bluuebunny/crossref_metadata_2025 huggingface dataset:
The Coordinated Universal Time (UTC)
Authors: Panfilo G , Arias F
Published: May 2019

Coordinated Universal Time (UTC) has considerably changed in recent years. The evolution of UTC follows the scientific and industrial progress by developing appropriate models, more adapted calculation algorithms, more efficient and rapid dissemination processes and a well defined traceability chain. The enormous technical progress worldwide has resulted in an impressive number of atomic clocks now available for UTC calculation. The refined time and frequency transfer techniques are approaching the accuracy requested for the new definition of the SI second. The more regular operation of primary frequency standards (PFS) increases the accuracy of UTC and opens a possible new development for time scale algorithms. From the metrological point of view all the ingredients are available for major improvements to UTC. Dissemination of UTC is done by the monthly publication of results in BIPM Circular T. This document makes a quality evaluation of local representations of UTC, named UTC(k), in national institutes, and other organizations, by giving the evolution of their offsets relative to UTC and their respective uncertainties. The clock models adopted and the time transfer techniques have progressively improved over the years, assuring the long-term stability of UTC. Each computation of UTC processes data over one month with five-day sampling and publication. A rapid solution of UTC (UTCr) has existed since 2013, and consists of the processing of daily sampled data over four consecutive weeks, computed and published weekly. It gives quick access to UTC, and allows participating laboratories to better monitor the offsets of their realizations to the reference UTC. The traditional monthly publication, containing results of all the laboratories contributing data to the BIPM for the computation of UTC was complemented after the establishment of the Mutual Recognition Arrangement of the International Committee on Weights and Measures (CIPM MRA). This time comparison, which has been the responsibility of the BIPM since 1988, added as a complement the key comparison on time defined by the Consultative Committee for Time and Frequency (CCTF) in 2006 as CCTF-K001.UTC, where the results published are those of national metrology institutes (NMIs) signatories of the CIPM MRA, or designated institutes (DIs). The traceability issues are formalized in the framework of the CIPM MRA. The development of time metrology activities in the different metrology regions, supports the actions of the BIPM time department to improve the accuracy of [UTC–UTC(k)], where the coordination with the Regional Metrology Organizations (RMOs) has a key role. This paper presents an overview of UTC.
SpikeDeeptector: a deep-learning based method for detection of neural spiking activity
Authors: Saif-ur-Rehman Muhammad , Lienkämper Robin , Parpaley Yaroslav , Wellmer Jörg , Liu Charles , Lee Brian , Kellis Spencer , Andersen Richard , Iossifidis Ioannis , Glasmachers Tobias , Klaes Christian
Published: May 2019

Objective. In electrophysiology, microelectrodes are the primary source for recording neural data (single unit activity). These microelectrodes can be implanted individually or in the form of arrays containing dozens to hundreds of channels. Recordings of some channels contain neural activity, which are often contaminated with noise. Another fraction of channels does not record any neural data, but only noise. By noise, we mean physiological activities unrelated to spiking, including technical artifacts and neural activities of neurons that are too far away from the electrode to be usefully processed. For further analysis, an automatic identification and continuous tracking of channels containing neural data is of great significance for many applications, e.g. automated selection of neural channels during online and offline spike sorting. Automated spike detection and sorting is also critical for online decoding in brain–computer interface (BCI) applications, in which only simple threshold crossing events are often considered for feature extraction. To our knowledge, there is no method that can universally and automatically identify channels containing neural data. In this study, we aim to identify and track channels containing neural data from implanted electrodes, automatically and more importantly universally. By universally, we mean across different recording technologies, different subjects and different brain areas. Approach. We propose a novel algorithm based on a new way of feature vector extraction and a deep learning method, which we call SpikeDeeptector. SpikeDeeptector considers a batch of waveforms to construct a single feature vector and enables contextual learning. The feature vectors are then fed to a deep learning method, which learns contextualized, temporal and spatial patterns, and classifies them as channels containing neural spike data or only noise. Main results. We trained the model of SpikeDeeptector on data recorded from a single tetraplegic patient with two Utah arrays implanted in different areas of the brain. The trained model was then evaluated on data collected from six epileptic patients implanted with depth electrodes, unseen data from the tetraplegic patient and data from another tetraplegic patient implanted with two Utah arrays. The cumulative evaluation accuracy was 97.20% on 1.56 million hand labeled test inputs. Significance. The results demonstrate that SpikeDeeptector generalizes not only to the new data, but also to different brain areas, subjects, and electrode types not used for training. Clinical trial registration number. The clinical trial registration number for patients implanted with the Utah array is NCT 01849822. For the epilepsy patients, approval from the local ethics committee at the Ruhr-University Bochum, Germany, was obtained prior to implantation.
Epidural recordings in cochlear implant users
Authors: Haumann S , Bauernfeind G , Teschner M J , Schierholz I , Bleichner M G , Büchner A , Lenarz T
Published: May 2019

Objective. In the long term it is desirable for CI users to control their device via brain signals. A possible strategy is the use of auditory evoked potentials (AEPs). Several studies have shown the suitability of auditory paradigms for such an approach. However, these investigations are based on non-invasive recordings. When thinking about everyday life applications, it would be more convenient to use implanted electrodes for signal acquisition. Ideally, the electrodes would be directly integrated into the CI. Further it is to be expected that invasively recorded signals have higher signal quality and are less affected by artifacts. Approach. In this project we investigated the feasibility of implanting epidural electrodes temporarily during CI surgery and the possibility to record AEPs in the course of several days after implantation. Intraoperatively, auditory brainstem responses were recorded, whereas various kinds of AEPs were recorded postoperatively. After a few days the epidural electrodes were removed. Main results. Data sets of ten subjects were obtained. Invasively recorded potentials were compared subjectively and objectively to clinical standard recordings using surface electrodes. Especially the cortical evoked response audiometry depicted clearer N1 waves for the epidural electrodes which were also visible at lower stimulation intensities compared to scalp electrodes. Furthermore the signal was less disturbed by artifacts. The objective quality measure (based on data sets of six patients) showed a significant better signal quality for the epidural compared to the scalp recordings. Significance. Altogether the approach revealed to be feasible and well tolerated by the patients. The epidural recordings showed a clearly better signal quality than the scalp recordings with AEPs being clearer recognizable. The results of the present study suggest that including epidural recording electrodes in future CI systems will improve the everyday life applicability of auditory closed loop systems for CI subjects.
Projected precipitation changes over the south Asian region for every 0.5 °C increase in global warming
Authors: Bhowmick Mansi , Sahany Sandeep , Mishra Saroj K
Published: May 2019

Using all ensemble members of NCAR CCSM4 for historical natural, RCP4.5 and RCP8.5 scenarios from CMIP5, we analyse changes in mean and extreme precipitation over the south Asian region for every 0.5 oC increase in global warming. An increase in mean annual precipitation is projected over majority of the south Asian region with increased levels of warming. Over Indian land, the spatially-averaged annual mean precipitation shows an increase in the range of ~2-14 % based on the RCP scenario and level of warming. However, a decrease in mean annual precipitation is projected over northwest parts of the Indian sub-continent and the equatorial Indian Ocean with increased levels of warming. In general, we find multifold increase in the frequency of occurrence of daily precipitation extremes over the Indian subcontinent and surrounding oceans. Over Indian land, frequency of occurrence of daily precipitation extremes show up to three-fold increase under both RCP scenarios for global warming levels in the range of 1.5 oC–2.5 oC. With further increase in warming we find that the frequency of occurrence of daily precipitation extremes could show a massive four- to six-fold increase over majority of Indian land. Notably, unlike the projected increase in the frequency of occurrence of daily precipitation extremes, the projected change in annual mean precipitation is found to be insignificant in a 1.5 oC warmer world, over majority of the south Asian region, under both RCP scenarios. Given the projected large increase in frequency of daily precipitation extremes with increased levels of warming, our study provides scientific support to the recommendations of the Paris Agreement of 2015.
Characterizations of cancellable groups
Authors: Harrison-Trainor Matthew , Ho Meng-Che
Published: May 2019

An abelian group

A
A

is said to be cancellable if whenever

A
⊕
G

A \oplus G

is isomorphic to

A
⊕
H

A \oplus H

,

G
G

is isomorphic to

H
H

. We show that the index set of cancellable rank 1 torsion-free abelian groups is

Π
4
0

\Pi ^0_4

m
m

-complete, showing that the classification by Fuchs and Loonstra cannot be simplified. For arbitrary non-finitely generated groups, we show that the cancellation property is

Π
1
1

\Pi ^1_1

m
m

-hard; we know of no upper bound, but we conjecture that it is

Π
2
1

\Pi ^1_2

m
m

-complete.
Aspherical 4-manifolds of odd Euler characteristic
Authors: Edmonds Allan
Published: May 2019

An explicit construction of closed, orientable, smooth, aspherical 4-manifolds with any odd Euler characteristic greater than 12 is presented. The constructed manifolds are all Haken manifolds in the sense of B. Foozwell and H. Rubinstein and can be systematically reduced to balls by suitably cutting them open along essential codimension-one submanifolds. Euler characteristics divisible by 3 are known to arise from complex algebraic geometry considerations. Examples with Euler characteristic 1, 5, 7, or 11 appear to be unknown.
Finite dimensional invariant KAM tori for tame vector fields
Authors: Corsi Livia , Feola Roberto , Procesi Michela
Published: May 2019

We discuss a Nash-Moser/KAM algorithm for the construction of invariant tori for tame vector fields. Similar algorithms have been studied widely both in finite and infinite dimensional contexts: we are particularly interested in the second case where tameness properties of the vector fields become very important. We focus on the formal aspects of the algorithm and particularly on the minimal hypotheses needed for convergence. We discuss various applications where we show how our algorithm allows one to reduce to solving only linear forced equations. We remark that our algorithm works at the same time in analytic and Sobolev classes.
Diffusions from infinity
Authors: Bansaye Vincent , Collet Pierre , Martinez Servet , Méléard Sylvie , San Martin Jaime
Published: May 2019

In this paper we consider diffusions on the half line

(
0
,
∞
)

(0,\infty )

such that the expectation of the arrival time at the origin is uniformly bounded in the initial point. This implies that there is a well defined diffusion process starting from infinity which takes finite values at positive times. We study the behavior of hitting times of large barriers and, in a dual way, the behavior of the process starting at infinity for small time. In particular, we prove that the process coming down from infinity is in small time governed by a specific deterministic function. Suitably normalized fluctuations of the hitting times are asymptotically Gaussian. We also derive the tail of the distribution of the hitting time of the origin and a Yaglom limit for the diffusion starting from infinity. We finally prove that the distribution of this process killed at the origin is absolutely continuous with respect to the speed measure. The density is expressed in terms of the eigenvalues and eigenfunctions of the generator of the killed diffusion.
Coupling Lévy measures and comparison principles for viscosity solutions
Authors: Guillen Nestor , Mou Chenchen , Świȩch Andrzej
Published: May 2019

We prove new comparison principles for viscosity solutions of nonlinear integro-differential equations. The operators to which the method applies include but are not limited to those of Lévy–Itô type. The main idea is to use an optimal transport map to couple two different Lévy measures and use the resulting coupling in a doubling of variables argument.
Multiple sources of signal amplification within the B-cell Ras/MAPK pathway
Authors: Mclaurin Justin D. , Weiner Orion D.
Published: May 2019

The Ras-Map kinase (MAPK) cascade underlies functional decisions in a wide range of cell types and organisms. In B-cells, positive feedback-driven Ras activation is the proposed source of the digital (all or none) MAPK responses following antigen stimulation. However, an inability to measure endogenous Ras activity in living cells has hampered our ability to test this model directly. Here we leverage biosensors of endogenous Ras and ERK activity to revisit this question. We find that B-cell receptor (BCR) ligation drives switch-like Ras activation and that lower BCR signaling output is required for the maintenance versus the initiation of Ras activation. Surprisingly, digital ERK responses persist in the absence of positive feedback-mediated Ras activation, and digital ERK is observed at a threshold level of Ras activation. These data suggest an independent analogue-to-digital switch downstream of Ras activation and reveal that multiple sources of signal amplification exist within the Ras-ERK module of the BCR pathway.
Crude Protein, Amino Acid, and Iron Content of Tenebrio molitor (Coleoptera, Tenebrionidae) Reared on an Agricultural Byproduct from Maize Production: An Exploratory Study
Authors: Stull Valerie J , Kersten Marjorie , Bergmans Rachel S , Patz Jonathan A , Paskewitz Susan
Published: May 2019

Edible insects offer environmental and nutritional benefits, as they are characteristically nutrient-dense, are efficient biotransformers of organic material, and emit fewer greenhouse gasses than traditional livestock. Cultivating Tenebrio molitor (yellow mealworm) as ‘minilivestock’ is one possible means of increasing access to insect protein for food insecure populations. Tenebrio molitor growth and nutrient content varies with diet and rearing conditions, but little is known about the precise impact of poor quality feedstocks, such as maize crop residue (stover). Stover is widely available across sub-Saharan Africa where maize is a common dietary staple. Early instar larvae were reared under controlled conditions on three feed substrates: a standard control; a mixed soy, maize grain, and stover diet; and a 100% stover diet. Larvae reared for 32 d were analyzed for total amino acid profile, crude protein, and iron content. Larvae fed the three diets contained all essential amino acids for human nutrition and compared favorably to other traditional protein sources. The mixed diet contained 40% stover by weight and yielded amino acid values similar to the control diet, suggesting that some grain feedstock could be replaced with stover without hampering nutrient content. A second experiment demonstrated that T. molitor were able to complete metamorphosis and survive on a 100% stover diet for multiple generations. These results suggest that stover could be a suitable dietary component for T. molitor, which could facilitate the development of low-cost insect farming systems in low-resource settings that stand to benefit from increased access nutrient-dense edible insects.
An Area-Level Indicator of Latent Soda Demand: Spatial Statistical Modeling of Grocery Store Transaction Data to Characterize the Nutritional Landscape in Montreal, Canada
Authors: Mamiya Hiroshi , Schmidt Alexandra M , Moodie Erica E M , Ma Yu , Buckeridge David L
Published: May 2019

Measurement of neighborhood dietary patterns at high spatial resolution allows public health agencies to identify and monitor communities with an elevated risk of nutrition-related chronic diseases. Currently, data on diet are obtained primarily through nutrition surveys, which produce measurements at low spatial resolutions. The availability of store-level grocery transaction data provides an opportunity to refine the measurement of neighborhood dietary patterns. We used these data to develop an indicator of area-level latent demand for soda in the Census Metropolitan Area of Montreal in 2012 by applying a hierarchical Bayesian spatial model to data on soda sales from 1,097 chain retail food outlets. The utility of the indicator of latent soda demand was evaluated by assessing its association with the neighborhood relative risk of prevalent type 2 diabetes mellitus. The indicator improved the fit of the disease-mapping model (deviance information criterion: 2,140 with the indicator and 2,148 without) and enables a novel approach to nutrition surveillance.
Prediction of tumor metastasis from sequencing data in the era of genome sequencing
Authors: Yuan Linlin , Guo Fei , Wang Lei , Zou Quan
Published: May 2019

Tumor metastasis is the key reason for the high mortality rate of tumor. Growing number of scholars have begun to pay attention to the research on tumor metastasis and have achieved satisfactory results in this field. The advent of the era of sequencing has enabled us to study cancer metastasis at the molecular level, which is essential for understanding the molecular mechanism of metastasis, identifying diagnostic markers and therapeutic targets and guiding clinical decision-making. We reviewed the metastasis-related studies using sequencing data, covering detection of metastasis origin sites, determination of metastasis potential and identification of distal metastasis sites. These findings include the discovery of relevant markers and the presentation of prediction tools. Finally, we discussed the challenge of studying metastasis considering the difficulty of obtaining metastatic cancer data, the complexity of tumor heterogeneity and the uncertainty of sample labels.
Machine learning and statistical methods for clustering single-cell RNA-sequencing data
Authors: Petegrosso Raphael , Li Zhuliu , Kuang Rui
Published: May 2019

Single-cell RNAsequencing (scRNA-seq) technologies have enabled the large-scale whole-transcriptome profiling of each individual single cell in a cell population. A core analysis of the scRNA-seq transcriptome profiles is to cluster the single cells to reveal cell subtypes and infer cell lineages based on the relations among the cells. This article reviews the machine learning and statistical methods for clustering scRNA-seq transcriptomes developed in the past few years. The review focuses on how conventional clustering techniques such as hierarchical clustering, graph-based clustering, mixture models, $k$-means, ensemble learning, neural networks and density-based clustering are modified or customized to tackle the unique challenges in scRNA-seq data analysis, such as the dropout of low-expression genes, low and uneven read coverage of transcripts, highly variable total mRNAs from single cells and ambiguous cell markers in the presence of technical biases and irrelevant confounding biological variations. We review how cell-specific normalization, the imputation of dropouts and dimension reduction methods can be applied with new statistical or optimization strategies to improve the clustering of single cells. We will also introduce those more advanced approaches to cluster scRNA-seq transcriptomes in time series data and multiple cell populations and to detect rare cell types. Several software packages developed to support the cluster analysis of scRNA-seq data are also reviewed and experimentally compared to evaluate their performance and efficiency. Finally, we conclude with useful observations and possible future directions in scRNA-seq data analytics.

Availability

All the source code and data are available at https://github.com/kuanglab/single-cell-review.
A Bayesian two-way latent structure model for genomic data integration reveals few pan-genomic cluster subtypes in a breast cancer cohort
Authors: Swanson David M , Lien Tonje , Bergholtz Helga , Sørlie Therese , Frigessi Arnoldo
Published: May 2019

Motivation

Unsupervised clustering is important in disease subtyping, among having other genomic applications. As genomic data has become more multifaceted, how to cluster across data sources for more precise subtyping is an ever more important area of research. Many of the methods proposed so far, including iCluster and Cluster of Cluster Assignments (COCAs), make an unreasonable assumption of a common clustering across all data sources, and those that do not are fewer and tend to be computationally intensive.

Results

We propose a Bayesian parametric model for integrative, unsupervised clustering across data sources. In our two-way latent structure model, samples are clustered in relation to each specific data source, distinguishing it from methods like COCAs and iCluster, but cluster labels have across-dataset meaning, allowing cluster information to be shared between data sources. A common scaling across data sources is not required, and inference is obtained by a Gibbs Sampler, which we improve with a warm start strategy and modified density functions to robustify and speed convergence. Posterior interpretation allows for inference on common clusterings occurring among subsets of data sources. An interesting statistical formulation of the model results in sampling from closed-form posteriors despite incorporation of a complex latent structure. We fit the model with Gaussian and more general densities, which influences the degree of across-dataset cluster label sharing. Uniquely among integrative clustering models, our formulation makes no nestedness assumptions of samples across data sources so that a sample missing data from one genomic source can be clustered according to its existing data sources. We apply our model to a Norwegian breast cancer cohort of ductal carcinoma in situ and invasive tumors, comprised of somatic copy-number alteration, methylation and expression datasets. We find enrichment in the Her2 subtype and ductal carcinoma among those observations exhibiting greater cluster correspondence across expression and CNA data. In general, there are few pan-genomic clusterings, suggesting that models assuming a common clustering across genomic data sources might yield misleading results.

Availability and implementation

The model is implemented in an R package called twl (‘two-way latent’), available on CRAN. Data for analysis are available within the R package.

Supplementary information

Supplementary data are available at Bioinformatics online.
The fallacy of biphasic growth allometry for the vertebrate brain
Authors: Packard Gary C
Published: May 2019

The concept of biphasic, loglinear growth of the vertebrate brain is based on graphical displays of logarithmic transformations of the original measurements. Such displays commonly give the appearance of two distinct mathematical distributions – one set of observations following a steep trajectory at the low end of the size range and another set following a shallow trajectory at the high end. However, the appearance of two distributions is an artefact resulting from the logarithmic transformations. Observations of brain mass vs. body mass in each of the eight vertebrate species examined in the current investigation conform to a single mathematical distribution that is well described by a single equation fitted to the original, untransformed data by non-linear regression. Data for carp, chickens, kangaroos and rabbits are described by three-parameter power equations whereas those for dolphins and primates are described by exponential functions that rise rapidly to a maximum. The brain continues to grow throughout life in carp, chickens, kangaroos and rabbits but not in dolphins and primates. Future investigations of relative growth of the brain should be based on graphical and analytical study of observations expressed on the native mathematical scale.
Constructing Causal Understanding in Complex Systems: Epistemic Strategies Used by Ecosystem Scientists
Authors: Kamarainen Amy M , Grotzer Tina A
Published: May 2019

Moving from a correlational to a causal account involves epistemological assumptions in any discipline. It presents particular challenges when phenomena involve multiple causes, time lags, feedback loops, or thresholds, as is the case in ecosystem science. Although reductionist approaches may contribute to explanatory efforts, investigation in ecosystems science requires a systems perspective. Understanding how ecosystem scientists arrive at causal accounts—and importantly, that they do—is critical to public understanding of science. Interviews with ten ecosystem scientists revealed the strategies and habits of mind that ecosystem scientists bring to examining complex systems. The scientists described challenges in conducting experiments at relevant scales and the epistemic strategies employed in response. The themes included constructing a body of evidence using multiple approaches, integrating results through statistical and process-based models, measuring and describing variability, conducting experiments in context, thinking across levels, considering the limits to generalizability, and exercising epistemic fluency. We discuss implications for K–20 education.
Intraductal fulvestrant for therapy of ERα-positive ductal carcinoma in situ of the breast: a preclinical study
Authors: Wang Guannan , Chen Chuang , Pai Priya , Korangath Preethi , Sun Shengrong , Merino Vanessa F , Yuan Jingping , Li Suping , Nie Guangjun , Stearns Vered , Sukumar Saraswati
Published: May 2019

Mammographic screening for breast cancer has led to increased detection of ductal carcinoma in situ (DCIS) and a reappraisal of the necessity of aggressive treatment with their attendant toxicities for a preneoplastic lesion. Fulvestrant, a selective estrogen receptor degrader, is very effective in the treatment of estrogen receptor positive (ER+) breast cancer, but delivery by the painful intramuscular (i.m) route is limiting. We hypothesized that intraductal (i.duc) administration of fulvestrant will provide a direct, safe and effective treatment for DCIS. Mice bearing mammary ductal xenografts of ER+, luciferase-tagged MCF-7 breast cancer cells were administered vehicle or fulvestrant i.m or i.duc. I.duc MCF-7-luc tumors in mice treated with fulvestrant i.duc or i.m grew significantly slower than vehicle control. Whole mount analysis and histopathology showed that i.duc fulvestrant achieved significantly larger cancer-free areas. Western blot analysis showed reduced levels of estrogen receptor alpha (ERα) and its downstream targets, c-Myc and Cyclin D1, and increased levels of ERβ, which is known to inhibit ERα function. Immunohistochemical analysis of tumor sections showed that Ki67 and ERα protein levels decreased by 3-fold, and neoangiogenesis was inhibited by i.duc fulvestrant treatment. I.duc fulvestrant also reduced outgrowth of ERα+, autochthonous N-methyl-N-nitrosourea-induced mammary tumors in rats. Overall, we have shown that i.duc fulvestrant was significantly more effective than, or equivalent in action to i.m fulvestrant in two preclinical models of breast cancer. These studies provide evidence for a novel and safe route for fulvestrant therapy of DCIS and prevention of breast cancer. This preclinical study provides a strong basis for conducting clinical trials for DCIS and early breast cancer.
Quality of Life in Patients With Olfactory Loss Is Better Predicted by Flavor Identification Than by Orthonasal Olfactory Function
Authors: Oleszkiewicz Anna , Park Dahae , Resler Katarzyna , Draf Julia , Schulze Anja , Zang Yunpeng , Hähner Antje , Hummel Thomas
Published: May 2019

To date, most studies on the relationship between chemosensory performance and quality of life have focused on orthonasal measures of olfactory function. In the current investigation, we examined the predictive value of orthonasal and flavor identification indices of olfactory function on a wide spectrum of health and sociopsychological factors, including quality of life, life satisfaction, overall health, and depressive symptoms. Participants were 178 ENT patients (Mage = 58 ± 1), representing various causes of olfactory loss: idiopathic smell loss (n = 51; Mage = 63 ± 2), sinunasal disease (n = 27; Mage = 56 ± 3), head trauma (n = 33; Mage = 51 ± 2), and infections of the upper respiratory tract (n = 67; Mage = 59 ± 2). They completed self-report questionnaires and underwent olfactory testing using Sniffin’ Sticks (orthonasal olfactory testing) and “Taste Powder” (intraorally applied flavors for retronasal olfactory testing, additionally inducing taste sensation). Data were analyzed with hierarchical regression models wherein the first step included subjects’ sex, age, and orthonasal olfaction score. In the second step, we included the “Taste Powder” score. Tested models revealed that the first step was not significantly predicting variables of interest; however, there was an improvement of the model’s predictive value when the “Taste Powder” score was added. Results of this study suggest that flavor identification significantly improves predictions of health and sociopsychological functioning of ENT patients with various etiologies.
A Validated HPTLC Densitometric Method for Determination of Lupeol, β-Sitosterol and Rotenone in Tephrosia purpurea: A Seasonal Study
Authors: Khatoon Sayyada , Irshad Saba , Pandey Madan Mohan , Rastogi Subha , Rawat Ajay Kumar Singh
Published: May 2019

Tephrosia purpurea (L.) Pers., commonly known as “sarpunkha” and “wild indigo”, is being used in traditional systems of medicine to treat liver disorders, spleen and kidney. In the present study, a validated High Performance Thin Layer Chromatography (HPTLC) method was established for the estimation of lupeol, β-sitosterol and rotenone in various extracts of T. purpurea with the aim to see the effect of seasons on the quantity of aforesaid phytoconstituents. The plant material was collected in summer (April), rainy (August) and winter (December) during 2013–2014 from Lucknow, India. The method was validated in terms of precision, repeatability, specificity, sensitivity linearity and robustness. The method permits reliable quantification and showed good resolution on silica gel with toluene-ethyl acetate-formic acid (9:1:1 v/v/v) as mobile phase, and characteristic bands of β-sitosterol, rotenone and lupeol were observed at Rf 0.38, 0.45 and 0.52, respectively. The content of aforesaid phytoconstituents varies from season to season and extract to extract. Our finding indicated that winter season (December) may not be appropriate for collection of T. purpurea for the preparation of therapeutic formulations because of the high content of rotenone, a known insecticide that is responsible for Parkinson’s disease and associated with heart failure, fatty liver and liver necrosis.
Decreased Cephalosporin Susceptibility of Oropharyngeal Neisseria Species in Antibiotic-using Men Who Have Sex With Men in Hanoi, Vietnam
Authors: Dong Huan V , Pham Loc Q , Nguyen Hoa T , Nguyen Minh X B , Nguyen Trung V , May Folasade , Le Giang M , Klausner Jeffrey D
Published: May 2019

Background

Neisseria gonorrhoeae (NG) infections are a global health burden. NG resistance to cephalosporins, which is increasingly reported, is an imminent threat to public health. Many hypothesize that commensal Neisseria species are an important reservoir for genetic material conferring antimicrobial resistance in NG; however, clinical data are lacking.

Methods

Men who have sex with men (MSM) in Hanoi, Vietnam, completed a questionnaire regarding antibiotic use. We collected pharyngeal specimens, cultured Neisseria species, and measured minimum inhibitory concentrations (MICs) to ciprofloxacin, cefixime, ceftriaxone, and cefpodoxime. Using MIC criteria for antimicrobial susceptibility in NG, we categorized the Neisseria species and compared mean MIC levels between different antibiotic user groups.

Results

Of 207 participants, 38% used at least 1 antibiotic in the past 6 months; 52% without a prescription. A median of 1 Neisseria species was cultured from each participant (range, 1–4) with 10 different Neisseria species identified overall. The proportion of Neisseria with reduced susceptibility to ciprofloxacin was 93%, cefpodoxime 84%, cefixime 31%, and ceftriaxone 28%. Antibiotic use within the past month was strongly associated with Neisseria species having increased MICs to cefixime, ceftriaxone, and cefpodoxime (mean MIC ratios of 6.27, 4.11, and 7.70, respectively), compared with those who used antibiotics between 1 and 6 months prior (P < .05, all comparisons).

Conclusions

MSM in our study often used antibiotics without a prescription. At least 1 commensal Neisseria species colonized all men. Recent use of any antibiotics may select for oropharyngeal Neisseria species with antimicrobial resistance. The normal flora of the oropharynx may be an important source of antimicrobial resistance in Neisseria gonorrhoeae.
A curated collection of transcriptome datasets to investigate the molecular mechanisms of immunoglobulin E-mediated atopic diseases
Authors: Huang Susie S Y , Al Ali Fatima , Boughorbel Sabri , Toufiq Mohammed , Chaussabel Damien , Garand Mathieu
Published: May 2019

Prevalence of allergies has reached ~20% of population in developed countries and sensitization rate to one or more allergens among school age children are approaching 50%. However, the combination of the complexity of atopic allergy susceptibility/development and environmental factors has made identification of gene biomarkers challenging. The amount of publicly accessible transcriptomic data presents an unprecedented opportunity for mechanistic discoveries and validation of complex disease signatures across studies. However, this necessitates structured methodologies and visual tools for the interpretation of results. Here, we present a curated collection of transcriptomic datasets relevant to immunoglobin E-mediated atopic diseases (ranging from allergies to primary immunodeficiencies). Thirty-three datasets from the Gene Expression Omnibus, encompassing 1860 transcriptome profiles, were made available on the Gene Expression Browser (GXB), an online and open-source web application that allows for the query, visualization and annotation of metadata. The thematic compositions, disease categories, sample number and platforms of the collection are described. Ranked gene lists and sample grouping are used to facilitate data visualization/interpretation and are available online via GXB (http://ige.gxbsidra.org/dm3/geneBrowser/list). Dataset validation using associated publications showed good concordance in GXB gene expression trend and fold-change.
Age-related analysis of the gut microbiome in a purebred dog colony
Authors: Mizukami Keijiro , Uchiyama Jumpei , Igarashi Hirotaka , Murakami Hironobu , Osumi Takafumi , Shima Ayaka , Ishiahra Genki , Nasukawa Tadahiro , Une Yumi , Sakaguchi Masahiro
Published: May 2019

Dogs are model animals that can be used to study the gut microbiome. Although the gut microbiome is assumed to be closely related to aging, information pertaining to this relationship in dogs is limited. Here, we examined the association between the canine gut microbiome and age via a bacterial 16S rRNA gene amplicon sequence analysis in a colony of 43 Japanese purebred Shiba Inu dogs. We found that microbial diversity tended to decrease with aging. A differential abundance analysis showed an association of a single specific microbe with aging. The age-related coabundance network analysis showed that two microbial network modules were positively and negatively associated with aging, respectively. These results suggest that the dog gut microbiome is likely to vary with aging.
A Category of Wide Subcategories
Authors: Buan Aslak Bakke , Marsh Bethany Rose
Published: May 2019

An algebra is said to be $\tau$-tilting finite provided it has only a finite number of $\tau$-rigid objects up to isomorphism. To each such algebra, we associate a category whose objects are the wide subcategories of its category of finite dimensional modules, and whose morphisms are indexed by support $\tau$-tilting pairs.
Multiple-Strain Infections of Human Cytomegalovirus With High Genomic Diversity Are Common in Breast Milk From Human Immunodeficiency Virus–Infected Women in Zambia
Authors: Suárez Nicolás M , Musonda Kunda G , Escriva Eric , Njenga Margaret , Agbueze Anthony , Camiolo Salvatore , Davison Andrew J , Gompels Ursula A
Published: May 2019

Background

In developed countries, human cytomegalovirus (HCMV) is a major pathogen in congenitally infected and immunocompromised individuals, where multiple-strain infection appears linked to disease severity. The situation is less documented in developing countries. In Zambia, breast milk is a key route for transmitting HCMV and carries higher viral loads in human immunodeficiency virus (HIV)–infected women. We investigated HCMV strain diversity.

Methods

High-throughput sequence datasets were generated from 28 HCMV-positive breast milk samples donated by 22 mothers (15 HIV-infected and 7 HIV-negative) at 4–16 weeks postpartum, then analyzed by genome assembly and novel motif-based genotyping in 12 hypervariable HCMV genes.

Results

Among the 20 samples from 14 donors (13 HIV-infected and one HIV-negative) who yielded data meeting quality thresholds, 89 of the possible 109 genotypes were detected, and multiple-strain infections involving up to 5 strains per person were apparent in 9 HIV-infected women. Strain diversity was extensive among individuals but conserved compartmentally and longitudinally within them. Genotypic linkage was maintained within hypervariable UL73/UL74 and RL12/RL13/UL1 loci for virus entry and immunomodulation, but not between genes more distant from each other.

Conclusions

Breast milk from HIV-infected women contains multiple HCMV strains of high genotypic complexity and thus constitutes a major source for transmitting viral diversity.
Plasma Fibronectin Levels Identified via Quantitative Proteomics Profiling Predicts Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B
Authors: Liu Fen , Seto Wai-Kay , Wong Danny Ka-Ho , Huang Fung-Yu , Cheung Ka-Shing , Mak Lung-Yi , Sharma Rakesh , Zhang Saisai , Fung James , Lai Ching-Lung , Yuen Man-Fung
Published: May 2019

Background

Seroclearance of hepatitis B surface antigen (HBsAg) is a potentially achievable target of chronic hepatitis B (CHB). Plasma proteins relevant to HBsAg seroclearance remain undetermined.

Methods

We prospectively recruited treatment-naive CHB patients with spontaneous HBsAg seroclearance and matched HBsAg-positive controls. Plasma protein profiling was performed using isobaric tags for relative and absolute quantitation-based proteomics, with the expression of candidate proteins validated in a separate cohort. The predictive value of fibronectin was assessed at 3 years, 1 year (Year -1) before, and at the time (Year 0) of HBsAg seroclearance.

Results

Four hundred eighty-seven plasma proteins were identified via proteomics, with 97 proteins showing altered expression. In the verification cohort (n = 90), median plasma fibronectin levels in patients with HBsAg seroclearance was higher than in controls (P = .009). In the longitudinal cohort (n = 164), patients with HBsAg seroclearance, compared with controls, had a higher median fibronectin levels at Year -1 (413.26 vs 227.95 µg/mL) and Year 0 (349.45 vs 208.72 µg/mL) (both P < .001). In patients with an annual HBsAg log reduction >0.5, Year -1 fibronectin level achieved an area under the receiving operator characteristic of 0.884 in predicting HBsAg seroclearance.

Conclusions

Using proteomics-based technology, plasma fibronectin may be associated with HBsAg seroclearance and a potential predictor of “functional cure”.
Tracing the Legacy: China's Historical Aid and Contemporary Investment in Africa
Authors: Morgan Pippa , Zheng Yu
Published: May 2019

In this article we depart from the classic model of foreign direct investment (FDI) determinants and examine the effect of sociohistorical factors on FDI. We argue that past foreign aid projects confer social capital that constitutes specific resources available to investors in the present, increasing their preferences for host countries in which their home country has accumulated more social capital. We use new data on China's historical aid in Africa to test these contentions, uncovering a positive, significant connection between China's historical aid program in Africa (1956–1999) and contemporary (2000–2015) investments by Chinese companies. While China's historical aid may have been politically driven, it has had important long-term consequences for its commercial investors. More broadly, these findings suggest a sociohistorical explanation of the puzzle of why Chinese foreign investments deviate from conventional FDI patterns.
Hybrid bag of approaches to characterize selection criteria for cohort identification
Authors: Vydiswaran V G Vinod , Strayhorn Asher , Zhao Xinyan , Robinson Phil , Agarwal Mahesh , Bagazinski Erin , Essiet Madia , Iott Bradley E , Joo Hyeon , Ko PingJui , Lee Dahee , Lu Jin Xiu , Liu Jinghui , Murali Adharsh , Sasagawa Koki , Wang Tianshi , Yuan Nalingna
Published: May 2019

Objective

The 2018 National NLP Clinical Challenge (2018 n2c2) focused on the task of cohort selection for clinical trials, where participating systems were tasked with analyzing longitudinal patient records to determine if the patients met or did not meet any of the 13 selection criteria. This article describes our participation in this shared task.

Materials and Methods

We followed a hybrid approach combining pattern-based, knowledge-intensive, and feature weighting techniques. After preprocessing the notes using publicly available natural language processing tools, we developed individual criterion-specific components that relied on collecting knowledge resources relevant for these criteria and pattern-based and weighting approaches to identify “met” and “not met” cases.

Results

As part of the 2018 n2c2 challenge, 3 runs were submitted. The overall micro-averaged F1 on the training set was 0.9444. On the test set, the micro-averaged F1 for the 3 submitted runs were 0.9075, 0.9065, and 0.9056. The best run was placed second in the overall challenge and all 3 runs were statistically similar to the top-ranked system. A reimplemented system achieved the best overall F1 of 0.9111 on the test set.

Discussion

We highlight the need for a focused resource-intensive effort to address the class imbalance in the cohort selection identification task.

Conclusion

Our hybrid approach was able to identify all selection criteria with high F1 performance on both training and test sets. Based on our participation in the 2018 n2c2 task, we conclude that there is merit in continuing a focused criterion-specific analysis and developing appropriate knowledge resources to build a quality cohort selection system.
‘Close confinement tells very much upon a man’: Prison Memoirs, Insanity and the Late Nineteenth- and Early Twentieth-Century Prison
Authors: Marland Hilary
Published: May 2019

This article explores prisoners’ observations of mental illness in late nineteenth- and early twentieth-century British prisons, recorded in memoirs published following their release. The discipline of separate confinement was lauded for its potential to improve prisoners’ minds, inducing reflection and reform, when it was introduced in the 1840s, but in practice led to high levels of mental breakdown. In order to maintain the integrity of the prison system, the prison authorities played down incidences of insanity, while prison chaplains lauded the beneficent influence of cellular isolation. In contrast, as this article demonstrates, prisoners’ memoirs offer insights into the prevalence of mental illness in prison, and its poor management, as well as inmates’ efforts to manage mental distress. As the prison system became more closed, uniform and penal after the 1860s, the volume of such publications increased. Oscar Wilde’s evocative prison writings have attracted considerable attention, but he was only one of many prison authors criticizing the penal system and decrying the damage it inflicted on the mind. Exploration of prison memoirs, it is argued, enhances our understanding of experiences of mental disorder in the underexplored context of the prison, highlighting the prisoners’ voice, agency and advocacy of reform.
Alkaline Ceramidase Mediates the Oxidative Stress Response in Drosophila melanogaster Through Sphingosine
Authors: Zhang Chun-Hong , Zhang Min-Jing , Shi Xiao-Xiao , Mao Cungui , Zhu Zeng-Rong
Published: May 2019

Alkaline ceramidase (Dacer) in Drosophila melanogaster was demonstrated to be resistant to paraquat-induced oxidative stress. However, the underlying mechanism for this resistance remained unclear. Here, we showed that sphingosine feeding triggered the accumulation of hydrogen peroxide (H2O2). Dacer-deficient D. melanogaster (Dacer mutant) has higher catalase (CAT) activity and CAT transcription level, leading to higher resistance to oxidative stress induced by paraquat. By performing a quantitative proteomic analysis, we identified 79 differentially expressed proteins in comparing Dacer mutant to wild type. Three oxidoreductases, including two cytochrome P450 (CG3050, CG9438) and an oxoglutarate/iron-dependent dioxygenase (CG17807), were most significantly upregulated in Dacer mutant. We presumed that altered antioxidative activity in Dacer mutant might be responsible for increased oxidative stress resistance. Our work provides a novel insight into the oxidative antistress response in D. melanogaster.