bluuebunny/crossref_metadata_2025 huggingface dataset:
Layer by layer surface engineering of poly(lactide‐co‐glycolide) nanoparticles for plasmid DNA delivery
Authors: San Juan Angela Michelle T. , Rodgers Tina , Bedolla Carlos , Noriega Francesca , Romero Gabriela
Published: May 2020

The administration of exogenous DNA has been proposed as a promising therapeutic approach for a variety of diseases. Unfortunately, exogenous DNA is unable to spontaneously penetrate mammalian cells. Although viral vectors facilitate DNA delivery at high transfection efficiency, they are restricted for in vivo applications as they could potentially induce immunogenicity and mutagenesis. To overcome the clinical challenge of viral delivery, a strategy for the encapsulation of plasmid DNA on the surface of poly(lactide‐co‐glycolide) nanoparticles (PLGA NPs) is shown. Plasmid green fluorescence protein (pEF‐GFP) or piggybac transposon (PBCAG‐eGFP) are assembled on the surface of PLGA NPs through layer by layer technique. The assembly of pEF‐GFP with biopolyelectrolytes is monitored on a planar support using a quartz crystal microbalance with dissipation. The assembly of the biopolymer multilayers on PLGA NPs is followed by ζ‐potential measurements. Encapsulation of plasmid DNA within the multilayers coating is confirmed by gel electrophoresis. Cellular uptake studies on HEK293 cells revealed that PLGA NPs are taken up by cells within the first 5 hr of co‐culturing. Intracellular release of cargo is confirmed by GFP expression in HEK293 cells. PLGA NPs encapsulating pEF‐GFP on their surface are able to transfect ~20% of HEK293 cells, while those encapsulating PBCAG‐eGFP can transfect up to 75% of cells after 72 hr, causing minimum to non‐cytotoxic effects.
Evaluation of inhibitor of apoptosis genes as targets for RNAi‐mediated control of insect pests
Authors: Yoon June‐Sun , Koo Jinmo , George Smitha , Palli Subba R.
Published: May 2020

Apoptosis has been widely studied from mammals to insects. Inhibitor of apoptosis (IAP) protein is a negative regulator of apoptosis. Recent studies suggest that iap genes could be excellent targets for RNA interference (RNAi)‐mediated control of insect pests. However, not much is known about iap genes in one of the well‐known insect model species, Tribolium castaneum. The orthologues of five iap genes were identified in T. castaneum by searching its genome at NCBI (https://www.ncbi.nlm.nih.gov/) and UniProt (https://www.uniprot.org/) databases using Drosophila melanogaster and Aedes aegypti IAP protein sequences as queries. RNAi assays were performed in T. castaneum cell line (TcA) and larvae. The knockdown of iap1 gene induced a distinct apoptotic phenotype in TcA cells and induced 91% mortality in T. castaneum larvae. Whereas, knockdown of iap5 resulted in a decrease in cell proliferation in TcA cells and developmental defects in T. castaneum larvae which led to 100% mortality. Knockdown of the other three iap genes identified did not cause a significant effect on cells or insects. These data increase our understanding of iap genes in insects and provide opportunities for developing iap1 and iap5 as targets for RNAi‐based insect pest control.
Development of RNAi methods to control the harlequin bug, Murgantia histrionica
Authors: Howell Jeffrey L. , Mogilicherla Kanakachari , Gurusamy Dhandapani , Palli Subba Reddy
Published: May 2020

The harlequin bug (HB), Murgantia histrionica, is a major pest of cabbage family plants throughout its range in the United States. RNA interference (RNAi) is a posttranscriptional gene silencing mechanism that is showing promise as a biopesticide due to the ability to target species‐specific genes necessary for growth and/or survival with synthetic double‐stranded RNA (dsRNA). In the present study, dsRNA stability assays revealed that nucleases present in the saliva of harlequin bugs did not rapidly degrade dsRNA. We tracked the movement and localization of radioactively labeled dsRNA in both mustard plant seedlings and harlequin bug nymphs that fed on treated host plants. Movement of 32P‐labeled‐dsRNA from soil to plant and plant to insect was detected. The efficacy of RNAi in inducing mortality in harlequin bug adults and nymphs injected or fed with dsRNA targeting inhibitor of apoptosis (IAP), ATPase N2B (ATPase), serine/threonine‐protein phosphatase PP1‐β catalytic subunit (PP1), signal recognition particle 54 kDa protein (SRP), and G protein-coupled receptor 161-like (GPCR) genes was evaluated. Injection of dsRNA targeting candidate genes into adults caused between 40% and 75% mortality and induced significant knockdown of target gene expression. Feeding dsRNA targeting the IAP gene to nymphs by plant‐mediated and droplet feeding methods induced knockdown of the target gene and caused 40–55% mortality. These findings suggest that RNAi may be a viable approach for managing this pest.
Antiproliferative effects of chalcones on T cell acute lymphoblastic leukemia‐derived cells: Role of PKCβ
Authors: Corsini Emanuela , Facchetti Giorgio , Esposito Sara , Maddalon Ambra , Rimoldi Isabella , Christodoulou Michael S.
Published: May 2020

In this study, a series of 20 chalcone derivatives was synthesized, and their antiproliferative activity was tested against the human T cell acute lymphoblastic leukemia‐derived cell line, CCRF‐CEM. On the basis of the structural features of the most active compounds, a new library of chalcone derivatives, according to the structure–activity relationship design, was synthesized, and their antiproliferative activity was tested against the same cancer cell line. Furthermore, four of these derivatives (compounds 3, 4, 8, 28), based on lower IC50 values (between 6.1 and 8.9 μM), were selected for further investigation regarding the modulation of the protein expression of RACK1 (receptor for activated C kinase), protein kinase C (PKC)α and PKCβ, and their action on the cell cycle level. The cell cycle analysis indicated a block in the G0/G1 phase for all four compounds, with a statistically significant decrease in the percentage of cells in the S phase, with no indication of apoptosis (sub‐G0/G1 phase). Compounds 4 and 8 showed a statistically significant reduction in the expression of PKCα and an increase in PKCβ, which together with the demonstration of an antiproliferative role of PKCβ, as assessed by treating cells with a selective PKCβ activator, indicated that the observed antiproliferative effect is likely to be mediated through PKCβ induction.
Hierarchical Equations of Motion Simulation of Temperature‐Dependent Two‐Dimensional Electronic Spectroscopy of the Chlorophyll a Manifold in LHCII
Authors: Leng Xuan , Do Thanh Nhut , Akhtar Parveen , Nguyen Hoang Long , Lambrev Petar H. , Tan Howe‐Siang
Published: May 2020

We simulated two‐dimensional electronic spectra (2DES) of the chlorophyll a manifold of light‐harvesting complex II (LHCII) at various temperatures (77, 110, 150, 190, 230, 273, and 293 K) using the hierarchical equations of the motion‐phase matching approach. We confirm the main excitation energy transfer pathways assignments within the chlorophyll a manifold of LHCII measured in a recent work (J. Phys. Chem. B 2019, 123, 6765–6775). The calculated transfer rates are also in general agreement with the measured rates. We also provided theoretical confirmation for the experimental assignments, as uphill and downhill energy transfer processes, of 2D spectral features that were reported in recent experimental reports. These temperature‐dependent features were also ascertained to follow the detailed‐balance principle.
Mucus blocks probiotics but increases penetration of motile pathogens and induces TNF‐α and IL‐8 secretion
Authors: Sharma Abhinav , Raman Vishnu , Lee Jungwoo , Forbes Neil S.
Published: May 2020

The mucosal barrier in combination with innate immune system are the first line of defense against luminal bacteria at the intestinal mucosa. Dysfunction of the mucus layer and bacterial infiltration are linked to tissue inflammation and disease. To study host–bacterial interactions at the mucosal interface, we created an experimental model that contains luminal space, a mucus layer, an epithelial layer, and suspended immune cells. Reconstituted porcine small intestinal mucus formed an 880 ± 230 µm thick gel layer and had a porous structure. In the presence of mucus, sevenfold less probiotic and nonmotile VSL#3 bacteria transmigrated across the epithelial barrier compared to no mucus. The higher bacterial transmigration caused immune cell differentiation and increased the concentration of interleukin‐8 (IL‐8) and tumor necrosis factor‐alpha (TNF‐α; p < .01). Surprisingly, the mucus layer increased transmigration of pathogenic Salmonella and increased secretion of TNF‐α and IL‐8 (p < .05). Nonmotile, flagella knockout Salmonella had lower transmigration and caused lower IL‐8 and TNF‐α secretion (p < .05). These results demonstrate that motility enables pathogenic bacteria to cross the mucus and epithelial layers, which could lead to infection. Using an in vitro coculture platform to understand the interactions of bacteria with the intestinal mucosa has the potential to improve the treatment of intestinal diseases.
Characterizing students' arguments and explanations of a discipline‐based computational modeling activity
Authors: Lyon Joseph A. , Fennell Hayden W. , Magana Alejandra J.
Published: May 2020

Computational modeling is an essential and growing topic of interest in engineering and STEM education, in general. In this paper, a case study of a course targeting first‐year materials science and engineering students is overviewed to investigate student arguments when explaining their implementation and understanding of their computational models. The presented study used argumentation to characterize the varied ways students interpreted and explained their computational models. Student solutions to a computational modeling activity were coded for argumentation characteristics and errors. The results indicate the various errors that were commonly found when students explained their computational models, as well as patterns of appropriate arguments. The analysis demonstrates the nature of the relationship between argumentation and the modeling processes. The use of an argumentation rubric demonstrates the usefulness of such assessment tools for computational modeling assignments.
Electric field stress determination tool for MV insulation system models
Authors: Szafraniak Bartlomiej , Fusnik Lukasz , Bonk Michal , Smugala Dariusz
Published: May 2020

The evolution of teaching methods concerned with electrical engineering enables the development of new measurement stands or the improvement of existing educational methods. The advancement in engineering equipment is affecting the formation of new methodologies in teaching. Nevertheless, new educational techniques should be implemented by taking into account understanding of a physical basis of studied phenomena. This goal may be achieved via a combination of practical exercises conducted on testing stands, during evaluation, by means of modern computerized tools. In this paper, we described the combination of a numeric study of electric field (EF) distribution and an improved analog method analysis performed on an educational set‐up. For an effective understanding of technical problems of high‐voltage (HV) and medium‐voltage technology, the presented educational tool combines an experimental method of EF equipotential line mapping and EF strength determination with an improved analog method of EF strength inside the HV insulation system, which is determined by means of differential equation calculation implemented on the developed software. For fast verification of the results, computer simulations were applied. It allows for presenting the strong and weak points of both used methods. Analyzed models reproducing real devices were built on different scales; thus, achieved results reflect the real values and may be used for study help during seminars.
Synthesis and Metabolic Fate of 4‐Methylthiouridine in Bacterial tRNA
Authors: Borek Christoph , Reichle Valentin F. , Kellner Stefanie
Published: May 2020

Ribonucleic acid (RNA) is central to many life processes and, to fulfill its function, it has a substantial chemical variety in its building blocks. Enzymatic thiolation of uridine introduces 4‐thiouridine (s4U) into many bacterial transfer RNAs (tRNAs), which is used as a sensor for UV radiation. A similar modified nucleoside, 2‐thiocytidine, was recently found to be sulfur‐methylated especially in bacteria exposed to antibiotics and simple methylating reagents. Herein, we report the synthesis of 4‐methylthiouridine (ms4U) and confirm its presence and additional formation under stress in Escherichia coli. We used the synthetic ms4U for isotope dilution mass spectrometry and compared its abundance to other reported tRNA damage products. In addition, we applied sophisticated stable‐isotope pulse chase studies (NAIL‐MS) and showed its AlkB‐independent removal in vivo. Our findings reveal the complex nature of bacterial RNA damage repair.
First‐in‐human transcatheter pledget‐assisted suture tricuspid annuloplasty for severe tricuspid insufficiency
Authors: Greenbaum Adam B. , Khan Jaffar M. , Rogers Toby , Babaliaros Vasilis C. , Eng Marvin H. K. , Wang Dee Dee , Paone Gaetano , Lederman Robert J.
Published: May 2020

Objectives

We report the first pledget‐assisted suture tricuspid annuloplasty (PASTA) in a patient with torrential tricuspid regurgitation (TR).

Background

Tricuspid valve regurgitation is a common malignant disease with no commercially available transcatheter therapy. PASTA is a “percutaneous surgical” procedure using pledgeted sutures to create a double‐orifice tricuspid valve.

Methods

An 83‐year‐old man had end‐stage TR caused by a defibrillator lead. He consented to undergo PASTA on a compassionate basis. A double‐orifice valve was created with pledgeted sutures from percutaneous right ventricular apical access.

Results

TR was reduced from torrential to trace. The vena contracta reduced to from 23 to 1 mm and annular area reduced from 1817 to 782 mm2. However, the annulus dehisced and required closure with a percutaneous nitinol plug. The patient was discharged home and was alive 6 months later but with persistent symptoms.

Conclusions

The anatomy of a double‐orifice valve can eliminate TR but a better solution is required to avoid excessive suture tension on annular tissue.
On the Limited Stability of BDPA Radicals
Authors: Mandal Sucharita , Sigurdsson Snorri Th.
Published: May 2020

1,3‐Bis(diphenylene)‐2‐phenylallyl (BDPA)‐based radicals are of interest as polarizing agents for dynamic nuclear polarization (DNP). For this purpose, a BDPA‐nitroxide biradical, employing a phosphodiester linkage, was synthesized. Contrary to what is commonly assumed, BDPA‐derived radicals were observed to have limited stability. Hence, the effects of various factors on the stability of BDPA radicals were investigated. Solvent polarity was found to play a significant role on degradation; a polar BDPA radical was observed to degrade faster in a non‐polar solvent, whereas non‐polar radicals were more unstable in polar solvents. The rate of decomposition was found to increase non‐linearly with increasing radical concentration; a 2‐fold increase in concentration led to a 3‐fold increase in the rate of degradation. Collectively, these results indicate that the dimerization is a significant degradation pathway for BDPA radicals and indeed, a dimer of one BDPA radical was detected by mass spectrometry.
Stereoselective Steady‐State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults
Authors: Kharasch Evan D. , Neiner Alicia , Kraus Kristin , Blood Jane , Stevens Angela , Miller J. Philip , Lenze Eric J.
Published: May 2020

The antidepressant bupropion is stereoselectively metabolized and metabolite enantiomers have differential pharmacologic effects, but steady‐state enantiomeric disposition is unknown. Controversy persists about bupropion XL 300 mg generic equivalence to brand product, and whether generics might have different stereoselective disposition leading to enantiomeric non‐bioequivalence and, thus, clinical nonequivalence. This preplanned follow‐on analysis of a prospective, randomized, double‐blinded, crossover study of brand and 3 generic bupropion XL 300 mg products measured steady‐state enantiomeric plasma and urine parent bupropion and primary and secondary metabolite concentrations and evaluated bioequivalence and pharmacokinetics. Steady‐state plasma and urine bupropion disposition was markedly stereoselective, with up to 40‐fold differences in plasma concentrations of the active metabolite S,S‐hydroxybupropion vs. R,R,‐hydroxybupropion. Urine metabolite glucuronides were prominent, but glucuronidation was metabolite‐specific and enantioselective. There were no differences between any generic and brand, or between generics, in plasma enantiomer concentrations of bupropion or the major metabolites. All generic products satisfied formal bioequivalence criteria (peak plasma concentration (Cmax) and area under the plasma concentration‐time curve over 24 hours (AUC0–24)) using enantiomers for bupropion as well as for metabolites, and generics were comparable to each other, and were considered bioequivalent, based on enantiomeric analysis. Enantiomeric bioequivalence explains the previously observed therapeutic equivalence of bupropion generics and brand in treating major depression. These results have important implications for understanding the clinical therapeutic effects of bupropion based on complex and stereoselective metabolism.
Photocatalytic Partial Oxidation of 5‐Hydroxymethylfurfural (HMF) to 2,5‐Diformylfuran (DFF) Over a Covalent Triazine Framework in Water
Authors: Ayed Cyrine , Huang Wei , Kizilsavas Gönül , Landfester Katharina , Zhang Kai A. I.
Published: May 2020

Conversion of biomass into high value products via environmentally benign processes remains a challenging task for chemists. Photocatalytic partial oxidation of the biochemical 5‐hydroxymethylfurfural (HMF) to 2,5‐diformylfuran (DFF) has attracted much attention as DFF is known to be a pivotal precursor in the biochemical industry. Previously, this reaction has been catalyzed with transition metal based catalytic systems in organic solvents. Herein, we report the use of a covalent triazine framework (CTF) as a highly stable and porous organic photoactive polymer for the photocatalytic partial oxidation of HMF to DFF in water, using molecular oxygen as a green oxidant. The photocatalyst showed high efficiency in affording DFF as the target product with good reusability.
Lignin from Tree Barks: Chemical Structure and Valorization
Authors: Neiva Duarte M. , Rencoret Jorge , Marques Gisela , Gutiérrez Ana , Gominho Jorge , Pereira Helena , del Río José C.
Published: May 2020

Lignins from different tree barks, including Norway spruce (Picea abies), eucalyptus (Eucalyptus globulus), mimosa (Acacia dealbata) and blackwood acacia (A. melanoxylon), are thoroughly characterized. The lignin from E. globulus bark is found to be enriched in syringyl (S) units, with lower amounts of guaiacyl (G) and p‐hydroxyphenyl (H) units (H/G/S ratio of 1:26:73), which produces a lignin that is highly enriched in β‐ether linkages (83 %), whereas those from the two Acacia barks have similar compositions (H/G/S ratio of ≈5:50:45), with a predominance of β‐ethers (73–75 %) and lower amounts of condensed carbon–carbon linkages; the lignin from A. dealbata bark also includes some resorcinol‐related compounds, that appear to be incorporated or intimately associated to the polymer. The lignin from P. abies bark is enriched in G units, with lower amounts of H units (H/G ratio of 14:86); this lignin is thus depleted in β‐O‐4′ alkyl–aryl ether linkages (44 %) and enriched in condensed linkages. Interestingly, this lignin contains large amounts of hydroxystilbene glucosides that seem to be integrally incorporated into the lignin structure. This study indicates that lignins from tree barks can be seen as an interesting source of valuable phenolic compounds. Moreover, this study is useful for tailoring conversion technologies for bark deconstruction and valorization.
‘Nid yw wedi’i fwriadu i gael ei asesu yn y ffordd rydyn ni’n asesu’: Ailfeddwl am asesu ar gyfer cymhwyster yng nghyddestun gweithredu’r Cwricwlwm i Gymru
Authors: Titley Elizabeth , Davies Andrew James , Atherton Stephen
Published: May 2020

Mae’r papur hwn yn adrodd am bersbectifau athrawon a dysgwyr ar y ffordd y mae asesu a diwygio’n dylanwadu ar arferion ac ymddygiadau addysgegol. Cynhaliwyd yr ymchwil yng nghyd‐destun diwygio polisi, mewn cyfnod pan oedd y manylebau diwygiedig ar gyfer TGAU yng Nghymru wedi cael eu gweithredu, a phan oedd dysgwyr yn paratoi ar gyfer eu hasesiadau; ond hefyd yn ystod cyfnod y dadlau ynghylch datblygu’r cwricwlwm newydd i Gymru, sydd wedi mabwysiadu safbwynt gwahanol a gwrthgyferbyniol ar asesu o’i gymharu â’r rhagdybiaethau a oedd yn sail i’r diwygiadau i gymwysterau TGAU yng Nghymru a weithredwyd o 2015. Felly mae’r data hyn yn cynnig mewnwelediadau unigryw i’r dibenion a chyfyngiadau mewn dwy system wrthgyferbyniol iawn mewn cyfnod o newid sylweddol, sy’n cynnig ffyrdd o feddwl am y cwricwlwm presennol a’r arferion asesu ar ei gyfer, yn ogystal â dadansoddiad amcanol o’r modd y byddai’r egwyddorion sy’n sail i’r cwricwlwm newydd yn gallu herio’r rhagdybiaethau a chonfensiynau presennol hyn. Mae canfyddiadau’n awgrymu bod y system y mae athrawon a dysgwyr ynddi ar hyn o bryd yn un wedi’i seilio ar asesu sy’n ysgogi arferion perfformiadol mewn addysgeg ac yn cael ei rheoli gan atebolrwydd allanol; a bod yr arferion hyn yn groes i’r egwyddorion asesu sydd wedi’u cyfleu yn Dyfodol Llwyddiannus. O ganlyniad i hyn, roedd athrawon yn yr astudiaeth hon wedi mynegi ansicrwydd ynghylch y posibilrwydd o gysoni asesu at ddibenion ardystio TGAU ag egwyddorion y Cwricwlwm i Gymru.
Curriculum and opportunity in Scottish secondary education: a half‐century of expansion and inequality
Authors: Paterson Lindsay
Published: May 2020

Debate about the curriculum of secondary schools has centred on two competing claims. One is the aspiration to provide a broad, liberal curriculum to all students as a route into common citizenship. The other is that a curriculum of this kind, far from being potentially universal, is intrinsically merely the culture of dominant social groups, is inaccessible to people who are not members of these, and is also harmful to most students’ vocational opportunities. The analysis here considers these debates through data from a unique series of surveys of school students in Scotland, covering the whole of the second half of the twentieth century. It thus deals with a period when selection for entry to secondary school was ended for all public‐sector schools, and when, following that reform, there were deliberate attempts in policy to extend a liberal curriculum to everyone. The analysis provides some vindication of the reformers’ intentions that a liberal education could be experienced by a wider range of students than in the selective system. But it also shows that inequality of access to a broad curriculum became greater than previously.
Structural and biological survey of 7‐chloro‐4‐(piperazin‐1‐yl)quinoline and its derivatives
Authors: El‐Azzouny Aida M. Abd El‐Sattar , Aboul‐Enein Mohamed Nabil , Hamissa Mohamed Farouk
Published: May 2020

The 7‐chloro‐4‐(piperazin‐1‐yl)quinoline structure is an important scaffold in medicinal chemistry. It exhibited either alone or as hybrid with other active pharmacophores diverse pharmacological profiles such as: antimalarial, antiparasitic, anti‐HIV, antidiabetic, anticancer, sirtuin Inhibitors, dopamine‐3 ligands, acetylcholinesterase inhibitors, and serotonin antagonists. In the presented review, a comprehensive discussion of compounds having this structural core is surveyed and illustrated.
Antinociceptive effects of ceftriaxone in formalin‐induced nociception
Authors: Baeza‐Flores Guadalupe del Carmen , Rodríguez‐Palma Erick J. , Reyes‐Pérez Valeria , Guzmán‐Priego Crystell G. , Torres‐López Jorge E.
Published: May 2020

Ceftriaxone (CFX) is a β‐lactam antibiotic with analgesic properties. However, its role in the formalin‐induced nociception remains unknown. The purpose of this study was to investigate the antinociceptive effect of CFX in the 1% formalin test in rats. Formalin induced a typical nociceptive response (flinching behavior) of two phases. Local peripheral pretreatment (20 min) with CFX (400–800 μg/paw) slightly attenuated the flinching behavior in phase 2, but not phase 1. Acute intraperitoneal pretreatment (20 min) also reduced phase 2 of the formalin test. In both cases, CFX induced a dose‐dependent antinociception. We also tested the effect of CFX 1 day after its administration and in two schedules of repeated administration. One‐day pretreatment with CFX (50–400 mg/kg, ip) induced a dose‐dependent antinociceptive effect in formalin‐treated rats. Repeated administration (daily during 3 or 7 days) with CFX (50–400 mg/kg, ip) diminished formalin‐induced nociception. Results suggest that local or systemic as well as single or repeated administration of CFX reduces formalin‐induced nociception.
Urinary detection of rapid‐acting insulin analogs in healthy humans
Authors: Judák Péter , Coppieters Gilles , Lapauw Bruno , Van Eenoo Peter , Deventer Koen
Published: May 2020

Human insulin and its synthetic analogs are considered as life‐saving drugs for people suffering from diabetes mellitus. Next to the therapeutic use, scientific and non‐scientific literature (e.g. bodybuilding forums; antidoping intelligence and investigation reports) indicate that these prohibited substances are used as performance enhancing agents. In the present report, the development and validation of a sensitive analytical strategy is described for the urinary detection of three rapid‐acting insulin analogs (Lispro, Aspart, Glulisine). The method is based on sample purification by the combination of ultrafiltration and immunoaffinity purification and subsequent analysis by nano‐flow liquid chromatography coupled to high resolution mass spectrometry. Next to the results on different validation parameters (LOD: 10 pg/mL; recovery: 25–48%; matrix effect: −3‐(−8) %), data on urinary elimination times, which were obtained in the frame of an administration study with the participation of healthy volunteers, are presented. The determined detection windows (~9 hours) are expected to help to evaluate current routine analytical methods and aim to aid doping authorities to set appropriate target windows for efficient testing.
Association of pulmonary hypertension and right ventricular function with exercise capacity in heart failure
Authors: Teramoto Kanako , Sengelov Morten , West Erin , Santos Mario , Nadruz Wilson , Skali Hicham , Shah Amil M.
Published: May 2020

Aim

Relationships of pulmonary artery systolic pressure (PASP) and right ventricular (RV) dysfunction with exercise capacity are understudied. To assess the relationship of PASP and RV function with functional capacity and ventilatory efficiency in heart failure (HF) with a wide range of left ventricular ejection fraction (LVEF).

Methods and results

Five hundred thirty‐two consecutive HF patients referred for cardiopulmonary exercise testing [percent predicted peak VO2 (ppVO2), VE/VCO2 slope] and echocardiography [LVEF, PASP, and RV fractional area change (RVFAC)] were studied. Associations of PASP and RVFAC with ppVO2 and VE/VCO2 slope were assessed by multivariable linear regression and restricted cubic splines. Associations with composite of death, heart transplant, and LV assist device (median 3.9 year follow‐up) was assessed using multivariable Cox proportional hazard models.

Mean age was 56 ± 14 years and mean LVEF was 35 ± 15%. Mean PASP was 34 ± 12 mmHg, RVFAC was 41 ± 13%, ppVO2 was 60 ± 21%, and VE/VCO2 slope was 35 ± 12. After adjusting for demographics, co‐morbidities, LVEF, mitral regurgitation severity, and left atrial volume index, higher PASP was associated with worse ppVO2 (P = 0.004) and was more robust in patients with LVEF ≥45% vs. <45% (Pinteraction = 0.006). Lower RVFAC was associated with both worse ppVO2 (P = 0.002) and higher VE/VCO2 slope (P = 0.002). Higher PASP and lower RVFAC were both associated with heightened risk of composite endpoint (HR 1.07 per 5 mmHg increase, P = 0.03; HR 1.17 per 5% decrease, P <0.001, respectively).

Conclusions

In HF across wide range of LVEF, greater PASP and worse RV function predict worse functional capacity and greater respiratory inefficiency, independent of LV structure and function.
Silver(I) and Copper(I) Complexes of Semi‐Bulky Nitrogen‐Confused C‐Scorpionates
Authors: Wang Denan , Jahan Fathiya , Meise Kristen J. , Lindeman Sergey V. , Gardinier James R.
Published: May 2020

Two new sterically demanding nitrogen‐confused C‐scorpionate ligands with a bis(3,5‐diisopropylpyrazol‐1‐yl)methyl group bound to the 3‐ position of a normal pyrazole (HLiPr2) or an N‐toluenesulfonyl pyrazole (TsLiPr2) have been prepared. Reactions between the ligands (xLiPr2) and silver trifluoromethanesulfonate, AgOTf, gave four new compounds of the types [Ag(xLiPr2)](OTf) (x = Ts, 1a; x = H, 2a) or [Ag(xLiPr2)2](OTf) (x = Ts, 1b; x = H, 2b) depending on the initial metal:ligand ratio. Similarly, the reactions with [Cu(CH3CN)4](PF6) produce four new compounds of the type [Cu(xLiPr2)(CH3CN)](PF6) (x = Ts, 3a; x = H, 4a) or [Cu(xLiPr2)2](PF6) (x = Ts, 3b; x = H, 4b). The solid‐state structures of four derivatives (1a·acetone, 3a, 3b·CH2Cl2, and 4b·2THF) were determined by single‐crystal X‐ray diffraction while all complexes were characterized in CH3CN solution by NMR spectroscopy and ESI(+) MS. The eight new complexes catalyze the aziridination of styrene. The copper complexes were generally (but not exclusively) more active catalysts than their silver counterparts.
Lithium Organoaluminate Complexes as Catalysts for the Conversion of CO2 into Cyclic Carbonates
Authors: Guo Zhiqiang , Xu Yuan , Chao Jianbin , Wei Xuehong
Published: May 2020

Four lithium organoaluminate complexes containing bidentate pyrrolyl ligand were successfully synthesized, and their structural features were provided. These complexes were used as catalysts for chemical fixation of carbon dioxide with epoxides under mild conditions. Among them, complex {[C4H3N(AlEt3)(2‐CH2NHLitBu)][C4H3NLi(2‐CH2NHtBu)]}2 (4), in conjunction with tetrabutyl‐ammonium iodide (TBAI) as cocatalyst, exhibits higher catalytic activities than other lithium organoaluminates. Epoxides reacted with CO2 at 50 °C and 1 atm pressure to give the corresponding cyclic carbonates in yields of 62–99 %.
Insomnia is a risk factor for spreading of chronic pain: A Swedish longitudinal population study (SwePain)
Authors: Wiklund Tobias , Gerdle Björn , Linton Steven J. , Dragioti Elena , Larsson Britt
Published: May 2020

Background

Recent evidence suggests that insomnia negatively influences the occurrence of generalized pain. This study examined whether insomnia is a risk factor for the transition from local pain (LP) to generalized pain (i.e. spreading of pain).

Methods

This longitudinal study, with a follow‐up of 24 months, included 959 participants (mean age: 55.8 years; SD: 13.9) with local or regional pain at baseline. Participants were grouped by insomnia symptoms as measured by the Insomnia Severity Index. Spreading of pain was measured by body manikins based on the spatial distribution of pain on the body. We defined two outcome categories; one with relatively localized pain (i.e. LP and moderate regional pain [MRP]), and one with relatively generalized pain (i.e. substantial regional pain and widespread pain [WSP]). Baseline age, sex, education, depressive symptoms, anxiety symptoms, catastrophizing, pain intensity and spread of pain were also included in the Generalized Linear Model analysis.

Results

The unadjusted model showed that the risk of spreading of pain increased with an increase in insomnia symptoms (no insomnia: 55.4%; subthreshold insomnia: 25.4% moderate insomnia: 16.5% and severe insomnia: 2.7%). The risk increased in a dose‐dependent manner; moderate insomnia risk ratio (RR) 2.34 (95% confidence interval [CI]: 1.34–4.09) and severe insomnia RR 4.13 (95% CI: 1.56–10.92). The results were maintained in the fully adjusted model although MRP was the strongest predictor RR 6.95 (95% CI: 3.11–15.54).

Conclusion

Our findings show a strong prospective relationship between insomnia symptoms and the transition from relatively localized to generalized pain.

Significance

This study shows that people with LP conditions are at much higher risk of developing WSP if they also have significant insomnia symptoms. The elevated risk is evident after 24 months and increases in a dose‐dependent manner regarding the degree of exposure to insomnia symptoms. Local pain conditions are quite common in primary care, and an evaluation of the insomnia symptoms is highly recommended since the most common sleep problems can be treated effectively if detected.
Grayscale surface patterning using electrophoretic motion through a heterogeneous hydrogel material
Authors: Ge Ning , Xu Ren , Trinkle Christine A.
Published: May 2020

Chemical surface patterning can be an incredibly powerful tool in a variety of applications, as it enables precise spatial control over surface properties. But the equipment required to create functional surface patterns—especially “grayscale” patterns where independent control over species placement and density are needed—is often expensive and inaccessible. In this work, we leveraged equipment and methods readily available to many research labs, namely 3D printing and electroblotting, to generate controlled grayscale surface patterns. Three‐dimensional‐printed molds were used to cast polyacrylamide hydrogels with regions of variable polymer density; regions of low polymer density within the hydrogels served as reservoirs for proteins that were later driven onto a target surface using electrophoresis. This mechanism was used to deposit grayscale patterns of fluorescently labeled proteins, and the fluorescent intensity of these patterns was measured and compared to a theoretical analysis of the deposition mechanism.
Importance of Energy‐Sector Investment in Technology and Infrastructure
Authors: DeCotis Paul A.
Published: May 2020

Energy is ubiquitous in everyday life, serving as the lifeblood of economic activity and personal and social well‐being. Without it, we can't manufacture, farm, work, care for the sick and elderly, bank, or shop. Nor can we remain socially and emotionally connected while sheltering in place or working remotely during the COVID‐19 pandemic sweeping across the globe. At no time in known history has the world's economy and civilization been so dependent on energy and our energy infrastructures for our economic, social, and physical well‐being.
Investigating the effect of the air inlet temperature on the combustion characteristics of a spark ignition engine fueled by biogas
Authors: Ebrahemi Abdullah Ebrahem , Bassiony Mohamed Abdallah , Syam Thaer Mahmoud Ibrahim , Ahmed Samer
Published: May 2020

This work has conducted a numerical study using AVL‐Boost engine simulation utilizing biogas (CH4 and CO2)–air mixtures in a SI engine model. The effect of varying the air manifold temperature from 25 to 50°C on the combustion characteristics as well as engine performance under full load condition in a SI engine fueled by gasoline and biogas mixtures has been investigated. The performed tests involved using variable concentrations of CO2 from 10% to 40% by volume. The current model has been validated with experimental results and it was found that the error in predicting the P‐θ behavior of the engine is about 4.89%. The results showed that, as the air inlet temperature increases, the volumetric efficiency decreases and the brake specific fuel consumption (BSFC) increases for gasoline and all biogas compositions. However, the peak pressure, brake output power, maximum pressure rise rate, and maximum heat release rate were decreased slightly with the increase in air inlet temperature. The effect was only observed for gasoline and the 10%‐CO2 biogas, whereas the effect on the maximum heat release rate was detected on gasoline and biogas compositions up to 20%‐CO2 only. On the other hand, the existence and growth of CO2 content in the biogas reduced significantly the peak pressure, brake output power, maximum pressure rise rate, volumetric efficiency, and both net and maximum heat release rates, though its effect in reducing the volumetric efficiency stopped at 20%‐CO2 biogas. Furthermore, BSFC rises noticeably with the increase in CO2 ratio in biogas. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd.
Amygdala subnuclei volume in bipolar spectrum disorders: Insights from diffusion‐based subsegmentation and a high‐risk design
Authors: Damme Katherine S. F. , Alloy Lauren B. , Young Christina B. , Kelley Nicholas J. , Chein Jason , Ng Tommy H. , Titone Madison K. , Black Chelsea L. , Nusslock Robin
Published: May 2020

Amygdala abnormalities are widely documented in bipolar spectrum disorders (BSD). Amygdala volume typically is measured after BSD onset; thus, it is not known whether amygdala abnormalities predict BSD risk or relate to the disorder. Additionally, past literature often treated the amygdala as a homogeneous structure, and did not consider its distinct subnuclei and their differential connectivity to other brain regions. To address these issues, we used a behavioral high‐risk design and diffusion‐based subsegmentation to examine amygdala subnuclei among medication‐free individuals with, and at risk for, BSD. The behavioral high‐risk design (N = 114) included low‐risk (N = 37), high‐risk (N = 47), and BSD groups (N = 30). Diffusion‐based subsegmentation of the amygdala was conducted to determine whether amygdala volume differences related to particular subnuclei. Individuals with a BSD diagnosis showed greater whole, bilateral amygdala volume compared to Low‐Risk individuals. Examination of subnuclei revealed that the BSD group had larger volumes compared to the High‐Risk group in both the left medial and central subnuclei, and showed larger volume in the right lateral subnucleus compared to the Low‐Risk group. Within the BSD group, specific amygdala subnuclei volumes related to time since first episode onset and number of lifetime episodes. Taken together, whole amygdala volume analyses replicated past findings of enlargement in BSD, but did not detect abnormalities in the high‐risk group. Examination of subnuclei volumes detected differences in volume between the high‐risk and BSD groups that were missed in the whole amygdala volume. Results have implications for understanding amygdala abnormalities among individuals with, and at risk for, a BSD.
Role delineation for pharmacotherapy specialists: Re‐evaluating the clinical relevance of a patient‐centered credential
Authors: Muckle Timothy , Blair Melissa , Badowski Melissa E. , Yam Felix , Johnson Samuel G.
Published: May 2020

This article presents results of the 2019 Role Delineation Study (RDS) for pharmacotherapy specialty certification, conducted by the Board of Pharmacy Specialties (BPS). This RDS used both qualitative (ie, focus group) and quantitative (ie, survey) methodologies to shape and empirically validate the knowledge, skills, and abilities characterized by the practice performance domain of the pharmacotherapy certification content outline. Over 1100 survey responses were collected from board‐certified pharmacotherapy specialists and then analyzed and reviewed by a representative panel of subject matter experts in pharmacotherapy and psychometric analyses. Using statistical summaries of rating scale data, the panelists recommended revisions to the certification content outline and examination blueprint. Descriptions of how the survey results were used to develop test specifications are also provided. This analysis provides validity evidence for the content scope for pharmacotherapy specialist certification and for the specifications (ie, domain weight percentages) of the high‐stakes examination. In particular, the study reaffirmed the pharmacotherapy specialist certification as a clinically relevant, patient‐focused credential, consistent with the mission of the BPS.
Comparison of the electrochemical behavior of CoCrWNi, CoCrFeNiMo, and CoNiCrMo alloys
Authors: Pound Bruce G.
Published: May 2020

Numerous studies have examined the electrochemical behavior of Co‐28Cr‐6Mo and Co‐35Ni‐20Cr‐10Mo in simulated physiological solutions. However, two other CoCr alloys—Co‐20Cr‐15W‐10Ni and Co‐20Cr‐16Fe‐15Ni‐7Mo—have received relatively little attention. In this work, cyclic potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) were used to investigate the electrochemical behavior of as‐received and passivated CoCrWNi and CoCrFeNiMo in phosphate‐buffered saline. Comparison of the potentiodynamic results with those for as‐received and electropolished CoNiCrMo showed marked differences in the passive behavior of the three alloys, even though they are all Co‐20Cr. The passive film on all three alloys underwent solid‐state oxidation involving Cr(III) to Cr(VI) and Co(II) to Co(III). However, the alloys then differed substantially in their behavior. CoCrFeNiMo exhibited no further changes up to the onset of water oxidation, whereas CoNiCrMo was subject to transpassive dissolution, while CoCrWNi underwent a second oxidation and then localized breakdown of the oxide. The EIS results also showed differences between the alloys with regard to the oxide thickness and resistivity. The thickness increased in the order CoCrFeNiMo < CoNiCrMo < CoCrWNi. Passivation increased the thickness but did not significantly affect the resistivity. For the as‐received alloys, the resistivity increased with thickness, suggesting that the oxide films became less defective with increasing thickness.
High‐throughput 3D bioprinting of corneal stromal equivalents
Authors: Kutlehria Shallu , Dinh Thanh Cong , Bagde Arvind , Patel Nilkumar , Gebeyehu Aragaw , Singh Mandip
Published: May 2020

In this study we designed high‐throughput 3D bioprinting of corneal equivalents which may address the need for in vitro models. In our digital 3D cornea model, average dimensions of adult cornea were converted to 3D shapes, then to G‐code files which were printed by BIOX printer (CELLINK). To maintain the curvature of cornea, a support scaffold was designed using stereolithographic printer. The support scaffold could facilitate the printing of 6–12 corneas at a time thus enabling high‐throughput printing. Human corneal keratocytes (HCKs) were incorporated in the optimized bio‐ink, and cell‐laden corneal stromal equivalents were printed. Printed structures were cross‐linked by calcium chloride 100 mM, washed with Hanks' Balanced Salt Solution and incubated at 37°C in fibroblast media. Printed corneas were analyzed for live dead assay, Alamar assay, and expression of fibronectin and actin green markers. Printed corneas were able to maintain their structure, integrity, and clarity. Live dead assay and Alamar assay demonstrated that HCKs maintained high viability (>95%) for 2 weeks. HCKs in the printed corneas showed expression for fibronectin and actin green. In conclusion, high‐throughput fabrication of 3D printed corneal stromal equivalents using a combination of stereolithography printing, extrusion based printing, and micro‐transfer molding techniques was achieved.
Bone forming ability of recombinant human collagen peptide granules applied with β‐tricalcium phosphate fine particles
Authors: Furihata Tomokazu , Miyaji Hirofumi , Nishida Erika , Kato Akihito , Miyata Saori , Shitomi Kanako , Mayumi Kayoko , Kanemoto Yukimi , Sugaya Tsutomu , Akasaka Tsukasa
Published: May 2020

Recombinant human collagen peptide, developed based on human collagen type I, contains an arginyl‐glycyl‐aspartic acid (RGD)‐rich motif to enhance cell behavior and is anticipated as a xeno‐free polymer material for use in tissue engineering. We fabricated granules containing recombinant human collagen peptide (RCP) applied with beta‐tricalcium phosphate fine particles (RCP/β‐TCP) as bone filling scaffold material and assessed the bone forming ability of RCP/β‐TCP. Recombinant peptide was thermal crosslinked and freeze‐dried to prepare RCP. An aqueous dispersion of β‐TCP fine particles was added to RCP to obtain RCP/β‐TCP. Subsequently, RCP/β‐TCP were characterized using scanning electron microscopy (SEM), energy dispersive X‐ray spectrometry (EDX), and cell culture assessments. Furthermore, RCP/β‐TCP were implanted into rat cranial bone defects for radiographic and histological evaluations. In SEM and EDX analyses of RCP/β‐TCP, β‐TCP particles dose‐dependently covered the surface of RCP. Cell culture tests showed that RCP/β‐TCP remarkably promoted proliferation and mRNA expression of various genes, such as integrin β1 and osteogenic markers, of osteoblastic MC3T3‐E1 cells. Histomorphometric assessment at 4 weeks showed that RCP/β‐TCP significantly promoted new skull bone formation compared to RCP (p < 0.05) and control (no application) (p < 0.01). Accordingly, these findings suggest RCP/β‐TCP possess bone forming capability and would be beneficial for bone tissue engineering therapy.
miR‐324‐5p promotes adipocyte differentiation and lipid droplet accumulation by targeting Krueppel‐like factor 3 (KLF3)
Authors: Zhou Xiaomin , Shi Xin'e , Wang Jie , Zhang Xiaoyu , Xu Yanting , Liu Yihao , Li Xiao , Yang Gongshe
Published: May 2020

miRNAs, a kind of noncoding small RNA, play a significant role in adipose differentiation. In this study, we explored the effect of miR‐324‐5p in adipose differentiation, and found that miR‐324‐5p could promote adipocytes differentiation and increase body weight in mice. We overexpressed miR‐324‐5p during adipocytes differentiation, by oil red O and bodipy staining found that lipid accumulation was increased, and the expression level of adipogenic related genes were significantly increased. And the opposite experimental results were obtained after inhibiting miR‐324‐5p. In vivo, we injected miR‐324‐5p agomiR in obese mice and found that body weight, adipocyte area, and adipogenic‐related gene expression level were significantly increased but lipolytic genes were decreased. To further explore the mechanism of miR‐324‐5p regulation in lipid accumulation, we constructed Krueppel‐like factor 3 (KLF3) 3′‐untranslated region luciferase reporter vector and KLF3 pcDNA 3.1 overexpression vector, and found that miR‐324‐5p was able to directly target KLF3. Overall, in this study we found that miR‐324‐5p could promote mice preadipoytes differentiation and increase mice fat accumulation by targeting KLF3.