bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphiceptin analogs as potential analgesic and anti-diarrheal agents
Authors: Gach-Janczak Katarzyna , Janeck Anna
Published: June 2019

Morphiceptin (Tyr-Pro-Phe-Pro-NH2) – an opioid peptide, originating
from enzymatic degradation of milk protein, β-casein, is a selective ligand μ-opioid receptors. These receptors play a an important role in
reduction of pain sensitivity and in the regulation of the functions of
many systems, including the gastrointestinal tract. Due to the rapid degradation
by proteolytic enzymes and low bioavailability, morphiceptin
can not be used as a medicine.

The aim of the project was the synthesis and evaluation of the pharmacological profile of novel morphiceptin analogs, in search of compounds with a strong analgesic and anti-diarrheal activity, which acted only peripherally and are active after oral administration.

We synthesized five series of morphiceptin analogs. The most interesting turned out compounds modified with the use of β-amino acids. Modification of morphiceptin at positions 2 or 3 by introduction of β2- or β3-amino acids and additionally in position 1 by replacing Tyr by Dmt (2’,6’-dimethyltyrosine), resulted in obtaining enzymatically stable analogs with mixed opioid receptor affinity profiles.

An analog of the sequence Dmt-D-Ala-(R)-β2-1-Nal-Pro-NH2</sub) [Nal= 3-(1-naphthyl)-alanine] was selected for in vivo experiments in mice. This peptide showed a strong antinociceptive effect (peripheral analgesic) and antidiarrheal activity (comparable to loperamide) after intraperitoneal as well as oral administration. The PAMPA test, showed that this compound did not cross the artificial membrane imitating the blood-brain barrier and therefore its action should be only peripheral. The new analog may become an interesting lead compound in the development of peripherally restricted drugs for the treatment of gastrointestinal disorders.
Natural terpenes as substances with multidirectional biological activities
Authors: Wojtunik-Kulesza Karolina A. , Waksmundzka- Hajnos Monika
Published: June 2019

Terpenes, secondary metabolites, are considered by scientists around
the World. Multidirectional biological activities of these substances encourage
researchers to their detail analysis towards numerous diseases
such as neurodegenerative or metabolic. In the presented paper, authors
have focused on Alzheimer’s disease and diabetes as potential direction
of terpenes’ activity. According to available literature, terpenes exhibit
satisfactory antioxidant activity and ability to inhibition AChE, BuChE
(Alzhiemer’s disease) and α-amylase, α-glucosidase (diabetes). Basis of
the presented research are both essential oils obtained from plants such
as salvia, rosemary, basil and lemon balm being one of the main source
of natural terpenes, and single compounds. Special attention is paid
to monoterpenes as the main components of numerous essential oils. Among terpenes presented in the paper, activity of ocimene, carvone,
pulegone, α-phellandrene exhibiting activity towards both free radical
scavenging as well as AChE and BuChE inhibition, and α-pinene, citral,
limonene that revealing inhibitory activity towards α-amylase and
α-glucosidase should be emphasized.
Significance of FGFR2 – RSK2 interdependence for breast cancer progression. In vitro studies and clinical material analyses
Authors: Czaplińska Dominika
Published: June 2019

The members of p90 ribosomal S6 kinase (RSK) family of Ser/Thr kinases are downstream effectors of MAPK/ERK pathway that regulate diverse cellular processes including cell growth, proliferation and survival. In carcinogenesis, RSKs are thought to modulate cell motility, invasion and metastasis. Elevated level of RSK1 and RSK2 was found in about 50% of breast tumours and is associated with a poor survival outcome.

The project aims to investigate the role of RSK2 kinase in breast cancer progression out at two complementary levels: in vitro studies and analyses of samples from breast cancer patients.

We demonstrated that in breast epithelial and cancer cell lines stimulation of FGFR2 (fibroblast growth factor receptor 2) with FGF2 induced activation of RSK2-Tyr529 and that this new signalling pathway promoted anchorage-independent cell proliferation, formation of focal adhesions and cell migration. In clinical analyses FGFR2 showed a positive correlation with RSK2 at both protein (p = 0.003) and mRNA (p = 0.001) levels. The values of correlation coefficients were the highest in triple- -negative breast cancer (TNBC), which is more aggressive and has a poorer prognosis than other breast cancer subtypes. Moreover, expression of FGFR2 and/or activated RSK (RSK-P) significantly correlated with poor disease-free survival (DFS) of patients (p = 0.01).

Taken together, our results suggest that FGFR2-RSK2 signalling pathway is associated with breast cancer progression and further studies of FGFR2-RSK2 interdependence may contribute to the development of new therapeutic strategies in the management of patients with breast cancer.
Hvordan lages barn? Bildebøker for barn om hvordan barn blir til – How to Make Children? Picturebooks for Children About How to Make A Baby
Authors: Maagerø Eva , Øines Anne Marie
Published: June 2019

I denne artikkelen analyseres fire bildebøker for barn der temaet er hvordan barn blir til. Målet er å undersøke hvordan voksensamfunnet formidler dette tilsynelatende tabubelagte og sensitive emnet til små barn gjennom verbal-språk og bilde. Spørsmålene som besvares i analysen, er: Hvilke litterære strategier benyttes i de fire bildebøkene for å informere om hvordan barn blir til, og hva kan en analyse av bilde og verbalspråk av utvalgte oppslag si om fordelingen av informasjon i de to modalitetene? De fire bøkene er Slik får man et barn av Per Holm Knudsen (1971), Hvor ble det av Benny? av Nicholas Allan (2004), Da Emma ble Emma - historien om hvordan et barn blir til av Peter Gotthardt og Kirsten Raagaard (2009) og Hvordan lager man en baby? av Anna Fiske (2019). I analysen undersøker vi i hvilken grad fortelling er brukt som en strategi for å formidle emnet, mens de utvalgte oppslagene analyseres ut fra et sosialsemiotisk rammeverk. Det viser seg at tre av bøkene har en tydelig fortellingsstruktur om enn på ulik måte. Analysen av oppslagene viser at det sannsynligvis er enklere å ta opp seksualitet gjennom modaliteten verbalspråk enn gjennom bilde. Funnene samsvarer med annen forskning på bildebøker om seksualitet.AbstractIn this article, four picturebooks for children with the topic how babies are made are analyzed. The aim is to investigate how adults present this controversial and sensitive theme to young children through verbal language and image. The analysis aims to answer the following research questions: Which literary strategies are used in the four picturebooks to inform about how babies are made, and what can an analysis of image and verbal language of selected spreads tell about the distribution of information in the two modes? The four books are How to get a child by Per Holm Knudsen (1971), Where Willi went by Nicholas Allan (2004), When Emma became Emma – the story about how a child is made by Peter Gotthardt and Kirsten Raagaard (2009) and How do you make a baby? by Anna Fiske (2019)[1]. The four books were analyzed to find out to which degree a narrative strategy was used, while a social semiotic framework was used to analyze the selected spreads. Three of the four books used a narrative structure to present the topic, but in different ways. The analysis of the spreads shows that verbal language carries more semantic weight than images do when it comes to sexuality. The findings support findings from other research conducted about sexuality.    [1] Three titles are translated into English by the authors of the article. Where Willi went is the book’s original title.
Tabusprachliches im Jukagirischen
Authors: Knüppel Michael
Published: June 2019

In this article, the author addresses the problem of taboos in the Yukaghir languages. These taboos (words as well as phonetic transformations) have not been sufficiently investigated, since their samples are only given in the existing literature. Some of the taboos were already mentioned by V. I. Iochel’son, while others were discussed by I. Nikolaev and G. D. S. Anderson. Yukaghir languages share most patterns of tabooization with the neighboring Altaic languages.
The Professionalization of Revivalist Shamans as Ministers of Justice in Tyva Republic, Siberia
Authors: Zorbas Konstantinos
Published: June 2019

This paper documents a strand of religious practices concerned with curse afflictions in Tyva Republic, south Siberia. Drawing on consultations dealing with misfortunes the paper probes a field of justice, which is governed by shamans. The analysis focuses on two cases which illuminate the shamans’ function as a judiciary against kinds of transgression which are sanctioned by the Russian justice system. The data reveal the rise of curse afflictions as a cause of misfortunes in Tyva. The paper concludes that, in remedying misfortunes attributed to cursing, shamans re-enact memories of their ancestors’ resistance against the Soviet regime.
Blood Feud in the Eastern Himalaya
Authors: Tamut Rebecca
Published: June 2019

This article brings to attention an event that occurred in January 1963, in which Indian police personnel were murdered by Nyishi tribesman in Chayangtajo, a remote administrative Circle in the North-East Frontier Agency (NEFA), today known as Arunachal Pradesh, India. This paper uses oral sources to illuminate how the event unfolded and how it was perceived locally. I will show that this deadly event was the consequence of an on-going tribal feud. By allying themselves with the wrong clan, the police force was considered the enemy of a group of clans among which they intended to establish an administrative outpost.
24/7 Study: Conducting a focus to improve services
Authors: Wagner Megan , Cho Richard M.
Published: June 2019

Many of us remember our own experiences with final exams during our college years: certain determination tinged with jitters, endless cups of coffee, and the lamp light illuminating the desk throughout the night. Final exams account for, for most classes, a substantial portion of students’ final grade, and at a university that puts keen emphasis on student success, it is imperative that students encounter their final exams with proper preparation. One way the library can help is to provide them with an optimal place to study for exams, any time of any day.
The Fulbright experience: Teaching Library and Information Science for one semester in China
Authors: Freedman Shin
Published: June 2019

I spent the fall of 2016 as a Fulbright Scholar in China. I was interested in China in part because of China’s rising intellectual power and increasing economic power in the global market. I was excited and anxious to arrive in China after the end of the 2016 G20 Summit in Hangzhou, my new home. Hangzhou is famous for its history: West Lake, the longest manmade canal in the world, Dragon Well Tea (Longjingcha), and innovations, such as being the home of Alibaba’s online enterprise.
Internet Reviews
Authors: Roberts Joni R. , Drost Carol A.
Published: June 2019

The Free Speech ProjectThe Plateau Peoples’ Web PortalUnited Nations University World Institute for Development Economics (UNU-WIDER)
Counterproductive: Time Management in the Knowledge Economy by Melissa Gregg
Authors: Guthro Clem
Published: June 2019

Gregg, the Principal Engineer and Research Director for Client Computing at Intel, has written an interesting and perhaps controversial book that attempts to recast the narrative on productivity away from the individual to the group. In four chapters, using both a feminist perspective as well as the work of German political philosopher Peter Sloterdijk, Gregg elucidates the problems that an obsession with time management and productivity have created for the modern worker. Her intent is to cause readers to rethink the advice being offered in such titles as Alex Genadinik’s 20 Principles of Productivity: Focus, Motivation, Organization, Habit Building, Time Management, Apps, Psychology, Goal Setting, Procrastination and More (2017), and David Allen’s Getting Things Done: The Art of Stress-Free Productivity (2015).
Open Divide: Critical Studies on Open Access, edited by Ulrich Herb and Joachim Schöpfel
Authors: Edge Samuel
Published: June 2019

Open access is frequently a topic of conversation in library and information studies courses. Usually imbued with hints of social justice, progressivism, and equality, professors and students alike often point to open access as something that librarianship “got right.” On a personal level, while working with document delivery in a large biomedical library, I became an enthusiastic supporter of open access articles and journals that allowed me to save staff time and deliver content to our patrons more expeditiously. After reading Open Divide: Critical Studies on Open Access, my relationship with open access is no longer quite so simple. Open Divide lays the concept of open access bare, making note of its benefits, but also clearly exposing its flaws, faults, and corruptions.
Censorship Dateline
Authors: Stone David R.
Published: June 2019

Libraries, Schools, Prisons, Public Art, International
From the Bench
Authors: Stone David R.
Published: June 2019

Supreme Court, Libraries, Schools, Colleges and Universities, Social Media, Privacy, Sexual Harrassment Allegations
Risk Factors for Overweight in early ages: longitudinal design with Spanish Preschoolers
Authors: Pérez-Bonaventura Iris , Granero Roser , Ezpeleta Ascaso Lourdes
Published: June 2019

Previous studies have shown that there are several significant early-life risk factors associated with childhood overweight. However, research has mainly focused on school-aged children. The aim of this study is to identify risk factors in early life for overweight in a community sample of Spanish preschoolers. A sample of 622 three-year-olds was monitored until the age of 5, and their height and weight were registered annually. Overweight status was defined by World Health Organization standards. A large set of risk factors including sociodemographic variables, family structure, pregnancy, birth, postnatal period, school and neighborhood were measured through semi-structured interviews. Stepwise logistic regressions created predictive models with the best predictors of overweight for each age group. This is the first longitudinal study to examine a large set of risk factors among Spanish preschoolers. Several potential early risk factors in preschool children were associated with later overweight: high birth weight, ethnicity, excess screen time, low attention span, maternal smoking during pregnancy, inconsistent discipline, fewer rules, corporal punishment and parents psychopathology. Among them, the most powerful factor was high birth-weight (odds ratio = 1.89 at age 3, 1.87 at age 4, and 2.35 at age 5), underlining the importance of weight monitoring from postpartum and routine screening for overweight in children who have high birth weight. With the increasing prevalence of overweight in children at early ages, understanding the determinants for overweight risk becomes crucial for public health professionals and policy-makers in order to implement effective prevention and intervention programs
Atuação do fisioterapeuta no tratamento da hemorragia peri-intraventricular em recém-nascidos
Authors: Watte Anderson Fazolo , Miranda Rivia da Silva Pereira , Maciel Daniela Maristane Vieira Lopes
Published: June 2019

Na evolução da assistência neonatal, ocorreu um grande esforço para a maior sobrevida de recém-nascidos prematuros. Diante desta necessidade da fisioterapia respiratória, as unidades de terapia intensiva neonatal (UTIN) se tornaram cada vez mais importantes no que diz respeito aos distúrbios respiratórios, que são responsáveis pela maior parcela problemas relacionadas à prematuridade. Este artigo tem como principal objetivo fazer levantamentos bibliográficos referentes à atuação do fisioterapeuta no que diz respeito ao tratamento da Hemorragia Perintraventricular (HIPV) em recém-nascidos, sendo levantadas técnicas e tipos de tratamentos desta patologia. Foi realizada uma revisão de literatura, utilizando as bases de dados da BIREME, SCIELO, LILACS E PUBMED, dos quais foram consultados artigos de revistas e jornais no período de 1993 a 2013, que tratam dos principais conceitos utilizados neste estudo, a fim de embasar teoricamente a pesquisa. Foram utilizados como descritores para a realização da pesquisa nos periódicos, os termos: Fisioterapeuta; Hemorragia Peri-Intraventricular; e Recém-nascidos, sendo a data das pesquisas feitas entre os meses de setembro e outubro do ano de 2017. A fisioterapia respiratória atua tanto na prevenção, quanto no tratamento das doenças respiratórias, sendo utilizado de diversas técnicas e procedimentos terapêuticos ao nível ambulatorial e hospitalar nas Unidades de Terapia Intensiva, com o objetivo de estabelecer/restabelecer o padrão respiratório para reduzir os gastos energéticos no momento da ventilação, possibilitando ao indivíduo realizar diferentes atividades de vida diária sem que tenha grandes transtornos e/ou repercussões negativas em seu sistema respiratório. Diante desta situação a assistência fisioterapêutica feita em recém-nascido tende a apresentar características próprias referentes ao seu peso; à imaturidade e às doenças prevalentes nessa população. Diante dessas particularidades, evidenciam-se dificuldades que exigem cuidados especiais pelo fisioterapeuta junto a recém-nascidos prematuros em unidades de terapia intensiva.
Presente y futuro de los sistemas de medición de audiencias de televisión Se ha habilitado la compatibilidad con lectores de pantalla.
Authors: Reig Roger
Published: June 2019

Estudio sobre el sistema actual de medición de audiencias de televisión y realización de una nueva propuesta.
Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion
Authors: Hardy Holly , Prendergast James GD , Patel Aara , Dutta Sunit , Trejo-Reveles Violeta , Kroeger Hannah , Yung Andrea R , Goodrich Lisa V , Brooks Brian , Sowden Jane C , Rainger Joe
Published: June 2019

Epithelial fusion underlies many vital organogenic processes during embryogenesis. Disruptions to these cause a significant number of human birth defects, including ocular coloboma. We provide robust spatial-temporal staging and unique anatomical detail of optic fissure closure (OFC) in the embryonic chick, including evidence for roles of apoptosis and epithelial remodelling. We performed complementary transcriptomic profiling and show thatNetrin-1 (NTN1) is precisely expressed in the chick fissure margin during fusion but is immediately downregulated after fusion. We further provide a combination of protein localisation and phenotypic evidence in chick, humans, mice and zebrafish that Netrin-1 has an evolutionarily conserved and essential requirement for OFC, and is likely to have an important role in palate fusion. Our data suggest thatNTN1is a strong candidate locus for human coloboma and other multi-system developmental fusion defects, and show that chick OFC is a powerful model for epithelial fusion research.
A four-DNA methylation biomarker is a superior predictor of survival of patients with cutaneous melanoma
Authors: Guo Wenna , Zhu Liucun , Zhu Rui , Chen Qihan , Wang Qiang , Chen Jian-Qun
Published: June 2019

Cutaneous melanoma (CM) is a life-threatening form of skin cancer. Prognostic biomarkers can reliably stratify patients at initial melanoma diagnosis according to risk, and may inform clinical decisions. Here, we performed a retrospective, cohort-based study analyzing genome-wide DNA methylation of 461 patients with CM from the TCGA database. Cox regression analyses were conducted to establish a four-DNA methylation signature that was significantly associated with the overall survival (OS) of patients with CM, and that was validated in an independent cohort. Corresponding Kaplan–Meier analysis displayed a distinct separation in OS. The ROC analysis confirmed that the predictive signature performed well. Notably, this signature exhibited much higher predictive accuracy in comparison with known biomarkers. This signature was significantly correlated with immune checkpoint blockade (ICB) immunotherapy-related signatures, and may have potential as a guide for measures of responsiveness to ICB immunotherapy.
Disentangling strictly self-serving mutations from win-win mutations in a mutualistic microbial community
Authors: Hart Samuel Frederick Mock , Pineda Jose Mario Bello , Chen Chi-Chun , Green Robin , Shou Wenying
Published: June 2019

Mutualisms can be promoted by pleiotropic win-win mutations which directly benefit self (self-serving) and partner (partner-serving). Intuitively, partner-serving phenotype could be quantified as an individual’s benefit supply rate to partners. Here, we demonstrate the inadequacy of this thinking, and propose an alternative. Specifically, we evolved well-mixed mutualistic communities where two engineered yeast strains exchanged essential metabolites lysine and hypoxanthine. Among cells that consumed lysine and released hypoxanthine, a chromosome duplication mutation seemed win-win: it improved cell’s affinity for lysine (self-serving), and increased hypoxanthine release rate per cell (partner-serving). However, increased release rate was due to increased cell size accompanied by increased lysine utilization per birth. Consequently, total hypoxanthine release rate per lysine utilization (defined as ‘exchange ratio’) remained unchanged. Indeed, this mutation did not increase the steady state growth rate of partner, and is thus solely self-serving during long-term growth. By extension, reduced benefit production rate by an individual may not imply cheating.
Exploring the feasibility, sustainability and the benefits of the GrACE + GAIT exercise programme in the residential aged care setting
Authors: Fien Samantha , Henwood Tim , Climstein Mike , Rathbone Evelyne , Keogh Justin W.L.
Published: June 2019

Background

The feasibility and benefits of a 24-week targeted progressive supervised resistance and weight-bearing exercise programme (Group Aged Care Exercise + GAIT (GrACE + GAIT)) in the residential aged care (RAC) setting was investigated as very little peer-reviewed research has been conducted in relation to exercise programmes of this duration in this cohort.

Methods

A quasi-experimental study design consisting of two groups (control and exercise) explored a 24-week targeted progressive supervised resistance and weight-bearing exercise programme (GrACE + GAIT) in two RAC facilities in Northern New South Wales, Australia. A total of 42 adults consented to participate from a total of 68 eligible residents (61.7%). The primary outcome measures were feasibility and sustainability of the exercise programme via intervention uptake, session adherence, attrition, acceptability and adverse events. Secondary measures included gait speed and the spatio-temporal parameters of gait, handgrip muscle strength and sit to stand performance.

Results

Twenty-three residents participated in the exercise intervention (mean (SD) 85.4 (8.1) years, 15 females) and 19 in the control group (87.4 (6.6) years 13 females). Exercise adherence was 79.3%, with 65% of exercise participants attending ≥70% of the sessions; 100% of those originally enrolled completed the programme and strongly agreed with the programme acceptability. Zero exercise-related adverse events were reported. ANCOVA results indicated that post-intervention gait speed significantly increased (p < 0.001) with an 18.8% increase in gait speed (m/s).

Discussion

The GrACE + GAIT programme was shown to be feasible and significantly improve adults living in RAC facilities gait speed, handgrip strength and sit to stand performance. These results suggest that the GrACE + GAIT programme is suitable for use in the RAC sector and that it has the potential to reduce disability and improve function and quality of life of the residents.
Value Addition to Beans: The Case of Bean Balls “Akara” Production in Idemili South Local Government of Anambra State, Nigeria
Authors: Nwankwo T. N. , Okoli T. O. , Ugwumba C. O. A.
Published: June 2019

Aims: The study examined socio-economic characteristics of the bean balls producers, the profitability of production, determinants of profit, reasons for starting the business and constraints to production of bean balls in Idemili South Local Government Area of Anambra State, Nigeria. The great need to help homemakers in Nigeria better appreciate and prepare cowpea bean balls as snacks for income generation and women empowerment in Nigeria informed this study.

Study Design: Multi-stage, purposive and random sampling techniques were used to select 50 respondents. Data were collected using structured questionnaire and analyzed by means of descriptive and inferential statistics.

Results: Findings on socio-economic factors of the respondents gave mean age, education level and years of experience of 42.4years, 13.5years and 8.9 years respectively; the majority (92%) of the respondents were females, the majority (60%) married and most (70%) had a household size of 4-6 persons. The enterprise proved profitable with monthly mean net income and net return on investment values of ₦75,990 and 0.39 respectively. Significant determinants of net production returns were gender, educational level and costs of inputs. Main reasons for starting the business were a scarcity of job, profitable nature of the business, high demand and small start-up capital. Serious constraints to production of bean balls in the area were conjunctivitis due to emitted smoke, high and unstable price of raw materials and high cost of production. Policy measures such as bulk purchasing of beans, regulation of market prices of the product, provision of infrastructures (water, electricity), use of cooking gas as a source of heat would mitigate the problems, improve productivity, output and enterprise profitability.

Conclusion: The bean ball production proved to be a profitable enterprise in the study area. Nevertheless, the efficiency and profitability would be improved if the constraints identified by the study are addressed as it will encourage many more people especially young, active and viable individuals, to venture into the enterprise.
Concentration of Heavy Metals (Cd, Co, Cr, & Fe) in Soil and Edible Vegetables in Obudu Urban Area of Cross River State, Nigeria
Authors: Akomaye Akpe, Michael , Unimuyi Ubua, Placcidus
Published: June 2019

The soil and edible vegetable samples were collected from Obudu Urban Area of Cross River State and were digested and analyzed for the Cd, Co, Cr, and Fe (heavy metals) concentration using Atomic Absorption Spectrometer (AAS) in the University of Calabar Laboratory. The eight vegetables considered for the study were Amaranthus spp., Corchorus olitorius, Murraya koenigii, Ocimum grattissimum, Solanum melongena, Talinum triangulare, Telferia occidentalis and Vernonia amygdalina. The results showed that the mean concentration of the metal in the soil in mgkg-1 ranged from (0.004-0.0048) and (0.005-0.046) in rainy and dry seasons respectively for Cd, (0.004-0.025) and (0.006-0.016) in rainy and dry season respectively for Cr, and (0.112-0.173) and (0.116-0.151) in rainy and dry season respectively for Fe. The concentration of Co was not detected in the soil or vegetables. The mean concentration accumulated by the vegetables and that present in the soil was in the order: Fe> Cd> Cr> Co. These results suggest that there is no significant difference between the amount of metals in the soil or that accumulated by the vegetables in rainy and dry seasons of the year. Also the amount of metals accumulated by most of the vegetables was directly proportional to the amount present in the soil where they are planted. The bioaccumulation ratios were all less than 1. These results indicate that the concentration of Cd, Co, Cr, & Fe in the soil and vegetables were still low and within the permissible limits of WHO/FAO. Thus, the consumption of the vegetables in the area may not cause any harm for now.
Quantitative Structure–Activity Relationship and Molecular Docking Studies of Imidazolopyrimidine Amides as Potent Dipeptidyl Peptidase-4 (DPP4) Inhibitors
Authors: Emami Leila , Sabet Razieh , Sakhteman Amirhossein , Zade Mehdi Khoshnevis
Published: June 2019

Type 2 diabetes (T2DM) is a metabolic disorder disease and DPP-4 inhibitors are a class of oral hypoglycemic that blocks the dipeptidyl peptidase-4 (DPP-4) enzyme.  DPP-4 inhibitors reduce glucagon and blood glucose levels and don’t have side effects such as hypoglycemia or weight gain. In this paper, a series of imidazolopyrimidine amides analogues as DPP4 inhibitors were selected for quantitative structure-activity relationship (QSAR) analysis and docking studies. A collection of chemometric methods such as multiple linear regression (MLR), factor analysis-based multiple linear regression (FA-MLR), principal component regression (PCR), genetic algorithm for variable selection-MLR (GA-MLR) and partial least squared combined with genetic algorithm for variable selection (GA-PLS), were conducted to make relations between structural features and DPP4 inhibitory of a variety of imidazolopyrimidine amides derivatives. GA-PLS represented superior results with high statistical quality (R2 = 0.94 and Q2 = 0.80) for predicting the activity of the compounds. Docking studies of these compounds reveals and confirms that compounds 15, 18, 25, 26, and 28 are introduced as good candidates for DPP-4 inhibitors were introduced as a good candidate for DPP-4 inhibitory compounds.
Gene expression profiles define molecular subtypes of prostate cancer bone metastases with different outcomes and morphology traceable back to the primary tumor
Authors: Thysell Elin , Vidman Linda , Ylitalo Erik Bovinder , Jernberg Emma , Crnalic Sead , Iglesias‐Gato Diego , Flores‐Morales Amilcar , Stattin Pär , Egevad Lars , Widmark Anders , Rydén Patrik , Bergh Anders , Wikström Pernilla
Published: June 2019

Bone metastasis is the lethal end‐stage of prostate cancer (PC), but the biology of bone metastases is poorly understood. The overall aim of this study was therefore to explore molecular variability in PC bone metastases of potential importance for therapy. Specifically, genome‐wide expression profiles of bone metastases from untreated patients (n = 12) and patients treated with androgen‐deprivation therapy (ADT, n = 60) were analyzed in relation to patient outcome and to morphological characteristics in metastases and paired primary tumors. Principal component analysis and unsupervised classification were used to identify sample clusters based on mRNA profiles. Clusters were characterized by gene set enrichment analysis and related to histological and clinical parameters using univariate and multivariate statistics. Selected proteins were analyzed by immunohistochemistry in metastases and matched primary tumors (n = 52) and in transurethral resected prostate (TUR‐P) tissue of a separate cohort (n = 59). Three molecular subtypes of bone metastases (MetA‐C) characterized by differences in gene expression pattern, morphology, and clinical behavior were identified. MetA (71% of the cases) showed increased expression of androgen receptor‐regulated genes, including prostate‐specific antigen (PSA), and glandular structures indicating a luminal cell phenotype. MetB (17%) showed expression profiles related to cell cycle activity and DNA damage, and a pronounced cellular atypia. MetC (12%) exhibited enriched stroma–epithelial cell interactions. MetB patients had the lowest serum PSA levels and the poorest prognosis after ADT. Combined analysis of PSA and Ki67 immunoreactivity (proliferation) in bone metastases, paired primary tumors, and TUR‐P samples was able to differentiate MetA‐like (high PSA, low Ki67) from MetB‐like (low PSA, high Ki67) tumors and demonstrate their different prognosis. In conclusion, bone metastases from PC patients are separated based on gene expression profiles into molecular subtypes with different morphology, biology, and clinical outcome. These findings deserve further exploration with the purpose of improving treatment of metastatic PC.
S‐allyl‐l‐cysteine (SAC) protects hepatocytes from alcohol‐induced apoptosis
Authors: Chen Peng , Hu Mingdao , Liu Feng , Yu Henghai , Chen Chen
Published: June 2019

Hepatocyte apoptosis is frequently observed in alcohol‐related liver disease (ARLD), which ranks among the 30 leading causes of death worldwide. In the current study, we explored the impact of S‐allyl‐l‐cysteine (SAC), an organosulfur component of garlic, on hepatocyte apoptosis induced by alcohol. Rat liver (BRL‐3A) cells were challenged by ethanol with or without SAC treatment. Cell death/viability, reactive oxygen species (ROS) generation, mitochondrial Cytochrome C release, and caspase 3 activity were then examined. We found that ethanol remarkably induced apoptosis of hepatocytes, while SAC treatment rescued ethanol‐induced hepatocyte injury, as demonstrated by cell counting kit‐8 (CCK8) assay, TUNEL assay, and annexin V/PI staining assay. Ethanol evoked ROS generation in BRL‐3A cells, and this was abated by SAC pretreatment, as indicated by 2′,7′‐dichlorofluorescin diacetate (DCFDA) staining assay. Moreover, ethanol suppressed cellular anti‐apoptotic protein B‐cell lymphoma‐2 (Bcl‐2) expression, increased pro‐apoptotic protein Bcl‐2‐associated X protein (Bax) expression, induced mitochondrial Cytochrome C release, and activated the caspase 3‐dependent apoptosis pathway in BRL‐3A cells. SAC was sufficient to abolish all these changes induced by ethanol, thereby revealing the molecular mechanisms underlying its protective effects. In conclusion, SAC protects hepatocytes from ethanol‐induced apoptosis and may be suitable for use as a novel anti‐apoptotic agent for treating ARLD.
The Inhibitive Effect of Artificial Seawater on Magnesium Corrosion
Authors: Cao Fuyong , Zhao Chen , You Jing , Hu Jingjie , Zheng Dajiang , Song Guang‐Ling
Published: June 2019

The corrosion behavior of pure magnesium (Mg) immersed in 3.5 wt% NaCl and artificial seawater is evaluated by immersion test, electrochemical impedance spectroscopy (EIS), polarization curve, scanning electrochemical microscopy (SECM), and corrosion morphology analysis. The results show that the corrosion rate of the pure Mg in the artificial seawater is nearly a half of that in the 3.5 wt% NaCl, and the serious localized corrosion of Mg in the NaCl is inhibited in the artificial seawater. The main constituents MgCl2 and Na2SO4 in artificial seawater are found to be inhibitive for the corrosion of Mg. The presence of Mg2+ ions could facilitate the formation of Mg(OH)2 film and thus to some extent retard the dissolution of Mg. The SO42– ions in the artificial seawater might be absorbed competitively against Cl− on the Mg surface to retard the corrosion of Mg. The corrosive and inhibitive effects of other anions and cations on Mg dissolution in the artificial seawater were also briefly analyzed.
Dual‐Action Flexible Antimicrobial Material: Switchable Self‐Cleaning, Antifouling, and Smart Drug Release
Authors: Děkanovský Lukáš , Elashnikov Roman , Kubiková Markéta , Vokatá Barbora , Švorčík Václav , Lyutakov Oleksiy
Published: June 2019

A switchable material with a smart antimicrobial dual‐action functionality, which is based on a highly stretchable silicon polymer gradiently doped with polyyrrole, is proposed. The material exhibits superhydrophobic and self‐cleaning properties, high aerophilicity as well as the possibility of smart, electrically triggerable release of an incorporated drug. During the immersion of the material in water, an air gap is formed on its surface which prevents a formation of biofouling, attachment of microorganisms, and burst release of the incorporated drug. An application of external electric field switches the surface properties from the superhydrophobic to highly hydrophilic state that enables a wetting of the material surface and electrically triggered release of a loaded drug. After the electric field switching off and sample drying, the material surface returns to its intrinsic superhydrophobic state with the original self‐cleaning properties so that the material surface can be simply cleaned, removing the bacteria. High flexibility and stretchability are additional favorable properties of the proposed smart antimicrobial material, making it a suitable candidate for a range of medical and related applications.
Self‐Assembly of rGO Coated Nanorods into Aligned Thick Films
Authors: Modarres Mohammad Hadi , Kosasih Felix Utama , Ducati Caterina , De Volder Michael
Published: June 2019

Self‐assembly is a very effective and popular method to create monolayers or thin films of aligned nanorods and ellipsoids. Nevertheless, there has been little attention to forming thick films of aligned nanorods using this approach. Here, the self‐assembly mechanism of nanorods coated with reduced graphene oxide in thick films with both a surface and a bulk alignment process is underpinned. The alignment method is robust and results in films with up to 50% higher volumetric density compared to nonaligned films of the same material. To optimize the coating process, an image processing script is implemented that quantifies the quality of the alignment based on a fast Fourier transform of nanorod electron microscope images. Based on this analysis, parameters are identified that influence the alignment to optimize the process for obtaining large area domains. Finally, dip‐coating, blade casting and zone coating are tested and compared and lithographically patterned substrates are used to template the self‐assembly process.
Soldering Grain Boundaries Yields Inverted Perovskite Solar Cells with Enhanced Open‐Circuit Voltages
Authors: Li Yunlong , Sun Weihai , Gu Feidan , Ouyang Dan , Bian Zuqiang , Liu Zhiwei , Choy Wallace C. H. , Kelly Timothy L.
Published: June 2019

Grain boundaries (GBs) are one of the major sources of defects in a polycrystalline perovskite solar cell and can greatly increase the rate of charge carrier recombination. In the push to optimize the efficiency of perovskite solar cells, it is therefore extremely important to maximize the grain size and minimize the number of GBs. In the present work, the number of GBs is effectively reduced by introducing a suitable number of formamidinium and chloride ions into the methylammonium lead iodide (MAPbI3) absorber layer. Inverted perovskite solar cells, using NiOx
nanocrystals as the low‐temperature‐fabricated hole transport layer, are prepared; the champion cell has an efficiency of 19.6%. This work demonstrates a simple method of minimizing the number of grain boundaries, which is critical to the future development of this technology.
Perforated and Endothelialized Elastomeric Tubes for Vascular Modeling
Authors: Duchamp Margaux , Bakht Syeda Mahwish , Ju Jie , Yazdi Iman K. , Zhang Weijia , Zhang Yu Shrike
Published: June 2019

Herein, the fabrication of a tubular polydimethylsiloxane (PDMS) platform containing arrays of small pores on the wall for modeling blood vessels in vitro is reported. The thin PDMS tubes are produced following a templating approach, while the pores are subsequently generated using focused laser ablation. As such, when these perforated PDMS tubes are populated with a monolayer of endothelial cells on the interior surfaces and embedded within an extracellular matrix (ECM)‐like environment, the endothelial cells can sprout out from the tubes into the surrounding matrix through the open pores. When a pair of perforated PDMS tubes is placed in parallel in the matrix, formation of an interconnected network of microvasculature or larger vessels occurs, which seems to be dependent on the flow dynamics within the PDMS tubes. Moreover, when cocultured with tumor spheroids, the onset of tumor angiogenesis is observed. Our perforated and endothelialized PDMS tubes are believed to enable convenient vascular modeling in vitro and will likely contribute to improved biological studies as well as therapeutic screening in the future with further optimizations.
Surface‐Wrinkle‐Modified Graphite Felt with High Effectiveness for Vanadium Redox Flow Batteries
Authors: Chen Zehua , Gao Yu , Zhang Chuanxiang , Zeng Xianxiang , Wu Xiongwei
Published: June 2019

Surface‐wrinkle‐modified graphite felt (GF) with abundant N and O is prefabricated by a hydrothermal method followed by calcination, and its surface morphology, elemental composition, and electrochemical properties are characterized by scanning electron microscopy, Raman spectroscopy, X‐ray photoelectron spectroscopy, cyclic voltammetry, electrochemical impedance spectroscopy, and charge/discharge tests. The highly folded coating has excellent wettability, abundant catalytic sites, a fast ion‐diffusion rate, ultralow interface transfer resistance, and high catalytic activity for VO2+/VO2+ and V2+/V3+ reaction couples. Compared with the original GF, the modified GF greatly increases the redox reversibility of the VO2+/VO2+ and V2+/V3+ couples according to cyclic voltammetry profiles. The cathodic and anodic peak potential difference for VO2+/VO2+ substantially decreases from 542 to 388 mV. A battery based on surface‐wrinkle‐modified GF exhibits overall improved efficiency, higher power density, and a high reversible efficiency with a stable average energy efficiency of 78% at a current density of 150 mA cm−2 for 200 charge/discharge cycles.
High‐Performance Visible‐Light Photodetectors built on 2D‐Nanoplate‐Assembled Large‐Scale BiI3 Films
Authors: Wei Qi , Wang Yiru , Yin Jiang , Xia Yidong , Liu Zhiguo
Published: June 2019

The growth of large‐scale films forms the cornerstone for future integrated photodetection applications of 2D materials. However, there is still an unwelcome trade‐off between the size of these films and the performances of devices fabricated using them. To deal with this issue, a possible scheme for film assembly is proposed using high‐quality nanolayers to achieve both outstanding device performance and large film area. Specifically, photodetectors are fabricated on nanostructured BiI3 films (1 × 1 cm2) assembled with interlaced, vertically grown 2D nanoplates. These devices inherent the excellent photodetecting capability of single‐BiI3‐nanoplate‐based photodetectors, showing responsivity of up to 2.22 AW−1, high speed photoresponse of 2 ms/5.3 ms for rise/decay times, and outstanding specific detectivity as high as 1.65 × 1012 Jones. This suggest that this approach to preparing large‐scale 2D BiI3 films holds potential for the realization of integrated high‐performance photosensing devices. Furthermore, it is anticipated that it can be to other 2D materials.
High‐Performance and Radiation‐Hard Carbon Nanotube Complementary Static Random‐Access Memory
Authors: Zhu Ma‐Guang , Zhang Zhiyong , Peng Lian‐Mao
Published: June 2019

Significant progress on carbon‐nanotube (CNT) electronics means that they are a serious candidate for use in high‐performance integrated circuits (ICs). However, few works have focused on fabricating and exploring CNT complementary metal–oxide‐semiconductor (CMOS) static random‐access memory (SRAM), which is an integral part of most digital ICs. High‐performance complementary top‐gated field‐effect transistors (FETs) are fabricated through a doping‐free technology based on solution‐derived CNT films and are used in SRAM cells with a high yield and high uniformity. CNT CMOS‐architecture 6‐transistor (6‐T) SRAM exhibits read/write margins as high as ≈0.4 V with a supply voltage of 1.0 V and stable dynamic properties. Furthermore, the effects of radiation the CNT CMOS FETs and SRAM ICs are explored. Owing to the robust CC bonds in the CNTs, the ultrathin gate insulator layer in the devices, and a lack of a requirement for an isolation region, CNT FETs and SRAM cells can withstand a 2.2 Mrad total ionizing dose (TID) with a high rate of 560 rad s−1, indicating that they could be used as radiation‐hard ICs for applications in hostile environments. TID hardness of CNT‐based SRAM ICs is reported for the first time, and a dose of 2.2 Mrad is the highest measured radiation dose for CNT FETs and ICs.
An Ultrastable Presodiated Titanium Disulfide Anode for Aqueous “Rocking‐Chair” Zinc Ion Battery
Authors: Li Wei , Wang Kangli , Cheng Shijie , Jiang Kai
Published: June 2019

Rechargeable aqueous Zn‐based batteries are attractive candidates as energy storage technology, but the uncontrollable Zn dendrites, low stripping/plating coulombic efficiency, and inefficient utilization of Zn metal limit the battery reliability and energy density. Herein, for the first time, a novel presodiated TiS2 (Na0.14TiS2) is proposed and investigated as an intercalated anode for aqueous Zn‐ion batteries, showing a capacity of 140 mAh g−1 with a suitable potential of 0.3 V (vs Zn2+/Zn) at 0.05 A g−1 and superior cyclability of 77% retention over 5000 cycles at 0.5 A g−1. The remarkable performance originates from the buffer phase formation of Na0.14TiS2 after chemically presodiating TiS2, which not only improves the structural reversibility and stability but also enhances the diffusion coefficient and electronic conductivity, and lowers cation migration barrier, as evidenced by a series of experimental and theoretical studies. Moreover, an aqueous “rocking‐chair” Zn‐ion full battery is successfully demonstrated by this Na0.14TiS2 anode and ZnMn2O4 cathode, which delivers a capacity of 105 mAh g−1 (for anode) with an average voltage of 0.95 V at 0.05 A g−1 and preserves 74% retention after 100 cycles at 0.2 A g−1, demonstrating the feasibility of Zn‐ion full batteries for energy storage applications.
Y chromosome gene copy number and lack of autism phenotype in a male with an isodicentric Y chromosome and absent NLGN4Y expression
Authors: Ross Judith L. , Bloy Luke , Roberts Timothy P. L. , Miller Judith , Xing Chao , Silverman Lawrence A. , Zinn Andrew R.
Published: June 2019

We describe a unique male with a dicentric Y chromosome whose phenotype was compared to that of males with 47,XYY (XYY). The male Y‐chromosome aneuploidy XYY is associated with physical, behavioral/cognitive phenotypes, and autism spectrum disorders. We hypothesize that increased risk for these phenotypes is caused by increased copy number/overexpression of Y‐encoded genes. Specifically, an extra copy of the neuroligin gene NLGN4Y might elevate the risk of autism in boys with XYY. We present a unique male with the karyotype 46,X,idic(Y)(q11.22), which includes duplication of the Y short arm and proximal long arm and deletion of the distal long arm, evaluated his physical, behavioral/cognitive, and neuroimaging/magnetoencephalography (MEG) phenotypes, and measured blood RNA expression of Y genes. The proband had tall stature and cognitive function within the typical range, without autism features. His blood RNA showed twofold increase in expression of Yp genes versus XY controls, and absent expression of deleted Yq genes, including NLGN4Y. The M100 latencies were similar to findings in typically developing males. In summary, the proband had overexpression of a subset of Yp genes, absent NLGN4Y expression, without ASD findings or XYY‐MEG latency findings. These results are consistent with a role for NLGN4Y overexpression in the etiology of behavioral phenotypes associated with XYY. Further investigation of NLGN4Y as an ASD risk gene in XYY is warranted. The genotype and phenotype(s) of this subject may also provide insight into how Y chromosome genes contribute to normal male development and the male predominance in ASD.