bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Value and Validity of Early Spondyloarthritis Features: Results From a National Spanish Cohort
Authors: Joven Beatriz E. , Navarro‐Compán Victoria , Rosas Jose , Fernandez Dapica Pilar , Zarco Pedro , de Miguel Eugenio ,   on behalf of the Esperanza Working Group
Published: January 2017

Objective

To evaluate the validity of different spondyloarthritis (SpA) features included in the Berlin diagnostic algorithm and the Assessment of SpondyloArthritis international Society (ASAS) classification criteria in an early SpA cohort.

Methods

This was a longitudinal multicenter study including patients from the ESPeranza program cohort who were suspected to have SpA. Subjects were ≤45 years old, and SpA symptom duration was 3–24 months. Patients with axial SpA symptoms were selected and categorized according to diagnosis (yes/no) of axial SpA. Descriptive analysis was performed, and the sensitivity, specificity, predictive value, and likelihood ratio (LR) of each feature were calculated.

Results

Of 775 patients suspected to have SpA, 665 had predominantly axial symptoms and 516 of these patients were diagnosed with axial SpA. The most useful SpA features were sacroiliitis on magnetic resonance imaging (positive LR 6.6) or radiograph (positive LR 31.1) and peripheral arthritis (positive LR 8.9). The features with the lowest diagnostic utility were a family history of SpA (positive LR 1.5) and good response to nonsteroidal antiinflammatory drugs (positive LR 1.6). Inflammatory back pain (IBP; according to ASAS criteria) was described in only 27% of SpA patients, with a positive LR of 2.3. HLA–B27 positivity was present in 245 (48%), and the positive LR was 2.8.

Conclusion

The diagnostic value of SpA features in patients with early axial SpA seems to be different than in patients with longstanding disease. Chronic back pain is better than IBP as an entry point to the diagnostic algorithm. Sacroiliitis on imaging is very important for early diagnosis, while the use of HLA–B27 status as a key factor is questionable.
Risk of Myocardial Infarction and Stroke in Newly Diagnosed Systemic Lupus Erythematosus: A General Population‐Based Study
Authors: Aviña‐Zubieta J. Antonio , To Fergus , Vostretsova Kateryna , De Vera Mary , Sayre Eric C. , Esdaile John M.
Published: January 2017

Objective

To estimate the future risk and time trends of newly diagnosed myocardial infarction (MI), ischemic stroke, or both (cardiovascular disease [CVD]) in individuals with systemic lupus erythematosus (SLE).

Methods

Using a population‐based database that includes all residents of British Columbia, Canada, we conducted a matched cohort study of all patients with incident SLE and up to 10 age‐, sex‐, and entry time–matched individuals from the general population. We compared incidence rates (IRs) of MI, ischemic stroke, or CVD (i.e., MI or ischemic stroke) between the 2 groups according to SLE disease duration. We calculated hazard ratios (HRs), adjusting for confounders.

Results

Among 4,863 individuals with SLE (86% female, mean age 48.9 years), the IRs of MI, stroke, and CVD were 6.4, 4.4, and 9.9 events per 1,000 person‐years, respectively, versus 2.8, 2.3, and 4.7 events per 1,000 person‐years in the comparison cohort. Compared with non‐SLE individuals, the fully adjusted multivariable HRs among SLE patients were 2.61 (95% confidence interval [95% CI] 2.12–3.20) for MI, 2.14 (95% CI 1.64–2.79) for stroke, and 2.28 (95% CI 1.90–2.73) for CVD. The age‐, sex‐, and entry time–matched HRs for MI, stroke, and CVD were highest during the first year after SLE diagnosis: 5.63 (95% CI 4.02–7.87), 6.47 (95% CI 4.42–9.47), and 6.28 (95% CI 4.83–8.17), respectively.

Conclusion

Patients with SLE have an increased risk of cardiovascular events, particularly during the first year after diagnosis. Increased vigilance in monitoring for these potentially fatal outcomes and their modifiable risk factors is recommended in this patient population.
Perceived Community Environmental Factors and Risk of Five‐Year Participation Restriction Among Older Adults With or at Risk of Knee Osteoarthritis
Authors: Vaughan Molly W. , Felson David T. , LaValley Michael P. , Orsmond Gael I. , Niu Jingbo , Lewis Cora E. , Segal Neil A. , Nevitt Michael C. , Keysor Julie J.
Published: January 2017

Objective

Older adults with knee osteoarthritis (OA) who live in environments with mobility barriers may be at greater risk of developing participation restrictions, defined as difficulties in engagement in life situations. We investigated the risk of participation restriction over 5 years due to self‐reported environmental features among older adults with knee OA.

Methods

Participants from the Multicenter Osteoarthritis (MOST) Study self‐reported participation at baseline, 30 months, and 60 months using the instrumental role subscale of the Late Life Disability Index (LLDI). Data on self‐reported environmental features were from the Home and Community Environment questionnaire administered in the MOST Knee Pain and Disability study, an ancillary study of MOST. The relative risks (RRs) of developing participation restriction at 60 months, indicated by an LLDI score <67.6 out of a possible 100, due to reported high community mobility barriers and high transportation facilitators, were calculated using robust Poisson regression, adjusting for covariates.

Results

Sixty‐nine of the 322 participants (27%) developed participation restriction by 60 months. Participants reporting high community mobility barriers at baseline had 1.8 times the risk (95% confidence interval [95% CI] 1.2–2.7) of participation restriction at 60 months, after adjusting for covariates. Self‐report of high transportation facilitators at baseline resulted in a reduced but statistically nonsignificant risk of participation restriction at 60 months (RR 0.7, 95% CI 0.4–1.1).

Conclusion

Higher perceived environmental barriers impact the risk of long‐term participation restriction among older adults with or at risk of knee OA. Approaches aimed at reducing the development of participation restrictions in this population should consider decreasing environmental barriers.
Association of Chondrocalcinosis in Knee Joints With Pain and Synovitis: Data From the Osteoarthritis Initiative
Authors: Han Bobby Kwanghoon , Kim Woojin , Niu Jingbo , Basnyat Shristi , Barshay Veniamin , Gaughan John P. , Williams Charlene , Kolasinski Sharon L. , Felson David T.
Published: January 2017

Objective

To evaluate the relationship between chondrocalcinosis and pain or synovitis in knee joints by examining data from the Osteoarthritis Initiative (OAI).

Methods

Data were obtained from the OAI public‐use data sets. The relationship between chondrocalcinosis on baseline knee radiograph and pain at baseline and at 4 years was examined. Analyses were adjusted for age, sex, body mass index, and Kellgren‐Lawrence (K/L) grade and the correlation between 2 knees in a subject was controlled using generalized estimating equations. The relationship between chondrocalcinosis and synovitis on magnetic resonance imaging (MRI) was examined by comparing knees with chondrocalcinosis at baseline and age, sex, and K/L grade–matched knees with no chondrocalcinosis. We read MRIs of a subset of knees for synovitis using the MRI Osteoarthritis Knee Score (MOAKS) on baseline and 4‐year MRI.

Results

Knees with chondrocalcinosis (n = 162) more often had pain compared to knees without chondrocalcinosis (n = 2,030) at baseline and had higher Western Ontario and McMaster Universities Osteoarthritis Index pain scores, both at baseline (mean 2.4 [95% confidence interval (95% CI) 1.9, 2.9]) versus mean 1.8 [95% CI 1.7, 1.9]) and at 4 years (mean 2.5 [95% CI 1.9, 3.1] versus mean 1.6 [95% CI 1.5, 1.8]), as well as higher Intermittent and Constant Osteoarthritis Pain intermittent pain scores at 4 years. There was no difference in MOAKS synovitis scores at baseline and at 4 years between the chondrocalcinosis group (n = 102) and the control group (n = 99).

Conclusion

Knees with chondrocalcinosis had increased pain and did not have higher synovitis scores on MRI compared to knees without chondrocalcinosis. The mechanisms by which chondrocalcinosis is associated with increased pain remain to be determined.
Cutaneous and Systemic Findings Associated With Nuclear Matrix Protein 2 Antibodies in Adult Dermatomyositis Patients
Authors: Rogers Anna , Chung Lorinda , Li Shufeng , Casciola‐Rosen Livia , Fiorentino David F.
Published: January 2017

Objective

To characterize the cutaneous and systemic clinical phenotype of dermatomyositis patients with antinuclear matrix protein 2 (anti–NXP‐2) antibodies.

Methods

We conducted a retrospective cohort analysis of 178 dermatomyositis patients seen at the Stanford University Clinic. An electronic chart review employing a keyword search strategy was performed to collect clinical and laboratory data. Anti–NXP‐2 antibodies were assayed by immunoprecipitation using NXP‐2 produced by in vitro transcription/translation.

Results

Antibodies to NXP‐2 were detected in 20 of the 178 patients (11%). Anti–NXP‐2 antibodies were associated with male sex (50% versus 25%; P = 0.02), dysphagia (74% versus 39%; P = 0.006), myalgia (89% versus 52%; P = 0.002), peripheral edema (35% versus 11%; P = 0.016), and calcinosis (37% versus 11%; P = 0.007). These patients were less likely to be clinically amyopathic (5% versus 23%; P = 0.08). Five of the 20 patients with anti–NXP‐2 antibodies (25%) had an associated internal malignancy. No other cutaneous characteristics were associated with anti–NXP‐2 antibodies, except a decreased frequency of Gottron's sign (44% versus 75%; P = 0.012) and a greater likelihood of having mild skin disease.

Conclusion

Dermatomyositis patients with anti–NXP‐2 antibodies have a distinct and often severe systemic phenotype that includes myalgia, peripheral edema, and significant dysphagia, despite having milder inflammatory skin disease.
Superior Fatigue Resistant Bioinspired Graphene‐Based Nanocomposite via Synergistic Interfacial Interactions
Authors: Wan Sijie , Xu Feiyu , Jiang Lei , Cheng Qunfeng
Published: January 2017

Excellent fatigue resistance is a prerequisite for flexible energy devices to achieve high and stable performance under repeated deformation state. Inspired by the sophisticated interfacial architecture of nacre, herein a super fatigue‐resistant graphene‐based nanocomposite with integrated high tensile strength and toughness through poly(dopamine)‐nickel ion (Ni2+) chelate architecture that mimics byssal threads is demonstrated. These kind of synergistic interfacial interactions of covalent and ionic bonding effectively suppress the crack propagation in the process of fatigue testing, resulting in superhigh fatigue life of this bioinspired graphene‐based nanocomposite (BGBN). In addition, the electrical conductivity is well kept after fatigue testing. The proposed synergistic interfacial interactions could serve as a guideline for fabricating high‐performance multifunctional BGBNs with promising applications in flexible energy devices, such as flexible electrodes for supercapacitors and lithium batteries, etc.
Synthesis of Medium‐Chain‐Length Polyhydroxyalkanoate Homopolymers, Random Copolymers, and Block Copolymers by an Engineered Strain of Pseudomonas entomophila
Authors: Wang Ying , Chung Ahleum , Chen Guo‐Qiang
Published: January 2017

Medium‐chain‐length polyhydroxyalkanoates (mcl‐PHAs), widely used in medical area, are commonly synthesized by Pseudomonas spp. This study tries to use β‐oxidation pathways engineered P. entomophila to achieve single source of a series of mcl‐monomers for microbial production of PHA homopolymers. The effort is proven successful for the first time to obtain a wide range of mcl‐PHA homopolymers from engineered P. entomophila LAC23 grown on various fatty acids, respectively, ranging from poly(3‐hydroxyheptanoate) to poly(3‐hydroxytetradecanoate). Effects of a PHA monomer chain length on thermal and crystallization properties including the changes of Tm, Tg, and Td5% are investigated. Additionally, strain LAC23 is used to synthesize random copolymers of 3‐hydroxyoctanoate (3HO) and 3‐hydroxydodecanoate (3HDD) or 3‐hydroxytetradecanoates, their compositions could be controlled by adjusting the ratios of two related fatty acids. Meanwhile, block copolymer P(3HO)‐b‐P(3HDD) is synthesized by the same strain. It is found for the first time that even‐ and odd number mcl‐PHA homopolymers have different physical properties. When the gene of the PHA synthase in the engineered P. entomophila is replaced by phaC from Aeromonas hydrophila 4AK4, poly(3‐hydroxybutyrate‐co‐30 mol%‐3‐hydroxyhexanoate) is synthesized. Therefore, P. entomophila can be used to synthesize the whole range of PHA (C7–C14) homopolymers, random‐ and block copolymers.
Evolution of the Coefficient of Friction with Surface Wear for Advanced Surface Textured Composites
Authors: Anwer Ali , Bagheri Zahra S. , Fernie Geoff , Dutta Tilak , Naguib Hani E.
Published: January 2017

In this study, textured composite surface with protruding fibers is developed, which exhibits extremely high coefficient of friction on ice. A novel composite material with improved wear resistibility is aimed to determine with the target to maintain its slip‐resistance properties over extended use. Particularly, two thermoplastic elastomers are compared, namely, thermoplastic polyurethanes (TPU) and Styrene–Butadiene–Styrene (SBS), reinforced with five types of fibers with varying stiffnesses and ductility, including alumina, basalt, glass, carbon, and poly(p‐phenylene‐2,6‐benzobisoxazole)) (PBO). The surface science of the composite is analyzed by using Fourier tranorm infrared spectroscopy to assess the intensity of existing interfacial bonding at fiber/matrix interface and scanning electron microscopy imaging for visual characterization. The results show that TPU composites have significantly higher abrasion resistance and slip resistance on ice as compared to SBS composites with the maximum abrasive resistance index (347.5 ± 29.5, p < 0.0001) and coefficient of friction on ice (0.375 ± 0.031, p < 0.0001) for PBO/TPU composite. Similarly, Fourier tranorm infrared spectroscopy spectrum demonstrates stronger existing bands in TPU compared to SBS composites indicative of better fiber wetting in TPU composites. The current PBO–TPU composite can be a potential candidate for various antislip applications as it has improved wear‐resistance (22%) and slip‐resistance (57%) properties, with respect to pure TPU.
Resistive Switching Properties through Iodine Migrations of a Hybrid Perovskite Insulating Layer
Authors: Kim Dong Jun , Tak Young Jun , Kim Won‐Gi , Kim Jin Kyu , Kim Jong Hak , Kim Hyun Jae
Published: January 2017

This study reports a low‐temperature processable, resistive switching (RS) device based on an inorganic–organic hybrid perovskite, i.e., methylammonium lead iodide (CH3NH3PbI3 or MAPbI3) via a fast deposition–crystallization method, as the multifunctional insulator layer to form metal/insulator/metal structure in which Al and p+‐Si wafer are used as the top and the bottom metal electrodes, respectively. The MAPbI3‐RS device shows acceptable RS characteristics with a switching window of 103 at a low voltage region (≈5 V), a stable endurance during 200 cycles, and a high retention for a prolonged time at 104 s. The operation mechanism of the MAPbI3‐RS device is based on ion (simultaneously vacancy) migration, especially iodine ions, which is analogous to that of oxygen ions in the conventional oxide‐based RS devices, confirmed through X‐ray photoelectron spectroscopy and energy‐dispersive X‐ray spectroscopy measurements. Furthermore, unusual multiresistance states are achieved from the MAPbI3‐RS device under light illumination due to the photosensitivity of MAPbI3.
Charge Transfer and Interface Engineering of the Pentacene and MoS2 Monolayer Complex
Authors: Shen Na , Tao Guohua
Published: January 2017

Molecular doping of monolayer MoS2 provides a great opportunity to modulate its electronic properties for the potential applications in high performance devices. Density functional theory computations are performed to investigate the charge transfer and electrostatic potential modulation upon the adsorption of pentacene molecule on the surface of MoS2 monolayer (ML). Theoretical calculations indicate that interfacial charge transfer is negligible between pentacene and 2H‐MoS2 ML while significant in the pentacene/1T‐MoS2 ML complex, which is attributed to the match of energy levels near the Fermi level in the latter case. Moreover, molecular doping of pentacene induces substantial structure changes of the substrate resulting in large adsorption energy, which helps stabilize the 1T‐MoS2 ML. Depending on different substrate phases and doping configurations, the interfacial dipole barrier and related work function of MoS2 ML may be modulated in a wide range of the order of about 1 eV. The findings therefore shed light on the possibility of developing the desired organic/inorganic complex for electrical and optoelectronic devices by molecular doping via charge transfer modulation and interface engineering.
New Electro‐Optic Salt Crystals for Efficient Terahertz Wave Generation by Direct Pumping at Ti:Sapphire Wavelength
Authors: Lee Seung‐Chul , Kang Bong Joo , Koo Min‐Jeong , Lee Seung‐Heon , Han Jae‐Hyun , Choi Jae‐Young , Kim Won Tae , Jazbinsek Mojca , Yun Hoseop , Kim Dongwook , Rotermund Fabian , Kwon O‐Pil
Published: January 2017

Broadband terahertz (THz) wave generators based on widely used ultrafast solid‐state lasers operating near 800 nm are very attractive for diverse linear and nonlinear THz applications. Here new electro‐optic molecular salt crystals are developed for efficient THz wave generation directly pumpable by a conventional femtosecond (fs) Ti:sapphire amplifier. Electron‐rich naphthalene‐sulfonate anions (naphthalene‐2‐sulfonate and naphthalene‐1‐sulfonate) are introduced in new electro‐optic quinolinium crystals, instead of previously used benzene‐sulfonate anions with smaller size. In new electro‐optic crystals, highly nonlinear quinolinium‐based molecular cations are optimally aligned for maximizing the diagonal electro‐optic response. The quinolinium‐based crystals prepared using a simple cleaving method exhibit excellent crystal characteristics suitable for efficient THz wave generation, good optical quality with two parallel surfaces having high flatness, and desired crystal thickness. Pumped with 100 fs pulses from a Ti:sapphire amplifier at 800 nm, the quinolinium‐based crystals enable efficient THz wave generation. Compared to the standard inorganic 1.0 mm thick ZnTe crystal, 4.7 times higher field amplitude and a broader bandwidth with the upper cutoff frequency of 6.0 THz are obtained. Therefore, introducing naphthalene‐sulfonate anions in molecular salt electro‐optic crystals is a promising way for designing electro‐optic crystals for THz wave generation by pumping at the technologically important Ti:sapphire wavelength.
Arbitrary Beam Steering Enabled by Photomechanically Bendable Cholesteric Liquid Crystal Polymers
Authors: Li Cheng‐Chang , Chen Chun‐Wei , Yu Chu‐Kuan , Jau Hung‐Chang , Lv Jiu‐An , Qing Xin , Lin Ching‐Fu , Cheng Chiao‐Yu , Wang Cheng‐Yu , Wei Jia , Yu Yanlei , Lin Tsung‐Hsien
Published: January 2017

Beam‐steering technology is now in widespread use in a variety of optical systems, spanning from fiber‐optic interconnector to Lidar. Most current techniques are based on optical grating diffractions; they are thus subject to not only finite tuning range, direction, and efficiency but also complex inorganic fabrication and circuit design. A high‐degree‐of‐freedom beam‐steering element makes such operations more efficient and versatile. Azobenzene cholesteric liquid crystal polymer (azo‐ChLCP) can be regarded as a soft self‐assembled Bragg mirror capable of being bent photomechanically. With proper control of pump polarization and exposure time, the output beam can be directly steered to an arbitrary direction. The deflection efficiency was achieved to be at least 90% with an angular tuning range of ≈54°, which is markedly superior to conventional grating‐based devices. Additionally, the angle of deflection is independent of wavelength, preventing the deflected beam from spreading out with colors. This work demonstrates and characterizes the azo‐ChLCP beam deflector, which features optical tunability, high efficiency, wide tuning range, and polarization‐selective deflection direction, making a significant breakthrough in beam‐steering technology.
The historical spread of Arabian Pastoralists to the eastern African Sahel evidenced by the lactase persistence −13,915*G allele and mitochondrial DNA
Authors: Priehodová Edita , Austerlitz Frédéric , Čížková Martina , Mokhtar Mohammed G. , Poloni Estella S. , Černý Viktor
Published: January 2017

Objectives

Thanks to the ability to digest lactose, Arabian nomads had become less dependent upon their sedentary neighbors and some of these populations spread to Africa. When and by which route they migrated to their current locations have previously been addressed only by historical and archaeological data.

Methods

To address the question of Arab expansion into Africa, we collected samples from several Arabic populations, especially the Baggara in Chad and Sudan. We analyzed mutations associated with lactase persistence and reconstructed the surrounding haplotypes defined by SNP polymorphisms. We also sequenced their mitochondrial DNA to investigate relative proportions of sub‐Saharan and Eurasian origins.

Results

We estimated the expansion age of the −13,915*G mutation in four different Arabian datasets. The oldest age was identified in Yemen (1,356–1,799 ya) and the youngest in a Sudanese group of Rashaayda Arabs (219–312 ya). We also found a negative correlation between the frequency of the −13,915*G allele and the frequency of sub‐Saharan mtDNA haplotypes.

Conclusions

Even if the age of the most recent common ancestor of −13,915*G is ∼4 ka as shown in a previous study, our results suggest that its spread to Africa was more recent, which is consistent with the migrations of Arabic tribes. Because the incidence of sub‐Saharan mtDNA haplotypes is negatively correlated with the occurrence of −13,915*G, we suggest that the decrease of its frequency in Africa has been caused by progressive admixture of the Arabian nomads with sub‐Saharan populations.
Effects of combined exposure to metals, solvents, and noise on permanent threshold shifts
Authors: Schaal Nicholas , Slagley Jeremy , Zreiqat Majed , Paschold Helmut
Published: January 2017

Background

Studies suggest metal and solvent exposure may damage hearing. This study evaluated the association between exposures classified as high for metals, solvents, and noise on permanent threshold shift (PTS) development.

Methods

A total of 1,546 personnel at an industrial shipyard were divided into five exposure groups based on level of concentration: high noise, high metals/solvents, high metals/noise, high metals/solvents/noise, and a low metals/solvents/noise reference group. Hearing threshold changes were analyzed to identify development of a PTS.

Results

Logistic regression indicated high metals/solvents and high metals/solvent/noise groups had significantly greater odds ratios of 2.4; 95%CI [1.02, 2.85] and 1.7; 95%CI [1.46, 3.94], respectively, compared to a reference group. Both groups were associated with PTSs while controlling for age, gender, and exposure duration.

Conclusions

Simultaneous exposures classified as high for metals and solvents may damage hearing. Results suggest the need for expanding hearing conservation programs to consider combinations of exposures to metals, solvents, and noise. Am. J. Ind. Med. 60:227–238, 2017. © 2017 Wiley Periodicals, Inc.
Evolution of the hominoid scapula and its implications for earliest hominid locomotion
Authors: Selby Michael S. , Lovejoy C. Owen
Published: January 2017

Objectives

The higher primate scapula has been subject to many explanations of the putative “adaptive value” of its individual traits. However, the shift from the bone's position in above branch quadrupeds to its more posterolateral position in recent hominoids obviously required fundamental changes to its general form. We hypothesize that most features argued to be individually adaptive are more likely secondary consequences of changes in its fundamental bauplan, a view more consistent with modern developmental biology.

Materials and Methods

We tested this hypothesis with scapular metrics and angles from a broad anthropoid sample.

Results

Our results support our hypothesis. Contrary to earlier predictions, vertebral border length differs little relative to body size in anthropoids, inferior angle position primarily reflects mediolateral scapular breadth, and supraspinous and infraspinous fossa sizes largely reflect scapular spine orientation. Suspensory taxa have cranially oriented glenoids, whereas slow clamberers and humans do not. Australopithecus most closely resembles the latter.

Discussion

Most scapular features can be explained by only two primary changes: (1) reduction in mediolateral breadth and (2) change in the glenoid position relative to the vertebral border with increased reliance on suspension, which led to a more cranially angled scapular spine. Virtually all other scapular traits appear to be byproducts of these two changes. Based on fossil morphology, hominids1 were derived from a last common ancestor primarily adapted for clambering and not for suspension. Scapular form in early hominids such as Australopithecus is therefore primitive and largely reflects the genus's general clambering heritage.
Funktionelle Isoeugenol‐modifizierte Nanogel‐Beschichtungen für biologische Grenzflächen
Authors: Kather Michael , Skischus Merle , Kandt Pierre , Pich Andrij , Conrads Georg , Neuss Sabine
Published: January 2017

Es wurde eine neue Route zur Synthese funktioneller wässriger Nanogele mit kontrollierter Isoeugenol‐Oberflächenbeladung entwickelt. Die so erhaltenen Nanogele haben zwei Schlüsselfunktionen: a) antibakterielle Aktivität gegen diverse orale Krankheitserreger sowie b) zelladhäsive und zellwachstumsfördernde Eigenschaften. Diese funktionellen Nanogele sind potenzielle Bausteine für bioaktive Beschichtungen auf verschiedenen Implantaten, die zur Verhinderung von Infektionen und zur Förderung von Zellwachstum genutzt werden können.
Protonendetektierte Festkörper‐NMR‐Spektroskopie an einem Zinktransporter‐Membranprotein in nativen Nanoscheiben
Authors: Bersch Beate , Dörr Jonas M. , Hessel Audrey , Killian J. Antoinette , Schanda Paul
Published: January 2017

Struktur, Dynamik und Funktion von Membranproteinen sind eng verknüpft mit den Eigenschaften der Membranumgebung, in die sie eingebettet sind. Im Allgemeinen müssen Membranproteine für strukturelle und biophysikalische Untersuchungen aber aus der Membran extrahiert und in einem geeigneten Membranmimetikum rekonstituiert werden. Ob die funktionelle und strukturelle Integrität in solchen künstlichen Umgebungen erhalten bleibt, ist oft nicht leicht zu evaluieren, aber für die Interpretation von höchster Wichtigkeit. Das Styrol‐Maleinsäure‐Copolymer ermöglicht es, Membranproteine mit den umgebenden Lipiden direkt aus nativen Membranen zu extrahieren. Die resultierenden scheibenförmigen Proteolipid‐Partikel werden auch native Nanoscheiben genannt. Wir zeigen hier, am Beispiel des 2×34 kDa großen bakteriellen Kationendiffusionsunterstützers CzcD, dass hochaufgelöste Festkörper‐NMR‐Spektren von integralen Membranproteinen in nativen Nanoscheiben erhalten werden können.
The Role of Holes in Borophenes: An Ab Initio Study of Their Structure and Stability with and without Metal Templates
Authors: Karmodak Naiwrit , Jemmis Eluvathingal D.
Published: January 2017

An electron‐counting strategy starting from magnesium boride was used to show the inevitability of hexagonal holes in 2D borophene. The number (hole density, HD) and distribution of the hexagonal holes determine the binding energy per boron atom in monolayer borophenes. The relationship between binding energy and HD changes dramatically when the borophene is placed on a Ag(111) surface. The distribution of holes in borophenes on Ag(111) surfaces depends on the temperature. DFT calculations show that aside from the previously reported S1 and S2 borophene phases, other polymorphs may also be competitive. Plots of the electron density distribution of the boron sheets suggest that the observed STM image of an S2 phase corresponds to a sheet with a HD of 2/15 instead of a sheet with a HD of 1/5. The hole density and the hole distribution echo the distribution of vacancies and extra occupancies in complex β‐rhombohedral boron.
N‐Heterocyclic‐Carbene‐Catalyzed Umpolung of Imines
Authors: Patra Atanu , Mukherjee Subrata , Das Tamal Kanti , Jain Shailja , Gonnade Rajesh G. , Biju Akkattu T.
Published: January 2017

N‐Heterocyclic carbene (NHC) catalysis has been widely used for the umpolung of aldehydes, and recently for the umpolung of Michael acceptors. Described herein is the umpolung of aldimines catalyzed by NHCs, and the reaction likely proceeds via aza‐Breslow intermediates. The NHC‐catalyzed intramolecular cyclization of aldimines bearing a Michael acceptor resulted in the formation of biologically important 2‐(hetero)aryl indole 3‐acetic‐acid derivatives in moderate to good yields. The carbene generated from the bicyclic triazolium salt was found to be efficient for this transformation.
Highly Multiplexed Single‐Cell In Situ Protein Analysis with Cleavable Fluorescent Antibodies
Authors: Mondal Manas , Liao Renjie , Xiao Lu , Eno Taylor , Guo Jia
Published: January 2017

Limitations on the number of proteins that can be quantified in single cells in situ impede advances in our deep understanding of normal cell physiology and disease pathogenesis. Herein, we present a highly multiplexed single‐cell in situ protein analysis approach that is based on chemically cleavable fluorescent antibodies. In this method, antibodies tethered to fluorophores through a novel azide‐based cleavable linker are utilized to detect their protein targets. After fluorescence imaging and data storage, the fluorophores coupled to the antibodies are efficiently cleaved without loss of protein target antigenicity. Upon continuous cycles of target recognition, fluorescence imaging, and fluorophore cleavage, this approach has the potential to quantify over 100 different proteins in individual cells at optical resolution. This single‐cell in situ protein profiling technology will have wide applications in signaling network analysis, molecular diagnosis, and cellular targeted therapies.
Bio‐Inspired Fragmentations: Rapid Assembly of Indolones, 2‐Quinolinones, and (−)‐Goniomitine
Authors: Li Haokun , Cheng Peng , Jiang Long , Yang Jin‐Liang , Zu Liansuo
Published: January 2017

Inspired by the biogenetic origin of goniomitine, new synthetic bio‐inspired fragmentation strategies for the synthesis of functionalized 2‐quinolinones and indolones have been developed. Remarkable synthetic efficiency was achieved by telescoping several transformations into one‐pot reactions, allowing for the direct coupling of 2‐alkynyl‐anilines and diazo ketones. The synthetic utility was demonstrated by the 5‐step asymmetric total synthesis of (−)‐goniomitine from 2‐ethyl‐cyclopentanone.
An Electron Acceptor with Porphyrin and Perylene Bisimides for Efficient Non‐Fullerene Solar Cells
Authors: Zhang Andong , Li Cheng , Yang Fan , Zhang Jianqi , Wang Zhaohui , Wei Zhixiang , Li Weiwei
Published: January 2017

A star‐shaped electron acceptor based on porphyrin as a core and perylene bisimide as end groups was constructed for application in non‐fullerene organic solar cells. The new conjugated molecule exhibits aligned energy levels, good electron mobility, and complementary absorption with a donor polymer. These advantages facilitate a high power conversion efficiency of 7.4 % in non‐fullerene solar cells, which represents the highest photovoltaic performance based on porphyrin derivatives as the acceptor.
Catalytic Enantioselective Synthesis of Lactams through Formal [4+2] Cycloaddition of Imines with Homophthalic Anhydride
Authors: Jarvis Claire L. , Hirschi Jennifer S. , Vetticatt Mathew J. , Seidel Daniel
Published: January 2017

An amide‐thiourea compound, operating through a novel ion pairing mechanism, is an efficient organocatalyst for the asymmetric reaction of homophthalic anhydride with imines. N‐aryl and N‐alkyl imines readily undergo formal [4+2] cycloaddition to provide lactams with high levels of enantio‐ and diastereoselectivity. The nature of the key chiral ion pair intermediate was elucidated by DFT calculations.
NHC‐Organocatalyzed CAr−O Bond Cleavage: Mild Access to 2‐Hydroxybenzophenones
Authors: Janssen‐Müller Daniel , Singha Santanu , Lied Fabian , Gottschalk Karin , Glorius Frank
Published: January 2017

A Truce–Smiles rearrangement of acyl‐anion equivalents generated by N‐heterocyclic carbene (NHC) catalysis has been achieved. The developed method includes CAr−O, CAr−S, or CAr−N bond cleavage for the formation of a CAr−C bond and enables access to 2‐hydroxybenzophenones, an important structural motif that is present in several bioactive natural products. By utilizing this procedure, the alkaloid taxilamine was synthesized in three steps. DFT calculations and control experiments support a classical SNAr mechanism with a catalyst‐bound Meisenheimer‐type intermediate. The method features mild reaction conditions, excellent functional‐group tolerance, and a broad substrate scope, including various classes of (hetero)arenes.
Presence of vacuoles in natural rubber–Cloisite 15A nanocomposites
Authors: Petković Didović Mirna , Klepac Damir , Meera A. P. , Thomas Sabu , Valić Srećko
Published: January 2017

We studied natural rubber (NR) filled with frequently used organoclay Cloisite 15A using transmission electron microscopy (TEM), cryoporosimetry, and electron spin resonance (ESR) spectroscopy. Quantitative analysis of the TEM micrographs showed a high level of dispersion without the formation of a rigid filler network. The presence of vacuoles was established on the surface of Cloisite 15A; this indicated weak filler–matrix interactions. The mechanism of reinforcement is, therefore, discussed. The volume of vacuoles was found to be proportional to the crosslinking density; this was confirmed with ESR spin‐probe method. The shape of the ESR spectra was highly influenced by the presence of vacuoles. In the NR–Cloisite 10A nanocomposites, vacuoles were absent. The strong interactions implied by this result were confirmed by ESR measurements and are discussed further. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44776.
Flexible perfluoroalkoxy films filled with carbon nanotubes and their electric heating property
Authors: Meng Xing , Liu Yangsi , Huang Meiyan , Cao Jian‐Ping
Published: January 2017

Carbon nanotubes (CNTs) filled perfluoroalkoxy (PFA) films with the thicknesses of about 10 μm have been prepared via blade coating. Both of the CNTs and PFA are aqueous dispersion, which are favorable for the uniform dispersion of fillers into the matrix. The morphology, direct current (DC) resistivity, electrothermal property, and thermal diffusivity of the composite films were studied. We find out that the fraction of CNTs played a vital role in the heating property and thermal transferring capacity of the composite films. Under the input voltage of 110 V, the temperature of PFA composite film with 15 wt % CNT reached to 200 °C, and the thermal diffusivity was about 3.3 mm2/s. We believe these CNTs/PFA films are promising alternatives to work as flexible electric heating devices. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44782.
Polydopamine dots as an ultrasensitive fluorescent probe switch for Cr(VI) in vitro
Authors: Zhao Shizhen , Song Xun , Bu Xiuming , Zhu Chong , Wang Gang , Liao Fang , Yang Siwei , Wang Miao
Published: January 2017

Because of the great demand for fluorescent materials, fluorescent dyes, semiconductor quantum dots, and carbon‐based quantum dots have been studied extensively. However, the poor photostability and potential biological toxicity need to be resolved. In this study, we demonstrated the synthesis of a new biomass quantum dot, the polydopamine dot (PDADs), via a simple hydrothermal method under an acidic environment. This new biomass quantum dot showed not only remarkable photoluminescence properties (quantum yield = 0.93) but also a high stability and low toxicity. Moreover, these PDADs could be used as a fluorescent probe for the rapid detection of Cr(VI) (response time = 0.01 s). The detection limit (1 × 10−11 M) is the lowest detection limit reported for Cr(VI) fluorescent probes. The mechanism efficient quenching progress could have been due to the fast redox progress between the PDADs and Cr(VI). Moreover, we also showed a practical application of PDADs for Cr(VI) detection in vitro. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44784.
Gene expression profiling analysis of the effects of low‐intensity pulsed ultrasound on induced pluripotent stem cell–derived neural crest stem cells
Authors: Xia Bin , Zou Yang , Xu Zhiling , Lv Yonggang
Published: January 2017

Low‐intensity pulsed ultrasound (LIPUS) is a noninvasive technique that has been shown to affect cell proliferation, migration, and differentiation and promote the regeneration of damaged peripheral nerve. Our previous studies had proved that LIPUS can significantly promote the neural differentiation of induced pluripotent stem cell–derived neural crest stem cells (iPSCs‐NCSCs) and enhance the repair of rat‐transected sciatic nerve. To further explore the underlying mechanisms of LIPUS treatment of iPSCs‐NCSCs, this study reported the gene expression profiling analysis of iPSCs‐NCSCs before and after LIPUS treatment using the RNA‐sequencing (RNA‐Seq) method. It was found that expression of 76 genes of iPSCs‐NCSCs cultured in a serum‐free neural induction medium and expression of 21 genes of iPSCs‐NCSCs cultured in a neuronal differentiation medium were significantly changed by LIPUS treatment. The differentially expressed genes are related to angiogenesis, nervous system activity and functions, cell activities, and so on. The RNA‐seq results were further verified by a quantitative real‐time reverse transcriptase polymerase chain reaction (qRT‐PCR). High correlation was observed between the results obtained from qRT‐PCR and RNA‐Seq. This study presented new information on the global gene expression patterns of iPSCs‐NCSCs after LIPUS treatment and may expand the understanding of the complex molecular mechanism of LIPUS treatment of iPSCs‐NCSCs.
A framework for quantitatively assessing the repurpose potential of existing industrial facilities as a biorefinery
Authors: Martinkus Natalie , Wolcott Michael
Published: January 2017

Constructing a commercial biorefinery involves significant financial and technical risks that may affect investor willingness to commit funds. Repurposing existing industrial facilities has been proposed as a means to lessen the investment risk in constructing a new biorefinery through reduced financial requirements and startup costs. This research provides a decision‐making tool for estimating the repurpose potential of existing industrial facilities considered for conversion to a biorefinery. It applies well‐established techniques for capital cost estimation of Greenfield biorefinery and pulp mill infrastructure and assets to determine their repurpose potential as a biorefinery. It demonstrates how capital cost reduction is highly dependent on the process technology present in the subject facility. A factored approach is employed to assign valuation to the major capital cost components of a Greenfield biorefinery. Existing facilities are then assessed for their compatibility through an infrastructure and asset analysis to determine an estimated capital percent savings that may be realized through repurposing into a biorefinery. Private and public databases and general facility process designs are used to determine the presence of equipment in each facility assessed. A yes/no analysis is performed to assign full cost to facility infrastructure and assets not present in the biorefinery and no cost to those that are present. This methodology provides an economic valuation tool for facility assessments as a metric for facility comparisons, and may be used to assist in decision‐making regarding the suitability of a facility for repurposing. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd
White paper on the study of birth defects
Authors: Khokha Mustafa K. , Mitchell Laura E. , Wallingford John B.
Published: January 2017

Birth defects are the leading cause of infant death in the United States and among the top causes of pediatric death and hospitalization. Despite the devastating impact of birth defects, we understand little of their etiology impeding progress towards treatment and prevention. Moreover, while surgical interventions have improved survival for many children to beyond their first year, our inability to accurately predict, diagnose and treat the common sequelae of birth defects leaves the economic, social and public health burden of birth defects unacceptably high.

An estimated one‐third of all pediatric hospital beds are occupied by a child with a genetic diagnosis, and emerging genomic sequencing technologies provide an unprecedented opportunity to identify the genetic variants, including those that cause birth defects. It is essential that we leverage these advances to enhance our understanding of birth defects. Such an effort will lead to new avenues for treatment and provide benefits to families, including improved understanding of the cause of a child's condition and the risks to any future children.

Understanding the genetics of human birth defects presents many challenges, some shared with other pathologies and some unique. This White Paper outlines the need for a birth defect genomics initiative, the challenges to overcome, and suggested solutions. Ultimately, we conclude that understanding birth defects must be a trans‐NIH effort and involve the development of a new type of interdisciplinary team comprised of clinicians, geneticists, genomicists, epidemiologists, biostatisticians and basic cellular and developmental biologists working together in all aspects of the enterprise. Birth Defects Research 109:180–185, 2017. © 2017 Wiley Periodicals, Inc.
Improved standard error estimator for maintaining the validity of inference in cluster randomized trials with a small number of clusters
Authors: Ford Whitney P. , Westgate Philip M.
Published: January 2017

Cluster randomized trials (CRTs) are studies in which clusters of subjects are randomized to different trial arms. Due to the nature of outcomes within the same cluster to be correlated, generalized estimating equations (GEE) are growing as a popular choice for the analysis of data arising from CRTs. In the past, research has shown that analyses using GEE could result in liberal inference due to the use of the empirical sandwich covariance matrix estimator, which can yield negatively biased standard error estimates when the number of clusters is not large. Many techniques have been presented to correct this negative bias; however, use of these corrections can still result in biased standard error estimates and thus test sizes that are not consistently at their nominal level. Therefore, there is a need for an improved correction such that nominal type I error rates will consistently result. In this manuscript, we study the use of recently developed corrections for empirical standard error estimation and the use of a combination of two popular corrections. In an extensive simulation study, we found that nominal type I error rates can be consistently attained when using an average of two popular corrections developed by Mancl and DeRouen (, Biometrics 57, 126–134) and Kauermann and Carroll (, Journal of the American Statistical Association 96, 1387–1396). Therefore, use of this new correction was found to notably outperform the use of previously recommended corrections.
Cell‐controlled hybrid perfusion fed‐batch CHO cell process provides significant productivity improvement over conventional fed‐batch cultures
Authors: Hiller Gregory W. , Ovalle Ana Maria , Gagnon Matthew P. , Curran Meredith L. , Wang Wenge
Published: January 2017

A simple method originally designed to control lactate accumulation in fed‐batch cultures of Chinese Hamster Ovary (CHO) cells has been modified and extended to allow cells in culture to control their own rate of perfusion to precisely deliver nutritional requirements. The method allows for very fast expansion of cells to high density while using a minimal volume of concentrated perfusion medium. When the short‐duration cell‐controlled perfusion is performed in the production bioreactor and is immediately followed by a conventional fed‐batch culture using highly concentrated feeds, the overall productivity of the culture is approximately doubled when compared with a highly optimized state‐of‐the‐art fed‐batch process. The technology was applied with near uniform success to five CHO cell processes producing five different humanized monoclonal antibodies. The increases in productivity were due to the increases in sustained viable cell densities. Biotechnol. Bioeng. 2017;114: 1438–1447. © 2017 Wiley Periodicals, Inc.
Toward a New International Standard on Governance of Organizations
Authors: Faber Rubina
Published: January 2017

As the new year gets under way, Rubina Faber, who has been closely involved in the creation of the British standard BS 13500: Code of Practice for Delivering Effective Governance of Organizations,1 reflects on that experience and the work under way to establish an ISO (International Organization for Standardization) standard on governance of organizations.
A robust feeding strategy to maintain set‐point glucose in mammalian fed‐batch cultures when input parameters have a large error
Authors: Konakovsky Viktor , Clemens Christoph , Müller Markus Michael , Bechmann Jan , Herwig Christoph
Published: January 2017

Industrial CHO cell cultures run under fed‐batch conditions are required to be controlled in particular ranges of glucose, while glucose is constantly consumed and must be replenished by a feed. The most appropriate feeding rate is ideally stoichiometric and adaptive in nature to balance the dynamically changing rate of glucose consumption. However, high errors in biomass and glucose estimation as well as limited knowledge of the true metabolic state challenge the control strategy. In this contribution, we take these errors into account and simulate the output with uncertainty trajectories in silico in order to control glucose concentration. Other than many control strategies, which require parameter estimation, our assumptions are founded on two pillars: (i) first principles and (ii) prior knowledge about the variability of fed‐batch CHO cell culture. The algorithm was exposed to an in‐silico Design of Experiments (DoE), in which variations of parameters were changed simultaneously, such as clone‐specific behavior, precision of equipment and desired control range used. The results demonstrate that our method achieved the target of holding the glucose concentration within an acceptable range. A robust and sufficient level of control could be demonstrated even with high errors for biomass or metabolic state estimation. In a time where blockbuster drugs are queuing up for time slots of their production, this transferable control strategy that is independent of tedious establishment runs may be a decisive advantage for rapid implementation during technology transfer and scale up and decrease in campaign change over time. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:317–336, 2017
NAS urges more research into cannabis, and cites Schedule I status as a barrier
Authors: Knopf Alison
Published: January 2017

It's no secret that marijuana legalization policies — both medical marijuana and recreational — have taken place with little to no research into the health effects of this drug. Last month, the National Academy of Sciences, Engineering, and Medicine (NAS) issued a report which called for more research into marijuana, or cannabis, as the plant is called.