bluuebunny/crossref_metadata_2025 huggingface dataset:
Catalytic Synthesis of 5‐Substituted Tetrazoles: Unexpected Reactions and Products
Authors: Wani Mohmmad Y. , Silva Manuela R. , Krishnakumar Balu , Kumar Santosh , Al‐Bogami Abdullah S. , Aqlan Faisal M. , Sobral Abilio J. F. N.
Published: April 2019

Tetrazoles are incredibly useful organic molecules with a wide range of applications from medicinal chemistry as carboxylic acid isosteres to high energy density materials in space research. In an effort to develop an easy protocol for the synthesis of tetrazoles from nitriles, we used nano‐Ag‐TiO2 as an efficient heterogeneous catalyst for the reaction of various nitriles and sodium azide to afford 5‐substituted tetrazoles in excellent yields. By this method, a wide variety of aryl nitriles underwent [3 + 2] cycloaddition to afford tetrazoles in excellent yields. Further reaction of tetrazoles with ethylchloroacetate resulted in the formation of expected products, except for a bis‐tetrazole, which underwent ring opening and subsequent reaction to afford an unusual product. The bis‐tetrazole also formed an unusual polymeric sodium complex in aq. NaOH solution. X‐ray crystallography revealed a distorted octahedral geometry for the complex, which forms a three‐dimensional network of chains interlinked by bis‐tetrazole moieties through a network of H‐bonds.
Improving safety through speaking up: An ethical and financial imperative
Authors: Novak Adam
Published: April 2019

Background

Fostering a culture that empowers staff to speak up when concerned about the quality or safety of patient care is both an ethically1 and economically2 responsible endeavor. The Michigan Health & Hospital Association (MHA) Keystone Center has implemented the Speak‐Up! Award program that acknowledges frontline health care staff for voicing their concerns and making care safer. The objective of this effort was to advance patient safety in Keystone Center member organizations through widespread, measurable culture improvement. After extensive data collection and analysis, there was a discernable improvement in culture survey results across a 2‐year period coinciding with the launch and sustainment of the award program. Furthermore, in an effort to demonstrate the power of speaking up among staff, the Keystone Center applied a cost‐savings framework to the types of harm avoided. Results from the cost‐savings analysis suggest that each instance of speaking up by staff saves patients, families, and health care organizations an average of more than $13,000.

Methods

Keystone Center Speak‐Up! Award nominations were submitted through an electronic form that collects open, closed, and Likert‐type question responses, producing a data array on type and severity of harm prevented, as well as the difficulty and magnitude of the decision to speak up. All data were then coded by harm type and subsequently applied to a tailored version of the cost‐savings estimation framework used in the Great Lakes Partnership for Patients Hospital Improvement and Innovation Network. Safety culture was measured through the use of a survey instrument called the Safety, Communication, Operational Reliability, and Engagement (SCORE) instrument.

Results

The Keystone Center Speak‐Up! Award program received 416 nominations across the 2‐year study period, of which 62% (n = 258) were coded as a specific harm type. Adverse drug events (n = 153), imaging errors (n = 42), and specimen errors (n = 27) were the most common harm types prevented by speaking up. After applying the cost‐savings framework to these data, it is estimated that for every instance of speaking up, approximately $13,000 in total expenses were avoided, which is in line with the findings from a report on the economic impact of medical errors sponsored by the Society of Actuaries.3 Furthermore, culture survey results improved by 6% between 2015 and 2017, coinciding with the Keystone Center Speak‐Up! Award program.

Conclusions

The Keystone Center Speak‐Up! Award has proven to be a valuable tool in recognizing staff awareness and willingness to raise concerns about quality and safety in health care. Data analysis from this program presents evidence that fostering a psychologically safe culture of speaking up yields fiscal and humanistic returns, both of which are crucial to sustainable, meaningful progress in safety and quality. However, further research is required to adequately gauge the degree to which safety culture improvement is proportional to cost savings.
Measurement of melatonin, indole‐dioxygenase, IL‐6, IL‐18, ferritin, CRP, and total homocysteine levels during herpes zoster
Authors: Khazan Marjan , Nasiri Soheila , Riahi Seyed M. , Robati Reza M. , Hedayati Mehdi
Published: April 2019

The risk of herpes zoster (HZ) increases with age and declining immune function. Increased oxidative stress and inflammatory conditions may cause a negative impact on the immune responses. The present study aimed to assess the levels of oxidative/inflammatory stress biomarkers in HZ patients compared with the controls. This case‐control study included 43 HZ patients and 47 age‐matched controls. Melatonin (MLT), Indole‐dioxygenase (IDO), Interleukin‐18 (IL‐18), Interleukin‐6 (IL‐6), ferritin, C‐reactive protein (hsCRP), and total homocysteine (tHcy) levels were measured and compared in both groups. The significant high levels of IDO, IL‐18, IL‐6, ferritin, hsCRP, and tHcy, as well as low levels of MLT were found in HZ patients compared with the controls (P < 0.001); these significant differences were also associated with rash and pain severity (P < 0.001). The final logistic regression model with the area under the curve (0.99; 95% confidence interval [CI], 0.98‐1.00) showed the association of HZ with decreased level of MLT (odds ratio [OR], 0.95; 95% CI, 0.92‐0.98; P = 0.007) and increased levels of tHcy (OR, 1.53; 95% CI, 1.06‐2.19; P = 0.02). The findings showed increased inflammation‐associated oxidative stress in HZ patients. Elevated tHcy levels and reduced MLT levels may be associated with the manifestation of HZ. More investigations are required to confirm the results.
Interval timing is disrupted in female 5xFAD mice: An indication of altered memory processes
Authors: Gür Ezgi , Fertan Emre , Alkins Kindree , Wong Aimée A. , Brown Richard E. , Balcı Fuat
Published: April 2019

Temporal information processing in the seconds‐to‐minutes range is disrupted in patients with Alzheimer's disease (AD). In this study, we investigated the timing behavior of the 5xFAD mouse model of AD in the peak interval (PI) procedure. Nine‐month‐old female mice were trained with sucrose solution reinforcement for their first response after a fixed‐interval (FI) and tested in the inter‐mixed non‐reinforced PI trials that lasted longer than FI. Timing performance indices were estimated from steady‐state timed anticipatory nose‐poking responses in the PI trials. We found that the time of maximal reward expectancy (peak time) of the 5xFAD mice was significantly earlier than that of the wild‐type (WT) controls with no differences in other indices of timing performance. These behavioral differences corroborate the findings of previous studies on the disruption of temporal associative memory abilities of 5xFAD mice and can be accounted for by the scalar timing theory based on altered long‐term memory consolidation of temporal information in the 5xFAD mice. This is the first study to directly show an interval timing phenotype in a genetic mouse model of AD.
Inappropriate implantable cardioverter defibrillator shocks due to atrial far‐field on the tip‐to‐ring channel for lead dislodgement
Authors: Ferretto Sonia , Brunzin Katia , Pettenuzzo Katiuscia , Nangah Suh René , Canali Cristina , Di Pede Francesco
Published: April 2019

We reported a case of inappropriate implantable cardioverter defibrillator shocks, due to atrial far‐field on the tip‐to‐ring channel of the fast electrical activity during atrial fibrillation, caused by lead dislocation in the right ventricle outflow tract. During these episodes the can‐to‐right ventricle coil signal correctly recorded the ventricular activity. The shock storm stopped when an antitachycardia pacing restored sinus rhythm.
Longitudinal Changes in the Total Knee Joint Moment After Anterior Cruciate Ligament Reconstruction Correlate With Cartilage Thickness Changes
Authors: Erhart‐Hledik JenniferC , Chu ConstanceR , Asay JessicaL , Favre Julien , Andriacchi ThomasP
Published: April 2019

This study investigated associations between changes in the total joint moment (TJM) at the knee and changes in cartilage thickness after anterior cruciate ligament reconstruction (ACLR). Seventeen subjects (five males; age: 29.6 ± 7.3 years) with unilateral ACLR underwent gait analysis and magnetic resonance imaging at baseline (2.2 ± 0.3 years post‐ACLR) and at long‐term follow‐up (7.7 ± 0.7 years post‐ACLR). Knee loading was assessed using the TJM, and differences in loading were analyzed using repeated measures analysis of variance. Pearson correlation coefficients assessed associations between changes in TJM and changes in (medial‐to‐lateral) M/L femoral cartilage thickness ratios in the ACLR limb. Bilaterally, there was no significant change in the magnitude of the TJM first peak (TJM1), however, there was a significant increase in the percent contribution of the knee flexion moment (KFM) (p < 0.001) and decrease in the percent contribution of the knee adduction moment (KAM) to TJM1 (p < 0.001). The change in the percent contributions of KFM and KAM to TJM1 were associated with changes in M/L femoral cartilage thickness in the ACLR limb. Specifically, subjects with smaller increases in KFM contribution (R = 0.521, p = 0.032) and smaller decreases in KAM contribution (R = −0.521, p = 0.032) had a reduction in the M/L ratio in the central femoral subregion over the follow‐up period, with similar trends in the external femoral subregion. The study results provide new insight into changes in the loading environment at the knee joint prospectively following ACL reconstruction and give evidence that there are modifiable gait metrics that are associated with cartilage changes after ACLR. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1546–1554, 2019.
Step Length Asymmetry and Its Associations With Mechanical Energy Exchange, Function, and Fatigue After Total Hip Replacement
Authors: Huang Chun‐Hao , Foucher Kharma C
Published: April 2019

Abnormalities in gait remain after total hip replacement (THR). The purpose of this study was to evaluate step length asymmetry and its links to other aspects of gait and physical function after THR and to investigate links with mechanical energy exchange. The rationale is that step length asymmetry may influence gait efficiency, which could adversely influence fatigue and physical function. We evaluated 18 participants (6 males and 12 females) 1–5 years post‐THR. Step length symmetry and mechanical energy exchange were assessed by instrumented gait analysis. Fatigue was assessed using a PROMIS Fatigue Short Form. We assessed physical function using a 6‐minute walk test (6MWT). We used a one sample T test to determine whether the symmetry index (SI) was significantly different from 0 and Pearson's correlations to explore associations among the variables. The step length SI was statistically significantly different from zero (p=0.01). A more symmetric step length was associated with better 6MWT (R=−0.57, p=0.03). Higher (better) mechanical energy exchange was associated with more fatigue (R=0.50, p=0.04). Mechanical energy exchange was not associated with step length SI or 6MWT. Better 6MWT was associated with less fatigue (R=−0.61, P=0.01). This suggests that the association between step length symmetry and function is not directly governed by its effect on the energy exchange. Additionally, after a relatively long period of postsurgery, participants may have adapted their gait by increasing mechanical energy exchange to minimize fatigue. Statement of Clinical Significance: A gait retraining intervention targeting step length symmetry could improve function without adversely affecting walking energetics in THR patients. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1563–1570, 2019.
OCY454 Osteocytes as an in Vitro Cell Model for Bone Remodeling Under Mechanical Loading
Authors: Xu Liangcheng Henry , Shao Han , Ma Yu‐Heng V. , You Lidan
Published: April 2019

Osteocytes’ mechano‐regulation of bone formation and resorption is key to maintaining appropriate bone health. Although extensive in vitro studies have explored osteocyte mechanobiology using the well‐established MLO‐Y4 cell model, the low amount of sclerostin secreted by this cell line renders it inadequate for studying cross‐talk between osteocytes and osteoblasts under mechanical loading. Here, we investigated the potential of the sclerostin‐expressing OCY454 osteocyte cell model in fulfilling this role. Fully differentiated OCY454 cells were tested for mechano‐sensitivity by measuring changes in protein secretion, total adenosine triphosphate (ATP) content, and intracellular calcium in response to oscillatory fluid flow. Increases in sclerostin expression and total ATP content were observed. However, very low levels of receptor activator of the nuclear factor κ‐B ligand were detected, and there was a great inconsistency in calcium response. Conditioned medium (CM) from OCY454 cells was then used to culture osteoblast and osteoclast precursors. Osteoblast activity was quantified with alkaline phosphatase (ALP) and Alizarin Red S stain, while osteoclast differentiation was quantified with tartrate‐resistant acid phosphatase (TRAP) staining. We demonstrated that mechanically stimulated OCY454 cells released soluble factors that increased osteoblasts’ ALP activity (p < 0.05) and calcium deposition (p < 0.05). There was also a significant decrease of large‐sized TRAP‐positive osteoclasts when osteoclast precursors were treated with CM from flow‐stimulated OCY454 cells (p < 0.05). Results from this study suggest that OCY454 cells respond to mechanical loading with the release of key factors such as sclerostin to regulate downstream bone cells, thus demonstrating its potential as a novel cell model for in vitro osteocyte mechanobiology studies. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1681–1689, 2019
Changes in Nerve Growth Factor Expression and Macrophage Phenotype Following Intervertebral Disc Injury in Mice
Authors: Nakawaki Mitsufumi , Uchida Kentaro , Miyagi Masayuki , Inoue Gen , Kawakubo Ayumu , Satoh Masashi , Takaso Masashi
Published: April 2019

Nerve growth factor (NGF) is increased in intervertebral discs (IVDs) after disc injury and anti‐NGF therapy improves low back pain in humans. Furthermore, M1 and M2 macrophage subtypes play a role in degenerative IVD injury. We examined M1 and M2 macrophage markers and NGF and cytokine expression in IVD‐derived cells from control and IVD‐injured mice for 28 days following injury. Ngf messenger RNA (mRNA) expression was increased 1 day after injury in injured compared with control mice, and persisted for up to 28 days. Flow cytometric analysis demonstrated that the proportion of F4/80+ CD11b+ cells was significantly increased from 1 day after injury for up to 28 days in injured compared to control mice. mRNA expression of M1 macrophage markers Tnfa, Il1b, and Nos2 was significantly increased 1 day after injury in injured compared to control mice, before gradually decreasing. At 28 days, no significant difference was observed in M1 markers. The M2a marker, Ym1, was significantly increased 1 day after injury in injured compared with control mice, while M2a and M2c markers Tgfb and Cd206 were significantly increased 7, 14, and 28 days after injury. Tumor necrosis factor α (TNF‐α) and transforming growth factor β (TGF‐β) stimulated Ngf mRNA and NGF protein expression in IVD cells. Our results suggest that TNF‐α and TGF‐β may stimulate NGF production under inflammatory and non‐inflammatory conditions following IVD injury. As TNF‐α and TGF‐β are produced by M1 and M2 macrophages, further investigations are needed to reveal the role of macrophages in NGF expression following IVD injury. Our results may aid in developing treatments for IVD‐related LBP pathology. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1798–1804, 2019
CCL25‐Supplemented Hyaluronic Acid Attenuates Cartilage Degeneration in a Guinea Pig Model of Knee Osteoarthritis
Authors: Ringe Jochen , Hemmati‐Sadeghi Shabnam , Fröhlich Kristin , Engels Andreas , Reiter Katja , Dehne Tilo , Sittinger Michael
Published: April 2019

There is evidence that the application of mesenchymal stromal cells (MSCs) counteracts osteoarthritis (OA) progression. However, the prospect of extracting and expanding these cells might be limited. The aim of this study was to investigate whether hyaluronic acid (HA) supplemented with MSC‐recruiting chemokine C‐C motif ligand 25 (CCL25) can influence the natural course of spontaneous OA in the guinea pig. CCL25 concentration in synovial fluid (SF) was quantified with enzyme‐linked immunosorbent assay. Boyden chamber cell migration assay was used to test CCL25‐mediated migration of guinea pig MSC. Forty‐nine 11‐month‐old male guinea pigs were divided into seven groups. The main treatments consisted of five intra‐articular injections of HA in pure form and in combination with three doses of CCL25 (63, 693, and 6,993 pg) given at a weekly interval. The severity of cartilage damage was assessed by using a modified Mankin score. The measured average physiological concentration of CCL25 in SF of animals is 85 ± 39 pg/ml. MSC showed a 3.2‐fold increase in cell migration at 1,000 nM CCL25 in vitro demonstrating the biological migratory activity of CCL25 on these cells. In vivo, treatment with HA alone did not reduce OA progression. Similarly, OA scores were not found significantly reduced after treatment with 63 pg CCL25 + HA. However, when compared to pure HA, treatment with 693 pg CCL25 + HA and 6,993 pg CCL25 + HA significantly reduced the OA score from 10.1 to 7.4 (−28%) and 8.4 (−20%), respectively. These data suggest that intra‐articular injections of HA supplemented with CCL25 attenuates OA. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1723–1729, 2019
Identification of wheat kernels by fusion of RGB, SWIR, and VNIR samples
Authors: Özkan Kemal , Işık Şahin , Yavuz Büşra Topsakal
Published: April 2019

Background

The sustainable management of agricultural resources requires the integration of cutting‐edge science with the observation and identification of crops. This assists experts to make correct decisions. The aim of this study is to assess the robustness of a commonly used deep learning tool, VGG16, in improving the categorization of wheat kernels. Two fusion methodologies were considered simultaneously. We performed experiments on visible light (RGB), short wave infrared (SWIR), and visible‐near infrared (VNIR) datasets, including 40 classes, with 200 samples in each class, giving 8000 samples in total.

Results

After making simulations with 6400 training and 1600 testing samples, we achieved excellent performance scores, with 98.19% and 100% accuracy rates, respectively.

Conclusion

The wheat identification system developed here serves as an effective identification framework and supports the view that deep learning tools can adequately discriminate between different types of wheat kernels. The proposed automated system would be useful for improving economic growth and in reducing the labor force, leading to greater efficiency and higher productivity in the wheat industry. © 2019 Society of Chemical Industry
Time effect on structural and functional properties of whey protein isolate‐gum acacia conjugates prepared via Maillard reaction
Authors: Chen Weijun , Lv Ruiling , Wang Wenjun , Ma Xiaobin , Muhammad Aliyu Idris , Guo Mingming , Ye Xingqian , Liu Donghong
Published: April 2019

BACKGROUND

The functional properties of whey protein isolate (WPI) are sensitive to pH, ionic strength, and temperature. This prevents its application in various food systems and processing technologies. The conjugation of proteins with polysaccharides via the Maillard reaction is an efficient method to improve the functionality of proteins. The purpose of this work was to conjugate gum acacia (GA) with WPI via the dry‐heating Maillard reaction and to investigate the effect of reaction time on the physicochemical and functional properties of WPI‐GA conjugates.

RESULTS

Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and high‐performance size exclusion chromatography confirmed the formation of higher molecular weight conjugates. The degrees of glycation for WPI‐GA conjugates incubated for 1, 3, 5, and 7 days were 28.14%, 44.98%, 49.50%, and 51.20%, respectively. The glycation reaction reduced the surface hydrophobicity and fluorescence intensity of WPI significantly (P < 0.05). Functional properties of the conjugates, such as solubility, stability against heat‐induced insolubility, and emulsion properties were all superior to the control WPI. However, a reaction time longer than a day resulted in a high degree of browning and decreased the functionality of the conjugate significantly (P < 0.05).

CONCLUSION

The results indicated that conjugation of WPI with GA can be a promising way to enhance its functional properties. However, the reaction time suitable for producing conjugates with superior functional properties was not necessarily the highest glycation degree that could be reached. © 2019 Society of Chemical Industry
Effectiveness of five flavored Tunisian olive oils on Anisakis larvae type 1: application of cinnamon and rosemary oil in industrial anchovy marinating process
Authors: Trabelsi Najla , Nalbone Luca , Marotta Stefania M , Taamali Amani , Abaza Leila , Giarratana Filippo
Published: April 2019

BACKGROUND

Anisakidosis is caused by the ingestion of raw or undercooked fish or cephalopods containing viable Anisakis larvae. Several natural extracts, oils, essential oils, and their compounds have been tested against Anisakis. In this study the effectiveness of Tunisian olive oil with different spices or plants (cardamom, cinnamon, ginger, laurel, and rosemary) was tested against Anisakis larvae type 1.

RESULTS

For the in vitro test, larvae were submerged separately in the oils mentioned above and observed to check viability. Cinnamon oil was the most effective against parasites with lethal time (LT) scores being LT50 = 1.5 days and LT100 = 3 days, followed by rosemary. Laurel, cardamom, and ginger oils were less effective. For the ex vivo experiment, cinnamon, and rosemary oils were tested in anchovy fillets, previously artificially parasitized. Cinnamon was the most effective against parasites (dead after 4 days) as compared to rosemary (7 days).

CONCLUSION

The use of cinnamon and rosemary‐flavored olive oil in the industrial marinating process can be considered as an efficient alternative to the freezing process required by European Regulation EC No 853/2004 to devitalize Anisakis. © 2019 Society of Chemical Industry
Effect of in vitro glyphosate on Fusarium spp. growth and disease severity in maize
Authors: Carranza Cecilia Soledad , Aluffi Melisa Eglé , Benito Nicolás , Magnoli Karen , Barberis Carla Lorena , Magnoli Carina Elizabeth
Published: April 2019

BACKGROUND

Glyphosate (GP) is one of the main pesticides used for maize production. Fusarium sp. is a fungal genus with several phytopathogenic species and toxigenic features. In this study, the culturable soil mycota was evaluated using the surface‐spray method. The effect of GP on the growth parameters (growth rate and lag phase) of Fusarium spp. was also tested on solid media conditioned with different water activities. Finally, the GP effect on disease severity caused by Fusarium sp. in maize seedlings was studied.

RESULTS

The results showed that Fusarium species are frequently isolated from GP‐exposed soils. The GP concentrations tested had a significant effect on F. graminearum, F. verticillioides and F. oxysporum growth parameters on solid media. The pathogenicity tests showed that the disease severity of the maize seedlings significantly increased with increasing GP concentrations.

CONCLUSIONS

This study showed that Fusarium species are frequently isolated from pesticide‐exposed soils and the GP concentrations tested had a significant effect both on growth parameters and disease severity in maize. This study provides an approach to the effect of GP on Fusarium sp. growth and pathogenicity that reinforces the importance of evaluating all the factors that could affect feed and food production. © 2019 Society of Chemical Industry
Laser‐addressed full‐color photo‐quality rewritable sheets based on thermochromic systems with leuco dyes
Authors: Kaino Yuriko , Kurihara Kenichi , Shuto Aya , Mizuno Hiroshi , Asaoka Satoko , Ishida Takehisa , Takagi Kenji , Takahashi Isao , Amago Hirohisa , Takeuchi Taichi , Tejima Asuka , Watanabe Maho , Oishi Yuki , Kamei Takahiro , Nomoto Kazumasa
Published: April 2019

We have developed a laser‐addressed full‐color photographic quality rewritable sheet. The sheet was composed of a vertically stacked Cyan/Magenta/Yellow‐thermochromic system with a mixture of leuco dyes, developers and photothermal conversion agents in a polymer matrix. The sheet was simply manufactured by roll‐to‐roll (R2R) processes. Writing and erasing were performed by scan of near‐infrared laser light. It achieved full‐color photographic quality images with a wide color gamut with 70% coverage of the Specifications for Web Offset Publications (SWOP) standards and a high resolution of 426 ppi. Clear rewritability has also been confirmed. Non‐contact laser writing has other advantages in that it can create an image under a protection film, and it has form factor flexibility. We have developed a reliability model for high‐temperature storage and a light fastness test. This model showed a good agreement with experimental data, and the lifetime of an image was estimated to be over 8 years under ambient conditions. This technology will create applications for on‐demand rewritable image design while saving power and reducing the use of paper, which will eventually contribute to a sustainable society.
Multivalent Interactions of Polyamide Based Sequence‐Controlled Glycomacromolecules with Concanavalin A
Authors: Camaleño de la Calle Alberto , Gerke Christoph , Chang Xi Jeffrey , Grafmüller Andrea , Hartmann Laura , Schmidt Stephan
Published: April 2019

Binding of mannose presenting macromolecules to the protein receptor concanavalin A (ConA) is investigated by means of single‐molecule atomic force spectroscopy (SMFS) in combination with dynamic light scattering and molecular modeling. Oligomeric (Mw ≈ 1.5–2.5 kDa) and polymeric (Mw ≈ 22–30 kDa) glycomacromolecules with controlled number and positioning of mannose units along the scaffolds accessible by combining solid phase synthesis and thiol–ene coupling are used as model systems to assess the molecular mechanisms that contribute to multivalent ConA–mannose complexes. SMFS measurements show increasing dissociation force from monovalent (≈57 pN) to pentavalent oligomers (≈75 pN) suggesting subsite binding to ConA. Polymeric glycomacromolecules with larger hydrodynamic diameters compared to the binding site spacing of ConA exhibit larger dissociation forces (≈80 pN), indicating simultaneous dissociation from multiple ConA binding sites. Nevertheless, although simultaneous dissociation of multiple ligands could be expected for such multivalent systems, predominantly single dissociation events are observed. This is rationalized by strong coiling of the macromolecules' polyamide backbone due to intramolecular hydrogen bonding hindering unfolding of the coil. Therefore, this study shows that the design of glycopolymers for multivalent receptor binding and clustering must consider 3D structure and intramolecular interactions of the scaffold.
Incorporation of silica nanocontainers and its impact on a waterborne polyurethane coating
Authors: Loison Pierre , Debout Vincent , Groult Hugo , Creus Juan , Touzain Sébastien
Published: April 2019

In the present work, we describe the development and characterization of a versatile smart coating containing an encapsulated inhibitor. This includes the synthesis and characterization of hollow spherical nanocapsules with diameters ranging from 180 to 200 nm. These particles are able to release their payload when exposed to an alkaline environment, what could be induced by corrosion‐linked processes. A corrosion inhibitor, namely 2‐mercaptobenzothiazole has been encapsulated, after what the capsules were incorporated in a polyurethane (PU) matrix; optimization of the process led to homogeneous coatings with a good dispersion of silica assessed by micro‐fluorescence spectroscopy. Electrochemical impedance spectroscopy highlighted a negative effect of the capsules’ addition to the PU network, affecting the coating's barrier properties. However, the release of the inhibitor upon water ingress in the coating and potential short‐term protection was seen. Nevertheless, tests conducted on coatings with artificial defects could not lead to a reduction of the corrosion rate, probably due to the large size of the defects.
Using Synergistic Multiple Dynamic Bonds to Construct Polymers with Engineered Properties
Authors: Jiang Zhen , Bhaskaran Ayana , Aitken Heather M. , Shackleford India C. G. , Connal Luke A.
Published: April 2019

Dynamic bonds have achieved significant attention for their ability to impart fascinating properties to polymeric materials, such as high mechanical strength, self‐healing, shape memory, 3D printability, and conductivity. Incorporating multiple dynamic bonds into polymer systems affords an attractive and efficient approach to endow multiple functionalities. This mini‐review focuses on the use of complementary dynamic interactions to control the properties of soft materials. Owing to the diversity in dynamic chemistries that can be explored, the scope of this article is restricted to polymers and does not include colloids, amphiphiles, liquid crystals, or biological soft matter.
lptG contributes to changes in membrane permeability and the emergence of multidrug hypersusceptibility in a cystic fibrosis isolate of Pseudomonas aeruginosa
Authors: Harrison Lucas B. , Fowler Randal C. , Abdalhamid Baha , Selmecki Anna , Hanson Nancy D.
Published: April 2019

Purpose

In the lungs of cystic fibrosis patients, Pseudomonas aeruginosa is exposed to a myriad of antibiotics leading to alterations in antibiotic susceptibility. This study identifies mutations resulting in hypersusceptibility in isogenic mutants of a P. aeruginosa clinical isolate, PA34.

Methods

PA34 was exposed to subinhibitory concentrations of doripenem or meropenem during growth to mid‐log phase. Antibiotic susceptibility of surviving colonies was determined by agar dilution. Two carbapenem‐resistant colonies hypersusceptible to non‐carbapenem antibiotics were selected for further analysis. Antibiotic resistance gene expression was evaluated by RT‐rtPCR and OprD production by SDS‐PAGE. PA34 and isogenic mutants were evaluated with whole genome sequencing. Sequence variants were confirmed by Sanger sequencing, and cognate genes in eight carbapenem‐resistant clinical isolates hypersusceptible to non‐carbapenem antibiotics were sequenced. Lipopolysaccharide preparations of PA34 and hypersusceptible mutants were evaluated with ProQ‐Emerald stain.

Results

Isogenic mutants showed 4‐ to 8‐fold MIC increase for imipenem, meropenem, and doripenem. However, they were hypersusceptible (≥4‐fold MIC decrease) to aminoglycosides, fluoroquinolones, and non‐carbapenem β‐lactams. Expression of ampC or mex‐opr efflux pumps was unchanged, but OprD production was decreased. Mutations causing Q86H AlgU and G77C LptG amino acid substitutions and nonsense mutations within OprD were observed in both mutants. Lipopolysaccharide modifications were observed between isogenic mutants and PA34. Non‐synonymous mutations in LptF or LptG were observed in 6/8 hypersusceptible clinical isolates resistant to carbapenem antibiotics.

Conclusion

Evaluation of hypersusceptible mutants identified the association between lptG and a hypersusceptible phenotype. Modifications in lipopolysaccharide profiles suggests LptG modification interferes with lipopolysaccharide transport and contributes to hypersusceptibility.
Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives
Authors: Sun Xin , Yan Peiyi , Zou Chang , Wong Yin‐Kwan , Shu Yuhan , Lee Yew Mun , Zhang Chongjing , Yang Nai‐Di , Wang Jigang , Zhang Jianbin
Published: April 2019

Artemisinin and its derivatives, with their outstanding clinical efficacy and safety, represent the most effective and impactful antimalarial drugs. Apart from its antimalarial effect, artemisinin has also been shown to exhibit selective anticancer properties against multiple cancer types both in vitro and in vivo. Specifically, our previous studies highlighted the therapeutic effects of artemisinin on autophagy regulation. Autophagy is a well‐conserved degradative process that recycles cytoplasmic contents and organelles in lysosomes to maintain cellular homeostasis. The deregulation of autophagy is often observed in cancer cells, where it contributes to tumor adaptation to nutrient‐deficient tumor microenvironments. This review discusses recent advances in the anticancer properties of artemisinin and its derivatives via their regulation of autophagy, mitophagy, and ferritinophagy. In particular, we will discuss the mechanisms of artemisinin activation in cancer and novel findings regarding the role of artemisinin in regulating autophagy, which involves changes in multiple signaling pathways. More importantly, with increasing failure rates and the high cost of the development of novel anticancer drugs, the strategy of repurposing traditional therapeutic Chinese medicinal agents such as artemisinin to treat cancer provides a more attractive alternative. We believe that the topics covered here will be important in demonstrating the potential of artemisinin and its derivatives as safe and potent anticancer agents.
Prediction of Protein Metal Binding Sites Using Deep Neural Networks
Authors: Haberal İsmail , Oğul Hasan
Published: April 2019

Metals have crucial roles for many physiological, pathological and diagnostic processes. Metal binding proteins or metalloproteins are important for metabolism functions. The proteins that reach the three‐dimensional structure by folding show which vital function is fulfilled. The prediction of metal‐binding in proteins will be considered as a step‐in function assignment for new proteins, which helps to obtain functional proteins in genomic studies, is critical to protein function annotation and drug discovery. Computational predictions made by using machine learning methods from the data obtained from amino acid sequences are widely used in the protein metal‐binding and various bioinformatics fields. In this work, we present three different deep learning architectures for prediction of metal‐binding of Histidines (HIS) and Cysteines (CYS) amino acids. These architectures are as follows: 2D Convolutional Neural Network, Long‐Short Term Memory and Recurrent Neural Network. Their comparison is carried out on the three different sets of attributes derived from a public dataset of protein sequences. These three sets of features extracted from the protein sequence were obtained using the PAM scoring matrix, protein composition server, and binary representation methods. The results show that a better performance for prediction of protein metal‐ binding sites is obtained through Convolutional Neural Network architecture.
Application of failure mode and effects analysis to optimization of linac quality controls protocol
Authors: Bonfantini Francesca , Giandini Tommaso , Meroni Silvia , Cavallo Anna , Stucchi Claudio , Carrara Mauro , Mongioj Valeria , Veronese Ivan , Pignoli Emanuele
Published: April 2019

Purpose

To apply Failure Mode and Effects Analysis (FMEA) to optimize linac quality control (QC) protocol in order to ensure patient safety and treatment quality, taking maximum advantage of the available resources.

Material and methods

Each parameter tested by the QC was considered as a potential failure mode (FM). For each FM, likelihood of occurrence (O), severity of effect (S), and lack of detectability (D) were evaluated and corresponding Risk Priority Number (RPN) was calculated from the product of three indexes. The scores were assigned using two methods: (a) A survey submitted to the medical physicists; (b) A semi‐quantitative analysis (SQA) performed through: simulation of FMs in the treatment planning system; studies reported in literature; results obtained by the QC data analysis. A weighted RPN for all FMs was calculated taking into account both the methods. For each linac, the tests were then sorted by their frequency and the RPN value.

Results

A high variability was found in the scores of the survey, although in many it was reduced in RPN values, highlighting the more relevant tests as on beam output and imaging system. Integrating these results with those obtained by SQA, the RPN‐based ranking of tests has been provided considering the specific use of the accelerator: for example, more accurate tests on dose modulation and multileaf collimator speed were required in linacs where intensity‐modulated treatment is performed, while, more specific tests on couch and jaw position indicators were necessary where treatments with multiple isocenters and/or junctions between adjacent fields were often delivered.

Conclusions

Failure Mode and Effects Analysis is a useful tool to prioritize the linac QCs, taking into account the specific equipment and clinical practice. The integration of SQA and survey results reduces subjectivity of the FMEA scoring and allows to optimize linac QCs without “losing” the expertise and experience of medical physicists and clinical staff.
Beyond VNFM: Filling the gaps of the ETSI VNF manager to fully support VNF life cycle operations
Authors: Venâncio Giovanni , Garcia Vinícius Fulber , da Cruz Marcuzzo Leonardo , Tavares Thales Nicolai , Franco Muriel Figueredo , Bondan Lucas , Schaeffer‐Filho Alberto Egon , Paula dos Santos Carlos Raniery , Granville Lisandro Zambenedetti , P. Duarte Elias
Published: April 2019

One of the main challenges to use network functions virtualization (NFV) is to properly manage the life cycle of the virtualized network functions (VNFs). Current solutions based on the ETSI standard NFV architectural framework are complex and require the knowledge of a myriad of details of the underlying infrastructure. This work proposes a VNF manager (VNFM) specification that supports different platforms and VNF utilization scenarios. The proposed VNFM specification defines a set of APIs, modules, and components, for both the end user and the back‐end that provide the fundamental set of operations required to fully manage the VNF life cycle. Our primary goal is to simplify the operations, in particular reducing the need for the network operator to know the details of the virtualized infrastructure. Note that the proposed solution fills a gap and complements the ETSI VNFM module. A prototype was implemented, and experimental results show the effectiveness and low overhead of the proposed solution.
Distributed model predictive control for energy management in a network of microgrids using the dual decomposition method
Authors: Razzanelli Matteo , Crisostomi Emanuele , Pallottino Lucia , Pannocchia Gabriele
Published: April 2019

This paper deals with the application of model predictive control (MPC) to optimize power flows in a network of interconnected microgrids (MGs). More specifically, a distributed MPC (DMPC) approach is used to compute for each MG how much active power should be exchanged with other MGs and with the outer power grid. Due to the presence of coupled variables, the DMPC approach must be used in a suitable way to guarantee the feasibility of the consensus procedure among the MGs. For this purpose, we adopt a tailored dual decomposition method that allows us to reach a feasible solution while guaranteeing the privacy of single MGs (ie, without having to share private information like the amount of generated energy or locally consumed energy). Simulation results demonstrate the features of the proposed cooperative control strategy and the obtained benefits with respect to other classical centralized control methods.
Optimal control measures for a susceptible‐carrier‐infectious‐recovered‐susceptible malware propagation model
Authors: Gonçalves João N.C. , Rodrigues Helena Sofia , Monteiro M. Teresa T.
Published: April 2019

Purposing to lessen malware propagation, this paper proposes optimal control measures for a susceptible‐carrier‐infectious‐recovered‐susceptible (SCIRS) epidemiological model formed by a system of ordinary differential equations. By taking advantage of real‐world data related to the number of reported cybercrimes in Japan from 2012 to 2017, an optimal control problem is formulated to minimize the number of infected devices in a cost‐effective way. The existence and uniqueness of the results related to the optimality system are proved. Overall, numerical simulations show the usefulness of the proposed control strategies in reducing the spread of malware infections.
Structure‐Activity Relationship of NF023 Derivatives Binding to XIAP‐BIR1
Authors: Sorrentino Luca , Cossu Federica , Milani Mario , Malkoc Bilge , Huang Wen‐Chieh , Tsay Shwu‐Chen , Ru Hwu Jih , Mastrangelo Eloise
Published: April 2019

Inhibitors of Apoptosis Proteins (IAPs) are conserved E3‐ligases that ubiquitylate substrates to prevent apoptosis and activate the NF‐kB survival pathway, often deregulated in cancer. IAPs‐mediated regulation of NF‐kB signaling is based on the formation of protein complexes by their type‐I BIR domains. The XIAP‐BIR1 domain dimerizes to bind two TAB1 monomers, leading to downstream NF‐kB activation. Thus, impairment of XIAP‐BIR1 dimerization could represent a novel strategy to hamper cell survival in cancer. To this aim, we previously reported NF023 as a potential inhibitor of XIAP‐BIR1 dimerization. Here we present a thorough analysis of NF023 binding to XIAP‐BIR1 through biochemical, biophysical and structural data. The results obtained indicate that XIAP‐BIR1 dimerization interface is involved in NF023 binding, and that NF023 overall symmetry and the chemical features of its central moiety are essential for an efficient interaction with the protein. Such strategy provides original hints for the development of novel BIR1‐specific compounds as pro‐apoptotic agents.
Who Benefits from Accountability‐Driven School Closure? Evidence from New York City
Authors: Bifulco Robert , Schwegman David J.
Published: April 2019

We estimate the effects of accountability‐driven school closure in New York City on students who attended middle schools that were closed at the time of closure and students who would have likely attended a closed middle school had it remained open. We find that students who would have entered the closed school had it not closed attended schools that perform better on standardized exams and have higher value‐added measures than did the closed schools. While we find that closure did not have any measurable effect on the average student in this group, we do find that high‐performing students in this group attended higher‐performing schools and experienced economically‐meaningful and statistically‐significant improvements in their 6th‐, 7th‐, and 8th‐grade math test scores. We find that these benefits persisted for several cohorts after closure. We also find that closure adversely affected students, low‐performing students in particular, who were attending schools that closed. For policymakers, our results highlight a key trade‐off of closing a low‐performing school: future cohorts of relatively high‐performing students may benefit from closure while low‐performing students in schools designated for closure are adversely affected.
Preparation and mechanism of polyurethane prepolymer and boric acid co‐modified phenolic foam composite: Mechanical properties, thermal stability, and flame retardant properties
Authors: Xu Wenzong , Chen Rui , Xu Jiaying , Wang Guisong , Cheng Chuanming , Yan Hongyi
Published: April 2019

In this work, a new kind of co‐modified phenolic foam was synthesized with polyurethane prepolymer (PUP) and H3BO3 by a simple preparation method. Firstly, in order to determine the optimal amount of PUP, the effects of different PUP additions on the mechanical properties, foam microstructure, and pulverization rate of phenolic foam were investigated. Then H3BO3 was added to toughened phenolic foam, in order to reduce its fire hazard. The results showed that the mechanical properties of the PFPUP8 phenolic foam composite were the best when the PUP content was 8 wt%. It had a small and regular cell structure, and its pulverization ratio was reduced by 80% compared with that of pristine phenolic foam. Meanwhile, the flame retardant properties of PFPUP8 were improved in different degrees with an increase in the amount of H3BO3. Particularly, when the addition of H3BO3 was 10 wt%, the peak heat release rate, the total heat release, and the total smoke release values of PFPUP10B were decreased by 35.4%, 42.4%, and 45.2%, respectively, compared with those of PFPUP8. The value of the limit oxygen index was increased by 33.1%. Besides, the addition of H3BO3 had no adverse effect on the mechanical properties and pulverization ratio of PFPUP8. In addition, the specific mechanisms of toughening, flame retardant, and smoke suppression are also discussed in this paper on the basis of an investigation into the thermal properties of the toughened flame retardant foam composites by thermogravimetric analysis in N2 atmosphere.
The influences of α/β compound nucleating agents based on octamethylenedicarboxylic dibenzoylhydrazide on crystallization and melting behavior of isotactic polypropylene
Authors: Zhang Yue‐Fei , Zhou Pei‐Zhang , Li Yan
Published: April 2019

The influences of α/β compound nucleating agents based on octamethylenedicarboxylic dibenzoylhydrazide on crystallization and melting behavior of isotactic polypropylene (iPP) were analyzed. It is found that the crystallization temperatures of nucleated iPP were increased by above 11.0°C and the relative contents of β‐crystals (Kβ) in iPP reached above 0.40 after addition of compound nucleating agents. The Kβ values depend on cooling rate, crystallization temperature in isothermal crystallization, and the difference between the crystallization temperatures of iPP nucleated by two individual nucleating agents. The nonisothermal crystallization kinetics were studied by Caze method and Mo method, respectively. The effective activation energy was calculated by the Friedman's method. The results illustrate that the half crystallization time was shortened and the crystallization rate was increased obviously after addition of nucleating agents, and the effective activation energy was increased with the relative crystallinity.