bluuebunny/crossref_metadata_2025 huggingface dataset:
Interfacial structure and strength on Ti(C,N) joint using liquid phase diffusion bonding with Ti/Ni interlayer
Authors: Wu M. , Zhao P. , Wang F. , Hu Q.
Published: January 2014

Partial transient liquid phase diffusion bonding (PTLP-DB) on Ti(C,N) cermet was studied in the present paper using Ti/Ni/Ti foil sandwich structure as the interlayer. The interfacial structure and element distribution at the interface were observed using SEM, electron probe microanalysis and X-ray diffraction. The joint strength was measured using four-point bending test. The results showed that metallurgical bonding between Ti(C,N) cermet was achieved using PTLP-DB. Near Ti(C,N) cermet side, a strong chemical reaction occurred to produce an interfacial multilayer containing Ti–Al and Ti–Ni intermetallics. Different bonding times during PTLP-DB were also studied, and there was an optimum time during bonding. With a shorter bonding time, voids were observed at the interface, while with a prolonged time, the bending strength on the joints also decreased due to the overgrowth on intermetallic layer and the existence of high gradient residual stress at the interface.
Dilatometric and microstructural response of variant selection during α′ transformation
Authors: Mangal A. , Biswas P. , Lenka S. , Singh V. , Singh S. B. , Kundu S.
Published: January 2014

Variant selection during displacive transformation is popularly monitored by assessing the pole figure or orientation density function of the bulk texture or pole figures from single prior austenite grains. It can also be done by measuring the physical orientation of α′ (bainite or marteniste) plates in the microstructure. It is known that when variants of α′ form randomly, i.e. there is no variant selection, the shear strain associated with each α′ plate gets canceled and transformation strain becomes equal to the volume strain. Under this condition, orientation of sheaves of α′ also shows random distribution. In this work, it has been shown how transformation strain and orientation of sheaves change when variant selection occurs. Mathematical models have already been developed to calculate the transformation strain under various loading conditions; extensive experiments have been conducted during the course of this work to show how the nature of externally applied stress influences the transformation strain. In addition to this, it has also been shown that the variant selection might leave its trace in the microstructure by affecting the alignment of the sheaves under externally applied stress and strain. Mathematical models have been developed to show that variant selection has negligible influence on physical orientation of α′ plates when transformation occurs under external stress, but prior plastic deformation can dictate the orientation to a great extent.
Kinetics of precipitation hardening phase in aluminium alloy AA 6110
Authors: Kongthep J. , Juijerm P.
Published: January 2014

The solid solution treated aluminium alloy AA 6110 was investigated using a differential scanning calorimetry (DSC) with different heating rates. Kinetic parameters, e.g. the activation energy and the Avrami exponent, were calculated. The peak temperatures of the hardening phase β″ from each heating rate were collected to calculate the activation energy of the aluminium alloy AA 6110 using various mathematical models: the Kissinger, Ozawa and Boswell models. It was found that the activation energies from each model were within the range of 106–114 kJ mol−1. These activation energies were found to be lesser than those for the bulk diffusion of aluminium, magnesium and silicon atoms in aluminium matrix. The average Avrami exponent, n of 2·36 was calculated using the developed Matusita model and corresponded to a one-dimensional linear growth of fresh nuclei of needle-like β″ in this aluminium alloy AA 6110.
High cyclic fatigue behaviour of ultrafine grained Al 5083 alloy
Authors: Singh D. , Nageswara Rao P. , Jayaganthan R.
Published: January 2014

The effects of cryorolling (CR) and CR followed by warm rolling (WR) on high cycle fatigue behaviour of Al 5083 alloy have been investigated in the present work. The Al 5083 alloy samples were rolled for different thickness reductions of 50 and 85 at cryogenic (liquid nitrogen) temperature. Fifty per cent cryorolled samples were subsequently warm rolled at 175°C for 70 reduction (WR). Hardness, tensile strength and fatigue life using constant amplitude stress controlled fatigue were investigated. The microstructural evolution of the alloy was characterised using optical microscopy, SEM and TEM techniques. The cryorolled Al alloy after 85 thickness reduction exhibits high dislocation density due to suppression of dynamic recovery, whereas WR alloy has shown fine subgrain structure in the range of 100–150 nm, associated with dynamic recovery and dynamic aging during WR. The Al 5083 alloy after WR has shown significant enhancement in fatigue strength as compared to the coarse grained solution treated (ST) bulk alloy and CR material. It can be attributed to the formation of fine precipitates during WR, which inhibits dynamic recovery during cyclic deformation; precipitate–dislocation tangled zones inhibits the crack propagation in the alloy.
Effect of current frequency on coating properties formed on aluminised steel by plasma electrolytic oxidation
Authors: Kharanagh V. Jafarniya , Sani M. A. Faghihi , Rafizadeh E.
Published: January 2014

In the present study, plasma electrolytic oxidation process was carried out on aluminised steel with a pulsed bipolar electrical source at different frequencies, namely, 50, 300, 600 and 1500 Hz with constant 50% duty cycle for 10 min in an alkaline silicate electrolyte. Morphology, wear behaviour and corrosion resistance of the coatings were investigated by scanning electron microscopy, pin on disc and potentiodynamic polarisation experiment in 3·5 wt-%NaCl solution. The results showed that with increasing the pulse frequency, the density of the residual pores increases, but their size as well as the coating thickness decreases. The corrosion current density of the coating processed at 1500 Hz was 1·14×10−8 A cm−2, which exhibited superior corrosion resistance compared with the bare substrate. Lower friction coefficient of the specimen processed at 600 Hz in comparison with that of the specimens prepared at lower frequencies was due to the formation of a less rough coating.
Influence of pH, chloride ion concentration and spraying time on the corrosion behaviour of atmospheric plasma sprayed alumina coatings
Authors: Thirumalaikumarasamy D. , Shanmugam K. , Balasubramanian V.
Published: January 2014

The corrosion behaviour of the plasma sprayed alumina coatings was evaluated by conducting salt fog test in NaCl solution at different chloride ion concentrations, pH value and spraying time. Empirical relationship was developed to predict the corrosion rate of alumina coatings by incorporating the corrosion process parameters. The corroded surface was characterised by scanning electron microscopy (SEM) and X-ray diffraction. The results showed that the corrosion deterioration of alumina coating was significantly influenced by chloride ion concentration and pH value. The alumina coatings were found to be highly susceptible to localised damage. It could not provide an effective corrosion protection to Mg alloy substrate in solutions containing acidic environments (pH 3), higher chloride concentrations and spraying time.
Corrosion protection of magnesium and its alloys by metal phosphate conversion coatings
Authors: Chen X.-B. , Yang H.-Y. , Abbott T. B. , Easton M. A. , Birbilis N.
Published: January 2014

This work describes a group of metal phosphate films, including calcium, manganese and strontium phosphate conversion coatings, for corrosion protection of magnesium alloys. These films have been developed by a process that is simple for implementation, chemically stable and non-toxic. The preparation and characterisation of these coatings, along with evaluation of their corrosion performance in 0·1M NaCl, are systematically described. Phase diagram of calcium phosphate was produced to elucidate the coating formation mechanism, which depends upon the chemistry of coating solution, in particular pH and ion concentration. A discussion of the advantages and disadvantages of the coatings is presented, along with perspectives for industrial applications.
Euler based finite element analysis on high velocity impact behaviour in cold spraying
Authors: Yin S. , Liao H. L. , Wang X. F.
Published: January 2014

Finite element analysis on the high velocity impact behaviour in cold spraying is conducted using the Euler method. The simulation results demonstrate that the Euler method is capable of realising the reliable simulation on some complicated impact processes. The comparative deformation ratio (CDR) is proposed, which is defined as the ratio of dimensionless crater depth to compressional ratio, to evaluate the comparative deformation degree between the particle and substrate. Proper CDR and sufficiently large compressional ratio can ensure the well bonding between the particle and substrate. Furthermore, for the multiparticle impact process, it is found that, after the deposition of the first layer coating, the subsequent impact process can be considered as particles impacting on the same material no matter what substrate is coated. When the velocity is increased to a hypervelocity (erosion velocity), extreme erosion occurs in the substrate or the formed coatings, resulting in the poor performance of the coating.
Moisture protection of wood coatings and its sensitivity to mechanical defects depending on surface hydrophobicity and solid content
Authors: Grüll G , Truskaller M
Published: January 2014

The moisture protection of wood coating systems is influenced by the total solid content applied as well as by the hydrophobic properties of the coating film. Water permeability, water vapour permeability and contact angle of water on wood surfaces treated with 21 different coating systems were measured. Water permeability tests were also carried out with artificial mechanical defects of the surfaces. The results showed that the influence of the total solid content applied was predominant, whereas the surface hydrophobicity was less efficient. Systems with a higher total solid content and in particular with continuous coating films showed a higher sensitivity to mechanical defects.
Approach for colour homogenisation of chestnut (Castanea sativa [Mill.]) by thermal modification
Authors: Correal-Mòdol E. , Wimmer T. , Huber H. , Schnabel T.
Published: January 2014

Decay problems are responsible for undesirable discolouration of chestnut timber, which lead to a decrease in the value of the wood. As the use of coloured chestnut wood is mainly concentrated on energy fuel, the potential for the use of this coloured wood should be demonstrated. Reference without discolouration and coloured samples from various boards of chestnut wood from Catalonia in north–east Spain were used for the thermal modification at 200°C. The surface colour was determined according to the CIEL*a*b* system before and after the heat treatment as well as after exposure to UV-light. Furthermore, the mass loss, differential swelling and Brinell hardness of untreated and heat treated chestnut samples were also measured. Heat treating homogenises the colour of the reference and coloured chestnut samples and modifies the physical properties. The results of this study demonstrate the possibilities of coloured chestnut wood to develop new applications for it.
Durability of thermally modified Pinus banksiana (Jack pine) wood against brown and white rot fungi
Authors: Lekounougou S. , Kocaefe D.
Published: January 2014

The resistance of thermally modified Canadian Pinus banksiana against four wood decaying fungi was evaluated. Wood samples were treated at different temperatures (190, 200 and 210°C) and exposed to three brown rot fungi as well as to a white rot fungus. Results showed that the untreated wood samples lost more weight when exposed to P. placenta, T. versicolor and G. trabeum compared to the weight loss observed in case of C. puteana. Thermal modification at 210°C improved the resistance of Pinus banksiana against G. trabeum and T. versicolor fungi as evident from the fact that reduction in weight loss of wood was found to be 98·3 and 96·3% respectively.
The Syndemic of AIDS and STDS among MSM
Authors: O'Leary Dale
Published: January 2014

The spread of HIV and other STDs among men who have sex with men (MSM) has been labeled a syndemic because in this population a number of different and interrelated health problems have come together and interact with one another. The various elements of the syndemic have an additive effect, each one intensifying the others. These factors include the number of infectious diseases endemic in this population, the high rate of substance abuse problems and psychological disorders, and the significant percentage of MSM who have experienced childhood sexual abuse and other adverse events. While MSM are disproportionately affected by HIV, syphilis, and other STDs, health activists from the gay community have systematically resisted the application of the full range of public health strategies traditionally used to prevent their spread. In the more than three decades since the beginning of the HIV/AIDS epidemic, there have been substantial advances in testing and treatment, yet the infection rate among MSM, and particularly young MSM, remains high, even as it has been dropping among other risk groups. This paper deals with the history of the syndemic, the failure of various risk reduction strategies, and treatment as prevention.
Assessing the construct validity and reliability of the parental perception on antibiotics (PAPA) scales
Authors: Alumran Arwa , Hou Xiang-Yu , Sun Jiandong , Yousef Abdullah A , Hurst Cameron
Published: January 2014

Background

The overuse of antibiotics is becoming an increasing concern. Antibiotic resistance, which increases both the burden of disease, and the cost of health services, is perhaps the most profound impact of antibiotics overuse. Attempts have been made to develop instruments to measure the psychosocial constructs underlying antibiotics use, however, none of these instruments have undergone thorough psychometric validation. This study evaluates the psychometric properties of the Parental Perceptions on Antibiotics (PAPA) scales. The PAPA scales attempt to measure the factors influencing parental use of antibiotics in children.

Methods

1111 parents of children younger than 12 years old were recruited from primary schools’ parental meetings in the Eastern Province of Saudi Arabia from September 2012 to January 2013. The structure of the PAPA instrument was validated using Confirmatory Factor Analysis (CFA) with measurement model fit evaluated using the raw and scaled χ
2, Goodness of Fit Index, and Root Mean Square Error of Approximation.

Results

A five-factor model was confirmed with the model showing good fit. Constructs in the model include: Knowledge and Beliefs, Behaviors, Sources of information, Adherence, and Awareness about antibiotics resistance. The instrument was shown to have good internal consistency, and good discriminant and convergent validity.

Conclusion

The availability of an instrument able to measure the psychosocial factors underlying antibiotics usage allows the risk factors underlying antibiotic use and overuse to now be investigated.
Synthetic cationic antimicrobial peptides bind with their hydrophobic parts to drug site II of human serum albumin
Authors: Sivertsen Annfrid , Isaksson Johan , Leiros Hanna-Kirsti S , Svenson Johan , Svendsen John-Sigurd , Brandsdal Bjørn Olav
Published: January 2014

Background

Many biologically active compounds bind to plasma transport proteins, and this binding can be either advantageous or disadvantageous from a drug design perspective. Human serum albumin (HSA) is one of the most important transport proteins in the cardiovascular system due to its great binding capacity and high physiological concentration. HSA has a preference for accommodating neutral lipophilic and acidic drug-like ligands, but is also surprisingly able to bind positively charged peptides. Understanding of how short cationic antimicrobial peptides interact with human serum albumin is of importance for developing such compounds into the clinics.

Results

The binding of a selection of short synthetic cationic antimicrobial peptides (CAPs) to human albumin with binding affinities in the μM range is described. Competitive isothermal titration calorimetry (ITC) and NMR WaterLOGSY experiments mapped the binding site of the CAPs to the well-known drug site II within subdomain IIIA of HSA. Thermodynamic and structural analysis revealed that the binding is exclusively driven by interactions with the hydrophobic moieties of the peptides, and is independent of the cationic residues that are vital for antimicrobial activity. Both of the hydrophobic moieties comprising the peptides were detected to interact with drug site II by NMR saturation transfer difference (STD) group epitope mapping (GEM) and INPHARMA experiments. Molecular models of the complexes between the peptides and albumin were constructed using docking experiments, and support the binding hypothesis and confirm the overall binding affinities of the CAPs.

Conclusions

The biophysical and structural characterizations of albumin-peptide complexes reported here provide detailed insight into how albumin can bind short cationic peptides. The hydrophobic elements of the peptides studied here are responsible for the main interaction with HSA. We suggest that albumin binding should be taken into careful consideration in antimicrobial peptide studies, as the systemic distribution can be significantly affected by HSA interactions.
Polymorphism of the merozoite surface protein-1 block 2 region in Plasmodium falciparum isolates from Mauritania
Authors: Ahmedou Salem Mohamed Salem O , Ndiaye Magatte , OuldAbdallahi Mohamed , Lekweiry Khadijetou M , Bogreau Hervé , Konaté Lassana , Faye Babacar , Gaye Oumar , Faye Ousmane , Mohamed Salem O Boukhary Ali O
Published: January 2014

Background

The genetic diversity of Plasmodium falciparum has been extensively studied in various parts of the world. However, limited data are available from Mauritania. The present study examined and compared the genetic diversity of P. falciparum isolates in Mauritania.

Methods

Plasmodium falciparum isolates blood samples were collected from 113 patients attending health facilities in Nouakchott and Hodh El Gharbi regions. K1, Mad20 and RO33 allelic family of msp-1 gene were determined by nested PCR amplification.

Results

K1 family was the predominant allelic type carried alone or in association with Ro33 and Mad20 types (90%; 102/113). Out of the 113 P. falciparum samples, 93(82.3%) harboured more than one parasite genotype. The overall multiplicity of infection was 3.2 genotypes per infection. There was no significant correlation between multiplicity of infection and age of patients. A significant increase of multiplicity of infection was correlated with parasite densities.

Conclusions

The polymorphism of P. falciparum populations from Mauritania was high. Infection with multiple P. falciparum clones was observed, as well as a high multiplicity of infection reflecting both the high endemicity level and malaria transmission in Mauritania.
RAD 51 Gene 135G/C polymorphism and the risk of four types of common cancers: a meta-analysis
Authors: Cheng Dan , Shi Huimin , Zhang Kan , Yi Lingling , Zhen Guohua
Published: January 2014

Objectives

RAD 51 gene plays an important role in the pathogenesis of squamous cell carcinoma of the head and neck (SCCHN), colorectal cancer, ovarian cancer and acute leukaemia. A number of studies assessed the association between RAD51 135G/C polymorphism and the risk of these cancers in different population. However, the results have been inconclusive. We performed a systematic meta-analysis to evaluate the association between RAD51 135G/C polymorphism and the risk of these four types of cancer.

Methods

Pubmed, Cochrane library and Chinese Biomedical Literature Database (CBM) were searched for case-control studies on RAD 51 135G/C polymorphism and the risk of SCCHN, colorectal cancer, ovarian cancer and acute leukaemia published up to Oct 31, 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association.

Results

A total of twenty-two published studies, with 6836 cases and 8507 controls were included. Overall, no significant association was found between RAD51 135G/C polymorphism and the risk of the four types of cancers (G/G vs. C/C: OR = 0.83, 95% CI: 0.43-1.59, P = 0.57). However, there was a significant association between this polymorphism and SCCHN risk in the subgroup analysis by cancer type (G/G vs. C/C: OR = 2.46, 95% CI: 1.08-5.61, P = 0.03).

Conclusion

The RAD 51 135G/C polymorphism was associated with the risk of SCCHN.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1383180234106945.
Mechanism of orthotic therapy for the painful cavus foot deformity
Authors: Najafi Bijan , Wrobel James S , Burns Joshua
Published: January 2014

Background

People who have extremely high arched feet or pes cavus often suffer from substantial foot pain. Custom‐made foot orthoses (CFO) have been shown to be an effective treatment option, but their specificity is unclear. It is generally thought that one of the primary functions of CFO is redistributing abnormal plantar pressures. This study sought to identify variables associated with pain relief after CFO intervention.

Methods

Plantar pressure data from a randomized controlled trial of 154 participants with painful pes cavus were retrospectively re‐analyzed at baseline and three month post CFO intervention. The participants were randomized to a treatment group given CFO or a control group given sham orthoses.

Results

No relationship between change in pressure magnitude and change in symptoms was found in either group. However, redistribution of plantar pressure, measured with the Dynamic Plantar Loading Index, had a significant effect on pain relief (p = 0.001). Our final model predicted 73% of the variance in pain relief from CFO and consisted of initial pain level, BMI, foot alignment, and changes in both Dynamic Plantar Loading Index and pressure–time integral.

Conclusion

Our data suggest that a primary function of effective orthotic therapy with CFO is redistribution of abnormal plantar pressures. Results of this study add to the growing body of literature providing mechanistic support for CFO providing pain relief in painful foot conditions. The proposed model may assist in better designing and assessing orthotic therapy for pain relief in patients suffering painful cavus foot deformity.

Trial registration

Randomized controlled trial: ISRCTN84913516
An exploration of emergency department presentations related to high heel footwear in Victoria, Australia, 2006–2010
Authors: Williams Cylie M , Haines Terry P
Published: January 2014

Background

Many women are warned against the dangers of wearing high heel footwear however there is limited empirical evidence demonstrating an association between wearing high heel with injury. Gait laboratory testing has found a higher heel height placed the foot in a position that increases the risk of ankle sprain. Women have also been surveyed about wearing high heels and approximately half of those reported inconvenience and pain after wearing a high heel shoe. This study aims to explore emergency department presentations of injuries and the estimated costs that have been directly attributed to wearing high heeled footwear within Victoria, Australia during 2006–2010.

Methods

The Victorian Emergency Minimum Dataset (VEMD) was searched for all injuries attributed to wearing high heel footwear presenting to emergency departments in Victoria Australia, between the years of 2006–2010. The VEMD produced a report detailing sex, age at presentation, month of presentation, time of day of presentation, day of presentation, location that injury occurred and type of injury for presentation. Monash Health in Victoria Australia, provided emergency department estimates for injury types to calculate an estimated cost of an acute injury related to wearing high heel footwear.

Results

There were 240 injuries presenting to Victorian emergency departments directly attributed to wearing high heeled footwear. The majority of people injured were women (n = 236) and all were less than 55 years of age. More injuries presented on a Sunday (n = 83) and more in the 8 am‐12 pm time bracket (n = 64). There were also more injuries presenting in the months of November, December and January (n = 80). The most commonly injured body part was the ankle (n = 123). The emergency department estimate of the cost of these injuries over this time‐frame was almost $72,000 (mean of $316.72 per presentation).

Conclusions

People who wear high heel footwear on weekends appear to be at higher risk for injury that leads to emergency department presentation. However, there was not a large cost associated with emergency department presentations attributable to wearing high heel footwear over a 5 year period.
Dynamic 3D shape of the plantar surface of the foot using coded structured light: a technical report
Authors: Thabet Ali K , Trucco Emanuele , Salvi Joaquim , Wang Weijie , Abboud Rami J
Published: January 2014

Background

The foot provides a crucial contribution to the balance and stability of the musculoskeletal system, and accurate foot measurements are important in applications such as designing custom insoles/footwear. With better understanding of the dynamic behavior of the foot, dynamic foot reconstruction techniques are surfacing as useful ways to properly measure the shape of the foot. This paper presents a novel design and implementation of a structured‐light prototype system providing dense three dimensional (3D) measurements of the foot in motion. The input to the system is a video sequence of a foot during a single step; the output is a 3D reconstruction of the plantar surface of the foot for each frame of the input.

Methods

Engineering and clinical tests were carried out to test the accuracy and repeatability of the system. Accuracy experiments involved imaging a planar surface from different orientations and elevations and measuring the fitting errors of the data to a plane. Repeatability experiments were done using reconstructions from 27 different subjects, where for each one both right and left feet were reconstructed in static and dynamic conditions over two different days.

Results

The static accuracy of the system was found to be 0.3 mm with planar test objects. In tests with real feet, the system proved repeatable, with reconstruction differences between trials one week apart averaging 2.4 mm (static case) and 2.8 mm (dynamic case).

Conclusion

The results obtained in the experiments show positive accuracy and repeatability results when compared to current literature. The design also shows to be superior to the systems available in the literature in several factors. Further studies need to be done to quantify the reliability of the system in clinical environments.
Inhibition of 6-phosphofructo-2-kinase (PFKFB3) induces autophagy as a survival mechanism
Authors: Klarer Alden C , O’Neal Julie , Imbert-Fernandez Yoannis , Clem Amy , Ellis Steve R , Clark Jennifer , Clem Brian , Chesney Jason , Telang Sucheta
Published: January 2014

Background

Unlike glycolytic enzymes that directly catabolize glucose to pyruvate, the family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFBs) control the conversion of fructose-6-phosphate to and from fructose-2,6-bisphosphate, a key regulator of the glycolytic enzyme phosphofructokinase-1 (PFK-1). One family member, PFKFB3, has been shown to be highly expressed and activated in human cancer cells, and derivatives of a PFKFB3 inhibitor, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), are currently being developed in clinical trials. However, the effectiveness of drugs such as 3PO that target energetic pathways is limited by survival pathways that can be activated by reduced ATP and nutrient uptake. One such pathway is the process of cellular self-catabolism termed autophagy. We hypothesized that the functional glucose starvation induced by inhibition of PFKFB3 in tumor cells would induce autophagy as a pro-survival mechanism and that inhibitors of autophagy could increase the anti-tumor effects of PFKFB3 inhibitors.

Results

We found that selective inhibition of PFKFB3 with either siRNA transfection or 3PO in HCT-116 colon adenocarcinoma cells caused a marked decrease in glucose uptake simultaneously with an increase in autophagy based on LC3-II and p62 protein expression, acridine orange fluorescence of acidic vacuoles and electron microscopic detection of autophagosomes. The induction of autophagy caused by PFKFB3 inhibition required an increase in reactive oxygen species since N-acetyl-cysteine blocked both the conversion of LC3-I to LC3-II and the increase in acridine orange fluorescence in acidic vesicles after exposure of HCT-116 cells to 3PO. We speculated that the induction of autophagy might protect cells from the pro-apoptotic effects of 3PO and found that agents that disrupt autophagy, including chloroquine, increased 3PO-induced apoptosis as measured by double staining with Annexin V and propidium iodide in both HCT-116 cells and Lewis lung carcinoma (LLC) cells. Chloroquine also increased the anti-growth effect of 3PO against LLCs in vivo and resulted in an increase in apoptotic cells within the tumors.

Conclusions

We conclude that PFKFB3 inhibitors suppress glucose uptake, which in turn causes an increase in autophagy. The addition of selective inhibitors of autophagy to 3PO and its more potent derivatives may prove useful as rational combinations for the treatment of cancer.
Direct inhibition of PI3K in combination with dual HER2 inhibitors is required for optimal antitumor activity in HER2+ breast cancer cells
Authors: Rexer Brent N , Chanthaphaychith Siprachanh , Dahlman Kimberly Brown , Arteaga Carlos L
Published: January 2014

Introduction

Despite multiple advances in the treatment of HER2+ breast cancers, resistance develops even to combinations of HER2 targeting agents. Inhibition of PI3K pathway signaling is critical for the efficacy of HER2 inhibitors. Activating mutations in PIK3CA can overlap with HER2 amplification and have been shown to confer resistance to HER2 inhibitors in preclinical studies.

Methods

Lapatinib-resistant cells were profiled for mutations in the PI3K pathway with the SNaPshot assay. Hotspot PIK3CA mutations were retrovirally transduced into HER2-amplified cells. The impact of PIK3CA mutations on the effect of HER2 and PI3K inhibitors was assayed by immunoblot, proliferation and apoptosis assays. Uncoupling of PI3K signaling from HER2 was investigated by ELISA for phosphoproteins in the HER2-PI3K signaling cascade. The combination of HER2 inhibitors with PI3K inhibition was studied in HER2-amplified xenograft models with wild-type or mutant PIK3CA.

Results

Here we describe the acquisition of a hotspot PIK3CA mutation in cells selected for resistance to the HER2 tyrosine kinase inhibitor lapatinib. We also show that the gain of function conferred by these PIK3CA mutations partially uncouples PI3K signaling from the HER2 receptor upstream. Drug resistance conferred by this uncoupling was overcome by blockade of PI3K with the pan-p110 inhibitor BKM120. In mice bearing HER2-amplified wild-type PIK3CA xenografts, dual HER2 targeting with trastuzumab and lapatinib resulted in tumor regression. The addition of a PI3K inhibitor further improved tumor regression and decreased tumor relapse after discontinuation of treatment. In a PIK3CA-mutant HER2+ xenograft, PI3K inhibition with BKM120 in combination with lapatinib and trastuzumab was required to achieve tumor regression.

Conclusion

These results suggest that the combination of PI3K inhibition with dual HER2 blockade is necessary to circumvent the resistance to HER2 inhibitors conferred by PIK3CA mutation and also provides benefit to HER2+ tumors with wild-type PIK3CA tumors.
PIK3CA mutations in breast cancer: reconciling findings from preclinical and clinical data
Authors: Zardavas Dimitrios , Phillips Wayne A , Loi Sherene
Published: January 2014

PIK3CA mutations represent one of the most common genetic aberrations in breast cancer. They have been reported to be present in over one-third of cases, with enrichment in the luminal and in human epidermal growth factor receptor 2-positive subtypes. Substantial preclinical data on the oncogenic properties of these mutations have been reported. However, whilst the preclinical data have clearly shown an association with robust activation of the pathway and resistance to common therapies used in breast cancer, the clinical data reported up to now do not support that the PIK3CA mutated genotype is associated with high levels of pathway activation or with a poor prognosis. We speculate that this may be due to the minimal use of transgenic mice models thus far. In this review, we discuss both the preclinical and clinical data associated with PIK3CA mutations and their potential implications. Prospective clinical trials stratifying by PIK3CA genotype will be necessary to determine if the mutation also predicts for increased sensitivity to agents targeting the phosphoinositide 3-kinase pathway.
Exon identity crisis: disease-causing mutations that disrupt the splicing code
Authors: Sterne-Weiler Timothy , Sanford Jeremy R
Published: January 2014

Cis-acting RNA elements control the accurate expression of human multi-exon protein coding genes. Single nucleotide variants altering the fidelity of this regulatory code and, consequently, pre-mRNA splicing are expected to contribute to the etiology of numerous human diseases.
Stem cell factor induces AP-1-dependent mast cell IL-6 production via MAPK kinase 3 activity
Authors: MacNeil Adam J , Junkins Robert D , Wu Zhengli , Lin Tong-Jun
Published: January 2014

Mast cells are critical immune effectors abundant in tissues interfacing with the environment and have major roles in allergen-induced inflammation and host responses to infection. SCF is a regulator of mast cell function and growth. However, the critical mechanisms in SCF-directed events remain incompletely defined. Here, we have investigated the role of MKK3 in mast cell SCF signaling-dependent functions by using BMMCs from MKK3-deficient mice. MKK3 was phosphorylated rapidly and persistently following SCF-induced activation and contributed to mast cell proliferation but not survival or migration in response to SCF. Analysis of SCF-induced mast cell mediator secretion demonstrated that IL-6 production is specifically dependent on MKK3 signals, both independently and in concert with IgE. Analysis of SCF-induced signaling showed that sustained p38 phosphorylation was impaired in MKK3-deficient mast cells, wheras early JNK and IκBα activation were enhanced. Notably, SCF-inducible expression and activation of c-Jun, a component of the AP-1 transcription factor, was significantly dependent on MKK3. Accordingly, AP-1 DNA-binding activity and interaction with the IL6 gene promoter was markedly impaired in MKK3-deficient mast cells, whereas transcription factors of the Egr family, NF-κB, and NFAT retained near-full activity. These results designate MKK3 as a novel, positive regulator of SCF-induced mast cell proliferation and a critical signaling protein for AP-1-dependent IL-6 production.
High-mobility group box-1 and its role in angiogenesis
Authors: Yang Shuai , Xu Linxinyu , Yang Tianshu , Wang Fang
Published: January 2014

HMGB1 is an architectural chromatin-binding protein that can be released actively by activated cells or passively by dying cells and can serve as a DAMP molecule to drive the pathogenesis of inflammatory and angiogenic diseases. Through TLR4 and RAGE signaling pathways, HMGB1 could regulate vascular growth in vivo and in vitro through diverse mechanisms, including induction of proangiogenic cytokine release and activation of ECs, macrophages, EPCs, and mesoangioblasts, all of which could contribute to vessel formation. Accordingly, HMGB1 plays a significant role in many angiogenesis-related conditions, such as tumors, PDR, wound-healing, and ischemia-induced angiogenesis. In this review, we focus on the regulatory role of HMGB1 in angiogenesis and recent progress in therapeutic strategies targeting HMGB1.
Photochemical Synthesis of Silica Nanoparticles
Authors: Liu Fengguo , Yang Wangjin , Wang Ying , Xue Xiangxin , Yang He
Published: January 2014

Silica nanoparticles were synthesized by a photochemical method in the presence of diphenyliodonium hexafluorophosphate as a superacid generator and tetraethyl orthosilicate as the silicon source. The addition of hexadecyltrimethylammonium bromide was found to have a profound influence on the morphology and surface structure of the silica nanoparticles.
Should the justification of medical exposures take account of radiation risks from previous examinations?
Authors: Walsh C , Murphy D
Published: January 2014

With the growing availability of dose histories for patients, the question of whether previous diagnostic radiation exposures should affect decisions on future examinations is coming into sharper focus. This article discusses ways in which cumulative dose information may affect our thinking in justifying exposures. Based on a common tendency to see a connection between past and future events even where we know them to be independent—the gambler's fallacy—we may find ourselves treating past risks as if they contribute to the present risk. We take the example of two patients scheduled for CT scans, one with no previous diagnostic radiation exposures, the other with a history of previous CT scans, to show that the risks, and justification process, are equivalent in both cases. For the patient with a history of diagnostic exposures, there are only two possibilities: either harm has been caused or there has been no effect. If previous CT examinations have not caused harm, then, as past risks, they are irrelevant. The patient is in precisely the same position with regard to risk as a patient with no dose history. If harm has been caused, avoiding further diagnostic exposures does not change this outcome; again in this case, a justified radiation examination should proceed. We argue that bringing dose history into the decision process for justifying examinations is contrary to our understanding of risk for low-dose radiation and, rather than improving patient safety, would unnecessarily restrict access to radiation-based diagnostic examinations.
Humanitarian culture as a phenomenon of spirituality
Authors: Шатило  , Shatilo I. , Кащенко  , Kashchenko T.
Published: January 2014

The substance of spiritual culture and humanitarian culture

and interrelations between these phenomena are analyzed. The levels,

functions and important attributes which differentiate humanitarian culture

and natural science culture are described. The author also highlights

the main characteristics of the Russian humanitarian culture, such as

cosmocentrism, integrity and «sobornost», the prevalence of moral and

spiritual regulators over the law restrictions and ontological realism.

The humanitarian culture influences the whole system of education and

determines the main body of the liberal education. The liberal education

not only reveals the reasons of human existence, but also provides the

techniques for resolving conflicts. Moral and psychological conflicts are

treated as forms, in which objective contradictions intrinsic to moral

progress of society are manifested.
Assessment of Genetic Diversity in Taro Using Morphometrics
Authors: Mandal Rupsanatan , Mukherjee Arijit , Mandal Nirmal , Tarafdar Jayanta , Mukharjee Archana
Published: January 2014

Taro is an important tropical tuber crop, used as a staple food or subsistence food by millions of people in the developing countries. A program was done to analyze and identify the same promising 20 selected local and Indian accessions taro, aiming at the characterization of the extent and distribution of genetic diversity using morphological marker with the define objectives ‘to find genetic variability amongst the 20 taro genotypes collected from different agro-climatic zones in India, in respect of plant physical (like length of main sucker, no of petioles, length of leaf lamina, wt. of side tuber, number of side tuber, estimated Corm yield, breadth of leaf lamina)’. The present study revealed that the genetic diversity recorded through physical parameters corresponded with the genetic diversity revealed through molecular data analysis. On the basis of D2 statistics the 20 genotypes were grouped into six different clusters (I-VI). Most of the local taro genotypes collected from different locations (BCC-1, BCC-2, BCC10, BCC15, BCC18, BCC-21, BCC24 and BCC-25) were placed in Cluster II with moderate intra cluster distance indicating their closeness, and showed similar phenotypic characters. The genotypes viz. FC-4, FC-11 and PKS-1 were found to distantly relate to other genotypes and were grouped into Cluster III.
Effect of Air Pollution on Chlorophyll Content of Leaves
Authors: Giri Sumitra , Shrivastava Deepali , Deshmukh Ketki , Dubey Pallavi
Published: January 2014

In the present investigation, comparative studies have been done, to find the effect of air pollutants generated from the exhaust of industries and automobiles on the chrorophyll content of leaves. The leaves samples of Azadirachta indica, Nerium oleander, Mangifera indica and­ Dalbergia sissoo were collected from areas with potentially higher and lower levels of air pollution Photosynthetic pigments chlorophyll a, chlorophyll b and carotenoids were quantified. A reduction in the photosynthetic pigments of plant leaves growing in higher polluted site as compared to non or less polluted ones.
Methods for Estimating Kidney Disease Stage Transition Probabilities Using
Electronic Medical Records
Authors: Luo Lola , Small Dylan , Stewart Walter F. , Roy Jason A.
Published: January 2014

Chronic diseases are often described by stages of severity. Clinical decisions
about what to do are influenced by the stage, whether a patient is progressing, and the
rate of progression. For chronic kidney disease (CKD), relatively little is known about
the transition rates between stages. To address this, we used electronic health records
(EHR) data on a large primary care population, which should have the advantage of having
both sufficient follow-up time and sample size to reliably estimate transition rates for
CKD. However, EHR data have some features that threaten the validity of any analysis. In
particular, the timing and frequency of labratory values and clinical measurements are
not determined a priori by research investigators, but rather, depend on many factors,
including the current health of the patient. We developed an approach for estimatating
CKD stage transition rates using hidden Markov models (HMMs), when the level of
information and observation time vary among individuals. To estimate the HMMs in a
computationally manageable way, we used a “discretization” method to transform daily
data into intervals of 30 days, 90 days, or 180 days. We assessed the accuracy and
computation time of this method via simulation studies. We also used simulations to
study the effect of informative observation times on the estimated transition rates. Our
simulation results showed good performance of the method, even when missing data are
non-ignorable. We applied the methods to EHR data from over 60,000 primary care patients
who have chronic kidney disease (stage 2 and above). We estimated transition rates
between six underlying disease states. The results were similar for men and
women.
Informal kinship care in rural China: the influence of Confucianism and attachment
Authors: Hu Yang , Lonne Bob , Burton Judith
Published: January 2014

This article examines the role of informal kinship care in addressing the emotional needs and mental health, along with relationships, of school-age children left behind in rural China. Rural–urban migration in China has caused many rural children to be left behind in their local communities. Based on semi-structured interview data, this article explores Confucianism’s impact on Chinese kin caregivers’ understandings of children’s needs and their childrearing practices to address these needs. Through the lens of attachment theory, this study identified a close affective bond between children left behind and their kin caregivers. This relationship is underpinned by kin caregivers’ high commitment and love for children, and the Confucian concept of ‘benevolence’. It not only provides children left behind with a sense of belonging, it also alleviates their trauma/grief due to separation from their parents.
Consumption of Acidic Water Alters the Gut Microbiome and Decreases the Risk of Diabetes in NOD Mice
Authors: Wolf Kyle J. , Daft Joseph G. , Tanner Scott M. , Hartmann Riley , Khafipour Ehsan , Lorenz Robin G.
Published: January 2014

Infant formula and breastfeeding are environmental factors that influence the incidence of Type 1 Diabetes (T1D) as well as the acidity of newborn diets. To determine if altering the intestinal microbiome is one mechanism through which an acidic liquid plays a role in T1D, we placed non-obese diabetic (NOD)/ShiLtJt mice on neutral (N) or acidified H2O and monitored the impact on microbial composition and diabetes incidence. NOD-N mice showed an increased development of diabetes, while exhibiting a decrease in Firmicutes and an increase in Bacteroidetes, Actinobacteria, and Proteobacteria from as early as 2 weeks of age. NOD-N mice had a decrease in the levels of Foxp3 expression in CD4+Foxp3+ cells, as well as decreased CD4+IL17+ cells, and a lower ratio of IL17/IFNγ CD4+ T-cells. Our data clearly indicates that a change in the acidity of liquids consumed dramatically alters the intestinal microbiome, the presence of protective Th17 and Treg cells, and the incidence of diabetes. This data suggests that early dietary manipulation of intestinal microbiota may be a novel mechanism to delay T1D onset in genetically pre-disposed individuals.
Quando os Jesuítas eram mestres da palavra: a retórica segundo a ratio studiorum
Authors: Miranda Margarida
Published: January 2014

Através da análise da Ratio Studiorum da Companhia de Jesus, este estudotem como objectivo descrever o ensino da Retórica nos Colégios dos Jesuítas,como ensino da eloquentio perfecta alcançada pela integração das suas cincopartes clássicas. Quer os escritos doutrinários quer a produção retórica dos jesuítas testemunham uma retórica consciente da sua elevada relevância para a vida pública; não uma retórica acantonada na teorização académica, nem transformada em normas de argumentação escolar ou de teoria literária restrita, mas uma retórica plenamente consciente da sua utilidade social.
Keats’s sonnet on Chapman’s translation of Homer: manuscript of early draft and initial publication
Authors: Head Brian Franklin
Published: January 2014

This study presents the earliest known manuscript of Keats's sonnet to Chapman’s translation of the Iliad (1611), in comparison with the first publication of the poem by Keats (1816). A comparative reading is provided, along with related philological and literary comments.
O que tem Esparta que ver com Jerusalém? A construção de um mito helenístico
Authors: Rodrigues Nuno Simões
Published: January 2014

Este estudo parte das referências a Esparta nos livros dos Macabeus, escritosno século II a. C., e propõe uma análise da relação que os textos estabelecem entre a cidade grega e os Judeus nesse período. Depois de discutir os aspectos políticos e ideológicos que subjazem a essa formulação, o autor conclui ser verosímil uma ligação política entre Espartanos e Judeus no século II a. C., no quadro da emergência da hegemonia romana no Mediterrâneo e definida por uma evocação retórica tipicamente helenística, apesar de persistirem as dúvidas no que diz respeito aos documentos citados pelos livros bíblicos.