bluuebunny/crossref_metadata_2025 huggingface dataset:
Formulation of an economical microemulsion of diesel/colza oil fuel and investigation of some physical parameters for its stability
Authors: Najjar Reza , Heidari Somaiyeh , Tazerout Mohand
Published: November 2017

The formulation of an economical diesel/colza oil/water microemulsion fuel is reported. The modification of diesel fuel significantly improves its fuel properties as well as environmental pollution issues. To investigate the possibility of using colza oil with diesel fuel and adding water to reduce emissions of diesel combustion, the phase diagrams of the system were constructed using titration method with co‐surfactant. n‐Butanol is selected as co‐surfactant among the investigated alcohols with different chain lengths as it formed wide single phase area. Using of n‐butanol was helped to tune solubilizing of water in diesel/colza oil blend and to reduce its viscosity. Here, a 4:1 blend of diesel:colza oil, 5% water and n‐butanol was selected as base system which was then optimized to obtain a reasonably economical formulation with acceptable physical properties. According to the measurements of physical properties, such as viscosity, temperature stability, water droplet size and considering an economical point of view, the optimum microemulsion system was composed of 75% diesel/colza oil (4:1), 5% water, 10% n‐butanol, 8% Brij 30 and 2% Tween 80, and was prepared in room temperature (21–25) °C by stirring with 500 rpm for 5 min. The optimum system was stable up to 45°C. © 2017 American Institute of Chemical Engineers Environ Prog, 37: 1762–1769, 2018
HPW anchored Meso‐HZ‐5, a novel catalyst for selective synthesis of ethyl levulinate biofuel by alcoholysis of biomass‐derived furfuryl alcohol
Authors: Nandiwale Kakasaheb Y. , Pande Ashwini M. , Bokade Vijay V.
Published: November 2017

Ethanolysis of biomass derived furfuryl alcohol (FA) produces ethyl levulinate (EL), a biofuel additive and precursor for γ‐valerolactone synthesis. The present study is devoted to develop an efficient and an environmentally benign catalytic system for one‐pot conversion of FA to EL biofuel, by revealing an insight of the catalytic mechanism. The catalytic activity of H‐ZSM‐5, Meso‐HZ‐5 (desilicated H‐ZSM‐5) and different percentage H3PW12O40(HPW) anchored to Meso‐HZ‐5 catalysts have been evaluated for the FA ethanolysis.

As per our knowledge, this is the first research reporting the application of HPW anchored to Meso‐HZ‐5 catalysts for the conversion of FA into EL in biomass utilization. These catalysts were synthesized and characterized by Powder X‐ray diffraction (XRD), N2 physisorption and temperature programmed NH3 desorption (TPAD). Products of FA ethanolysis viz., 4,5,5‐triethoxypentan‐2‐one (TEP), ethoxy‐methyl‐ furan (EMF), diethyl ether (DEE), EL were identified by Gas Chromatography‐Mass Spectroscopy (GC‐MS) and quantified by flame ionization detector (GC‐FID). The physicochemical properties of catalysts were found to correlate to the product distribution matrix.

Moreover, influences of several process parameters such as catalyst amount, reactant molar ratio, temperature and time on the extent of FA ethanolysis were systematically investigated. Under optimized conditions, 15% (w/w) HPW/Meso‐HZ‐5 exhibited a remarkable catalytic performance with complete FA conversion (100%) along with 97% yield of EL, these activity values are superior than the previously reported studies. The present study provides an insight of the catalytic mechanism along with a potential environmental benign and the economic catalyst for the efficient synthesis of EL biofuel from the biomass‐derived FA. © 2017 American Institute of Chemical Engineers Environ Prog, 37: 1736–1742, 2018
Performance analysis of a new hybrid cooling–drying system
Authors: Senturk Acar Merve , Arslan Oguz
Published: November 2017

In this study, the Ranque–Hilsch vortex tube (RHVT)‐aided hybrid cooling and drying system (RHVTHCD), nonhybrid cooling and drying system (NCDS), and RHVT‐aided hybrid cooling and drying system in which used the input stream of RHVT is obtained from the different system as a waste (RHVTHCDW) were investigated using energy and exergy analysis. In this aim, many systems were designed and evaluated with net present value (NPV) in the viewpoint of life cycle cost (LCC). Additionally, several RHVTs with the 9 different helical vortex generators, 3 different control valve angle (α = 30°, 45°, and 60°), 3 different vortex tube body (480, 350, and 210 mm), 5 different opening position of the control valve, and 5 different inlet flow pressure of RHVT (201.325–601.325 kPa) were performed experimentally. The cold outlet flow of RHVT was integrated to the vapor compression system with a heat exchanger, where the hot one was integrated in the drying system. The energy and exergy efficiencies of RHVTHCD system increase with the increase of the evaporator temperature. The maximum NPV value of the RHVTHCD system obtained was 37256.63 €. The highest energy and exergy efficiencies were calculated as 24.74% and 9.69%, respectively. © 2017 American Institute of Chemical Engineers Environ Prog, 37: 1808–1828, 2018
Evaluation of mustard oil for the synthesis of biodiesel: Pretreatment and optimization study
Authors: Shahzadi Iram , Sadaf Sana , Iqbal Javed , Ullah Inam , Bhatti Haq Nawaz
Published: November 2017

Mustard is an important oil crop in Pakistan. The present investigation deals with the evaluation of mustard oil biodiesel as an alternative and renewable fuel to compensate the energy requirements in the world. Because of the presence of high free fatty acids, the mustard oil was first esterified. Important process parameters including the methanol to oil ratio, catalyst dose, reaction temperature, and reaction time were optimized. About 94% of free fatty acids have been successfully esterified by using 1:3.3 methanol to oil ratio, 0.8% catalyst, 60°C temperature, and 280 min of contact time. The pretreated oil was transesterified for biodiesel production. Important influencing parameters have been optimized and study results indicated that 98% biodiesel yield was obtained within 70 min. Physico‐chemical properties of synthesized biodiesel were also analyzed with standard procedures. All characterization results were found in good agreement with recommended ASTM standards. The composition of synthesized biodiesel was determined by GC analysis. The results indicated that, mustard crop can be used as a potential resource for biodiesel production and alkali catalyzed transesterification is an efficient and economical method to synthesize good quality biodiesel. © 2017 American Institute of Chemical Engineers Environ Prog, 37: 1829–1835, 2018
Repetitive transcranial magnetic stimulation for the treatment of drug‐resistant epilepsy: A systematic review and individual participant data meta‐analysis of real‐world evidence
Authors: Cooper Yonatan A. , Pianka Sean T. , Alotaibi Naif M. , Babayan Diana , Salavati Bahar , Weil Alexander G. , Ibrahim George M. , Wang Anthony C. , Fallah Aria
Published: November 2017

Objective

To perform a systematic review and meta‐analysis of real‐world evidence for the use of low‐frequency repetitive transcranial magnetic stimulation (rTMS) in the treatment of drug‐resistant epilepsy.

Methods

We systematically searched PubMed, Scopus, Medline, and clinicaltrials.gov for all relevant articles. Relevant patient and stimulation predictors as well as seizure outcomes were assessed. For studies with and without individual participant data (IPD), the primary outcomes were the rate of “favorable response” (reduction in seizure frequency ≥50%) and pooled event rate of mean reduction in seizure frequency, respectively. Outcomes were assessed with comparative statistics and random‐effects meta‐analysis models.

Results

Of 3,477 identified articles, 12 met eligibility and were included in this review. We were able to obtain IPD for 5 articles constituting 34 participants. Univariate analysis on IPD identified greater favorable response event rates between participants with temporal seizure focus versus extratemporal (50% vs. 14%, p = 0.045) and between participants who were stimulated with a figure‐8 coil versus other types (47% vs. 0%, p = 0.01). We also performed study‐level meta‐analysis on the remaining 7 studies without IPD, which included 212 participants. The pooled mean event rate of 50% seizure reduction using low‐frequency rTMS was 30% (95% confidence interval [CI] 12–57%). Sensitivity analysis revealed that studies with a mean age ≤21 years and studies using targeted stimulation had the highest seizure reduction rates compared to studies with a mean age >21 years (69% vs. 18%) and not using a targeted stimulation (47% vs. 14–20%). Moreover, we identified high interstudy heterogeneity, moderate study bias, and high publication bias.

Significance

Real‐world evidence suggests that low‐frequency rTMS using a figure‐8 coil may be an effective therapy for the treatment of drug‐resistant epilepsy in pediatric patients. This meta‐analysis can inform the design and expedite recruitment of a subsequent randomized clinical trial.
Emotion Regulation as a Transdiagnostic Feature Among Eating Disorders: Cross‐sectional and Longitudinal Approach
Authors: Mallorquí‐Bagué Núria , Vintró‐Alcaraz Cristina , Sánchez Isabel , Riesco Nadine , Agüera Zaida , Granero Roser , Jiménez‐Múrcia Susana , Menchón José M. , Treasure Janet , Fernández‐Aranda Fernando
Published: November 2017

Emotion regulation (ER) difficulties are observed in eating disorders (EDs). However, few studies have explored ER before and after treatment. The aims are as follows: to explore ER difficulties across ED types and a healthy control (HC) group (Study 1) and to assess pretreatment and post‐treatment changes among ED types (Study 2). In Study 1, adult women with EDs (n = 438) and HC (n = 126) completed an assessment including Eating Disorders Inventory‐2, Difficulties in Emotion Regulation Scale and Symptom Checklist‐90‐Revised. Patients in Study 2 (n = 69) were also reassessed after treatment. All ED types reported worse ER compared with HC (p < .001); also, ER differences were found between ED types. Prospective analyses show ER improvements after treatment (p < .001; |d| = 0.51), especially in patients with bulimia nervosa (p < .001; |d| = 1.03; Reliable Change Index = 9.79) with greater improvement in those with a better treatment outcome (p = .034). In conclusion, emotion dysregulation is a part of all forms of EDs. Furthermore, emotional dysregulation can be modified. ED treatments for anorexia nervosa and binge eating disorder might be enhanced by targeting ER skills. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
How to make key 5G wireless technologies environmental friendly: A review
Authors: Alsharif Mohammed H. , Nordin Rosdiadee , Abdullah Nor Fadzilah , Kelechi Anabi Hilary
Published: November 2017

Energy efficiency in cellular networks has increasingly become important to the cellular network operators due to its significant economic and ecological influence in the forthcoming generation of wireless networks, ie, the fifth‐generation (5G) network. To pursue a vision of green communication, this study presents a comprehensive overview and discusses how the key physical layer techniques that will be adopted in the 5G technology can improve energy efficiency to achieve a sustainable wireless network. Among the key 5G technologies discussed are massive multiple‐input multiple‐output, green heterogeneous networks, green millimeter wave, green 5G device‐to‐device communication, green machine‐to‐machine communication, and energy‐efficient 5G architecture. The review concludes that the 5G technology will soon fulfill the critical requirements of low‐energy network while maintaining services with high performance. Potential research opportunities related to green 5G are also highlighted at the end of the article.
The arginine metabolome in acute lymphoblastic leukemia can be targeted by the pegylated‐recombinant arginase I BCT‐100
Authors: De Santo Carmela , Booth Sarah , Vardon Ashley , Cousins Antony , Tubb Vanessa , Perry Tracey , Noyvert Boris , Beggs Andrew , Ng Margaret , Halsey Christina , Kearns Pamela , Cheng Paul , Mussai Francis
Published: November 2017

Arginine is a semi‐essential amino acid that plays a key role in cell survival and proliferation in normal and malignant cells. BCT‐100, a pegylated (PEG) recombinant human arginase, can deplete arginine and starve malignant cells of the amino acid. Acute lymphoblastic leukemia (ALL) is the most common cancer of childhood, yet for patients with high risk or relapsed disease prognosis remains poor. We show that BCT‐100 is cytotoxic to ALL blasts from patients in vitro by necrosis, and is synergistic in combination with dexamethasone. Against ALL xenografts, BCT‐100 leads to a reduction in ALL engraftment and a prolongation of survival. ALL blasts express the arginine transporter CAT‐1, yet the majority of blasts are arginine auxotrophic due to deficiency in either argininosuccinate synthase (ASS) or ornithine transcarbamylase (OTC). Although endogenous upregulation or retroviral transduced increases in ASS or OTC may promote ALL survival under moderately low arginine conditions, expression of these enzymes cannot prevent BCT‐100 cytotoxicity at arginine depleting doses. RNA‐sequencing of ALL blasts and supporting stromal cells treated with BCT‐100 identifies a number of candidate pathways which are altered in the presence of arginine depletion. Therefore, BCT‐100 provides a new clinically relevant therapeutic approach to target arginine metabolism in ALL.
Genetic variants in the platelet‐derived growth factor subunit B gene associated with pancreatic cancer risk
Authors: Duan Bensong , Hu Jiangfeng , Liu Hongliang , Wang Yanru , Li Hongyu , Liu Shun , Xie Jichun , Owzar Kouros , Abbruzzese James , Hurwitz Herbert , Gao Hengjun , Wei Qingyi
Published: November 2017

The platelet‐derived growth factor (PDGF) signaling pathway plays important roles in development and progression of human cancers. In our study, we aimed to identify genetic variants of the PDGF pathway genes associated with pancreatic cancer (PC) risk in European populations using three published genome‐wide association study datasets, which consisted of 9,381 cases and 7,719 controls. The expression quantitative trait loci (eQTL) analysis was also performed using data from the 1000 Genomes, TCGA and GTEx projects. As a result, we identified two potential susceptibility loci (rs5757573 and rs6001516) of PDGFB associated with PC risk [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.05–1.16, and p = 4.70 × 10−5 for the rs5757573 C allele and 1.21, 1.11–1.32, and 2.01 × 10−5 for the rs6001516 T allele]. Haplotype analysis revealed that the C‐T haplotype carriers had a significantly increased risk of PC than those carrying the T‐C haplotype (OR = 1.23, 95% CI = 1.12–1.34, p =5.00 × 10−6). The multivariate regression model incorporating the number of unfavorable genotypes (NUGs) with age and sex showed that carriers with 1–2 NUGs, particularly among 60–70 age group or males, had an increased risk of PC, compared to those without NUG. Furthermore, the eQTL analysis revealed that both loci were correlated with a decreased mRNA expression level of PDGFB in lymphoblastoid cell lines and pancreatic tumor tissues (p = 0.015 and 0.071, respectively). Our results suggest that genetic variants in PDGFB may play a role in susceptibility to PC. Further population and functional validations of our findings are warranted.
Case series of outcomes of a standardized surgical approach for placenta percreta for prevention of ureteral lesions
Authors: Atallah David , Moubarak Malak , Nassar Malek , Kassab Bernard , Ghossain Michel , El Kassis Nadine
Published: November 2017

Objective

To report the outcomes of women with placenta percreta who were surgically treated by a specialized technique based on gynecologic oncology experience, and to demonstrate its safety in preventing ureteral lesions and reducing blood loss.

Methods

In the present retrospective study, data from patients with placenta percreta radically treated at Hôtel‐Dieu de France, Beirut, Lebanon, between December 2012 and January 2017 were reviewed. Demographic, pathology, and delivery data, medical history, per‐operative and postoperative information, and neonatal data were assessed. Operative and postoperative outcomes were compared between emergency and scheduled cases.

Results

Data from 35 patients were reviewed. Median gestational age at delivery was 34 weeks. Cesarean hysterectomy was scheduled in 20 (60%) cases. No ureteral lesions were noted. The median estimated blood loss was 1 L and a median of 3 units of red blood cells units was transfused. Emergency and scheduled cases presented comparable estimated blood loss, intra‐operative transfusion, bladder injury incidence, and surgery duration (all P>0.05). The mean delivery weight was 2100 g; admission to the neonatal intensive care unit was needed for 30 (86%) neonates.

Conclusion

The surgical technique developed for placenta percreta was found to be effective (operative and postoperative outcomes) and safe (prevention of ureteral lesions).
Identification of polystyrene nanoparticle penetration across intact skin barrier as rare event at sites of focal particle aggregations
Authors: Döge Nadine , Hadam Sabrina , Volz Pierre , Wolf Alexander , Schönborn Karl‐Heinz , Blume‐Peytavi Ulrike , Alexiev Ulrike , Vogt Annika
Published: November 2017

The question whether nanoparticles can cross the skin barrier is highly debated. Even in intact skin rare events of deeper penetration have been reported, but technical limitations and possible artifacts require careful interpretation. In this study, horizontal scanning by 2‐photon microscopy (2 PM) of full‐thickness human skin samples placed in a lateral position yielded highly informative images for skin penetration studies of fluorescently tagged nanoparticles. Scanning of large fields of view allowed for detailed information on interfollicular and follicular penetration in tissue blocks without damaging the sample. Images in histomorphological correlation showed that 2P‐excited fluorescence signals of fluorescently tagged 20 and 200 nm polystyrene nanoparticles preferentially accumulated in the stratum corneum (SC) and in the upper part of vellus hair follicles (HFs). Rare events of deeper penetration in the SC and in the infundibulum of vellus HFs were observed at sites of high focal particle aggregations. Wide‐field 2 PM allows for imaging of nanoparticle penetration in large tissue blocks, whereas total internal reflection microscopy (TIRFM) enables selective detection of individual nanoparticles as well as clusters of nanoparticles in the SC and within the epidermal layer directly beneath the SC, thus confirming barrier crossing with high sensitivity.
Expanding the Clinical Spectrum of Phenotypes Caused by Pathogenic Variants in PLOD2
Authors: Leal Gabriela Ferraz , Nishimura Gen , Voss Ulrika , Bertola Débora Romeo , Åström Eva , Svensson Johan , Yamamoto Guilherme Lopes , Hammarsjö Anna , Horemuzova Eva , Papadogiannakis Nikos , Iwarsson Erik , Grigelioniene Giedre , Tham Emma
Published: November 2017

Osteogenesis imperfecta (OI) is a strikingly heterogeneous group of disorders with a broad range of phenotypic variations. It is also one of the differential diagnoses in bent bone dysplasias along with campomelic dysplasia and thanatophoric dysplasia and can usually be distinguished by decreased bone mineralization and bone fractures. Bent bone dysplasias also include syndromes such as kyphomelic dysplasia (MIM:211350) and mesomelic dysplasia Kozlowski-Reardon (MIM249710), both of which have been under debate regarding whether or not they are a real entity or simply a phenotypic manifestation of another dysplasia including OI. Bruck syndrome type 2 (BRKS2; MIM:609220) is a rare form of autosomal recessive OI caused by biallelic PLOD2 variants and is associated with congenital joint contractures with pterygia. In this report, we present six patients from four families with novel PLOD2 variants. All cases had multiple fractures. Other features ranged from prenatal lethal severe angulation of the long bones as in kyphomelic dysplasia and mesomelic dysplasia Kozlowski-Reardon through classical Bruck syndrome to moderate OI with normal joints. Two siblings with a kyphomelic dysplasia-like phenotype who were stillborn had compound heterozygous variants in PLOD2 (p.Asp585Val and p.Ser166*). One infant who succumbed at age 4 months had a bent bone phenotype phenotypically like skeletal dysplasia Kozlowski-Reardon (with mesomelic shortening, camptodactyly, retrognathia, cleft palate, skin dimples, but also with fractures). He was homozygous for the nonsense variant (p.Trp561*). Two siblings had various degrees of Bruck syndrome caused by the homozygous missense variant, p.His687Arg. Furthermore a boy with a clinical presentation of moderate OI had a possibly pathogenic homozygous variant p.Trp588Cys. Our experience of six patients with biallelic pathogenic variants in PLOD2 expands the phenotypic spectrum in the PLOD2-related phenotypes. © 2017 American Society for Bone and Mineral Research.

Abstract
The prognostic impact of serum bilirubin in stage IV colorectal cancer patients
Authors: Yang Lin , Ge Lu‐Yao , Yu Ting , Liang Yan , Yin Ying , Chen Hong
Published: November 2017

Background

Bilirubin played a great role in antioxidation and anticancer and has been considered as a promising prognostic factor of non‐liver disease‐related death in various cancers. The aim of this study was to assess the prognostic value of pre‐treatment serum bilirubin in stage IV CRC patients.

Methods

Serum bilirubin including TBIL, DBIL, and IBI which were tested at pre‐treatment were investigated in 154 stage IV CRC patients in Zhongda Hospital, Nanjing, China, from July 2005 to July 2011. X‐tile program was used to determine the optimal cut‐off values of these three biomarkers. Kaplan‐Meier analysis, univariate, and multivariate cox regression as well as time‐dependent ROC curve analysis were performed to evaluate the relations between serum bilirubin and survival outcomes.

Results

We got the results that the optimal cut‐off points of serum TBIL, DBIL, and IBI levels were 12.9, 6.1, and 4.8 μmol/L, respectively. Univariate analysis showed that elevated TBIL, DBIL, and CEA were significantly associated with poor 5‐year OS in stage IV CRC patients. Multivariate cox analysis indicated that the high DBIL (HR=1.603, 95%CI=1.053‐2.442, P<.028) and CEA (HR=1.785, 95%CI=1.123‐2.837, P=.014) could be identified as independent factors for poor OS. Furthermore, time‐dependent ROC curves demonstrated that high DBIL had similar prognostic efficacy as elevated CEA for poor OS (AUC=0.63 and 0.61, respectively).

Conclusions

Pre‐treatment elevated TBIL and DBIL levels were associated with poor OS in stage IV CRC patients. Moreover, DBIL could be considered as an independent prognostic biomarker for OS. Furthermore, DBIL had similar prognostic efficacy as CEA for OS.
Pharmacokinetic and Pharmacodynamic Modeling of Serum Etrolizumab and Circulating β7 Receptor Occupancy in Patients With Ulcerative Colitis
Authors: Wei Xiaohui , Gibiansky Leonid , Wang Yehong , Fuh Franklin , Erickson Rich , O'Byrne Sharon , Tang Meina T.
Published: November 2017

Etrolizumab, a humanized monoclonal antibody, specifically binds to the β7 subunit of the heterodimeric integrins α4β7 and αEβ7. Pharmacokinetic (PK) and pharmacodynamic (PD) data were collected from an etrolizumab phase 1 trial in patients with moderate to severe ulcerative colitis (UC). We developed a mechanism‐based model to simultaneously describe the kinetics of serum etrolizumab concentration and free β7 receptors on circulating intestinal‐homing CD4+T lymphocytes. Included in the analysis were 38 phase 1 UC patients who received single or 3 monthly doses of etrolizumab intravenously or subcutaneously across a dose range of 0.3 to 10 mg/kg. A quasi–steady‐state target‐mediated drug disposition model was developed to describe the dynamic interaction between serum etrolizumab concentration and free β7 receptors on intestinal‐homing CD4+T lymphocytes in UC patients. The time profiles of serum etrolizumab and absolute counts of β7+lymphocytes (expressed as percentage of baseline level) were well described by the quasi–steady‐state target‐mediated drug disposition model. The model was able to characterize the maximum drug occupancy of β7 receptors on intestinal‐homing CD4+T lymphocytes and the concentration‐dependent duration of occupancy. The 90% effective concentration for etrolizumab to saturate the β7 receptors on intestinal homing CD4+T cells was 1.3 μg/mL. PK and PD profiles predicted by the model were consistent with observations from a subsequent phase 2 study. In conclusion, an integrated PK/PD model developed in this analysis reasonably described serum etrolizumab PK profiles and the relationship between PK and PD (free β7 receptors on circulating intestinal‐homing CD4+T lymphocytes) in UC patients.
The Effect of Food or Omeprazole on the Pharmacokinetics of Osimertinib in Patients With Non‐Small‐Cell Lung Cancer and in Healthy Volunteers
Authors: Vishwanathan Karthick , Dickinson Paul A. , Bui Khanh , Cassier Philippe A. , Greystoke Alastair , Lisbon Eleanor , Moreno Victor , So Karen , Thomas Karen , Weilert Doris , Yap Timothy A. , Plummer Ruth
Published: November 2017

Two phase 1, open‐label studies assessed the impact of food or gastric pH modification (omeprazole) on the exposure and safety/tolerability of osimertinib and its metabolites. The food effect study was an open‐label, 2‐period crossover study in patients with advanced non‐small‐cell lung cancer, randomized into 2 treatment sequences: single‐dose osimertinib 80 mg in a fed then fasted state or fasted then fed. The gastric pH study was an open‐label, 2‐period fixed sequence study assessing the effect of omeprazole on osimertinib exposure in healthy male volunteers. In period 1, volunteers received omeprazole 40 mg (days 1‐4), then omeprazole 40 mg plus osimertinib 80 mg (day 5). In period 2, volunteers received osimertinib 80 mg alone (single dose). Blood samples were collected at prespecified time points for pharmacokinetic analyses. Safety/tolerability was also assessed. In the food effect study 38 patients were randomized to fed/fasted (n = 18) or fasted/fed (n = 20) sequences with all patients completing treatment. Coadministration with food did not affect osimertinib exposure (geometric least‐squares mean ratios [90% confidence intervals]: 106.05% [94.82%, 118.60%] [area under the plasma concentration time curve from zero to 72 hours] and 92.75% [81.40%, 105.68%] [maximum plasma concentration]). In the gastric pH study (n = 68 received treatment, n = 47 completed the study), coadministration with omeprazole did not affect osimertinib exposure (geometric least‐squares mean ratios 106.66% [100.26%, 113.46%] [area under the concentration‐time curve], 101.65% [94.65%, 109.16%] [peak concentration]). Osimertinib was well tolerated in both studies. Osimertinib may be administered without regard to food. Dose restriction is not required in patients whose gastric pH may be altered by concomitant agents or medical conditions. ClinicalTrials.gov: NCT02224053, NCT02163733.
Thoroughly dispersed colorings
Authors: Goddard Wayne , Henning Michael A.
Published: November 2017

We consider (not necessarily proper) colorings of the vertices of a graph where every color is thoroughly dispersed, that is, appears in every open neighborhood. Equivalently, every color is a total dominating set. We define as the maximum number of colors in such a coloring and as the fractional version thereof. In particular, we show that every claw‐free graph with minimum degree at least  two has  and this is best possible. For planar graphs, we show that every triangular disc has and this is best possible, and that every planar graph has and this is best possible, while we conjecture that every planar triangulation has . Further, although there are arbitrarily large examples of connected, cubic graphs with , we show that for a connected cubic graph . We also consider the related concepts in hypergraphs.
Physical stability of moisture‐sensitive tablets stored in a canister or as a unit‐dose
Authors: Bjerknes Kathrin , Helmizadeh Zahra , Brustugun Jørgen , Smistad Gro
Published: November 2017

Background

Knowledge about the long‐term stability of tablets outside the original container, e.g. as unit‐doses, is limited. This leaves the pharmacist with the dilemma of seeking improved patient safety by use of unit‐doses on one side, versus the lack of knowledge about the stability of the repackaged drug on the other.

Aim

To screen the physical stability of moisture‐sensitive repackaged tablets to identify those with the need for further chemical stability testing.

Method

The physical stability of commercially available tablets (16 products) was investigated after 6 months of storage at ambient conditions in canisters for unit‐dose production and after 3 months of storage as unit‐doses in a climate chamber at 25°C/60% relative humidity (RH). Changes in appearance, colour and mass were investigated in addition to changes in disintegration time, friability and resistance to crushing.

Results

The appearance and results of the physical tests for all products were acceptable and within the requirements of the European Pharmacopoeia, except for sodium valproate enteric‐coated tablets (Orfiril). These tablets were significantly altered after 3 months of storage as unit‐doses at 25°C/60% RH. However, when stored at ambient conditions the tablets complied with the tests.

Conclusions

The current study was a screening study limited to the investigation of the physical stability of a selection of moisture‐sensitive repackaged tablets. However, although the physical stability is acceptable, the chemical stability and dissolution rate may be altered. The physical tests outlined are simple but could be suitable for selecting candidates for further chemical stability testing.
Discrimination between oral cancer and healthy cells based on the adenine signature detected by using Raman spectroscopy
Authors: Dai Wei‐Yun , Lee Szetsen , Hsu Yih‐Chih
Published: November 2017

We report the detection of oral cancer cells using Raman spectroscopy as a noninvasive diagnostic tool. Gold nanoparticles, synthesized by using sodium citrate as a reducing agent, were used as surface‐enhanced Raman scattering substrates to detect human oral squamous cell carcinoma cell lines (SAS and SCC4) with fibroblasts cell lines as the control. We have observed the characteristic Raman signal of adenine at 735 cm−1, which indicates the oral cancer from nucleic acid. The result showed that there were significant differences (p < .05) between oral cancer cell and normal fibroblast cell lines. To prove that adenine is a robust biomarker for cancer cells, we have also compared the Raman spectra of esophageal cancer (CE48T and CE81T) and normal (Het‐1A) cells. Significant differences (p < .05) were also observed between esophageal cancer and normal cells. The detection of adenine Raman signal from cell lines has been proven to be potential to establish a highly distinguishable Raman diagnostic method for cancer detection.
Phenolic and physicochemical stability of a functional beverage powder mixture during storage: effect of the microencapsulant inulin and food ingredients
Authors: de Beer Dalene , Pauck Claire E , Aucamp Marique , Liebenberg Wilna , Stieger Nicole , van der Rijst Marieta , Joubert Elizabeth
Published: November 2017

BACKGROUND

The need for a convenience herbal iced tea product with reduced kilojoules merited investigation of the shelf‐life of powder mixtures containing a green Cyclopia subternata Vogel (honeybush) extract with proven blood glucose‐lowering activity and alternative sweetener mixture.

RESULTS

Prior to long‐term storage testing, the wettability of powder mixtures containing food ingredients and the compatibility of their components were confirmed using the static sessile drop method and isothermal microcalorimetry, respectively. The powders packed in semi‐sealed containers remained stable during storage at 25 °C/60% relative humidity (RH) for 6 months, except for small losses of specific phenolic compounds, namely mangiferin, isomangiferin, 3‐β‐d‐glucopyranosyliriflophenone, vicenin‐2 and 3′,5′‐di‐β‐d‐glucopyranosylphloretin, especially when both citric acid and ascorbic acid were present. These acids drastically increased the degradation of phenolic compounds under accelerated storage conditions (40 °C/75% RH). Accelerated storage also caused changes in the appearance of powders and the colour of the reconstituted beverage solutions. Increased moisture content and aw of the powders, as well as moisture released due to dehydration of citric acid monohydrate, contributed to these changes.

CONCLUSION

A low‐kilojoule honeybush iced tea powder mixture will retain its functional phenolic compounds and physicochemical properties during shelf‐life storage at 25 °C for 6 months. © 2017 Society of Chemical Industry
Exposure to Trauma and Mental Health Service Engagement Among Adults Who Were Children of the Northern Ireland Troubles of 1968 to 1998
Authors: Ferry Finola , Ennis Edel , Bunting Brendan , Murphy Samuel , Bolton David , O'Neill Siobhan
Published: November 2017

Northern Ireland is an appropriate region to examine the impact of traumatic experiences, owing to the many years of civil violence that have characterized its recent history, known colloquially as the “Troubles.” Given the prominence of traumatic experiences among the aging population of Northern Ireland (NI), an evidence base is required to inform the planning and provision of effective mental health and other services. We analyzed the follow‐up interviews (n = 225) of individuals from the Northern Ireland Study of Health and Stress (NISHS), aged 45 years and older, who experienced one or more conflict‐related traumatic events. This study demonstrated that in NI traumatic events, such as being involved in an explosion, seeing someone killed or seriously injured, and living in a region of terror were most likely to be related to the Troubles. However, event types that we had not previously known to be related to conflict (such as the sudden death of a loved one), were also often related to the Troubles. Two‐thirds of participants (67.1%) reported exposure to a Troubles‐related event, and 57.8% reported being a civilian in a region of terror. The vast majority (85.9%) of participants who experienced a Troubles‐related trauma never sought help, despite 59.1% meeting the criteria for a lifetime mental disorder. The reasons for not seeking help and sources of help are outlined. Policy makers must address Troubles‐related mental health effects, in terms of how they carry forward into aging, and consider ways of improving engagement with services and treatments.
Mass spectrometry of aerosol particle analogues in molecular beam experiments
Authors: Fárník Michal , Lengyel Jozef
Published: November 2017

Nanometer‐size particles such as ultrafine aerosol particles, ice nanoparticles, water nanodroplets, etc, play an important, however, not yet fully understood role in the atmospheric chemistry and physics. These species are often composed of water with admixture of other atmospherically relevant molecules. To mimic and investigate such particles in laboratory experiments, mixed water clusters with atmospherically relevant molecules can be generated in molecular beams and studied by various mass spectrometric methods. The present review demonstrates that such experiments can provide unprecedented details of reaction mechanisms, and detailed insight into the photon‐, electron‐, and ion‐induced processes relevant to the atmospheric chemistry. After a brief outline of the molecular beam preparation, cluster properties, and ionization methods, we focus on the mixed clusters with various atmospheric molecules, such as hydrated sulfuric acid and nitric acid clusters, NxOy and halogen‐containing molecules with water. A special attention is paid to their reactivity and solvent effects of water molecules on the observed processes.
Rating Scales for Motor Symptoms and Signs in Huntington's Disease: Critique and Recommendations
Authors: Mestre Tiago A. , Forjaz Maria João , Mahlknecht Philipp , Cardoso Francisco , Ferreira Joaquim J. , Reilmann Ralf , Sampaio Cristina , Goetz Christopher G. , Cubo Esther , Martinez‐Martin Pablo , Stebbins Glenn T. ,   the Members of the Movement Disorder Society Committee on Rating Scales Development
Published: November 2017

Motor symptoms are a major feature of Huntington's disease (HD). The International Parkinson and Movement Disorder Society (MDS) commissioned the assessment of the clinimetric properties of motor rating scales in HD to make recommendations regarding their use, following previously established standardized criteria. After a systematic literature search, a total of 6 rating scales assessing motor symptoms and signs in HD were included for review. Performance testing (reviewed elsewhere) and quantitative motor rating methods were excluded. Only the Unified Huntington's Disease Rating Scale‐Total Motor Score (UHDRS‐TMS) was classified as “recommended” for assessing the severity of motor signs in HD. The following scales were classified as “suggested”: Abnormal Involuntary Movement Scale, the UHDRS‐TMS4, the Quantified Neurological Examination, and the Marsden and Quinn Chorea Severity Scale. The committee also concluded that further assessment of existing rating scales, including the UHDRS‐TMS, is necessary to determine sensitivity to change and to screening for the presence of motor signs specific to HD. There is also a need to develop a motor rating scale to be used in positive gene carriers with subtle but not definite motor signs.
Prediction of the thermomechanical behavior of particle reinforced shape memory polymers
Authors: Pan Zhouzhou , Huang Rong , Liu Zishun
Published: November 2017

Shape memory polymers (SMPs) have drawn wide attention because they can recover from a deformed shape to their original shape by a certain external stimulus. However, Low modulus and recovery stress limit the application and development of SMPs. It is imperative to find an approach to improve or reinforce these mechanical properties of SMPs. In the present study, the mechanical properties and shape memory effect of spherical particle reinforced shape memory polymer composite (SMPC) are studied numerically through a representative volume element created by using the random sequential adsorption algorithm. The linear viscoelastic model is used to describe the thermomechanical behavior of the SMP matrix while the fillers are regarded as linear elastic glass beads. From our study, we find the elastic modulus and recovery stress are increased considerably by adding 15% volume fraction glass beads into the SMP. Furthermore, it is observed that filling particles slightly deteriorates the shape fixity ratio, however, hardly changes the effective shape recovery ratio for dilute inclusion cases. Our research demonstrates the feasibility of using glass beads to adjust the modulus and recovery stress of SMPs without dramatically affect the shape memory effects. We hope our findings would provide researchers with guides in designing and optimizing SMPC applications. POLYM. COMPOS., 40:353–363, 2019. © 2017 Society of Plastics Engineers
Numerical modeling of moisture diffusion in an unidirectional fiber‐reinforced polymer composite
Authors: Pan Yunfeng , Xian Guijun , Li Hui
Published: November 2017

The durability of a fiber‐reinforced polymer (FRP) composite is dependent on the diffusion of water or corrosive media in them. In this paper, the finite element method (FEM) is adopted to investigate the effects of neighborhood filaments in cell model process, as well as the fiber volume fraction, fiber arrangements and fiber in contact on the moisture diffusion in FRPs. The diffusivity coefficient determined by the modified predicted theoretical model is larger than the FEM results. The filaments affect the moisture diffusion process significantly within the 1.2∼1.4 times of the fiber radius, while the fiber arrangement plays a slight effect relatively. In addition, the tortuosity of the diffusion path owing to the fiber contact is found to play a dominant role on the moisture diffusion. The diffusivity coefficient of the water in the fiber‐resin interphase zone is much smaller than that of the matrix, due to the effect of the existence of the carbon fibers. For the current CFRP system, the diffusivity of resin matrix is 1.12 × 10−7mm2/s and the diffusivity coefficient of the water in the interphase is only 25% of that of the matrix. POLYM. COMPOS., 40:401–413, 2019. © 2017 Society of Plastics Engineers
Hyperoxia induces paracellular leak and alters claudin expression by neonatal alveolar epithelial cells
Authors: Vyas‐Read Shilpa , Vance Rachel J. , Wang Wenyi , Colvocoresses‐Dodds Jennifer , Brown Lou Ann , Koval Michael
Published: November 2017

Background

Premature neonates frequently require oxygen supplementation as a therapeutic intervention that, while necessary, also exposes the lung to significant oxidant stress. We hypothesized that hyperoxia has a deleterious effect on alveolar epithelial barrier function rendering the neonatal lung susceptible to injury and/or bronchopulmonary dysplasia (BPD).

Materials and Methods

We examined the effects of exposure to 85% oxygen on neonatal rat alveolar barrier function in vitro and in vivo. Whole lung was measured using wet‐to‐dry weight ratios and bronchoalveolar lavage protein content and cultured primary neonatal alveolar epithelial cells (AECs) were measured using transepithelial electrical resistance (TEER) and paracellular flux measurements. Expression of claudin‐family tight junction proteins, E‐cadherin and the Snail transcription factor SNAI1 were measured by Q‐PCR, immunoblot and confocal immunofluorescence microscopy.

Results

Cultured neonatal AECs exposed to 85% oxygen showed impaired barrier function. This oxygen‐induced increase in paracellular leak was associated with altered claudin expression, where claudin‐3 and ‐18 were downregulated at both the mRNA and protein level. Claudin‐4 and ‐5 mRNA were also decreased, although protein expression of these claudins was largely maintained. Lung alveolarization and barrier function in vivo were impaired in response to hyperoxia. Oxygen exposure also significantly decreased E‐cadherin expression and induced expression of the SNAI1 transcription factor in vivo and in vitro.

Conclusions

These data support a model in which hyperoxia has a direct impact on alveolar tight and adherens junctions to impair barrier function. Strategies to antagonize the effects of high oxygen on alveolar junctions may potentially reverse this deleterious effect.
Homology‐based hydrogen bond information improves crystallographic structures in the PDB
Authors: van Beusekom Bart , Touw Wouter G. , Tatineni Mahidhar , Somani Sandeep , Rajagopal Gunaretnam , Luo Jinquan , Gilliland Gary L. , Perrakis Anastassis , Joosten Robbie P.
Published: November 2017

The Protein Data Bank (PDB) is the global archive for structural information on macromolecules, and a popular resource for researchers, teachers, and students, amassing more than one million unique users each year. Crystallographic structure models in the PDB (more than 100,000 entries) are optimized against the crystal diffraction data and geometrical restraints. This process of crystallographic refinement typically ignored hydrogen bond (H‐bond) distances as a source of information. However, H‐bond restraints can improve structures at low resolution where diffraction data are limited. To improve low‐resolution structure refinement, we present methods for deriving H‐bond information either globally from well‐refined high‐resolution structures from the PDB‐REDO databank, or specifically from on‐the‐fly constructed sets of homologous high‐resolution structures. Refinement incorporating HOmology DErived Restraints (HODER), improves geometrical quality and the fit to the diffraction data for many low‐resolution structures. To make these improvements readily available to the general public, we applied our new algorithms to all crystallographic structures in the PDB: using massively parallel computing, we constructed a new instance of the PDB‐REDO databank (https://pdb-redo.eu). This resource is useful for researchers to gain insight on individual structures, on specific protein families (as we demonstrate with examples), and on general features of protein structure using data mining approaches on a uniformly treated dataset.
Predictive Performance of Physiologically Based Pharmacokinetic Models for the Effect of Food on Oral Drug Absorption: Current Status
Authors: Li Mengyao , Zhao Ping , Pan Yuzhuo , Wagner Christian
Published: November 2017

A comprehensive search in literature and published US Food and Drug Administration reviews was conducted to assess whether physiologically based pharmacokinetic (PBPK) modeling could be prospectively used to predict clinical food effect on oral drug absorption. Among the 48 resulted food effect predictions, ∼50% were predicted within 1.25‐fold of observed, and 75% within 2‐fold. Dissolution rate and precipitation time were commonly optimized parameters when PBPK modeling was not able to capture the food effect. The current work presents a knowledgebase for documenting PBPK experience to predict food effect.
Highly Resistant Zero‐Order Waveplates Based on All‐Silica Multilayer Coatings
Authors: Grinevičiūtė Lina , Andrulevičius Mindaugas , Melninkaitis Andrius , Buzelis Rytis , Selskis Algirdas , Lazauskas Algirdas , Tolenis Tomas
Published: November 2017

Waveplates, used to modify polarization state of light, are integral part of high‐power lasers. Classical approach to waveplate manufacturing is based on combination of birefringent crystalline materials and deposition of nonpolarizing antireflection (AR) coatings. Their limitation to withstand maximal peak power is determined by laser‐induced damage (LID) phenomena, mainly determined by low band‐gap materials used in AR coatings. In this study, a novel multi‐layer approach of high band‐gap birefringent coatings was proposed and investigated to overcome this limitation. Three eligible candidate materials, namely LaF3, Al2O3, and SiO2 are investigated. Structural and optical analysis reveal superior properties of silica for UV spectral range. Zero‐order thin film retarders based on all‐silica nano‐structures are fabricated by oblique angle deposition process. Low optical losses and high transparency (T ∼ 99%) are demonstrated while indicating potential to withstand high laser fluence of 40 J cm−2 in nanosecond regime at 355 nm wavelength. Such waveplates can essentially improve maximal tolerated peak power and thus allow production of more compact optical systems, even when high laser power is used.