bluuebunny/crossref_metadata_2025 huggingface dataset:
nab-Paclitaxel in Combination With Weekly Carboplatin With Concurrent Radiotherapy in Stage III Non-Small Cell Lung Cancer
Authors: Lammers Philip Edward , Lu Bo , Horn Leora , Shyr Yu , Keedy Vicki
Published: April 2015

Lessons Learned

The concomitant use of weekly nab-paclitaxel and carboplatin with concurrent radiotherapy was demonstrated to be a safe therapeutic approach in this phase I trial of 10 evaluable patients with stage III NSCLC. Despite the lack of systemic glucocorticoids, there were no reported infusion reactions or cases of peripheral neuropathy in this trial, both of which are known to occur with the use of paclitaxel.

Background.

Unresectable stage III non-small cell lung cancer (NSCLC) has a 5-year survival rate of 20%, and concurrent chemoradiotherapy results in significant toxicity with the use of current chemotherapeutic agents. nab-Paclitaxel was approved by the U.S. Food and Drug Administration in October 2012 for use along with carboplatin in advanced NSCLC. This study was undertaken to determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of weekly nab-paclitaxel given in combination with carboplatin and concurrent radiotherapy in patients with unresectable stage III NSCLC.

Methods.

Escalating doses of once-weekly nab-paclitaxel were given along with once-weekly carboplatin area under the plasma concentration time curve (AUC) of 2 and concurrent radiotherapy 66 Gy in 33 fractions, followed by 2 cycles of carboplatin and nab-paclitaxel consolidation chemotherapy.

Results.

Eleven patients were enrolled and received treatment per protocol, with 10 evaluable for efficacy and toxicity. At dose level 1 (nab-paclitaxel 60 mg/m2), 2 DLTs were observed: esophagitis and radiation dermatitis. Six patients were enrolled at dose level 0 (nab-paclitaxel 40 mg/m2) with no DLTs. Nine of 10 evaluable patients had a partial response.

Conclusion.

Concurrent chemoradiotherapy with nab-paclitaxel 40 mg/m2 and carboplatin AUC 2 is a safe and well-tolerated therapeutic regimen in patients with stage III NSCLC. A separate phase I/II study to evaluate the efficacy of this regimen is under way.
A Model of Endogenous Loan Quality and the Collapse of the Shadow Banking System
Authors: Ferrante Francesco
Published: April 2015

I develop a macroeconomic model with a financial sector, in which banks can finance risky projects (loans) and can affect their quality by exerting a costly screening effort. Informational frictions regarding the observability of loan characteristics limit the amount of external funds that banks can raise. In this framework I consider two possible types of financial intermediation, traditional banking (TB) and shadow banking (SB), differing in the level of diversification across projects. In particular, shadow banks, by pooling different loans, improve on the diversification of their idiosyncratic risk and increase the marketability of their assets. Due to their ability to pledge a larger share of the return on their projects, shadow banks will have a higher endogenous leverage compared to traditional banks, despite choosing a lower screening level. As a result, on the one hand, the introduction of SB will imply a higher amount of capital intermediated. On the other hand it will make the economy more fragile via three channels. First, by being highly leveraged and more exposed to risky projects, shadow banks will amplify exogenous negative shocks. Second, during a recession, the quality of projects intermediated by shadow banks will endogenously deteriorate even further, causing a slower recovery of the financial sector. A final source of instability is that the SB-system will be vulnerable to runs. When a run occurs, shadow banks will have to sell their assets to traditional banks, and this fire sale, because of the limited leverage capacity of the TB-system, will depress asset prices, making the run self-fulfilling and negatively affecting investment. In this framework I study how central bank credit intermediation helps reduce the impact of a crisis and the likelihood of a run.
Self-Image Profile in Children and Adolescents with Attention Deficit/ Hyperactivity Disorder and the Quality of Life in Their Parents
Authors: Gormez Vahdet , Forbes Fiona C. M.
Published: April 2015

Objective

We explored the impact of clinical response to treatment for Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents on the subsequent changes in their self-image profile, the quality of life of their parents, and its effect on socio-demographic variables.

Method

Conners Rating Scales for Parents (CPRS-R) and for Teachers (CTRS-R) completed at the time of entry to the service were repeated to measure clinical response to treatment; the Self-image Profiles for Children (SIP-C) and Adolescents (SIP-A), the World Health Organization Quality of Life (WHOQoL) questionnaire and postcode data were used to evaluate other domains.

Results

Data was collected for 53 boys (84%) and 10 girls (16%) with current mean age 11.5 years. Four-fifths (51/63) received pharmacological treatment and all parents were offered group parent training program. The only subscale in CPRS-R to show significance was the ADHD Index. The CTRS-R demonstrated statistically significant improvement ( p < 0.01) in most subscales. On the Self-image Profile, children reported themselves as more Kind ( p < 0.012), more Helpful ( p < 0.038) and less Bossy ( p < 0.047). Comparison of pre- and post-treatment scores on QoL revealed no significant changes; however, correlations of QoL responses against CPRS post-treatment revealed significant negative relationships in a number of instances. Parents living in less deprived areas felt their lives were more meaningful and less likely felt negatively about themselves (p = 0.04, N = 26, rho = 0.405).

Conclusion

Clinical improvement in ADHD symptoms was positively correlated with some improvement in the Self-image Profile of children and adolescents, but its impact on the QoL in parents was limited.
A Guide to Introducing and Integrating Reflective Practices in Medical Education
Authors: Sternlieb Jeffrey L.
Published: April 2015

It is a significant challenge for any medical education program to provide adequate training in medical knowledge. It can be just as daunting to include appropriate opportunity to learn about and manage the emotional impact of illness experiences, the healing process, and provider-patient relationships. While there may be only a few basic changes to the core of medical knowledge, advances in medical practice regularly have an impact on the nature of patient care. Life-long learning is essential to maintain one's competence. However, everything doctors and other medical professionals learn about relationships with patients during their training is relevant for the rest of their career. One primary source of this learning are reflective practices. However, there is no guide or description of or comparison among the distinguishing characteristics of reflective processes. In addition, there are no criteria for the selection or integration of reflective processes in medical training or beyond. This article proposes understanding reflection as a complex, three-level process and identifies dimensions which differentiate a variety of reflective process activities. The discussion includes considerations for selecting which activities might be usefully incorporated in education curricula, and identifies conditions of medical training cultures that will support successful integration.
Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a Diet-Induced Type 2 Diabetes Model
Authors: Amrutkar Manoj , Cansby Emmelie , Chursa Urszula , Nuñez-Durán Esther , Chanclón Belén , Ståhlman Marcus , Fridén Vincent , Mannerås-Holm Louise , Wickman Anna , Smith Ulf , Bäckhed Fredrik , Borén Jan , Howell Brian W. , Mahlapuu Margit
Published: April 2015

Understanding the molecular networks controlling ectopic lipid deposition, glucose tolerance, and insulin sensitivity is essential to identifying new pharmacological approaches to treat type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a negative regulator of glucose and insulin homeostasis based on observations in myoblasts with acute depletion of STK25 and in STK25-overexpressing transgenic mice. Here, we challenged Stk25 knockout mice and wild-type littermates with a high-fat diet and showed that STK25 deficiency suppressed development of hyperglycemia and hyperinsulinemia, improved systemic glucose tolerance, reduced hepatic gluconeogenesis, and increased insulin sensitivity. Stk25−/− mice were protected from diet-induced liver steatosis accompanied by decreased protein levels of acetyl-CoA carboxylase, a key regulator of both lipid oxidation and synthesis. Lipid accumulation in Stk25−/− skeletal muscle was reduced, and expression of enzymes controlling the muscle oxidative capacity (Cpt1, Acox1, Cs, Cycs, Ucp3) and glucose metabolism (Glut1, Glut4, Hk2) was increased. These data are consistent with our previous study of STK25 knockdown in myoblasts and reciprocal to the metabolic phenotype of Stk25 transgenic mice, reinforcing the validity of the results. The findings suggest that STK25 deficiency protects against the metabolic consequences of chronic exposure to dietary lipids and highlight the potential of STK25 antagonists for the treatment of type 2 diabetes.
Dexmedetomidine, Ketamine, and Midazolam for Oral Rehabilitation: A Case Report
Authors: Kim Bill W. S. , Peskin Robert M.
Published: April 2015

Intravenous sedation is frequently provided by anesthesiologists for phobic patients undergoing elective dental treatment in outpatient settings. Propofol is one of the most commonly used anesthetic agents that can result in apnea and respiratory depression, thereby posing potential difficulties with perioperative airway management. Dexmedetomidine has been utilized successfully in intravenous sedation for a wide variety of procedures and holds potential as an alternative to propofol in outpatient dental settings. However, as a single agent, it may not provide adequate depth of sedation and analgesia for oral rehabilitation. In this case report we demonstrate an effective alternative intravenous deep-sedation technique for an adult phobic patient undergoing oral rehabilitation utilizing 3 agents in combination: dexmedetomidine, ketamine, and midazolam. This combination of agents may be especially useful for those patients with a history of substance abuse, where administration of opioids may be undesirable or contraindicated.
Recent progress in the thermodynamics of ferrotoroidic materials
Authors: Planes Antoni , Castán Teresa , Saxena Avadh
Published: April 2015

Recent theoretical and experimental progress on the study of ferrotoroidic materials is reviewed. The basic field equations are first described and then the expressions for magnetic toroidal moment and toroidization are derived. Relevant materials and experimental observation of magnetic toroidal moment and toroidal domains are summarized next. The thermodynamics of such magnetic materials is discussed in detail with examples of ferrorotoidic phase transition studied using Landau modelling. Specifically, an example of application of Landau modelling to the study of toroidocaloric effect is also provided. Recent results of polar nanostructures with electrical toroidal moment are finally reviewed.
Structural and magnetic studies on praseodymium and transition-metal co-substituted BiFeO3 ceramics
Authors: Coondoo Indrani , Panwar Neeraj , Puli Venkata S. , Ramana Venkata E. , Kholkin A. L. , Katiyar Ram S.
Published: April 2015

Bulk ceramic compositions of BiFeO
Gust Alleviation of a Large Aircraft with a Passive Twist Wingtip
Authors: Guo Shijun , De Los Monteros Jaime , Liu Ying
Published: April 2015

This paper presents an investigation into the gust response and wing structure load alleviation of a 200-seater aircraft by employing a passive twist wingtip (PTWT). The research was divided into three stages. The first stage was the design and analysis of the baseline aircraft, including aerodynamic analysis, structural design using the finite element (FE) method and flutter analysis to meet the design requirements. Dynamic response analysis of the aircraft to discrete (one-cosin) gust was also performed in a range of gust radiances specified in the airworthiness standards. In the second stage, a PTWT of a length of 1.13 m was designed with the key parameters determined based on design constraints and, in particular, the aeroelastic stability and gust response. Subsequent gust response analysis was performed to evaluate the effectiveness of the PTWT for gust alleviation. The results show that the PTWT produced a significant reduction of gust-induced wingtip deflection by 21% and the bending moment at the wing root by 14% in the most critical flight case. In the third stage, effort was made to study the interaction and influence of the PTWT on the symmetric and unsymmetrical manoeuvring of the aircraft when ailerons were in operation. The results show the that PTWT influence with a reduction of the aircraft normal velocity and heave motion by 1.7% and 3%, respectively, is negligible. However, the PTWT influence on the aircraft roll moment with a 20.5% reduction is significant. A locking system is therefore required in such a manoeuvring condition. The investigation has shown that the PTWT is an effective means for gust alleviation and, therefore, has potential for large aircraft application.
Environmental Enrichment Reverses Histone Methylation Changes in the Aged Hippocampus and Restores Age-Related Memory Deficits
Authors: Morse Sarah , Butler Anderson , Davis Robin , Soller Ian , Lubin Farah
Published: April 2015

A decline in long-term memory (LTM) formation is a common feature of the normal aging process, which corresponds with abnormal expression of memory-related genes in the aged hippocampus. Epigenetic modulation of chromatin structure is required for proper transcriptional control of genes, such as the brain-derived neurotrophic factor (Bdnf) and Zif268 in the hippocampus during the consolidation of new memories. Recently, the view has emerged that aberrant transcriptional regulation of memory-related genes may be reflective of an altered epigenetic landscape within the aged hippocampus, resulting in memory deficits with aging. Here, we found that baseline resting levels for tri-methylation of histone H3 at lysine 4 (H3K4me3) and acetylation of histone H3 at lysine 9 and 14 (H3K9,K14ac) were altered in the aged hippocampus as compared to levels in the hippocampus of young adult rats. Interestingly, object learning failed to increase activity-dependent H3K4me3 and di-methylation of histone H3 at lysine 9 (H3K9me2) levels in the hippocampus of aged adults as compared to young adults. Treatment with the LSD-1 histone demethylase inhibitor, t-PCP, increased baseline resting H3K4me3 and H3K9,K14ac levels in the young adult hippocampus, while young adult rats exhibited similar memory deficits as observed in aged rats. After environmental enrichment (EE), we found that object learning induced increases in H3K4me3 levels around the Bdnf, but not the Zif268, gene region in the aged hippocampus and rescued memory deficits in aged adults. Collectively, these results suggest that histone lysine methylation levels are abnormally regulated in the aged hippocampus and identify histone lysine methylation as a transcriptional mechanism by which EE may serve to restore memory formation with aging.
Driving Innovative Thinking in the New Zealand Construction Industry
Authors: Noktehdan Mohammadali , Shahbazpour Mehdi , Wilkinson Suzanne
Published: April 2015

This paper examines the relationship between innovation and productivity improvement in the construction industry. It is argued that this relationship is not well understood due to lack of in-depth understanding of innovation in construction. To overcome this obstacle, the authors present a multi-dimensional innovation classification system which aims at better defining and classifying what is meant by innovation in construction. The use of this classification system is demonstrated by applying it to a database of 500 innovations reported by the construction alliance, the Stronger Christchurch Infrastructure Rebuild Team. The results clearly demonstrate the diversity of types, degree of novelty and performance improvement benefits among construction innovations. Such diversity means that the impact of the reported innovations on productivity and performance are of different levels of significance. The classification system developed in this study can be used by construction organisations and alliances in the future to develop more detailed methods of calculating innovation performance indicators, based on the innovation type, novelty and benefits factors. By using this system, they can also put in place mechanisms to influence the types of innovation developed in their projects with the aim of maximising their productivity performance.
The Evaluation of Magnetic Polymethacrylate-based Microspheres Used for Solid Phase DNA Micro-Extraction
Authors: Trachtová Štěpánka , Zapletalová Hana , Španová Alena , Horák Daniel , Kolářová Hana , Rittich Bohuslav
Published: April 2015

Using magnetic particles as a solid-phase extraction system is the most frequently used micro-technique for DNA isolation. Particles with a complete covering of magnetic cores by a polymer are hence preferred. Quantitative polymerase chain reaction (qPCR) was used for the evaluation of the polymer coating efficiency of hydrophilic magnetic poly(2-hydroxyethyl methacrylate-co-glycidyl methacrylate) (P(HEMA-co-GMA)) and poly(glycidyl methacrylate) (PGMA) microspheres with/without carboxyl groups. The inhibition effect of magnetic microspheres was identified by the shift in Cq values (ΔCq) after the addition of different amounts of microspheres to PCR mixtures. With the increase of microsphere concentrations, the shift in Cq values to higher values was usually observed. P(HEMA-co-GMA) microspheres containing carboxyl groups extinguished the fluorescence at concentrations over 2 mg mL−1 in a PCR mixture without any influence on the synthesis of PCR products. No PCR products (inhibition of DNA amplification) were detected in the presence of more than 0.8 mg mL−1 in the PCR mixture of PGMA microspheres. Atomic force microscopy (AFM) was used for the determination of the surface morphology of the microspheres. The microspheres were spherical, and their surface was non-porous.
The Peri-Implant and Periodontal Microbiota in Patients with and without Clinical Signs of Inflammation
Authors: Jakobi Meike , Stumpp Sascha , Stiesch Meike , Eberhard Jörg , Heuer Wieland
Published: April 2015

Late implant failures, caused by the inflammation of surrounding tissues are a problem in implant dentistry. The path of bacterial transmission from teeth to implants is not completely understood. Therefore, the purpose of this study was to analyze intraindividual bacterial transmission characterizing subgingival microbiomes in teeth and implants, both in healthy subjects and in those with signs of periodontitis or peri-implantitis. Samples of peri-implant and dental sulcus fluid were collected. To identify the predominant microbiota, amplified fragments of bacterial 16S rRNA gene were separated by single strand conformation polymorphism analysis, sequenced and taxonomically classified. A total of 25 different predominant genera were found in the diseased group and 14 genera in the healthy group. Species richness did not differ significantly between implants, neighboring teeth and teeth with largest probing depth in the diseased group. Additionally, no differences between teeth and implants in the healthy group were detected. In contrast, microbial diversity varied between the different sampling points. Species richness is similar in healthy and diseased sites, but the composition of the bacterial community differed within the individual subjects. The underlying analyses strongly suggest that complete transmission from neighboring teeth to implants is unlikely.
Pressure Tensor of Nanoscopic Liquid Drops
Authors: G. Segovia-López José , Carbajal-Domínguez Adrian
Published: April 2015

This study describes the structure of an inhomogeneous fluid of one or several components that forms a spherical interface. Using the stress tensor of Percus–Romero, which depends on the density of one particle and the intermolecular potential, it provides an analytical development leading to the microscopic expressions of the pressure differences and the interfacial properties of both systems. The results are compared with a previous study and agree with the description of the mean field.
A Simple Decoder for Topological Codes
Authors: Wootton James
Published: April 2015

Here we study an efficient algorithm for decoding topological codes. It is a simple form of HDRG decoder, which could be straightforwardly generalized to complex decoding problems. Specific results are obtained for the planar code with both i.i.d. and spatially correlated errors. The method is shown to compare well with existing ones, despite its simplicity.
Resource Requirements and Speed versus Geometry of Unconditionally Secure Physical Key Exchanges
Authors: Gonzalez Elias , Balog Robert , Kish Laszlo
Published: April 2015

The imperative need for unconditional secure key exchange is expounded by the increasing connectivity of networks and by the increasing number and level of sophistication of cyberattacks. Two concepts that are theoretically information-secure are quantum key distribution (QKD) and Kirchoff-Law-Johnson-Noise (KLJN). However, these concepts require a dedicated connection between hosts in peer-to-peer (P2P) networks which can be impractical and or cost prohibitive. A practical and cost effective method is to have each host share their respective cable(s) with other hosts such that two remote hosts can realize a secure key exchange without the need of an additional cable or key exchanger. In this article we analyze the cost complexities of cable, key exchangers, and time required in the star network. We mentioned the reliability of the star network and compare it with other network geometries. We also conceived a protocol and equation for the number of secure bit exchange periods needed in a star network. We then outline other network geometries and trade-off possibilities that seem interesting to explore.
Vacuum Insulation Panels: Analysis of the Thermal Performance of Both Single Panel and Multilayer Boards
Authors: Capozzoli Alfonso , Fantucci Stefano , Favoino Fabio , Perino Marco
Published: April 2015

The requirements for improvement in the energy efficiency of buildings, mandatory in many EU countries, entail a high level of thermal insulation of the building envelope. In recent years, super-insulation materials with very low thermal conductivity have been developed. These materials provide satisfactory thermal insulation, but allow the total thickness of the envelope components to be kept below a certain thickness. Nevertheless, in order to penetrate the building construction market, some barriers have to be overcome. One of the main issues is that testing procedures and useful data that are able to give a reliable picture of their performance when applied to real buildings have to be provided. Vacuum Insulation Panels (VIPs) are one of the most promising high performing technologies. The overall, effective, performance of a panel under actual working conditions is influenced by thermal bridging, due to the edge of the panel envelope and to the type of joint. In this paper, a study on the critical issues related to the laboratory measurement of the equivalent thermal conductivity of VIPs and their performance degradation due to vacuum loss has been carried out utilizing guarded heat flux meter apparatus. A numerical analysis has also been developed to study thermal bridging effect when VIP panels are adopted to create multilayer boards for building applications.
Effects of Electric Fields on the Combustion Characteristics of Lean Burn Methane-Air Mixtures
Authors: Fang Jianfeng , Wu Xiaomin , Duan Hao , Li Chao , Gao Zhongquan
Published: April 2015

In this work, the effects of the electric fields on the flame propagation and combustion characteristics of lean premixed methane–air mixtures were experimentally investigated in a constant volume chamber. Results show that the flame front is remarkably stretched by the applied electric field, the stretched flame propagation velocity and the average flame propagation velocity are all accelerated significantly as the input voltage increases. This indicates that the applied electric field can augment the stretch in flame, and the result is more obvious for leaner mixture. According to the analyses of the combustion pressure variation and the heat release rate, the peak combustion pressure Pmax increases and its appearance time tp is advanced with the increase of the input voltage. For the mixture of λ = 1.6 at the input voltage of −12 kV, Pmax increases by almost 12.3%, and tp is advanced by almost 31.4%, compared to the case of without electric fields. In addition, the normalized mass burning rate and the accumulated mass fraction burned are all enhanced substantially, and the flame development duration and the rapid burning duration are remarkably reduced with the increase of the input voltage, and again, the influence of electric field is more profound for leaner mixtures. The results can be explained by the electric field-induced stretch effects on lean burn methane-air mixture.
Dynamic Simulation and Exergo-Economic Optimization of a Hybrid Solar–Geothermal Cogeneration Plant
Authors: Calise Francesco , Capuano Davide , Vanoli Laura
Published: April 2015

This paper presents a dynamic simulation model and a parametric analysis of a solar-geothermal hybrid cogeneration plant based on an Organic Rankine Cycle (ORC) powered by a medium-enthalpy geothermal resource and a Parabolic Trough Collector solar field. The fluid temperature supplying heat to the ORC varies continuously as a function of the solar irradiation, affecting both the electrical and thermal energies produced by the system. Thus, a dynamic simulation was performed. The ORC model, developed in Engineering Equation Solver, is based on zero-dimensional energy and mass balances and includes specific algorithms to evaluate the off-design system performance. The overall simulation model of the solar-geothermal cogenerative plant was implemented in the TRNSYS environment. Here, the ORC model is imported, whereas the models of the other components of the system are developed on the basis of literature data. Results are analyzed on different time bases presenting energetic, economic and exergetic performance data. Finally, a rigorous optimization has been performed to determine the set of system design/control parameters minimizing simple payback period and exergy destruction rate. The system is profitable when a significant amount of the heat produced is consumed. The highest irreversibilities are due to the solar field and to the heat exchangers.
Available Nitrogen and Responses to Nitrogen Fertilizer in Brazilian Eucalypt Plantations on Soils of Contrasting Texture
Authors: Pulito Ana , Leonardo de Moraes Gonçalves José , Smethurst Philip , Junior José , Alcarde Alvares Clayton , Henrique Tertulino Rocha José , Hübner Ayeska , Fabiano de Moraes Luiz , Miranda Aline , Kamogawa Marcos , Gava José , Chaves Raul , Silva Claudio
Published: April 2015

Eucalyptus plantations have seldom responded to N fertilization in tropical and subtropical regions of Brazil. This implies that rates of N mineralization have been adequate to supply tree needs. However, subsequent crop rotations with low N fertilization may result in declining concentrations of organic and potentially mineralizable N (N0), and consequent loss of wood productivity. This study investigated (a) in situ N mineralization and N0 in soils of eucalypt plantations in São Paulo state, Brazil; (b) tree growth responses to N fertilizer applied 6–18 months after planting; and (c) the relationships between N0, other soil attributes and tree growth. We established eleven N fertilizer trials (maximum 240 kg ha−1 of N) in E. grandis and E. grandis x urophylla plantations. The soil types at most sites were Oxisols and Quartzipsamments, with a range of organic matter (18 to 55 g kg−1) and clay contents (8% to 67%) in the 0–20 cm layer. Concentrations of N0 were measured using anaerobic incubation on soil samples collected every three months (different seasons). The samples collected in spring and summer had N0 140–400 kg ha−1 (10%–19% total soil N), which were best correlated with soil texture and organic matter content. Rates of in situ net N mineralization (0–20 cm) ranged from 100 to 200 kg ha−1 year−1 and were not correlated with clay, total N, or N0. These high N mineralization rates resulted in a low response to N fertilizer application during the early ages of stand growth, which were highest on sandy soils. At the end of the crop rotation, the response to N fertilizer was negligible and non-significant at all sites.
EMAST is a Form of Microsatellite Instability That is Initiated by Inflammation and Modulates Colorectal Cancer Progression
Authors: Carethers John , Koi Minoru , Tseng-Rogenski Stephanie
Published: April 2015

DNA mismatch repair (MMR) function is critical for correcting errors coincident with polymerase-driven DNA replication, and its proteins are frequent targets for inactivation (germline or somatic), generating a hypermutable tumor that drives cancer progression. The biomarker for defective DNA MMR is microsatellite instability-high (MSI-H), observed in ~15% of colorectal cancers, and defined by mono- and dinucleotide microsatellite frameshift mutations. MSI-H is highly correlated with loss of MMR protein expression, is commonly diploid, is often located in the right side of the colon, prognosticates good patient outcome, and predicts poor efficacy with 5-fluorouracil treatment. Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) is another form of MSI at tetranucleotide repeats that has been observed in multiple cancers, but its etiology and clinical relevance to patient care has only been recently illuminated. Specifically, EMAST is an acquired somatic defect observed in up to 60% of colorectal cancers and caused by unique dysfunction of the DNA MMR protein MSH3 (and its DNA MMR complex MutSβ, a heterodimer of MSH2-MSH3), and in particular a loss-of-function phenotype due to a reversible shift from its normal nuclear location into the cytosol in response to oxidative stress and the pro-inflammatory cytokine interleukin-6. Tumor hypoxia may also be a contributor. Patients with EMAST colorectal cancers show diminished prognosis compared to patients without the presence of EMAST in their cancer. In addition to defective DNA MMR recognized by tetranucleotide (and di- and tri-nucleotide) frameshifts, loss of MSH3 also contributes to homologous recombination-mediated repair of DNA double stranded breaks, indicating the MSH3 dysfunction is a complex defect for cancer cells that generates not only EMAST but also may contribute to chromosomal instability and aneuploidy. Areas for future investigation for this most common DNA MMR defect among colorectal cancers include relationships between EMAST and chemotherapy response, patient outcome with aneuploid changes in colorectal cancers, target gene mutation analysis, and mechanisms related to inflammation-induced compartmentalization and inactivation for MSH3.
Epigenetics: Its Understanding Is Crucial to a Sustainable Healthcare System
Authors: Thunders Michelle
Published: April 2015

Understanding the molecular impact of lifestyle factors has never been so important; a period in time where there are so many adults above retirement age has been previously unknown. As a species, our life expectancy is increasing yet the period of our lives where we enjoy good health is not expanding proportionately. Over the next 50 years we will need to almost double the percentage of GDP spent on health care, largely due to the increasing incidence of obesity related chronic diseases. A greater understanding and implementation of an integrated approach to health is required. Research exploring the impact of nutritional and exercise intervention on the epigenetically flexible genome is up front in terms of addressing healthy aging. Alongside this, we need a greater understanding of the interaction with our immune and nervous systems in preserving and maintaining health and cognition.
Climate Change Impacts on Environmental and Human Exposure to Mercury in the Arctic
Authors: Sundseth Kyrre , Pacyna Jozef , Banel Anna , Pacyna Elisabeth , Rautio Arja
Published: April 2015

This paper reviews information from the literature and the EU ArcRisk project to assess whether climate change results in an increase or decrease in exposure to mercury (Hg) in the Arctic, and if this in turn will impact the risks related to its harmful effects. It presents the state-of-the art of knowledge on atmospheric mercury emissions from anthropogenic sources worldwide, the long-range transport to the Arctic, and it discusses the likely environmental fate and exposure effects on population groups in the Arctic under climate change conditions. The paper also includes information about the likely synergy effects (co-benefits) current and new climate change polices and mitigation options might have on mercury emissions reductions in the future. The review concludes that reductions of mercury emission from anthropogenic sources worldwide would need to be introduced as soon as possible in order to assure lowering the adverse impact of climate change on human health. Scientific information currently available, however, is not in the position to clearly answer whether climate change will increase or decrease the risk of exposure to mercury in the Arctic. New research should therefore be undertaken to model the relationships between climate change and mercury exposure.
Exposure to Airborne Particles and Volatile Organic Compounds from Polyurethane Molding, Spray Painting, Lacquering, and Gluing in a Workshop
Authors: Mølgaard Bjarke , Viitanen Anna-Kaisa , Kangas Anneli , Huhtiniemi Marika , Larsen Søren , Vanhala Esa , Hussein Tareq , Boor Brandon , Hämeri Kaarle , Koivisto Antti
Published: April 2015

Due to the health risk related to occupational air pollution exposure, we assessed concentrations and identified sources of particles and volatile organic compounds (VOCs) in a handcraft workshop producing fishing lures. The work processes in the site included polyurethane molding, spray painting, lacquering, and gluing. We measured total VOC (TVOC) concentrations and particle size distributions at three locations representing the various phases of the manufacturing and assembly process. The mean working-hour TVOC concentrations in three locations studied were 41, 37, and 24 ppm according to photo-ionization detector measurements. The mean working-hour particle number concentration varied between locations from 3000 to 36,000 cm−3. Analysis of temporal and spatial variations of TVOC concentrations revealed that there were at least four substantial VOC sources: spray gluing, mold-release agent spraying, continuous evaporation from various lacquer and paint containers, and either spray painting or lacquering (probably both). The mold-release agent spray was indirectly also a major source of ultrafine particles. The workers’ exposure can be reduced by improving the local exhaust ventilation at the known sources and by increasing the ventilation rate in the area with the continuous source.
Conceptual and Operational Considerations in Identifying Socioenvironmental Factors Associated with Disability among Community-Dwelling Adults
Authors: Philibert Mathieu , Pampalon Robert , Daniel Mark
Published: April 2015

Disability is conceived as a person–context interaction. Physical and social environments are identified as intervention targets for improving social participation and independence. In comparison to the body of research on place and health, relatively few reports have been published on residential environments and disability in the health sciences literature. We reviewed studies evaluating the socioenvironmental correlates of disability. Searches were conducted in Medline, Embase and CINAHL databases for peer-reviewed articles published between 1997 and 2014. We found many environmental factors to be associated with disability, particularly area-level socioeconomic status and rurality. However, diversity in conceptual and methodological approaches to such research yields a limited basis for comparing studies. Conceptual inconsistencies in operational measures of disability and conceptual disagreement between studies potentially affect understanding of socioenvironmental influences. Similarly, greater precision in socioenvironmental measures and in study designs are likely to improve inference. Consistent and generalisable support for socioenvironmental influences on disability in the general adult population is scarce.
Health Impact Assessment: Improving Its Effectiveness in the Enhancement of Health and Well-Being
Authors: Spickett Jeffery , Katscherian Dianne , Brown Helen , Rumchev Krassi
Published: April 2015

Most countries in the world have Environmental Impact Assessment (EIA) processes and procedures to evaluate the potential impact of development projects on the environment. This process, which attempts to predict the potential adverse effects of the proposed development project on the environment, is normally legislated and is part of the approval process for the project. Although these processes have been effective in reducing the adverse impacts on the environment they have been limited in their ability to provide protection for the health and well-being of people affected by the development. [...]
Simulating Urban Growth Using a Random Forest-Cellular Automata (RF-CA) Model
Authors: Kamusoko Courage , Gamba Jonah
Published: April 2015

Sustainable urban planning and management require reliable land change models, which can be used to improve decision making. The objective of this study was to test a random forest-cellular automata (RF-CA) model, which combines random forest (RF) and cellular automata (CA) models. The Kappa simulation (KSimulation), figure of merit, and components of agreement and disagreement statistics were used to validate the RF-CA model. Furthermore, the RF-CA model was compared with support vector machine cellular automata (SVM-CA) and logistic regression cellular automata (LR-CA) models. Results show that the RF-CA model outperformed the SVM-CA and LR-CA models. The RF-CA model had a Kappa simulation (KSimulation) accuracy of 0.51 (with a figure of merit statistic of 47%), while SVM-CA and LR-CA models had a KSimulation accuracy of 0.39 and −0.22 (with figure of merit statistics of 39% and 6%), respectively. Generally, the RF-CA model was relatively accurate at allocating “non-built-up to built-up” changes as reflected by the correct “non-built-up to built-up” components of agreement of 15%. The performance of the RF-CA model was attributed to the relatively accurate RF transition potential maps. Therefore, this study highlights the potential of the RF-CA model for simulating urban growth.
In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid
Authors: Wei Wen-Hao , Dong Xue-Meng , Liu Chen-Guang
Published: April 2015

Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model drug. The human cervical cancer (HeLa) cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE), which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy.
Male Reproductive Cancers and Infertility: A Mutual Relationship
Authors: Tvrda Eva , Agarwal Ashok , Alkuhaimi Nawaf
Published: April 2015

Reproductive dysfunction and malignancies related to the male gender represent a serious health concern, whose incidence has significantly risen over the past years. Prior to treatment, testicular or prostate cancer patients often display poor semen characteristics similar to subfertile or infertile patients. This fact is underscored by cases where the malignancy is often diagnosed in males who undergo a general fertility screening. This review aims to examine the associations between male infertility and reproductive cancers focusing on common etiologies and biological mechanisms underlining these pathologies. Furthermore, we discuss compelling epidemiological data hypothesizing that male reproductive failure may act as a precursor of future andrological malignancies, including testicular or prostate cancer, thus providing a stimulus for a more specific research in male reproductive health and emphasizing the importance of this relation for physicians taking care of male patients with a reproductive disease.
Enhancement of Phenol Biodegradation by Pseudochrobactrum sp. through Ultraviolet-Induced Mutation
Authors: Mao Zhen , Yu Chenyang , Xin Lingling
Published: April 2015

The phenol-degrading efficiency of Pseudochrobactrum sp. was enhanced by ultraviolet (UV) irradiation. First, a bacterial strain, Pseudochrobactrum sp. XF1, was isolated from the activated sludge in a coking plant. It was subjected to mutation by UV radiation for 120 s and a mutant strain with higher phenol-degrading efficiency, Pseudochrobactrum sp. XF1-UV, was selected. The mutant strain XF1-UV was capable of degrading 1800 mg/L phenol completely within 48 h and had higher tolerance to hydrogen ion concentration and temperature variation than the wild type. Haldane’s kinetic model was used to fit the exponential growth data and the following kinetic parameters were obtained: μmax = 0.092 h−1, Ks = 22.517 mg/L, and Ki = 1126.725 mg/L for XF1, whereas μmax = 0.110 h−1, Ks = 23.934 mg/L, and Ki = 1579.134 mg/L for XF1-UV. Both XF1 and XF1-UV degraded phenol through the ortho-pathway; but the phenol hydroxylase activity of XF1-UV1 was higher than that of XF1, therefore, the mutant strain biodegraded phenol faster. Taken together, our results suggest that Pseudochrobactrum sp. XF1-UV could be a promising candidate for bioremediation of phenol-containing wastewaters.
The Relevance of miRNA-21 in HSV-Induced Inflammation in a Mouse Model
Authors: Choi Bunsoon , Kim Hyoun-Ah , Suh Chang-Hee , Byun Hae , Jung Ju-Yang , Sohn Seonghyang
Published: April 2015

The purpose of this study was to clarify the correlation between microRNA-21 (miR-21) expression and inflammation in a herpes simplex virus (HSV)-induced Behçet’s Disease (BD) mouse model. miR-21 was compared between BD patients and healthy controls in peripheral blood mononuclear cells (PBMC). For miR-21 inhibition, miR-21 antagomir was applied to BD mice. The change of symptoms was monitored. The levels of cytokines and related molecules were determined by ELISA and real time qPCR. Treatment with colchicine or pentoxifylline down-regulated the level of miR-21 with improved symptoms in mice. miR-21 inhibition was accompanied by down-regulated serum levels of IL-17 and IL-6. The expression levels of PDCD4, RhoB, PD-1, IL-12p35, and toll-like receptor-4 were also regulated by miR-21 inhibition. miR-21 was correlated with HSV-induced BD-like inflammation in mice and BD patients. The expression of miR-21 was regulated by antagomir in mice.
SLM Produced Porous Titanium Implant Improvements for Enhanced Vascularization and Osteoblast Seeding
Authors: Matena Julia , Petersen Svea , Gieseke Matthias , Kampmann Andreas , Teske Michael , Beyerbach Martin , Escobar Hugo , Haferkamp Heinz , Gellrich Nils-Claudius , Nolte Ingo
Published: April 2015

To improve well-known titanium implants, pores can be used for increasing bone formation and close bone-implant interface. Selective Laser Melting (SLM) enables the production of any geometry and was used for implant production with 250-µm pore size. The used pore size supports vessel ingrowth, as bone formation is strongly dependent on fast vascularization. Additionally, proangiogenic factors promote implant vascularization. To functionalize the titanium with proangiogenic factors, polycaprolactone (PCL) coating can be used. The following proangiogenic factors were examined: vascular endothelial growth factor (VEGF), high mobility group box 1 (HMGB1) and chemokine (C-X-C motif) ligand 12 (CXCL12). As different surfaces lead to different cell reactions, titanium and PCL coating were compared. The growing into the porous titanium structure of primary osteoblasts was examined by cross sections. Primary osteoblasts seeded on the different surfaces were compared using Live Cell Imaging (LCI). Cross sections showed cells had proliferated, but not migrated after seven days. Although the cell count was lower on titanium PCL implants in LCI, the cell count and cell spreading area development showed promising results for titanium PCL implants. HMGB1 showed the highest migration capacity for stimulating the endothelial cell line. Future perspective would be the incorporation of HMGB1 into PCL polymer for the realization of a slow factor release.
Impacts of Gut Bacteria on Human Health and Diseases
Authors: Zhang Yu-Jie , Li Sha , Gan Ren-You , Zhou Tong , Xu Dong-Ping , Li Hua-Bin
Published: April 2015

Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases.
A New Series of Kinked Liquid Crystals: 2-(6-Alkoxynaphthalen-2-yl)-6-methoxyquinolines
Authors: Chia Win-Long , Liu Chih-Wei
Published: April 2015

A new series of 2-(6-alkoxynaphthalen-2-yl)-6-methoxyquinolines (nO-NpQOMe, n = 3–8) liquid crystal compounds, a linear molecular structure with two kinks, were synthesized using a short two-step reaction with overall yields between 43% and 58%. Spectral analyses were in accord with the expected structures. Thermotropic behavior of these liquid crystal compounds were investigated using polarized optical microscopy and differential scanning calorimetry. All compounds exhibited purely enantiotropic nematic phase at the medium–high temperature range of 162.4–234.2 °C. However, short ranges of nematic phase, 20.5–16.6 °C at heating and 46.7–37.0 °C at cooling, were observed in these linear liquid-crystalline compounds with two kinks.