bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term changes in vocal function after supracricoid partial laryngectomy with cricohyoidoepiglottopexy for laryngeal cancer
Authors: Miyamaru Satoru , Minoda Ryosei , Kodama Narihiro
Published: December 2018

Background

The purpose of this study was to assess changes in vocal function over time following supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCL‐CHEP).

Methods

A total of 17 patients who underwent SCL‐CHEP for laryngeal squamous cell carcinoma between 2007 and 2015 were reviewed. We examined maximum phonation time (MPT), mean airflow rate (MFR), voice intensity, the grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, Voice Handicap Index‐10 (VHI‐10), and voice‐related quality of life (V‐RQOL) scores. To assess changes over time in these parameters, we set 3 evaluation periods after surgery: within the first 12 months (term A), 13‐36 months (term B), and after 37 months (term C).

Results

The mean MPT, MFR, G and B GRBAS subscale, VHI‐10, and V‐RQOL scores improved significantly over time postoperatively.

Conclusion

Multiple vocal function parameters improved significantly with time due to self‐adaptation to a newly created glottis after surgery.
Pathway based prognostic gene expression profile of buccal and gingivo‐buccal oral squamous cell carcinoma in smokeless tobacco chewers
Authors: Prasad Kavitha , Rao Roopa , Augustine Dominic , Sowmya Samudrala Venkatesiah , Haragannavar Vanishri , Sagar Parimala , Sreedhar Prathibha
Published: December 2018

Background

The objective was to study comprehensive mRNA expression profiles of buccal mucosa oral squamous cell carcinoma (OSCC‐BM) and gingivo‐buccal OSCC (OSCC‐GB) in smokeless tobacco chewers to understand the biological behavior of OSCC at these specific sites and identify diagnostic and prognostic markers.

Methods

High throughput RNA sequencing transcriptome of fresh buccal mucosa (4 samples) and gingivo‐buccal (4 samples) OSCC with normal oral mucosa (3 samples) was performed on Illumina NextSeq500 paired end sequencing with 75x2bp.

Results

In the comparison between OSCC and normal, there were 402 differentially expressed genes (DEGs); between OSCC‐BM and normal, there were 467 DEGs; and between OSCC‐GB and normal oral tissue, there were 608 DEGs. Pathway‐based analysis of gene expression was done. The inflammation mediated by chemokine and cytokine signaling pathway had the maximum gene hits.

Conclusions

FZD2 and its interactions with the cadherins have a role in invasion and metastasis. immunosurveillance is evident in OSCC‐GB with the downregulation of CADM1.
Comparative assessment of the intrinsic sensitivity of crop species and wild plant species to plant protection products and their active substances and potential implications for the risk assessment: A literature review
Authors: Christl Heino , Morilla Jaime , Hoen Thierry , Zumkier Ulrich
Published: December 2018

A comprehensive critical review was undertaken aiming to compare the intrinsic sensitivity of terrestrial plant species (crop species and noncrop wild species) with published literature and unpublished proprietary data generated for the registration of plant protection products (PPPs), and a database was compiled. Data were assessed to answer the question whether crops differ from noncrop plants in their intrinsic sensitivity to PPPs. Endpoints were assessed considering further potentially relevant parameters by means of different methods, including a quotient approach, in which overall crop endpoints were divided by matching wild species endpoints. Quotients above 1 indicated that wild species were more sensitive than crops, quotients below 1 the opposite. Further methods included a multiple regression analysis and different approaches to assess the statistical power. The overall finding was that there were no consistent differences in sensitivity between wild plant species and crop species, based on ER50, ER25, and ER10 vegetative endpoints (the largest fraction of data). This was also true when censored endpoints, seedling emergence data, and other measured variables such as shoot height were included. Statistically significant differences occurred in both directions and were balanced, that is, there was no clear trend for either crops or noncrop species to be more sensitive than the other. On the basis of multivariate regression analysis, crops were found to be significantly more sensitive than wild plant species, albeit by a small margin (factor ≈1.4). Minimum detectable difference (MDD) analysis and multivariate regression analysis of modified datasets indicated that when using a data set of this size and heterogeneity, any dissimilarity between crop and wild species was detectable if exceeding a factor of 1.4 in either direction. For the taxonomic groups assessed here (i.e., with data), no intrinsic difference in sensitivity to PPPs between crop species and wild plant species was found. Integr Environ Assess Manag 2019;15:176–189. © 2018 SETAC
Effects of co‐exposure of lipopolysaccharide and β‐glucan (Zymosan A) in exacerbating murine allergic asthma associated with Asian sand dust
Authors: Sadakane Kaori , Ichinose Takamichi , Nishikawa Masataka
Published: December 2018

During the 2000s, Asian sand dust (ASD) was implicated in the increasing prevalence of respiratory disorders, including asthma. We previously demonstrated that a fungus from ASD aerosol exacerbated ovalbumin (OVA)‐induced airways inflammation. Exposure to heat‐inactivated ASD (H‐ASD) and either Zymosan A (ZymA, containing β‐glucan) or lipopolysaccharide (LPS) exacerbated allergic airways inflammation in a mouse model, but the effects of co‐exposure of LPS and β‐glucan are unclear. We investigated the effects of co‐exposure of LPS and ZymA in OVA‐induced allergic airways inflammation with ASD using BALB/c mice. Exposure to OVA + LPS enhanced the recruitment of inflammatory cells to the lungs, particularly neutrophils; exposure to OVA + LPS + H‐ASD potentiated this effect. Exposure to OVA + ZymA + H‐ASD stimulated the recruitment of inflammatory cells to the lungs, particularly eosinophils, and serum levels of OVA‐specific IgE and IgG1 antibodies, whereas exposure to OVA + ZymA did not affect most indicators of lung inflammation. Although exposure to OVA + LPS + ZymA + H‐ASD affected a few allergic parameters additively or synergistically, most allergic parameters in this group indicated the same level of exposure to OVA + LPS + H‐ASD or OVA + ZymA + H‐ASD. These results suggest that LPS and ZymA play different roles in allergic airways inflammation with ASD; LPS mainly enhances neutrophil recruitment through H‐ASD, and ZymA enhances eosinophil recruitment through H‐ASD.
A readily usable two‐photon fluorescence lifetime microendoscope
Authors: Hage Charles‐Henri , Leclerc Pierre , Fabert Marc , Bardet Sylvia M. , Brevier Julien , Ducourthial Guillaume , Mansuryan Tigran , Leray Aymeric , Kudlinski Alexandre , Louradour Frédéric
Published: December 2018

A two‐photon fluorescence lifetime (2P‐FLIM) microendoscope, capable of energetic metabolism imaging through the intracellular nicotinamide adenine dinucleotide (NADH) autofluorescence, at sub‐cellular resolution, is demonstrated. It exhibits readily usable characteristics such as convenient endoscope probe diameter (≈2 mm), fiber length (>5 m) and data accumulation rate (16 frames per second (fps)), leading to a FLIM refreshing rate of ≈0.1 to 1 fps depending on the sample. The spiral scanning image formation does not influence the instrument response function (IRF) characteristics of the system. Near table‐top microscope performances are achieved through a comprehensive system including a home‐designed spectro‐temporal pulse shaper and a custom air‐silica double‐clad photonic crystal fiber, which enables to reach up to 40 mW of ≈100 fs pulses @ 760 nm with a 80 MHz repetition rate. A GRadient INdex (GRIN) lens provides a lateral resolution of 0.67 μm at the focus of the fiber probe. Intracellular NADH fluorescence lifetime data are finally acquired on cultured cells at 16 fps.
High and ultra‐high definition of infrared spectral histopathology gives an insight into chemical environment of lung metastases in breast cancer
Authors: Augustyniak Karolina , Chrabaszcz Karolina , Jasztal Agnieszka , Smeda Marta , Quintas Guillermo , Kuligowski Julia , Marzec Katarzyna M. , Malek Kamilla
Published: December 2018

Using high definition (HD) and ultra‐high definition (UHD) of Fourier‐transform infrared (FTIR) spectroscopic imaging, we characterized spectrally pulmonary metastases in a murine model of breast cancer comparing them with histopathological results (Hematoxylin and eosin [H&E] staining). This comparison showed excellent agreement between the methods in case of localization of metastases with size below 1 mm and revealed that label‐free HD and UHD IR spectral histopathology distinguish the type of neoplastic cells. We primary focused on differentiation between metastatic foci in the pleural cavity from cancer cells present in lung parenchyma and inflamed cells present in extracellular matrix of lungs due to growing of advanced metastases. In addition, a combination of unsupervised clustering and IR imaging indicated the high sensitivity of FTIR spectroscopy to identify chemical features of small macrometastases located under the pleural cavity and during epithelial‐mesenchymal transition. FTIR‐based spectral histopathology was proved to detect not only phases of breast cancer metastasis to lungs but also to differentiate various origins of metastases seeded from breast cancer.
Poly‐allylamine hydrochloride and fucoidan‐based self‐assembled polyelectrolyte complex nanoparticles for cancer therapeutics
Authors: Wang Pei , Kankala Ranjith Kumar , Chen Biaoqi , Long Ruimin , Cai Duanhua , Liu Yuangang , Wang Shibin
Published: December 2018

Herein, we fabricated the novel drug delivery system based on the self‐assembly of two polyelectrolytes, poly‐allylamine hydrochloride (PAH) and fucoidan, as the polycation and polyanion, respectively, under mild conditions for cancer therapeutics. Furthermore, the designed polyelectrolyte complex nanoparticles as well as the methotrexate (MTX) disodium salt‐loaded composites were systematically characterized using various techniques. The MTX loading in the nanoparticles was confirmed by zeta potential values that changed from −36.2 ± 2.2 to −28.3 ± 3.1 mV at a loading amount of 13.3 ± 1.2%. Furthermore, the obtained eventual particle sizes of nanoparticles were various with different concentrations and ratios of polyelectrolytes. The particle size also has increased from 130 ± 2.6 to 162.9 ± 2.3 nm after loading MTX. The drug release investigations in vitro at a pH value of 6.0 (acid environment) showed that the release of MTX was sustained in the conditions provided. Finally, we investigated the anticancer efficacy of MTX‐loaded nanoparticles on MCF‐7 cells and HeLa cells and the satisfactory results were obtained. Together, these self‐assembled PAH/fucoidan nanoparticles with sustained drug release property will become the promising delivery system for cancer therapeutics. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 339–347, 2019.
Ectopic expression of CC chemokine receptor 7 promotes prostate cancer cells metastasis via Notch1 signaling
Authors: Du Ruoyang , Tang Guanlin , Tang Zhaobing , Kuang Youlin
Published: December 2018

There currently exists no satisfactory treatment for patients with prostate cancer with local evolution and distant metastasis. Previous studies have confirmed the importance of CC chemokine receptor 7 (CCR7) in the invasion and metastasis of prostate cancer. And increasing evidence prove that Notch1 can play diametrically opposite roles in the development and progression of different tumors. To demonstrate the correlation between CCR7 and Notch1, PC‐3 cells were transfected with pcDNA3.1‐CCR7 or CCR7 si‐RNA, respectively. Then Western blot analysis was used to detect the expressions of Notch1, ERK, P38, JNK, NF‐κB, MMP‐9, and epithelial‐mesenchymal transition (EMT)‐related proteins. Moreover, matrigel invasion assays were performed to assess the migratory and invasive activities of PC‐3 cells. PcDNA3.1‐CCR7 increased the expression of Notch1, phospho‐MAPK, phospho‐P65, MMP‐9, N‐cadherin, and Snail in PC‐3 cells, but decreased the expression of E‐cadherin. PcDNA3.1‐CCR7 also promoted the migration and invasion of PC‐3 cells. However, CCR7 si‐RNA reversed the effect of pcDNA3.1‐CCR7 in PC‐3 cells. And MAPK and NF‐κB pathway inhibitors were used to testify that activation of Notch1 induces EMT through MAPK and NF‐κB pathway. All these results indicate that upregulation of Notch1 by CCR7 can accelerate the evolution of EMT and develop the invasion and metastasis in prostate cancer cells by activating MAPK and NF‐κB signaling pathways in prostate cancer cells, which provides a new molecular evidence for targeted therapy in metastatic prostate cancer.
Long noncoding RNA OIP5‐AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATβ/PI3K/AKT/mTOR signaling pathway by sponging the miR‐340‐5p
Authors: Song Lei , Zhou Zhigang , Gan Yibo , Li Pei , Xu Yuan , Zhang Zehua , Luo Fei , Xu Jianzhong , Zhou Qiang , Dai Fei
Published: December 2018

The abnormal expression of long noncoding RNAs (lncRNAs) plays an important role in the regulation of human cancer progression and drug resistance. The lncRNA OPI5‐AS1 is a crucial regulator in some cancers; however, its role in cisplatin resistance of osteosarcoma remains unclear. We found that OIP5‐AS1 was significantly upregulated in cisplatin‐resistant (CR) osteosarcoma cells MG63‐CR and SaOS2‐CR compared with the corresponding parental cells. OIP5‐AS1 silencing suppressed cell growth in vitro and in vivo, and promoted apoptosis of MG63‐CR and SaOS2‐CR cells, indicating that knockdown of OIP5‐AS1 significantly decreased cisplatin resistance in MG63‐CR and SaOS2‐CR cells. This conclusion was supported by the decreased expression of the drug resistance‐related factors multidrug resistance‐associated protein 1 (MRP1) and P‐glycoprotein (P‐gp) upon OIP5‐AS1 silencing. In addition, OIP5‐AS1 downregulation suppressed the PI3K/AKT/mTOR signaling pathway. Importantly, we demonstrated that OIP5‐AS1 functions as a competing endogenous RNA of miR‐340‐5p and regulates the expression of lysophosphatidic acid acyltransferase (LPAATβ), which is a target of miR‐340‐5p. Moreover, downregulation of miR‐340‐5p partly reversed the inhibitory effect of OIP5‐AS1 knockdown on the PI3K/AKT/mTOR pathway and therefore counteracted cisplatin resistance in MG63‐CR and SaOS2‐CR cells. In conclusion, OIP5‐AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATβ/PI3K/AKT/mTOR signaling pathway by sponging the miR‐340‐5p. Our results contribute to a better understanding of the function and mechanism of OIP5‐AS1 in osteosarcoma cisplatin resistance.
PACAP through EGFR transactivation preserves human corneal endothelial integrity
Authors: Maugeri Grazia , D'Amico Agata Grazia , Castrogiovanni Paola , Saccone Salvatore , Federico Concetta , Reibaldi Michele , Russo Andrea , Bonfiglio Vincenza , Avitabile Teresio , Longo Antonio , D'Agata Velia
Published: December 2018

The corneal endothelium is composed of a single hexagonal‐shaped cells layer adherent to the Descemet's membrane. The primary function of these cells is maintaining of tissue clarity by regulating its hydration. Trauma, aging or other pathologies cause their loss, counterbalanced by enlargement of survived cells unable to guarantee an efficient fluid pumping to and from the stroma. Regenerative medicine using human corneal endothelial cells (HCECs) isolated from peripheral corneal‐scleral tissue of a donor could be an attractive solution, overcoming transplantation problems. In a previous study, we have demonstrated that HCECs treatment with pituitary adenylate cyclase–activating polypeptide (PACAP) following growth factors deprivation prevents their degeneration. However, the molecular mechanism mediating this effect has not been clarified, yet. Here, we have shown for the first time the expression of PACAP and its receptor (PAC1R) in human corneal endothelium and demonstrated that this peptide, selectively binding to PAC1R, induces epidermal growth factor receptor (EGFR) phosphorylation and the MAPK/ERK1/2 signaling pathway activation. In conclusion, our data have suggested that PACAP could represent an important trophic factor in maintaining human corneal endothelial integrity through EGFR transactivation. Therefore, PACAP, as well as epidermal growth factor and fibroblast growth factor, could co‐operate to guarantee tissue physiological functioning by supporting corneal endothelial barrier integrity.
Safety, Tolerability, and Pharmacodynamics of Intrathecal Injection of Recombinant Human HGF (KP‐100) in Subjects With Amyotrophic Lateral Sclerosis: A Phase I Trial
Authors: Warita Hitoshi , Kato Masaaki , Asada Ryuta , Yamashita Atsuko , Hayata Daichika , Adachi Kiichi , Aoki Masashi
Published: December 2018

Hepatocyte growth factor is an endogenous pleiotropic factor shown to act as a potent neuroprotectant against disease progression in animal models of amyotrophic lateral sclerosis, which is a devastating, adult‐onset motor neuron disease. To evaluate the safety, tolerability, and pharmacokinetics of recombinant 5‐residue‐deleted human hepatocyte growth factor (KP‐100) injected intrathecally through an implantable catheter connected to a subcutaneous port, we conducted a first‐in‐human phase I trial of intrathecal KP‐100 in 15 Japanese patients with amyotrophic lateral sclerosis. The regimen was a single injection of 3 escalating doses (0.2, 0.6, and 2.0 mg/body) in 9 subjects followed by 2 doses (0.6 and 2.0 mg/body) repeated 5 times at 1‐week intervals in 6 subjects (3 subjects/group). With single‐dose administration, the mean half‐life of KP‐100 in the cerebrospinal fluid was 1.2 to 1.4 days, with its maximum concentration increasing in a dose‐dependent manner. With multiple‐dose administration, the trough KP‐100 concentrations in the cerebrospinal fluid generally remained constant for any dose, despite multiple dosing. There were no deaths, serious adverse events, or device malfunctions leading to discontinuation. In all subjects, plasma KP‐100 concentrations were <1 ng/mL, or below the lower limit of detection at all time points of measurement. Anti–KP‐100 antibody was not detected in the cerebrospinal fluid or plasma specimens from any of the subjects throughout the KP‐100 dosing period. These results suggest that KP‐100, as well as the device used to administer it, is safe and tolerable. A phase II trial is warranted in patients with various central nervous system diseases such as amyotrophic lateral sclerosis.
The Consumption Consequences of Couples Pooling Finances
Authors: Garbinsky Emily N. , Gladstone Joe J.
Published: December 2018

When couples decide to share their lives, they must also decide how to pool their finances. In this article, we ask: Does the type of bank account from which one spends (joint vs. separate) affect the type of products one chooses to buy (utilitarian vs. hedonic)? Real‐world evidence from analyzing bank transaction records (study 5), as well as data collected from experiments in the field (studies 1 and 2) and lab (studies 3 and 4), converge to support the hypothesis that couple members who spend from a joint bank account are more likely to choose utilitarian (vs. hedonic) products, than those who spend from a separate bank account. We find that these different spending patterns are driven by an increased need to justify spending to one's partner that is experienced when money is pooled together. If a hedonic product becomes easier to justify (study 4), the effect of account type on spending patterns disappears. These findings have important theoretical and practical implications for better understanding financial decision‐making within romantic couples.
One‐pot Synthesis of Fused Dipyranocoumarins from Dihydroxycoumarins and Propargyl Chlorides under Microwave Irradiation
Authors: Vlachou Evangelia‐Eirini N. , Gabriel Catherine , Litinas Konstantinos E.
Published: December 2018

Dipetalolactone and 4‐methyldipetalolactone are prepared in excellent yield by a one‐pot tandem propargylation/Claisen rearrangement/cyclization reaction of the corresponding 5,7‐dihydroxycoumarins with 3‐chloro‐3‐methylbut‐1‐yne in the presence of Cs2CO3 under microwave irradiation. The analogous reactions of propargyl chloride with esculetins or 5,7‐dihydroxycoumarins led to dipropargyloxy derivatives. The later by treatment with gold nanoparticles supported on TiO2 or BF3.Et2O in N,N‐dimethylformamide (DMF) under microwave irradiation resulted in very good to excellent yield to the corresponding fused dipyranocoumarins. The reactions of esculetins with 3‐chloro‐3‐methylbut‐1‐yne gave mainly exomethylene fused dioxino[g]coumarins.
Synthesis and Reactions of the Novel 6‐ethyl‐4‐hydroxy‐2,5‐dioxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carboxaldehyde
Authors: Ibrahim Magdy A. , Hassanin Hany M.
Published: December 2018

The novel 6‐ethyl‐4‐hydroxy‐2,5‐dioxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carboxaldehyde (2) was efficiently synthesized from Vilsmeier–Haack formylation of 3‐(1‐ethy1‐4‐hydroxy‐2‐oxo‐(1H)‐quinolin‐3‐yl)‐3‐oxopropanoic acid (1). The aldehyde 2 was allowed to react with some nitrogen nucleophiles producing a variety of hydrazones 3–7. Reaction of aldehyde 2 with hydrazine hydrate and hydroxylamine hydrochloride afforded pyrazole and isoxazole annulated pyrano[3,2‐c]quinoline‐2,5(6H)‐dione, respectively. The reactivity of aldehyde 2 was examined toward some active methylene nitrile, namely, malononitrile, ethyl cyanoacetate, and cyanoacetamide leading to 2‐iminopyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines 10–12, respectively. Also, some novel pyrazolo[4″,3″:5′,6′]pyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines (13, 14) and thiazolo[5″,4″:5′,6′]pyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines (15, 16) were synthesized. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.
Pharmaceutical quality by design in academic nanomedicine research: stifling innovation or creativity through constraint?
Authors: Dailey Lea Ann
Published: December 2018

Pharmaceutical quality by design (QbD) is a systematic approach to drug development that begins with predefined objectives and emphasises product and process understanding and control based on sound science and quality risk management. First and foremost, QbD is an experimental design philosophy, which emphasises the value of thorough intellectual planning prior to the commencement of laboratory studies. Academic researchers whose ambitions lie in translational science may benefit from the lessons learned by the pharmaceutical industry following implementation of QbD into their development philosophy. However, because of the very interdisciplinary nature of academic nanomedicine research, it is likely that very few investigators are aware of QbD and how aspects of it may be judiciously implemented in an academic research setting. This review provides an introduction to the main elements of QbD and gives examples of case studies where QbD has been applied to nanomedicine research.
A high‐throughput glutathione trapping assay with combined high sensitivity and specificity in high‐resolution mass spectrometry by applying product ion extraction and data‐dependent neutral loss
Authors: Wang Qingping , Liu Hanlan , Slavsky Marina , Fitzgerald Maria , Lu Chuang , O'Shea Thomas
Published: December 2018

Reactive metabolites are thought to play a pivotal role in the pathogenesis of some drug‐induced liver injury (DILI) and idiosyncratic adverse drug reactions (IADRs), which is of concern to patient safety and has been a cause of drugs being withdrawn from the market place. To identify drugs with a lower propensity for causing DILI and/or IADRs, high‐throughput assays to capture reactive metabolites are required in pharmaceutical industry for early drug discovery risk assessment. We describe the development of an assay to detect glutathione adducts with combined high sensitivity, enhanced specificity, and rapid data analysis. In this assay, compounds were incubated with human liver microsomes and a mixture of 1:1 of GSH (γ‐GluCysGly): GSX(γ‐GluCysGly‐13C215N) in a 96‐well plate format. UPLC‐UV and LTQ Orbitrap XL were employed to detect GSH‐adducts using the following mass spectrometry setups: (a) selected ion monitoring (SIM) at m/z of 274 ± 3 Da in negative mode with in‐source fragmentation (SCID), which enables simultaneously monitoring two characteristic product ions of m/z 272.0888 (γ‐glutamyl‐dehydroalanyl‐glycine) and 275.0926 (γ‐glutamyl‐dehydroalanyl‐glycine‐13C215N); (b) full scan mode for acquisition of exact mass of glutathione adducts; (c) data‐dependent MS2 scan through isotopic matching (M:M + 3.00375 = 1:1) for monitoring neutral loss fragments (144 Da from dehydroalanyl‐glycine) and for structural information of glutathione adducts. This approach was qualified using eight compounds known to form GSH conjugates as reported in the literature. The high sensitivity and specificity were demonstrated in identifying unique CysGly adducts in the case of clozapine, diclofenac, and raloxifene and in identifying GSH‐adducts of fragmented parent molecules in the case of amodiaquine and troglitazone. In addition, LC‐UV chromatograms in the presence or absence of GSH/GSX allowed for identification of the rearranged glutathione adducts without aforementioned characteristic fragment ions. Implement of this assay in drug discovery small molecule programs has successfully guided drug design.
Hind‐ and midfoot bone morphology varies with foot type and sex
Authors: Moore Erik S. , Kindig Matthew W. , McKearney Daniel A. , Telfer Scott , Sangeorzan Bruce J. , Ledoux William R.
Published: December 2018

Foot type has been associated with pain, injury, and altered gait mechanics. Morphological variations in foot bones due to foot type variation may impact surgical and therapeutic treatments. The purpose of this study was to utilize principal component analysis (PCA) to determine how morphology of the hind‐ and midfoot bones differs among foot types and sex. The calcaneus, talus, navicular, and cuboid were segmented using previously obtained computed tomography (CT) scans and converted to surface models. The CTs were sorted into four foot types—cavus, neutrally aligned, asymptomatic planus, and symptomatic planus. Morphometric shape analysis software (Geomorph) was used to perform a PCA to determine which components varied between foot types and between sexes. The calcaneus showed planus feet of both types to have calcanei that have decreased height and increased length compared to neutrally aligned feet. The talus demonstrated increased posterior mass for cavus feet compared to neutrally aligned feet. For the navicular, symptomatic planus had a more posteriorly positioned tuberosity and were wider than asymptomatic planus feet. The cuboid did not exhibit any differences between foot types. Sex differences, found only at the talus and navicular, were subtle. PCA is an objective technique that helped elucidate differences in bone morphology between foot types and sex without needing to determine the features of interest before comparing groups. Understanding these variations can help inform diagnosis of foot pathologies and surgical protocols as well as improve computer models of the foot. Published 2018. This article is a U.S. Government work and is in the public domain in the USA. J Orthop Res 9999:1–16, 2019.
Recent Progress on Photomultiplication Type Organic Photodetectors
Authors: Miao Jianli , Zhang Fujun
Published: December 2018

Photodetectors as a significant unit of intelligent optoelectronic systems have stimulated immense attention from multidisciplinary areas. Photomultiplication (PM) is desirable for sensitive photodetectors with strong detection capability of weak light, which can further simplify the photo‐detection systems without pre‐amplifier circuit. For organic photodetectors (OPDs), PM phenomenon cannot be realized by utilizing the principle of avalanche effect or impact ionization as in inorganic materials, stemming from organic semiconductor materials with large exciton binding energy and disordered structure. In this review, the recent progress on PM type OPDs is comprehensively summarized from the perspective of device physics and material science. Charge tunneling injection induced by interfacial traps becomes the mainstream working mechanism for obtaining PM phenomenon. A series of PM type OPDs was achieved by utilizing interfacial blocking layer and introducing trap states into active layer or interfacial layer. The filter‐free PM type narrowband OPDs are realized by combining the concept of charge injection narrowing with the mechanism of PM. Meanwhile, further development on this hot topic is proposed and fully discussed, including multifunctional OPDs, organic–inorganic hybrid photodetectors, and photodetector systems.
A parametric cut size prediction model for a turbo air classifier
Authors: Yu Y. , Liu J.
Published: December 2018

A new parametric cut size prediction model is put forward based on the simplified single particle motion rule. According to analysis of the inner flow field of a turbo air classifier and Lagrangian equation of particle motion, the particle's trajectory in the annular region is calculated and simulated using MATLAB. Since particles with different sizes have different trajectories in the same flow field, the cut size of a turbo air classifier can also be obtained. The simulated results show the cut size increases by widening the annular region and it decreases by narrowing the annular region. Talc powder classification experiments are carried out to verify this cut size prediction model. The calculated cut sizes using the proposed prediction model are in agreement with the experimental results. A new way to predict cut size is put forward, which provides a theoretical guidance to optimize operational parameters and the structure of the turbo air classifier.
In vitro analysis of a microwave sensor for noninvasive glucose monitoring
Authors: Sethi Waleed Tariq , Issa Khaled , Ashraf Muhammad Ahmed , Alshebeili Saleh
Published: December 2018

In this article, we present in vitro analysis for a microwave sensor proposed for noninvasive glucose monitoring. The sensor is a microstrip‐fed rectangular slot with a dielectric resonator having an elliptical shape resembling a human thumb. It has been demonstrated experimentally and by simulations that the microwave sensor is capable of detecting variations in glucose concentrations (40‐400 mg/dL) by observing shifts in the sensor's resonant frequencies. A Debye model is first developed to predict permittivity and loss tangent values of given glucose concentrations. Knowledge of such values is essential to facilitate simulation of glucose sensor. The simulations and measuremental results show similar behaviors with respect to resonances in the frequency band of interest, which makes the proposed microwave sensor a potential and convenient choice for noninvasive glucose monitoring.
Consumer return policies in competitive markets: An operations perspective
Authors: Huang Tingliang , Ren Hang , Chen Ying‐Ju
Published: December 2018

The recent literature argues that offering consumer returns, such as money‐back guarantees (MBGs), reduces quality differentiation in competitive markets. We show that this argument does not hold in general. We propose a new certainty‐equivalent approach, which shows that offering product returns only changes the two firms' marginal costs without affecting their quality differentiation. Our proposed approach directly reveals that asymmetry of salvage values may overturn the recent finding that MBGs help the low‐quality firm. Since MBGs only lead to marginal cost reductions, we show that each firm should adopt MBGs in equilibrium irrespective of the competitor's choice. We then examine the role of offering consumer returns in determining the firms' competitive product strategies. We demonstrate that offering MBGs does not directly affect the quality differentiation choices, and discuss the impacts of production technology and consumer valuation.
Analysis of condensed tannins in Populus spp. using reversed phase UPLC‐PDA‐(−)esi‐MS following thiolytic depolymerisation
Authors: Rubert‐Nason Kennedy F. , Lindroth Richard L.
Published: December 2018

Introduction

Condensed tannins (CTs) are proanthocyanidin heteropolymers that are widely distributed among plants. Their biochemical properties are determined by molecular structure (e.g. polymer size, hydroxylation, stereochemistry). In Populus, genetically and environmentally‐determined CT concentrations have been related to ecological effects, while the potential role of CT molecular structure has received little attention.

Objective

Evaluate CT polymerisation, major constituent monomers, stereochemistry and overall content in Populus tremuloides foliage using ultra‐high‐performance liquid chromatography with photodiode array and mass spectrometry (UPLC‐PDA‐(−)esi‐MS) detection following thiolytic depolymerisation of the CTs.

Methodology

CTs were extracted from dried foliage of six P. tremuloides genotypes into methanol and thiolytically depolymerised into constituent monomers. Calibration standards were prepared by thiolysis of CT mixtures isolated from P. tremuloides foliage on Sephadex LH‐20, followed by preparative high‐performance liquid chromatography (HPLC).

Results

Populus tremuloides CTs contained predominantly repeating subunits of three putative stereoisomers each of catechin and gallocatechin. Linear calibrations for standards of these subunits and their thioethers (purities 44–87%, UPLC‐(−)esi‐MS) were generally stable over the course of 10 months. CT polymer size, hydroxylation, stereochemistry and concentrations differed among genotypes.

Conclusion

This thiolysis‐UPLC‐PDA‐(−)esiMS method was optimised for analysis of CT polymer size, hydroxylation, stereochemistry, and total concentration in Populus foliage. It revealed significant variation in each of these properties among P. tremuloides genotypes, and will facilitate evaluation of how environmental factors affect CT molecular structures.
From reading strategy instruction to student reading achievement: The mediating role of student motivational factors
Authors: Huang Jing , Chen Gaowei
Published: December 2018

This study investigated the associations among reading strategy instruction, student motivational factors (i.e., attitudes toward reading, reading self‐concept, and motivation to read), gender, and reading achievement. The analyses were conducted using the Hong Kong sample (students at Level 1, n = 3,875 and teachers at Level 2,
n = 133) from the Progress in International Reading Literacy Study 2011 through multilevel structural equation modeling. The results showed that, first, the relation between the frequency of reading strategy instruction and student reading achievement was mediated by student attitudes toward reading. Second, the frequency of reading strategy instruction was significantly related to student attitudes toward reading and motivation to read and student attitudes toward reading was significantly associated with reading achievement. Finally, girls had more positive attitudes toward reading, more positive reading self‐concept, higher motivation to read, and higher reading achievement than boys. These findings may shed light on how teachers should arrange their reading strategy instruction to interplay with student attitudes toward reading and motivation to read and to help improve reading achievement.
Handling Missing Dosing History in Population Pharmacokinetic Modeling: An Extension to MDM Method
Authors: Wang Yuhuan , Liu Xiaoxi
Published: December 2018

A major challenge in population pharmacokinetic modeling is handling data with missing or potentially incorrect dosing records. Leaving such records untreated or “commented out” will cause bias in parameter estimates. Several approaches were previously developed to address this challenge. Published in 2004, the missing dose method (MDM) demonstrated its robustness in handling missing dosing history in pharmacokinetic (PK) modeling. In this study, we presented two new extensions: a modified MDM method (MDM2) and a compartment initialization method (CIM). Their performance was examined with a large batch of simulated PK studies. For each method, 8,000 models were run, including different model structures, dosing routes, and missing dosing record scenarios. Both MDM2 and CIM exhibited robust performance and improved parameter estimation results. Specifically, CIM consistently outperformed other methods in fixed‐effect and random‐effect PK parameter estimation. The new methods demonstrate great potential in addressing missing dosing records challenges in PK analysis.
Integrated Photonic and Plasmonic Resonant Devices for Label‐Free Biosensing and Trapping at the Nanoscale
Authors: Ciminelli Caterina , Dell'Olio Francesco , Conteduca Donato , Armenise Mario Nicola
Published: December 2018

In the last few years, integrated photonic and plasmonic devices based on resonant cavities have become key building blocks in new microsystems, instruments, and diagnostic tools for a wide range of biomedical applications including point‐of‐care (POC) diagnostics, new drug development, and proteomics. Several resonant label‐free photonic and plasmonic biosensors for early diagnosis and monitoring of a wide range of pathologies have attracted a remarkable research interest due to their characteristic features such as high resolution, small size, immunity to electromagnetic interferences, compatibility with the CMOS technology, and strong light–matter interaction. Moreover, recently, photonic, plasmonic, and hybrid photonic/plasmonic micro and nano‐cavities have experimentally demonstrated a great potential also for trapping at the nanoscale and the interest toward these devices in the field of healthcare is quickly rising. Here, the recent advances in the field of integrated photonic and plasmonic devices based on resonant cavities for label‐free biosensing and trapping at the nanoscale are critically reviewed, with a special emphasis on the specific applications of these devices such as diseases diagnostics and new drugs development.
Multivariate process incapability vector
Authors: Ganji Zainab Abbasi
Published: December 2018

Process capability indices evaluate the capability of the processes in satisfying customer's requirements. This paper introduces a superstructure multivariate process incapability vector for multivariate normal processes and then, compares it with four recently proposed multivariate process capability indices to show its better performance. In addition, the effects of two modification factors are investigated. Also, bootstrap confidence intervals for the first component of the proposed vector are obtained. Furthermore, real manufacturing data sets are presented to demonstrate the applicability of the proposed vector.
Parallel data transmission for navigation satellite network with agility link
Authors: Zhao Yue , Yi Xianqing , Hou Zhenwei , Zhang YaoHong , Li Chong
Published: December 2018

The topology of the navigation satellite network with agility link evolves with chain‐building slots periodically. The navigation data are transmitted in a “store, carry and forward” manner without requiring end‐to‐end paths. Thus, the navigation satellite network with agility link can be considered as a deterministic delay tolerant network (DTN). The data transmission of navigation satellite network is limited by chain‐building slot and bandwidth. To utilize network transmission link and communication bandwidth fully, this paper proposed an algorithm called parallel data transmission for the navigation satellite network with agility link. Based on the network characteristics, the algorithm is designed with polling pattern of link establishment and formulated as parallel data transmission problem based on deterministic scheduling DTN. Then, we design the method based on Dynamic Game from the view of data, while the Dynamic Programming method is proposed referring to Linear Programming–based method for optimization. Finally, the results were compared with three methods using the standard network routing metrics and showed that the proposed algorithm is better than the existing methods.
Inclusive Talk: Weaving Fiction Discussions Across the School Day
Authors: Coakley‐Fields Mary R.
Published: December 2018

The author presents findings from a yearlong study of the ways an inclusive fourth‐grade teacher and her students talked about reading outside of formal reading lessons. Findings indicated that across the school day, especially during informal moments, students narrated connections and disconnections between their experiences and realistic fiction read‐aloud books the class had read together. These improvised spoken narratives created opportunities for students’ inclusion and affirmation in the social space of the classroom as they helped students know each other as readers and people outside of labels, levels, and assessment instruments. Using children's literature as a point of reference, this pattern of dialogue honored students’ life experiences and interests while supporting ongoing reflection, community building, and interpretation strategies.
Comparison of various approaches to design wind‐PV rural electrification projects in remote areas of developing countries
Authors: Domenech Bruno , Ferrer‐Martí Laia , Pastor Rafael
Published: December 2018

Nowadays, around 1.1 billion people in rural and remote areas of developing countries remain without electricity. Stand‐alone projects that combine the wind and photovoltaic generation technologies as well as microgrids and individual supplies for the distribution network are an adequate strategy to reach such isolated regions. However, the design of electrification projects is complex, having to define the best combination of generation and distribution technologies, under a challenging social context and tight technoeconomic resources. In order to ease decision‐making, several tools have been developed in the literature and are here reviewed, grouped into three main categories: optimization processes, aiming to minimize project costs subject to technical constraints, through exact or heuristic algorithms; multicriteria processes, using different methods to select the best among a set of predefined scenarios according to economic, technical, social, and environmental criteria; and systematized tools, that have been developed to provide user‐friendly interface for their larger dissemination in different regions and contexts. Hence, this paper aims to provide researchers and practitioners an analysis of the advantages and limitations of approaches used over the last decade when addressing the designing of wind and/or photovoltaic electrification projects for extremely poor and isolated areas in developing countries, as well as some areas for further research.

This article is categorized under:

Concentrating Solar Power > Systems and Infrastructure

Photovoltaics > Systems and Infrastructure

Wind Power > Systems and Infrastructure

Energy Infrastructure > Economics and Policy
Integrating molecular networks with genetic variant interpretation for precision medicine
Authors: Capriotti Emidio , Ozturk Kivilcim , Carter Hannah
Published: December 2018

More reliable and cheaper sequencing technologies have revealed the vast mutational landscapes characteristic of many phenotypes. The analysis of such genetic variants has led to successful identification of altered proteins underlying many Mendelian disorders. Nevertheless the simple one‐variant one‐phenotype model valid for many monogenic diseases does not capture the complexity of polygenic traits and disorders. Although experimental and computational approaches have improved detection of functionally deleterious variants and important interactions between gene products, the development of comprehensive models relating genotype and phenotypes remains a challenge in the field of genomic medicine. In this context, a new view of the pathologic state as significant perturbation of the network of interactions between biomolecules is crucial for the identification of biochemical pathways associated with complex phenotypes. Seminal studies in systems biology combined the analysis of genetic variation with protein–protein interaction networks to demonstrate that even as biological systems evolve to be robust to genetic variation, their topologies create disease vulnerabilities. More recent analyses model the impact of genetic variants as changes to the “wiring” of the interactome to better capture heterogeneity in genotype–phenotype relationships. These studies lay the foundation for using networks to predict variant effects at scale using machine‐learning or algorithmic approaches. A wealth of databases and resources for the annotation of genotype–phenotype relationships have been developed to support developments in this area. This overview describes how study of the molecular interactome has generated insights linking the organization of biological systems to disease mechanism, and how this information can enable precision medicine.

This article is categorized under:

Translational, Genomic, and Systems Medicine > Translational Medicine

Biological Mechanisms > Cell Signaling

Models of Systems Properties and Processes > Mechanistic Models

Analytical and Computational Methods > Computational Methods