paper, we propose a robust video hashing based on discrete cosine transform (DCT) and non-negative matrix decomposition (NMF). The proposed video hashing extracts secure features from a normalized video via random partition and dominant DCT coefficients, and exploits NMF to learn a compact representation from the secure features. Experiments with 2050 videos are carried out to validate efficiency of the proposed video hashing. The results show that the proposed video hashing is robust to many digital operations and reaches good discrimination. Receiver operating characteristic (ROC) curve comparisons illustrate that the proposed video hashing outperforms some state-of-the-art algorithms in classification between robustness and discrimination.
Bonus or Burden? Care Work, Inequality, and Job Satisfaction in Eighteen European Countries
Authors: Lightman Naomi , Kevins Anthony
Published: May 2019

While existing research highlights the feminized and devalued nature of care work, the relationship between care work and job satisfaction has not yet been tested cross-nationally. England (2005) outlines two theoretical frameworks that guide our thinking about this potential relationship: the Prisoner of Love framework suggests that, notwithstanding the explicit and implicit costs of care work, the intrinsic benefits of caring provide ‘psychic income’ and lead to greater job satisfaction; while the Commodification of Emotion framework suggests, instead, that care work generates additional stress and/or alienation for the worker, thereby resulting in lower job satisfaction. This article empirically tests this relationship in 18 countries using European Social Survey data and incorporating national-level factors. The results provide support for the Prisoner of Love framework, with variation based on the degree of professionalization. Although we find broad evidence of a care work-job satisfaction bonus, non-professional care workers experience a substantively larger bonus than their paraprofessional and professional counterparts. However, national-level economic inequality is also found to play a role in this relationship, with higher inequality amplifying the care work bonus at all levels of professionalization.
Structural change and relative demand for skilled workers: new evidence from the US manufacturing
Authors: Chongvilaivan Aekapol , Hur Jung
Published: May 2019

The present paper empirically investigates the effects of structural change—change in labor productivity fueled by labor reallocation across industries—on relative demand for skilled workers, using the NBER-CES Manufacturing Industry Database for the period of 1958–2011. The measures unveil that the US manufacturing sectors had experienced dramatic structural change since the 1990s when labor was reallocated from high-productivity to low-productivity industries. Furthermore, we find the evidence that the growth-reducing structural change impinges positively on relative demand for skilled workers and is therefore another driving force of rising wage inequality, apart from high-tech capital investment and outsourcing activities, in the US manufacturing sectors.
Boundary Operators Associated With the Sixth-Order GJMS Operator
Authors: Case Jeffrey S , Luo Weiyu
Published: May 2019

We describe a set of conformally covariant boundary operators associated with the 6th-order Graham--Jenne--Mason--Sparling (GJMS) operator on a conformally invariant class of manifolds that includes compactifications of Poincaré–Einstein manifolds. This yields a conformally covariant energy functional for the 6th-order GJMS operator on such manifolds. Our boundary operators also provide a new realization of the fractional GJMS operators of order one, three, and five as generalized Dirichlet-to-Neumann operators. This allows us to prove some sharp Sobolev trace inequalities involving the interior $W^{3,2}$-seminorm, including an analogue of the Lebedev–Milin inequality on six-dimensional manifolds.
How to Address the Risk of HIV Transmission in Remission Studies With Treatment Interruption: The Low-Hanging Fruit Approach
Authors: Eyal Nir
Published: May 2019

Some HIV remission studies include a treatment interruption that seriously risks infecting participants’ sex partners with HIV. What, ethically, is owed to these nonparticipants? Until greater certainty emerges on what protections should be afforded nonparticipants of research studies, what I call a “low-hanging fruit” approach may help researchers and review bodies determine how to address infection risks to nonparticipants in these studies.
A regression framework to uncover pleiotropy in large-scale electronic health record data
Authors: Li Ruowang , Duan Rui , Kember Rachel L , Rader Daniel J , Damrauer Scott M , Moore Jason H , Chen Yong
Published: May 2019

Objective

Pleiotropy, where 1 genetic locus affects multiple phenotypes, can offer significant insights in understanding the complex genotype–phenotype relationship. Although individual genotype–phenotype associations have been thoroughly explored, seemingly unrelated phenotypes can be connected genetically through common pleiotropic loci or genes. However, current analyses of pleiotropy have been challenged by both methodologic limitations and a lack of available suitable data sources.

Materials and Methods

In this study, we propose to utilize a new regression framework, reduced rank regression, to simultaneously analyze multiple phenotypes and genotypes to detect pleiotropic effects. We used a large-scale biobank linked electronic health record data from the Penn Medicine BioBank to select 5 cardiovascular diseases (hypertension, cardiac dysrhythmias, ischemic heart disease, congestive heart failure, and heart valve disorders) and 5 mental disorders (mood disorders; anxiety, phobic and dissociative disorders; alcohol-related disorders; neurological disorders; and delirium dementia) to validate our framework.

Results

Compared with existing methods, reduced rank regression showed a higher power to distinguish known associated single-nucleotide polymorphisms from random single-nucleotide polymorphisms. In addition, genome-wide gene-based investigation of pleiotropy showed that reduced rank regression was able to identify candidate genetic variants with novel pleiotropic effects compared to existing methods.

Conclusion

The proposed regression framework offers a new approach to account for the phenotype and genotype correlations when identifying pleiotropic effects. By jointly modeling multiple phenotypes and genotypes together, the method has the potential to distinguish confounding from causal genotype and phenotype associations.
A primer on quantitative bias analysis with positive predictive values in research using electronic health data
Authors: Newcomer Sophia R , Xu Stan , Kulldorff Martin , Daley Matthew F , Fireman Bruce , Glanz Jason M
Published: May 2019

Objective

In health informatics, there have been concerns with reuse of electronic health data for research, including potential bias from incorrect or incomplete outcome ascertainment. In this tutorial, we provide a concise review of predictive value–based quantitative bias analysis (QBA), which comprises epidemiologic methods that use estimates of data quality accuracy to quantify the bias caused by outcome misclassification.

Target Audience

Health informaticians and investigators reusing large, electronic health data sources for research.

Scope

When electronic health data are reused for research, validation of outcome case definitions is recommended, and positive predictive values (PPVs) are the most commonly reported measure. Typically, case definitions with high PPVs are considered to be appropriate for use in research. However, in some studies, even small amounts of misclassification can cause bias. In this tutorial, we introduce methods for quantifying this bias that use predictive values as inputs. Using epidemiologic principles and examples, we first describe how multiple factors influence misclassification bias, including outcome misclassification levels, outcome prevalence, and whether outcome misclassification levels are the same or different by exposure. We then review 2 predictive value–based QBA methods and why outcome PPVs should be stratified by exposure for bias assessment. Using simulations, we apply and evaluate the methods in hypothetical electronic health record–based immunization schedule safety studies. By providing an overview of predictive value–based QBA, we hope to bridge the disciplines of health informatics and epidemiology to inform how the impact of data quality issues can be quantified in research using electronic health data sources.
The studiolo of Rudolf II at Prague Castle
Authors: Fornasiero Alice , Zlatohlávková Eliška
Published: May 2019

The collection of Rudolf II (1552–1612), housed in various spaces at Prague Castle, has attracted attention from the time of its foundation to the present day. Most research effort in the past few decades has been focused on the set of chambers designated the Kunstkammer, and has given little consideration to the existence of a further private space, often cited in the archival sources or inventories. Since the time of Rudolf’s arrival at Prague Castle, there existed a room named in the records as the Schreibstüblein or Schreibstuben, which is to be regarded as the studiolo of the emperor – an intimate retreat and the repository for a number of select pieces from Rudolf’s vast collections. The inventories of Prague Castle and the correspondence of foreign envoys confirm the presence of this space and help to define its position and function.
A Mixed Frequency Stochastic Volatility Model for Intraday Stock Market Returns
Authors: Bekierman Jeremias , Gribisch Bastian
Published: May 2019

We propose a mixed frequency stochastic volatility model for intraday returns. To account for long-memory type of dependence patterns we introduce a long-run component that changes daily and a short-run component that captures the remaining intraday volatility dynamics. We analyze the model’s stochastic properties and extend it to capture leverage effects and overnight return information. The model is estimated by simulated maximum likelihood using efficient importance sampling. We apply the model to 30-min returns of 12 stocks. The results show that the model successfully accounts for the complex dynamic and distributional properties of asset returns both on the intraday and the daily frequency.
Proton-irradiated breast cells: molecular points of view
Authors: Bravatà Valentina , Cammarata Francesco P , Minafra Luigi , Pisciotta Pietro , Scazzone Concetta , Manti Lorenzo , Savoca Gaetano , Petringa Giada , Cirrone Giuseppe A P , Cuttone Giacomo , Gilardi Maria C , Forte Giusi I , Russo Giorgio
Published: May 2019

Breast cancer (BC) is the most common cancer in women, highly heterogeneous at both the clinical and molecular level. Radiation therapy (RT) represents an efficient modality to treat localized tumor in BC care, although the choice of a unique treatment plan for all BC patients, including RT, may not be the best option. Technological advances in RT are evolving with the use of charged particle beams (i.e. protons) which, due to a more localized delivery of the radiation dose, reduce the dose administered to the heart compared with conventional RT. However, few data regarding proton-induced molecular changes are currently available. The aim of this study was to investigate and describe the production of immunological molecules and gene expression profiles induced by proton irradiation. We performed Luminex assay and cDNA microarray analyses to study the biological processes activated following irradiation with proton beams, both in the non-tumorigenic MCF10A cell line and in two tumorigenic BC cell lines, MCF7 and MDA-MB-231. The immunological signatures were dose dependent in MCF10A and MCF7 cell lines, whereas MDA-MB-231 cells show a strong pro-inflammatory profile regardless of the dose delivered. Clonogenic assay revealed different surviving fractions according to the breast cell lines analyzed. We found the involvement of genes related to cell response to proton irradiation and reported specific cell line- and dose-dependent gene signatures, able to drive cell fate after radiation exposure. Our data could represent a useful tool to better understand the molecular mechanisms elicited by proton irradiation and to predict treatment outcome
Phi thickenings in roots: novel secondary wall structures responsive to biotic and abiotic stresses
Authors: Aleamotu‘a Maketalena , McCurdy David W , Collings David A
Published: May 2019

Phi thickenings are specialized secondary walls found in root cortical cells. Despite their widespread occurrence throughout the plant kingdom, these specialized thickenings remain poorly understood. First identified by Van Tieghem in 1871, phi thickenings are a lignified and thickened cell wall band that is deposited inside the primary wall, as a ring around the cells’ radial walls. Phi thickenings can, however, display structural variations including a fine, reticulate network of wall thickenings extending laterally from the central lignified band. While phi thickenings have been proposed to mechanically strengthen roots, act as a permeability barrier to modulate solute movement, and regulate fungal interactions, these possibilities remain to be experimentally confirmed. Furthermore, since temporal and spatial development of phi thickenings varies widely between species, thickenings may perform diverse roles in different species. Phi thickenings can be induced by abiotic stresses in different species; they can, for example, be induced by heavy metals in the Zn/Cd hyperaccumulator Thlaspi caerulescens, and in a cultivar-specific manner by water stress in Brassica. This latter observation provides an experimental platform to probe phi thickening function, and to identify genetic pathways responsible for their formation. These pathways might be expected to differ from those involved in secondary wall formation in xylem, since phi thickening deposition in not linked to programmed cell death.
The multitasking abilities of MATE transporters in plants
Authors: Upadhyay Neha , Kar Debojyoti , Deepak Mahajan Bhagyashri , Nanda Sanchali , Rahiman Rini , Panchakshari Nimisha , Bhagavatula Lavanya , Datta Sourav
Published: May 2019

As sessile organisms, plants constantly monitor environmental cues and respond appropriately to modulate their growth and development. Membrane transporters act as gatekeepers of the cell regulating both the inflow of useful materials as well as exudation of harmful substances. Members of the multidrug and toxic compound extrusion (MATE) family of transporters are ubiquitously present in almost all forms of life including prokaryotes and eukaryotes. In bacteria, MATE proteins were originally characterized as efflux transporters conferring drug resistance. There are 58 MATE transporters in Arabidopsis thaliana, which are also known as DETOXIFICATION (DTX) proteins. In plants, these integral membrane proteins are involved in a diverse array of functions, encompassing secondary metabolite transport, xenobiotic detoxification, aluminium tolerance, and disease resistance. MATE proteins also regulate overall plant development by controlling phytohormone transport, tip growth processes, and senescence. While most of the functional characterizations of MATE proteins have been reported in Arabidopsis, recent reports suggest that their diverse roles extend to numerous other plant species. The wide array of functions exhibited by MATE proteins highlight their multitasking ability. In this review, we integrate information related to structure and functions of MATE transporters in plants. Since these transporters are central to mechanisms that allow plants to adapt to abiotic and biotic stresses, their study can potentially contribute to improving stress tolerance under changing climatic conditions.
A new analytic framework for prediction of migration patterns and locations of historical manuscripts based on their script types
Authors: Prebor Gila , Zhitomirsky-Geffet Maayan , Miller Yitzchak
Published: May 2019

In this article, we utilized large-scale statistical analysis and data visualization techniques of the greatest collection in the world of Hebrew manuscript metadata records to develop a new methodology for quantitative investigation of the palaeographic, geographic, and temporal characteristics of historical manuscripts. The study aims to explore whether and to what extent the script type of the manuscript and its changes over time can be used to automatically predict and complete missing geospatial data of the manuscripts. To this end, various ontological entities were used as features to train supervised machine-learning algorithms to predict the places of writing of manuscripts which were often absent in the catalogue records. The obtained results show that while the script type as an only feature might not be sufficient for prediction of the location of the manuscript’s writing, its combination with temporal data of the manuscript yielded about 80% accuracy. Eventually, our system was able to complete the missing places of writing for over 60% of the manuscripts in the corpus. Moreover, we found that through typical and marginal script types in different regions and their changes over time, it is possible to draw the migration map of the Jewish communities over the centuries. This reinforces the findings of historical research on Jewish migration patterns and communal formation. For example, the waves of immigration from Western Europe can be seen clearly from the second half of the 13th century, which continued until the 17th century and greatly increased the Eastern European Jewish community.
Usefulness of ICU criteria for diagnosis of invasive pulmonary aspergillosis in nonhematologic critically ill patients
Authors: Lee Song-I , Sung Heungsup , Hong Sang-Bum , Lim Chae-Man , Koh Younsuck , Huh Jin-Won
Published: May 2019

Invasive pulmonary aspergillosis (IPA) is a life-threatening disease in the intensive care unit (ICU). The ICU criteria were proposed to diagnose IPA in critically ill patients. This study aims to evaluate the usefulness of ICU criteria for diagnosis and treatment of IPA in nonhematologic patients in the ICU. We retrospectively reviewed 103 ICU patients with positive galactomannan test in blood and respiratory tract from January 1, 2016, to May 31, 2017. We excluded patients with hematologic malignancy. We divided the treatment and non-treatment groups according to the IPA treatment. We compared the baseline characteristics and outcomes between two groups and the agreement with ICU criteria. There were 49 patients in treatment groups and 54 patients in non-treatment groups. There were more cases of solid organ transplantation (P = .003), immunosuppressive therapy (P < .001) and bacterial viral coinfection (P = .048) in the treatment group compared to nontreatment group. There was no statistically significant difference in mortality, the use of ventilator, and septic shock between the two groups. The agreement rate between the putative group and treatment was low (59.2%). There was no statistically significant difference in outcome between the putative and colonization groups according to the ICU criteria in each group. The treatment of IPA based on the symptom, radiologic finding and galactomannan test did not showed the better outcome. Also, the treatment based on the ICU criteria didn’t show the difference of outcome. The new criteria for diagnosis of IPA in critically ill patients are needed.
A near-infrared study of the multiphase outflow in the type-2 quasar J1509+0434
Authors: Ramos Almeida C , Acosta-Pulido J A , Tadhunter C N , González-Fernández C , Cicone C , Fernández-Torreiro M
Published: May 2019

Based on new near-infrared spectroscopic data from the instrument Espectrógrafo Multiobjeto Infra-Rojo (EMIR) on the 10.4 m Gran Telescopio Canarias, we report the presence of an ionized and warm molecular outflow in the luminous type-2 quasar J150904.22+043441.8 (z = 0.1118). The ionized outflow is faster than its molecular counterpart, although the outflow sizes that we derive for them are consistent within the errors (1.34 ± 0.18 and 1.46 ± 0.20 kpc, respectively). We use these radii, the broad emission-line luminosities and in the case of the ionized outflow, the density calculated from the trans-auroral [O ii] and [S ii] lines, to derive mass outflow rates and kinetic coupling efficiencies. While the ionized and warm molecular outflows represent a small fraction of the AGN power (≤0.033 and 0.0001 per cent of Lbol, respectively), the total molecular outflow, whose mass is estimated from an assumed warm-to-cold gas mass ratio of 6 × 10−5, has a kinetic coupling efficiency of ∼1.7 per cent Lbol. Despite the large uncertainty, this molecular outflow represents a significant fraction ofLbol and it could potentially have a significant impact on the host galaxy. In addition, the quasar spectrum reveals bright and patchy narrow Paα emission extending out to 4 arcsec (8 kpc) south-east and north-west from the active nucleus.
Prophage Hunter: an integrative hunting tool for active prophages
Authors: Song Wenchen , Sun Hai-Xi , Zhang Carolyn , Cheng Li , Peng Ye , Deng Ziqing , Wang Dan , Wang Yun , Hu Ming , Liu Wenen , Yang Huanming , Shen Yue , Li Junhua , You Lingchong , Xiao Minfeng
Published: May 2019

Identifying active prophages is critical for studying coevolution of phage and bacteria, investigating phage physiology and biochemistry, and engineering designer phages for diverse applications. We present Prophage Hunter, a tool aimed at hunting for active prophages from whole genome assembly of bacteria. Combining sequence similarity-based matching and genetic features-based machine learning classification, we developed a novel scoring system that exhibits higher accuracy than current tools in predicting active prophages on the validation datasets. The option of skipping similarity matching is also available so that there's higher chance for novel phages to be discovered. Prophage Hunter provides a one-stop web service to extract prophage genomes from bacterial genomes, evaluate the activity of the prophages, identify phylogenetically related phages, and annotate the function of phage proteins. Prophage Hunter is freely available at https://pro-hunter.bgi.com/.
Primary transcriptome and translatome analysis determines transcriptional and translational regulatory elements encoded in the Streptomyces clavuligerus genome
Authors: Hwang Soonkyu , Lee Namil , Jeong Yujin , Lee Yongjae , Kim Woori , Cho Suhyung , Palsson Bernhard O , Cho Byung-Kwan
Published: May 2019

Determining transcriptional and translational regulatory elements in GC-rich Streptomyces genomes is essential to elucidating the complex regulatory networks that govern secondary metabolite biosynthetic gene cluster (BGC) expression. However, information about such regulatory elements has been limited for Streptomyces genomes. To address this limitation, a high-quality genome sequence of β-lactam antibiotic-producing Streptomyces clavuligerus ATCC 27 064 is completed, which contains 7163 newly annotated genes. This provides a fundamental reference genome sequence to integrate multiple genome-scale data types, including dRNA-Seq, RNA-Seq and ribosome profiling. Data integration results in the precise determination of 2659 transcription start sites which reveal transcriptional and translational regulatory elements, including −10 and −35 promoter components specific to sigma (σ) factors, and 5′-untranslated region as a determinant for translation efficiency regulation. Particularly, sequence analysis of a wide diversity of the −35 components enables us to predict potential σ-factor regulons, along with various spacer lengths between the −10 and −35 elements. At last, the primary transcriptome landscape of the β-lactam biosynthetic pathway is analyzed, suggesting temporal changes in metabolism for the synthesis of secondary metabolites driven by transcriptional regulation. This comprehensive genetic information provides a versatile genetic resource for rational engineering of secondary metabolite BGCs in Streptomyces.
Understanding mitochondrial DNA maintenance disorders at the single muscle fibre level
Authors: Lehmann Diana , Tuppen Helen A L , Campbell Georgia E , Alston Charlotte L , Lawless Conor , Rosa Hannah S , Rocha Mariana C , Reeve Amy K , Nicholls Thomas J , Deschauer Marcus , Zierz Stephan , Taylor Robert W , Turnbull Doug M , Vincent Amy E
Published: May 2019

Clonal expansion of mitochondrial DNA (mtDNA) deletions is an important pathological mechanism in adults with mtDNA maintenance disorders, leading to a mosaic mitochondrial respiratory chain deficiency in skeletal muscle. This study had two aims: (i) to determine if different Mendelian mtDNA maintenance disorders showed similar pattern of mtDNA deletions and respiratory chain deficiency and (ii) to investigate the correlation between the mitochondrial genetic defect and corresponding respiratory chain deficiency. We performed a quantitative analysis of respiratory chain deficiency, at a single cell level, in a cohort of patients with mutations in mtDNA maintenance genes. Using the same tissue section, we performed laser microdissection and single cell genetic analysis to investigate the relationship between mtDNA deletion characteristics and the respiratory chain deficiency. The pattern of respiratory chain deficiency is similar with different genetic defects. We demonstrate a clear correlation between the level of mtDNA deletion and extent of respiratory chain deficiency within a single cell. Long-range and single molecule PCR shows the presence of multiple mtDNA deletions in approximately one-third of all muscle fibres. We did not detect evidence of a replicative advantage for smaller mtDNA molecules in the majority of fibres, but further analysis is needed to provide conclusive evidence.
A kinetochore-based ATM/ATR-independent DNA damage checkpoint maintains genomic integrity in trypanosomes
Authors: Zhou Qing , Pham Kieu T M , Hu Huiqing , Kurasawa Yasuhiro , Li Ziyin
Published: May 2019

DNA damage-induced cell cycle checkpoints serve as surveillance mechanisms to maintain genomic stability, and are regulated by ATM/ATR-mediated signaling pathways that are conserved from yeast to humans. Trypanosoma brucei, an early divergent microbial eukaryote, lacks key components of the conventional DNA damage-induced G2/M cell cycle checkpoint and the spindle assembly checkpoint, and nothing is known about how T. brucei controls its cell cycle checkpoints. Here we discover a kinetochore-based, DNA damage-induced metaphase checkpoint in T. brucei. MMS-induced DNA damage triggers a metaphase arrest by modulating the abundance of the outer kinetochore protein KKIP5 in an Aurora B kinase- and kinetochore-dependent, but ATM/ATR-independent manner. Overexpression of KKIP5 arrests cells at metaphase through stabilizing the mitotic cyclin CYC6 and the cohesin subunit SCC1, mimicking DNA damage-induced metaphase arrest, whereas depletion of KKIP5 alleviates the DNA damage-induced metaphase arrest and causes chromosome mis-segregation and aneuploidy. These findings suggest that trypanosomes employ a novel DNA damage-induced metaphase checkpoint to maintain genomic integrity.