bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of purge and trap‐atmospheric pressure chemical ionization‐tandem mass spectrometry for the determination of dimethyl sulfide in seawater
Authors: McCulloch Ross D. , Herr Alysia , Dacey John , Tortell Philippe D.
Published: July 2020

We describe a method for measuring trace concentrations of dimethyl sulfide (DMS) in seawater using a commercial tandem mass spectrometer configured for atmospheric pressure chemical ionization (PT‐APCI‐MS/MS), coupled with a custom‐built purge and trap gas extraction system. DMS was ionized through proton transfer, generating abundant [M + H]+ ions. The semiautomated method analyzes samples in under 6 min, and is capable of processing up to 10 samples in a single batch. A detection limit of 0.9 pmol L−1 was determined for the analysis of 5 mL sample volumes, with a precision of 3.9% between replicates. Practical performance was evaluated during two oceanographic research cruises within the coastal waters around Vancouver Island, British Columbia. To demonstrate method utility, a series of DMS depth profiles were obtained along two transects extending from the west coast of Vancouver Island into deep water off the continental shelf. Additional depth profile sampling was conducted in Saanich Inlet, a coastal anoxic fjord with active chemotrophic sulfur cycling. This method enabled us to capture the deep‐water accumulation of subnanomolar DMS in the anoxic water of Saanich Inlet, providing evidence of cryptic sulfur cycling. The method was also leveraged to facilitate stable isotope rate measurement experiments, in which the consumption of isotopically labeled DMS, dimethylsulfoxide, and dimethylsulfoniopropionate tracers was monitored in the low picomolar range. These measurements enable metabolic rate determinations using low‐level tracer additions that do not perturb in situ microbial activity. Our sensitive, high throughput method helps to improve understanding of the natural marine cycling of volatile sulfur compounds.
The incidence of antibiotic resistance within and beyond the agricultural ecosystem: A concern for public health
Authors: Iwu Chidozie D. , Korsten Lise , Okoh Anthony I.
Published: July 2020

The agricultural ecosystem creates a platform for the development and dissemination of antimicrobial resistance, which is promoted by the indiscriminate use of antibiotics in the veterinary, agricultural, and medical sectors. This results in the selective pressure for the intrinsic and extrinsic development of the antimicrobial resistance phenomenon, especially within the aquaculture‐animal‐manure‐soil‐water‐plant nexus. The existence of antimicrobial resistance in the environment has been well documented in the literature. However, the possible transmission routes of antimicrobial agents, their resistance genes, and naturally selected antibiotic‐resistant bacteria within and between the various niches of the agricultural environment and humans remain poorly understood. This study, therefore, outlines an overview of the discovery and development of commonly used antibiotics; the timeline of resistance development; transmission routes of antimicrobial resistance in the agro‐ecosystem; detection methods of environmental antimicrobial resistance determinants; factors involved in the evolution and transmission of antibiotic resistance in the environment and the agro‐ecosystem; and possible ways to curtail the menace of antimicrobial resistance.
Visual Acuity and Development of Parkinson's Disease: A Nationwide Cohort Study
Authors: Han Gyule , Han Jisang , Han Kyungdo , Youn Jinyoung , Chung Tae‐Young , Lim Dong Hui
Published: July 2020

Background

Visual dysfunction in Parkinson's disease (PD) is well known from previous reports, but the association of visual deficits with PD development has not yet been studied. The aim of this research was to evaluate the association of visual acuity with the risk of PD occurrence using a nationwide cohort in South Korea.

Methods

Among the population participating in the National Health Insurance Service, which is mandatory for all South Koreans, 6,055,113 individuals who had taken part in health screening programs between January 1, 2009, and December 31, 2012, were included in the cohort and followed until December 31, 2017. The hazard ratio was calculated for groups with high and low visual acuity using multivariate adjusted Cox regression analysis.

Results

A total of 22,872 subjects (0.38%) were diagnosed as having PD within the study period. Groups with low visual acuity showed a higher incidence of PD compared with groups with good visual acuity. Compared with the reference group (visual acuity better than 20/20), the adjusted hazard ratios and 95% confidence intervals (CIs) was 1.315 (95% CI, 1.261–1.371) for the group with visual acuity between 20/20 and 20/60, 1.357 (95% CI, 1.277–1.442) for the group with visual acuity between 20/60 and 10/100, and 1.267 (95% CI, 1.193–1.343) for the group with visual acuity less than 10/100.

Conclusions

Low visual acuity was associated with the development of PD. This suggests that visual dysfunction is one of the premotor symptoms for PD development. © 2020 International Parkinson and Movement Disorder Society
Precision Neurology for Parkinson’s Disease: Coupling Miro1‐Based Diagnosis With Drug Discovery
Authors: Bharat Vinita , Wang Xinnan
Published: July 2020

Parkinson’s disease (PD) is a debilitating movement disorder, significantly afflicting the aging population. Efforts to develop an effective treatment have been challenged by the lack of understanding of the pathological mechanisms underlying neurodegeneration. We have shown that Miro1, an outer mitochondrial membrane protein, situates at the intersection of the complex genetic and functional network of PD. Removing Miro1 from the surface of damaged mitochondria is a prerequisite for mitochondrial clearance via mitophagy. Parkinson’s proteins PINK1, Parkin, and LRRK2 are the molecular helpers to remove Miro1 from dysfunctional mitochondria destined for mitophagy. We have found a delay in clearing Miro1 and initiating mitophagy in postmortem brains and induced pluripotent stem cell–derived neurons from PD patients harboring mutations in LRRK2, PINK1, or Parkin, or from sporadic PD patients with no known mutations. In addition, we have shown that reducing Miro1 by both genetic and pharmacological approaches can correct this Miro1 phenotype and rescue Parkinson’s‐relevant phenotypes in human neurons and fly PD models. These results suggest that the Miro1 defect may be a common denominator for PD, and compounds that reduce Miro1 promise a new class of drugs to battle PD. We propose to couple this Miro1 phenotype with Miro1‐based drug discovery in future therapeutic studies, which could significantly improve the success of clinical trials. © 2020 International Parkinson and Movement Disorder Society
Tryptophan Metabolites Are Associated With Symptoms and Nigral Pathology in Parkinson's Disease
Authors: Heilman Patrick L. , Wang Ernest W. , Lewis Mechelle M. , Krzyzanowski Stanislaw , Capan Colt D. , Burmeister Amanda R. , Du Guangwei , Escobar Galvis Martha L. , Brundin Patrik , Huang Xuemei , Brundin Lena
Published: July 2020

Background

The objective of this study was to determine whether neurotoxic kynurenine metabolites, induced by inflammation, in plasma and cerebrospinal fluid (CSF) are associated with symptom severity and nigral pathology in Parkinson's disease (PD).

Methods

Clinical and MRI data were obtained from 97 PD and 89 controls. We used ultra‐performance liquid chromatography to quantify kynurenine metabolites and high‐sensitivity multiplex assays to quantify inflammation in plasma and CSF. We evaluated group‐wise differences as well as associations between the biomarkers, motor and nonmotor symptoms, and nigral R2* (MRI metric reflecting iron content).

Results

PD subjects had >100% higher 3‐hydroxykynurenine and 14% lower 3‐hydroxyanthranilic acid in plasma. The 3‐HK in plasma was closely associated with both symptom severity and disease duration. PD subjects also had 23% lower kynurenic acid in the CSF. Higher CSF levels of the excitotoxin quinolinic acid were associated with more severe symptoms, whereas lower levels of the neuroprotective kynurenic acid were linked to olfactory deficits. An elevated quinolinic acid/picolinic acid ratio in the CSF correlated with higher R2* values in the substantia nigra in the entire cohort. Plasma C‐reactive protein and serum amyloid alpha were associated with signs of increased kynurenine pathway activity in the CSF of PD patients, but not in controls.

Conclusions

In PD, the kynurenine pathway metabolite levels are altered in both the periphery and the central nervous system, and these changes are associated with symptom severity. Replication studies are warranted in other cohorts, and these can also explore if kynurenine metabolites might be PD biomarkers and/or are involved in PD pathogenesis. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Addressing the challenges of engaging young adults with SMI in treatment
Authors: Canady Valerie A.
Published: July 2020

Although young people with serious mental illness may find it difficult to engage in treatment, they can be helped in the engagement process by learning to open up to their providers about their feelings and advocating for themselves to determine the right treatment, suggests a researcher whose work centers on adolescents and young adults, during a webinar developed under contract by the National Association of State Mental Health Program Directors (NASMHPD).
Maryland SUD treatment center offering expanded MH services
Authors: Canady Valerie A.
Published: July 2020

Founded in 1980, a Salisbury, Maryland–based treatment program on the Eastern Shore, which opened its doors to help primarily male patients recover from substance abuse issues, has since then treated thousands more men and women through its residential treatment programs. To celebrate its 40th anniversary, the organization changed its name and integrated its services to include expanded mental health care during a time when it is sorely needed, officials said.
Food Processing Does Not Abolish the Allergenicity of the Carrot Allergen Dau c 1: Influence of pH, Temperature, and the Food Matrix
Authors: Jacob Thessa , Vogel Lothar , Reuter Andreas , Wangorsch Andrea , Kring Carolin , Mahler Vera , Wöhrl Birgitta M.
Published: July 2020

Scope

The major carrot allergen Dau c 1 belongs to the group of pathogenesis related class 10 (PR‐10) proteins and is homologous to the birch pollen allergen Bet v 1. In contrast to most other PR‐10 allergens, Dau c 1 can elicit Bet v 1 independent sensitization. Although Dau c 1 is considered heat labile, allergic reactions against cooked carrots are possible.

Methods and results

The pH and temperature stability as well as the allergenic potential before and after treatment of purified natural (n) Dau c 1 and different recombinant (r) isoallergens is investigated: rDau c 1.0104, rDau c 1.0105, rDau c 1.0201, rDau c 1.0301. All proteins except rDau c 1.0201 are able to refold at physiological pH. pH conditions around the pI (4.4–5.5) or the presence of the carrot matrix reduce the refolding capacity. Below the pI, most isoallergens are heat resistant and still able to cause mediator release, indicating allergenicity. Moreover, cooked carrot extract is still able to provoke mediator release due to remaining soluble Dau c 1.

Conclusion

Patients allergic to carrots should avoid processed carrot containing foodstuff because heating or pH treatment do not completely abolish the allergenicity of Dau c 1.
Optimized rectification of fiber orientation density function
Authors: Moss Hunter G. , Jensen Jens H.
Published: July 2020

Purpose

To demonstrate an optimized rectification strategy for fiber orientation density functions (fODFs).

Theory and Methods

In white matter, fODFs can be estimated with diffusion MRI. However, because of signal noise, imaging artifacts and other factors, experimentally determined fODFs may take on unphysical negative values in some directions. Here, we show how to rectify such fODFs to eliminate all negative values while minimizing the mean square difference between the original and rectified fODFs. The method is demonstrated for a mathematical model and for fODFs estimated from experimental human data using both constrained spherical deconvolution and fiber ball imaging. Comparison with an alternative nonoptimized rectification approach is also provided.

Results

For the mathematical model, it is found that the optimized rectification procedure removes negative fODF values while at the same time reducing the mean square error. Relative to the alternative rectification approach, the optimized fODFs are substantially more accurate. For the experimental data, the optimized fODFs have a lower average fractional anisotropy axonal and often fewer small peaks than the original, unrectified fODFs. The calculation of optimized fODFs is straightforward where the main step is the finding of the root to an equation in one variable, as may be efficiently accomplished with the bisection method.

Conclusion

Unphysical negative fODF values can be easily eliminated in a manner that minimizes the mean square difference between the original and rectified fODFs. Optimized fODF rectification may be useful in applications for which negative values are problematic.
Hamiltonian direct differentiation and adjoint approaches for multibody system sensitivity analysis
Authors: Maciąg Paweł , Malczyk Paweł , Frączek Janusz
Published: July 2020

The design of multibody systems involves high fidelity and reliable techniques and formulations that should help the analyst to make reasonable decisions. Given that constrained equations of motion for the simplest of multibody systems are highly nonlinear, determining the sensitivity terms is a computationally intensive and complex process that requires the application of special procedures. In this article, two novel Hamiltonian‐based approaches are presented for efficient sensitivity analysis of general multibody systems. The developed direct differentiation and the adjoint methods are based on constrained Hamilton's canonical equations of motion. This formulation provides solutions, which are more stable as compared to the results of direct integration of equations of motion expressed in terms of accelerations due to a reduced differential index of the underlying system of differential‐algebraic equations and explicit constraint imposition at the velocity level.The proposed Hamiltonian based methods are both capable of calculating the sensitivity derivatives and keeping the growth of constraint violation errors at a reasonable rate. The Hamiltonian‐based procedures derived herein appear to be good alternatives to existing methods for sensitivity analysis of general multibody systems.
Examining whether order of instruction matters in an experiential learning activity
Authors: Higley Corrine , Hayes Daniel
Published: July 2020

Experiential learning is a pedagogical technique that places students in direct contact with the material being studied. Students progress through four stages in a continuous cycle of learning. Because it is conceptualized as a continuous cycle, we question whether student comprehension varies according to where in the learning cycle they begin. Using an experiential outdoor survival shelter building activity, we tested whether student comprehension of experiential course material varied when receiving instruction prior to the activity vs. interactive discussion after the activity. Our results indicate that students who received advance instruction created significantly higher quality survival shelters during the activity, but there was no difference in post‐activity summative learning assessments between groups. Furthermore, prior outdoor survival experience was the only covariate in our analysis that affected student comprehension. No other covariates considered (treatment, gender, class rank, and participation in various outdoor activities) in our analysis affected student comprehension in this activity. Although the order of instruction did not influence student comprehension in this activity, more research is needed to explore whether instructional order matters in other experiential learning activities. Researchers are encouraged to apply this approach to other situations to further understand the ramifications of instructional order on experiential learning outcomes.
Association between end‐induction response according to the revised International Neuroblastoma Response Criteria (INRC) and outcome in high‐risk neuroblastoma patients
Authors: Barr Erin K. , Laurie Kathryn , Wroblewski Kristen , Applebaum Mark A. , Cohn Susan L.
Published: July 2020

Background

The 1993 International Neuroblastoma Response Criteria (INRC) were revised in 2017 to include modern functional imaging studies and methods for quantifying disease in bone marrow. We hypothesized the 2017 INRC would enable more precise assessment of response to treatment and provide superior prognostic information compared with the 1993 criteria.

Methods

High‐risk (HR) neuroblastoma patients from two institutions in Chicago diagnosed between 2006 and 2016 were identified. Patients were assessed post induction chemotherapy via the 1993 and 2017 INRC and classified as responder (≥ mixed response [MXR] or ≥ minor response [MR], respectively) or nonresponder (< MXR or < MR). Event‐free survival (EFS) and overall survival (OS) for responders versus nonresponders were determined from end induction and stratified by Cox regression. Patients with progressive disease at end induction were eliminated from the EFS analyses but included in the OS analysis.

Results

The 1993 criteria classified 52 of the 60 HR patients as responders, whereas 54 responders were identified using the 2017 criteria (Spearman correlation r = 0.82, P < 0.001). No statistically significant difference in EFS was observed for responders versus nonresponders using either criteria (P = 0.48 and P = 0.08). However, superior OS was observed for responders (P = 0.01) using either criteria. Both criteria were sensitive in identifying responders among those with good outcomes. The specificity to identify nonresponders among those with poor outcomes was poor.

Conclusions

In HR neuroblastoma, end‐induction response defined by the 1993 or 2017 INRC is associated with survival. Larger cohorts are needed to determine if the 2017 INRC provides more precise prognostication.
Cost‐effectiveness of levofloxacin prophylaxis against bacterial infection in pediatric patients with acute myeloid leukemia
Authors: McCormick Meghan , Friehling Erika , Kalpatthi Ramasubramanian , Siripong Nalyn , Smith Kenneth
Published: July 2020

Background

Infections are the leading cause of therapy‐related mortality in pediatric patients with acute myeloid leukemia (AML). Although effectiveness of levofloxacin antibacterial prophylaxis in oncology patients is recognized, its cost‐effectiveness is unknown. This study evaluated epidemiologic data regarding levofloxacin use and the cost‐effectiveness of this strategy as the cost per bacteremia episode, intensive care unit (ICU) admission, and death avoided in children with AML.

Procedure

A retrospective cohort study using the Pediatric Health Information System (PHIS) database compared demographic and clinical characteristics and receipt of levofloxacin prophylaxis in children with AML admitted for chemotherapy from January 1, 2014, through December 31, 2018. We then developed a decision analysis model in this population that compared costs associated with bacteremia, ICU admission, or death secondary to bacteremia to levofloxacin prophylaxis cost from a healthcare perspective. Time horizon is one chemotherapy cycle. Probabilistic and one‐way sensitivity analyses evaluated model uncertainty.

Results

Prophylaxis cost $8491 per bacteremia episode prevented compared with an average added hospital cost of $119 478. Prophylaxis cost $81 609 per ICU admission avoided, compared with an average added hospital cost of $94 181. Prophylaxis cost $220 457 per death avoided. In sensitivity analysis, at a willingness‐to‐pay threshold of $100 000 per bacteremia episode avoided, prophylaxis remained cost‐effective in 94.6% of simulations. Prophylaxis use was more common in recent years in patients with relapsed disease and with chemotherapy regimens considered more intensive.

Conclusion

Prophylaxis is cost‐effective in preventing bacterial infections in patients with AML. Findings support increased use in patients considered at high risk of bacterial infection secondary to myelosuppression.
Chest computed tomography findings for a cohort of children with pulmonary Langerhans cell histiocytosis
Authors: Della Valle Valeria , Donadieu Jean , Sileo Chiara , Barkaoui Mohamed Aziz , Héritier Sébastien , Brisse Hervé , Boutry Nathalie , Tréguier Catherine , Chateil Jean‐François , Petit Philippe , Pracros Jean‐Pierre , Chastagner Pascal , Boyer Corinne , Veillon Francis , Durand Chantal , Mounayer Charbel , Kambouchner Marianne , Brauner Michel , Tazi Abdellatif , Epaud Ralp , Ducou le Pointe Hubert
Published: July 2020

Objective

This study was undertaken to describe the spectrum of lung computed‐tomography (CT) findings in children with pulmonary Langerhans cell histiocytosis (PLCH) and to evaluate for this population the CT‐scan nodule and cyst scores proposed by adult pulmonologists at diagnosis and during follow‐up.

Methods

Among 175 children with PLCH identified in the French national population‐based Langerhans cell histiocytosis cohort, 60 were retrospectively selected by the availability of CT for a central review by three pediatric radiologists. These 60 patients are representative of childhood PLCH for almost all clinical aspects, except a lower percentage of risk organ involvement (38% vs 54%; P = 0.05).

Results

The 60 children's chest CT scans (n = 218) were reviewed. At diagnosis, 63% of them had nodules, 53% had cysts, and 29% had both. The percentages of patients with nodules or cysts increased from diagnosis to peak disease activity, respectively, from 63% to 73% and from 53% to 66%. The costophrenic angle was involved in 71%. Patients with pneumothorax (25%) had a higher median cyst score. Alveolar consolidation was observed in 34%. Patients with low CT‐scan nodule and cyst scores had no long‐term pulmonary sequelae.

Conclusions

Well‐known characteristics of adult PLCH (nodules and cysts) were observed in children. The chest CT scores proposed by adult pulmonologists could easily be applied to childhood PLCH. Lesions in children, unlike those in adults, are frequently located near the costophrenic angles. Alveolar consolidation might be considered an atypical feature of childhood PLCH.
Microbiology and radiographic features of osteomyelitis in children and adolescents with sickle cell disease
Authors: Kao Carol M. , Yee Marianne E. , Maillis Alexander , Lai Kristina , Bakshi Nitya , Rostad Bradley S. , Jerris Robert C. , Lane Peter A. , Yildirim Inci
Published: July 2020

Background

Children with sickle cell disease (SCD) are at increased risk for bacterial infections including osteomyelitis (OM). Fever and bone pain, key presenting symptoms of OM, are common in SCD, thus complicating diagnosis. We reviewed presentation, imaging features, and microbiologic etiologies of children with SCD treated for OM.

Methods

The comprehensive SCD clinical database of children and adolescents with SCD followed at a single, large tertiary pediatric center were searched to identify all diagnostic coding for potential cases of osteomyelitis in children ages 6 months to 21 years from 2010 to 2019. Medical charts were reviewed to determine OM diagnostic probability based on radiographic and microbiologic findings and the duration of prescribed antibiotic treatment for OM.

Results

Review of 3553 patients (18 039 person‐years) identified 20 episodes of probable OM in 19 children. Magnetic resonance imaging (MRI) findings to support OM were definitive in 4/19 (21%), probable in 10/19 (53%), suspected in 5/19 (26%), based on blinded radiologist review. Blood and/or operative cultures from bone and tissue debridement isolated Salmonella species in seven (35%) cases and methicillin‐susceptible Staphylococcus aureus (MSSA) in two (10%). Six patients received antibiotic treatment prior to obtainment of cultures. Of culture‐positive cases, MRI findings for OM were definitive or probable in six of nine (67%), suspected in three of nine (33%).

Conclusions

Distinction between OM and sickle‐related bone infarct or vasoocclusion is difficult based on imaging findings alone. Early attainment of blood and operative cultures increases the likelihood of identifying and adequately treating OM.
Prolongation of radiotherapy duration is associated with inferior overall survival in patients with pediatric medulloblastoma and central nervous system primitive neuroectodermal tumors
Authors: Baliga Sujith , Bajaj Benjamin V. M. , Kabarriti Rafi , Grassberger Clemens , Patteson Brooke , Yeap Beow , Fox Jana L. , Garg Madhur K. , Yock Torunn I.
Published: July 2020

Background

The importance of radiotherapy (RT) duration in medulloblastoma in the modern era of chemotherapy has not been well elucidated. The aim of this study was to determine the impact of RT treatment duration on overall survival (OS) in pediatric medulloblastoma and cenral nervous system neuroectodermal tumors (PNETs).

Methods

The National Cancer Database (NCDB) was queried to identify patients with newly diagnosed medulloblastoma and CNS PNETs diagnosed between 2004 and 2014. Patients were excluded if they had extraneural metastasis, did not receive standard craniospinal irradiation dose, had a nonstandard total dose outside of 54 or 55.8 Gy, did not receive adjuvant chemotherapy, or if the RT duration was outside of the expected range of 37 to 80 days. The Kaplan‐Meier estimator was used to estimate the association between RT duration (≤45 days or >45 days) and OS. Multivariate Cox regression was used to assess other confounders of OS.

Results

Six‐hundred twenty‐five patients met inclusion criteria, of which 181 were assigned to the “RT long" (>45 days) cohort (29.0%) and 444 (71.0%) to the “RT short” group (≤45 days). The five‐year OS for the “RT short” compared with “RT long” cohort was 82.2% versus 70.9%, respectively (log‐rank, P < 0.0037). For average risk patients, the five‐year OS was 84.6% versus 86.4% for “RT short” and “RT long,” respectively (log‐rank, P = 0.40). However, for high‐risk patients, five‐year OS was 77.7% versus 51.0% (log‐rank, P < 0.0001) in the “RT short” and “RT long” cohorts.

Conclusion

For patients with high‐risk medulloblastoma and CNS PNETs, RT duration >45 days was associated with inferior OS.
Comprehensive promotion of mechanical properties of epoxy by electrical insulating filler of Si3N4 whiskers at low content
Authors: Zhang Dian , Liu Jing , Liu Xuan , Liu Yijun , Yang Xiaofeng , Gao Yunqin , Ma Aiqiong
Published: July 2020

The improvement of the mechanical properties of brittle epoxies by various fillers, especially by carbon‐related materials, has attracted significant attention and achieved impressive results. However, the dielectric properties of an epoxy may be compromised along with the improvement, and there is an urgent need to develop electrical insulating fillers to address this issue. In this study, Si3N4 whiskers (Si3N4w) are first introduced as the filler used to prepare a composite of Si3N4w/epoxy. The results indicate that Si3N4w has an outstanding capability to comprehensively improve the mechanical properties of an epoxy. The maximal reinforcing and toughening effect could be obtained at a low filler content of 3.0%. The bending strength, Young's modulus, KIC and work of fracture of the composite can be augmented by 34.05%, 23.00%, 57.53%, and 513.50%, respectively, in comparison with those of the neat epoxy. The abundant energy dissipation mechanisms responsible for these effects are observed and interpreted. Finally, a brief phenomenological fracture process of Si3N4w/epoxy is proposed.
Using physical features of protein core packing to distinguish real proteins from decoys
Authors: Grigas Alex T. , Mei Zhe , Treado John D. , Levine Zachary A. , Regan Lynne , O'Hern Corey S.
Published: July 2020

The ability to consistently distinguish real protein structures from computationally generated model decoys is not yet a solved problem. One route to distinguish real protein structures from decoys is to delineate the important physical features that specify a real protein. For example, it has long been appreciated that the hydrophobic cores of proteins contribute significantly to their stability. We used two sources to obtain datasets of decoys to compare with real protein structures: submissions to the biennial Critical Assessment of protein Structure Prediction competition, in which researchers attempt to predict the structure of a protein only knowing its amino acid sequence, and also decoys generated by 3DRobot, which have user‐specified global root‐mean‐squared deviations from experimentally determined structures. Our analysis revealed that both sets of decoys possess cores that do not recapitulate the key features that define real protein cores. In particular, the model structures appear more densely packed (because of energetically unfavorable atomic overlaps), contain too few residues in the core, and have improper distributions of hydrophobic residues throughout the structure. Based on these observations, we developed a feed‐forward neural network, which incorporates key physical features of protein cores, to predict how well a computational model recapitulates the real protein structure without knowledge of the structure of the target sequence. By identifying the important features of protein structure, our method is able to rank decoy structures with similar accuracy to that obtained by state‐of‐the‐art methods that incorporate many additional features. The small number of physical features makes our model interpretable, emphasizing the importance of protein packing and hydrophobicity in protein structure prediction.
Drivers of recombinant soluble influenza A virus hemagglutinin and neuraminidase expression in mammalian cells
Authors: van der Woude Roosmarijn , Turner Hannah L. , Tomris Ilhan , Bouwman Kim M. , Ward Andrew B. , de Vries Robert P.
Published: July 2020

Recombinant soluble trimeric influenza A virus hemagglutinins (HA) and tetrameric neuraminidases (NAs) have proven to be excellent tools to decipher biological properties. Receptor binding and sialic acid cleavage by recombinant proteins correlate satisfactorily compared to whole viruses. Expression of HA and NA can be achieved in a plethora of different laboratory hosts. For immunological and receptor interaction studies however, insect and mammalian cell expressed proteins are preferred due to the presence of N‐linked glycosylation and disulfide bond formation. Because mammalian‐cell expression is widely applied, an increased expression yield is an important goal. Here we report that using codon‐optimized genes and sfGFP fusions, the expression yield of HA can be significantly improved. sfGFP also significantly increased expression yields when fused to the N‐terminus of NA. In this study, a suite of different hemagglutinin and neuraminidase constructs are described, which can be valuable tools to study a wide array of different HAs, NAs and their mutants.
Low‐Temperature Silicon‐Vacancy Luminescence of Individual Chemical Vapor Deposition Nanodiamonds Grown by Seeding and Spontaneous Nucleation
Authors: Pasternak Dmitrii G. , Dai Jibo , Kalashnikov Dmitry A. , Sedov Vadim S. , Martyanov Artem K. , Ralchenko Victor G. , Krivitsky Leonid A. , Vlasov Igor I.
Published: July 2020

Diamond nanoparticles with optically active color centers can be used in nanoscale devices for quantum networking and sensing. A particular interest is focused on nanodiamonds (NDs) containing a small ensemble of negatively charged silicon‐vacancy (SiV) centers. Such NDs can be integrated with on‐chip optical structures. Here, chemical vapor deposition (CVD) is used to synthesize diamond particles of less than 100 nm in size containing 10–20 centers per ND. Two types of NDs grown on a Si substrate are studied, seeded with detonation NDs and without any seeding. The SiV luminescence under off‐resonant and resonant laser excitation at the temperature of 15 K is investigated. The emission lines of SiVs of individual NDs are well resolved and found to be spread in the range of 730–750 nm. The typical SiV linewidth is within 1–2 GHz for spontaneous NDs, which is only a factor of 2.5–5 broader than the lifetime limited linewidth of the SiV at 15 K. The emission of a single SiV is highly stable for both types of samples. This work is a critical step toward the synthesis of SiVs suitable for the realization of integrated quantum photonic devices.
Metal–Semiconductor–Metal Thin‐Film X‐Ray Detector Based on Halide Perovskites
Authors: Yang Zhaohui , Wen Kaige , Lin Hai
Published: July 2020

Halide perovskite materials as emerging optoelectronic materials are very appealing for the X‐ray detection due to their superior charge transport, high‐absorption cross section for X‐rays and solution processability. Herein, thin‐film X‐ray detectors are demonstrated using methylammonium lead iodide perovskite (MAPbI3) thin films. Controlled nucleation of halide perovskites is realized using patterned Au dots as nucleation promoters, resulting in uniform thin films with large grains. A metal–semiconductor–metal (MSM) device architecture with coplanar electrodes is used, and the thin‐film detectors with an active layer thickness of 700 nm exhibit a sensitivity of 2.48 × 10−2 μC Gyair−1 cm−2 under a bias of 10 V. The device is relatively stable in air without encapsulation, showing no degradation after 15 min continuous biasing at 5 V. Such solution‐based perovskite detector can enable X‐ray detecting and imaging with low‐cost, high efficiency, and high sensitivity.
Artificial Indium‐Tin‐Oxide Synaptic Transistor by Inkjet Printing Using Solution‐Processed ZrOx Gate Dielectric
Authors: Kim Youn Goo , Lv Dongxu , Huang Jinsong , Bukke Ravindra Naik , Chen Huipeng , Jang Jin
Published: July 2020

Inkjet‐printed indium‐tin‐oxide (ITO) synaptic thin‐film transistors (TFTs) using solution‐processed high‐k zirconium oxide (ZrOx) gate dielectric layer are reported. The effect of ZrOx annealing temperature from 300 to 500 °C on the TFT performance is investigated. The optimized ZrOx gate dielectric layer of the ITO TFT can mimic biological synaptic response for the realization of intelligent computers and artificial bionic brain. The strong synaptic behavior of the ITO TFT exhibiting the on/off current ratio of ≈106 can be obtained at the ZrOx annealing temperature of 300 °C. The amount of hydroxyl (OH) groups in the dielectric film can be a crucial factor for the formation of an electric double layer (EDL) on the top region of the gate dielectric. The device exhibits the excitatory post‐synaptic current (EPSC), inhibitory postsynaptic current (IPSC), and paired‐pulse facilitation (PPF). Therefore, the inkjet‐printed ITO TFT using printed ZrOx gate dielectric can be used for low‐cost synaptic TFTs.
Calibration of computational Mössbauer spectroscopy to unravel active sites in FeNC catalysts for the oxygen reduction reaction
Authors: Gallenkamp Charlotte , Kramm Ulrike I. , Proppe Jonny , Krewald Vera
Published: July 2020

Single‐atom catalysts with iron ions in the active site, known as FeNC catalysts, show high activity for the oxygen reduction reaction and hence hold promise for access to low‐cost fuel cells. Because of the amorphous, multiphase structure of the FeNC catalysts, the iron environment and its electronic structure are poorly understood. While it is widely accepted that the catalytically active site contains an iron ion ligated by several nitrogen donors embedded in a graphene‐like plane, the exact structural details, such as the presence or nature of axial ligands, are unknown. Computational chemistry in combination with Mössbauer spectroscopy can help unravel the geometric and electronic structures of the active sites. As a first step toward this goal, we present a calibration of computational Mössbauer spectroscopy for FeN4‐like environments. The uncertainty of both the isomer shift and the quadrupole splitting prediction is determined, from which trust regions for the Mössbauer parameter predictions of computational FeNC models are derived. We find that TPSSh, B3LYP, and PBE0 perform equally well; the trust regions with B3LYP are 0.13 mm s−1for the isomer shift and 0.36 mm s−1for the quadrupole splitting. The calibration data is made publicly available in an interactive notebook that provides predicted Mössbauer parameters with individual uncertainty estimates from computed contact densities and quadrupole splitting values. We show that a differentiation of common FeNC Mössbauer signals by a separate analysis of isomer shift and quadrupole splitting will most likely be insufficient, whereas their simultaneous evaluation will allow the assignment to adequate computational FeNC models.
Metabolic profiling of synthetic cannabinoid 5F‐ADB and identification of metabolites in authentic human blood samples via human liver microsome incubation and ultra‐high‐performance liquid chromatography/high‐resolution mass spectrometry
Authors: Presley Brandon C. , Castaneto Marisol S. , Logan Barry K. , Jansen‐Varnum Susan A.
Published: July 2020

Rationale

Indazole carboxamide synthetic cannabinoids, a prevalent class of recreational drugs, are a major clinical, forensic and public health challenge. One such compound, 5F‐ADB, has been implicated in fatalities worldwide. Understanding its metabolism and distribution facilitates the development of laboratory assays to substantiate its consumption. Synthetic cannabinoid metabolites have been extensively studied in urine; studies identifying metabolites in blood are limited and no data on the metabolic stability (half‐life, clearance and extraction ratio) of 5F‐ADB have been published prior to this report.

Methods

The in vitro metabolism of 5F‐ADB was elucidated via incubation with human liver microsomes for 2 h at 37°C. Samples were collected at multiple time points to determine its metabolic stability. Upon identification of metabolites, authentic forensic human blood samples underwent liquid–liquid extraction and were screened for metabolites. Extracts were analyzed via ultra‐high‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry (UHPLC/QTOFMS) operated in positive electrospray ionization mode.

Results

Seven metabolites were identified including oxidative defluorination (M1); carboxypentyl (M2); monohydroxylation of the fluoropentyl chain (M3.1/M3.2) and indazole ring system (M4); ester hydrolysis (M5); and ester hydrolysis with oxidative defluorination (M6). The half‐life (3.1 min), intrinsic clearance (256.2 mL min−1 kg−1), hepatic clearance (18.6 mL min−1 kg−1) and extraction ratio (0.93) were determined for the first time. In blood, M1 was present in each sample as the most abundant substance; two samples contained M5; one contained 5F‐ADB, M1 and M5.

Conclusions

5F‐ADB is rapidly metabolized in HLM. 5F‐ADB, M1 and M5 are pharmacologically active at the cannabinoid receptors (CB1/CB2) and M1 and M5 may contribute to a user's impairment profile. The results demonstrate that it is imperative that synthetic cannabinoid assays screen for pharmacologically active metabolites, especially for drugs with short half‐lives. The authors propose that M1 and M5 are appropriate markers to include in laboratory blood tests screening for 5F‐ADB.
The next wave: We will all be data scientists
Authors: Betz Margaret , Gundlach Ellen , Hillery Elizabett , Rickus Jenna , Ward Mark D.
Published: July 2020

In the next wave of educating future data scientists, we need to think of all undergraduate students, regardless of background or major, as future data scientists. We should train them in supportive, interdisciplinary environments. Starting from their first day at college, they should be given the opportunity to apply powerful tools to large data sets, using real‐world problems. Partnerships with research computing, academic departments, research centers, companies, government, and nonprofits will all be necessary to fully prepare these students for the breadth of the data science workforce.
Can public surveillance promote corporate environmental innovation? The mediating role of environmental law enforcement
Authors: Liao Zhongju , Weng Chen , Shen Chen
Published: July 2020

With the increase in public environmental awareness, firms are continuously being required to fulfill environmental responsibilities. Based on stakeholder theory and institutional theory, this study examines the impact of public surveillance on corporate environmental innovation and the mediating role of environmental law enforcement. We selected 30 provinces in China as the research sample from 2011 to 2015. Multiple regression analysis was used to analyze the data by Stata software. We found that public surveillance had a significant positive promoting effect on corporate radical eco‐innovation, but had no significant effect on incremental eco‐innovation; environmental law enforcement had a significant positive promoting effect on both radical and incremental eco‐innovations. In addition, public surveillance was conducive to enhancing environmental law enforcement, which in turn promoted corporate radical eco‐innovation.
Molecular Cobalt Catalysts Grafted onto Polymers for Efficient Hydrogen Generation Cathodes
Authors: Li Cheng-Bo , Chu Yilong , Xie Pengfei , Xiong Lunqiao , Wang Ning , Wang Hongyan , Tang Junwang
Published: July 2020

A conjugated microporous polymer is in situ electropolymerized to form a basis for immobilization of a molecular catalyst onto glassy carbon. A cost‐effective molecular catalyst is then grafted onto the polymer by π–π interactions as evidenced by X‐ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and UV–vis spectra. The prepared cathode represents a high activity toward hydrogen evolution (109 100 turnovers in 2 h) in mild acidic aqueous solutions with a ≈100% faradaic efficiency. The cathode also shows a very good stability. In total, this article introduces a facile means to design and prepare a hydrogen generation cathode using widely available and inexpensive materials.
Influences of Quinoid Structures on Stability and Photovoltaic Performance of Nonfullerene Acceptors
Authors: Lv Ruizhi , Geng Shizhe , Li Shuixing , Wu Fei , Li Yaokai , Andersen Thomas Rieks , Li Yuhao , Lu Xinhui , Shi Minmin , Chen Hongzheng
Published: July 2020

Although benzoazole‐fused rings with strong quinoid character have successfully been used to construct high‐performance small‐molecule non‐fullerene acceptors (NFAs), studies into how these units influence the stabilities of NFAs and their corresponding device performances are few to date. To address it, four new NFAs, SSTI, SNTI, NTI and NTTI, which adopt BBT, TBZ, and BTAZ as the cores, respectively, are designed and investigated. It is found that SSTI and SNTI based on BBT and TBZ cores with stronger quinoid resonance effects show features of more red‐shifted absorptions and deeper energy levels, but worse thermal and light stabilities than NTI and NTTI with a BTAZ core, especially in solutions and/or films blended with polymer donors. Through matrix‐assisted laser desorption ionization time of flight mass spectrometry analysis of the degradation products, it is disclosed that the CC double bond cleavage would be accelerated by stronger quinoid effects. Therefore, NTI and NTTI with relatively weaker quinoid characteristics show improved photovoltaic properties. Especially, NTTI based devices yield a good efficiency of 8.61% as the side chains on sp3‐hybrid C atoms can prevent the formation of large aggregates. These findings can provide invaluable knowledge for the molecular design of NFAs with both high‐efficiency and high‐stability
A new small, mesorostrine inioid (Cetacea, Odontoceti, Delphinida) from four upper Miocene localities in the Pisco Basin, Peru
Authors: Lambert Olivier , Collareta Alberto , Benites‐Palomino Aldo , Di Celma Claudio , de Muizon Christian , Urbina Mario , Bianucci Giovanni
Published: July 2020

The moderately rich past diversity of the superfamily Inioidea (Cetacea, Odontoceti) in both the Atlantic and Pacific oceans contrasts with the present survival of a single genus (Inia, Amazon river dolphin, family Iniidae) in freshwater deposits of South America and of a single species (Pontoporia blainvillei, franciscana, family Pontoporiidae) along the eastern coast of that continent. However, part of the late Miocene – Pliocene inioid fossil record consists of relatively fragmentarily known species, for which systematic affinities remain poorly understood. Based on a sample of six cranial specimens from lower upper Miocene (Tortonian, 9.5–8.6 Ma) marine deposits of the Pisco Formation exposed at four localities of the East Pisco Basin (southern coast of Peru), we describe a new genus and species of inioid, Samaydelphis chacaltanae. This mesorostrine, small‐sized species is characterized by an upper tooth count of c. 30 teeth per row, a moderately elevated vertex of the cranium displaying a long anteromedial projection of the frontals and interparietal, and the plesiomorphic retention of a premaxilla–nasal contact. Recovered as a member of the family Pontoporiidae in our phylogenetic analysis, S. chacaltanae falls as sister group to Meherrinia isoni, from the upper Miocene of North Carolina (USA), which has previously been tentatively referred to the Iniidae or regarded as a stem Inioidea. Originating from the P1 allomember of the Pisco Formation, the mesorostrine S. chacaltanae was contemporaneous and sympatric with two other inioids, the brevirostrine pontoporiid Brachydelphis mazeasi and the longirostrine iniid Brujadelphis ankylorostris.
Application of Generalized Depletion Model to Recruitment of American Eel Elvers and Empirical Support from Survey Data
Authors: Lin Yu‐Jia , Jessop Brian M.
Published: July 2020

Recruitment is one of the driving forces determining the population dynamics of a stock, and knowledge about recruitment is crucial in providing reliable results in modern stock assessment. The population of the American Eel Anguilla rostra is at risk, and the fisheries on the elvers are one threat for its persistence. We applied a generalized depletion model on the catch and effort data of the elver fishery of the East River, Chester, Nova Scotia, from 1996 to 2018. The elver fishery of the East River did not have high exploitation pressure on the elver waves passing through. The natural mortality rate varied substantially among years, with a mean generally in agreement with other studies. The estimates of the model parameters did not exhibit significant temporal trends. Moreover, the estimate of annual elver abundance matched well with the fishery‐independent abundance index, providing the first empirical support of the generalized depletion model. The generalized depletion model is an effective method to assess the exploitation status of elver fisheries, as well as providing an estimate of recruitment strength and natural mortality that can be used for stock assessment on the adult stocks when only fisheries‐dependent catch and effort data are available.