bluuebunny/crossref_metadata_2025 huggingface dataset:
METHOD DEVELOPMENT AND VALIDATION OF VALACYCLOVIR HYDROCHLORIDE AND RITONAVIR IN TABLET DOSAGE FORM USING REVERSE PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY
Authors: Sathis Kumar D. , Prashanthi B. D. N , Harani A. , Anusha P.
Published: September 2015

Our main objective is to develop an accurate and precise RP-HPLC method for the simultaneous determination of Valacyclovir HCl and Ritonavir in tablet dosage form. An Agilent TC-C18 (2) column is used for the Separation of drugs by a mobile phase consisting of methanol, acetonitrile and water mixture in the ratio of 35:41.5:23.5v/v. The flow rate maintained was 1.3 mL/min and the wavelength used for detection was 222 nm. The linearity was observed in the range of 12.5-125µg/ml for Valacyclovir HCl (VC) and Ritonavir (RT) with a correlation coefficient of 0.9987 and 0.9981 respectively. The mean percentage recoveries for 80%, 100% and 120% accuracy were found to be 101.7%±2.09, 100%±2.49 and 101.5%±1.61 respectively for VC. The mean percentage recoveries for 80%, 100% and 120% accuracy were found to be 104.3%±0.99, 100%±1.77and 99.0%±1.22 respectively for RT. Linearity, accuracy, precision and robustness parameters for the suggested method were estimated for validation. The developed method can be utilized in the analysis of VC and RT tablets.
PRESENCE AND ABUNDANCE OF CYANOBACTERIA IN SELECTED AQUACULTURE PONDS IN PERAK, MALAYSIA AND THE RELATIONSHIPS WITH SELECTED PHYSICOCHEMICAL PARAMETERS OF WATER
Authors: Sinden Ann , Sinang Som Cit
Published: September 2015

The presence of cyanobacteria in aquaculture ponds can disrupt the water quality. This study was conducted to determine the abundance of cyanobacteria in selected aquaculture systems in Perak, Malaysia. This study also aimed to identify the relationships between cyanobacterial biomass with physicochemical properties of water. In this study, a total of 40 aquaculture fish ponds were sampled between December 2013 to March 2014 from 10 locations in Perak, Malaysia. The results revealed that cyanobacteria were present in all of the sampled aquaculture ponds. Among all, 75% of the sampled ponds contained chlorophyll-a exceeded 50 µg chl-a L-1 and the highest chlorophyll-a concentration was recorded at 436 µg chl-a L-1. This indicates that cyanobacteria are present in abundance in aquaculture water and could pose health risk to human through aquaculture fish consumption. Pearson’s correlation analysis suggests that cyanobacterial biomass was significantly correlated to temperature, DO and pH. However, there was no correlation detected among nutrients with cyanobacterial concentration in water column. Regular monitoring of temperature, DO and pH are crucial for an early detection of cyanobacterial occurrence in aquaculture industry in order to avoid economic losses, as well as adverse health impact to consumer.
INHIBITORY EFFECT OF ARTOCARPUS LOWII KING COMPOUNDS ON COX-2 AND 15-LO ACTIVITIES
Authors: Mohamad Rosdi Mohamad Norisham , Mohd Sirat Hasnah , Abdullah Siti Awanis , Jamil Shajarahtunnur , Muhamad Ida Idayu , Mohamed Zulkifli Razauden
Published: September 2015

Artocarpus lowii King is a rare species of plant in Moraceae family. In this study, the anti-inflammatory activity of cycloheterophyllin, isobavachalcone, 4-hydroxylonchocarpin and 2’,4’-dihydroxy-4-methoxy-3’-prenyldihydroxychalcone isolated from A. lowii King were investigated on classical enzymes in arachidonic acid metabolism pathways; cyclooxygenase and lipoxygenase. Isobavachalcone directly inhibited cyclooxygenase-2 enzyme in dose dependent manner, with IC50 value of 0.95 μM. No noticeable effect has been observed with the other tested compounds. In addition, none of the tested compounds displays a direct inhibition on 15-lipoxygenase when compared to the resveratrol as control with the IC50 value of 1.5 μM. Isobavachalcone showed inhibitory effect on cyclooxygenase-2. This study suggests that A. lowii King contains potential anti-inflammatory activity.
KAJIAN KEMAMPUAN RUMPAI LAUT ULVA INTESTINALIS SEBAGAI PENAPIS AIR LAUT SEMULA JADI BAGI PENGKULTURAN SECARA INTENSIF ROTIFER BRACHIONUS PLICATILIS
Authors: Abd Rahman Abdull Razak , Che Cob Zaidi , Jamari Zainoddin , Mohamed Abdul Majid , Toda Tatsuki , Hj Ross Othman
Published: September 2015

The ability of Ulva intestinalis as a biofilter in the intensive culture of rotifer Brachionus plicatilis was evaluated. 20 g wet weight of U. intestinalis was added into a 40 liters beaker containing 10 liters sea water of the cultured rotifer with quality index 0.36 ± 0.28 mg/L of NH3–N, 0.069 ± 0.025 mg/L of NO2––N, 0.90 ± 0.77 mg/L of NO3––N and 0.993 ± 0.0058 mg/L of PO43– and the alkalinity reading 114 ± 0.1 mg/L, pH 7.23 ± 0.08, temperature 26.3 ± 0.1OC and salinity was 30 ± 0.1 psu. The result of the following day of treatment with U. intestinalis, the water quality index changed to 0.001 mg/L of NH3–N, 0.090 ± 0.014 mg/L of NO2––N, 0.70 ± 0.60 mg/L of NO3––N and 0.89 ± 0.03 mg/L of PO43– while the alkalinity was 114 ± 0.1 mg/L, pH 7.45 ± 0.05, temperature 26.0 ± 0.10OC and the salinity was 30.0 ± 0.1 psu. The biofiltration capacity of U. intestinalis was confirmed by significantly reduced concentration of the NH3–N and 10% of PO43–  compared to control only 2% over one day treatment. However from day two onwards the readings were conflicting from the first day readings. These findings were probably because U. intestinalis live in intertidal zone and flushing area therefore the use of U. intestinalis as a biofilter by continuous immersion in cultured water is unnatural. Therefore using U. intestinalis as a biofilter should be used not more than 24 hours.
INVESTIGATING THE ENVIRONMENTAL IMPACTS OF GREEN ROOF INSTALLATION
Authors: Mahdiyar Amir , Abdullah Arham , Tabatabaee Sanaz , Mahdiyar Leily , Mohandes Saeed Reza
Published: September 2015

Green roof installation has been used as a sustainable approach for many years in order to reduce the adverse impacts of environmental issues all around the world. These environmental issues include: global warming, air pollution, flood, carbon footprint and so on. Green roofs are practical as a sustainable approach, especially in developed countries; however, there is an increasing trend of implementing green roofs in developing countries. This paper is reviewing the benefits of green roof installation and how green roof might contribute to reduce the negative environmental issues. The environmental problems that can be solved or reduced by these benefits are discussed separately in this paper. It is concluded that due to the environmental benefits of green roof installation, it leads to many economic benefits. Moreover, green roof implementation is beneficial in both urban areas and rural places.
COMPARATIVE ANALYSIS OF ASTER DEM, ASTER GDEM, AND SRTM DEM BASED ON GROUND-TRUTH GPS DATA
Authors: Rokni Komeil , Ahmad Anuar , Hazini Sharifeh
Published: September 2015

This study aims to compare the accuracies of ASTER DEM, ASTER GDEM, and SRTM DEM for the area of Universiti Teknologi Malaysia (UTM) and surrounding. In doing so, a number of Ground Control Points (GCPs) were collected using GPS technology and used to generate an absolute DEM using the ASTER stereo imagery. Moreover, two well-known DEMs including ASTER GDEM and SRTM DEM were obtained for the same area with ASTER image. Subsequently, several high accuracy ground-truth points were established around UTM using dual frequency GPS and used to assess the accuracies of the obtained DEMs. The results indicate that an elevation Root Mean Square Error (RMSE) of ±14.86m is achieved for the generated ASTER DEM, which is less than the 15m pixel size of ASTER image. The results further show that the elevation RMSEs of the ASTER GDEM and SRTM DEM are respectively ±4.52m and ±4.14m for the study area. The results illustrate although the resolution of SRTM DEM is much lower than ASTER GDEM, it could provide higher elevation accuracy. Finally, although the accuracy of the ASTER DEM in this study is not high in comparison with the accuracies of ASTER GDEM and SRTM DEM, based on the selected number of check points and resolution of ASTER image, it could be useful for various geoinformation applications.
THE EQUIVALENT IDENTITIES OF THE MACWILLIAMS IDENTITIES FOR LINEAR CODES
Authors: Xiaomin Bao
Published: September 2015

We use derivatives to prove the equivalences between MacWilliams identity and its four equivalent forms, and present new interpretations for the four equivalent forms.
MONITORING OF TRAFFIC USING UNMANNED AERIAL VEHICLE IN MALAYSIA LANDSCAPE PERSPECTIVE
Authors: Abdullah Azizul , Abu Bakar Elmi , Mohamed Pauzi Muhammad Zaim
Published: September 2015

Collecting information on traffic flows are important for provide high quality road system. At present, fixed camera is widely used for the monitoring system which covers limited area.  Therefore, the unmanned aerial vehicle (UAV) such as quadrotor is developed for monitoring traffic flow since the UAV is responsive mobile sensing system. This development of UAV platform is a starting point for developed a highway traffic and management system which is in future can be enhance by connected the system with graphical user interface (GUI) on ground control station that can defined types of vehicles and analyze level of congestion. At present, the system that developed only transmits a real time video to ground control station without any interpretation by software that detects types of vehicles and analyzes traffic condition. Through the surveillance and monitoring of traffic flows that done at Engineering Campus, Universiti Sains Malaysia, the system provides suitable information for authorities to analyse level of congestion happened on the road and provide alternative solution for users in order to avoid the traffic jam.
TREND ANALYSIS IN AGEING AND ICT RESEARCH
Authors: Yow Cherng Loo , Ahamed Hassain Malim Nurul Hashimah , Mahinderjit Singh Manmeet
Published: September 2015

The population of the elderly is growing rapidly and become a major concern in twentieth- century. The impact of this global ageing phenomenon is significant to the human life in all aspect including social, political and economic of all social class. The implementation of ICT application can help to cope with this phenomenon and improve the quality of life of the elderly. This study aims to perform a bibliometric analysis on the field of ageing and ICT to reveal the trend of research and technologies related in the recent years. Bibliometric information such as keywords and number of publication is extracted from the search result of online publication databases and then further analyzed using computational technique such as growth rate analysis and Latent Semantic Analysis (LSA) to identify the relationship and the growth of the information extracted. The outcome is a set of terms that are grouped and ranked according to their relevance and growth in the recent year. This result can then provide a brief understanding on the trend of ageing and ICT for the researchers that wish to research on this field.
Natural Convection Immersion Cooling With Enhanced Optical Performance of Light-Emitting Diode Systems
Authors: Tamdogan Enes , Arik Mehmet
Published: September 2015

Electronics driven at high currents may experience local hot spots, which may cause thermal degradation or even catastrophic failures. This common problem occurs at light-emitting diode (LED) chips and it is not easily observed by end-users. Driving over 700 mA over a 1 mm2 chip is expected to generate local temperature gradients. In addition, bonding failures at manufacturing or during operation (cracks, delamination, etc.) may also lead to local hot spots. Therefore, possible hot spots over an LED chip have turned attention to direct cooling with dielectric liquids comprises the current study. Computational and experimental studies have been performed to understand the impact of conduction and alternatively convection with various dielectric fluids to abate local hot spots in a multichip LED light engine. To capture the local temperature distributions over the LED light engine with a dome in the domain especially over the LED chip; first, computational models have been built with a commercial computational fluid dynamics (CFD) software. Later, attention has been turned into experimental validation by using a multichip high brightness LED (HB LED) light engine. An optothermal evaluation has been made at single and multiphase heat transfer modes with dielectric fluids (LS5252, HFE7000, and silicone oil, etc.) to compare with a series of CFD models and experimental studies. While multiphase liquid-cooled LED system has a better cooling performance but lower optical extraction, single-phase liquid-cooled LED system has shown a reasonable thermal performance with a 15% enhancement at light extraction.
Finite Element-Based Brownian Dynamics Simulation of Nanofiber Suspensions Using Monte Carlo Method1
Authors: Zhang Dongdong , Smith Douglas E.
Published: September 2015

This paper presents a computational approach for simulating the motion of nanofibers during fiber-filled composites processing. A finite element-based Brownian dynamics simulation (BDS) is proposed to solve for the motion of nanofibers suspended within a viscous fluid. We employ a Langevin approach to account for both hydrodynamic and Brownian effects. The finite element method (FEM) is used to compute the hydrodynamic force and torque exerted from the surrounding fluid. The Brownian force and torque are regarded as the random thermal disturbing effects which are modeled as a Gaussian process. Our approach seeks solutions using an iterative Newton–Raphson method for a fiber's linear and angular velocities such that the net forces and torques, including both hydrodynamic and Brownian effects, acting on the fiber are zero. In the Newton–Raphson method, the analytical Jacobian matrix is derived from our finite element model. Fiber motion is then computed with a Runge–Kutta method to update fiber position and orientation as a function of time. Instead of remeshing the fluid domain as a fiber migrates, the essential boundary condition is transformed on the boundary of the fluid domain, so the tedious process of updating the stiffness matrix of finite element model is avoided. Since the Brownian disturbance from the surrounding fluid molecules is a stochastic process, Monte Carlo simulation is used to evaluate a large quantity of motions of a single fiber associated with different random Brownian forces and torques. The final fiber motion is obtained by averaging numerous fiber motion paths. Examples of fiber motions with various Péclet numbers are presented in this paper. The proposed computational methodology may be used to gain insight on how to control fiber orientation in micro- and nanopolymer composite suspensions in order to obtain the best engineered products.
Radiation Shielding for Diagnostic Radiology, Second Edition
Authors: Martin Melissa C.
Published: September 2015

Radiation Shielding for Diagnostic Radiology, Second Edition Editors: D. G. Sutton, C. J. Martin, J. R. Williams, and D. J. Peet. British Institute of Radiology, London, UK, 2012. 148 pp. (paperback), Price: £22.50 (members), £30.00 (non‐members). ISBN‐13: 978‐0905749747.
Inactivation of PYR/PYL/RCAR ABA receptors by tyrosine nitration may enable rapid inhibition of ABA signaling by nitric oxide in plants
Authors: Castillo Mari-Cruz , Lozano-Juste Jorge , González-Guzmán Miguel , Rodriguez Lesia , Rodriguez Pedro L. , León José
Published: September 2015

Nitric oxide may limit ABA signaling in plants by rapid inactivation of the receptors through tyrosine nitration.
Dissecting the signaling pathways that mediate cancer in
PTEN
and
LKB1
double-knockout mice
Authors: Chen Jiezhong , Zhang Xu Dong , Proud Christopher
Published: September 2015

Loss of both
LKB1
and
PTEN
cooperatively promotes cancer by enabling tumor growth and immune tolerance.
Engineering cell population behavior
Authors: Ray L. Bryan
Published: September 2015

Two strains of bacteria are designed to synchronize transcription in culture.
Channeling brain cancer
Authors: Ferrarelli Leslie K.
Published: September 2015

Drug development based on the antipsychotic drug thioridazine may lead to treatments for metastatic medulloblastoma without compromising quality of life.
Clinical and Economic Benefits of Fidaxomicin Compared to Vancomycin for Clostridium difficile Infection
Authors: Gallagher Jason C. , Reilly Joseph P. , Navalkele Bhagyashri , Downham Gemma , Haynes Kevin , Trivedi Manish
Published: September 2015

We studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment of
Clostridium difficile
infection (CDI) in patients hospitalized during a 2-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for administration of fidaxomicin via a protocol that encouraged its use for selected patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (
P
= 0.027). In a multivariate analysis that included determinations of severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly associated with decreased recurrence (adjusted odds ratio [aOR], 0.33; 95% confidence interval [CI], 0.12 to 0.93). The total lengths of stay of readmitted patients were 183 days for vancomycin and 87 days for fidaxomicin, with costs of $454,800 and $196,200, respectively. Readmissions for CDI were reimbursed on the basis of the severity of CDI, totaling $151,136 for vancomycin and $107,176 for fidaxomicin. Fidaxomicin drug costs totaled $62,112, and vancomycin drug costs were $6,646. We calculated that the hospital lost an average of $3,286 per fidaxomicin-treated patient and $6,333 per vancomycin-treated patient, thus saving $3,047 per patient with fidaxomicin. Fidaxomicin use for CDI treatment prevented readmission and decreased hospital costs compared to use of oral vancomycin.
Increased Antifungal Drug Resistance in Clinical Isolates of Cryptococcus neoformans in Uganda
Authors: Smith Kyle D. , Achan Beatrice , Hullsiek Kathy Huppler , McDonald Tami R. , Okagaki Laura H. , Alhadab Ali A. , Akampurira Andrew , Rhein Joshua R. , Meya David B. , Boulware David R. , Nielsen Kirsten , Musubire Abdu , Nabeta Henry W. , Williams Darlisha A. , Morawski Bozena , Rolfes Melissa A. , Ndyetukira Jane Francis , Ahimbisibwe Cynthia , Kugonza Florence , Sadiq Alisat , Dyal Jonathan , Neborak Julie M. , King Alexa M. , Yueh Nathan , Velamakanni Sruti S. , Namudde Alice , Kandole Tadeo Kiiza , Eva Laker Julian Kaboggoza , Luggya Tony , Tugume Liliane , Abassi Mahsa , Birkenkamp Kate , Butler Elissa K. , Fujita A. Wendy , Halupnick Ryan , Strain Anna K. , Vedula Priya , Rajasingham Radha , Kambugu Andrew , Bohjanen Paul R.
Published: September 2015

Cryptococcal antigen screening is recommended among people living with AIDS when entering HIV care with a CD4 count of <100 cells/μl, and preemptive fluconazole monotherapy treatment is recommended for those with subclinical cryptococcal antigenemia. Yet, knowledge is limited of current antimicrobial resistance in Africa. We examined antifungal drug susceptibility in 198 clinical isolates collected from Kampala, Uganda, between 2010 and 2014 using the CLSI broth microdilution assay. In comparison with two previous studies from 1998 to 1999 that reported an MIC
50
of 4 μg/ml and an MIC
90
of 8 μg/ml prior to widespread human fluconazole and agricultural azole fungicide usage, we report an upward shift in the fluconazole MIC
50
to 8 μg/ml and an MIC
90
value of 32 μg/ml, with 31% of isolates with a fluconazole MIC of ≥16 μg/ml. We observed an amphotericin B MIC
50
of 0.5 μg/ml and an MIC
90
of 1 μg/ml, of which 99.5% of isolates (197 of 198 isolates) were still susceptible. No correlation between MIC and clinical outcome was observed in the context of amphotericin B and fluconazole combination induction therapy. We also analyzed
Cryptococcus
susceptibility to sertraline, with an MIC
50
of 4 μg/ml, suggesting that sertraline is a promising oral, low-cost, available, novel medication and a possible alternative to fluconazole. Although the CLSI broth microdilution assay is ideal to standardize results, limit human bias, and increase assay capacity, such assays are often inaccessible in low-income countries. Thus, we also developed and validated an assay that could easily be implemented in a resource-limited setting, with similar susceptibility results (
P
= 0.52).
Stepwise Decrease in Daptomycin Susceptibility in Clinical Staphylococcus aureus Isolates Associated with an Initial Mutation in
rpoB
and a Compensatory Inactivation of the
clpX
Gene
Authors: Bæk Kristoffer T. , Thøgersen Louise , Mogenssen René G. , Mellergaard Maiken , Thomsen Line E. , Petersen Andreas , Skov Søren , Cameron David R. , Peleg Anton Y. , Frees Dorte
Published: September 2015

Daptomycin is a lipopeptide antibiotic used clinically for the treatment of methicillin-resistant
Staphylococcus aureus
(MRSA) infections. The emergence of daptomycin-nonsusceptible
S. aureus
isolates during therapy is often associated with multiple genetic changes; however, the relative contributions of these changes to resistance and other phenotypic changes usually remain unclear. The present study was undertaken to investigate this issue using a genetically characterized series of four isogenic clinical MRSA strains derived from a patient with bacteremia before and during daptomycin treatment. The first strain obtained after daptomycin therapy carried a single-nucleotide polymorphism (SNP) in
rpoB
(RpoB A
477
D) that decreased susceptibility not only to daptomycin but also to vancomycin, β-lactams, and rifampin. Furthermore, the
rpoB
mutant exhibited pleiotropic phenotypes, including increased cell wall thickness, reduced expression of virulence traits, induced expression of the stress-associated transcriptional regulator Spx, and slow growth. A subsequently acquired loss-of-function mutation in
clpX
partly alleviated the growth defect conferred by the
rpoB
mutation without changing antibiotic susceptibility. The final isolate acquired three additional mutations, including an SNP in
mprF
(MprF S
295
L) known to confer daptomycin nonsusceptibility, and accordingly, this isolate was the only daptomycin-nonsusceptible strain of this series. Interestingly, in this isolate, the cell wall had regained the same thickness as that of the parental strain, while the level of transcription of the
vraSR
(cell wall stress regulator) was increased. In conclusion, this study illustrates how serial genetic changes selected
in vivo
contribute to daptomycin nonsusceptibility, growth fitness, and virulence traits.
Ribosome Hibernation Facilitates Tolerance of Stationary-Phase Bacteria to Aminoglycosides
Authors: McKay Susannah L. , Portnoy Daniel A.
Published: September 2015

Upon entry into stationary phase, bacteria dimerize 70S ribosomes into translationally inactive 100S particles by a process called ribosome hibernation. Previously, we reported that the hibernation-promoting factor (HPF) ofListeria monocytogenesis required for 100S particle formation and facilitates adaptation to a number of stresses. Here, we demonstrate that HPF is required for the high tolerance of stationary-phase cultures to aminoglycosides but not to beta-lactam or quinolone antibiotics. The sensitivity of a Δhpfmutant to gentamicin was suppressed by the bacteriostatic antibiotics chloramphenicol and rifampin, which inhibit translation and transcription, respectively. Disruption of the proton motive force by the ionophore carbonyl cyanidem-chlorophenylhydrazone or mutation of genes involved in respiration also suppressed the sensitivity of the Δhpfmutant. Accordingly, Δhpfmutants had aberrantly high levels of ATP and reducing equivalents during prolonged stationary phase. Analysis of bacterial uptake of fluorescently labeled gentamicin demonstrated that the Δhpfmutant harbored increased intracellular levels of the drug. Finally, deletion of the main ribosome hibernation factor ofEscherichia coli, ribosome modulation factor (rmf), rendered these bacteria susceptible to gentamicin. Taken together, these data suggest that HPF-mediated ribosome hibernation results in repression of the metabolic activity that underlies aminoglycoside tolerance. HPF is conserved in nearly every bacterial pathogen, and the role of ribosome hibernation in antibiotic tolerance may have clinical implications.
Inhibitors of Methionyl-tRNA Synthetase Have Potent Activity against Giardia intestinalis Trophozoites
Authors: Ranade Ranae M. , Zhang Zhongsheng , Gillespie J. Robert , Shibata Sayaka , Verlinde Christophe L. M. J. , Hol Wim G. J. , Fan Erkang , Buckner Frederick S.
Published: September 2015

The methionyl-tRNA synthetase (MetRS) is a novel drug target for the protozoan pathogen
Giardia intestinalis
. This protist contains a single MetRS that is distinct from the human cytoplasmic MetRS. A panel of MetRS inhibitors was tested against recombinant
Giardia
MetRS,
Giardia
trophozoites, and mammalian cell lines. The best compounds inhibited trophozoite growth at 500 nM (metronidazole did so at ∼5,000 nM) and had low cytotoxicity against mammalian cells, indicating excellent potential for further development as anti-
Giardia
drugs.
Analysis of the Zidovudine Resistance Mutations T215Y, M41L, and L210W in HIV-1 Reverse Transcriptase
Authors: Boyer Paul L. , Das Kalyan , Arnold Eddy , Hughes Stephen H.
Published: September 2015

Although anti-human immunodeficiency virus type 1 (HIV-1) therapies have become more sophisticated and more effective, drug resistance continues to be a major problem. Zidovudine (azidothymidine; AZT) was the first nucleoside reverse transcriptase (RT) inhibitor (NRTI) approved for the treatment of HIV-1 infections and is still being used, particularly in the developing world. This drug targets the conversion of single-stranded RNA to double-stranded DNA by HIV-1 RT. However, resistance to the drug quickly appeared both in viruses replicating in cells in culture and in patients undergoing AZT monotherapy. The primary resistance pathway selects for mutations of T215 that change the threonine to either a tyrosine or a phenylalanine (T215Y/F); this resistance pathway involves an ATP-dependent excision mechanism. The pseudo-sugar ring of AZT lacks a 3′ OH; RT incorporates AZT monophosphate (AZTMP), which blocks the end of the viral DNA primer. AZT-resistant forms of HIV-1 RT use ATP in an excision reaction to unblock the 3′ end of the primer strand, allowing its extension by RT. The T215Y AZT resistance mutation is often accompanied by two other mutations, M41L and L210W. In this study, the roles of these mutations, in combination with T215Y, were examined to determine whether they affect polymerization and excision by HIV-1 RT. The M41L mutation appears to help restore the DNA polymerization activity of RT containing the T215Y mutation and also enhances AZTMP excision. The L210W mutation plays a similar role, but it enhances excision by RTs that carry the T215Y mutation when ATP is present at a low concentration.
Analysis of Bacterial Communities during Clostridium difficile Infection in the Mouse
Authors: Semenyuk Ekaterina G. , Poroyko Valeriy A. , Johnston Pehga F. , Jones Sara E. , Knight Katherine L. , Gerding Dale N. , Driks Adam
Published: September 2015

Clostridium difficile
infection (CDI) is a major cause of health care-associated disease. CDI initiates with ingestion of
C. difficile
spores, germination in the gastrointestinal (GI) tract, and then colonization of the large intestine. The interactions between
C. difficile
cells and other bacteria and with host mucosa during CDI remain poorly understood. Here, we addressed the hypothesis that, in a mouse model of CDI,
C. difficile
resides in multicellular communities (biofilms) in association with host mucosa. To do this, we paraffin embedded and then sectioned the GI tracts of infected mice at various days postinfection (p.i.). We then used fluorescent
in situ
hybridization (FISH) with 16S rRNA probes targeting most bacteria as well as
C. difficile
specifically. The results revealed that
C. difficile
is present as a minority member of communities in the outer (loose) mucus layer, in the cecum and colon, starting at day 1 p.i. To generate FISH probes that identify bacteria within mucus-associated communities harboring
C. difficile
, we characterized bacterial populations in the infected mouse GI tract using 16S rRNA gene sequence analysis of bacterial DNA prepared from intestinal content. This analysis revealed the presence of genera of several families belonging to
Bacteroidetes
and
Firmicutes
. These data suggest that formation of multispecies communities associated with the mucus of the cecum and colon is an important early step in GI tract colonization. They raise the possibility that other bacterial species in these communities modulate the ability of
C. difficile
to successfully colonize and, thereby, cause disease.
Application of Synthetic Peptide Arrays To Uncover Cyclic Di-GMP Binding Motifs
Authors: Düvel Juliane , Bense Sarina , Möller Stefan , Bertinetti Daniela , Schwede Frank , Morr Michael , Eckweiler Denitsa , Genieser Hans-Gottfried , Jänsch Lothar , Herberg Friedrich W. , Frank Ronald , Häussler Susanne
Published: September 2015

High levels of the universal bacterial second messenger cyclic di-GMP (c-di-GMP) promote the establishment of surface-attached growth in many bacteria. Not only can c-di-GMP bind to nucleic acids and directly control gene expression, but it also binds to a diverse array of proteins of specialized functions and orchestrates their activity. Since its development in the early 1990s, the synthetic peptide array technique has become a powerful tool for high-throughput approaches and was successfully applied to investigate the binding specificity of protein-ligand interactions. In this study, we used peptide arrays to uncover the c-di-GMP binding site of a
Pseudomonas aeruginosa
protein (PA3740) that was isolated in a chemical proteomics approach. PA3740 was shown to bind c-di-GMP with a high affinity, and peptide arrays uncovered LKKALKKQTNLR to be a putative c-di-GMP binding motif. Most interestingly, different from the previously identified c-di-GMP binding motif of the PilZ domain (RXXXR) or the I site of diguanylate cyclases (RXXD), two leucine residues and a glutamine residue and not the charged amino acids provided the key residues of the binding sequence. Those three amino acids are highly conserved across PA3740 homologs, and their singular exchange to alanine reduced c-di-GMP binding within the full-length protein.

IMPORTANCE
In many bacterial pathogens the universal bacterial second messenger c-di-GMP governs the switch from the planktonic, motile mode of growth to the sessile, biofilm mode of growth. Bacteria adapt their intracellular c-di-GMP levels to a variety of environmental challenges. Several classes of c-di-GMP binding proteins have been structurally characterized, and diverse c-di-GMP binding domains have been identified. Nevertheless, for several c-di-GMP receptors, the binding motif remains to be determined. Here we show that the use of a synthetic peptide array allowed the identification of a c-di-GMP binding motif of a putative c-di-GMP receptor protein in the opportunistic pathogen
P. aeruginosa
. The application of synthetic peptide arrays will facilitate the search for additional c-di-GMP receptor proteins and aid in the characterization of c-di-GMP binding motifs.
Long non-coding RNA chromogenic in situ hybridisation signal pattern correlation with breast tumour pathology
Authors: Zhang Zhouwei , Weaver Donald L , Olsen Daniel , deKay James , Peng Zhihua , Ashikaga Takamaru , Evans Mark F
Published: September 2015

Aim

Long non-coding RNAs (lncRNAs) are potential biomarkers for breast cancer risk stratification. LncRNA expression has been investigated primarily by RNA sequencing, quantitative reverse transcription PCR or microarray techniques. In this study, six breast cancer-implicated lncRNAs were investigated by chromogenic in situ hybridisation (CISH).

Methods

Invasive breast carcinoma (IBC), ductal carcinoma in situ (DCIS) and normal adjacent (NA) breast tissues from 52 patients were screened by CISH. Staining was graded by modified Allred scoring.

Results

HOTAIR,H19andKCNQ1OT1had significantly higher expression levels in IBC and DCIS than NA (p<0.05), andHOTAIRandH19were expressed more strongly in IBC than in DCIS tissues (p<0.05).HOTAIRandKCNQ101Twere expressed in tumour cells;H19andMEG3were expressed in stromal microenvironment cells;MALAT1was expressed in all cells strongly andZFAS1was negative or weakly expressed in all specimens.

Conclusion

These data corroborate the involvement of three lncRNAs (HOTAIR,H19andKCNQ1OT1) in breast tumourigenesis and support lncRNA CISH as a potential clinical assay. Importantly, CISH allows identification of the tissue compartment expressing lncRNA.
Initial hospital management of patients with emergent large vessel occlusion (ELVO): report of the standards and guidelines committee of the Society of NeuroInterventional Surgery
Authors: McTaggart Ryan A , Ansari Sameer A , Goyal Mayank , Abruzzo Todd A , Albani Barb , Arthur Adam J , Alexander Michael J , Albuquerque Felipe C , Baxter Blaise , Bulsara Ketan R , Chen Michael , Almandoz Josser E Delgado , Fraser Justin F , Frei Donald , Gandhi Chirag D , Heck Don V , Hetts Steven W , Hussain M Shazam , Kelly Michael , Klucznik Richard , Lee Seon-Kyu , Leslie-Mawzi Thabele , Meyers Philip M , Prestigiacomo Charles J , Pride G Lee , Patsalides Athos , Starke Robert M , Sunenshine Peter , Rasmussen Peter A , Jayaraman Mahesh V
Published: September 2015

Objective

To summarize the current literature regarding the initial hospital management of patients with acute ischemic stroke (AIS) secondary to emergent large vessel occlusion (ELVO), and to offer recommendations designed to decrease the time to endovascular treatment (EVT) for appropriately selected patients with stroke.

Methods

Using guidelines for evidenced-based medicine proposed by the Stroke Council of the American Heart Association, a critical review of all available medical literature supporting best initial medical management of patients with AIS secondary to ELVO was performed. The purpose was to identify processes of care that most expeditiously determine the eligibility of a patient with an acute stroke for interventions including intravenous fibrinolysis with recombinant tissue plasminogen activator (IV tPA) and EVT using mechanical embolectomy.

Results

This review identifies four elements that are required to achieve timely revascularization in ELVO. (1) In addition to non-contrast CT (NCCT) brain scan, CT angiography should be performed in all patients who meet an institutional threshold for clinical stroke severity. The use of any advanced imaging beyond NCCT should not delay the administration of IV tPA in eligible patients. (2) Activation of the neurointerventional team should occur as soon as possible, based on either confirmation of large vessel occlusion or a prespecified clinical severity threshold. (3) Additional imaging techniques, particularly those intended to physiologically select patients for EVT (CT perfusion and diffusion–perfusion mismatch imaging), may provide additional value, but should not delay EVT. (4) Routine use of general anesthesia during EVT procedures, should be avoided if possible. These workflow recommendations apply to both primary and comprehensive stroke centers and should be tailored to meet the needs of individual institutions.

Conclusions

Patients with ELVO are at risk for severe neurologic morbidity and mortality. To achieve the best possible clinical outcomes stroke centers must optimize their triage strategies. Strategies that provide patients with ELVO with the fastest access to reperfusion depend upon detail-oriented process improvement.
Ice-proximal Labrador Sea Heinrich layers: a sedimentological approach
Authors: Hesse Reinhard
Published: September 2015

During Late Pleistocene Heinrich events (H-events), distinct, decimetre- to centimetre-thick layers of ice-rafted debris (IRD) were deposited in the North Atlantic as Heinrich layers (H-layers). These layers are characterized by high detrital carbonate content, low foraminifera content, a high percentage of Neogloboquadrina pachyderma (sinistral) among the planktonic foraminifera, high magnetic susceptibility, and high grey colour values. In contrast, H-layers in the Labrador Sea reach metre thickness at core sites proximal to the iceberg source off the Hudson Strait ice stream (HSIS), and show low magnetic susceptibility and relatively low grey levels on the colour scale. To provide the reader with some background information, four hypotheses concerning the origin of H-events are discussed at the outset: (1) the binge–purge (internal forcing) model, (2) the subglacial outburst flood model, (3) the external forcing model, and (4) the catastrophic ice shelf breakup model. The higher thickness of ice-proximal H-layers is due to the supply of large amounts of terrigenous sediments that were eroded from country rocks underlying the northeastern sector of the Laurentide Ice Sheet (LIS). These sediments were transported to the deep Labrador Sea by the efficient processes of bottom-following mass and surface plume movement, where they mixed with ice-rafted sediment. Four distinct depositional facies of H-layers (Types I to IV) have been identified: Type I H-layers occur within 300 km from the presumed HSIS terminus and consist of stacked thin layers of graded muds containing IRD. The graded muds that are spiked with IRD are the result of deposition of fine-grained sediment from lofting sediment columns that collected dropstones and grains under the iceberg route. Type II H-layers occur on the slope and rise at a greater distance south of the Hudson Strait outlet, on the levees of tributary canyons to the Northwest Atlantic Mid-Ocean Channel (NAMOC). These layers consist of alternating thin mud turbidites with intercalated laminae of IRD. Type III H-layers exist on the levees of the main channel of the NAMOC, and consist of layers of IRD alternating with fewer fine-grained spillover turbidites, reflecting the lower spillover frequency from the deep channel compared to the less deep slope canyons. Type IV H-layers are made up of bioturbated hemipelagic muds with IRD, and occur in regions between canyons not reached by spillover turbidity currents, and in distal regions of the open ocean or on seamounts. The anomalously high thickness of individual H-layers on the slope and rise off Hudson Strait is explained by the transport of significant portions of H-layer sediment by suspended sediment columns lofted from sand-carrying freshwater turbidity currents (Type I), and by low density turbidity currents (Types II and III). Isopach maps for H-layers 1–3 give hints of the drift routes of the lofted suspended sediment during its ascent to the surface, and of iceberg drift directions in the Labrador Sea.
Energies, Landé g-factors, oscillator strengths, and transition probabilities in Cs-like Pr V
Authors: Karaçoban Usta Betül , Doğan Sevda
Published: September 2015

We have calculated relativistic energies and Landé g-factors for the levels of 5p6nf (n = 4–30), 5p6np (n = 6–30), 5p6nd (n = 5–30), 5p6ng (n = 5–30) and 5p6ns (n = 6–30) configurations and the transition parameters, such as wavelengths, oscillator strengths, and transition probabilities (or rates), for the electric dipole (E1) transitions between these levels in quadruply ionized praseodymium (Pr V, Z = 59) by using the relativistic Hartree–Fock method. We have compared the results with available calculations and experiments in the literature.
Tranilast ameliorates cyclophosphamide-induced lung injury and nephrotoxicity
Authors: Said Eman , Elkashef Wagdi F. , Abdelaziz Rania R.
Published: September 2015

The world-wide increase in cancer incidence imposes a corresponding significant increase in the use of chemotherapeutic agents. Nephrotoxicity is a side effect frequently encountered with cyclophosphamide (CP), which is also well-known to cause acute and chronic lung toxicities. The current study focuses on the evaluation of the potential protective efficacy of tranilast against acute and subacute CP-induced lung and kidney injuries in male Swiss Albino mice. Intraperitoneal CP significantly impaired oxidant/anti-oxidant balance and increased inflammatory cell count in bronchoalveolar lavage fluid, serum creatinine, blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α) and lactate dehydrogenase (LDH) levels, with significant impairment of lung and kidney architectures. Tranilast taken orally for 8 and 14 days significantly enhanced mice anti-oxidant defense mechanisms; it increased lung and kidney SOD activity, GSH content and reduced lipid peroxidation. Tranilast significantly reduced serum creatinine and BUN. Furthermore, it decreased accumulation of inflammatory cells in the lungs. Serum TNF-α, LDH, total lung and kidney protein contents significantly declined as well. Histopathological examination revealed concomitant significant tissue recovery. Such results show a significant protective potential of tranilast against deleterious lung and kidney damage induced by CP, probably by enhancing host antioxidant defense mechanism, decreasing cytotoxicity, and decreasing expression of inflammatory cytokines.
POPULATION AGING AND PUBLIC PENSION: THE CASE OF BEIJING ANALYZED BY AN OLG MODEL
Authors: YANG ZAIGUI
Published: September 2015

This paper employs an overlapping-generations (OLG) model with altruistic motive and lifetime uncertainty to investigate the urban public pension system in China. Focusing on the case of Beijing, we examine the effects of the individual contribution rate, firm contribution rate, life expectancy and population growth rate on the capital-labor ratio, savings, per capita consumption and pension benefits. By controlling the firm contribution rate to adjust the capital-labor ratio of the market economy to the modified golden rule level, we find the optimal firm contribution rate. We also discuss the optimal firm contribution rate in Beijing under three cases: risen life expectancy, fallen population growth rate and the joint case of risen life expectancy and fallen population growth rate, and estimate the optimal firm contribution rate in 2020s. Integrating the established effects and the current economic goals, it is concluded that it will do more good than harm to strictly implement Beijing municipal population policy, improve the living and medical conditions, reduce the firm contribution rate, and raise the individual contribution rate.
Presymmetry in the Standard Model with adulterated Dirac neutrinos
Authors: Matute Ernesto A.
Published: August 2015

Recently we proposed a model for light Dirac neutrinos in which two right-handed (RH) neutrinos per generation are added to the particles of the Standard Model (SM), implemented with the symmetry of fermionic contents. The ordinary one is decoupled via the high scale type-I seesaw mechanism, while the extra pairs off with its left-handed (LH) partner. The symmetry of lepton and quark contents was merely used as a guideline to the choice of parameters because it is not a proper symmetry. Here we argue that the underlying symmetry to take for this correspondence is presymmetry, the hidden electroweak symmetry of the SM extended with RH neutrinos defined by transformations which exchange lepton and quark bare states with the same electroweak charges and no Majorana mass terms in the underlying Lagrangian. It gives a topological character to fractional charges, relates the number of families to the number of quark colors, and now guarantees the great disparity between the couplings of the two RH neutrinos. Thus, Dirac neutrinos with extremely small masses appear as natural predictions of presymmetry, satisfying the ’t Hooft’s naturalness conditions in the extended seesaw where the extra RH neutrinos serve to adulterate the mass properties in the low scale effective theory, which retains without extensions the gauge and Higgs sectors of the SM. However, the high energy threshold for the seesaw implies new physics to stabilize the quantum corrections to the Higgs boson mass in agreement with the naturalness requirement.
STM/STS studies for interplane disorder effects on the electronic states of the Cu–O plane in Bi2201
Authors: Kurosawa T. , Hatta G. , Miyazaki H. , Yamaji J. , Yoshikawa K. , Nakagawa Y. , Shibata Y. , Yoshida H. , Oda M. , Ido M. , Takeyama K. , Momono N.
Published: September 2015

STM/STS experiments have been performed in [Formula: see text] (R-Bi2201) systems with [Formula: see text] and Eu, which are of a nearly optimal doping level [Formula: see text] but have different [Formula: see text] values, 35 K and 20 K, respectively, to examine interplane disorder effects on the superconducting (SC) gap and the pseudogap (PG) that is accompanied by a checkerboard-type charge order (CCO). We report that as interplane disorders are strengthened by replacing La with Eu in optimal Bi2201, the antinodal PG size [Formula: see text] increases from [Formula: see text] to [Formula: see text], which is comparable to the value for an underdoping level [Formula: see text] in La-Bi2201. On the other hand, the period of CCO in optimal Eu-Bi2201 is the same as in optimal La-Bi2201, about five times lattice constant [Formula: see text] along the Cu–O bond directions; it remains unchanged even if the PG develops markedly to the same degree as for [Formula: see text] in La-Bi2201, whose period is [Formula: see text].
Superconductivity in the Institute for Low Temperature Physics and Engineering of the National Academy of Sciences of Ukraine
Authors: Bondarenko Stanislav , Koverya Valentin
Published: September 2015

The report contains a brief history of the superconductor’s researches and their applications carried out in the Institute for Low Temperature Physics and Engineering (ILTPE) of the National Academy of Sciences of Ukraine since the ILTPE foundation in 1960. The most important results of the researches in the field of the low- and high-temperature superconductors (HTS) are stated more detailed. The experimental validation of an electromagnetic radiation of Josephson junctions; the electron pairing and existence of the distant order in the HTS; a creation of the superconducting quantum interference devices (SQUIDs) on the basis of the HTS; formation and moving of the local frozen magnetic field along the surface of the HTS; the transport properties of new Fe-based superconductors can be referred to such results.
Nodal gap behavior of Bi2Sr2−xLnxCuO6+δ (Ln = La, Eu) investigated by specific heat measurements
Authors: Shimizu M. , Moriya Y. , Baar S. , Momono N. , Amakai Y. , Takano H. , Murayama S. , Kurosawa T. , Oda M. , Ido M.
Published: September 2015

We performed low-temperature specific heat measurements on slightly underdoped samples of monolayer cuprate superconductors [Formula: see text] (Ln = La, Eu, Ln-Bi2201) under magnetic fields [Formula: see text]. In La-Bi2201, the coefficient [Formula: see text] of [Formula: see text]-linear term in the electronic specific heat [Formula: see text] at [Formula: see text] shows [Formula: see text] dependence, as expected in [Formula: see text] -wave superconductors. In Eu-Bi2201, [Formula: see text] shows almost the same [Formula: see text] dependence as that of La-Bi2201 below [Formula: see text] T, while [Formula: see text] is suppressed above [Formula: see text] T and deviates downward from the [Formula: see text] curve of La-Bi2201. This result suggests the the gap and the electronic excitation spectrum near nodes are modified in Eu-Bi2201 except the region of the Fermi surface in the immediate vicinity of nodes.