bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C: A randomized phase II study
Authors: Manns Michael P. , Gane Edward , Rodriguez-Torres Maribel , Stoehr Albrecht , Yeh Chau-Ting , Marcellin Patrick , Wiedmann Richard T. , Hwang Peggy M. , Caro Luzelena , Barnard Richard J.O. , Lee Andrew W.
Published: April 2012

Vaniprevir (MK-7009) is a macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. The aim of the present phase II study was to examine virologic response rates with vaniprevir in combination with pegylated interferon alpha-2a (Peg-IFN-α-2a) plus ribavirin (RBV). In this double-blind, placebo-controlled, dose-ranging study, treatment-naïve patients with HCV genotype 1 infection (n = 94) were randomized to receive open-label Peg-IFN-α-2a (180 μg/week) and RBV (1,000–1,200 mg/day) in combination with blinded placebo or vaniprevir (300 mg twice-daily [BID], 600 mg BID, 600 mg once-daily [QD], or 800 mg QD) for 28 days, then open-label Peg-IFN-α-2a and RBV for an additional 44 weeks. The primary efficacy endpoint was rapid viral response (RVR), defined as undetectable plasma HCV RNA at week 4. Across all doses, vaniprevir was associated with a rapid two-phase decline in viral load, with HCV RNA levels approximately 3log10 IU/mL lower in vaniprevir-treated patients, compared to placebo recipients. Rates of RVR were significantly higher in each of the vaniprevir dose groups, compared to the control regimen (68.8%-83.3% versus 5.6%;

P

< 0.001 for all comparisons). There were numerically higher, but not statistically significant, early and sustained virologic response rates with vaniprevir, as compared to placebo. Resistance profile was predictable, with variants at R155 and D168 detected in a small number of patients. No relationship between interleukin-28B genotype and treatment outcomes was demonstrated in this study. The incidence of adverse events was generally comparable between vaniprevir and placebo recipients; however, vomiting appeared to be more common at higher vaniprevir doses.

Conclusion
: Vaniprevir is a potent HCV protease inhibitor with a predictable resistance profile and favorable safety profile that is suitable for QD or BID administration.
Hepatic vein arrival time as assessed by contrast-enhanced ultrasonography is useful for the assessment of portal hypertension in compensated cirrhosis
Authors: Kim Moon Young , Suk Ki Tae , Baik Soon Koo , Kim Hyoun A. , Kim Young Ju , Cha Seung Hwan , Kwak Hwa Ryun , Cho Mee Yon , Park Hong Jun , Jeon Hyo Keun , Park So Yeon , Kim Bo Ra , Hong Jin Heon , Jo Ki Won , Kim Jae Woo , Kim Hyun Soo , Kwon Sang Ok , Chang Sei Jin , Baik Gwang Ho , Kim Dong Joon
Published: April 2012

The measurement of the hepatic venous pressure gradient (HVPG) for the estimation of portal hypertension (PH) in cirrhosis has some limitations, including its invasiveness. Hepatic vein arrival time (HVAT), as assessed by microbubble contrast-enhanced ultrasonography (CEUS), is negatively correlated with the histological grade of liver fibrosis because of the associated hemodynamic abnormalities. Anatomical and pathophysiological changes in liver microcirculation are the initial events leading to PH. However, the direct relationship between HVAT and PH has not been evaluated. The present study measured both HVPG and HVAT in 71 consecutive patients with compensated cirrhosis and analyzed the relationship between the two parameters (i.e., the derivation set). Results were validated in 35 compensated patients with cirrhosis at another medical center (i.e., the validation set). The derivation set had HVPG and HVAT values of 11.4 ± 5.0 mmHg (mean ± standard deviation; range, 2–23) and 14.1 ± 3.4 seconds (range, 8.4–24.2), respectively; there was a statistically significant negative correlation between HVPG and HVAT (r2 = 0.545;

P

< 0.001). The area under the receiver operating characteristic curve (AUROC) was 0.973 for clinically significant PH (CSPH; HVPG, ≥10 mmHg), and the sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios for CSPH for an HVAT cut-off value of 14 seconds were 92.7%, 86.7%, 90.5%, 89.7%, 6.95, and 0.08, respectively. In addition, a shorter HVAT was associated with worse Child-Pugh score (
P

< 0.001) and esophageal varices (
P

= 0.018). In the validation set, there was also a significant negative correlation between HVAT and HVPG (r2 = 0.538;

P

< 0.001), and AUROC = 0.953 for CSPH. HVAT was significantly correlated with PH. These results indicate that measuring HVAT is useful for the noninvasive prediction of CSPH in patients with compensated cirrhosis.
Distinct contribution of human cord blood-derived endothelial colony forming cells to liver and gut in a fetal sheep model
Authors: Wood Joshua A. , Colletti Evan , Mead Laura E. , Ingram David , Porada Christopher D. , Zanjani Esmail D. , Yoder Mervin C. , Almeida-Porada Graça
Published: April 2012

Although the vasculogenic potential of circulating and cord blood (CB)-derived endothelial colony-forming cells (ECFC) has been demonstrated

in vitro

and

in vivo,

little is known about the inherent biologic ability of these cells to home to different organs and contribute to tissue-specific cell populations. Here we used a fetal sheep model of

in utero

transplantation to investigate and compare the intrinsic ability of human CB-derived ECFC to migrate to the liver and to the intestine, and to define ECFC's intrinsic ability to integrate and contribute to the cytoarchitecture of these same organs. ECFCs were transplanted by an intraperitoneal or intrahepatic route (IH) into fetal sheep at concentrations ranging from 1.1–2.6 × 106 cells/fetus. Recipients were evaluated at 85 days posttransplant for donor (human) cells using flow cytometry and confocal microscopy. We found that, regardless of the route of injection, and despite the IH delivery of ECFC, the overall liver engraftment was low, but a significant percentage of cells were located in the perivascular regions and retained the expression of hallmark endothelial makers. By contrast, ECFC migrated preferentially to the intestinal crypt region and contributed significantly to the myofibroblast population. Furthermore, ECFC expressing CD133 and CD117 lodged in areas where endogenous cells expressed those same phenotypes.

Conclusion:

ECFC inherently constitute a potential source of cells for the treatment of intestinal diseases, but strategies to increase the numbers of ECFC persisting within the hepatic parenchyma are needed in order to enhance ECFC therapeutic potential for this organ.
Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation
Authors: Perugorria Maria Jesus , Wilson Caroline L. , Zeybel Mujdat , Walsh Meagan , Amin Shilu , Robinson Stuart , White Steven A. , Burt Alastair D. , Oakley Fiona , Tsukamoto Hidekazu , Mann Derek A. , Mann Jelena
Published: April 2012

Transdifferentiation of hepatic stellate cells (HSCs) to a myofibroblast-like phenotype is the pivotal event in liver fibrosis. The dramatic change in phenotype associated with transdifferentiation is underpinned by a global change in gene expression. Orchestrated changes in gene expression take place at the level of chromatin packaging which is regulated by enzymatic activity of epigenetic regulators that in turn affect histone modifications. Using expression profiling of epigenetic regulators in quiescent and activated primary HSCs we found a number of histone methyltranferases including MLL1, MLL5, Set1 and ASH1 to be highly up-regulated during transdifferentiation of HSCs. All of these histone methyltranferases regulate methylation of lysine 4 of histone H3, which is a signature of actively transcribed genes. We therefore postulated that one or more of these enzymes may be involved in positively influencing expression of profibrogenic genes.

Conclusion:

We find that ASH1 directly binds to the regulatory regions of alpha smooth muscle actin (αSMA), collagen I, tissue inhibitor of metalloproteinase-1 (TIMP1) and transforming growth factor beta1 (TGFβ1) in activated HSCs while depletion of ASH1 caused broad suppression of fibrogenic gene expression. We also discovered that MeCP2 positively regulates ASH1 expression and therefore identify ASH1 as a key transcriptional activator component of the MeCP2 epigenetic relay pathway that orchestrates coordinated induction of multiple profibrogenic genes.
B7‐H3 expression in colorectal cancer: Nuclear localization strongly predicts poor outcome in colon cancer
Authors: Ingebrigtsen Vibeke Anett , Boye Kjetil , Tekle Christina , Nesland Jahn Martin , Flatmark Kjersti , Fodstad Øystein
Published: April 2012

In colorectal cancer there is a need for molecular markers that can complement the histopathological staging in predicting the likelihood of disease recurrence following curatively intended surgery. B7‐H3 is an immunoregulatory protein shown to be overexpressed in several cancer forms, often associated with more advanced disease and poor prognosis. We wanted to examine whether B7‐H3 could be a potential prognostic marker in colorectal cancer. Paraffin‐embedded samples from 277 colorectal cancer patients were immunostained with anti‐B7‐H3 antibody. B7‐H3 was expressed in the tumor cell cytoplasm and cell membrane in 62% and 46% of the samples, respectively. Unexpectedly, B7‐H3 was expressed in the nucleus in 30% of the tumors. The nuclear localization was confirmed by Western immunoblotting of subcellular fractions. Importantly, in colon cancer, nuclear B7‐H3 expression was independently and significantly associated with reduced metastasis‐free, disease‐specific and overall survival. B7‐H3 expression in tumor‐associated vasculature and fibroblasts was observed in the majority of samples, and endothelial B7‐H3 expression was also significantly associated with poor outcome in colon cancer. In rectal cancer patients, the only significant association was between fibroblast B7‐H3 expression and shorter metastasis‐free survival. Few significant associations to clinicopathological parameters were seen. The results indicate that nuclear B7‐H3 might be involved in colon cancer progression and metastasis, and suggest that nuclear B7‐H3 could become a useful prognostic marker in colon cancer.
A comprehensive study of polymorphisms in ABCB1, ABCC2 and ABCG2 and lung cancer chemotherapy response and prognosis
Authors: Campa Daniele , Müller Phillip , Edler Lutz , Knoefel Lena , Barale Roberto , Heussel Claus P. , Thomas Michael , Canzian Federico , Risch Angela
Published: April 2012

ATP‐binding cassette (ABC) transporter expression and genetic heterogeneity have been implicated in response to anticancer therapy. This study characterized genetic variability of the ABCB1 (also known as MDR1), ABCC2 (MRP2) and ABCG2 (BCRP) genes, which are key players in the metabolism of many chemotherapeutic agents including those used in the treatment of lung cancer. We genotyped 53 polymorphisms in the candidate genes in genomic DNA samples of 171 cases of small cell lung carcinoma (SCLC) and 206 cases of non‐small cell lung carcinoma (NSCLC), and studied their impact on early response to chemotherapy, progression‐free survival and overall survival. SNP rs717620 in ABCC2 was moderately associated with a poor response to chemotherapy but strongly with shorter progression‐free survival and overall survival in SCLC but not NSCLC patients, indicating that ABCC2 genetic variation is an important factor in SCLC survival after chemotherapy.
Influence of uric acid amendment on the in‐vessel process of composting composite food waste
Authors: An Chun‐jiang , Huang Guo‐he , Li Sheng , Yu Hui , Sun Wei , Peng Kuang
Published: April 2012

BACKGROUND: The food waste produced in small cities, rural areas and small communities often coexists with agroindustrial waste, such as livestock and poultry manure, which include high levels of uric acid (UA). This study investigated the influence of UA on the composting of food waste in an in‐vessel system.

RESULTS: Results showed that the performance of food waste composting was significantly different in systems with UA amendment and without UA amendment. Treatment with UA addition was the first to reach the thermophilic phase. More intensive mass reduction took place in the UA‐amended treatments at an early stage. The variations of pH and O2 uptake were also correlated with the added UA. A decreasing trend in C/N ratio and a general increasing trend for NH$_{4}^{+}$‐N concentration were observed when UA was added.

CONCLUSIONS: The overall effect of UA can be assumed to be the sum of a large number of individual events with different mechanisms. Appropriate strategies could be applied to adjust the composting process, mediating both positive and negative effects of the coexistence of food waste and UA as well as manure. The results from this study may have important implications for composting technologies used to treat food waste. Copyright © 2012 Society of Chemical Industry
Star Chromatic Index
Authors: Dvořák Zdeněk , Mohar Bojan , Šámal Robert
Published: April 2012

The star chromatic index of a graph G is the minimum number of colors needed to properly color the edges of the graph so that no path or cycle of length four is bi‐colored. We obtain a near‐linear upper bound in terms of the maximum degree . Our best lower bound on in terms of Δ is valid for complete graphs. We also consider the special case of cubic graphs, for which we show that the star chromatic index lies between 4 and 7 and characterize the graphs attaining the lower bound. The proofs involve a variety of notions from other branches of mathematics and may therefore be of certain independent interest.
Amplified water vapour feedback at high altitudes during winter
Authors: Rangwala Imtiaz
Published: April 2012

During the last five decades, the Tibetan Plateau has experienced a warming trend of 0.4 °C/decade in winter, which is at least twice that of any other season. Some studies have suggested that this anomalous winter warming is caused, in part, by the observed increases in near‐surface water vapour and its amplifying effect on the surface longwave downward radiation (LDR). This study uses observations of surface‐specific humidity (q) and temperature as input to a one‐dimensional radiative transfer model to assess the influence of lower atmospheric increases in water vapour on surface LDR, and the sensitivity of this process to different elevations and seasons on the Tibetan Plateau. The results from three idealized experiments are examined based on realistic atmospheric column profiles of temperature and moisture. They show that when an equal mass of water vapour is added into the atmospheric boundary layer during winter, a substantially greater increase (8×) in LDR is found at the high‐elevation site relative to the low‐elevation site. During summer, the LDR increases are much smaller as are the differences between the two sites. Experiments, where both q and temperature are increased, suggest that the influence of temperature changes on LDR is much greater than those caused by changes in q in all cases, except for the high‐elevation‐winter case when the opposite is true. These results provide further evidence for the possibility of a strong modulation of surface LDR caused by increases in atmospheric water vapour in high altitude regions (>3000 m) during the cold season. Copyright © 2012 Royal Meteorological Society
Effect of slaughter season and muscle type on the fatty acid composition, including conjugated linoleic acid isomers, and nutritional value of intramuscular fat in organic beef
Authors: Pestana José M , Costa Ana SH , Martins Susana V , Alfaia Cristina M , Alves Susana P , Lopes Paula A , Bessa Rui JB , Prates José AM
Published: April 2012

BACKGROUND: Consumer awareness regarding the intake of beef of organic origin is strongly associated with the beneficial outcomes to human health, the environment and animal welfare. In this paper the effects of slaughter season and muscle type on the fatty acid composition, conjugated linoleic acid (CLA) isomeric profile, total cholesterol, α‐tocopherol and β‐carotene contents and nutritional quality of intramuscular fat in organic beef (n = 30) are reported for the first time.

RESULTS: Organic beef showed a very low total lipid content, with seasonal changes in the levels of some fatty acids, CLA isomers, n‐6/n‐3 polyunsaturated fatty acid (PUFA) ratio, total cholesterol and β‐carotene. In addition, differences between longissimus lumborum (relatively red) and semitendinosus (relatively white) muscles were found for many fatty acids, specific CLA contents, many CLA isomers and both PUFA/saturated fatty acid (SFA) and n‐6/n‐3 ratios. However, in spite of the seasonal and carcass variations, all organic meats analysed had values of beef similar to pasture‐fed cattle.

CONCLUSION: From a nutritional perspective, organic meat from both slaughter seasons seems to have high CLA contents, PUFA/SFA and n‐6/n‐3 indices within the recommended values for the human diet. The data indicate that intramuscular fat in organic meat has a high nutritional value throughout the year. Copyright © 2012 Society of Chemical Industry
Plant phytochemicals as new potential drugs for immune disorders and cancer therapy: really a promising path?
Authors: Chirumbolo Salvatore
Published: April 2012

Plant phytochemicals represent an exciting opportunity to maintain best health conditions through a balanced and properly administered daily nutrition or dietary supplement and have often been considered a good option for obtaining a few promising, expensive new drugs from plants. Several polyphenolic compounds, such as resveratrol, tea catechins and flavonoids, which are commonly found in vegetables, fruits and plant‐derived juices or beverages, exert well‐evidenced cardioprotective, neuroprotective, chemopreventive and anti‐inflammatory properties, but, nevertheless, further clinical and epidemiological research is required. Most of these botanical byproducts are produced as noxious components by plants, in order to prevent pathogen colonization, insect‐mediated damage and also to discourage animals from eating them. An evolutionary theory of stress adaptation would explain how these toxic substances from nature act as protective molecules. A future challenge to achieve a rather complete understanding of these chemical phenol derivatives for human health should deal with the complexity of cellular signalling networks, the epigenetic machinery endowment of the cell and the nonlinear relationship between dose and effectiveness. Copyright © 2012 Society of Chemical Industry
No adverse affect after harvesting of free fibula osteoseptocutaneous flaps on gait function
Authors: Maurer‐ertl Werner , Glehr Mathias , Friesenbichler Joerg , Sadoghi Patrick , Wiedner Maria , Haas Franz , Leithner Andreas , Windhager Reinhard , Zwick Ernst B.
Published: April 2012

The aim of this study was to analyze gait function and muscular strength on donor site after harvesting of a vascularized fibula osteoseptocutaneous flap. Nine patients with a mean follow‐up of 33 months (range, 7–59) and a mean resection length of the middle portion of the fibula of 18.0 cm (range, 14.0–23.0) underwent an instrumented three‐dimensional gait analysis to evaluate gait function. Furthermore, CYBEX II extremity system was used for muscular strength measurements. Subjective muscle strength measurements were performed according to Kendall et al. and were classified according to the British Medical Research Council. Intraindividual comparison between the operated and the nonoperated leg revealed no significant differences for gait function parameters (cadence, velocity, and stride length, P > 1.00) and for muscular strength measurements for flexion (knee: P = 0.93, ankle: P = 0.54) and extension (knee: P = 0.97, ankle: P= 0.21), respectively. In conclusion, intraindividual comparison of the operated and nonoperated sides after harvesting of the middle portion of the fibula for gaining a free fibula osteoseptocutaneous flap has no adverse affect on gait function or muscular flexion and extension strength on donor site at a mean follow‐up of 33 months. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012.
Receiver operating characteristic analysis of sphincter electromyography for parkinsonian syndrome
Authors: Yamamoto Tatsuya , Sakakibara Ryuji , Uchiyama Tomoyuki , Yamaguchi Chiharu , Nomura Fumio , Ito Takashi , Yanagisawa Mitsuru , Yano Masashi , Awa Yusuke , Yamanishi Tomonori , Hattori Takamichi , Kuwabara Satoshi
Published: April 2012

Aims

We performed receiver operating characteristic (ROC) analysis to determine the ability of sphincter electromyography (EMG) to distinguish multiple system atrophy (MSA) from other parkinsonisms. The following was determined: (1) the appropriate motor unit potential (MUP) parameter among duration, phase, and amplitude; (2) the desirable parameter of our duration criteria; that is, more than 20% MUPs having >10 ms duration (criteria a) or mean duration >10 ms (criteria b).

Methods

We retrospectively reviewed 441 case records where sphincter EMG were performed in patients with parkinsonian syndromes: MSA, n = 263; Parkinson's disease, n = 129; dementia with Lewy bodies, n = 25; and progressive supranuclear palsy, n = 24. We performed ROC analysis of the data sets.

Results

The area under the curve used to differentiate MSA from other parkinsonian syndromes was 0.68 in duration, 0.57 in phase, and 0.51 in amplitude, respectively; these values were statistically significant. With regard to our duration criteria, area under the curve was 0.69 for the average duration of MUPs (criteria b) and 0.67 for percentage of MUPs of duration >10 ms (criteria a); these values were also statistically significant.

Conclusions

This study suggests that duration is appropriate parameter for the differentiation of MSA. However, the area under the curve of the mean duration was insufficient to confirm the diagnosis; sphincter EMG should be used as a supportive diagnostic tool for the diagnosis of MSA. Neurourol. Urodynam. 31:1128–1134, 2012. © 2012 Wiley Periodicals, Inc.
T‐stress evaluations for nonhomogeneous materials using an interaction integral method
Authors: Yu Hongjun , Wu Linzhi , Guo Licheng , Li Hui , Du Shanyi
Published: April 2012

A new equivalent domain integral of the interaction integral is derived for the computation of the T‐stress in nonhomogeneous materials with continuous or discontinuous properties. It can be found that the derived expression does not involve any derivatives of material properties. Moreover, the formulation can be proved valid even when the integral domain contains material interfaces. Therefore, the present method can be used to extract the T‐stress of nonhomogeneous materials with complex interfaces effectively. The interaction integral method in conjunction with the extended FEM is used to solve several representative examples to show its validity. Finally, using this method, the influences of material properties on the T‐stress are investigated. Numerical results show that the mechanical properties and their first‐order derivatives affect the T‐stress greatly, while the higher‐order derivatives affect the T‐stress slightly. Copyright © 2012 John Wiley & Sons, Ltd.
Convergence analysis of the LDG method applied to singularly perturbed problems
Authors: Zhu Huiqing , Zhang Zhimin
Published: April 2012

Considering a two‐dimensional singularly perturbed convection–diffusion problem with exponential boundary layers, we analyze the local discontinuous Galerkin (DG) method that uses piecewise bilinear polynomials on Shishkin mesh. A convergence rate O(N‐1 lnN) in a DG‐norm is established under the regularity assumptions, while the total number of mesh points is O(N2). The rate of convergence is uniformly valid with respect to the singular perturbation parameter ε. Numerical experiments indicate that the theoretical error estimate is sharp. © 2012 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2013
Solving complex PDE systems for pricing American options with regime‐switching by efficient exponential time differencing schemes
Authors: Khaliq A.Q.M. , Kleefeld B. , Liu R.H.
Published: April 2012

In this article, we study the numerical solutions of a class of complex partial differential equation (PDE) systems with free boundary conditions. This problem arises naturally in pricing American options with regime‐switching, which adds significant complexity in the PDE systems due to regime coupling. Developing efficient numerical schemes will have important applications in computational finance. We propose a new method to solve the PDE systems by using a penalty method approach and an exponential time differencing scheme. First, the penalty method approach is applied to convert the free boundary value PDE system to a system of PDEs over a fixed rectangular region for the time and spatial variables. Then, a new exponential time differncing Crank–Nicolson (ETD‐CN) method is used to solve the resulting PDE system. This ETD‐CN scheme is shown to be second order convergent. We establish an upper bound condition for the time step size and prove that this ETD‐CN scheme satisfies a discrete version of the positivity constraint for American option values. The ETD‐CN scheme is compared numerically with a linearly implicit penalty method scheme and with a tree method. Numerical results are reported to illustrate the convergence of the new scheme. © 2012 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2013
Multi‐period mean‐variance portfolio selection in a regime‐switching market with a bankruptcy state
Authors: Wu Huiling , Zeng Yan
Published: April 2012

This paper first develops a discrete‐time multi‐period mean‐variance portfolio selection model under the assumption that return of a risky asset depends on the states of a stochastic market with a bankruptcy state. When bankruptcy happens, the investor can only retrieve a random fraction δ of the wealth that she or he should acquire and then invests her or his retrieved money in a risk‐free asset until the terminal time. Then, by dynamic programming approach and induction method, explicit closed‐form expressions for the optimal strategy and efficient frontier are derived. Analysis of the optimal results is also provided. Finally, some numerical examples are presented to illustrate the effects of bankruptcy probability and fraction δ on the efficient frontier and optimal strategy. Specially, (i) our results under the mean‐variance model have quite different properties compared with those under power‐utility criterion, and (ii) our model generalizes the existing mean‐variance portfolio selection with regime switching without bankruptcy state. Copyright © 2012 John Wiley & Sons, Ltd.
Bilinear matrix inequality approaches to robust guaranteed cost control for uncertain discrete‐time delay system
Authors: Nian Xiaohong , Sun Zhaomei , Wang Haibo , Zhang Hang , Wang Xia
Published: April 2012

The robust guaranteed cost control problem for uncertain discrete‐time delay system is considered in this paper. Sufficient conditions for the existence of the robust guaranteed cost controllers via memoryless state feedback and static output feedback are expressed as bilinear matrix inequality (BMI). Furthermore, the design methods of optimal robust guaranteed cost controllers, which minimize the upper bound of a given quadratic cost function are presented. Alternate iterative algorithms are proposed to solve the nonconvex optimization problems with BMI constrains. A numerical example is given to illustrate the effectiveness of the proposed methods.Copyright © 2012 John Wiley & Sons, Ltd.
Genomic microarrays: a technology overview
Authors: Brady Paul D. , Vermeesch Joris R.
Published: April 2012

Genomic microarrays are now widely used diagnostically for the molecular karyotyping of patients with intellectual disability, congenital anomalies and autistic spectrum disorder and have more recently been applied for the detection of genomic imbalances in prenatal genetic diagnosis. We present an overview of the different arrays, protocols used and discuss methods of genomic array data analysis. © 2012 John Wiley & Sons, Ltd.
Non‐targeted whole genome 250K SNP array analysis as replacement for karyotyping in fetuses with structural ultrasound anomalies: evaluation of a one‐year experience
Authors: Faas Brigitte HW , Feenstra Ilse , Eggink Alex J. , Kooper Angelique JA , Pfundt Rolph , van Vugt John MG , de Leeuw Nicole
Published: April 2012

Objective

We evaluated both clinical and laboratory aspects of our new strategy offering quantitative fluorescence (QF)‐PCR followed by non‐targeted whole genome 250K single‐nucleotide polymorphism array analysis instead of routine karyotyping for prenatal diagnosis of fetuses with structural anomalies.

Methods

Upon the detection of structural fetal anomalies, parents were offered a choice between QF‐PCR and 250K single‐nucleotide polymorphism array analysis (QF/array) or QF‐PCR and routine karyotyping (QF/karyo).

Results

Two hundred twenty fetal samples were included. In 153/220 cases (70%), QF/array analysis was requested. In 35/153 (23%), an abnormal QF‐PCR result was found. The remaining samples were analyzed by array, which revealed clinically relevant aberrations, including two known microdeletions, in 5/118 cases. Inherited copy number variants were detected in 11/118 fetuses, copy number variants with uncertain clinical relevance in 3/118 and homozygous stretches in 2/118. In 67/220 (30%) fetuses, QF/karyo was requested: 23/67 (34%) were abnormal with QF‐PCR, and in 3/67, an abnormal karyotype was found.

Conclusion

Even though QF/array does not reveal a high percentage of submicroscopic aberrations in fetuses with unselected structural anomalies, it is preferred over QF/karyo, as it provides a whole genome scan at high resolution, without additional tests needed and with a low chance on findings not related to the ultrasound anomalies. © 2012 John Wiley & Sons, Ltd.
The role of DNA microarrays in the evaluation of fetal death
Authors: Reddy Uma M. , Page Grier P. , Saade George R.
Published: April 2012

Fetal death occurs in 15% of clinically recognized pregnancies. Cytogenetic abnormalities are present in 50% of spontaneous abortions (fetal deaths < 20 weeks) whereas the rate is 6% to 13% for stillbirths (fetal deaths ≥ 20 weeks). Microarray has been demonstrated to increase the diagnosis of genetic abnormalities by providing coverage of the entire genome at a higher density, detecting as small as 50 to 100 kb deletions or duplications, known as copy number changes. Microarray is particularly suited for evaluation of fetal death because DNA can still be analyzed in macerated fetuses and nonviable tissue, two situations where culturing and karyotyping is known to have low yield. Microarray has already proven successful in providing additional genetic information beyond karyotype in spontaneous abortion. The few studies on the use of microarray in stillbirth evaluation have been promising, demonstrating an increase in the diagnosis of clinically relevant genetic abnormalities when compared with karyotype. As the cost and technology improve, microarray may ultimately become the first line screen for genetic abnormalities in stillbirth. The accurate diagnosis of a genetic abnormality as the cause for fetal death may provide closure for families, prevent unnecessary treatments, and enable clinicians to more accurately counsel and manage subsequent pregnancies. © 2012 John Wiley & Sons, Ltd.
Novel series connection concept for thin film solar modules
Authors: Haas Stefan , Krumscheid Sebastian , Bauer Andreas , Lambertz Andreas , Rau Uwe
Published: April 2012

The paper introduces a new type of series connection that considerably increases the active area and thus the efficiency of a thin film module by a superior arrangement of the patterning grooves. The new concept is mainly based on pointwise contacts instead of continuous, stripe‐like contacts between adjacent cell stripes combined with a modified arrangement of the isolation grooves. We describe the functionality of the innovative series connection and present a method to calculate the optimal cell stripe geometry for cells based on the new series connection concept. Finally, the applicability of the new concept for a laser‐patterned thin film silicon solar module is demonstrated. The new series connection leads to a relative efficiency increase of approximately 3% compared with the standard series connection for thin film modules. Copyright © 2012 John Wiley & Sons, Ltd.
New guests for the cucurbit[8]uril host. Formation of G2H ternary complexes
Authors: Senler Sanem , Cui Lu , Broomes Ana Michelle , Smith Erika L. , Wilson James N. , Kaifer Angel E.
Published: April 2012

On the basis of the highly stable G2H (2 : 1) ternary complex formed by two methyl viologen cation radicals inside the cavity of cucurbit[8]uril, we prepared three monocationic 4‐phenylpyridinium derivatives: 1‐(hydroxyethyl)‐4‐phenyl‐pyridinium (1+) bromide, 1‐(octaethyleneglycol)‐4‐phenyl‐pyridinium (2+) chloride, and 4‐[4‐(methoxymethoxy)phenyl]pyridinium (3+) iodide, as possible guests for 2 : 1 complexation inside cucurbit[8]uril. We also investigated a fourth monocationic guest (4+), in which a central vinylidene group is inserted to elongate the 4‐phenyl‐pyridinium residue. Using 1H NMR and UV–Vis spectroscopic data and mass spectrometric data, we obtained unequivocal evidence for the formation of G2H (2 : 1) ternary complexes in all cases. The stoichiometry of the complexes was further verified by continuous variation (Job) plots, and in some cases, high resolution ESI‐MS spectrometric data. Diffusion coefficient measurements, using 1H NMR pulse gradient spin echo techniques, yielded values consistent with the formation and expected structures of the ternary complexes. Copyright © 2012 John Wiley & Sons, Ltd.
Investigating the Mechanical Properties of RDX Crystals Using Nano‐Indentation
Authors: Hudson Robert J. , Zioupos Peter , Gill Philip P.
Published: April 2012

The shock sensitivity of RDX is of major interest for the development of insensitive munitions. Previous research has implied that internal defects that form within RDX crystals have a strong sensitising effect, increasing the probability of shock initiation. During the NATO Reduced sensitivity RDX Round Robin (R4) program the number of internal defects within RDX crystals of differing qualities were assessed by optical microscopy and a scoring system. The results suggested that RDX crystals with many internal defects were more sensitive. Studies investigating the mechanical properties of bulk RDX have shown that lots consisting of poorer crystals are weaker. This study investigates the mechanical properties of individual crystals from different RDX lots using nano‐indentation. It is shown that crystals with many internal defects have reduced modulus of elasticity, stiffness and prone to greater deformation under applied load. The results also show a correlation between these parameters and previously reported shock sensitivity data.
Small molecule tolfenamic acid inhibits PC‐3 cell proliferation and invasion in vitro, and tumor growth in orthotopic mouse model for prostate cancer
Authors: Sankpal Umesh T. , Abdelrahim Maen , Connelly Sarah F. , Lee Chris M. , Madero‐Visbal Rafael , Colon Jimmie , Smith Joshua , Safe Stephen , Maliakal Pius , Basha Riyaz
Published: April 2012

BACKGROUND

Specificity protein (Sp) transcription factors are implicated in critical cellular and molecular processes associated with cancer that impact tumor growth and metastasis. The non‐steroidal anti‐inflammatory drug, tolfenamic acid (TA) is known to inhibit Sp proteins in some human cancer cells and laboratory animal models. We evaluated the anti‐cancer activity of TA using in vitro and in vivo models for prostate cancer.

METHODS

The anti‐proliferative efficacy of TA was evaluated using DU‐145, PC‐3, and LNCaP cells. PC‐3 cells were treated with DMSO or 50 µM TA for 48 hr. Whole cell lysates were evaluated for the expression of Sp1, survivin, c‐PARP, Akt/p‐Akt, c‐Met, cdk4, cdc2, cyclin D3, and E2F1 by Western blot analysis. Cell invasion was assessed by Boyden‐chamber assay and flow cytometry analysis was used to study apoptosis and cell cycle distribution. An orthotopic mouse model for prostate cancer with PC‐3‐Luc cells was used to study the in vivo effect of TA.

RESULTS

TA inhibited the expression of Sp1, c‐Met, p‐Akt, and survivin; increased c‐PARP expression and caspases activity in PC‐3 cells. TA caused cell arrest at G0/G1 phase accompanied by a decrease in cdk4, cdc2, cyclin D3, and E2F1 and an increase in critical apoptotic markers. TA augmented annexin‐V staining, caspase activity, and c‐PARP expression indicating the activation of apoptotic pathways. TA also decreased PC‐3 cell invasion. TA significantly decreased the tumor weight and volume which was associated with low expression of Sp1 and survivin in tumor sections.

CONCLUSION

TA targets critical pathways associated with tumorigenesis and invasion. These pre‐clinical data strongly demonstrated the anti‐cancer activity of TA in prostate cancer. Prostate 72:1648–1658, 2012. © 2012 Wiley Periodicals, Inc.
Concise Review: Blood Relatives: Formation and regulation of hematopoietic stem cells by the basic helix-loop-helix transcription factors stem cell leukemia and lymphoblastic leukemia-derived sequence 1
Authors: Curtis David J. , Salmon Jessica M. , Pimanda John E.
Published: April 2012

The basic helix-loop-helix (bHLH) proteins are a large family of transcription factors that regulate the formation and fate of tissue stem cells. In hematopoiesis, the two major bHLH factors are stem cell leukemia (SCL) and lymphoblastic leukemia-derived sequence 1 (LYL1), both identified more than 20 years ago in chromosomal translocations occurring in T-cell acute lymphoblastic leukemia. SCL was termed the master regulator of hematopoiesis following the observation that SCL knockout mice die from complete lack of blood formation. However, once established, SCL is no longer required for maintenance of hematopoiesis. Pull-down experiments together with add-back experiments in SCL-null embryonic stem cells and generation of mice carrying a germline DNA binding mutation of SCL demonstrates that most of SCL function is mediated through the formation of a large DNA binding multiprotein complex with both repressor and activator potential. Recent genome-wide binding studies in a hematopoietic stem progenitor cell line suggest that SCL and LYL1 preferentially bind target DNA sequences as components of a heptad of transcription factors. LYL1, a paralog of SCL has been the forgotten sibling until recent mouse studies demonstrated that LYL1 replaced the function of SCL in adult hematopoiesis. Why LYL1 can replace the function of SCL for the maintenance but not formation of hematopoiesis remains a fundamental question. This review will compare and contrast the roles of these two transcription factors in hematopoiesis focusing on recent functional and genome-wide binding studies.

Disclosure of potential conflicts of interest is found at the end of this article.
Prenatal immune challenge in rats: Altered responses to dopaminergic and glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route‐based learning as a function of maternal body weight gain after prenatal exposure to poly IC
Authors: Vorhees Charles V. , Graham Devon L. , Braun Amanda A. , Schaefer Tori L. , Skelton Matthew R. , Richtand Neil M. , Williams Michael T.
Published: April 2012

Prenatal maternal immune activation has been used to test the neurodevelopmental hypothesis of schizophrenia. Most of the data are in mouse models; far less is available for rats. We previously showed that maternal weight change in response to the immune activator polyinosinic‐polycytidylic acid (Poly IC) in rats differentially affects offspring. Therefore, we treated gravid Harlan Sprague‐Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly IC group was divided into those that lost or gained the least weight, Poly IC (L), versus those that gained the most weight, Poly IC (H), following treatment. The study design controlled for litter size, litter sampling, sex distribution, and test experience. We found no effects of Poly IC on elevated zero maze, open‐field activity, object burying, light–dark test, straight channel swimming, Morris water maze spatial acquisition, reversal, or shift navigation or spatial working or reference memory, or conditioned contextual or cued fear or latent inhibition. The Poly IC (H) group showed a significant decrease in the rate of route‐based learning when visible cues were unavailable in the Cincinnati water maze and reduced prepulse inhibition of acoustic startle in females, but not males. The Poly IC (L) group exhibited altered responses to acute pharmacological challenges: exaggerated hyperactivity in response to (+)‐amphetamine and an attenuated hyperactivity in response to MK‐801. This model did not exhibit the cognitive, or latent inhibition deficits reported in Poly IC‐treated rats but showed changes in response to drugs acting on neurotransmitter systems implicated in the pathophysiology of schizophrenia (dopaminergic hyperfunction and glutamatergic hypofunction). Synapse 2012. © 2012 Wiley Periodicals, Inc.
Risk Factors for Medically Treated Hypocalcemia after Surgery for Graves’ Disease: A Swedish Multicenter Study of 1,157 Patients
Authors: Hallgrimsson P. , Nordenström E. , Almquist M. , Bergenfelz A. O. J.
Published: April 2012

Background

For reasons that remain unclear, surgery for Graves’ disease is associated with a higher risk of hypocalcemia than surgery for benign atoxic goiter. In the present study, we evaluated risk factors for postoperative hypocalcemia in patients undergoing operation for Graves’ disease.

Methods

Data from 1,157 patients who underwent operation for Graves’ disease between 2004 and 2008 were extracted from the Scandinavian database for Thyroid and Parathyroid Surgery. Risk factors for postoperative hypocalcemia (in‐hospital i. v. calcium; treatment with vitamin D analog at discharge, at 6 weeks, and at 6 months postoperatively) were evaluated by logistic regression analysis.

Results

Risk factors for i. v. calcium were low hospital volume of thyroid surgery (odds ratio [OR]: 95 % confidence interval [95 % CI], 0.99: 0.99–1.00), age (0.95: 0.91–1.00), operative time (1.02: 1.01–1.02), university hospital (12.91: 2.68–62.30), and reoperation for bleeding (10.32: 1.51–70.69).

The risk for treatment with vitamin D at discharge increased with operative time (1.01: 1.00–1.02), excised gland weight (1.01: 1.00–1.01), parathyroid autotransplantation (5.19: 2.28–11.84), and reoperation for bleeding (12.00: 2.43–59.28). At 6 weeks, vitamin D medication was associated with gland weight (1.00: 1.00–1.01), and preoperative medication with β‐blockers (4.20: 1.67–10.55). At 6 months, vitamin D medication was associated with gland weight (1.00: 1.00–1.01) and reoperation for bleeding (10.59: 1.58–71.22).

Conclusions

Risk factors for medically treated hypocalcemia varied at different times of follow‐up. Young age, operative time, type of hospital, and parathyroid autotransplantation were associated with early postoperatively hypocalcemia. Preoperative β‐blocker treatment was a risk factor at the first follow‐up. At early and late follow‐up, gland weight and reoperation for bleeding were associated with medically treated hypocalcemia.
Feeding habits of the pelagic stingray Pteroplatytrygon violacea (Chondrichthyes: Dasyatidae) in the Adriatic Sea
Authors: Lipej L. , Mavrič B. , Paliska D. , Capapé C.
Published: April 2012

The feeding habits of the pelagic stingray (Pteroplatytrygon violacea) were studied using 84 stomachs of specimens caught in the northern Adriatic Sea in the period from April 2004 to October 2005. Percentage of empty stomachs found was overall very low, being a bit bigger in smaller specimens. The diet consisted of two main taxonomic groups such as teleost fish and cephalopods, but few specimens of crustaceans were recorded as well. The main food item was represented by anchovy, while cuttlefish and red band fish represented the alternative preys. Prey size was positively correlated with the size of predator. The proportion of anchovies in the diet grew with size of predator, while the one for red band fish decreased. The stingray was confirmed to be a top predator of pelagic fish species, although the presence of benthic prey shows that it feeds also at the bottom.
Tulle as Tool: Embracing the Conflict of the Ballerina as Powerhouse
Authors: Fisher Jennifer
Published: April 2012

The image and interpretation of the ballerina has shifted over time since she first took her place in the pantheon of romantic female performers in the early nineteenth century. For many, she is still romanticized, respected, and revered; in other circles, she has become suspect as a creature who may be obsessed, exploited, and retrogressive in light of the egalitarian strides women have made or are still trying to make. The female ballet dancer's basic contradiction—her ethereal exterior and her iron-willed interior—has not been sufficiently accounted for in either scheme, nor has it been woven into the kind of complex, contextualized analysis that includes practitioners who embody the form, audience members of various kinds, and the multiple, shifting locales and attitudes that surround them. As an elite art form, ballet has until recently relied on the more univocal discourse of bouquets and brickbats from critics and other specialists. In 1993, when dance anthropologist Cynthia Jean Cohen Bull called for a consideration of ballet's relationship of dance to life in ways that other cultural forms are investigated, few took up the call.
Inside the Knot that Two Bodies Make
Authors: Spier Steven
Published: April 2012

The film From a Classical Position (1997) is a fully collaborative work between a notable dancer and performer and a notable choreographer, being danced, directed, and edited by Dana Caspersen and William Forsythe of the late Ballett Frankfurt. By looking closely at the film, its origins, and its process of creation, we gain an understanding of Caspersen and Forsythe's way of collaborating and their interest in working with other media and formats. Uncompromising if not difficult for a general dance audience, it is also somewhat didactic and offers insights into some of the Ballett Frankfurt's methods of generating movement, choreographic structures, and the importance of classical technique to a distinctive movement vocabulary:

[The film] was also a little message to the British, who I'm sure were curious about us. It was a little missile to them, saying yes we are the Frankfurt Ballet, yes we perform before so many seats in the Opera House. We are the same people and this is what we do … There is the obvious classical training and this is how we are dealing with it. (Forsythe 1999)