bluuebunny/crossref_metadata_2025 huggingface dataset:
Activin A: a novel urinary biomarker of renal impairment in multiple myeloma
Authors: Iriuchishima Hirono , Maeshima Akito , Takahashi Shunsuke , Ishizaki Takuma , Yokohama Akihiko , Tsukamoto Norifumi , Saitoh Takayuki , Murakami Hirokazu , Handa Hiroshi
Published: May 2019

Renal impairment (RI) is a common complication of multiple myeloma (MM) that significantly affects treatment efficacy and mortality. However, no useful biomarkers for early detection of renal damage in MM exist. Reports indicate that activin A, a multifunctional cytokine of the TGF-β superfamily, is involved in the development and progression of various kidney diseases. In the present study, we measured urinary activin A levels in patients with newly diagnosed MM (NDMM) (n=41), smoldering MM (SMM) (n=10), and monoclonal gammopathy of undetermined significance (MGUS) (n=28), including monoclonal gammopathy of renal significance (MGRS), and assessed the correlation between urinary activin A and several clinical parameters. Urinary activin A, undetectable in healthy volunteers, was significantly increased in NDMM patients but not in patients with SMM and MGUS (97.3, 25.0, and 6.61 mg/gCr, respectively, P<0.05). In all patients with NDMM, urinary activin A levels were significantly reduced after initial treatment regardless of the therapy regimen. There was a significant correlation of urinary activin A with spot urinary protein level (P<0.001) and serum M-protein (P=0.029) but not with estimated glomerular filtration rate (eGFR), serum creatinine (Cr), N-acetyl-glucosaminidase (NAG), and serum activin A level. Histological analysis using renal biopsy samples revealed that activin A, which was absent from normal kidneys, was detected in the renal tubular cells of patients with MGRS. These data suggest that urinary activin A reflects tubular injury in MM and might aid the early detection of RI in plasma cell neoplasms.
Prevention of lipopolysaccharide-induced CD11b+ immune cell infiltration in the kidney: role of AT2 receptors
Authors: Patel Sanket , Dhande Isha , Gray Elizabeth Alana , Ali Quaisar , Hussain Tahir
Published: May 2019

Immune cell infiltration plays a central role in mediating endotoxemic acute kidney injury (AKI). Recently, we have reported the anti-inflammatory and reno-protective role of angiotensin-II type-2 receptor (AT2R) activation under chronic low-grade inflammatory condition in the obese Zucker rat model. However, the role of AT2R activation in preventing lipopolysaccharide (LPS)-induced early infiltration of immune cells, inflammation and AKI is not known. Mice were treated with AT2R agonist C21 (0.3 mg/kg), with and without AT2R antagonist PD123319 (5 mg/kg) prior to or concurrently with LPS (5 mg/kg) challenge. Prior-treatment with C21, but not concurrent treatment, significantly prevented the LPS-induced renal infiltration of CD11b+ immune cells, increase in the levels of circulating and/or renal chemotactic cytokines, particularly interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) and markers of renal dysfunction (blood urea nitrogen and albuminuria), while preserving anti-inflammatory interleukin-10 (IL-10) production. Moreover, C21 treatment in the absence of LPS increased renal and circulating IL-10 levels. To investigate the role of IL-10 in a cross-talk between epithelial cells and monocytes, we performed in vitro conditioned media (CM) studies in human kidney proximal tubular epithelial (HK-2) cells and macrophages (differentiated human monocytes, THP-1 cells). These studies revealed that the conditioned-media derived from the C21-treated HK-2 cells reduced LPS-induced THP-1 tumor necrosis factor-α (TNF-α) production via IL-10 originating from HK-2 cells. Our findings suggest that prior activation of AT2R is prophylactic in preventing LPS-induced renal immune cell infiltration and dysfunction, possibly via IL-10 pathway.
Modelling and analysis for two‐tier HCNs with co‐tier and cross‐tier separation dependencies
Authors: Sinnen Meshal , Li Kwok Hung , Teh Kah Chan
Published: May 2019

Heterogeneous cellular networks (HCNs) present an attractive solution to increased demands in mobile user capacity. Comprehensive studies have been conducted in stochastic geometric models that represent the relatively random placement of base transmitting stations (BTSs) operating at different power levels. This study considers the design of two‐tier HCNs for which picocell BTSs from the second tier are separated simultaneously from each other and from their tier‐1 macrocell counterparts. These separations, introduced in detail in the study, are termed the co‐tier and cross‐tier separations, with each parameter characterised by a minimum distance separation. Subsequently, expressions are obtained for distance distributions of BTSs from specific tiers to typical users, followed by conditional probabilities of association with each tier. We show that a minimum radius of association can be guaranteed for a tier‐2 BTS based on the values of co‐tier and cross‐tier separations. Furthermore, we analyse the Laplace transform of interference to the typical user and the resultant formulae for coverage probability, and by extension, area spectral efficiency. Numerical results demonstrating the effect of co‐tier and cross‐tier separation on these performance parameters support the analysis and provide insights into cell planning based on this concept.
Joint admission control and beamforming in max–min fairness networks
Authors: Lin Jingran , Gu Chenglu , Yang Jian , Li Qiang , Wang Wen‐Qin
Published: May 2019

The max–min fairness (MMF) strategy has been widely employed to manage wireless networks since it guarantees fairness among users. However, with a large number of users awaiting service, the network tends to be congested and the quality‐of‐service (QoS) will degrade substantially. This motivates us to study the MMF problem jointly with the consideration of admission control. Specifically, the authors consider a downlink network consisting of a multi‐antenna base station (BS) and multiple single‐antenna users. By jointly optimising the admissible users and the BS transmit beamformers, they aim to maximise the minimum signal‐to‐interference‐plus‐noise‐ratio of the admissible users, such that high QoS and fairness can be guaranteed simultaneously for them. This problem is essentially NP‐hard, and hence they pursue an efficient approximate solution to it. To this end, they first reformulate this problem from the perspective of sparse optimisation, and then develop a low‐complexity algorithm to iteratively solve the approximate problem. Moreover, to facilitate the algorithm's implementation, they further recast the subproblem in each iteration, such that it fits into the framework of the alternating direction methods of multipliers. Finally, an efficient distributed algorithm is designed, with each step being simply computed in a closed form.
Planning, operation and flexibility contribution of multi‐carrier energy storage systems in integrated energy systems
Authors: Keihan Asl Dariush , Hamedi Alireza , Reza Seifi Ali
Published: May 2019

Development in utilising the energy storage system (ESS) has led to increasing flexibility in the planning of energy networks. This study presents optimal day‐ahead scheduling for multi‐carrier energy networks in the presence of ESS. To achieve this purpose, a new economic approach for ESS is proposed that aims to utilise for generation management in the multi‐carrier networks. Also, the proposed economic approach presents a novel pricing policy that reduces the total cost of the system at each time interval. Therefore, the proposed pricing policy results in obtaining the charging and discharging pattern of ESS adaptively. To solve the multi‐period optimal energy flow problem in multi‐carrier energy networks, this study utilises the well‐known teaching‐learning based optimisation algorithm. The investigated multi‐carrier energy system consists of electrical, natural gas and district heating sub‐networks in which an ESS is included in the electrical sub‐network. The performance of the proposed approach is validated by comparing the ESS daily charging and discharging pattern and the daily load demand curve. The results show that the proposed method could be utilised for load shedding and tracking the load demand curve more effectively.
Lipid Profiles in Lyme Borreliosis: A Potential Role for Apheresis?
Authors: Straube Richard , Voit-Bak Karin , Gor A. , Steinmeier Til , Chrousos George P. , Boehm Bernhard Otto , Birkenfeld Andreas L. , Barbir Mahmoud , Balanzew Wladimir , Bornstein Stefan R.
Published: May 2019

Dyslipidemia and dyslipoproteinemia are common causes of metabolic and cardiovascular diseases. On the other hand, intracellular bacteria, such as Borrelia burgdorferi, utilize host lipids to survive and disseminate within the host. Recent data suggest that elevated lipids are a contributing factor to the maintenance and severity of Lyme disease and its complications. Here we review and discuss the role of lipids in Borreliosis and report on a pilot trial to examine the potential roles of circulating lipids and lipoproteins in patients with Borrelia infection. In this analysis we assessed the clinical and lipid profiles of 519 patients (319 women, 200 men) with a proven history of Lyme disease, before and after an extracorporeal double membrane filtration. Lipid profiles pre- and post-apheresis were analyzed in conjunction with clinical symptoms and parameters of inflammation. Circulating cholesterol, triglycerides, LDL, LP(a), and other inflammatory lipids were significantly reduced after the apheresis, while symptoms of the disorder and bioindexes of inflammation such as CRP improved. Further studies should be initiated to investigate the possibly causal relation between Lyme disease and circulating lipids and to design appropriate therapeutic strategies.
Standards bei der operativen Behandlung des Ulcus cruris
Authors: Hermanns Hans Joachim
Published: May 2019

Die operative Therapie chronischer Beingeschwüre bietet heute ein breites Spektrum an Behandlungsmöglichkeiten, die überwiegend auf Standards als einheitlich anerkannte Behandlungs konzepte beruhen und sich gegenüber anderen Techniken durchgesetzt haben. Beim Ulcus cruris venosum steht die Ausschaltung des venösen Refluxes im Vordergrund und reduziert die Rezidivrate im Vergleich zur alleinigen konservativen Therapie erheblich. Hierzu stehen neben der klassischen Venenchirurgie moderne endovenöse Therapieoptionen wie Laser-Therapie, Radiofrequenz-Obliteration, Schaumsklerosierung oder Cyanoacrylatembolisation zur Verfügung.

In der lokalen operativen Therapie chronischer Ulzerationen hat sich die Shave-Therapie mit simultaner Meshgraft-Plastik als Methode der ersten Wahl etabliert. Langzeitergebnisse mit Heilungsraten von bis zu 85 % sind mit keinem anderen Verfahren zu erreichen. Der kruralen Fasziektomie sind heute einige spezielle Indikationen vorbehalten: Transfasziale Nekrosen, Mehrfachrezidive nach Shave-Therapie und metaplastische Ossifikationen sind erfolgreich durch eine Fasziektomie zu behandeln. Neben der richtigen Wahl des Operationsverfahrens ist der langfristige Heilungserfolg geprägt von einer standardisierten postoperativen und poststationären Langzeitbetreuung.
Pushing resolution limits for extracting 1H–1H scalar coupling constants by a resolution-enhanced selective refocusing method
Authors: Zeng Qing , Lin Yanqin , Chen Zhong
Published: May 2019

Nuclear magnetic resonance (NMR) spectroscopy enables one to study molecular structure and dynamics in a noninvasive manner and has long served as a versatile and indispensable analytical tool in physics, chemistry, and biology. Scalar coupling, an essential feature in NMR spectroscopy, provides rich information regarding molecular structure and conformation. The measurement of scalar coupling constants, therefore, constitutes an important issue in NMR spectroscopy. Homonuclear 2D J-resolved spectroscopy is a powerful tool for multiplet analysis and coupling measurement. Recently, a number of phase-sensitive J-resolved methods and selective measuring methods have been developed to facilitate the extraction of coupling constants. However, resolution remains a crucial challenge when extracting small coupling constants or under inhomogeneous fields. In this paper, we present a resolution-enhanced selective refocusing (RESERF) method for the extraction of coupling constants. The effect of magnetic field inhomogeneity can be eliminated, resulting in very narrow linewidths. Therefore, samples with small coupling constants or under inhomogeneous fields can be well analyzed. The RESERF method may be of great value for structural and conformational studies in chemistry and biology.
Thin reaction zones in constant-density turbulent flows at low Damköhler numbers: Theory and simulations
Authors: Sabelnikov V. A. , Yu R. , Lipatnikov A. N.
Published: May 2019

Propagation of a single-reaction wave in a constant-density turbulent flow is studied by considering reaction rates that depend on the reaction progress variable c in a highly nonlinear manner. Analysis of Direct Numerical Simulation (DNS) data obtained recently from 26 reaction waves characterized by low Damköhler (0.01 < Da < 1) and high Karlovitz (6.5 < Ka < 587) numbers reveals the following trends. First, the ratio of consumption velocity UT to rms turbulent velocity u′ scales as square root of Da in line with Damköhler’s classical hypothesis. Second, the ratio of fully developed turbulent wave thickness to an integral length scale of turbulence decreases with increasing Da and tends to scale with inverse square root of Da, in line with the same hypothesis. Third, contrary to the widely accepted concept of distributed reaction zones, reaction-zone broadening is quite moderate even at Da = 0.01 and Ka = 587. Fourth, contrary to the same concept, UT/u′ is mainly controlled by the reaction-surface area. Fifth, UT/u′ does not vary with the laminar-reaction-zone thickness, provided that Da is constant. To explain the totality of these DNS results, a new theory is developed by (i) exploring the propagation of a molecular mixing layer attached to an infinitely thin reaction sheet in a highly turbulent flow and (ii) hypothesizing that the area of the reaction sheet is controlled by turbulent mixing. This hypothesis is supported by order-of-magnitude estimates and results in the aforementioned Damköhler’s scaling for UT/u′. The theory is also consistent with other aforementioned DNS results and, in particular, explains the weak influence of the laminar-reaction-zone thickness on UT/u′.
An open-type microdevice to improve the quality of fluorescence labeling for axonal transport analysis in neurons
Authors: Yokoyama S. , Otomo A. , Hadano S. , Kimura H.
Published: May 2019

Abnormal axonal transport of vesicles as well as organelles in a particular set of neurons is implicated in the pathogenesis of many neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. Although various types of microfluidic multicompartmental devices with closed microchannels have been recently developed and widely used for axonal transport analysis, most of the existing devices are troublesome and time-consuming to handle, such as culture maintenances, sample collections, and immunocytochemistry. In this study, we overcome such inherent shortcomings by developing a novel open-type device that enables easy cell maintenance and sample collections. In our device, microgrooves instead of microchannels were directly fabricated on a glass substrate, thereby making possible a high-resolution optical observation. Compared with the conventional closed-type devices, our newly designed device allowed us to efficiently and precisely label the axonal acidic vesicles by fluorescent dyes, facilitating a high-throughput analysis of axonal vesicular transport. The present novel device, as a user-friendly and powerful tool, can be implemented in molecular and cellular pathogenesis studies on neurological diseases.
Theoretical phase diagram of boron carbide from ambient to high pressure and temperature
Authors: Jay Antoine , Hardouin Duparc Olivier , Sjakste Jelena , Vast Nathalie
Published: May 2019

The phase diagram of boron carbide is calculated within the density functional theory as a function of temperature and pressure up to 80 GPa, accounting for icosahedral, graphitelike, and diamondlike atomic structures. Only some icosahedral phases turn out to be thermodynamically stable with atomic carbon concentrations (c) of 8.7% (B10.5C), 13.0% (B6.7C), 20% (B4C), and 28.6% (B2.5C), respectively. Their respective ranges of stability under pressure and temperature are calculated, and the theoretical T-P-c phase diagram boundaries are discussed. At ambient conditions, the introduction in the phase diagram of the new phase B10.5C with an ordered crystalline motif of 414 atoms is shown to bring the theoretical solubility range of carbon in boron close to the experimental one. The link with the experimental phase diagram consisting of one single phase having the R3¯m space group is discussed, and the concept of partial occupation of Wyckoff’s site is introduced. At high pressure, the phase diagram is defined by a new carbon-rich phase B2.5C, which is stabilized by both pressure and temperature in our calculations. All of the other diamond and graphite phases reported previously turn out to be thermodynamically unstable in our calculations, although some of them are observed in high pressure experiments.
Density functional orbitals in quantum Monte Carlo: The importance of accurate densities
Authors: Per Manolo C. , Fletcher Emily K. , Cleland Deidre M.
Published: May 2019

There has been significant recent attention surrounding the accuracy of electronic densities produced by modern parameterized density functional approximations (DFAs). Here, we investigate the impact of using orbitals from density functional calculations in fixed-node Diffusion Monte Carlo (DMC) methods, which is common practice in the calculation of large systems. We find that the accuracy of the density is a strong indicator of the quality of the many-body nodal surface produced by a determinant of the corresponding Kohn-Sham orbitals. Functionals which produce the most accurate electronic densities also produce the lowest variational DMC energies, while functionals that produce poor densities lead to significantly higher energies. This result simplifies the process of choosing orbitals for DMC calculations of large systems and suggests that prioritizing accurate densities in the future development of DFAs would also contribute to the continued improvement of DMC.
Self-assembly of biological networks via adaptive patterning revealed by avian intradermal muscle network formation
Authors: Wu Xiao-shan , Yeh Chao-yuan , Harn Hans I-Chen , Jiang Ting-Xing , Wu Ping , Widelitz Randall B. , Baker Ruth E. , Chuong Cheng-Ming
Published: May 2019

Significance

Humans have the most elaborate facial expressions, controlled by muscle networks anchored at distinct sites within the facial skin. Here, we reveal how muscle networks assemble robustly, adapting to external perturbations and insults, using avian intradermal muscle networks as a model. The muscle network is established with simple, local rules. Muscle fibers extend from feather buds in every direction, and connect to nearest neighbor buds. The network can be reconfigured, adapting to perturbed bud arrangement or mechanical cues. Our computational model validates the local rules, providing a potential mechanism for forming adaptive networks that could be useful in understanding other biological networks or designing nonbiological networks.
Humans adapt to social diversity over time
Authors: Ramos Miguel R. , Bennett Matthew R. , Massey Douglas S. , Hewstone Miles
Published: May 2019

Significance

Changes in social diversity constitute a key factor shaping today’s world, yet scholarly work about the consequences of diversity has been marked by a critical lack of consensus. To address this concern, we propose a multidisciplinary approach where psychological, sociological, and evolutionary perspectives are integrated to provide an account of how individuals adapt to changes in social diversity. With an analysis of 22 y of worldwide data, our results suggest that humans are initially inclined to react negatively to threats to homogeneity, but that these negative effects are compensated in the long term by the beneficial effects of intergroup contact. Our findings advance knowledge and inform political debate about one of the defining challenges of modern societies.
Structure of lipoprotein lipase in complex with GPIHBP1
Authors: Arora Rishi , Nimonkar Amitabh V. , Baird Daniel , Wang Chunhua , Chiu Chun-Hao , Horton Patricia A. , Hanrahan Susan , Cubbon Rose , Weldon Stephen , Tschantz William R. , Mueller Sascha , Brunner Reto , Lehr Philipp , Meier Peter , Ottl Johannes , Voznesensky Andrei , Pandey Pramod , Smith Thomas M. , Stojanovic Aleksandar , Flyer Alec , Benson Timothy E. , Romanowski Michael J. , Trauger John W.
Published: May 2019

Lipoprotein lipase (LPL) plays a central role in triglyceride (TG) metabolism. By catalyzing the hydrolysis of TGs present in TG-rich lipoproteins (TRLs), LPL facilitates TG utilization and regulates circulating TG and TRL concentrations. Until very recently, structural information for LPL was limited to homology models, presumably due to the propensity of LPL to unfold and aggregate. By coexpressing LPL with a soluble variant of its accessory protein glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) and with its chaperone protein lipase maturation factor 1 (LMF1), we obtained a stable and homogenous LPL/GPIHBP1 complex that was suitable for structure determination. We report here X-ray crystal structures of human LPL in complex with human GPIHBP1 at 2.5–3.0 Å resolution, including a structure with a novel inhibitor bound to LPL. Binding of the inhibitor resulted in ordering of the LPL lid and lipid-binding regions and thus enabled determination of the first crystal structure of LPL that includes these important regions of the protein. It was assumed for many years that LPL was only active as a homodimer. The structures and additional biochemical data reported here are consistent with a new report that LPL, in complex with GPIHBP1, can be active as a monomeric 1:1 complex. The crystal structures illuminate the structural basis for LPL-mediated TRL lipolysis as well as LPL stabilization and transport by GPIHBP1.
Objecting to experiments that compare two unobjectionable policies or treatments
Authors: Meyer Michelle N. , Heck Patrick R. , Holtzman Geoffrey S. , Anderson Stephen M. , Cai William , Watts Duncan J. , Chabris Christopher F.
Published: May 2019

Randomized experiments have enormous potential to improve human welfare in many domains, including healthcare, education, finance, and public policy. However, such “A/B tests” are often criticized on ethical grounds even as similar, untested interventions are implemented without objection. We find robust evidence across 16 studies of 5,873 participants from three diverse populations spanning nine domains—from healthcare to autonomous vehicle design to poverty reduction—that people frequently rate A/B tests designed to establish the comparative effectiveness of two policies or treatments as inappropriate even when universally implementing either A or B, untested, is seen as appropriate. This “A/B effect” is as strong among those with higher educational attainment and science literacy and among relevant professionals. It persists even when there is no reason to prefer A to B and even when recipients are treated unequally and randomly in all conditions (A, B, and A/B). Several remaining explanations for the effect—a belief that consent is required to impose a policy on half of a population but not on the entire population; an aversion to controlled but not to uncontrolled experiments; and a proxy form of the illusion of knowledge (according to which randomized evaluations are unnecessary because experts already do or should know “what works”)—appear to contribute to the effect, but none dominates or fully accounts for it. We conclude that rigorously evaluating policies or treatments via pragmatic randomized trials may provoke greater objection than simply implementing those same policies or treatments untested.
RNA ligands activate the Machupo virus polymerase and guide promoter usage
Authors: Pyle Jesse D. , Whelan Sean P. J.
Published: May 2019

Significance

Atomic structures of the polymerase–endonuclease complex of the orthomyxovirus influenza and the orthobunyavirus La Crosse—two distinct segmented negative-sense (SNS) RNA viruses—demonstrate that binding of the genomic 5′ RNA rearranges the catalytic residues of the RNA-dependent RNA-polymerase (RdRP). Working with the arenavirus, Machupo, we demonstrate that 5′ RNAs from the genomic and antigenomic copies of both segments activate the RdRP in conjunction with a specific promoter. This study builds upon structural studies with two different SNS RNA viruses to reveal a previously unappreciated mechanism of RNA-guided promoter-specific polymerase regulation in SNS RNA viruses. The conservation of activating RNA elements among the polymerase–endonuclease complexes of SNS RNA viruses suggests new avenues for developing antiviral therapeutics.
Aspirations and Job Success of Highly Qualified Second Generation Iranians in Germany
Authors: Müller Lars , Kooij René
Published: May 2019

This study pioneers the quantitative research of second generation Iranian graduates in Germany. Second generation immigrants in Germany, immigrants raised in Germany with at least one parent born abroad, are relevant as they are a crucial part of German society. Second generation immigrants in general as well as Iranians in particular are assumed to have high extrinsic aspirations. But a dataset big enough to study the employment situation of second generation Iranian graduates in Germany did not exist. Therefore, the article uses the KOAB dataset from 2011 to 2015, which contains data from 53,429 full-time employed higher education graduates in Germany (among those are 161 second generation Iranians). Their extrinsic job aspirations and career success (income, job satisfaction) are analyzed. Multivariate analyses reveal the higher extrinsic job aspirations of second generation Iranian graduates compared to many other migrant groups and Germans but similar to second generation Turkish graduates. Nevertheless, the extrinsic job aspiration is relevant, though only one factor among others to predict career success.
Strengthening mechanism of age-hardenable Al–xMg–3Zn alloys
Authors: Ding Qingwei , Zhang Di , Pan Yanlin , Hou Shengli , Zhuang Linzhong , Zhang Jishan
Published: May 2019

The addition of 3 wt-% Zn to the traditional Al–Mg alloy doubled its strength. To understand the strengthening mechanism, the enhancement in strength with the variation in Mg content was studied. The grain boundary and solid solution strengthening decrease with the reduction in the Mg content; however, their contributions to the yield strength are insignificant. The contribution of precipitation strengthening to the yield strength is more than 80%; however, due to the unchanged precipitate characteristics, the strengthening effect changes slightly with the variation in the Mg content. The reduction in strength is primarily due to Mg solid solution strengthening. The variation in the ductility of Al–Mg–Zn alloys was studied by fracture analysis.
The torsion in symmetric powers on congruence subgroups of Bianchi groups
Authors: Pfaff Jonathan , Raimbault Jean
Published: May 2019

In this paper we prove that for a fixed neat principal congruence subgroup of a Bianchi group the order of the torsion part of its second cohomology group with coefficients in an integral lattice associated with the

m
m

th symmetric power of the standard representation of

SL
2

⁡
(

C

)

\operatorname {SL}_2(\mathbb {C})

grows exponentially in

m
2

m^2

. We give upper and lower bounds for the growth rate. Our result extends a result of W. Müller and S. Marshall, who proved the corresponding statement for closed arithmetic

3
3

-manifolds, to the finite-volume case. We also prove a limit multiplicity formula for combinatorial Reidemeister torsions on higher-dimensional hyperbolic manifolds.
Normative Data for Derived Measures and Discrepancy Scores for the Uniform Data Set 3.0 Neuropsychological Battery
Authors: Devora Paulina V , Beevers Samantha , Kiselica Andrew M , Benge Jared F
Published: May 2019

Objective

The Uniform Data Set 3.0 (UDS 3.0) neuropsychological battery is a recently published battery intended for clinical research with older adult populations. While normative data for the core measures has been published, several additional discrepancy and derived scores can also be calculated. We present normative data for Trail Making Test (TMT) A & B discrepancy and ratio scores, semantic and phonemic fluency discrepancy scores, Craft Story percent retention score, Benson Figure percent retention score, difference between verbal and visual percent retention, and an error index.

Method

Cross-Sectional data from 1803 English speaking, cognitively normal control participants were obtained from the NACC central data repository.

Results

Descriptive information for derived indices is presented. Demographic variables, most commonly age, demonstrated small but significant associations with the measures. Regression values were used to create a normative calculator, made available in a downloadable supplement. Statistically abnormal values (i.e., raw scores corresponding to the 5th, 10th, 90th, and 95th percentiles) were calculated to assist in practical application of normative findings to individual cases. Preliminary validity of the indices are demonstrated by a case study and group comparisons between a sample of individuals with Alzheimer's (N = 81) and Dementia with Lewy Bodies (DLB; N = 100).

Conclusions

Clinically useful normative data of such derived indices from the UDS 3.0 neuropsychological battery are presented to help researchers and clinicians interpret these scores, accounting for demographic factors. Preliminary validity data is presented as well along with limitations and future directions.
Predicting drug-induced transcriptome responses of a wide range of human cell lines by a novel tensor-train decomposition algorithm
Authors: Iwata Michio , Yuan Longhao , Zhao Qibin , Tabei Yasuo , Berenger Francois , Sawada Ryusuke , Akiyoshi Sayaka , Hamano Momoko , Yamanishi Yoshihiro
Published: May 2019

Motivation

Genome-wide identification of the transcriptomic responses of human cell lines to drug treatments is a challenging issue in medical and pharmaceutical research. However, drug-induced gene expression profiles are largely unknown and unobserved for all combinations of drugs and human cell lines, which is a serious obstacle in practical applications.

Results

Here, we developed a novel computational method to predict unknown parts of drug-induced gene expression profiles for various human cell lines and predict new drug therapeutic indications for a wide range of diseases. We proposed a tensor-train weighted optimization (TT-WOPT) algorithm to predict the potential values for unknown parts in tensor-structured gene expression data. Our results revealed that the proposed TT-WOPT algorithm can accurately reconstruct drug-induced gene expression data for a range of human cell lines in the Library of Integrated Network-based Cellular Signatures. The results also revealed that in comparison with the use of original gene expression profiles, the use of imputed gene expression profiles improved the accuracy of drug repositioning. We also performed a comprehensive prediction of drug indications for diseases with gene expression profiles, which suggested many potential drug indications that were not predicted by previous approaches.

Supplementary information

Supplementary data are available at Bioinformatics online.
Integrating read-based and population-based phasing for dense and accurate haplotyping of individual genomes
Authors: Bansal Vikas
Published: May 2019

Motivation

Reconstruction of haplotypes for human genomes is an important problem in medical and population genetics. Hi-C sequencing generates read pairs with long-range haplotype information that can be computationally assembled to generate chromosome-spanning haplotypes. However, the haplotypes have limited completeness and low accuracy. Haplotype information from population reference panels can potentially be used to improve the completeness and accuracy of Hi-C haplotyping.

Results

In this paper, we describe a likelihood based method to integrate short-range haplotype information from a population reference panel of haplotypes with the long-range haplotype information present in sequence reads from methods such as Hi-C to assemble dense and highly accurate haplotypes for individual genomes. Our method leverages a statistical phasing method and a maximum spanning tree algorithm to determine the optimal second-order approximation of the population-based haplotype likelihood for an individual genome. The population-based likelihood is encoded using pseudo-reads which are then used as input along with sequence reads for haplotype assembly using an existing tool, HapCUT2. Using whole-genome Hi-C data for two human genomes (NA19240 and NA12878), we demonstrate that this integrated phasing method enables the phasing of 97–98% of variants, reduces the switch error rates by 3–6-fold, and outperforms an existing method for combining phase information from sequence reads with population-based phasing. On Strand-seq data for NA12878, our method improves the haplotype completeness from 71.4 to 94.6% and reduces the switch error rate 2-fold, demonstrating its utility for phasing using multiple sequencing technologies.

Availability and implementation

Code and datasets are available at https://github.com/vibansal/IntegratedPhasing.
Unsupervised segmentation of mass spectrometric ion images characterizes morphology of tissues
Authors: Guo Dan , Bemis Kylie , Rawlins Catherine , Agar Jeffrey , Vitek Olga
Published: May 2019

Motivation

Mass spectrometry imaging (MSI) characterizes the spatial distribution of ions in complex biological samples such as tissues. Since many tissues have complex morphology, treatments and conditions often affect the spatial distribution of the ions in morphology-specific ways. Evaluating the selectivity and the specificity of ion localization and regulation across morphology types is biologically important. However, MSI lacks algorithms for segmenting images at both single-ion and spatial resolution.

Results

This article contributes spatial-Dirichlet Gaussian mixture model (DGMM), an algorithm and a workflow for the analyses of MSI experiments, that detects components of single-ion images with homogeneous spatial composition. The approach extends DGMMs to account for the spatial structure of MSI. Evaluations on simulated and experimental datasets with diverse MSI workflows demonstrated that spatial-DGMM accurately segments ion images, and can distinguish ions with homogeneous and heterogeneous spatial distribution. We also demonstrated that the extracted spatial information is useful for downstream analyses, such as detecting morphology-specific ions, finding groups of ions with similar spatial patterns, and detecting changes in chemical composition of tissues between conditions.

Availability and implementation

The data and code are available at https://github.com/Vitek-Lab/IonSpattern.

Supplementary information

Supplementary data are available at Bioinformatics online.
Efficient merging of genome profile alignments
Authors: Hennig André , Nieselt Kay
Published: May 2019

Motivation

Whole-genome alignment (WGA) methods show insufficient scalability toward the generation of large-scale WGAs. Profile alignment-based approaches revolutionized the fields of multiple sequence alignment construction methods by significantly reducing computational complexity and runtime. However, WGAs need to consider genomic rearrangements between genomes, which make the profile-based extension of several whole-genomes challenging. Currently, none of the available methods offer the possibility to align or extend WGA profiles.

Results

Here, we present genome profile alignment, an approach that aligns the profiles of WGAs and that is capable of producing large-scale WGAs many times faster than conventional methods. Our concept relies on already available whole-genome aligners, which are used to compute several smaller sets of aligned genomes that are combined to a full WGA with a divide and conquer approach. To align or extend WGA profiles, we make use of the SuperGenome data structure, which features a bidirectional mapping between individual sequence and alignment coordinates. This data structure is used to efficiently transfer different coordinate systems into a common one based on the principles of profiles alignments. The approach allows the computation of a WGA where alignments are subsequently merged along a guide tree. The current implementation uses progressiveMauve and offers the possibility for parallel computation of independent genome alignments. Our results based on various bacterial datasets up to several hundred genomes show that we can reduce the runtime from months to hours with a quality that is negligibly worse than the WGA computed with the conventional progressiveMauve tool.

Availability and implementation

GPA is freely available at https://lambda.informatik.uni-tuebingen.de/gitlab/ahennig/GPA. GPA is implemented in Java, uses progressiveMauve and offers a parallel computation of WGAs.

Supplementary information

Supplementary data are available at Bioinformatics online.
Ecological Effects of Free-Roaming Horses in North American Rangelands
Authors: Davies Kirk W , Boyd Chad S
Published: May 2019

Free-roaming horses are a widespread conservation challenge. Horse use (grazing and related impacts) is largely unmanaged, leading to concerns about its impact on native plant communities and ecosystem function. We synthesized the literature to determine the ecological effects of free-roaming horses in North American rangelands. Largely unmanaged horse use can alter plant community composition, diversity, and structure and can increase bare ground and erosion potential. Free-roaming-horse use has also been linked to negative impacts on native fauna. Horses have repeatedly been shown to limit and even exclude native wildlife's use of water sources. These effects would likely be greatly reduced if the horse populations were better managed, but sociopolitical factors often preclude improved management. Using rigorous ecological research to educate politicians and the general public may facilitate the development of science-based management of free-roaming horses; however, ecological effects may have to become more severe before such changes can be realized.
Subtherapeutic Rifampicin Concentration Is Associated With Unfavorable Tuberculosis Treatment Outcomes
Authors: Ramachandran Geetha , Chandrasekaran Padmapriyadarshini , Gaikwad Sanjay , Agibothu Kupparam Hemanth Kumar , Thiruvengadam Kannan , Gupte Nikhil , Paradkar Mandar , Dhanasekaran Kavitha , Sivaramakrishnan Gomathi Narayan , Kagal Anju , Thomas Beena , Pradhan Neeta , Kadam Dileep , Hanna Luke Elizabeth , Balasubramanian Usha , Kulkarni Vandana , Murali Lakshmi , Golub Jonathan , Gupte Akshay , Shivakumar Shri Vijay Bala Yogendra , Swaminathan Soumya , Dooley Kelly E , Gupta Amita , Mave Vidya
Published: May 2019

Background

The relationships between first-line drug concentrations and clinically important outcomes among patients with tuberculosis (TB) remain poorly understood.

Methods

We enrolled a prospective cohort of patients with new pulmonary TB receiving thrice-weekly treatment in India. The maximum plasma concentration of each drug was determined at months 1 and 5 using blood samples drawn 2 hours postdose. Subtherapeutic cutoffs were: rifampicin <8 µg/mL, isoniazid <3 µg/mL, and pyrazinamide <20 µg/mL. Factors associated with lower log-transformed drug concentrations, unfavorable outcomes (composite of treatment failure, all-cause mortality, and recurrence), and individual outcomes were examined using Poisson regression models.

Results

Among 404 participants, rifampicin, isoniazid, and pyrazinamide concentrations were subtherapeutic in 85%, 29%, and 13%, respectively, at month 1 (with similar results for rifampicin and isoniazid at month 5). Rifampicin concentrations were lower with human immunodeficiency virus coinfection (median, 1.6 vs 4.6 µg/mL; P = .015). Unfavorable outcome was observed in 19%; a 1-μg/mL decrease in rifampicin concentration was independently associated with unfavorable outcome (adjusted incidence rate ratio [aIRR], 1.21 [95% confidence interval {CI}, 1.01–1.47]) and treatment failure (aIRR, 1.16 [95% CI, 1.05–1.28]). A 1-μg/mL decrease in pyrazinamide concentration was associated with recurrence (aIRR, 1.05 [95% CI, 1.01–1.11]).

Conclusions

Rifampicin concentrations were subtherapeutic in most Indian patients taking a thrice-weekly TB regimen, and low rifampicin and pyrazinamide concentrations were associated with poor outcomes. Higher or more frequent dosing is needed to improve TB treatment outcomes in India.
Vedolizumab Treatment in Extra-Intestinal Manifestations in Inflammatory Bowel Disease: A Systematic Review
Authors: Chateau Thomas , Bonovas Stefanos , Le Berre Catherine , Mathieu Nicolas , Danese Silvio , Peyrin-Biroulet Laurent
Published: May 2019

Background and Aims

We aimed to summarize existing data on the effectiveness of vedolizumab in extra-intestinal manifestations [EIMs] in inflammatory bowel disease [IBD].

Methods

We conducted a systematic literature search in PubMed and the Cochrane Library, up to October 2018. Interventional and non-interventional studies as well as case-series studying vedolizumab and EIMs in adult patients with IBD were considered eligible.

Results

Three interventional studies [one randomized trial, n = 1032; and two open-label trials, n = 347], five non-interventional studies [n = 1496] and three case-series [n = 17] were included. Vedolizumab did not show any effectiveness in primary sclerosing cholangitis [PSC]. While no effect was seen in pre-existing manifestations regarding arthralgia and arthritis, the occurrence of new rheumatic symptoms was lower among vedolizumab users compared to placebo; occurrence was higher, however, with vedolizumab than with tumour necrosis factor inhibitors. Finally, vedolizumab appears not to be efficacious for the treatment of cutaneous manifestations.

Conclusions

There is no strong evidence to suggest that vedolizumab may be efficacious for the treatment of pre-existing EIMs [especially PSC, rheumatic and cutaneous manifestations], although it may reduce the occurrence of new EIMs.
The Individual in Context(s): Research Potentials of the Socio-Economic Panel Study (SOEP) in Sociology
Authors: Giesselmann Marco , Bohmann Sandra , Goebel Jan , Krause Peter , Liebau Elisabeth , Richter David , Schacht Diana , Schröder Carsten , Schupp Jürgen , Liebig Stefan
Published: May 2019

The German Socio-Economic Panel (SOEP) study is a rich resource for sociologists, mainly because it offers direct measures of respondents’ contexts. The SOEP data provide (i) information retrieved from individuals themselves, (ii) direct information retrieved from their parents, partners, and organizations, (iii) prospectively collected information on past characteristics, and (iv) regional and spatial identifiers allowing researchers to link the data with regional-level characteristics. As the study has been in the field since 1984, the data also reflect variation in institutional and structural settings over time. Regular refreshment samples provide options to identify cohort effects. Together, these features allow multi-layered contextual designs that offer substantive insights into the effects of formal and informal institutions on individual behaviour and living conditions. This article introduces the main types of SOEP-based sociological research designs and discusses their survey methodological origins. It also points to underexplored potentials as well as limitations of the SOEP. Finally, it offers basic suggestions for approaching the data in each of the research designs presented.
Prevalence and genetic diversity of Vibrio parahaemolyticus strains from salmon in Chinese markets
Authors: Xie Tengfei , Wu Gang , He Xujun , Lai Zengzhe , Zhang Huatong , Zhao Jing
Published: May 2019

Consumption of contaminated salmon in China has led to pathogenic Vibrio parahaemolyticus infections in humans. In this study, 420 salmon samples were collected from supermarkets and restaurants in China that showed a contamination rate of 9.05 and 15.24%, respectively. Eighteen antibiotics were used to test the antibiotic susceptibility of all 51 isolates. The most common resistance was observed to β-lactam antibiotics and aminoglycosides, including ampicillin (92.16%), streptomycin (88.24%), kanamycin (45.10%) and cephazolin (45.10%). Meanwhile, many strains were resistant to more than two antibiotics (48/51, 94.12%). Only two and five isolates were positive for tdh and trh, respectively. Serotyping results demonstrated that O2 was most prevalence serotype (15/51, 29.41%). Molecular typing (enterobacterial repetitive intergenic consensus sequence polymerase chain reaction and multilocus sequence typing) allowed classification of all the isolates into 5 clusters and 44 sequence types, highlighting genetic variation and relatedness. In general, the high antibiotic resistance is alarming and raises public health concerns. Frequent monitoring of salmon for V. parahaemolyticus contamination, genetic diversity and antibiotic susceptibility is essential to improve seafood safety.
Misinformation Effect in Aging: A New Light with Equivalence Testing
Authors: Tessoulin Marine , Galharret Jean-Michel , Gilet Anne-Laure , Colombel Fabienne
Published: May 2019

Objectives

To better characterize the formation of false memories in older adults, we conducted a study using a French adaptation of the misinformation paradigm from Loftus, Levidow, and Duensing (1992). We aimed to show higher false memory production in older than in younger adults.

Method

One hundred and four younger adults (18–30 years) and 104 older adults (70–95 years) took part in the study. Participants were presented with a misinformation paradigm through the viewing of a short video followed by a questionnaire containing misinformation about the film. After a short delay (45 min), they performed a recognition task.

Results

Contrary to our hypothesis, the results analyzed with a Welch t test did not reveal a greater misinformation effect in older adults than in younger adults. Results were reanalyzed using the equivalence test which indicated that younger and older adults are statistically equivalent and not statistically different.

Discussion

The equivalence test helped to clarify the contradictory results of the literature. Furthermore, such results show the interest to reconsider misinformation effect in aging.