bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbiologic profile of endodontic infections from HIV− and HIV+ patients using Multiple‐Displacement Amplification and Checkerboard DNA‐DNA Hybridization
Authors: Brito LCN , Sobrinho AP Ribeiro , Teles RP , Socransky SS , Haffajee AD , Vieira LQ , Teles FRF
Published: January 2012

Oral Diseases (2012) 18, 558–567

Objective:  To compare the microbiota of endodontic infections in necrotic pulp from HIV‐negative and HIV‐positive subjects.

Materials and Methods:  Root canal samples from necrotic pulp were collected from 40 HIV− and 20 HIV+ subjects. Pulps were amplified using multiple displacement amplification (MDA). Then, checkerboard DNA–DNA hybridization was employed to assess the levels of 107 microbial taxa. The percentage of DNA probe count and the percentage of teeth colonized by each test species were investigated. Significant differences between groups regarding proportions of taxa and prevalence of the test species were sought using the Mann–Whitney test and the Chi‐square analysis, respectively.

Results:  The most prevalent taxa detected were Dialister pneumosintes, Stenotrophomonas maltophilia, Streptococcus sobrinus, Corynebacterium diphteriae, and Helicobacter pylori among HIV‐ subjects and D. pneumosintes, Prevotella tannerae, Porphyromonas gingivalis, Parvimonas micra, Prevotella nigrescens, and Corynebacterium diphtheriae among HIV+ individuals. D. pneumosintes, C. diphtheria, and C. albicans were the most abundant species in the HIV‐ group, whereas the predominant taxa in HIV+ samples were P. tannerae, D. pneumosintes and Olsenella uli. P. tannerae, O. uli, Veilonella dispar, Bacteroides fragilis, and Actinomyces meyeri were significantly more abundant in HIV+ samples.

Conclusions:  There were significant differences in the prevalence and proportions of specific microbial taxa between HIV− and HIV+ individuals. The root canal microbiota may represent a reservoir of important oral and medical pathogens, mainly in HIV+ individuals.
Towards a more transparent use of the potential natural vegetation concept – an answer to Chiarucci et al.
Authors: Somodi Imelda , Molnár Zsolt , Ewald Jörg
Published: January 2012

In this paper, the concerns of Chiarucci et al. () regarding use of the potential natural vegetation (PNV) concept are addressed, as voiced in the forum section of theJournal of Vegetation Science. First, we rectify some unfounded expectations concerningPNV, including a relationship with prehuman vegetation and phytosociology. Second, we point out issues that pose considerable challenges inPNVand require common agreement. Here, we address the issue of time and disturbance. We propose to use the staticPNVconcept as a baseline, a null model for landscape assessment and in comparisons. Instead of changing thePNVconcept itself, we introduce a new term, potential future natural vegetation (PFV) to cover estimations of potential successional outcomes. Finally, we offer a new view ofPNVwith which we intend to make the use ofPNVestimates more transparent. We formalize thePNVtheory into a partial cause‐effect model of vegetation that clearly states which effects on vegetation are factored out during its estimation. Further, we also propose to assessPNVin a probabilistic setting, rather than providing a single estimate for one location. This multiplePNVwould reflect our uncertainty about the vegetation entity that could persist at the locality concerned. Such uncertainty arises from the overlap of environmental preferences of different mature vegetation types. Thus reformulated, we argue that thePNVconcept has much to offer as a null model, especially in landscape ecology and in site comparisons in space and time.
Associations of instrumental activities of daily living and handgrip strength with oral self‐care among home‐dwelling elderly 75+
Authors: Komulainen Kaija , Ylöstalo Pekka , Syrjälä Anna‐Maija , Ruoppi Piia , Knuuttila Matti , Sulkava Raimo , Hartikainen Sirpa
Published: January 2012

doi: 10.1111/j.1741‐2358.2010.00427.x

Associations of instrumental activities of daily living and handgrip strength with oral self‐care among home‐dwelling elderly 75+

Objective:  To study the associations of instrumental activities of daily living (IADL) and the handgrip strength with oral self‐care among dentate home‐dwelling elderly people in Finland.

Materials and methods:  The study analysed data for 168 dentate participants (mean age 80.6 years) in the population‐based Geriatric Multidisciplinary Strategy for Good Care of the Elderly (GeMS) study. Each participant received a clinical oral examination and structured interview in 2004–2005. Functional status was assessed using the IADL scale and handgrip strength was measured using handheld dynamometry.

Results:  Study participants with high IADL (scores 7–8) had odds ratios (ORs) for brushing their teeth at least twice a day of 2.7 [95% confidence intervals (CI) 1.1–6.8], for using toothpaste at least twice a day of 2.0 (CI 0.8–5.2) and for having good oral hygiene of 2.8 (CI 1.0–8.3) when compared with participants with low IADL (scores ≤6). Participants in the upper tertiles of the handgrip strength had ORs for brushing the teeth at least twice a day of 0.9 (CI 0.4–1.9), for using the toothpaste at least twice a day of 0.9 (CI 0.4–1.8) and for good oral hygiene of 1.1 (CI 0.5–2.4) in comparison with the study subjects in the lowest tertile of handgrip strength.

Conclusion:  The results of this study suggest that the functional status, measured by means of the IADL scale, but not handgrip strength, is an important determinant of oral self‐care among the home‐dwelling elderly.
Capecitabine and weekly paclitaxel as first‐line therapy in Thai patients with metastatic breast cancer
Authors: CHITAPANARUX Imjai , KAMNERDSUPAPHON Pimkhuan , THARAVICHITKUL Ekasit , LORVIDHAYA Vicharn , TRAKULTIVAKORN Hongsin , SRISUKHO Songpol , SOMWANGPRASERT Areewan , WATCHARACHAN Kirati , SUKTHOMYA Vimol
Published: January 2012

Aim:  The combination of a taxane and capecitabine offers synergistic antitumor activity. This study aimed to determine the efficacy and tolerability of a paclitaxel and capecitabine combination in Thai patients with metastatic breast cancer (MBC) not previously treated for metastatic disease.

Methods:  This open‐label, single‐center, non‐comparative phase II study was conducted between December 2006 and March 2009. In all 40 MBC patients were treated with oral capecitabine 1000 mg/m2 twice daily on days 1 to 14, and weekly paclitaxel 80 mg/m2 in a 3‐week cycle for a total of six cycles.

Results:  After a median follow up of 13.4 months, an overall objective response rate of 80%, with a partial response of 74% and a complete response of 5% were achieved. While 8% of patients achieved stable disease, 13% had progressive disease. Median time to progress was 8 months and median overall survival was 24.4 months. One patient discontinued because of hypersensitivity to paclitaxel. There was no grade 4 toxicity. Skin and nail toxicity was found in 75% of patients (with 25% in grade 2 or 3), followed by neutropenia (45% in all with 15% in grades 2 or 3), neuropathy (25% in total with 5% in grade 2) and stomatitis and diarrhea (in both of which 5% experienced grade 1 severity).

Conclusion:  A first‐line regimen of weekly paclitaxel plus capecitabine is effective and tolerable in Thai MBC patients.
(100) Three‐Axis‐Oriented BaTiO3, (Ba0.7Sr0.3)TiO3 Thin Film Prepared by Chemical Solution Deposition Method
Authors: Hosokura Tadasu , Kageyama Keisuke , Takagi Hiroshi , Sakabe Yukio
Published: January 2012

Epitaxially grown (100) three‐axis‐oriented (Ba0.7Sr0.3)TiO3 thin film on (100) platinum (Pt) coated (100) magnesium oxide (MgO) substrate and (100) three‐axis‐oriented BaTiO3 thin film with BaZrO3 buffer layer were prepared on an MgO(100) substrate using the chemical solution deposition method. The growth of the film was found to depend on the annealing condition. Transmission electron microscope revealed cube‐on‐cube epitaxial growth. The thin films exhibited a (100) three‐axis‐orientation that followed the (100) orientation of the MgO substrate and the (100) orientation of the Pt or BaZrO3 bottom layer, as observed from an X‐ray pole figure measurement and the selected area electron diffraction patterns.
Electrical Properties of Pb0.92La0.08Zr0.52Ti0.48O3 Thin Films Grown on SrRuO3 Buffered Nickel and Silicon Substrates by Chemical Solution Deposition
Authors: Narayanan Manoj , Ma Beihai , Tong Sheng , Koritala Rachel , Balachandran Uthamalingam
Published: January 2012

Ferroelectric film‐on‐foil capacitors are suitable to replace discrete passive components in the quest to develop electronic devices that show superior performance and are smaller in size. The film‐on‐foil approach is the most practical method to fabricate such components. Films of Pb0.92La0.08Zr0.52Ti0.48O3 (PLZT) were deposited on SrRuO3 (SRO) buffer films over nickel and silicon substrates. High‐quality polycrystalline SRO thin‐film electrodes were first deposited by chemical solution deposition. A phase pure, dense, uniform microstructure with grain size <100 nm was obtained in films crystallized at 700°C. The room‐temperature resistivity of the SRO films crystallized at 700°C was ~800–900 μΩ‐cm. The dielectric properties of sol–gel derived PLZT capacitors on SRO‐buffered nickel were evaluated as a function of temperature, bias field, and frequency, and the results were compared to those of the same films on silicon substrates. The comparison demonstrated the integrity of the buffer layer and its compatibility with nickel substrates. Device‐quality dielectric properties were measured on PLZT films deposited on SRO‐buffered nickel foils and found to be superior to those for PLZT on SRO‐buffered silicon and expensive platinized silicon. These results suggest that SRO films can act as an effective barrier layer on nickel substrates suitable for embedded capacitor applications.
The boreal forest as a cultural landscape
Authors: Johnson Edward A. , Miyanishi Kiyoko
Published: January 2012

Because of its generally low density of humans and few settlements, the circumpolar boreal forest is often viewed as an untouched wilderness. However, archeological evidence indicates that humans have inhabited the region since the continental glaciers disappeared 8,000–12,000 years ago. This paper discusses the ecological impacts that humans have had on the boreal forest ecosystem through their activities in prehistoric, historic, and recent times and argues that the boreal forest has always been a cultural landscape with a gradient of impacts both spatially and temporally. These activities include hunting, trapping, herding, agriculture, forestry, hydroelectric dam projects, oil and natural gas development, and mining. In prehistoric times, human impacts would generally have been more temporary and spatially localized. However, the megafaunal extinctions coincident with arrival of humans were very significant ecological impacts. In historic times, the spread of Europeans and their exploitation of the boreal's natural resources as well as agricultural expansion has altered the composition and continuity of the boreal forest ecosystem in North America, Fennoscandia, and Asia. Particularly over the last century, these impacts have increased significantly (e.g., some hydroelectric dams and tar sands developments that have altered and destroyed vast areas of the boreal forest). Although the atmospheric changes and resulting climatic changes due to human activities are causing the most significant changes to the high‐latitude boreal forest ecosystem, any discussion of these impacts are beyond the limits of this paper and therefore are not included.
Group cognitive behavioural therapy for first episode psychosis: who's referred, who attends and who completes it?
Authors: Fanning Felicity , Foley Sharon , Lawlor Elizabeth , McWilliams Stephen , Jackson Deirdre , Renwick Laoise , Sutton Marie , Turner Niall , Kinsella Anthony , Trimble Timothy , O'Callaghan Eadbhard
Published: January 2012

Aim: Most national guidelines recommend psychological therapy for people with first‐episode psychosis (FEP) but interventions proven effective in randomized control trials (RCTs) conducted in research settings do not always translate effectively to real‐world clinical environments. In a limited health system, it is important to understand the system and patient barriers to participation in effective treatment. We sought to determine what patient characteristics influenced clinicians' decision to refer or not to refer to group cognitive behavioural therapy for FEP and what characteristics were associated with those referred attending/not attending and adhering/not adhering to the programme.

Methods: Between 2006 and 2008, all cases of confirmed FEP from a defined geographical region were examined using the Structured Clinical Interview for DSM‐IV‐TR Axis I Disorders for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV) diagnoses, the Scale for Assessment of Positive Symptoms, Scale for Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia and Birchwood Insight Scale. Duration of untreated psychosis was established using the Beiser Scale.

Results: Of the 124 (77 males, 47 females) people in the final sample, 88 (72%) were referred for cognitive behavioural therapy (CBT), 52 (59%) attended and 12 (23%) did not complete CBT. Those with higher levels of insight into the need for treatment (U = 740.00, z = −2.63, P = 0.008) and higher levels of positive symptoms (t (120) = −3.064, P = 0.003) were more likely to be referred to CBT. Those with higher educational attainment (χ2 = 9.48, P = 0.03) and fewer negative symptoms, particularly in relation to global attention (t (85) = 2.32, P = 0.03), were more likely to attend and complete CBT.

Conclusion: Within an early intervention service for FEP, it appears that individuals with less education, more negative symptoms and less insight experienced significant barriers to successfully completing group CBT. More information for referring clinicians about the benefits of CBT for FEP could help increase referral rates. Assertive outreach for people at risk of disengaging or non‐adherence should also be considered.
Reversible and pH-dependent weak drug-excipient binding does not affect oral bioavailability of high dose drugs
Authors: Narang Ajit S , Yamniuk Aaron P , Zhang Limin , Comezoglu S Nilgun , Bindra Dilbir S , Varia Sailesh , Doyle Michael L , Badawy Sherif
Published: January 2012

Objectives

Drug-excipient binding can affect in-vitro drug release. Literature suggests that drug-excipient ionic binding interaction that is not disrupted by physiological salt concentration in the dissolution medium can impact a drug's oral bioavailability. We investigated whether nondisruption of interaction by physiological salt concentration was an adequate predictor of its biorelevance using the binding of a model amine high dose drug brivanib alaninate (BA) to croscarmellose sodium (CCS) as an example.

Methods

BA was formulated into an immediate release tablet using CCS as disintegrant by a wet granulation process. In-vitro drug release was carried out as a function of pH and buffer concentration of the medium. BA-CCS binding was studied in buffer solution and data fitted to a Langmuir isotherm. A simulation model and an isothermal titration calorimetry method were developed to assess the bioavailability risk and strength of drug-excipient binding interaction, independent of physiological salt concentration consideration.

Key findings

BA-CCS binding was pH-dependent, reversible, ionic, and not disrupted by increasing the buffer concentration in the dissolution medium. Absorption simulation predictions of no effect of CCS binding on BA's bioavailability were confirmed by a monkey pharmacokinetic study.

Conclusions

A pH-dependent and reversible weak drug-excipient binding interaction is unlikely to affect the oral bioavailability of high dose drugs.
Multiple-Scale Wavelet Decomposition, 3D Surface Feature Exaction and Applications
Authors: Liao Yi , Stephenson David A. , Ni Jun
Published: January 2012

This paper presents a method of applying wavelets to decompose three-dimensional surface into multiple-scale subsurfaces, and of using the subsurface features to predict surface functions and detect machining errors. The one-dimensional discrete wavelet decomposition is first introduced, and then, it is extended to decompose and analyze three-dimensional surfaces. In this study, applications of wavelets decomposition are demonstrated in several automotive case studies, including abrupt tool breakage detection, chatter detection, cylinder head sealing/mating surface leak path detection, and transmission clutch piston surface nonclean up region detection. These case studies successfully demonstrate that the proposed multiple-scale two-channel wavelet decomposition method can be served as a useful tool for surface functions prediction and machining errors detection.
Probabilistic Control for Uncertain Systems
Authors: Herzallah Randa
Published: January 2012

In this paper a new framework has been applied to the design of controllers which encompasses nonlinearity, hysteresis and arbitrary density functions of forward models and inverse controllers. Using mixture density networks, the probabilistic models of both the forward and inverse dynamics are estimated such that they are dependent on the state and the control input. The optimal control strategy is then derived which minimizes uncertainty of the closed loop system. In the absence of reliable plant models, the proposed control algorithm incorporates uncertainties in model parameters, observations, and latent processes. The local stability of the closed loop system has been established. The efficacy of the control algorithm is demonstrated on two nonlinear stochastic control examples with additive and multiplicative noise.
Size Reduction of Cellulosic Biomass in Biofuel Manufacturing: A Study on Confounding Effects of Particle Size and Biomass Crystallinity
Authors: Zhang Meng , Song Xiaoxu , Zhang Pengfei , Pei Z. J. , Deines T. W. , Wang Donghai
Published: January 2012

Biofuels derived from cellulosic biomass offer an alternative to petroleum-based liquid transportation fuels. In order to convert cellulosic biomass into biofuels, size reduction is a necessary step along with pretreatment, enzymatic hydrolysis, and fermentation. In the literature, there are inconsistent reports about why size reduction affects sugar yield (proportional to biofuel yield). An important reason for the inconsistence is that particle formation in current size reduction methods is not well controlled, causing effects of some biomass structural parameters confounded. In this study, a metal-cutting (milling) process is used for size reduction of poplar wood, where particle formation can be well controlled to prevent the effects of multiple parameters from being confounded. The results of this study provide explanations for some inconsistent reports in the literature. These results also reveal some opportunities for future research to understand the effects of size reduction on cellulosic biofuel manufacturing.
Roughness optimization of electron-beam exposed hydrogen silsesquioxane for immobilization of DNA origami
Authors: Shah Faisal A. , Nan Kim Kyoung , Lieberman Marya , Bernstein Gary H.
Published: January 2012

A novel way to immobilize deoxyribonucleic acid (DNA) origami on a conventional substrate using hydrogen silsesquioxane (HSQ) as a functionalized platform is demonstrated. An alternative approach to quantifying roughness of the HSQ surfaces for 2D DNA origami immobilization is also introduced. Effects of oxygen plasma treatment on the surface roughness and functionalization (for DNA origami immobilization) of exposed and developed HSQ patterns are characterized. Surface root mean square roughness of electron-beam exposed HSQ with various thicknesses is investigated and optimized down to 0.2 nm for ultrathin (sub-15 nm) HSQ patterns.
On the scaling of rf and dc self-bias voltages with pressure in electronegative capacitively coupled plasmas
Authors: Agarwal Ankur , Dorf Leonid , Rauf Shahid , Collins Ken
Published: January 2012

Higher gas densities and lower diffusion losses at higher operating pressures typically lead to increased charged species densities (and hence flux) for a constant power deposition in capacitively coupled plasmas (CCP). As a result, one would expect that the bias radio-frequency (rf) voltage required to deposit a given power in a CCP reactor decreases with increasing operating pressure. These observations may not hold true in multiple frequency CCPs, commonly used for dielectric etching in microelectronics fabrication, due to nonlinear interactions between the rf sources. Wafer-based measurements of the rf and self-generated direct current (dc) bias voltages in a dual-frequency capacitively coupled electronegative plasma were made, which indicate that the rf and dc voltages vary nonmonotonically with pressure. These experimental results are presented in this paper and a computational plasma model is used to explain the experimental observations for varying 60 MHz and 13 MHz powers in the Ar/CF4/CHF3 plasma over a pressure range of 25 to 400 mTorr. The authors found that while the ion density increases with pressure, the increase is most dominant near the electrode with the high frequency source (60 MHz). The rf and dc bias voltages are ultimately influenced by both charged species density magnitudes and spatial profiles.
17O NMR study of ortho and alkyl substituent effects in substituted phenyl and alkyl esters of benzoic acids
Authors: Nummert Vilve , Mäemets Vahur , Piirsalu Mare , Vahur Signe , Koppel Ilmar A.
Published: January 2012

17O NMR spectra for 44ortho-,meta- andpara-substituted phenyl and alkyl benzoates (C6H5CO2C6H4-X, C6H5CO2R) at natural abundance in acetonitrile were recorded. Substituent effects on the17O NMR chemical shifts, δ(17O), of the carbonyl oxygen and the single-bonded phenoxy (OPh) and alkoxy (OR) oxygens have been studied. The δ(17O) values of the carbonyl oxygen forparaderivatives showed a good correlation with the σ° constants. The δ(17O) values of carbonyl oxygen fororthoderivatives were found to be described well with the Charton equation containing the inductive, σI, resonance, σ°R, and steric,EsB, substituent constants in case the data treatment was performed separately for electron-donating +Rand electron-attracting –Rsubstituents. The electron-donating +Rorthoandparasubstituents in substituted benzoates caused shielding and the electron-withdrawing –Rsubstituents produced deshielding of the O signal. The steric interaction oforthosubstituents with the ester group decreased the electron density at the carbonyl oxygen. In alkyl benzoates the δ(17O) values were found to be described well with the inductive, σI, and the steric,EsB, substituent constants.
Accuracy of LightCycler® SeptiFastfor the detection and identification of pathogens in the blood of patients with suspected sepsis: a systematic review protocol
Authors: Dark Paul , Wilson Claire , Blackwood Bronagh , McAuley Danny F , Perkins Gavin D , McMullan Ronan , Gates Simon , Warhurst Geoffrey
Published: January 2012

Background

There is growing interest in the potential utility of molecular diagnostics in improving the detection of life-threatening infection (sepsis). LightCycler® SeptiFastis a multipathogen probe-based real-time PCR system targeting DNA sequences of bacteria and fungi present in blood samples within a few hours. We report here the protocol of the first systematic review of published clinical diagnostic accuracy studies of this technology when compared with blood culture in the setting of suspected sepsis.

Methods/design

Data sources: the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), The Cochrane Library, MEDLINE, EMBASE, ISI Web of Science, BIOSIS Previews, MEDION and the Aggressive Research Intelligence Facility Database (ARIF). Study selection: diagnostic accuracy studies that compare the real-time PCR technology with standard culture results performed on a patient's blood sample during the management of sepsis. Data extraction: three reviewers, working independently, will determine the level of evidence, methodological quality and a standard data set relating to demographics and diagnostic accuracy metrics for each study. Statistical analysis/data synthesis: heterogeneity of studies will be investigated using a coupled forest plot of sensitivity and specificity and a scatter plot in Receiver Operator Characteristic (ROC) space. Bivariate model method will be used to estimate summary sensitivity and specificity. The authors will investigate reporting biases using funnel plots based on effective sample size and regression tests of asymmetry. Subgroup analyses are planned for adults, children and infection setting (hospital vs community) if sufficient data are uncovered.

Dissemination

Recommendations will be made to the Department of Health (as part of an open-access HTA report) as to whether the real-time PCR technology has sufficient clinical diagnostic accuracy potential to move forward to efficacy testing during the provision of routine clinical care.

Registration

PROSPERO—NIHR Prospective Register of Systematic Reviews (CRD42011001289).
POINTED HOPF ALGEBRAS WITH CLASSICAL WEYL GROUPS
Authors: ZHANG SHOUCHUAN , ZHANG YAO-ZHONG
Published: January 2012

We prove that Nichols algebras of irreducible Yetter–Drinfeld modules over classical Weyl groups A ⋊ 𝕊nsupported by 𝕊nare infinite dimensional, except in three cases. We give necessary and sufficient conditions for Nichols algebras of Yetter–Drinfeld modules over classical Weyl groups A ⋊ 𝕊nsupported by A to be finite dimensional.
ON CORRELATIONS IN HIGH-ENERGY HADRONIC PROCESSES AND THE CMS RIDGE: A MANIFESTATION OF QUANTUM ENTANGLEMENT?
Authors: CHEREDNIKOV I. O. , STEFANIS N. G.
Published: January 2012

We discuss the possibility of quantum entanglement for pairs of charged particles produced in high-energy pp-collisions at the LHC. Using a framework of interacting Wilson lines, we calculate 2D and 1D two-particle angular correlation functions in terms of the differences of the pseudorapidities and azimuthal angles of the produced particles. The calculated near-side angular correlation shows a localized maximum around Δϕ≈0, though it is less pronounced compared to the peak observed by the CMS Collaboration. We argue that this soft correlation is universal and insensitive to the specific properties of the matter (quark–gluon plasma, QCD vacuum, etc.) used to describe hadronic states — though such properties can be included to further improve the results.
Attitudes of Singaporean Chinese towards Retirement Planning
Authors: Gurd Bruce , Or Francis Kum Hoong
Published: January 2012

While there is a strong research tradition in exploring attitudes to and behavior in relation to retirement planning in Western countries, (e.g., Grable and Lytton, 1997; Jacobs-Lawson and Hershey, 2005) there is less research in Asian societies. Not only are we unaware of whether demographic factors, such as marital status, income level, level of education and gender, have a different impact in Asian countries, we also do not know the impact of Asian cultural values on retirement planning. Using a sample of 613 working Singaporean Chinese between the ages of 20 and 59 we establish that Chinese cultural heritage such as the belief in luck, destiny and the belief that children will support their elderly parents are not important. However, feng shui is statistically significant in this study.
International Diversification Through Emerging Market Investment: Selection of Appropriate Portfolio Strategy
Authors: Arora Ravinder Kumar , Jain Pramod Kumar , Das Himadri
Published: January 2012

The main purpose of this paper is to compare the performance of portfolio strategies, comprising investments in emerging markets alone, and those strategies of combining investment in emerging and developed markets. The major finding of this paper is: the portfolio strategy combining investment in emerging markets with that in developed markets does not offer any additional value over a portfolio strategy confining investments to the emerging markets only. This paper, therefore, recommends a strategy that emphasizes country selection from emerging markets alone.
Colonic microbiome is altered in alcoholism
Authors: Mutlu Ece A. , Gillevet Patrick M. , Rangwala Huzefa , Sikaroodi Masoumeh , Naqvi Ammar , Engen Phillip A. , Kwasny Mary , Lau Cynthia K. , Keshavarzian Ali
Published: January 2012

Several studies indicate the importance of colonic microbiota in metabolic and inflammatory disorders and importance of diet on microbiota composition. The effects of alcohol, one of the prominent components of diet, on colonic bacterial composition is largely unknown. Mounting evidence suggests that gut-derived bacterial endotoxins are cofactors for alcohol-induced tissue injury and organ failure like alcoholic liver disease (ALD) that only occur in a subset of alcoholics. We hypothesized that chronic alcohol consumption results in alterations of the gut microbiome in a subgroup of alcoholics, and this may be responsible for the observed inflammatory state and endotoxemia in alcoholics. Thus we interrogated the mucosa-associated colonic microbiome in 48 alcoholics with and without ALD as well as 18 healthy subjects. Colonic biopsy samples from subjects were analyzed for microbiota composition using length heterogeneity PCR fingerprinting and multitag pyrosequencing. A subgroup of alcoholics have an altered colonic microbiome (dysbiosis). The alcoholics with dysbiosis had lower median abundances of Bacteroidetes and higher ones of Proteobacteria. The observed alterations appear to correlate with high levels of serum endotoxin in a subset of the samples. Network topology analysis indicated that alcohol use is correlated with decreased connectivity of the microbial network, and this alteration is seen even after an extended period of sobriety. We show that the colonic mucosa-associated bacterial microbiome is altered in a subset of alcoholics. The altered microbiota composition is persistent and correlates with endotoxemia in a subgroup of alcoholics.
Impaired adaptation of gastrointestinal motility following chronic stress in maternally separated rats
Authors: Bülbül Mehmet , Babygirija Reji , Cerjak Diana , Yoshimoto Sazu , Ludwig Kirk , Takahashi Toku
Published: January 2012

Exposure to early life stress causes increased stress responsiveness and permanent changes in the central nervous system. We recently showed that delayed gastric emptying (GE) and accelerated colonic transit (CT) in response to acute restraint stress (ARS) were completely restored following chronic homotypic stress (CHS) in rats via upregulation of hypothalamic oxytocin (OXT) expression. However, it is unknown whether early life stress affects hypothalamic OXT circuits and gastrointestinal motor function. Neonatal rats were subjected to maternal separation (MS) for 180 min/day for 2 wk. Anxiety-like behaviors were evaluated by the elevated-plus-maze test. GE and CT were measured under nonstressed (NS), ARS, and CHS conditions. Expression of corticotropin-releasing factor (CRF) and OXT in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real time RT-PCR and immunohistochemistry. MS increased anxiety-like behaviors. ARS delayed GE and accelerated CT in control and MS rats. After CHS, delayed GE and accelerated CT were restored in control, but not MS, rats. CRF mRNA expression was significantly increased in response to ARS in control and MS rats. Increased CRF mRNA expression was still observed following CHS in MS, but not control, rats. In response to CHS, OXT mRNA expression was significantly increased in control, but not MS, rats. The number of OXT-immunoreactive cells was increased following CHS in the magnocellular part of the PVN in control, but not MS, rats. MS impairs the adaptation response of gastrointestinal motility following CHS. The mechanism of the impaired adaptation involves downregulation of OXT and upregulation of CRF in the hypothalamus in MS rats.
Sweat rate prediction equations for outdoor exercise with transient solar radiation
Authors: Gonzalez Richard R. , Cheuvront Samuel N. , Ely Brett R. , Moran Daniel S. , Hadid Amir , Endrusick Thomas L. , Sawka Michael N.
Published: January 2012

We investigated the validity of employing a fuzzy piecewise prediction equation (PW) [Gonzalez et al. J Appl Physiol 107: 379–388, 2009] defined by sweat rate (msw, g·m−2·h−1) = 147 + 1.527·(Ereq) − 0.87·(Emax), which integrates evaporation required (Ereq) and the maximum evaporative capacity of the environment (Emax). Heat exchange and physiological responses were determined throughout the trials. Environmental conditions were ambient temperature (Ta) = 16–26°C, relative humidity (RH) = 51–55%, and wind speed ( V) = 0.5–1.5 m/s. Volunteers wore military fatigues [clothing evaporative potential (im/clo) = 0.33] and carried loads (15–31 kg) while marching 14–37 km over variable terrains either at night ( N = 77, trials 1–5) or night with increasing daylight ( N = 33, trials 6 and 7). PW was modified ( Ṗw,sol) for transient solar radiation (Rsol, W) determined from measured solar loads and verified in trials 6 and 7. PW provided a valid msw prediction during night trials ( 1–5) matching previous laboratory values and verified by bootstrap correlation (rbs of 0.81, SE ± 0.014, SEE = ± 69.2 g·m−2·h−1). For trials 6 and 7, Ereq and Emax components included Rsol applying a modified equation Ṗw,sol, in which msw = 147 + 1.527·(Ereq,sol) − 0.87·(Emax). Linear prediction of msw = 0.72· Ṗw,sol + 135 ( N = 33) was validated ( R2 = 0.92; SEE = ±33.8 g·m−2·h−1) with PW β-coefficients unaltered during field marches between 16°C and 26°C Ta for msw ≤ 700 g·m−2·h−1. PW was additionally derived for cool laboratory/night conditions (Ta < 20°C) in which Ereq is low but Emax is high, as: PW,cool (g·m−2·h−1) = 350 + 1.527·Ereq − 0.87·Emax. These sweat prediction equations allow valid tools for civilian, sports, and military medicine communities to predict water needs during a variety of heat stress/exercise conditions.
Effects of corticosteroid treatment on airway inflammation, mechanics, and hyperpolarized 3He magnetic resonance imaging in an allergic mouse model
Authors: Thomas Abraham C. , Kaushik S. Sivaram , Nouls John , Potts Erin N. , Slipetz Deborah M. , Foster W. Michael , Driehuys Bastiaan
Published: January 2012

The purpose of this study was to assess the effects of corticosteroid therapy on a murine model of allergic asthma using hyperpolarized 3He magnetic resonance imaging (MRI) and respiratory mechanics measurements before, during, and after methacholine (MCh) challenge. Three groups of mice were prepared, consisting of ovalbumin sensitized/ovalbumin challenged (Ova/Ova, n = 5), Ova/Ova challenged but treated with the corticosteroid dexamethasone (Ova/Ova+Dex, n = 3), and ovalbumin-sensitized/saline-challenged (Ova/PBS, n = 4) control animals. All mice underwent baseline 3D 3He MRI, then received a MCh challenge while 10 2D 3He MR images were acquired for 2 min, followed by post-MCh 3D 3He MRI. Identically treated groups underwent respiratory mechanics evaluation ( n = 4/group) and inflammatory cell counts ( n = 4/group). Ova/Ova animals exhibited predominantly large whole lobar defects at baseline, with significantly higher ventilation defect percentage (VDP = 19 ± 4%) than Ova/PBS (+2 ± 1%, P = 0.01) animals. Such baseline defects were suppressed by dexamethasone (0%, P = 0.009). In the Ova/Ova group, MCh challenge increased VDP on both 2D (+30 ± 8%) and 3D MRI scans (+14 ± 2%). MCh-induced VDP changes were diminished in Ova/Ova+Dex animals on both 2D (+21 ± 9%, P = 0.63) and 3D scans (+7 ± 2%, P = 0.11) and also in Ova/PBS animals on 2D (+6 ± 3%, P = 0.07) and 3D (+4 ± 1%, P = 0.01) scans. Because MCh challenge caused near complete cessation of ventilation in four of five Ova/Ova animals, even as large airways remained patent, this implies that small airway (<188 μm) obstruction predominates in this model. This corresponds with respiratory mechanics observations that MCh challenge significantly increases elastance and tissue damping but only modestly affects Newtonian airway resistance.
Recurrent laryngeal nerve activity exhibits a 5-HT-mediated long-term facilitation and enhanced response to hypoxia following acute intermittent hypoxia in rat
Authors: Bautista Tara G. , Xing Tao , Fong Angelina Y. , Pilowsky Paul M.
Published: January 2012

A progressive and sustained increase in inspiratory-related motor output (“long-term facilitation”) and an augmented ventilatory response to hypoxia occur following acute intermittent hypoxia (AIH). To date, acute plasticity in respiratory motor outputs active in the postinspiratory and expiratory phases has not been studied. The recurrent laryngeal nerve (RLN) innervates laryngeal abductor muscles that widen the glottic aperture during inspiration. Other efferent fibers in the RLN innervate adductor muscles that partially narrow the glottic aperture during postinspiration. The aim of this study was to investigate whether or not AIH elicits a serotonin-mediated long-term facilitation of laryngeal abductor muscles, and if recruitment of adductor muscle activity occurs following AIH. Urethane anesthetized, paralyzed, unilaterally vagotomized, and artificially ventilated adult male Sprague-Dawley rats were subjected to 10 exposures of hypoxia (10% O2 in N2, 45 s, separated by 5 min, n = 7). At 60 min post-AIH, phrenic nerve activity and inspiratory RLN activity were elevated (39 ± 11 and 23 ± 6% above baseline, respectively). These responses were abolished by pretreatment with the serotonin-receptor antagonist, methysergide ( n = 4). No increase occurred in time control animals ( n = 7). Animals that did not exhibit postinspiratory RLN activity at baseline did not show recruitment of this activity post-AIH ( n = 6). A repeat hypoxia 60 min after AIH produced a significantly greater peak response in both phrenic and RLN activity, accompanied by a prolonged recovery time that was also prevented by pretreatment with methysergide. We conclude that AIH induces neural plasticity in laryngeal motoneurons, via serotonin-mediated mechanisms similar to that observed in phrenic motoneurons: the so-called “Q-pathway”. We also provide evidence that the augmented responsiveness to repeat hypoxia following AIH also involves a serotonergic mechanism.
B Effector Cells Activated by a Chimeric Protein Consisting of IL-2 and the Ectodomain of TGF-β Receptor II Induce Potent Antitumor Immunity
Authors: Penafuerte Claudia , Ng Spencer , Bautista-Lopez Norma , Birman Elena , Forner Kathy , Galipeau Jacques
Published: January 2012

We have previously shown that interleukin (IL)-2 receptor–expressing lymphoid cells stimulated with a chimeric protein linking IL-2 to the ectodomain of TGF-β receptor II (also known as FIST) become resistant to TGF-β–mediated suppression and produce significant amounts of proinflammatory cytokines. In this study, we have characterized the antigen presentation properties of FIST-stimulated B cells (hereafter inducible B effector cells, iBEC). FIST converts naïve splenic B cells to B effector cells characterized by potent antigen presentation properties and production of TNFα and IFNγ. iBECs display hyperphosphorylation of STAT3 and STAT5 downstream of the IL-2 receptor and upregulation of T-bet expression. iBECs maintain B-cell identity based on the expression of PAX5 and CD19 and overexpress Smad7, which confers resistance to TGF-β–mediated suppression of B-cell activation. iBEC antitumor immunity was determined by a mouse model of lymphoma-expressing ovalbumin (E.G7-OVA) as a specific tumor antigen. OVA-pulsed iBECs function as antigen-presenting cells (APC) in vitro by inducing the activation of OVA-specific CD4+ and CD8+ T cells, respectively, and in vivo by conferring complete protective immunity against E.G7-OVA tumor challenge. In addition, OVA-pulsed iBECs promote tumor regression in immunocompetent C57Bl/6 mice bearing E.G7-OVA tumors. In conclusion, iBECs represent an entirely novel B cell–derived APC for immune therapy of cancer. Cancer Res; 72(5); 1210–20. ©2012 AACR.
Copy Number Losses Define Subgroups of Dedifferentiated Liposarcoma with Poor Prognosis and Genomic Instability
Authors: Crago Aimee M. , Socci Nicholas D. , DeCarolis Penelope , O'Connor Rachael , Taylor Barry S. , Qin Li-Xuan , Antonescu Cristina R. , Singer Samuel
Published: January 2012

Purpose: Molecular events underlying progression of well-differentiated liposarcoma (WDLS) to dedifferentiated liposarcoma (DDLS) are poorly defined. This study sought to identify copy number alterations (CNA) associated with dedifferentiation of WDLS, with DDLS morphology, and with patient outcomes.

Experimental Design: Fifty-five WDLS and 52 DDLS were analyzed using Agilent 244K comparative genomic hybridization and Affymetrix U133A expression arrays. CNAs were identified by RAE analysis. Thirty-nine of the DDLS specimens were categorized morphologically by a single pathologist.

Results: Nine regions of CNA were identified as recurrent in DDLS but not WDLS; 79% of DDLS had at least one of these CNAs. Loss of the chromosome segment 11q23–24, the most common event, was observed only in DDLS that morphologically resembled the genomically complex sarcomas, undifferentiated pleomorphic sarcoma and myxofibrosarcoma. 11q23–24 loss was itself associated with increased genomic complexity in DDLS. Loss of 19q13, but not 11q23–24, was associated with poor prognosis. Median disease-specific survival was shorter for patients with19q13 loss (27 months) than for patients with diploid 19q13 (>90 months; P < 0.0025), and 19q13 loss was associated with local recurrence (HR, 2.86; P = 0.013). Common copy number losses were associated with transcriptional downregulation of potential tumor suppressors and adipogenesis-related genes (e.g., EI24 and CEBPA).

Conclusions: Dedifferentiation of WDLS is associated with recurrent CNAs in 79% of tumors. In DDLS, loss of 11q23–24 is associated with genomic complexity and distinct morphology whereas loss of 19q13 predicts poor prognosis. CNAs in liposarcoma improve risk stratification for patients and will help identify potential tumor suppressors driving liposarcoma progression. Clin Cancer Res; 18(5); 1334–40. ©2012 AACR.
The Novel Oral Hsp90 Inhibitor NVP-HSP990 Exhibits Potent and Broad-spectrum Antitumor ActivitiesIn VitroandIn Vivo
Authors: Menezes Daniel L. , Taverna Pietro , Jensen Michael R. , Abrams Tinya , Stuart Darrin , Yu Guoying Karen , Duhl David , Machajewski Timothy , Sellers William R. , Pryer Nancy K. , Gao Zhenhai
Published: January 2012

A novel oral Hsp90 inhibitor, NVP-HSP990, has been developed and characterized in vitro and in vivo. In vitro, NVP-HSP990 exhibits single digit nanomolar IC50 values on three of the Hsp90 isoforms (Hsp90α, Hsp90β, and GRP94) and 320 nanomolar IC50 value on the fourth (TRAP-1), with selectivity against unrelated enzymes, receptors, and kinases. In c-Met amplified GTL-16 gastric tumor cells, NVP-HSP990 dissociated the Hsp90-p23 complex, depleted client protein c-Met, and induced Hsp70. NVP-HSP990 potently inhibited the growth of human cell lines and primary patient samples from a variety of tumor types. In vivo, NVP-HSP990 exhibits drug-like pharmaceutical and pharmacologic properties with high oral bioavailability. In the GTL-16 xenograft model, a single oral administration of 15 mg/kg of NVP-HSP990 induced sustained downregulation of c-Met and upregulation of Hsp70. In repeat dosing studies, NVP-HSP990 treatment resulted in tumor growth inhibition of GTL-16 and other human tumor xenograft models driven by well-defined oncogenic Hsp90 client proteins. On the basis of its pharmacologic profile and broad-spectrum antitumor activities, clinical trials have been initiated to evaluate NVP-HSP990 in advanced solid tumors. Mol Cancer Ther; 11(3); 730–9. ©2012 AACR.
Deletion or Epigenetic Silencing of AJAP1 on 1p36 in Glioblastoma
Authors: Lin Ningjing , Di Chunhui , Bortoff Kathy , Fu Jinrong , Truszkowski Peter , Killela Patrick , Duncan Chris , McLendon Roger , Bigner Darell , Gregory Simon , Adamson David Cory
Published: January 2012

Glioblastoma is universally fatal because of its propensity for rapid recurrence due to highly migratory tumor cells. Unraveling the genomic complexity that underlies this migratory characteristic could provide therapeutic targets that would greatly complement current surgical therapy. Using multiple high-resolution genomic screening methods, we identified a single locus, adherens junctional associated protein 1 (AJAP1) on chromosome 1p36 that is lost or epigenetically silenced in many glioblastomas. We found AJAP1 expression absent or reduced in 86% and 100% of primary glioblastoma tumors and cell lines, respectively, and the loss of expression correlates with AJAP1 methylation. Restoration of AJAP1 gene expression by transfection or demethylation agents results in decreased tumor cell migration in glioblastoma cell lines. This work shows the significant loss of expression of AJAP1 in glioblastoma and provides evidence of its role in the highly migratory characteristic of these tumors. Mol Cancer Res; 10(2); 208–17. ©2012 AACR.
The Activation of MEK/ERK Signaling Pathway by Bone Morphogenetic Protein 4 to Increase Hepatocellular Carcinoma Cell Proliferation and Migration
Authors: Chiu Chiang-Yen , Kuo Kung-Kai , Kuo Tzu-Lei , Lee King-The , Cheng Kuang-Hung
Published: January 2012

Hepatocellular carcinoma (HCC) is one of the most common visceral malignancies worldwide, with a very high incidence and poor prognosis. Bone morphogenesis protein 4 (BMP4), which belongs to the TGF-β superfamily of proteins, is a multifunctional cytokine, which exerts its biologic effects through SMAD- and non-SMAD-dependent pathways, and is also known to be involved in human carcinogenesis. However, the effects of the BMP4 signaling in liver carcinogenesis are not yet clearly defined. Here, we first show that BMP4 and its receptor, BMPR1A, are overexpressed in a majority of primary HCCs and that it promotes the growth and migration of HCC cell lines in vitro. We also establish that BMP4 can induce HCC cyclin-dependent kinase (CDK)1 and cyclin B1 upregulation to accelerate cell-cycle progression. Our study indicates that the induction of HCC cell proliferation is independent of the SMAD signaling pathway, as Smad4 knockdown of HCC cell lines still leads to the upregulation of CDK1 and cyclin B1 expression after BMP4 treatment. Using mitogen-activated protein/extracellular signal-regulated kinase (MEK) selective inhibitors, the induction of CDK1, cyclin B1 mRNA and protein were shown to be dependent on the activation of MEK/extracellular signal-regulated kinase (ERK) signaling. In vivo xenograft studies confirmed that the BMPR1A-knockdown cells were significantly less tumorigenic than the control groups. Our findings show that the upregulation of BMP4 and BMPR1A in HCC promotes the proliferation and metastasis of HCC cells and that CDK1 and cyclin B1 are important SMAD-independent molecular targets in BMP4 signaling pathways, during the HCC tumorigenesis. It is proposed that BMP4 signaling pathways may have potential as new therapeutic targets in HCC treatment. Mol Cancer Res; 10(3); 415–27. ©2012 AACR.