bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, Synthesis and Antiplasmodial Evaluation of Sulfoximine-triazole Hybrids as Potential Antimalarial Prototypes
Authors: Mabasa Tommy F. , Awe Babatunde , Laming Dustin , Kinfe Henok H. 
Published: February 2019

Background:Malaria, caused by the deadly Plasmodium falciparum strain, claims the lives of millions of people annually. The emergence of drug-resistant strains of P. falciparum to the artemisinin-based combination therapy (ACT), the last line of defense against malaria, is worrisome and urges for the development of new chemo-types with a new mode of action. In the search of new antimalarial agents, hybrids of triazoles and other known antimalarial drugs have been reported to possess better activity than either of the parent compounds administered individually. Despite their better activity, no hybrid antimalarial drugs have been developed so far.Objective:In the hope of developing new antimalarial prototypes, we propose the design, synthesis and antimalarial evaluation of novel sulfoximine-triazole hybrids owing to their interesting biological and physiological properties.Methods:The sulfoximine part of the hybrid will be synthesized via imidation of the corresponding sulfoxide. Propargylation of the NH moiety of the sulfoximine followed by copper-catalyzed click chemistry with benzyl azide was envisaged to provide the target sulfoximine-triazole hybrids.Results:Five novel sulfoximine-triazole hybrids possessing various substituents on the sulfoximine moiety have been successfully synthesized and evaluated for their antiplasmodial and cytotoxicity activities. The results revealed that the co-presence of the sulfoximine and triazole moieties along with a lipophilic alkyl substituent on the sulfur atom impart significant activity.Conclusion:Sulfoximine-triazole hybrids could be used as a prototype for the synthesis of new derivatives with better antiplasmodial activities.
Polyethylene Glycol Acts as a Mechanistic Stabilizer of L-asparaginase: A Computational Probing
Authors: Sindhu Rajashekar , Pradeep Hanumanthappa , Manonmani Haravey K. 
Published: February 2019

Background:
L-asparaginase (L-ASN) is an anti-cancer enzyme therapeutic drug that
exerts cytotoxicity via inhibition of protein synthesis through depletion of L-asparagine in the tumor
microenvironment. The therapeutic performance of the native drug is partial due to the associated
instability, reduced half-life and immunogenic complications.

Objective:
In this study, we attempted the modification of recombinant L-asparaginase with PEG
and an integrated computational strategy to probe the PEGylation in the protein to understand the
biological stability/activity imparted by PEG.

Methods:
In vitro PEGylation of recombinant L-ASN was carried out and further evaluated in
silico.

Results:
PEGylation enhanced thermal and pH activities with extended serum half-life and resistance
to proteases compared to the native enzyme. The molecular dynamics analysis revealed intricate
interactions required in the coupling of PEG to L-asparaginase to bestow stronger binding affinity
of L-asparagine moiety towards L-asparaginase. PEG-asparagine complex ensured stable
conformation over both the native protein and asparagine-protein complex thus elucidating the
PEG-induced stable conformation in the protein. PEG mechanistically stabilized L-asparaginase
through inducing pocket modification at the receptor to adapt to the cavity.

Conclusion:
The study provides the rationale of PEGylation in imparting the stability towards Lasparaginase
which would expand the potential application of L-asparaginase enzyme for the effective
treatment of cancer.
Target Based Virtual Screening of New Leads Inhibitor against Bacterial Cell Division Protein FtsZ for the Discovery of Antibacterial Agents
Authors: Mishra Ratish C. , Kumari Rosy , Yadav Shivani , Yadav Jaya P. 
Published: February 2019

Background:Staphylococus epidermidis coagulase negative and gram positive streptococci have emerged as major nosocomial pathogens associated with the infection of implanted medical devices and dandruff on human scalp. S. epidermidis filamenting temperature-sensitive mutant Z (FtsZ) gene encoded FtsZ protein that assembles at future bacterial cell division site that forms Z-ring structure. FtsZ is a tubulin homolog protein with low sequence similarity; this makes it possible to inhibit bacterial FtsZ protein without affecting the eukaryote cell division.Objective:In the present study, phytochemicals of Cinnamomum zeylanicum, Punica granatum and Glycyrrhiza glabra were virtually screened for their antibacterial activity against Staphylococcus epidermidis cell division protein, FtsZ.Methods:Molecular docking method was used to investigate new lead inhibitor against bacterial cell division protein FtsZ. SwissADME and ProTox tool were used to evaluate the toxicity of the lead molecule.Results:Molecular docking based screening confirmed that among 122 phytochemicals, β- sitosterol and glabrol showed the highest inhibitory activity against FtsZ. SwissADME tool showed β-sitosterol and glabrol as the ideal antibacterial agents.Conclusion:Structure based drug design strategy has been broadly used to optimize antimicrobial activity of small molecule/ligand against large protein receptor of disease, causing pathogens which gives a major breakthrough in pharmaceuticals industries. The molecular docking and SwissADME tool showed that β-sitosterol and glabrol may be developed to be potential topical and sublingual antibacterial agents, respectively.
Novel 1,3,4-Triaryl Pyrazoles: Synthesis, QSAR Studies and Cytotoxicity against Breast Cancer
Authors: Ismail Magda M.F. , Farrag Amel M. , Harras Marwa F. 
Published: February 2019

Background:The existence of drug-resistance and lack of selectivity encourages scientists to search for novel and more selective cytotoxic agents.Objective:In this work, novel 1,3,4-triarylpyrazole derivatives were synthesized to study their cytotoxicity on MCF7 (human breast Cell Line). In addition, QSAR studies were performed to show the relation between the cytotoxic activity and the structural features of our new synthesized pyrazole derivatives.Methods:Pyrazole-4-carbaldehyde derivative 3 was utilized as a starting material for the preparation of the new pyarazole derivatives. These target compounds were screened for their cytotoxic activity against MCF-7 followed by study cell cycle of the most active compounds. Finally, pharmacophore modeling and QSAR Studies was carried out.Results:Among these compounds; 5d and 8b showed the highest anti-proliferative activity (IC50 = 4.9 and 2.11 µM, respectively). Flow cytometric analysis showed that, compounds 5d and 8b arrested the cell cycle in addition to induction of apoptosis in MCF7 cells. Moreover, their stimulation effect on caspases 3/7 was examined to explore their mechanism of induction of apoptosis and the results showed that their proapoptotic activity could be due to the activation of caspases 3/7.Conclusion:Pyrazole derivatives 5d and 8b displayed potent bioactivities, indicating that these compounds could be considered as a new lead for more investigation in the future
Biomarkers of Osteoporosis: An Update
Authors: Parveen Bushra , Parveen Abida , Vohora Divya 
Published: February 2019

Background:
Osteoporosis, characterized by compromised bone quality and strength is
associated with bone fragility and fracture risk. Biomarkers are crucial for the diagnosis or prognosis
of a disease as well as elucidating the mechanism of drug action and improve decision making.

Objective:
An exhaustive description of traditional markers including bone mineral density, vitamin D,
alkaline phosphatase, along with potential markers such as microarchitectural determination, trabecular
bone score, osteocalcin, etc. is provided in the current piece of work. This review provides insight into
novel pathways such as the Wnt signaling pathway, neuro-osseous control, adipogenic hormonal imbalance,
gut-bone axis, genetic markers and the role of inflammation that has been recently implicated
in osteoporosis.

Methods:
We extensively reviewed articles from the following databases: PubMed, Medline and Science
direct. The primary search was conducted using a combination of the following keywords: osteoporosis,
bone, biomarkers, bone turnover markers, diagnosis, density, architecture, genetics, inflammation.

Conclusion:
Early diagnosis and intervention delay the development of disease and improve treatment
outcome. Therefore, probing for novel biomarkers that are able to recognize people at high risk for
developing osteoporosis is an effective way to improve the quality of life of patients and to understand
the pathomechanism of the disease in a better way.
Elucidation of the Chemopreventive Role of Stigmasterol Against Jab1 in Gall Bladder Carcinoma
Authors: Pandey Pratibha , Bajpai Preeti , Siddiqui Mohammad H. , Sayyed Uzma , Tiwari Rohit , Shekh Rafia , Mishra Kumudesh , Kapoor V.K. 
Published: February 2019

Background:Plant sterols have proven a potent anti-proliferative and apoptosis inducing agent against several carcinomas including breast and prostate cancers. Jab1 has been reported to be involved in the progression of numerous carcinomas. However, antiproliferative effects of sterols against Jab1 in gall bladder cancer have not been explored yet.Objective:In the current study, we elucidated the mechanism of action of stigmasterol regarding apoptosis induction mediated via downregulation of Jab1 protein in human gall bladder cancer cells.Methods:In our study, we performed MTT and Trypan blue assay to assess the effect of stigmasterol on cell proliferation. In addition, RT-PCR and western blotting were performed to identify the effect of stigmasterol on Jab1 and p27 expression in human gall bladder cancer cells. We further performed cell cycle, Caspase-3, Hoechst and FITC-Annexin V analysis, to confirm the apoptosis induction in stigmasterol treated human gall bladder cancer cells.Results:Our results clearly indicated that stigmasterol has up-regulated the p27 expression and down-regulated Jab1 gene. These modulations of genes might occur via mitochondrial apoptosis signaling pathway. Caspase-3 gets activated with the apoptotic induction. Increase in apoptotic cells and DNA were confirmed through annexin V staining, Hoechst staining, and cell cycle analysis.Conclusion:Thus, these results strongly suggest that stigmasterol has the potential to be considered as an anticancerous therapeutic agent against Jab1 in gall bladder cancer.
PHARMACOGNOSTICAL AND PHYSICOCHEMICAL ANALYSIS OF TODDALIA ASIATICA (L.) LAM. RUTACEAE
Authors: Bangajavalli S. 
Published: February 2019

Objective: To characterize macroscopical and microscopical features of the leaf and stem of Toddalia asiatica (L.) Lam. RUTACEAE. Explore and establish the micro-morphology and quality control methods for this plant.Methods: leaves and stem ofÂ Toddalia asiatica (L.) Lam. wereÂ collected for Pharmacognostic studies involving macros, microscopic evaluation and physicochemical parameters analysis like Ash value, Moisture content, Fluorescence analysis and phytochemicals.Results: The leaf even and smooth on the adaxial side and highly undulate and densely hairy on the abaxial side. The midrib is very thick projecting much below the lower side of the leaf. The midrib is slightly revised above the adaxial side. It is thick and semicircular on the abaxial side. It is 950 Âµm thick and 900 Âµm wide. The lateral vein hangs from the abaxial surface of the lamina. It is thick and prominent. There is no distinct differentiation of palisade and spongy mesophyll tissue. The lamina is 100 Âµm thick. In the region of lateral veins, it is 160 Âµm thick. Calcium oxalate crystals are fairly abundant in the secondary xylem parenchyma cells of the stem. Prismatic crystals also sparsly seen in the parenchyma cells outside the gelatinous fibre. The powder was also treated with different chemical reagents and changes in colour were studied in ordinary light and UV light. These fluorescence characters were determined according to the methods of Chase and Pratt. The total moisture content of the Toddalia asiatica was 46%. The total ash content of the whole plant was found 96%, the acid insoluble ash content of the whole plant was found 5%, the water-soluble ash content of the whole plant was found 2%, and the sulphated ash content of the whole plant was found 85%. The extractive values obtained from different solvents were found in the Toddalia asiatica among all the extracts chloroform showed the highest percentage (81%) followed by Ethanol (45%) and Benzene (44%). The distribution of different phytochemical constitutes in ethanol, benzene, chloroform acetone, petroleum ether and water of whole plant powder was evaluated qualitatively. The phytochemical such as carbohydrates, saponins, flavonoid, alkaloids, cardiac glycosides, phenols, coumarins, and steroids have been confirmed in the all the above extracts of the selected plant. Moreover, phytochemicals such as alkaloids, flavonoid, cardiac glycosides, courmarins, and steroids are also present in the sample and absence of, anthraquinone, steroid, terpenoid and fixed oil.Conclusion: The observations confirmed thatÂ Toddalia asiatica obvious Pharmacognostic characteristics, which will be useful towards providing a reliable basis for identification, purity, quality, and classification of the plant. Results shall pave a way in the standardization of the drug.
Extracción de ADN con material cotidiano: diseño, implementación y validación de una intervención activa interdisciplinar
Authors: Gómez Ochoa de Alda Jesús , Esteban Gallego Rocío , Marcos-Merino José María 
Published: February 2019

<span lang="ES">Las prácticas tradicionales de ciencias, basadas en seguir instrucciones cerradas, no proporcionan resultados de aprendizaje satisfactorios. Esto se debe, en parte, a que no tienen una aplicación inmediata, carecen de una perspectiva interdisciplinar y el alumno no desarrolla un papel activo en su resolución. Una alternativa es su planteamiento como pequeñas investigaciones en las que los alumnos desarrollan su propio guion a través de preguntas elaboradas por el docente. Con el fin de aumentar el número de propuestas de prácticas activas, en este trabajo se describe y valida una intervención didáctica, la extracción de ADN con material cotidiano, centrada en el aprendizaje activo interdisciplinar. Esta práctica es muy atractiva para los alumnos de educación secundaria, bachiller o maestros en formación ya que, al desarrollarse bajo investigación dirigida, hace que los estudiantes participen en la búsqueda, interpretación y utilización de algunos fundamentos científicos de Química, Física y Biología. El análisis de la efectividad de la implementación de esta intervención durante 3 cursos académicos muestra que esta favorece el aprendizaje interdisciplinar. </span>
Doluluk Oranlarının PLA ve PET Malzemelerin Mekanik Özellikleri Üzerine Etkileri
Authors: EVLEN Hatice , ÖZDEMİR Merve Ayfer , ÇALIŞKAN Aydın 
Published: February 2019

Gerçekleştirilen çalışmada, yığma teknolojisi ile üretim yapan bir yazıcı
modellemek ve modellenen üç boyutlu yazıcıda doluluk oranının mekanik
özellikler üzerine etkilerinin incelenmesi amaçlanmıştır. Bu amaç kapsamında
kartezyen tipi açık kaynaklı bir üç boyutlu yazıcı modellenmiştir. Prototip
imalatı yapılan üç boyutlu yazıcı kullanılarak PET ve PLA malzemelerin %10, 20,
30, 40 ve %50 doluluk oranlarında mekanik test numuneleri yazdırılmıştır. Elde
edilen numuneler tek eksenli çekme testleri tabi tutulmuş, sertlik ve
pürüzlülük değerleri ölçülmüştür. Yapılan ölçümler neticesinde PET ve PLA
malzemelerde sertlik değerinin malzemenin doluluk oranı ile doğru orantılı
olduğu, doluluk oranı arttıkça malzemelerin sertliklerinin de arttığı
görülmüştür. PLA ve PET malzemelerden üretilen numunelerin pürüzlülük ve çekme
değerlerinin birbiriyle ters orantılı olduğu, pürüzlülük ve çekme mukavemeti
değerlerinin %30 doluluk oranından itibaren
%10 ve %20 doluluk oranındakinin aksi yönde seyrettiği görülmüştür.
Morphology Characteristics of Rattan (Calamus SP.) Tourism Forest In Bariat The South Sorong Regency
Authors: Irnawati Irnawati , Nanlohy Lona 
Published: February 2019

Rattan grows naturally inbeaches and mountains. Ecologically, it could grow rapidly in various places especially with high humidity areas such as riverside. The research conducted to identify and discover the morphology characteristics of botanical rattans which are being used by the local communities in Bariat natural Park Forest.Theresults of this research can be used for the cultivation and conservation of rattan (calamus SP.). The methodology of research is descriptive which is conducted with field visits. The first samples were collected randoml, however, the second and third sample was collected systematically. These collection method to determine the distribution of rattan growth. Five types of rattan were found in the research area which is divided into three classifications. Two of them are classified as Calamus, the other two are Daemonorops and the last one is Korthalsia. Turning into the way of the rattan grow in Bariat, four of them grow as clumping plants while the other one is single trunk (solitary). In Bariat, the rattan has low diversity but high quantity. It is potentially to be used as a source of biodiversity which has high economy value for the local community
Peer Assessment in Writing: A Critical Review of Previous Studies
Authors: Gupta Sonia Dutta , Abdullah Fatimah , Li Gu , Xueshuang Yang 
Published: February 2019

Peer assessment has attracted more attention an effective assessment tool in recent years. Peer assessment refers to the arrangement for peers to consider the quality of learning outcomes of others of similar status, it received attention of various studies due to the growing interest in the student centered approach as learners need to be involved in the learning process even in the assessment. This paper is a critical review of previous studies on peer assessment in English as Second/Foreign Language (ESL/EFL) context. Fifteen peer assessment studies from 2004 to 2017 were extensively reviewed and systematically analyzed. Peer assessment of the reviewed studies were on the quality of the writing outcomes of students in the EFL/ESL contexts, as writing skill occupies an important role in teaching English language. As a critical review paper of these studies, this paper highlights practical use of peer assessment and the important challenges or issues that need to be considered when utilizing peer assessment in the classroom. This paper hopes that practical measures of peer assessment will be utilized effectively by educators in the ESL and EFL classrooms in the near future.
A comparative study of teachers perspectives in city center of Fars and its remotest towns or villages toward high schools' Junior Secondary book
Authors: Bagheri Masoud , Karampour Fatemeh 
Published: February 2019

Regarding the textbook evaluation a whole slew of studies are done and each of which is taken into account different aspects of the books. Since the book entitled Prospectone is a recently released one and there was no investigation about it the researcher decided to scrutinize it. The investigator administered a questionnaire and a semi-structured interview. The study was intended to investigate and compare the teachers perspectives in center of Fars Province and in its remotest villages or towns such as Lamerd, Mohr, Galedar, Ashkanan and Alamarvdasht. A total population of 100 people participated in this research. To gather the data, Litz questionnaire was used. Regarding the obtained findings from the questionnaires and semi-structures interviews, it revealed that the teachers in remotest villages ran through more difficulties. And it is believed that most of their problems are due to the lack of background knowledge. The learners who attended grade7th had no background knowledge in English. As Krashen(1975) stated the input that the learners receive should be comprehensible and one level higher than the student immediate knowledge.Â Although most of the learners in Fars province participated in extra curricular classes, mostly institute classes, the students in rural places had never attended in any. Another revealed result is that there was not any balance between the skills in the book and most of the empathies are on oral skills. To put all the aforementioned statements into a nutshell, it can be said that there is a big gap between students current knowledge in Fars province and the ones in villages.
New Drug Delivery Systems Concept in Anaesthesia and Intensive Care—Controlled Release of Active Compounds
Authors: Bratu Tiberiu , Dinu Anca , Sandesc Mihai , Popovici Sonia Elena , Dragoi Razvan Gabriel , Elena Amaricai , Sandesc Dorel 
Published: February 2019

Abstract
With time, medical and pharmaceutical research has advanced significantly. However, one of the major issues is how to administer the active substance. Among these, it counts over- or under-dosage of the active substance, low re­sponse to treatment, or increased clinical risk of the patient. An innovative method able to avoid these obstacles is represented by controlled release systems for active substances. The interest for these systems came with allowing encapsulation in the antibiotic release matrices, local anesthetics, protein or other substances. Moreover, a number of such vehicles are now available to release controlled substances used predominantly in the anesthesia and intensive care unit.
«Existir» e «existência» em Platão
Authors: Trindade José 
Published: February 2019

Abstract
Parmenides’ argument in the Way of Truth and Plato’s theory of Forms are usually seen as mighty metaphysical constructions. But what if they are motivated by the semantic complexity of the Greek verb ‘be’? This is the approach followed throughout this paper, mostly dealing with the debate on the emergence of a separate existential reading of ‘einai,’ and the problems arising from the use of the Latin verb ‘existere’ to translate it. The analysis of some sophistic puzzles provides examples of this fused reading of the verb. They suggest that Plato’s philosophical program was intended as a correction of current sophistic views on reality and discourse, both through his theory of Forms, and the analysis of being and not being, carried out in the Sophist.