bluuebunny/crossref_metadata_2025 huggingface dataset:
The Application of Ultrasonic Vibration in Human Sperm Cryopreservation as a Novel Method for the Modification of Physicochemical Characteristics of Freezing Media
Authors: Dariush Gholami , Gholamhossein Riazi , Rouhollah Fathi , Mahmood Ghaffari Seyed , Abdolhossein Shahverdi , Mohsen Sharafi , Loghman Alaei
Published: July 2019

The application of ultrasonic vibration was performed to modify the water molecules as the main compositions of the freezing medium used for human sperm cryopreservation. Different time periods of ultrasonic vibration (ULV) at the frequency of 28 kHz were applied for the evaluation of physicochemical properties of the water molecules. The most significant bubble size, zeta potential, and pH were obtained for the water molecules exposed to ultrasonic vibrations for 18 minutes and this time period was selected for further experiments due to the optimum results. In the next stage, semen samples were diluted with freezing medium containing ULV-exposed water and then cryopreserved. All the semen parameters were significantly reduced in cryopreserved groups as compared with the fresh control group. The highest percentage of total and progressive motility, viability, membrane and DNA integrity, and mitochondrial membrane potential were observed in frozen ULV compared with the frozen control. The rate of apoptosis in frozen ULV was significantly lower than that of in the frozen control. Furthermore, the gene expression ratios of α- and β-tubulins were significantly increased during cryopreservation, while the expression ratio of the tubulin polymerization promoting protein (TPPP) gene was decreased. Similar results were also observed when the protein levels of the genes mentioned earlier were evaluated by the ELISA method. Therefore, the changes in physicochemical properties of the freezing medium of human sperm cryopreservation using ULV can improve the quality of frozen products.
High Fat Diet Triggers a Reduction in Body Fat Mass in Female Mice Deficient for Utx demethylase
Authors: Ota Kazushige , Komuro Akiyoshi , Amano Hisayuki , Kanai Akinori , Ge Kai , Ueda Takeshi , Okada Hitoshi
Published: July 2019

Obesity increases the risk of metabolic disorders like diabetes mellitus and dyslipidemia. However, how metabolic status is sensed and regulates cellular behavior is unclear. Utx is an H3K27 demethylase that influences adipocyte function in vitro. To examine its role in vivo, we generated mice lacking Utx in adipocytes (UtxAKO). Although all UtxAKO mice grew normally on a normal chow diet (NCD), female UtxAKO mice on a high fat diet (HFD) showed striking reductions in body fat compared to control mice (Ctrl). Gene expression profiling of adipose tissues of HFD-fed UtxAKO female mice revealed decreased expression of rate-limiting enzymes of triacylglycerol synthesis but increased expression of those of cholesterol/steroid hormone synthesis. Moreover, these animals resisted adiposity induced by ovariectomy and exhibited increased estrogen in visceral adipose tissues. Thus, upon HFD feeding, Utx regulates lipid metabolism in adipose tissues by influencing the local hormonal microenvironment. Conversely, Utx deficiency skews lipid catabolism to enhance cholesterol/steroid hormone production and repress obesity.
Identification of GSK3β inhibitor kenpaullone as a temozolomide enhancer against glioblastoma
Authors: Kitabayashi Tomohiro , Dong Yu , Furuta Takuya , Sabit Hemragul , Jiapaer Shabierjiang , Zhang Jiakang , Zhang Guangtao , Hayashi Yasuhiko , Kobayashi Masahiko , Domoto Takahiro , Minamoto Toshinari , Hirao Atsushi , Nakada Mitsutoshi
Published: July 2019

Cancer stem cells are associated with chemoresistance and rapid recurrence of malignant tumors, including glioblastoma (GBM). Although temozolomide (TMZ) is the most effective drug treatment for GBM, GBM cells acquire resistance and become refractory to TMZ during treatment. Therefore, glioma stem cell (GSC)-targeted therapy and TMZ-enhancing therapy may be effective approaches to improve GBM prognosis. Many drugs that suppress the signaling pathways that maintain GSC or enhance the effects of TMZ have been reported. However, there are no established therapies beyond TMZ treatment currently in use. In this study, we screened drug libraries composed of 1,301 existing drugs using cell viability assays to evaluate effects on GSCs, which led to selection of kenpaullone, a kinase inhibitor, as a TMZ enhancer targeting GSCs. Kenpaullone efficiently suppressed activity of glycogen synthase kinase (GSK) 3β. Combination therapy with kenpaullone and TMZ suppressed stem cell phenotype and viability of both GSCs and glioma cell lines. Combination therapy in mouse models significantly prolonged survival time compared with TMZ monotherapy. Taken together, kenpaullone is a promising drug for treatment of GBM by targeting GSCs and overcoming chemoresistance to TMZ.
Evidence for potassium transport activity of Arabidopsis KEA1-KEA6
Authors: Tsujii Masaru , Kera Kota , Hamamoto Shin , Kuromori Takashi , Shikanai Toshiharu , Uozumi Nobuyuki
Published: July 2019

Arabidopsis thaliana contains the putative K+ efflux transporters KEA1-KEA6, similar to KefB and KefC of Escherichia coli. KEA1-KEA3 are involved in the regulation of photosynthetic electron transport and chloroplast development. KEA4-KEA6 mediate pH regulation of the endomembrane network during salinity stress. However, the ion transport activities of KEA1-KEA6 have not been directly characterized. In this study, we used an E. coli expression system to examine KEA activity. KEA1-KEA3 and KEA5 showed bi-directional K+ transport activity, whereas KEA4 and KEA6 functioned as a K+ uptake system. The thylakoid membrane-localized Na+/H+ antiporter NhaS3 from the model cyanobacterium Synechocystis is the closest homolog of KEA3. Changing the putative Na+/H+ selective site of KEA3 (Gln-Asp) to that of NhaS3 (Asp-Asp) did not alter the ion selectivity without loss of K+ transport activity. The first residue in the conserved motif was not a determinant for K+ or Na+ selectivity. Deletion of the possible nucleotide-binding KTN domain from KEA3 lowered K+ transport activity, indicating that the KTN domain was important for this function. The KEA3-G422R mutation discovered in the Arabidopsis dpgr mutant increased K+ transport activity, consistent with the mutant phenotype. These results indicate that Arabidopsis KEA1-KEA6 act as K+ transport systems, and support the interpretation that KEA3 promotes dissipation of ΔpH in the thylakoid membrane.
Realization of Bidirectional, Bandwidth-Enhanced Metamaterial Absorber for Microwave Applications
Authors: Stephen Lincy , Yogesh N. , Subramanian V.
Published: July 2019

The ever-increasing interest towards metamaterial absorbers owes to its remarkable features such as ultra-thin nature and design flexibility. Subduing the inherent narrow bandwidth of such absorbers is the prime goal in metamaterial absorber research, as this can widen the applications areas. A greater challenge is to construct bidirectional absorber, which provides direction-insensitive absorption, as most of the existing designs exhibit single sided absorption due to the complete metal film used in the design. This work presents the realization of a bidirectional, bandwidth-enhanced metamaterial absorber with basic elements such as strips and squares optimized to have adjacent resonances leading to a bandwidth-enhanced absorption. The structural evolution of the constituent metallic components towards the formation of bandwidth-enhanced absorption is described. The bidirectional absorber exhibits more than 90% absorption between 13.40 GHz and 14.25 GHz from the two incident directions. The mechanism of absorption is studied with the surface current analysis and the effective parameters of the structure. The choice of the metallic components with four-fold rotation symmetry renders the proposed design to be polarization independent and wide-angle receptive. The numerical studies are verified experimentally at microwave frequencies, which shows a good agreement between them.
Novel acoustic flat focusing based on the asymmetric response in parity-time-symmetric phononic crystals
Authors: Yang Hang , Zhang Xin , Liu Yuechang , Yao Yuanwei , Wu Fugen , Zhao Degang
Published: July 2019

We present a two-dimensional (2D) parity-time-symmetric (PT-symmetry) phononic crystals (PCs) with balanced gain and loss medium. Using the super cell method of rectangular lattice, we exhibit the thresholdless spontaneous PT-symmetry breaking in the band structure. The numerical results show that the asymmetric scattering properties obviously occur in a non-Hermitian system. At two specific incident frequencies, unidirectional reflectionless and perfect transmission behaviors exist individually in opposite directions, which are accompanied by a phase transition of π. Based on the generalized Snell’s law, combining such a PT-symmetric medium, we design a novel metamaterial crystal for PT-symmetric acoustic flat focusing. Its focus frequency can also be modulated by the gain/loss parameter. The novel flat focusing based on the PT-symmetry that we propose opens a new door for high-dimensional applications of non-Hermitian metamaterials in acoustic wave manipulation.
ToF-SIMS mediated analysis of human lung tissue reveals increased iron deposition in COPD (GOLD IV) patients
Authors: Najafinobar Neda , Venkatesan Shalini , von Sydow Lena , Klarqvist Magnus , Olsson Henric , Zhou Xiao-Hong , Cloonan Suzanne M. , Malmberg Per
Published: July 2019

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease that is currently the third leading cause of death worldwide. Recent reports have indicated that dysfunctional iron handling in the lungs of COPD patients may be one contributing factor. However, a number of these studies have been limited to the qualitative assessment of iron levels through histochemical staining or to the expression levels of iron-carrier proteins in cells or bronchoalveolar lavage fluid. In this study, we have used time of flight secondary ion mass spectrometry (ToF-SIMS) to visualize and relatively quantify iron accumulation in lung tissue sections of healthy donors versus severe COPD patients. An IONTOF 5 instrument was used to perform the analysis, and further multivariate analysis was used to analyze the data. An orthogonal partial least squares discriminant analysis (OPLS-DA) score plot revealed good separation between the two groups. This separation was primarily attributed to differences in iron content, as well as differences in other chemical signals possibly associated with lipid species. Further, relative quantitative analysis revealed twelve times higher iron levels in lung tissue sections of COPD patients when compared to healthy donors. In addition, iron accumulation observed within the cells was heterogeneously distributed, indicating cellular compartmentalization.
Independent Predictors of Cardiac Mortality and Hospitalization for Heart Failure in a Multi-Ethnic Asian ST-segment Elevation Myocardial Infarction Population Treated by Primary Percutaneous Coronary Intervention
Authors: Bulluck Heerajnarain , Zheng Huili , Chan Mark Y. , Foin Nicolas , Foo David C. , Lee Chee W. , Lim Soo T. , Sahlen Anders , Tan Huay C. , Tan Jack W. , Tong Khim L. , Wong Aaron S. , Wong Philip E. , Yeo Khung K. , Foo Ling L. , Chua Terrance S. , Koh Tian H. , Hausenloy Derek J.
Published: July 2019

We aimed to identify independent predictors of cardiac mortality and hospitalization for heart failure (HHF) from a real-world, multi-ethnic Asian registry [the Singapore Myocardial Infarction Registry] of ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention. 11,546 eligible STEMI patients between 2008 and 2015 were identified. In-hospital, 30-day and 1-year cardiac mortality and 1-year HHF rates were 6.4%, 6.8%, 8.3% and 5.2%, respectively. From the derivation cohort (70% of patients), age, Killip class and cardiac arrest, creatinine, hemoglobin and troponin on admission and left ventricular ejection fraction (LVEF) during hospitalization were predictors of in-hospital, 30-day and 1-year cardiac mortality. Previous ischemic heart disease (IHD) was a predictor of in-hospital and 30-day cardiac mortality only, whereas diabetes was a predictor of 1-year cardiac mortality only. Age, previous IHD and diabetes, Killip class, creatinine, hemoglobin and troponin on admission, symptom-to-balloon-time and LVEF were predictors of 1-year HHF. The c-statistics were 0.921, 0.901, 0.881, 0.869, respectively. Applying these models to the validation cohort (30% of patients) showed good fit and discrimination (c-statistic 0.922, 0.913, 0.903 and 0.855 respectively; misclassification rate 14.0%, 14.7%, 16.2% and 24.0% respectively). These predictors could be incorporated into specific risk scores to stratify reperfused STEMI patients by their risk level for targeted intervention.
Fast stimulated Raman and second harmonic generation imaging for intraoperative gastro-intestinal cancer detection
Authors: Sarri Barbara , Canonge Rafaël , Audier Xavier , Simon Emma , Wojak Julien , Caillol Fabrice , Cador Cécile , Marguet Didier , Poizat Flora , Giovannini Marc , Rigneault Hervé
Published: July 2019

Conventional haematoxylin, eosin and saffron (HES) histopathology, currently the ‘gold-standard’ for pathological diagnosis of cancer, requires extensive sample preparations that are achieved within time scales that are not compatible with intra-operative situations where quick decisions must be taken. Providing to pathologists a close to real-time technology revealing tissue structures at the cellular level with HES histologic quality would provide an invaluable tool for surgery guidance with evident clinical benefit. Here, we specifically develop a stimulated Raman imaging based framework that demonstrates gastro-intestinal (GI) cancer detection of unprocessed human surgical specimens. The generated stimulated Raman histology (SRH) images combine chemical and collagen information to mimic conventional HES histopathology staining. We report excellent agreements between SRH and HES images acquire on the same patients for healthy, pre-cancerous and cancerous colon and pancreas tissue sections. We also develop a novel fast SRH imaging modality that captures at the pixel level all the information necessary to provide instantaneous SRH images. These developments pave the way for instantaneous label free GI histology in an intra-operative context.
A composite of platelet-like orientated BiVO4 fused with MIL-125(Ti): Synthesis and characterization
Authors: Hlophe Philani Vusumuzi , Mahlalela Lwazi Charles , Dlamini Langelihle Nsikayezwe
Published: July 2019

The development of heterojunctions is the current focus of the scientific community as these materials are visible light active and the staggered positioning of their band edges combats electron-hole recombination which is the downside of most photocatalysts. In this work, a two- step hydrothermal synthesis protocol was utilized to fabricate a novel observable-light active material, composed of platelet-like BiVO4 and a titanium-based metal organic framework (MOF) called MIL-125(Ti). The tuning of specific morphologies, such as platelet-like in BiVO4, provides the exposure of most reactive facets which are more reactive towards photooxidation of organics in water, thus increasing their efficiency. The as-synthesized heterojunction was characterized by Transmission electron microscopy (TEM), scanning transmission microscopy (SEM), X-Ray diffraction (XRD), Raman spectroscopy, ultraviolet-visible diffuse reflectance spectra (UV-Vis DRS), X-Ray photoelectron spectroscopy (XPS) and photoluminescence (PL) spectra. The formation of the heterojunction lead to a positive shift of the 3-2 Bi:Ti valence band (VB) (1.78 eV) when compared to 1.27 eV VB position of BiVO4. The PL and photoelectrochemical measurements revealed that the heterojunction photocatalyst designated 3-2 Bi-Ti demonstrated inhibited recombination rate (platelet-like BiVO4 > 3-2 Bi:Ti (PM) > MIL-125 > 1–1 Bi:Ti > 2–3 Bi:Ti > 3-2 Bi:Ti) and highly efficient interfacial charge shuttle between platelet-like BiVO4 and MIL-125(Ti) through the formed n-n junction.
Differences in prognostic relevance of rectal magnetic resonance imaging findings before and after neoadjuvant chemoradiotherapy
Authors: Song Kwang-Seop , Lee Dong Woon , Kim Bun , Hur Bo Yun , Kim Min Jung , Kim Min Ju , Hong Chang Won , Park Sung Chan , Park Hyoung-Chul , Sohn Dae Kyung , Kim Byung Chang , Han Kyung Su , Oh Jae Hwan
Published: July 2019

This retrospective study was designed to compare prognostic relevance of magnetic resonance imaging (MRI) findings before and after neoadjuvant chemoradiotherapy (CRT). From 2002 to 2010, 399 patients who underwent surgery after CRT for rectal cancer (≥T3) and had adequate pre-CRT (mr) and post-CRT (ymr) MRI findings were examined. Factors examined included tumour (T), lymph node (N), mesorectal fascia (MRF), extramural venous invasion (EMVI), and tumour regression grade (TRG). Two Cox proportional hazard models were created using mr and ymr findings separately for overall survival (OS), disease-free survival (DFS), and local recurrence rate (LRR). Among mr findings, only mrEMVI was a significant prognostic factor for OS and DFS. Among ymr findings, ymrN, ymrMRF, and ymrEMVI were significant prognostic factors for OS and DFS, whereas ymrMRF and ymrEMVI were significant prognostic factors for LRR. C-indices tended to be higher for ymr findings than for mr findings (OS, 0.682 vs. 0.635; DFS, 0.660 vs. 0.631; LRR, 0.701 vs. 0.617). Survival outcomes of patients having all ymr risk factors were significantly poor (5-year OS, 52.4%; 5-year DFS, 38.1%; 5-year LRR, 27.7%). ymr findings showed better prognostic significance than mr findings. Among ymr findings, ymrN, ymrMRF, and ymrEMVI were independent prognostic factors for oncologic outcomes.
Sub-threshold micropulse laser treatment reduces inflammatory biomarkers in aqueous humour of diabetic patients with macular edema
Authors: Midena Edoardo , Micera Alessandra , Frizziero Luisa , Pilotto Elisabetta , Esposito Graziana , Bini Silvia
Published: July 2019

Subthreshold micropulse laser (SMPL) is a tissue-sparing technique whose efficacy is demonstrated for diabetic macular edema (DME) treatment. However, its mechanism of action is poorly known. A prospective observational study was performed on naïve DME patients treated with SMPL, to evaluate the changes of aqueous humor (AH) inflammatory and vaso-active biomarkers after treatments. AH samples of eighteen DME eyes were collected before and after SMPL. Ten non-diabetic AH samples served as controls. Full ophthalmic evaluation, spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography were performed in DME group. Glass chip protein array was used to quantify 58 inflammatory molecules. Central retinal thickness (CRT) and visual acuity were also monitored. Several molecules showed different concentrations in DME eyes versus controls (p value < 0.05). Fas Ligand (FasL), Macrophage Inflammatory Proteins (MIP)-1α, Regulated on Activation Normal T Cell Expressed and Secreted (RANTES) and Vascular Endothelial Growth Factor (VEGF) were increased in DME at baseline versus controls and decreased after SMPL treatments (p < 0.05). CRT reduction and visual acuity improvement were also found. Inflammatory cytokines, mainly produced by the retinal microglia, were significantly reduced after treatments, suggesting that SMPL may act by de-activating microglial cells, and reducing local inflammatory diabetes-related response.
Comparative clinical features and short-term outcomes of gastric and small intestinal gastrointestinal stromal tumours: a retrospective study
Authors: Yang Zhengyang , Wang Feng , Liu Song , Guan Wenxian
Published: July 2019

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract. Recent research has shown that small intestinal GISTs exhibit more aggressive features than gastric GISTs. To compare the clinical features of gastric and small intestinal GISTs for the further prediction of different prognoses, we conducted a retrospective study. 43 patients in the small intestine group and 97 in the gastric group were collected between January 2016 and December 2017. Data on demographics, preoperative lab results, clinicopathological results and surgical management were compared between groups. Significant elements were subsequently included in logistic regression analysis for further identification. The Kaplan-Meier method and log-rank test were used to calculate the relapse-free survival (RFS) rate and cumulative survival rate. Univariable analysis demonstrated that underlying disease, gastrointestinal (GI) bleeding, lymphocyte count, haemoglobin (Hb), albumin (ALB), platelet-to-lymphocyte ratio (PLR), thrombin time (TT), National Institutes of Health (NIH) category, Dog1, surgical procedure types and postoperative hospitalization were different between the two groups. Among these factors, logistic regression analysis identified that patients in small intestinal group exhibited significantly higher GI bleeding rate (p = 0.022), NIH category (p = 0.031), longer postoperative hospitalization time (p = 0.001) with lower TT value (p = 0.030) than those in gastric group. The log-rank test indicated that the location of the GIST (p = 0.022), GIST with GI bleeding (p = 0.027) and NIH category (p = 0.031) were independent prognostic predictors for poor outcome regarding RFS. Regarding cumulative survival, only the location of the GIST (p = 0.027) was an independent prognostic predictor for poor outcome. Thus, we concluded that small intestine GISTs were associated with lower TT, recurrent GI bleeding, advanced NIH category and extended postoperative hospitalization. Nevertheless, future multicentre prospective study are expected to validate our results.
Escitalopram Ameliorates Cognitive Impairment in D-Galactose-Injected Ovariectomized Rats: Modulation of JNK, GSK-3β, and ERK Signalling Pathways
Authors: Ibrahim Weam W. , Abdelkader Noha F. , Ismail Hesham M. , Khattab Mahmoud M.
Published: July 2019

Though selective serotonin reuptake inhibitors (SSRIs) have been found to increase cognitive performance in some studies on patients and animal models of Alzheimer’s disease (AD), other studies have reported contradictory results, and the mechanism of action has not been fully described. This study aimed to examine the effect of escitalopram, an SSRI, in an experimental model of AD and to determine the involved intracellular signalling pathways. Ovariectomized rats were administered D-galactose (150 mg/kg/day, i.p) over ten weeks to induce AD. Treatment with escitalopram (10 mg/kg/day, p.o) for four weeks, starting from the 7th week of D-galactose injection, enhanced memory performance and attenuated associated histopathological changes. Escitalopram reduced hippocampal amyloid β 42, β-secretase, and p-tau, while increasing α-secretase levels. Furthermore, it decreased tumor necrosis factor-α, nuclear factor-kappa B p65, and NADPH oxidase, while enhancing brain-derived neurotrophic factor, phospho-cAMP response element binding protein, and synaptophysin levels. Moreover, escitalopram diminished the protein expression of the phosphorylated forms of c-Jun N-terminal kinase (JNK)/c-Jun, while increasing those of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), extracellular signal-regulated kinase (ERK) and its upstream kinases MEK and Raf-1. In conclusion, escitalopram ameliorated D-galactose/ovariectomy-induced AD-like features through modulation of PI3K/Akt/GSK-3β, Raf-1/MEK/ERK, and JNK/c-Jun pathways.
Auristatin Payloads for Antibody–Drug Conjugates (ADCs)
Authors: Doronina Svetlana O. , Senter Peter D.
Published: July 2019

The auristatins are a synthetic-peptide-based drug class that inhibit tubulin polymerization and can display exceptionally high potency on a broad array of cancer cells. Consequently, a tremendous amount of research has been focused the design and utilization of auristatin family members within antibody–drug conjugates (ADCs) that deliver the drug to antigen-positive tumour cells. Molecules within the drug class are present within nearly half of all ADCs currently in clinical use, and one of them, monomethyl auristatin E (MMAE) is the active payload in the clinically-approved drug, brentuximab vedotin (ADCETRIS™). The history of the auristatins is described, starting from the discovery of the parental natural product dolastatin 10 to the design and validation of novel synthetic auristatins for targeted delivery. Focus is placed on the most well-known family members, MMAE and monomethyl auristatin F (MMAF), both of which have been extensively investigated in clinical settings. Also discussed are the unique features of the auristatins, such as synthetic accessibility and the ability to modify the drug for control of potency, cell permeability, bystander effects, susceptibility to multidrug resistance efflux, pharmacokinetics, activity and tolerability. The auristatins have featured prominently within modern ADC research, and new developments within the drug class indicate that they will continue to do so.
Traditional Cytotoxic Agents as Antibody–Drug Conjugate (ADC) Payloads
Authors: Pysz Ilona , Andriollo Paolo , Thurston David E.
Published: July 2019

In the second half of the last century, when the antibody–drug conjugate (ADC) approach was still in its infancy, the choice of potential payloads was based on a small group of cytotoxic molecules already exploited clinically as cancer chemotherapeutic agents. The three best known agents to be investigated in this context were the DNA cross-linking agent mitomycin C, the DNA intercalating agent, doxorubicin and the antimetabolite methotrexate. The mechanisms of action, pre-clinical and clinical use and toxicity of these three agents and their analogues are described in this chapter, along with examples of ADCs that incorporate them as payloads. The new ADC payload Eribulin is also described. The vinca alkaloids and Taxol™ analogues have also been used as ADC payloads, but these are described in Chapter 6.
Duocarmycin–PBD Dimers as Antibody–Drug Conjugate (ADC) Payloads
Authors: Pillow Thomas H. , Tercel Moana
Published: July 2019

Duocarmycin–pyrrolobenzodiazepine (PBD) dimers are DNA minor groove cross-linking agents formed by linking together an alkylating subunit from the duocarmycin and pyrrolobenzodiazepine classes of natural products. This chapter describes the structures of the 14 known examples, along with representative syntheses, and characterisation of the dimers' DNA alkylating ability (sequence selectivity and cross-linking efficiency) and cytotoxicity in a diverse range of tumour cell lines. One particular dimer example, with a relatively simple structure and concentrations giving 50% of maximum inhibition (IC50) values in the low pM range, has been incorporated into a variety of payload–linkers suitable for ADC application. The synthesis of one such payload–linker is described, along with antibody conjugation strategies, and preclinical anti-tumour activity of the resulting ADCs. The chapter concludes with a summary of closely-related duocarmycin–piperidinobenzodiazepine dimers which have also recently been disclosed as ADC payloads.
Tubulysins as Antibody–Drug Conjugate (ADC) Payloads
Authors: Parker Jeremy S.
Published: July 2019

The tubulysins are a family of naturally occurring tetrapeptides, originally isolated from a culture broth of strains of myxobacteria (soil bacterial). They are potent inhibitors of microtubule polymerisation, causing rapid disintegration of the cytoskeleton of dividing cells leading to apoptosis, and their potent activity against multidrug-resistant carcinoma cell lines has made them of interest as antibody–drug conjugate (ADC) payloads. As part of ADC development programs, significant work has been completed on increasing potency, structural simplification and molecular stability, as well as developing effective strategies for linking to antibodies. This work has been successful, with a number of antibody–tubulysin conjugates progressing into clinical use.
Protein Toxins as Antibody–Drug Conjugate (ADC) Payloads
Authors: Gehlsen Kurt R.
Published: July 2019

Targeted therapeutics such as antibody–drug conjugates and immunotoxins represent a new era of therapeutic intervention aimed at improving patient outcomes by reducing off-target toxicities and increasing drug concentrations at the intended disease target. Targeted delivery of protein-based therapeutic payloads and biological-response-modifying proteins, like cytokines, provides another approach and therapeutic mechanisms to modify the tissue microenvironment. This chapter will focus on protein-based payloads that can be delivered with targeting agents, such as antibodies, antibody-like scaffolds, ligands or peptides.
Core–shell CdSeTe/ZnS quantum dots for the detection of microRNA-155 based on the fluorescence resonance energy transfer technique via the formation of a network structure
Authors: Cui Feng , Qiu Qianying , Peng Gang , Li Xiaoyan , Liu Xi , Chen Xiaojun
Published: July 2019

A fluorescence sensor was designed for miR155. When target hybridized with HP, numerous H1-AuNPs@SiO2 could be produced. The FL of A1-QDs was quenched by H1-AuNPs@SiO2via FRET function. The decrease of FL was proportional with miR155 concentration.
An axially chiral 1,1′-biazulene and its π-extended derivative: synthesis, structures and properties
Authors: Chaolumen Chaolumen , Ito Hideto , Itami Kenichiro
Published: July 2019

Chiral organic π-conjugated molecules have been intensively investigated in the fields of chiral electronic materials and devices.
Mechanosynthesis of sydnone-containing coordination complexes
Authors: Pétry Nicolas , Vanderbeeken Thibaut , Malher Astrid , Bringer Yoan , Retailleau Pascal , Bantreil Xavier , Lamaty Frédéric
Published: July 2019

Mechanochemistry provides a powerful approach to the multistep synthesis of novel coordination complexes, featuring sydnones as ligands, starting with N-arylglycines.
How to add a five-membered ring to polycyclic aromatic hydrocarbons (PAHs) – molecular mass growth of the 2-naphthyl radical (C10H7) to benzindenes (C13H10) as a case study
Authors: Zhao Long , Prendergast Matthew , Kaiser Ralf I. , Xu Bo , Ablikim Utuq , Lu Wenchao , Ahmed Musahid , Oleinikov Artem D. , Azyazov Valeriy N. , Howlader A. Hasan , Wnuk Stanislaw F. , Mebel Alexander M.
Published: July 2019

The reaction of aryl radicals with allene/methylacetylene leads to five-membered ring addition in PAH growth processes.
Intercalation chemistry of graphite: alkali metal ions and beyond
Authors: Li Yuqi , Lu Yaxiang , Adelhelm Philipp , Titirici Maria-Magdalena , Hu Yong-Sheng
Published: July 2019

This review compares the intercalation behaviors of alkali metal ions in graphite, offers insight for the host-guest interaction mechanisms, and expands the intercalation chemistry of pure ions to complex anions, ion-solvent, and multivalent ions.
Effective luminescence sensing of Fe3+, Cr2O72−, MnO4− and 4-nitrophenol by lanthanide metal–organic frameworks with a new topology type
Authors: Ma Jing-Jing , Liu Wei-sheng
Published: July 2019

A new topology type of Ln-MOFs exhibit an excellent luminescent sensing response to Fe3+, Cr2O72−, MnO4− and 4-nitrophenol. By time-resolved photoluminescence techniques, complex 1 can effectively eliminate interference of background fluorescence.
A hydrogen-bonded assembly of cucurbit[6]uril and [MoO2Cl2(H2O)2] with catalytic efficacy for the one-pot conversion of olefins to alkoxy products
Authors: Nogueira Lucie S. , Antunes Margarida M. , Gomes Ana C. , Cunha-Silva Luís , Pillinger Martyn , Lopes André D. , Valente Anabela A. , Gonçalves Isabel S.
Published: July 2019

A supramolecular cucurbit[6]uril/MoVI hydrogen-bonded assembly displays dual-function (oxidation/acid) catalytic behavior for the one-pot conversion of olefins to alkoxy products.
Correction: Magnetic relaxation in cobalt(ii)-based single-ion magnets influenced by distortion of the pseudotetrahedral [N2O2] coordination environment
Authors: Böhme Michael , Ziegenbalg Sven , Aliabadi Azar , Schnegg Alexander , Görls Helmar , Plass Winfried
Published: July 2019

Correction for ‘Magnetic relaxation in cobalt(ii)-based single-ion magnets influenced by distortion of the pseudotetrahedral [N2O2] coordination environment’ by Michael Böhme et al., Dalton Trans., 2018, 47, 10861–10873.
Sheathless separation of microalgae from bacteria using a simple straight channel based on viscoelastic microfluidics
Authors: Yuan Dan , Zhao Qianbin , Yan Sheng , Tang Shi-Yang , Zhang Yuxin , Yun Guolin , Nguyen Nam-Trung , Zhang Jun , Li Ming , Li Weihua
Published: July 2019

Sheathless separation of microalgae from bacteria using a simple straight channel based on viscoelastic microfluidics.
Diameter distribution by deconvolution (DdD): absorption spectra as a practical tool for semiconductor nanoparticle PSD determination
Authors: Onna Diego , Perez Ipiña Ignacio , Fernández Casafuz Agustina , Mayoral Álvaro , Ibarra García M. Ricardo , Bilmes Sara A. , Martínez Ricci María Luz
Published: July 2019

DdD method allows obtaining the SNPs PSD just from absorption spectra.
Synthesis of novel isoindole-containing phakellistatin 2 analogs and the conformation features affecting their antitumor activities
Authors: Zhao Lishuang , Wu Jingwan , Bao Yujun , Jiang Shitian , Wang Zhiqiang , Guo Changhong , Jin Yingxue , Qu Fengyu
Published: July 2019

Two novel phakellistatin 2 analogs were synthesized and the conformational features affecting their antitumor activities were studied.
Estimation of hydrogen sulfide from crude petroleum: a unique invention using a simple chemosensor
Authors: Kundu Shampa , Sahoo Prithidipa
Published: July 2019

Naphthalimide–salicylaldehyde based imine (NPSI) has been developed as the first chemosensor for selective detection and estimation of hydrogen sulfide in crude petroleum oil.
Structures, fluorescence properties and magnetic properties of a series of rhombus-shaped LnIII4 clusters: magnetocaloric effect and single-molecule-magnet behavior
Authors: Wang Wen-Min , Zhang Li , Li Xian-Zhen , He Li-Yuan , Wang Xin-Xin , Shi Ying , Wang Jie , Dong Jie , Wu Zhi-Lei
Published: July 2019

A family LnIII4 clusters were successfully synthesized and structurally characterized. Magnetic studies show that Gd4 cluster displays magnetic refrigeration, while Dy4 cluster demonstrates two distinct slow magnetic relaxation processes.
NiPS3 nanoflakes: a nonlinear optical material for ultrafast photonics
Authors: Liu Jiefeng , Li Xinzhe , Xu Yijun , Ge Yanqi , Wang Yunzheng , Zhang Feng , Wang Yingwei , Fang Yiyun , Yang Fumei , Wang Cong , Song Yufeng , Xu Shixiang , Fan Dianyuan , Zhang Han
Published: July 2019

A NiPS3-coated microfiber with strong nonlinear optical response is developed as a saturable absorber for ultrafast pulse generation.
Boosting the singlet oxygen photosensitization abilities of Zn(ii) phthalocyanines through functionalization with bulky fluorinated substituents
Authors: Revuelta-Maza Miguel A. , Nonell Santi , de la Torre Gema , Torres Tomás
Published: July 2019

Non-aggregated, crosswise ZnPcs functionalized with bis(trifluoromethyl)phenyl groups in facing isoindoles have proved efficient photosensitizers for singlet oxygen generation.
Single-component gold(i)-containing highly white-emissive crystals based on a polymorph doping strategy
Authors: Dong Yubao , Zhu Fei , Chen Zhao , Yin Jun , Liu Sheng Hua
Published: July 2019

A single-component white phosphorescent light-emitting gold(i)-based crystalline material is reported. The high-efficiency white phosphorescence is resulted from “polymorph doping”.
Novel designed azo substituted semi-cyanine fluorescent probe for cytochrome P450 reductase detection and hypoxia imaging in cancer cells
Authors: Wang Caiyue , Zhang Shuping , Huang Junhai , Cui Lei , Hu Jin , Tan Shaoying
Published: July 2019

An NIR hypoxia activated fluorescent probe was designed with fast performance and sensitivity response to hypoxic conditions.
Aspect ratio-controlled preparation of α-CaSO4·0.5H2O from phosphogypsum in potassium tartrate aqueous solution
Authors: Sun Xiangbin , Zhang Genlei , Cui Peng
Published: July 2019

The conversion of industrial gypsum to rod-shaped α-CaSO4·0.5H2O crystals with tunable aspect ratio in a H2O system is realized with potassium tartrate.
A comprehensive optical analysis of nanoscale structures: from thin films to asymmetric nanocavities
Authors: Lio Giuseppe Emanuele , Palermo Giovanna , Caputo Roberto , De Luca Antonio
Published: July 2019

Hyper transmission of asymmetric nanocavity metamaterials; a comprehensive optical analysis of multi-layered nanostructures.
A quantitative uncertainty metric controls error in neural network-driven chemical discovery
Authors: Janet Jon Paul , Duan Chenru , Yang Tzuhsiung , Nandy Aditya , Kulik Heather J.
Published: July 2019

A predictive approach for driving down machine learning model errors is introduced and demonstrated across discovery for inorganic and organic chemistry.
Poly(ethylene glycol) nanocomposites of sub-nanometer metal oxide clusters for dynamic semi-solid proton conductive electrolytes
Authors: Zheng Zhao , Zhou Qianjie , Li Mu , Yin Panchao
Published: July 2019

PEG–POM nanocomposites are ideal candidates for semi-solid proton conductors with high proton conductivities and devisable mechanical performances.
Diffusion controlled porous WO3 thin film photoanodes for efficient solar-driven photoelectrochemical permanganic acid production
Authors: Nakajima Tomohiko , Kanaori Megumi , Tateno Hiroyuki , Nomoto Junichi , Miseki Yugo , Tsuchiya Tetsuo , Sayama Kazuhiro
Published: July 2019

Photoelectrochemical (PEC) oxidation of the divalent manganese ion to the permanganate ion was achieved by using porous WO3 thin film photoanodes in sulfuric acid electrolytes under simulated sunlight.
Role of confinement, molecular connectivity and flexibility in entropic driven surface segregation of polymer–colloid mixtures
Authors: Mehta Spand Bharat , Kumar Avishek , Radhakrishna Mithun
Published: July 2019

Stiff chains segregate onto the surface driven by surface nematization in slit-pore geometry and looping under spherical confinement.
High loading accessible active sitesviadesignable 3D-printed metal architecture towards promoting electrocatalytic performance
Authors: Chang Shuai , Huang Xiaolei , Aaron Ong Chun Yee , Zhao Liping , Li Liqun , Wang Xuesen , Ding Jun
Published: July 2019

3D printing of a tailor-designed support architecture with a tunable electrochemically active surface area for improving catalyst loading contributions to catalytic activity.
A mixed solvent for rapid fabrication of large-area methylammonium lead iodide layers by one-step coating at room temperature
Authors: Liu Qiuju , Zhao Yanan , Ma Yinxing , Sun Xuan , Ge Wenqi , Fang Zhuliang , Bai Hua , Tian Qingyong , Fan Bin , Zhang Tongyi
Published: July 2019

A new mixed solvent enables rapid fabrication of high-quality perovskite films directly by one-step spin-coating or blade-coating.
Synthesis, characterization and catalytic performance of nanostructured dysprosium molybdate catalyst for selective biomolecule detection in biological and pharmaceutical samples
Authors: Karthik Raj , Mutharani Bhuvanenthiran , Chen Shen-Ming , Vinoth Kumar Jeyaraj , Abinaya Manickavasagan , Chen Tse-Wei , Lei Wu , Hao Qingli
Published: July 2019

The current study reports a new, simple and fast method using a flake-like dysprosium molybdate (Dy2MoO6; FL-DyM) nanostructured material to detect the antibiotic drug metronidazole (METZ).
An efficient post-doping strategy creating electrospun conductive nanofibers with multi-functionalities for biomedical applications
Authors: Simsek Marcel , von Kruechten Lara , Buchner Markus , Duerkop Axel , Baeumner Antje J. , Wongkaew Nongnoot
Published: July 2019

Highly conductive and uniform electrospun nanofibers bearing inherent desirable bioanalytical functionalities have been enabled through a facile fabrication strategy, namely post-doping.
TEM apparent resistivity imaging for grounding grid detection using artificial neural network
Authors: Qin Shanqiang , Wang Yao , Tai Heng‐Ming , Wang Haowen , Liao Xian , Fu Zhihong
Published: July 2019

Transient electromagnetic (TEM) method is a reliable means of non‐destructive testing for fault diagnosis of grounding grid in substation. In view of the small transmitter loop of the TEM system and many measuring points and survey lines of grounding grid detection in substation. This study presents a fast solution to TEM apparent resistivity imaging for grounding grid detection using artificial neural networks. The input ‐output mapping relation of neural network is established based on TEM response characteristics of the grounding grid. The built network could map the recorded TEM data of grounding grid detection and quickly obtain the resistivity image. The proposed method offers accuracy and fast computation for the resistivity imaging of grounding grid. Feasibility and technical attractiveness of the proposed method in fast imaging of apparent resistivity is investigated with the measurement of grounding grids in the actual substations. It can be used in real time so that the recorded TEM data in substation can be calculated without re‐training, which avoids time‐consuming inversion computation. The rapid processing of massive data and submitting the detection results of the grounding grid to customers rapidly and in real time, which is expectation for a modern power industry.
Fleckmentation: rapid segmentation using repeated 2‐means
Authors: Rasche Christoph
Published: July 2019

A procedure for segmentation is introduced that uses the K‐means algorithm to decompose an image by recursively applying the K‐means with . This 2‐means decomposition procedure finds any region that corresponds to a scene part, but it is also prone to oversegmentation. The procedure has already been used in two tasks previously: a scene classification task and a foreground–background segregation task (skin lesion detection). Here, the authors explain its operation in more detail and analyse its lower performance. It is sufficient to apply the procedure with only three to four recursions, making the process of almost minimal complexity in case of four recursions. It is thus suitable for large‐image analysis and frame processing.
Transmitarray antenna based on parallel‐plate transmission line with high efficiency and large gain bandwidth
Authors: Eskandari Hossein , Reza Hassani Hamid
Published: July 2019

A dual‐polarised transmitarray antenna unit cell based on conventional parallel‐plate with low loss and wide bandwidth is proposed. A conventional parallel‐plate is developed into two new structures; the first structure consists of two sets of parallel‐plates forming a four‐wall transmission line, while in the second structure the plates of the first structure are replaced by sets of strips. To ease the fabrication, in both cases, the plates are etched on FR4 substrates. These two structures are evaluated as the unit cell of transmitarray antenna to improve the efficiency and gain bandwidth. There is a basic difference between these two unit cells: the first unit cell increases the phase velocity and the second unit cell reduces the phase velocity while passing through the unit cells. Therefore, the layout of the metal antenna plates designed based on the first unit cell becomes concave‐like and the layout of the metal antenna plates designed based on the second unit cell becomes convex‐like. The antenna designed based on the second unit cell results in higher efficiency as such this antenna is fabricated and measured. The measured results show that the antenna has a peak efficiency of 85.6% and 1 dB gain bandwidth of 22.6%.
Drug repositioning via matrix completion with multi‐view side information
Authors: Hao Yunda , Cai Menglan , Li Limin
Published: July 2019

In the process of drug discovery and disease treatment, drug repositioning is broadly studied to identify biological targets for existing drugs. Many methods have been proposed for drug–target interaction prediction by taking into account different kinds of data sources. However, most of the existing methods only use one side information for drugs or targets to predict new targets for drugs. Some recent works have improved the prediction accuracy by jointly considering multiple representations of drugs and targets. In this work, the authors propose a drug–target prediction approach by matrix completion with multi‐view side information (MCM) of drugs and proteins from both structural view and chemical view. Different from existing studies for drug–target prediction, they predict drug–target interaction by directly completing the interaction matrix between them. The experimental results show that the MCM method could obtain significantly higher accuracies than the comparison methods. They finally report new drug–target interactions for 26 FDA‐approved drugs, and biologically discuss these targets using existing references.
Inlet pressure simulation of pigging in uphill gas pipeline
Authors: He Honggang , Liang Zheng , Guo Yishan
Published: July 2019

Pipe cleaning is a common operation in the oil and gas industry. In this paper, the governing equation of the pipeline inspection gauge (PIG, lowercase pig is commonly used) speed is combined with the gas flow equations. The method of characteristics (MOC) is used to solve the transient equations of gas flow. And the process of a pig passing over an uphill section of a gas pipeline is simulated. The results indicate that a pig may get stuck in uphill gas pipeline, due to the coupling of the gas and the pig. Under these circumstances, a higher pressure of the upstream could be helpful for driving the pig in motion. Additionally, the ratio of inlet pressure rise during the pigging process is primarily determined by the inclination of the uphill section. In addition, a formula to predict the inlet pressure during pigging in an uphill pipe is presented. Furthermore, the proposed method and solution can be utilized to predict the speed and position of the pig, as well as the gas pressure and the stoppage of the pig in hilly gas pipelines.
Molecular cloning and transcriptional and functional analysis of glycogen synthase kinase-3β inHaemaphysalis longicornis(Acari, Ixodidae)
Authors: Rahman Md. Khalesur , You Myungjo
Published: July 2019

Glycogen synthase kinase 3 (GSK-3), which belongs to the serine/threonine kinase family, regulates glycogen metabolism, Wnt signaling, hormonal regulation, and embryonic development in many eukaryotes. Here, we cloned a complete open reading frame (ORF) of glycogen synthase kinase 3β (GSK-3β) fromHaemaphysalis longicornisand characterized its transcriptional and functional status. The ORF of GSK-3β possesses 1242 nucleotides encoding a mature protein of 413 amino acid residues. GSK-3β nucleotide and protein sequences are highly conserved among different vertebrate and invertebrate animals, with identity between 47.8–100% and 63.2–88.7%, respectively. Sequence comparison showed one signature domain between the residues of 51 and 335 amino acids, which was identified as a protein kinase (serine/threonine). RT-PCR showed GSK-3β mRNA present in all developmental stages ofH. longicornis. Interestingly, a higher transcript level was observed in nymph and 7-day-old eggs compared with others by real-time PCR, indicating a role of GSK-3β in the early stages of life. The functional status of GSK-3β was characterized by RNA interference (RNAi) and caused significant (p < 0.05) reduction in feeding and reproduction, as well as an abnormality in eggs and hatching. Taken together, our results suggest that GSK-3β may be an important candidate for a multiple antigen vaccine for controlling the tick population.