bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of the full‐length Serratia marcescens acetyltransferase AAC(3)‐Ia in complex with coenzyme A
Authors: Popov Georgy , Evdokimova Elena , Stogios Peter J. , Savchenko Alexei
Published: December 2019

Acyl‐coenzyme A‐dependent N‐acetyltransferases (AACs) catalyze the modification of aminoglycosides rendering the bacteria carrying such enzymes resistant to this class of antibiotics. Here we present the crystal structure of AAC(3)‐Ia enzyme from Serratia marcescens in complex with coenzyme A determined to 1.8 Å resolution. This enzyme served as an architype for the AAC enzymes targeting the amino group at Position 3 of aminoglycoside main aminocyclitol ring. The structure of this enzyme has been previously determined only in truncated form and was interpreted as distinct from subsequently characterized AACs. The reason for the unusual arrangement of secondary structure elements of AAC(3)‐Ia was not further investigated. By determining the full‐length structure of AAC(3)‐Ia we establish that this enzyme adopts the canonical AAC fold conserved across this family and it does not undergo through significant rearrangement of secondary structure elements upon ligand binding as was proposed previously. In addition, our results suggest that the C‐terminal tail in AAC(3)‐Ia monomer forms intramolecular hydrogen bonds that contributes to formation of stable dimer, representing the predominant oligomeric state for this enzyme.
Stakeholder outreach on process safety for process industry using risk based approaches
Authors: Fauzi Rahman Jayaraman Siti Nur Balqis , Shariff Azmi Mohd , Zaini Dzulkarnain
Published: December 2019

For past decades, the industry and academician realized the core of effective process safety management (PSM) is closely related to good process safety culture. Major accidents in process industry occur at low frequency but the consequences on people, environmental, and assets damage are catastrophic. Previous accidents in process industry recorded many deaths and injuries of facility personnel and public. Hence, many regulations and best practices were introduced to avoid major accidents from occurring and to mitigate the consequences. Risk based process safety (RBPS) Guideline is one of best practices to manage PSM, using risk‐based approaches. When accidents happened, internal and external stakeholders are greatly impacted if it is not mitigated effectively. Thus, element stakeholder outreach which lies in Commit to Process Safety pillars are considered as important elements to protect the stakeholders and promoting good safety culture. This article presents a structured technique for stakeholder outreach using RBPS approaches and a work‐aid model to ease its implementation in process industry. The technique and work‐aid model are beneficial to help the organization managing stakeholders, educating the public on risk management and the importance of embracing safety culture in their life.
Chemical components, pharmacological actions, and clinical applications of Rhizoma Picrorhizae
Authors: Guo Ning , Jin Cheng , Shen Lan , Wu Fei , Lin Xiao , Feng Yi
Published: December 2019

Rhizoma Picrorhizae (RP) is a traditional Chinese medicine, which has always been used to treat many diseases like infantile epilepsy and malnutrition. In modern applications, it has been used to treat hepatitis B and various liver injuries with remarkable curative effects. So far, more than 90 chemical components have been reported in RP, mainly including iridoid glycosides, cucurbitacins, phenylethanoid glycosides, and phenolic glycosides. Among these, iridoid glycosides are the most important active ingredients, and about 30 such compounds have been isolated at present. In pharmacology, RP is beneficial to the choleresis, liver protection, anti‐inflammation, asthma relief, immune regulation, and protection of heart, brain, kidney, and other organs. There have been many investigations on this medicinal herb in recent years, and it has attracted much attention in the medicine domain. In this paper, through systematically consulting the relevant books and electronic databases, we analyzed, arranged, and summarized the available information on this herb to provide reference for its further research.
Hydraulic and turbulence structure of triangular labyrinth weir‐pool fishways
Authors: Dizabadi Shahram , Azimi Amir H.
Published: December 2019

Detailed laboratory experiments were conducted to analyze and evaluate a new weir‐pool fishway design. The new design consisted of a series of one‐cycle, triangular labyrinth weirs that formed a weir‐pool fish passage. Hydraulic characteristics of flow over the proposed fishway were examined for three pool lengths and a wide range of discharges. It was found that the new design had superior discharge capacity over classical weir‐pool fishways in plunging flow regime. Spatial and point analyses of measured velocity data were carried out to understand turbulence structure and distribution of turbulent flow. The power dissipation per unit volume was calculated for different tests, and it varied nonlinearly with discharge. Based on the limiting criteria for energy dissipation rates of different fish species, the maximum operating discharge for different slopes was extracted for the proposed design. The model‐to‐prototype scaling analysis was performed based on the recommended scaling factor of three for prototype. It was found that the approach velocity of prototype increased by 12%, whereas the total discharge increased by more than five times. The contour plots of time‐averaged velocity indicated that the proposed fishways offered diversified flow fields without exceeding the maximum velocity above the standards recommended for weir‐pool fishways. To study the size, direction, and periodicity of turbulent eddies, magnitude of the most energetic eddy and dominant frequencies were extracted using power spectrum analysis. Quadrant analysis consistently showed that Reynolds shear stresses in ejection and sweep events became weaker as the pool length increased. The small region of strong ejection and sweep events evidenced a good resting place for fish migration, whereas the generated turbulence was large enough to attract fish species to use the passage.
Gestational diabetes impacts fetal precursor cell responses with potential consequences for offspring
Authors: Algaba-Chueca Francisco , Maymó-Masip Elsa , Ejarque Miriam , Ballesteros Mónica , Llauradó Gemma , López Carlos , Guarque Albert , Serena Carolina , Martínez-Guasch Laia , Gutiérrez Cristina , Bosch Ramón , Vendrell Joan , Megía Ana , Fernández-Veledo Sonia
Published: December 2019

Fetal programming has been proposed as a key mechanism underlying the association between intrauterine exposure to maternal diabetes and negative health outcomes in offspring. To determine whether gestational diabetes mellitus (GDM) might leave an imprint in fetal precursors of the amniotic membrane and whether it might be related to adverse outcomes in offspring, a prospective case-control study was conducted, in which amniotic mesenchymal stem cells (AMSCs) and resident macrophages were isolated from pregnant patients, with either GDM or normal glucose tolerance, scheduled for cesarean section. After characterization, functional characteristics of AMSCs were analyzed and correlated with anthropometrical and clinical variables from both mother and offspring. GDM-derived AMSCs displayed an impaired proliferation and osteogenic potential when compared with control cells, accompanied by superior invasive and chemotactic capacity. The expression of genes involved in the inflammatory response (TNFα, MCP-1, CD40, and CTSS) was upregulated in GDM-derived AMSCs, whereas anti-inflammatory IL-33 was downregulated. Macrophages isolated from the amniotic membrane of GDM mothers consistently showed higher expression of MCP-1 as well. In vitro studies in which AMSCs from healthy control women were exposed to hyperglycemia, hyperinsulinemia, and palmitic acid confirmed these results. Finally, genes involved in the inflammatory response were associated with maternal insulin sensitivity and prepregnancy body mass index, as well as with fetal metabolic parameters. These results suggest that the GDM environment could program stem cells and subsequently favor metabolic dysfunction later in life. Fetal adaptive programming in the setting of GDM might have a direct negative impact on insulin resistance of offspring.

Significance statement Signatures of metabolic deregulation seem to remain in cells early in development. Given the location on the inner side of the placenta, amniotic membrane stem cells might be a good indicator of how the intrauterine environment impacts the fetus. To the best of authors' knowledge, this study showed for the first time how gestational diabetes disturbs both the phenotype and the functional characteristics of amniotic mesenchymal stem cells, and these alterations are related to maternal and fetal metabolic status, suggesting that fetal adaptive programming in the setting of gestational diabetes might have a direct impact on offspring.
Active Targeting of Dendritic Polyglycerols for Diagnostic Cancer Imaging
Authors: Pant Kritee , Neuber Christin , Zarschler Kristof , Wodtke Johanna , Meister Sebastian , Haag Rainer , Pietzsch Jens , Stephan Holger
Published: December 2019

Active tumor targeting involves the decoration of nanomaterials (NMs) with oncotropic vector biomolecules that selectively recognize certain antigens on malignant cells or in the tumor microenvironment. This strategy can facilitate intracellular uptake of NM through specific interactions such as receptor‐mediated endocytosis and can lead to prolonged retention in the malignant tissues by preventing rapid efflux from the tumor. Here, the design of actively targeting, renally excretible bimodal dendritic polyglycerols (dPGs) for diagnostic cancer imaging is described. Single‐domain antibodies (sdAbs) specifically binding to the epidermal growth factor receptor (EGFR) are employed herein as targeting warheads owing to their small size and high affinity for their corresponding antigen. The dPGs equipped with EGFR‐targeting feature are compared head‐to‐head with their nontargeting counterparts in terms of interaction with EGFR‐overexpressing cells in vitro as well as accumulation at receptor‐positive tumors in vivo. Experimental results reveal a higher specificity and preferential tumor accumulation for the α‐EGFR dPGs, resulting from the introduction of active targeting capabilities on their backbone. These results highlight the potential for improving the tumor uptake properties of dPGs by strategic use of sdAb functionalization, which can ultimately prove useful to the development of ultrasmall NM with highly specific tumor accumulation.
Simulations of the Oxidation and Degradation of Platinum Electrocatalysts
Authors: Kirchhoff Björn , Braunwarth Laura , Jung Christoph , Jónsson Hannes , Fantauzzi Donato , Jacob Timo
Published: December 2019

Improved understanding of the fundamental processes leading to degradation of platinum nanoparticle electrocatalysts is essential to the continued advancement of their catalytic activity and stability. To this end, the oxidation of platinum nanoparticles is simulated using a ReaxFF reactive force field within a grand‐canonical Monte Carlo scheme. 2–4 nm cuboctahedral particles serve as model systems, for which electrochemical potential‐dependent phase diagrams are constructed from the thermodynamically most stable oxide structures, including solvation and thermochemical contributions. Calculations in this study suggest that surface oxide structures should become thermodynamically stable at voltages around 0.80–0.85 V versus standard hydrogen electrode, which corresponds to typical fuel cell operating conditions. The potential presence of a surface oxide during catalysis is usually not accounted for in theoretical studies of Pt electrocatalysts. Beyond 1.1 V, fragmentation of the catalyst particles into [Pt6O8]4− clusters is observed. Density functional theory calculations confirm that [Pt6O8]4− is indeed stable and hydrophilic. These results suggest that the formation of [Pt6O8]4− may play an important role in platinum catalyst degradation as well as the electromotoric transport of Pt2+/4+ ions in fuel cells.
Dual Functional Monocytes Modulate Bactericidal and Anti‐Inflammation Process for Severe Osteomyelitis Treatment
Authors: Shi Miusi , Zhang Peng , Zhao Qin , Shen Kailun , Qiu Yun , Xiao Yin , Yuan Quan , Zhang Yufeng
Published: December 2019

Osteomyelitis is an inflammatory bone disease caused by infection microorganisms which leads to progressive bone destruction and loss. Drug resistance and inflammatory damage make it urgent to develop new dual‐functional therapies. Based on the powerful bactericidal effect of monocyte/macrophage cells by nature, a functional monocyte with programed anti‐inflammatory ability is promising for osteomyelitis treatment. Herein, gold nanocage (GNC)–modified monocytes are developed which contain aspirin to realize the controlled antibacterial and anti‐inflammatory process for bone infection treatment effectively. Aspirin@GNC‐laden monocytes inherit the biological functions of origin monocytes such as chemotaxis to bacteria, differentiation potential, and phagocytic ability. The controlled release of aspirin from GNC has a beneficial effect on improving the rate and amount of bone regeneration after the anti‐infection stage due to its ability to suppress the activity of natural immunity and induce osteoblast differentiation during the treatment of osteomyelitis. The present work described here is the first to utilize living monocytes to achieve a dual effect to antibacteria and anti‐inflammation in a time‐oriented and programed way, and provides an inspiration for future therapy based on this concept.
Factors associated with failure of dog's weight loss programmes
Authors: Porsani Mariana Y. H. , Teixeira Fábio A. , Amaral Andressa R. , Pedrinelli Vivian , Vasques Vinícius , de Oliveira Ariane G. , Vendramini Thiago H. A. , Brunetto Marcio A.
Published: December 2019

Background

Canine obesity is the cause of several health issues, and may predispose other diseases, such as orthopaedic disorders, endocrinopathies, metabolic abnormalities and cardiorespiratory disease which can lead to a decreased quality of life and reduced lifespan. Dog are considered overweight when their body weight is ≥15% above their ideal body weight, and as obese when their body weight exceeds 30% of optimal. Prevalence of canine obesity is estimated to be around 5%–20%, and up to 30%–40% when all overweight dogs are considered. Treatment is based on weight loss programmes, focused on caloric restriction associated with exercise. However, success rate of treatment is low.

Objectives

The aim of this study was to investigate the reasons for weight loss failure of obese dogs during treatment with low‐calorie diets.

Methods

Records of obese dogs undergoing weight loss programmes between May 2014 and May 2017, assessed by a team specialized in veterinary nutrition, were retrospectively evaluated. Dogs were classified according to weekly weight loss rate (WWLR) (<1%, between 1% and 2%, and more than 2%) and owner compliance with a dietary prescription and physical activity recommendations.

Results

The mean WWLR was not satisfactory (<1%) in 64.4% (n = 47/73) of dogs. Regarding owner compliance with the dietary prescription, 44.7% (n = 21/47) of owners did not follow diet prescriptions and physical activity recommendations for their dogs. There was a significant association (p = .01) between compliance of owners and satisfactory weight loss rate; however, there was no association between weight loss success, diet composition sex, reproductive status, age of the dogs and their physical activity (p ≥ .05).

Conclusions

Non‐compliance represents a great challenge in the treatment of canine obesity, and may be of more importance than other aspects.
Black holes in Sol minore
Authors: Faedo Federico , Farotti Daniele Angelo , Klemm Silke
Published: December 2019

Abstract

We consider black holes in five-dimensional N = 2 U(1)-gauged supergravity coupled to vector multiplets, with horizons that are homogeneous but not isotropic. We write down the equations of motion for electric and magnetic ansätze, and solve them explicitely for the case of pure gauged supergravity with magnetic U(1) field strength and Sol horizon. The thermodynamics of the resulting solution, which exhibits anisotropic scaling, is discussed. If the horizon is compactified, the geometry approaches asymptotically a torus bundle over AdS3. Furthermore, we prove a no-go theorem that states the nonexistence of supersymmetric, static, Sol-invariant, electrically or magnetically charged solutions with spatial cross-sections modelled on solvegeometry. Finally, we study the attractor mechanism for extremal static non-BPS black holes with nil- or solvegeometry horizons. It turns out that there are no such attractors for purely electric field strengths, while in the magnetic case there are attractor geometries, where the values of the scalar fields on the horizon are computed by extremization of an effective potential V
eff, which contains the charges as well as the scalar potential of the gauged supergravity theory. The entropy density of the extremal black hole is then given by the value of V
eff in the extremum.
Timing of anterior cruciate ligament reconstruction and preoperative pain are important predictors for postoperative kinesiophobia
Authors: Theunissen W. W. E. S. , van der Steen M. C. , Liu W. Y. , Janssen R. P. A.
Published: December 2019

Purpose

Fear of movement (kinesiophobia) is a major limiting factor in the return to pre-injury sport level after anterior cruciate ligament reconstruction (ACLR). The aim of this study was to gain insight into the prevalence of kinesiophobia pre-ACLR, 3 months post-ACLR and 12 months post-ACLR. Furthermore, the preoperative predictability of kinesiophobia at 3 months post-ACLR was addressed.

Methods

A retrospective study with data, which were prospectively collected as part of standard care, was conducted to evaluate patients who underwent ACLR between January 2017 and December 2018 in an orthopaedic outpatient clinic. Patient characteristics (age, sex, body mass index), injury-to-surgery time, preoperative pain level (KOOS pain subscale) and preoperative knee function (IKDC-2000) were used as potential predictor variables for kinesiophobia (TSK-17) at 3 months post-ACLR in linear regression analysis.

Results

The number of patients with a high level of kinesiophobia (TSK > 37) reduced from 92 patients (69.2%) preoperatively to 44 patients (43.1%) 3 months postoperatively and 36 patients (30.8%) 12 months postoperatively. The prediction model, based on a multivariable regression analysis, showed a positive correlation between four predictor variables (prolonged injury-to-surgery time, high preoperative pain level, male sex and low body mass index) and a high level of kinesiophobia at 3 months postoperatively (R2 = 0.384, p = 0.02).

Conclusion

The prevalence of kinesiophobia decreases during postoperative rehabilitation, but high kinesiophobia is still present in a large portion of the patients after ACLR. Timing of reconstruction seems to be the strongest predictor for high kinesiophobia 3 months post-ACLR. This study is the first step in the development of a screening tool to detect patients with kinesiophobia after ACLR. Identifying patients preoperatively opens the possibility to treat patients and thereby potentially increase the return to pre-injury sport level rate after ACLR.

Level of evidence

III.
Intermediate dimensions
Authors: Falconer Kenneth J. , Fraser Jonathan M. , Kempton Tom
Published: December 2019

We introduce a continuum of dimensions which are ‘intermediate’ between the familiar Hausdorff and box dimensions. This is done by restricting the families of allowable covers in the definition of Hausdorff dimension by insisting that $$|U| \le |V|^\theta $$

|
U
|

≤

|
V
|

θ

for all sets U, V used in a particular cover, where $$\theta \in [0,1]$$

θ
∈
[
0
,
1
]

is a parameter. Thus, when $$\theta =1$$

θ
=
1

only covers using sets of the same size are allowable, and we recover the box dimensions, and when $$\theta =0$$

θ
=
0

there are no restrictions, and we recover Hausdorff dimension. We investigate many properties of the intermediate dimension (as a function of $$\theta $$
θ
), including proving that it is continuous on (0, 1] but not necessarily continuous at 0, as well as establishing appropriate analogues of the mass distribution principle, Frostman’s lemma, and the dimension formulae for products. We also compute, or estimate, the intermediate dimensions of some familiar sets, including sequences formed by negative powers of integers, and Bedford–McMullen carpets.
Crossover and peaks in the Pleistocene climate spectrum; understanding from simple ice age models
Authors: Ditlevsen Peter , Mitsui Takahito , Crucifix Michel
Published: December 2019

The power spectrum provides a compact representation of the scale dependence of the variability in time series. At multi-millennial time scales the spectrum of the Pleistocene climate is composed of a set of narrow band spectral modes attributed to the regularly varying changes in insolation from the astronomical change in Earth’s orbit and rotation superimposed on a continuous background generally attributed to stochastic variations. Quantitative analyses of paleoclimatic records indicate that the continuous part comprises a dominant part of the variance. It exhibits a power-law dependency typical of stochastic, self-similar processes, but with a scale break at the frequency of glacial-interglacial cycles. Here we discuss possible origins of this scale break, the connection between the continuous background and the narrow bands, and the apparently modest spectral power above the continuum at these scales. We demonstrate that the observed scale break around 100 ka can have a variety of different origins and does not imply an internal time scale of correlation as implied by the simplest linear stochastic model.
High prevalence and genetic diversity of Haemoproteus columbae (Haemosporida: Haemoproteidae) in feral pigeons Columba livia in Cape Town, South Africa
Authors: Nebel Carina , Harl Josef , Pajot Adrien , Weissenböck Herbert , Amar Arjun , Sumasgutner Petra
Published: December 2019

In this study, we explore blood parasite prevalence, infection intensity, and co-infection levels in an urban population of feral pigeonsColumba liviain Cape Town. We analyze the effect of blood parasites on host body condition and the association between melanin expression in the host’s plumage and parasite infection intensity and co-infection levels. Relating to the haemosporidian parasite itself, we study their genetic diversity by means of DNA barcoding (cytochrome b) and show the geographic and host distribution of related parasite lineages in pigeons worldwide. Blood from 195C. liviaindividuals was collected from April to June 2018. Morphometric measurements and plumage melanism were recorded from every captured bird. Haemosporidian prevalence and infection intensity were determined by screening blood smears and parasite lineages by DNA sequencing. Prevalence ofHaemoproteusspp. was high at 96.9%. The body condition of the hosts was negatively associated with infection intensity. However, infection intensity was unrelated to plumage melanism. Thecytochrome bsequences revealed the presence of fourHaemoproteuslineages in our population of pigeons, which show high levels of co-occurrence within individual birds. Three lineages (HAECOL1, COLIV03, COQUI05) belong toHaemoproteus columbaeand differ only by 0.1% to 0.8% in thecytochrome bgene. Another lineage (COLIV06) differs by 8.3% from the latter ones and is not linked to a morphospecies, yet. No parasites of the generaLeucocytozoonandPlasmodiumwere detected.
Effect of platelet-rich fibrin on cell proliferation, migration, differentiation, inflammation, and osteoclastogenesis: a systematic review of in vitro studies
Authors: Strauss Franz-Josef , Nasirzade Jila , Kargarpoor Zahra , Stähli Alexandra , Gruber Reinhard
Published: December 2019

Objective

To systematically assess the effects of platelet-rich fibrin (PRF) on in vitro cellular behavior.

Methods

A systematic electronic search using MEDLINE database was performed. In vitro studies using PRF were considered and articles published up to June 31, 2018 were screened. Eligible studies were selected based on the use of human PRF.

Results

In total, 1746 titles were identified with the search terms, from these 37 met the inclusion criteria and were chosen for data extraction. In addition, 16 new studies, mainly published in 2019, were also included in the analysis resulting in 53 studies. No meta-analysis could be performed due to the heterogeneity of study designs. Included studies show that PRF enhances proliferation, migration, adhesion, and osteogenic differentiation on a variety of cell types along with cell signaling activation. Furthermore, PRF reduces inflammation, suppresses osteoclastogenesis, and increases the expression of various growth factors in mesenchymal cells.

Summary and conclusions

Despite some notable differences of the studies, the overall findings suggest a positive effect of PRF on cell proliferation, migration, adhesion, differentiation, and inflammation pointing towards a therapeutic potential in regenerative dentistry.

Clinical relevance

PRF serves as a reservoir of bioactive molecules to support wound healing and bone regeneration. Although the cellular mechanisms by which PRF supports the clinical outcomes remain unclear, in vitro research provides possible explanations. This systematic review aims to provide an update of the existing research on how PRF affects basic physiological processes in vitro. The overall findings suggest that PRF induces cell proliferation, migration, adhesion, and differentiation along with possessing anti-inflammatory properties further supporting its therapeutic potential in wound healing and bone regeneration.
Open-label study of long-term administration of dotinurad in Japanese hyperuricemic patients with or without gout
Authors: Hosoya Tatsuo , Fushimi Masahiko , Okui Daisuke , Sasaki Tomomitsu , Ohashi Tetsuo
Published: December 2019

Background

Dotinurad is a novel selective urate reabsorption inhibitor (SURI) which reduces serum uric acid levels by selectively inhibiting urate transporter 1 (URAT1). This study was intended to verify the efficacy and safety of dotinurad following treatment for 34 or 58 weeks in hyperuricemic patients with or without gout.

Methods

This long-term study had an open-label design with dose escalation. The dose of dotinurad started at 0.5 mg/day and was increased progressively to 2 mg/day. If the serum uric acid level of patients did not reach ≤ 6 mg/dL at week 14, the dose was increased to 4 mg/day. The primary endpoint was the percent change in serum uric acid level from the baseline to each visit.

Results

At a dose of 2 mg, serum uric acid levels at week 34 and 58 were reduced from the baseline by 46.73% and 47.17%, respectively; at 4 mg, the respective values were 54.92% and 57.35%. At week 34 and 58, the percentages of patients achieving a serum uric acid levels ≤ 6.0 mg/dL with 2-mg dose were 89.11% and 91.30%, respectively; with 4 mg, the respective rates were 97.50% and 100.00%. In addition, the incidences of adverse events and adverse drug reactions were 65.2% and 21.8%, respectively.

Conclusion

Dotinurad at doses of 2–4-mg sufficiently reduced serum uric acid levels in hyperuricemic patients with or without gout, and its efficacy and safety were verified for long-term administration.

ClinicalTrials.gov Identifier: NCT03006445
Sialic Acid-Engineered IL4–10 Fusion Protein is Bioactive and Rapidly Cleared from the Circulation
Authors: Steen-Louws Cristine , Boross Peter , Prado Judith , Meeldijk Jan , Langenhorst Jurgen B. , Huitema Alwin D. R. , den Hartog Marcel T. , Boon Louis , Lafeber Floris P. J. G. , Hack C. Erik , Eijkelkamp Niels , Popov-Celeketic Jelena
Published: December 2019

Purpose

Modulating sialylation of therapeutic glycoproteins may be used to influence their clearance and systemic exposure. We studied the effect of low and high sialylated IL4–10 fusion protein (IL4–10 FP) onin vitroandin vivobioactivity and evaluated the effect of differential sialylation on pharmacokinetic parameters.

Methods

CHO cell lines producing low (IL4–10 FP lowSA) and high sialylated (IL4–10 FP highSA) fusion protein were generated. Bioactivity of the proteins was evaluated in an LPS-stimulated whole blood assay. Pharmacokinetics were studied in rats, analyzing plasma levels of IL4–10 FP upon intravenous injection.In vivoactivity was assessed in an inflammatory pain mice model upon intrathecal injection.

Results

IL4–10 FP lowSA and IL4–10 FP highSA had similar potencyin vitro. The pharmacokinetics study showed a 4-fold higher initial systemic clearance of IL4–10 FP lowSA, whereas the calculated half-life of both IL4–10 FP lowSA and IL4–10 FP highSA was 20.7 min. Finally, both IL4–10 FP glycoforms inhibited persistent inflammatory pain in mice to the same extent.

Conclusions

Differential sialylation of IL4–10 fusion protein does not affect thein vitroandin vivoactivity, but clearly results in a difference in systemic exposure. The rapid systemic clearance of low sialylated IL4–10 FP could be a favorable characteristic to minimize systemic exposure after administration in a local compartment.
Predictive factors for responses to primary medical treatment with lanreotide autogel 120 mg in acromegaly: post hoc analyses from the PRIMARYS study
Authors:   the PRIMARYS Study Group, Petersenn Stephan , Houchard Aude , Sert Caroline , Caron Philippe J.
Published: December 2019

Purpose

PRIMARYS (NCT00690898) was a 48-week, open-label, phase 3b study, evaluating treatment with the somatostatin receptor ligand lanreotide autogel (stable dose: 120 mg/28 days) in treatment-naïve patients with growth hormone (GH)-secreting pituitary macroadenoma. This post hoc analysis aimed to evaluate factors predictive of long-term responses.

Methods

Potential predictive factors evaluated were: sex, age, and body mass index at baseline; and GH, insulin-like growth factor-1 (IGF-1), and tumor volume (TV) at baseline and week 12, using univariate regression analyses. Treatment responses were defined as hormonal control (GH ≤ 2.5 µg/L and age- and sex-normalized IGF-1), tight hormonal control (GH < 1.0 µg/L and normalized IGF-1), or ≥ 20% TV reduction (TVR). Receiver-operating-characteristic (ROC) curves were constructed using predictive factors significant in univariate analyses. Cut-off values for predicting treatment responses at 12 months were derived by maximizing the Youden index (J).

Results

At baseline, older age, female sex, and lower IGF-1 levels were associated with an increased probability of achieving long-term hormonal control. ROC area-under-the curve (AUC) values for hormonal control were high for week-12 GH and IGF-1 levels (0.87 and 0.93, respectively); associated cut-off values were 1.19 μg/L and 110% of the upper limit of normal (ULN), respectively. Results were similar for tight hormonal control (AUC values: 0.92 [GH] and 0.87 [IGF-1]; cut-off values: 1.11 μg/L and 125% ULN, respectively). AUC and J values associated with TVR were low.

Conclusions

The use of predictive factors at baseline and week 12 of treatment could inform clinical expectations of the long-term efficacy of lanreotide autogel.
The trick does not work if you have already seen the gorilla: how anticipatory effects contaminate pre-treatment measures in field experiments
Authors: Ariel Barak , Sutherland Alex , Bland Matthew
Published: December 2019

Objectives

If participants can anticipate the intervention, they may alter their responses prior to exposure to treatment. One often-ignored consequence of these “anticipatory effects” (AE) is an impact on the pre-treatment measurement. We explore this potential contamination and present practical options for mitigating AE.

Methods

A multidisciplinary review of AE.

Results

Pre-treatment measures, especially pre-treatment dependent variables, can be contaminated by AE. Experimenters need to understand the following: (1) When did the treatment ‘commence’? (2) How is the pretest measured? (3) Are AE specific or global? (4) What conclusions can we draw where pretest measures are contaminated by AE?

Conclusions

AE are often ignored for both research and policy, which may lead to erroneous conclusions regarding effectiveness, benefits being underestimated, or both. AE can be resolved by collecting ‘clean’ baseline measures prior to the commencement of the AE, but the first step is to be aware of the potential bias due to this treatment × pre-measurement interaction.
Process simulation and gate-to-gate life cycle assessment of hydrometallurgical refractory gold concentrate processing
Authors: Elomaa Heini , Sinisalo Pia , Rintala Lotta , Aromaa Jari , Lundström Mari
Published: December 2019

Purpose

Currently, almost all cyanide-free gold leaching processes are still in the development stage. Proactively investigating their environmental impacts prior to commercialization is of utmost importance. In this study, a detailed refractory gold concentrate process simulation with mass and energy balance was built for state-of-the-art technology with (i) pressure oxidation followed by cyanidation and, compared to alternative cyanide-free technology, with (ii) pressure oxidation followed by halogen leaching. Subsequently, the simulated mass balance was used as life cycle inventory data in order to evaluate the environmental impacts of the predominant cyanidation process and a cyanide-free alternative.

Methods

The environmental indicators for each scenario are based on the mass balance produced with HSC Sim steady-state simulation. The simulated mass balances were evaluated to identify the challenges in used technologies. The HSC Sim software is compatible with the GaBi LCA software, where LCI data from HSC-Sim is directly exported to. The simulation produces a consistent life cycle inventory (LCI). In GaBi LCA software, the environmental indicators of global warming potential (GWP), acidification potential (AP), terrestrial eutrophication potential (EP), and water depletion (Water) are estimated.

Results and discussion

The life cycle assessment revealed that the GWP for cyanidation was 10.1 t CO2-e/kg Au, whereas the halogen process indicated a slightly higher GWP of 12.6 t CO2-e/kg Au. The difference is partially explained by the fact that the footprint is calculated against produced units of Au; total recovery by the halogen leaching route for gold was only 87.3%, whereas the cyanidation route could extract as much as 98.5% of gold. The addition of a second gold recovery unit to extract gold also from the washing water in the halogen process increased gold recovery up to 98.5%, decreasing the GWP of the halogen process to 11.5 t CO2-e/kg Au. However, both evaluated halogen processing scenarios indicated a slightly higher global warming potential when compared to the dominating cyanidation technology.

Conclusions

The estimated environmental impacts predict that the development-stage cyanide-free process still has some challenges compared to cyanidation; as in the investigated scenarios, the environmental impacts were generally higher for halogen leaching. Further process improvements, for example in the form of decreased moisture in the feed for halide leaching, and the adaptation of in situ gold recovery practices in chloride leaching may give the cyanide-free processing options a competitive edge.
Performance Improvement Technology for Building a Sustainable OER Initiative in an Academic Library
Authors: Essmiller Kathy , Thompson Penny , Alvarado-Albertorio Frances
Published: December 2019

In keeping with its land grant mission, a university campus library partnered with several OER advocacy efforts on both national and state levels to promote the creation and use of OER at the university. While the program had some initial success in inspiring faculty to create and use OER in their courses, the effort proved difficult to sustain. This paper presents the application of the Performance Improvement/HPT model to an Open Educational Resources (OER) initiative in a university library. This paper focuses specifically on three phases of the process: organizational analysis, environmental analysis, and gap analysis We share results of that application and discuss how the HPT model might effectively be applied to other similar programs.
Correction to: Toward a Pedagogy for Professional Noticing: Learning through Observation
Authors: Rooney Donna , Boud David
Published: December 2019

The article “Toward a Pedagogy for Professional Noticing: Learning through Observation”, written by Donna Rooney and David Boud, was originally published Online First without Open Access.
Effects of Wetland Presence and Upland Land Use on Wild Hymenopteran and Dipteran Pollinators in the Rainwater Basin of Nebraska, USA
Authors: Begosh Angela , Smith Loren M. , Park Cynthia N. , Mcmurry Scott T. , Lagrange Ted G.
Published: December 2019

Pollination is an ecosystem service that is in jeopardy globally. Decreasing trends in wild pollinator populations are primarily attributed to habitat loss and degradation. These concerns are especially apparent in the Rainwater Basin of Nebraska, USA where more than 90% of the land has been cultivated and 90% of the wetlands have been lost. We compared hymenopteran and dipteran pollinator abundance, richness, and diversity in 28 wetlands and their adjacent uplands within 3 dominant land-condition types: cropped, restored, and reference state. We used vane traps to capture local pollinator insects and sweep nets to collect insect pollinators on flowers. Vane-trap captures revealed a greater abundance, richness, and diversity of hymenopteran pollinators in uplands as compared to wetlands over the entire growing season in all land-condition types. However, net collections showed that hymenopterans foraged more in wetlands than in uplands, especially in restored wetlands. The exception was September when hymenopterans were captured in uplands more than wetlands while feeding on late season forbs. Dipteran vane-trap and sweep-net captures primarily consisted of hoverflies (Syrphidae). Hoverflies were more abundant in wetlands than uplands. All pollinators used both wetlands and uplands for resources. Thus, insect-pollinator conservation can be enhanced by promoting native forb communities and pollinator habitat through wetland restoration and the planting of buffer strips.
Correction to: Effects of organic amendment on some soil physicochemical characteristics and vegetative properties of Zea mays in wetland soils of the Niger Delta impacted with crude oil
Authors: Egobueze Francis E. , Ayotamuno Josiah M. , Iwegbue Chukwujindu M. A. , Eze Chibogwu , Okparanma Reuben N.
Published: December 2019

In the original publication of the article, the author’s name Reuben N. Okparanma was misspelled.
Development of novel supported iridium nanocatalysts for special catalytic beds
Authors: Amirsardari Zahra , Dourani Akram , Amirifar Mohamad Ali , Ghadiri Massoom Nooredin , Ehsani Rahim
Published: December 2019

In the present paper, an experimental study of the catalytic decomposition of hydrous hydrazine was investigated on the different structural forms of the catalyst. The synthesized iridium catalysts have been usually used directly and have not been evaluated in the laboratory reactor. This study includes the preparation of iridium-based catalysts supported on spherical (alumina), honeycomb monoliths (cordierite) and foams (alumina) for the evaluation of catalytic activity in the laboratory reactor. The characterizations of these catalysts were evaluated by the TGA, FESEM and BET analysis. The result of the catalytic characterization of monolithic support was shown a homogeneous distribution of active metal without any problem of sintering (average size 25 nm) on the support surface. While the surface of the spherical and foam supports were shown non-uniform distribution of nanoparticles on the support skeleton (average size 55 nm). The monolithic catalyst exhibits higher decomposition rate and H2 selectivity than other supports due to uniform in shape and particle size distribution.

Graphic abstract
Computation of the unipotent Albanese map on elliptic and hyperelliptic curves
Authors: Beacom Jamie
Published: December 2019

We study the unipotent Albanese map appearing in the non-abelian Chabauty method of Minhyong Kim. In particular we explore the explicit computation of thep-adic de Rham period map$$j^{dr}_n$$jndron elliptic and hyperelliptic curves over number fields via their universal unipotent connections$${\mathscr {U}}$$U. Several algorithms forming part of the computation of finite level versions$$j^{dr}_n$$jndrof the unipotent Albanese maps are presented. The computation of the logarithmic extension of$${\mathscr {U}}$$Uin general requires a description in terms of an open covering, and can be regarded as a simple example of computational descent theory. We also demonstrate a constructive version of a lemma of Hadian used in the computation of the Hodge filtration on$${\mathscr {U}}$$Uover affine elliptic and odd hyperelliptic curves. We use these algorithms to present some new examples describing the co-ordinates of some of these period maps. This description will be given in terms iteratedp-adic Coleman integrals. We also consider the computation of the co-ordinates if we replace the rational basepoint with a tangential basepoint, and present some new examples here as well.
Food Vendor Beware! On Ordinary Morality and Unhealthy Marketing
Authors: Tempels Tjidde , Blok Vincent , Verweij Marcel
Published: December 2019

Food and beverage firms are frequently criticised for their impact on the spread of non-communicable diseases like obesity and diabetes type 2. In this article we explore under what conditions the sales and marketing of unhealthy food and beverage products is irresponsible. Starting from the notion of ordinary morality we argue that firms have a duty to respect people’s autonomy and adhere to the principle of non-maleficence in both market and non-market environments. We show how these considerations are relevant when thinking about immoral behaviour in the food and beverage industry, and identify under what conditions sales and marketing of unhealthy foods and beverages to adults and children is wrong. Based on this analysis we argue that firms should take into account: whether consumers are able to identify manipulative marketing, the degree of manipulation, as well as the negative impact a product has on health. We hold that for the food industry to act responsible it should re-evaluate the marketing of unhealthy products to adults and refrain from marketing to children. We conclude this study by making several recommendations on how the food industry should interact with consumers and highlight what changes need to be made in corporate practice.
Dynamics of crime activities in the network of city community areas
Authors: Niu Xiang , Elsisy Amr , Derzsy Noemi , Szymanski Boleslaw K.
Published: December 2019

Understanding criminal activities, their structure and dynamics are fundamental for designing tools for crime prediction that can also guide crime prevention. Here, we study crimes committed in city community areas based on police crime reports and demographic data for the City of Chicago collected over 16 consecutive years. Our goal is to understand how the network of city community areas shapes dynamics of criminal offenses and demographic characteristics of their inhabitants. Our results reveal the presence of criminal hot-spots and expose the dynamic nature of criminal activities. We identify the most influential features for forecasting the per capita crime rate in each community. Our results indicate that city community crime is driven by spatio-temporal dynamics since the number of crimes committed in the past among the spatial neighbors of each community area and in the community itself are the most important features in our predictive models. Moreover, certain urban characteristics appear to act as triggers for the spatial spreading of criminal activities. Using the k-Means clustering algorithm, we obtained three clearly separated clusters of community areas, each with different levels of crimes and unique demographic characteristics of the district’s inhabitants. Further, we demonstrate that crime predictive models incorporating both demographic characteristics of a community and its crime rate perform better than models relying only on one type of features. We develop predictive algorithms to forecast the number of future crimes in city community areas over the periods of one-month and one-year using varying sets of features. For one-month predictions using just the number of prior incidents as a feature, the critical length of historical data, τc, of 12 months arises. Using more than τc months ensures high accuracy of prediction, while using fewer months negatively impacts prediction quality. Using features based on demographic characteristics of the district’s inhabitants weakens this impact somewhat. We also forecast the number of crimes in each community area in the given year. Then, we study in which community area and over what period an increase in crime reduction funding in this area will yield the largest reduction of the crime in the entire city. Finally, we study and compare the performance of various supervised machine learning algorithms classifying reported crime incidents into the correct crime category. Using the temporal patterns of various crime categories improves the classification accuracy. The methodologies introduced here are general and can be applied to other cities for which data about criminal activities and demographics are available.
Where did all the men go? The changing sex composition of the Russian North in the post-Soviet period, 1989–2010
Authors: Heleniak Timothy
Published: December 2019

Like the northern periphery regions of other Arctic countries, the Russian North had a higher male–female sex ratio than the rest of the country. During the two decades following the breakup of the Soviet Union, the male sex ratio in the Russian North declined considerably, from 101 males per 100 females in 1989 to 92 in 2010. The regions and population of the Russian North were greatly impacted by the shift in northern development approaches from the centrally planned system of the Soviet Union to the market-oriented system of Russia. This paper examines the decline in the male population in the Russian North based on data from the 1989, 2002 and 2010 population censuses. The paper finds that only one quarter of the decline in the male sex ratio in the Russian North can be attributed to higher male outmigration and that three quarters are the result of significantly higher and widening gaps between females and males in life expectancy. The conclusion is that men in the Russian North coped with the social and economic upheavals by dying prematurely not by migrating. The leading causes of death for men were cardiovascular diseases and external causes such as murder, suicide and accidents.