To get best conformers of each molecule the Sybyl X-2.1.1 software package was used for energy minimization. The energy minimizations were done using Tripos force field and the Powell gradient algorithm with a convergence criterion of 0.05 kcal/(mol*Å) and maximum iteration count of 1000. The partial atomic charges were calculated using Gasteiger- Huckel method 3 .
Tropical diseases are responsible for worldwide health problem is affected by millions of people annually. The bifunctional enzyme DHFR-TS from parasites as Toxoplasma gondii, Cryptosporidium parvum and four species of Plasmodium plays a crucial role in pyrimidine biosynthesis has been used as target for structure-based drug design. Plasmodium falciparum DHFR structural data to develop novel inhibitors with higher potency and selectivity data would be useful for molecular modeling DHFRs from species of parasites. Crystallographic analyses of the Leishmania major in binary and ternary complexes identified the interactions can be exploited in a structure-based development of novel enzyme inhibitors with potential therapeutic value. A structural comparison with the human enzyme identified a potentially important difference in the substrate- binding cleft assist to the development of TbGalE specific inhibitors. The xenobiotic electrophiles have identified antischistosomal antimalarial and antifilarial activity of compounds known for their GST inhibiting activity.
The CoMFA steric and electrostatic Þ elds based PLS analysis are represented as 3D contour plots in (Þ gs. 6 and 7), using compound 18 as reference structure. The steric contour map shows that the phenyl ring attached at C-5 of the molecules is surrounded by sterically favored region that are ß anked with a small unfavorable yellow region, suggesting that there is a deÞ nite requirement of substructure with appropriate shape to exhibit biological activity at C-5 of the molecule. This is further supported by analyzing compounds 9, 33, 14 and 15. Compound 9 and 33, have a penta ring attached at C-5 but greatly differ in their activity (Compound 9 has pIC 50 = 4.60 and compound 33 has pIC 50 = 3.7) because attachment is having different orientation. Compound 14 and 15 both have aliphatic chain system at C-5 but compound 15 is more active (pIC 50 = 4.6) than compound 14 (pIC 50 = 4.3) because compound 14 has isopropyl group at C-5 and compound 15 has more bulky isobutyl at same place.
3DRISM solvent model to capture specific molecular interactions. Extensive benchmarking over datasets for six diﬀerent protein-ligand systems demonstrates that the original CARMa method performs better than CoMFA in most cases. Using solvent density distribution functions ( g O (r) , g H (r) ) gives consistently more accurate predictions than using solvation
39 Read more
0.732, respectively. Furthermore, bioactive conformation was explored and explained by docking of the potent compound 25 into the binding site of androgen receptor. Present study deals with comparative molecular field analysis, comparative similarity indices analysis and hologram quantitative structure activity relationship and molecular docking studies of the ionone-based chalcones and their derivatives, obtained from literature. The model obtained could be effectively used as a channeling tool for further structure modification and designing of some novel potent anti-prostate cancer compounds. Key words: Prostate cancer, CoMFA, CoMSIA, HQSAR, MOLCAD docking
11 Read more
To verify the confidence of the proteome data, the expression patterns of four HFF proteins (FN1, GAPDH, KLK3, and WFDC2) from 20 normal weight women and 20 overweight status women were ana- lyzed by Western blot (Fig. 6a). The results indicated that the levels of the four proteins were consistent with the proteomic result. ELISA was used to detect the lev- els of WFDC2 in HFF of 25 normal weight women and 25 overweight status women. The result showed that WFDC2 protein level was elevated in the HFF of over- weight status women (33.1 ± 1.6 pmol/L) compared with that of normal weight women (28.8 ± 1.3 pmol/L) (p = 0.0484). ROC curve analysis showed that the AUC was 0.7 to distinguish the overweight status women from the normal weight women, with a sensitivity of 64% and a specificity of 72% (Fig. 6b). This result indi- cated that WFDC2 could be a potential candidate HFF marker for the diagnosis of oocyte maturation arrest of the overweight status women with a relatively higher sensitivity.
12 Read more
Our results suggest that the tissue culture process probably may lead to modifications at the epigenome of micro-propagated derived materials. According to Kaeppler et al. (2000), DNA methylation variation frequently occurs in the tissue culture process. Indeed, we observed that even in the in vitro normal plantlets (plantlets without symptoms of somaclonal variation) it was possible to detect differences in the MSAP molecular profile in comparison to the mother plant. Thus, not all changes associated with DNA methylation due to the tissue culture process may produce abnormal plants. These results were similar to that described by Matthes et al. (2001) in oil palm where changes in methylation were not necessarily associated with the abnormal phenotype derived from tissue culture.
12 Read more
neoplastic disorders, especially in conjunction with conventional chromosome studies. Using FISH, cytogeneticists can detect chromosomal abnormalities that involve small segments of DNA if their probe is situated, fortuitously or by design, in the affected chromosomal segment (41). FISH can be used to establish the order of DNA clones relative to bands, naturally occurring breakpoints, and other clones. Even more importantly, FISH permits karyotype analysis of nuclei in non-dividing cells. FISH has been used for the detection of t(2;5) (p23;q35) translocation in anaplastic large-cell lymphoma (42), for minimal residual disease in haematopoietic stem cell assays from peripheral blood stem cells of acute myeloid leukaemia (AML) patients with trisomy 8 (43), and for analysing chromosomal abnormalities of tumours in children (44).
The Web development has drastically changed the human interaction and communication, leading to an exponential growth of data generated by us- ers in various digital media. This mass of data provides opportunities for understanding people’s opinions about products, services, processes, events, political movements, and organizational strategies. In this context, it be- comes important for companies to be able to assess customer satisfaction about their products or services. One of the ways to evaluate customer sen- timent is the use of Sentiment Analysis, also known as Opinion Mining. This research aims to compare the efficiency of an automatic classifier based on dictionary with the classification by human jurors in a set of comments made by customers in Portuguese language. The data consist of opinions of service users of one of the largest Brazilian online employment agencies. The performance evaluation of the classification models was done using Kappa index and a Confusion Matrix. As the main finding, it is noteworthy that the agreement between the classifier and the human jurors came to moderate, with better performance for the dictionary-based clas- sifier. This result was considered satisfactory, considering that the Senti- ment Analysis in Portuguese language is a complex task and demands more research and development.
10 Read more
In vitro drug susceptibility testing of clinical isolates Adult patients with falciparum malaria were invited to provide a blood sample before starting treatment for in vitro drug susceptibility testing of their isolates. The heparinized venous blood sample (2 mL) was centri- fuged at 295×g for 10 min, the plasma was removed and remaining red blood cells were preserved by add- ing Glycerolyte57 solution (Baxter, Deerfield, IL, USA) and stored in liquid nitrogen at the field site. The cryo- preserved parasites were transferred to the Australian Defence Force Malaria and Infectious Disease Institute (ADFMIDI) on dry-ice, where they were adapted to cul- ture over a 2–3 week period . For in vitro anti-malar- ial activity assessment, stocks of the following drugs: atovaquone (ATQ) was obtained from GlaxoSmithKline (Hertfordshire, UK); desethylamodiaquine (DAQ), dihy- droartemisinin (DHA), piperaquine tetraphosphate (PPQ) were obtained from the WorldWide Antimalarial Resistance Network (WWARN QA/QC Reference Mate- rial Programme, Bangkok, Thailand), and chloroquine diphosphate (CQ), mefloquine hydrochloride (MQ), and pyronaridine tetraphosphate (PRN) were purchased from Sigma (St. Louis, MO, USA). The drugs were prepared to 1 mM in either dimethyl sulfoxide (DMSO), methanol or 50% methanol/50% water and subsequently diluted in culture media lacking hypoxanthine. Drug susceptibility of the field isolates was evaluated by measuring the inhi- bition of the radioactive [ 3 H]-hypoxanthine uptake by
11 Read more
The computational drug designing is the principal streamline to evaluate the affinity of small molecules toward specific targets that unveils a potential to disparage the consumption of time in industries with the combination of computational, biological and chemical knowledge. In-silico approaches in drug development play a key role to reconnoiter molecular aspects of targeting specific proteins through various tools and softwares, and analyzing the bioactivities and inhibitory effects across mechanisms underlying for treatment of several chronic diseases. An enigmatic suffering that killed a farmer in Kansas, US has led to the discovery of a new virus called the Bourbon Virus as reported by Vox media on February 25 th , 2015. Because the virus has been recently discovered and tagged with various life
14 Read more
predictive capacity for thienopyridine carbonitriles Src inhibitors in the present studies. The models can provide quantitative estimations of inhibitory activity of thienopyridine carbonitriles on Src. In the CoMFA model, the addition of a bulky group or the electropositive group to the R 1 group can enhance the inhibitory activity of the compound. In addition, reducing the bulky group or increasing the electronegative group on the R 2 group can also increase the inhibitory activity of the compound (fig. 4A). The effect of methoxy as an electronegative group on the activity was greater than the effect of its steric hindrance. However, after comparing the structure and activity of compounds 7, 8 and 9, it was found that the activity of a compound is reduced when a methyl group was added to the methoxy group, indicating that effect of steric hindrance of thienopyridine carbonitriles might have a higher priority than the effect of electrostatic field in the inhibitory activity on Src. That could explain the differences in the inhibitory activity among compounds 2, 3 and 4 as well. Therefore, both steric and electrostatic factors play key roles in the inhibitory activity of thienopyridine carbonitriles on Src. According to the 3D Contour maps of the CoMSIA model, the hydrophilic and hydrogen bond acceptor groups at the R 1 group are advantageous for the activity of these compounds (fig. 5A-B). However, hydrogen bond donating groups, which are located at the R2 group might increase the activity of the compounds (fig. 5C). In fact, hydrogen bond donor groups are not exclusively located on the R 2 group and are also located on the imino group of the skeleton, which is contained by each thienopyridine carbonitrile compound. Therefore, the imino group in
12 Read more
The magnetic measurements reported in this thesis were performed on SQUID (Super conducting QUantum Interference Device) magnetometers. DC magnetic measurements were recorded on the MPMS7 Quantum Design SQUID Magnetometer equipped with a 7 Tesla magnet^^. Measurements were carried out in the temperature range 2-300K. In SQUID magnetometers the dipole field of the magnetised sample and its holder are measured as they are moved through detector coils. In order to avoid sample holder contributions to the measured magnetisation the sample holder must, therefore, maintain a constant susceptibility along the length of measurement (>4cm). Sample mounting was as follows; Powder samples of around ~30mg (~3x3x6mm3) were loaded into gel caps and then placed in tight fitting transparent straws, which had been periodically punctured with tiny holes along their length. The straws were then loaded with three compensatory empty gel caps on either side of the sample containing gel cap. The loaded straws were then firmly fixed to the SQUID sample mount with Quantum Design magnetic (non-magnetic) tape.
182 Read more
The second layer of analysis occurs through a systematic examina- tion of the interviews using a constant comparative method (Glaser and Strauss 1967). Specifically, for each question, interviews should be examined to identify patterns in the way respondents interpret and pro- cess the question. By making comparisons across all of the interviews, interpretive patterns can be identified and examined for consistency. If a question asks respondents to evaluate ‘‘the system of public benefits and services in their country,’’ for example, it would be important to under- stand the degree to which respondents are considering the same types of benefits and services. From this layer of analysis, patterns of calculation across respondents can be identified. This is particularly useful in understanding how qualifying clauses such as ‘‘in the past 2 weeks’’ or ‘‘on average’’ impact the way respondents form an answer, whether respondents consistently use the clause in their calculation, and how inconsistencies might impact reliability of the resulting survey data. At this point, it is possible to identify a theoretical framework for understanding the interpretive meaning behind respondents’ answers and the type of information that is ultimately transported through the survey statistic.
19 Read more
Three typical stations were adopted in this paper for analysis of the characteris- tics of the haze in Chengdu. Shuangliu is located in Southwestern Chengdu, 12 km away from the downtown area straightly. There is no clear boundary be- tween it and the downtown area due to the high urbanization speed. Dujiangyan is located in northwestern Chengdu, where urbanization is slower than other districts and counties. The environmental protection bureau has taken Dujian- gyan as the environmental background field. Also, Dujiangyan has been taken as the climatic and environmental background field in this paper. Wenjiang is lo- cated in northern Chengdu, which is a national base station.
14 Read more
X-ray diffraction (Cu–K , Siemens D-5000) was employed to identify the crystal Structure of the samples at room temperature. Field Emission-Scanning Electron Microscopy (FESEM) (JEOL JSM– 7600 F) was used to examine the grain size and morphology. Magnetization curves were measured using a vibrating sample magnetometer (VSM, DMS 880) in the temperature range of 80–570 K and in applied magnetic fields up to 10 kOe. For the magnetic measurements, the powders were pressed in the forms of platelets.
Chovancova, E., Pavelka, A., Benes, P., Strnad, O., Brezovsky, J., Kozlikova, B., Gora, A., Sustr, V., Klvana, M., Medek, P., Biedermannova, L., Sochor, J. and Damborsky, J. (2012) ‘CAVER 3.0: A Tool for the Analysis o f Transport Pathways in Dynamic Protein Structures’, PLoS Computational Biology. Edited by A. Prlic, 8(10), p. e1002708. doi: 10.1371/journal.pcbi.1002708. Chukwuma, C. I. and Islam, M. S. (2016) ‘Xylitol: One Name, Numerous Benefits’,
48 Read more
The amplified fragment length polymorphism (AFLP) marker system (Zabeau and Vos 1993; Vos et al. 1995) has the highest multiplex ratio of all PCR-based marker systems. More than 100 restriction fragments can be amplified simultaneously (Schwarz et al. 2000). The high multiplex ratio of AFLP analysis makes it the most efficient method for generating large numbers of anonymous DNA markers for use in genetic linkage and diversity studies. The efficiency and relatively low cost of AFLP analysis have enabled de novo genetic map construction in many species (Marques et al. 1998; Bert et al. 1999; Debener and Mattiesch 1999; Remington et al. 1999; Lespinasse et al. 2000; Van Heusden et al. 2000; Schwarz et al. 2000) as well as the saturation of existing linkage maps (Keim et al. 1997; Qi et al. 1998; Boivin et al. 1999; Haanstra et al. 1999; Vuylsteke et al. 1999) and high-resolution mapping of genomic regions of interest (Ballvora et al. 1995; Meksem et al. 1995; Cnops et al. 1996; Simons et al. 1997; Bendahmane et al. 1997; Hartl et al. 1999). In addition, the marker system has provided a fast, low-cost approach for studying genetic diversity (Hartl and Seefelder 1998; Marsan et al. 1998; Breyne et al. 1999) and obtaining molecular phylogenies (Hill et al. 1996; Heun et al. 1997; Kardolus et al. 1998; Aggarwal et al. 1999).
249 Read more
What I am less enthusiastic about, are the alignment-free methods the authors discuss, in particular the k-mer-based approaches. To my knowledge, the prospects of these particular methods are very limited. Certainly, alignment-free approaches are attractive but from an information-theoretical standpoint, I find it dubious that they promise much progress, at least when large phylogenetic depths are involved. At this juncture, I am more optimistic about clever algorithmic improvements on the “ conventional ” phylogenomic methods. The prime example is FastTree  that, in my experience, has changed the practice of phylogenetic analysis by combining the (nearly) full rigour of maximum likelihood with the speed of methods like neighbour joining. Although the MSA problem itself may be even more challenging, promising developments are appearing in this area as well, e.g. .
The antifungal activity data against Candida albicans for a series of 3-aryl-4-[α-(1H-imidazol-1-yl) aryl methyl] pyrroles containing 40 compounds as anticandida agents was used in this analysis. General structure of the compounds is shown in (fig. 1). Training set was formed by selecting 33 compounds from the original series. Test set compounds were no. 11, 12, 33, 34, 35, 37 and 42 (total 7 compounds), selected randomly. These compounds were not included in the analysis to generate the CoMFA model. The robustness and predictive ability of models were evaluated by selecting biological activity with chemical