bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of cytochrome P450 isoform responsible for metabolizing a drug molecule
Authors: Mishra Nitish K , Agarwal Sandhya , Raghava Gajendra PS 
Published: July 2010

Abstract

Background
Different isoforms of Cytochrome P450 (CYP) metabolized different types of substrates (or drugs molecule) and make them soluble during biotransformation. Therefore, fate of any drug molecule depends on how they are treated or metabolized by CYP isoform. There is a need to develop models for predicting substrate specificity of major isoforms of P450, in order to understand whether a given drug will be metabolized or not. This paper describes an in-silico method for predicting the metabolizing capability of major isoforms (e.g. CYP 3A4, 2D6, 1A2, 2C9 and 2C19).

Results
All models were trained and tested on 226 approved drug molecules. Firstly, 2392 molecular descriptors for each drug molecule were calculated using various softwares. Secondly, best 41 descriptors were selected using general and genetic algorithm. Thirdly, Support Vector Machine (SVM) based QSAR models were developed using 41 best descriptors and achieved an average accuracy of 86.02%, evaluated using fivefold cross-validation. We have also evaluated the performance of our model on an independent dataset of 146 drug molecules and achieved average accuracy 70.55%. In addition, SVM based models were developed using 26 Chemistry Development Kit (CDK) molecular descriptors and achieved an average accuracy of 86.60%.

Conclusions
This study demonstrates that SVM based QSAR model can predict substrate specificity of major CYP isoforms with high accuracy. These models can be used to predict isoform responsible for metabolizing a drug molecule. Thus these models can used to understand whether a molecule will be metabolized or not. This is possible to develop highly accurate models for predicting substrate specificity of major isoforms using CDK descriptors. A web server MetaPred has been developed for predicting metabolizing isoform of a drug molecule http://crdd.osdd.net/raghava/metapred/.
SMAD4 - Molecular gladiator of the TGF-β signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRASproto-oncogene
Authors: Sameer A Syed , Chowdri Nissar A , Syeed Nidda , Banday Mujeeb Z , Shah Zaffar A , Siddiqi Mushtaq A 
Published: July 2010

Abstract

Background
The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the SMAD4 gene mutations with KRAS mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of SMAD4 gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and KRAS mutant genotype.

Methods
We examined the paired tumor and normal tissue specimens of 86 CRC patients for the occurrence of aberrations in MCR region of SMAD4 and exon 1 of KRAS by PCR-SSCP and/or PCR-Direct sequencing.

Results
The overall mutation rate of mutation cluster region (MCR) region of SMAD4 gene among 86 patients was 18.6% (16 of 86). 68.75% (11/16) of the SMAD4 gene mutants were found to have mutations in KRAS gene as well. The association between the KRAS mutant genotype with SMAD4 mutants was found to be significant (P =< 0.05). Further more, we found a significant association of tumor location, tumor grade, node status, occupational exposure to pesticides and bleeding PR/Constipation with the mutation status of the SMAD4 gene (P =< 0.05).

Conclusion
Our study suggests that SMAD4 gene aberrations are the common event in CRC development but play a differential role in the progression of CRC in higher tumor grade (C+D) and its association with the KRAS mutant status suggest that these two molecules together are responsible for the progression of the tumor to higher/advanced stage.
The HAC1 gene from Pichia pastoris: characterization and effect of its overexpression on the production of secreted, surface displayed and membrane proteins
Authors: Guerfal Mouna , Ryckaert Stefan , Jacobs Pieter P , Ameloot Paul , Van Craenenbroeck Kathleen , Derycke Riet , Callewaert Nico 
Published: July 2010

Abstract

Background
The unfolded protein response (UPR) in eukaryotes upregulates factors that restore ER homeostasis upon protein folding stress and in yeast is activated by a non-conventional splicing of the HAC1 mRNA. The spliced HAC1 mRNA encodes an active transcription factor that binds to UPR-responsive elements in the promoter of UPR target genes. Overexpression of the HAC1 gene of S. cerevisiae can reportedly lead to increased production of heterologous proteins. To further such studies in the biotechnology favored yeast Pichia pastoris, we cloned and characterized the P. pastoris HAC1 gene and the splice event.

Results
We identified the HAC1 homologue of P. pastoris and its splice sites. Surprisingly, we could not find evidence for the non-spliced HAC1 mRNA when P. pastoris was cultivated in a standard growth medium without any endoplasmic reticulum stress inducers, indicating that the UPR is constitutively active to some extent in this organism. After identification of the sequence encoding active Hac1p we evaluated the effect of its overexpression in Pichia. The KAR2 UPR-responsive gene was strongly upregulated. Electron microscopy revealed an expansion of the intracellular membranes in Hac1p-overexpressing strains. We then evaluated the effect of inducible and constitutive UPR induction on the production of secreted, surface displayed and membrane proteins. Wherever Hac1p overexpression affected heterologous protein expression levels, this effect was always stronger when Hac1p expression was inducible rather than constitutive. Depending on the heterologous protein, co-expression of Hac1p increased, decreased or had no effect on expression level. Moreover, α-mating factor prepro signal processing of a G-protein coupled receptor was more efficient with Hac1p overexpression; resulting in a significantly improved homogeneity.

Conclusions
Overexpression of P. pastoris Hac1p can be used to increase the production of heterologous proteins but needs to be evaluated on a case by case basis. Inducible Hac1p expression is more effective than constitutive expression. Correct processing and thus homogeneity of proteins that are difficult to express, such as GPCRs, can be increased by co-expression with Hac1p.
Evaluation of medication adherence methods in the treatment of malaria in Rwandan infants
Authors: Twagirumukiza Marc , Kayumba Pierre Claver , Kips Jan G , Vrijens Bernard , Stichele Robert Vander , Vervaet Chris , Remon Jean Paul , Van Bortel M Luc 
Published: July 2010

Abstract

Objectives
To compare three methods for evaluating treatment adherence in a 7-day controlled treatment period for malaria in children in Rwanda.

Methods
Fifty-six children (< 5 years) with malaria were recruited at the University Hospital of Butare, Rwanda. Patients were treated with quinine sulfate, taste-masked, pellets during seven days: three days in hospital (in-patient) followed by a four-day out-patient period. Three methods to evaluate medication adherence among patients were compared: manual pill count of returned tablets, patient self-report and electronic pill-box monitoring. These pill-boxes were equipped with a microchip registering date and time of every opening. Medication adherence was defined as the proportion of prescribed doses taken. The inter-dose intervals were analysed as well.

Results
Medication adherence data were available for 54 of the 56 patients. Manual pill count and patient self-report yielded a medication adherence of 100% for the in- and out-patient treatment periods. Based on electronic pill-box monitoring, medication adherence during the seven-day treatment period was 90.5 ± 8.3%. Based on electronic pill-box monitoring inpatient medication adherence (99.3 ± 2.7%) was markedly higher (p < 0.03) than out-patient adherence (82.7 ± 14.7%), showing a clear difference between health workers' and consumers' medication adherence.

Conclusion
Health workers' medication adherence was good. However, a significant lower medication adherence was observed for consumers' adherence in the outpatient setting. This was only detected by electronic pill-box monitoring. Therefore, this latter method is more accurate than the two other methods used in this study.
Kinematic evidence for superfast locomotory muscle in two species of teneriffiid mites
Authors: Wu Grace C. , Wright Jonathan C. , Whitaker Dwight L. , Ahn A. N. 
Published: July 2010

SUMMARYLocomotory muscles typically operate over a narrow range of contraction frequencies, characterized by the predominant fiber types and functional roles. The highest documented frequencies in the synchronous sound-producing muscles of insects (550 Hz) and toadfish (200 Hz) far exceed the contraction frequencies observed in weight-bearing locomotory muscles, which have maximum documented frequencies below 15–30 Hz. Laws of scaling, however, predict that smaller arthropods may employ stride frequencies exceeding this range. In this study we measured running speed and stride frequency in two undescribed species of teneriffiid mites from the coastal sage scrub of southern California. Relative speeds of both species [129–133 body lengths (BL)s–1] are among the fastest documented for any animal. Measured stride frequencies for both species far exceed those documented for any weight-bearing locomotory muscle, with measured values for one species ranging from 93 Hz at 25°C to 111 Hz at 45°C. Stride frequencies either closely approximate or, for one species, exceed predicted values based on an interspecific scaling of frequency and animal mass. Consequently, while the ultra-high frequencies of these muscles must depend on appropriately scaled kinetics of the calcium transient and contraction–relaxation cycle, these do not appear to limit the operating frequencies during running. The predicted low muscle forces operating at these very high frequencies evidently suffice for locomotion, probably because of the larger relative muscle force generated by smaller animals.
Immediate spectral flexibility in singing chiffchaffs during experimental exposure to highway noise
Authors: Verzijden M. N. , Ripmeester E. A. P. , Ohms V. R. , Snelderwaard P. , Slabbekoorn H. 
Published: July 2010

SUMMARY
Sound plays an important role in the life of many animals, including many bird species. Typically, male birds sing to defend a territory and to attract mates. Ambient noise may negatively affect the signal efficiency of their songs, which may be critical to reproductive success. Consequently, anthropogenic noise may be detrimental to individual birds and to populations in cities and along highways. Several bird species that are still common in urban areas have been shown to sing at higher frequency at locations where there is more low-frequency traffic noise. Here we show that chiffchaffs along noisy highways also sing with a higher minimum frequency than chiffchaffs nearby at a quiet riverside. Furthermore, through experimental exposure to highway noise we show that these birds are capable of making such adjustments over a very short time scale. The first 10 songs sung during the noise exposure revealed an immediate shift to higher frequencies, with a return to pre-exposure levels in recordings without noise the following day. In a transmission re-recording experiment we tested the impact of a potential measurement artifact by recording playback of the same songs repeatedly under different controlled noise conditions. We found an upward shift in the minimum frequency measurement associated with more noisy recordings of the same song, but this artifact was not of a scale that it could explain the noise-dependent spectral shifts in chiffchaffs.
Thermobiology, energetics and activity patterns of the Eastern tube-nosed bat (Nyctimene robinsoni) in the Australian tropics: effect of temperature and lunar cycle
Authors: Riek Alexander , Körtner Gerhard , Geiser Fritz 
Published: July 2010

SUMMARYCurrently, there are no data on the thermal biology of free-ranging pteropodid bats (Chiroptera). Therefore, our aim was to investigate physiological and behavioural strategies employed by the fruit bat Nyctimene robinsoni (body mass ∼50 g) in winter in tropical Northern Queensland in relation to ambient temperature (Ta) and the lunar cycle. Daily body temperature (Tb) fluctuations in free-ranging bats were measured via radio-telemetry and metabolic rate was measured in captivity via open-flow respirometry (Ta, 15–30°C). Free-ranging bats showed a significant 24 h circadian cycle in Tb, with the lowest Tb at the end of the rest phase just after sunset and the highest Tb at the end of the activity phase just before sunrise. Average daily core Tb ranged from 34.7±0.6 to 37.3±0.8°C (mean ± s.d.) over an average daily Ta range of 17.1±1.1 to 23.5±1.8°C. Tb never fell below 30°C but Tb was significantly reduced during the full moon period compared with that during the new moon period. Tb was correlated with Ta during the second half of the rest phase (P&lt;0.001) but not during the active phase. Resting metabolic rate of bats was significantly affected by Ta (P&lt;0.001, R2=0.856). Our results show that tube-nosed bats exhibit reduced Tb on moonlit nights when they reduce foraging activity, but during our study torpor was not expressed. The energy constraints experienced here by tube-nosed bats with relatively moderate Ta fluctuations, short commuting distances between roosting and feeding locations, and high availability of food were probably not substantial enough to require use of torpor.
Low Viscosity Pore Fluid to Manufacture Transparent Soil
Authors: Zhao Honghua , Ge Louis , Luna Ronaldo 
Published: July 2010

Abstract
Transparent soil has been investigated for its potential as a substitute research media for natural soil. The mechanism for manufacturing the transparent soil is through adding an appropriate pore fluid to silica gel particles with the same refractive index. Two types of high viscosity pore fluids were identified by Iskander in 1994. However, because of the high viscosity of these two pore fluids, air was easily entrapped, which made the manufacture of a large mass of transparent soil difficult. In addition, the identified pore fluids caused serious membrane deterioration during triaxial laboratory testing. This research presented herein is an experimental investigation on low viscosity pore fluids to manufacture transparent soil, including the fluid/particle interaction in the stimulant matrix. Two low viscosity pore fluids were identified with minimum interaction with latex membranes.
Photoelectrochemical Investigation of Radiation-Enhanced Shadow Corrosion Phenomenon
Authors: Kim Young-Jin , Rebak Raul , Lin Yang-Pi , Lutz Daniel , Crawford Douglas , Kucuk Aylin , Cheng Bo 
Published: July 2010

Abstract
The photoelectrochemical investigation was performed by measuring the photoelectrochemical behavior of various alloys such as Zircaloy 2, 304 stainless steel (SS) and Alloy X-750 in 0.01M Na2SO4 at 25°C or in high purity water at 300°C under intense ultraviolet (UV) illumination. UV was selected because its photon energy (∼5 eV) is similar to the energy gap of the electron-hole pairs in zirconium oxide. The data show that the photoexcitation of ZrO2 caused the corrosion potential to shift in the anodic direction and produced anodic photocurrents under the oxidizing water chemistry condition when Zircaloy 2 electrode was galvanically coupled with dissimilar electrodes, such as Alloy X-750, 304 SS, or Pt, causing accelerated corrosion of Zircaloy. It is thus postulated that the photoelectrochemical enhancement of surface reaction kinetics at the ZrO2 surface may be responsible for the radiation-enhanced corrosion on Zircaloy (i.e., shadow corrosion). In addition, it is revealed that no significant change in galvanic current between Zircaloy 2 and other dissimilar electrodes was measured in high temperature water containing only hydrogen that resulted in similar ECPs. These data thus clearly provide an explanation for why the radiation-enhanced corrosion of Zircaloy only occurs in BWRs but not PWRs. Based on galvanic corrosion, impedance, and transmission electron microscopy analysis, it is proposed that the defect structure of equiaxed grain layers may be responsible for the photoelectrochemical response of ZrO2 in high temperature water. The mechanism of shadow corrosion is still highly debated but it appears to be similar to a process of galvanic corrosion in connection with sufficiently conducting Zr oxide structure. The galvanic corrosion data suggests that a Zr coating on the fuel assembly spacer (Alloy X-750 or 304 SS) may mitigate the shadow corrosion in BWRs.
School-Based Screening for Suicide Risk: Balancing Costs and Benefits
Authors: Scott Michelle , Wilcox Holly , Huo Yanling , Turner J. Blake , Fisher Prudence , Shaffer David 
Published: July 2010

Objectives. We examined the effects of a scoring algorithm change on the burden and sensitivity of a screen for adolescent suicide risk. Methods. The Columbia Suicide Screen was used to screen 641 high school students for high suicide risk (recent ideation or lifetime attempt and depression, or anxiety, or substance use), determined by subsequent blind assessment with the Diagnostic Interview Schedule for Children. We compared the accuracy of different screen algorithms in identifying high-risk cases. Results. A screen algorithm comprising recent ideation or lifetime attempt or depression, anxiety, or substance-use problems set at moderate-severity level classed 35% of students as positive and identified 96% of high-risk students. Increasing the algorithm's threshold reduced the proportion identified to 24% and identified 92% of high-risk cases. Asking only about recent suicidal ideation or lifetime suicide attempt identified 17% of the students and 89% of high-risk cases. The proportion of nonsuicidal diagnosis–bearing students found with the 3 algorithms was 62%, 34%, and 12%, respectively. Conclusions. The Columbia Suicide Screen threshold can be altered to reduce the screen-positive population, saving costs and time while identifying almost all students at high risk for suicide.
Television Food Advertising to Children: A Global Perspective
Authors: Kelly Bridget , Halford Jason C.G. , Boyland Emma J. , Chapman Kathy , Bautista-Castaño Inmaculada , Berg Christina , Caroli Margherita , Cook Brian , Coutinho Janine G. , Effertz Tobias , Grammatikaki Evangelia , Keller Kathleen , Leung Raymond , Manios Yannis , Monteiro Renata , Pedley Claire , Prell Hillevi , Raine Kim , Recine Elisabetta , Serra-Majem Lluis , Singh Sonia , Summerbell Carolyn 
Published: July 2010

Objectives. We compared television food advertising to children in several countries. Methods. We undertook a collaboration among 13 research groups in Australia, Asia, Western Europe, and North and South America. Each group recorded programming for 2 weekdays and 2 weekend days between 6:00 and 22:00, for the 3 channels most watched by children, between October 2007 and March 2008. We classified food advertisements as core (nutrient dense, low in energy), noncore (high in undesirable nutrients or energy, as defined by dietary standards), or miscellaneous. We also categorized thematic content (promotional characters and premiums). Results. Food advertisements composed 11% to 29% of advertisements. Noncore foods were featured in 53% to 87% of food advertisements, and the rate of noncore food advertising was higher during children's peak viewing times. Most food advertisements containing persuasive marketing were for noncore products. Conclusions. Across all sampled countries, children were exposed to high volumes of television advertising for unhealthy foods, featuring child-oriented persuasive techniques. Because of the proven connections between food advertising, preferences, and consumption, our findings lend support to calls for regulation of food advertising during children's peak viewing times.
Changes in Tdap and MCV4 Vaccine Coverage Following Enactment of a Statewide Requirement of Tdap Vaccination for Entry Into Sixth Grade
Authors: Olshen Kharbanda Elyse , Stockwell Melissa S. , Colgrove James , Natarajan Karthik , Rickert Vaughn I. 
Published: July 2010

Objectives. We evaluated changes in tetanus toxoid, reduced diptheria toxoid, acellular pertussis (Tdap), and tetravalen meningococcal (MCV4) vaccine coverage following enactment of a New York State mandate requiring Tdap before entering sixth grade. Methods. Using data from a hospital-based immunization registry, we measured Tdap and MCV4 coverage among youths aged 11 to 14 years in New York City at 3 time points: premandate, mandate year 1, and mandate year 2. Results. Among overlapping cohorts of 4316 (premandate), 4131 (mandate year 1), and 3639 (mandate year 2) youths, Tdap coverage increased steadily over time (29%, 58%, and 83%, respectively). Increases were observed among all ages. Across the same time points, MCV4 coverage also increased (10%, 30%, and 60%, respectively). Most adolescents did not receive MCV4 during the same visit they received Tdap. Conclusions. A Tdap school-entry mandate was associated with substantial increases in immunization coverage, even in age groups not directly affected by the mandate. At the postmandate time points, MCV4 coverage remained lower than Tdap coverage. Provider education should emphasize the importance of reviewing vaccine records and administering all recommended vaccines at every clinical encounter.
Assessing Targeted Screening and Low Rates of HIV Testing
Authors: Kennedy Leigh A. , Gordin Fred M. , Kan Virginia L. 
Published: July 2010

Objectives. We assessed rates of HIV testing based on targeting patients with identified risk factors at the Veterans Affairs Medical Center in Washington, DC (VAMC-DC), where written informed consent along with pretest and posttest counseling had, until recently, been required by federal law. Methods. A cumulative retrospective review of the period 2000 through 2007 was conducted to assess the number of patients who were provided medical care at VAMC-DC, tested for HIV, and underwent confirmatory testing. Data on demographic characteristics and risks for HIV acquisition were also collected. Results. At VAMC-DC, 3.8% to 4.9% (mean = 4.25%) of patients in care without known HIV infection underwent HIV screening annually. On average, HIV was confirmed at a yearly rate of 3.4% among those tested. During the study period, HIV prevalence ranged from 2.1% to 2.5%. Among patients receiving HIV care, 41.5% disclosed no risk factors for HIV acquisition. Conclusions. Given that the HIV prevalence observed in this study was above 2% and that 41.5% of patients in care did not disclose any acquisition risks, targeted HIV screening has not been sufficient. HIV testing must be broadened and offered as part of routine medical care.