bluuebunny/crossref_metadata_2025 huggingface dataset:
Private Equity and Asset Characteristics: The Case of Agricultural Production
Authors: Mondelli Mario P. , Klein Peter G.
Published: October 2013

Unlike most other mature industries, family firms, partnerships, and cooperatives dominate the agricultural production sector, with few corporations and limited access to capital derived from a source other than retained earnings and existing owners. However, the use of external equity capital in agriculture has increased dramatically since 1990. This funding source allows farms to exploit entrepreneurial opportunities not easily financed by debt. Following O. Williamson, we view debt and equity as alternative governance structures and argue that transaction cost economics offers insights on firms' financial structure beyond those provided by agency theory. We relate capital structure to asset specificity, a particularly important attribute in agricultural production. We construct an international dataset of agricultural companies receiving external private equity and show that the attributes of the assets involved in production are important determinants of financial structure. Copyright © 2013 John Wiley & Sons, Ltd.
Fall risk and gait in Parkinson's disease: The role of the LRRK2 G2019S mutation
Authors: Mirelman Anat , Heman Talia , Yasinovsky Kira , Thaler Avner , Gurevich Tanya , Marder Karen , Bressman Susan , Bar‐Shira Anat , Orr‐Urtreger Avi , Giladi Nir , Hausdorff Jeffrey M. ,   on behalf of the LRRK2 Ashkenazi Jewish Consortium
Published: October 2013

Patients with Parkinson's disease (PD) who carry the G2019S mutation (a glycine to serine substitution at amino acid 2019) in the leucine‐rich repeat kinase 2 (LRRK2) gene are generally believed to be clinically indistinguishable from patients with sporadic PD. There are, however, conflicting reports on the relationship between the mutation and the motor phenotype. We quantitatively compared gait and mobility in patients with PD carriers of the G2019S mutation to non‐carrier patients with PD to better understand the genotype‐phenotype relationship. Fifty patients with PD carriers of the G2019S LRRK2 mutation and 50 age, disease duration, and disease severity matched PD non‐carriers were studied. An accelerometer quantified gait under three walking conditions: usual‐walking, dual‐tasking, and fast‐walking. The Unified Parkinson's Disease Rating Scale classified patients into PD sub‐types and the Timed Up and Go quantified mobility and fall risk. In all three walking conditions, gait variability was larger and the walking pattern was less consistent among the PD mutation carriers (P < 0.016). The PD carriers also took longer to complete the Timed Up and Go (P = 0.011) and were more likely to report having fallen in the previous year (P = 0.018). 64% of the PD carriers were classified as belonging to the postural‐instability‐gait‐difficulty (PIGD) sub‐type compared to only 17% of the PD non‐carriers (P < 0.0001). Among patients with PD, the G2019S mutation in the LRRK2 gene is apparently associated with increased gait variability, an increased fall risk, and the PIGD sub‐type. Therapeutic approach specifically designed to delay gait disturbances and falls may be justified in patients who carry the G2019S mutation. © 2013 International Parkinson and Movement Disorder Society
Phase II safety, tolerability, and dose selection study of isradipine as a potential disease‐modifying intervention in early Parkinson's disease (STEADY‐PD)
Authors:   Parkinson Study Group
Published: October 2013

Isradipine, a dihydropyridine calcium channel antagonist, has been shown to be neuroprotective in animal models of Parkinson's disease (PD). To establish a dosage of isradipine controlled‐release (CR) that is tolerable and demonstrates preliminary efficacy for use in a future pivotal efficacy trial a Phase 2, randomized, double‐blind, parallel group trial (Safety, Tolerability and Efficacy Assessment of Dynacirc CR in Parkinson Disease [STEADY‐PD]) was undertaken in subjects with early PD not requiring dopaminergic therapy (dopamine agonists or levodopa) randomized 1:1:1:1 to 5, 10, or 20 mg of isradipine CR or matching placebo daily. The primary outcome was tolerability defined as no more than a 30% difference in the proportion of patients completing the study on the originally assigned dosage between an active and placebo group. If more than one isradipine dosage was tolerable, then a 3‐point difference in total Unified Parkinson's Disease Rating Scale (UPDRS) change between baseline and week 52 (or time to sufficient disability to require dopaminergic therapy) was taken as a criterion for selection of the most desirable dosage for future study. STEADY‐PD enrolled 99 subjects. The tolerability of isradipine was dose dependent: placebo, 25 of 26 patients (96%); 5 mg, 19 of 23 patients (83%); 10 mg 19 of 26 patients (73%); and 20 mg 9 of 24 patients (37%). There was no difference in change in UPDRS among dosages. The most common adverse events were peripheral edema (30) and dizziness (24). Isradipine 10 mg daily was the maximal tolerable dosage in this study of early PD. A large placebo‐controlled trial will be necessary and is planned to assess efficacy of isradipine 10 mg daily to slow progression of PD disability. © 2013 International Parkinson and Movement Disorder Society.
Dementia in Parkinson's disease: Usefulness of the pill questionnaire
Authors: Martinez‐Martin Pablo
Published: October 2013

The Level I algorithm for the diagnosis of dementia associated with Parkinson's disease (PD‐D) recommended by the Movement Disorder Society task force includes a Pill Questionnaire to determine the impact of cognitive decline on daily activities. The objective of this study was to test the performance of the Pill Questionnaire as a screening tool for the detection of dementia (all‐cause) in patients with PD and to test the performance of another functional scale substituting the Pill Questionnaire for the diagnosis of “probable PD‐D” (pPD‐D). Data were collected from 529 patients who had PD in Hoehn and Yahr stages 1 through 5. The measures used include the Scales for Outcomes in PD‐Motor (SCOPA‐Motor), scales for psychiatric complications, the Mini Mental State Examination, the Clinical Impression of Severity Index, and the Pill Questionnaire. The SCOPA‐Motor functional subscale score was categorized as “impact” or “no impact” of PD on daily activities. According to clinical judgment, 13.3% of patients had dementia. For detecting dementia, the Pill Questionnaire had 89% accuracy, although its positive predictive value was 55%. Performance was worse with the categorized SCOPA‐Motor subscale. According to the Movement Disorder Society task force criterion, 85 patients (16.1%) had pPD‐D. When the Pill Questionnaire was substituted by the categorized SCOPA‐Motor subscale, the modified algorithm showed sensitivity, specificity, and accuracy indexes over 90% but had positive predictive value of 66% for pPD‐D diagnosis. Although the Pill Questionnaire demonstrated acceptable basic properties as a screening tool for dementia, its positive predictive value was low. The SCOPA‐Motor subscale cannot be proposed as a substitute for the Pill Questionnaire. © 2013 International Parkinson and Movement Disorder Society
Defining optimal cutoff scores for cognitive impairment using Movement Disorder Society Task Force criteria for mild cognitive impairment in Parkinson's disease
Authors: Goldman Jennifer G. , Holden Samantha , Bernard Bryan , Ouyang Bichun , Goetz Christopher G. , Stebbins Glenn T.
Published: October 2013

The recently proposed Movement Disorder Society (MDS) Task Force diagnostic criteria for mild cognitive impairment in Parkinson's disease (PD‐MCI) represent a first step toward a uniform definition of PD‐MCI across multiple clinical and research settings. However, several questions regarding specific criteria remain unanswered, including optimal cutoff scores by which to define impairment on neuropsychological tests. Seventy‐six non‐demented PD patients underwent comprehensive neuropsychological assessment and were classified as PD‐MCI or PD with normal cognition (PD‐NC). The concordance of PD‐MCI diagnosis by MDS Task Force Level II criteria (comprehensive assessment), using a range of standard deviation (SD) cutoff scores, was compared with our consensus diagnosis of PD‐MCI or PD‐NC. Sensitivity, specificity, and positive and negative predictive values were examined for each cutoff score. PD‐MCI subtype classification and distribution of cognitive domains impaired were evaluated. Concordance for PD‐MCI diagnosis was greatest for defining impairment on neuropsychological tests using a 2 SD cutoff score below appropriate norms. This cutoff also provided the best discriminatory properties for separating PD‐MCI from PD‐NC compared with other cutoff scores. With the MDS PD‐MCI criteria, multiple domain impairment was more frequent than single domain impairment, with predominant executive function, memory, and visuospatial function deficits. Application of the MDS Task Force PD‐MCI Level II diagnostic criteria demonstrates good sensitivity and specificity at a 2 SD cutoff score. The predominance of multiple domain impairment in PD‐MCI with the Level II criteria suggests not only influences of testing abnormality requirements, but also the widespread nature of cognitive deficits within PD‐MCI. © 2013 International Parkinson and Movement Disorder Society
Primary motor cortex long‐term plasticity in multiple system atrophy
Authors: Suppa Antonio , Marsili Luca , Di Stasio Flavio , Latorre Anna , Parvez AK. , Colosimo Carlo , Berardelli Alfredo
Published: October 2013

In humans, intermittent and continuous theta‐burst stimulation (iTBS and cTBS) elicit long‐term changes in motor‐evoked potentials (MEPs) reflecting long‐term potentiation (LTP)‐ and depression (LTD)‐like plasticity in the primary motor cortex (M1). In this study, we used TBS to investigate M1 plasticity in patients with MSA. We also assessed whether responses to TBS reflect M1 excitability as tested by short‐interval intracortical inhibition (SICI), intracortical facilitation (ICF), short‐interval intracortical facilitation (SICF), and the input/output curves. We studied 20 patients with MSA and 20 healthy subjects (HS). Patients were clinically evaluated with the Unified Multiple System Atrophy Rating Scale. The left M1 was conditioned with TBS. Twenty MEPs were recorded from the right first dorsal interosseous muscle before TBS and 5, 15, and 30 minutes thereafter. In a subgroup of 10 patients, we also tested MEPs elicited by SICI, ICF, SICF, and input/output curves, before TBS. Between‐group analysis of variance showed that at all time points after iTBS MEPs increased, whereas after cTBS they decreased only in HS. In both subgroups tested, patients with predominant parkinsonian and cerebellar features, iTBS and cTBS left MEPs unchanged. MSA patients had reduced SICI, but normal ICF, SICF, and input/output curves. No correlation was found between patients' clinical features and responses to TBS and M1 excitability variables. These findings suggest impaired M1 plasticity in MSA. © 2013 International Parkinson and Movement Disorder Society
The unified huntington's disease rating scale for advanced patients: Validation and follow‐up study
Authors: Youssov Katia , Dolbeau Guillaume , Maison Patrick , Boissé Marie‐Françoise , de Langavant Laurent Cleret , Roos Raymund A. C. , Bachoud‐Lévi Anne‐Catherine
Published: October 2013

The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In patients with advanced HD, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS‐For Advanced Patients (UHDRS‐FAP) to improve longitudinal assessment of patients at the advanced disease stage. Sixty‐nine patients with a Total Functional Capacity score ≤ 5 were recruited in France and the Netherlands. Among them, 45 patients were followed longitudinally (mean ± standard deviation, 1.6 ± 1.2 years) with the UHDRS‐FAP; 30 patients also were assessed with the UHDRS. In cross‐sectional analyses, the psychometric properties and inter‐rater reliability of the scale were evaluated. Longitudinal analyses were used to evaluate the sensitivity to decline of the UHDRS‐FAP compared with the UHDRS. Internal consistency was higher for motor (0.84) and cognitive (0.91) scores than for somatic (0.70) and behavioral (0.49) scores. Inter‐rater reliability was ≥ 0.88 for all scores. The somatic score, which was specific to the UHDRS‐FAP, declined over time along with motor and cognitive performance on both scales. Although performance with the two scales was correlated, the UHDRS‐FAP appeared to be more sensitive to change and was the only scale that detected decline in patients with a Total Functional Capacity score ≤ 1. Neither scale detected a significant decline in behavioral scores. The results indicate that the UHDRS‐FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items that are relevant for daily care. Behavioral scores tended to decline, but this may reflect the decline in patients' communicative abilities. © 2013 International Parkinson and Movement Disorder Society
Cortical gyrification reductions and subcortical atrophy in Parkinson's disease
Authors: Zhang Yuanchao , Zhang Jiuqun , Xu Jinping , Wu Xiu , Zhang Yanling , Feng Hua , Wang Jian , Jiang Tianzi
Published: October 2013

Background

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and non‐motor symptoms. Previous morphometric studies of PD were mainly conducted by measuring gray matter volume and cortical thickness, and little attention has been paid to the morphology of the cortical surface.

Methods

Using a surface‐based local gyrification index (lGI), this study compared the cortical gyrification patterns of 37 PD patients and 34 matched healthy controls. Volumetric analyses also were performed on the subcortical structures.

Results

Compared with the control group, patients with PD had significantly reduced cortical gyrification in multiple brain regions, which the authors speculated were associated with disruptions in white matter connectivity and suboptimal intracortical organization. In addition, subcortical volume atrophy was identified in the bilateral hippocampus and bilateral caudate of the patients with PD.

Conclusions

Further studies are needed to identify the clinical correlates of the structural abnormalities observed in PD. © 2013 International Parkinson and Movement Disorder Society
Impaired force control in writer's cramp showing a bilateral deficit in sensorimotor integration
Authors: Bleton Jean‐Pierre , Teremetz Maxime , Vidailhet Marie , Mesure Serge , Maier Marc A. , Lindberg Påvel G.
Published: October 2013

Background

Abnormal cortical processing of sensory inputs has been found bilaterally in writer's cramp (WC). This study tested the hypothesis that patients with WC have an impaired ability to adjust grip forces according to visual and somatosensory cues in both hands.

Methods

A unimanual visuomotor force‐tracking task and a bimanual sense of effort force‐matching task were performed by WC patients and healthy controls.

Results

In visuomotor tracking, WC patients showed increased error, greater variability, and longer release duration than controls. In the force‐matching task, patients underestimated, whereas controls overestimated, the force applied in the other hand. Visuomotor tracking and force matching were equally impaired in both the symptomatic and nonsymptomatic hand in WC patients.

Conclusions

This study provides evidence of bilaterally impaired grip‐force control in WC, when using visual or sense of effort cues. This suggests a generalized subclinical deficit in sensorimotor integration in WC. © 2013 International Parkinson and Movement Disorder Society
The distally based peroneus brevis muscle flap—clinical series and review of the literature
Authors: Ensat Florian , Hladik Michaela , Larcher Lorenz , Mattiassich Georg , Wechselberger Gottfried
Published: October 2013

The distally pedicled peroneus brevis muscle flap is rarely used for defect coverage in the distal lower leg. The purpose of this article was to present our clinical series and provide a review of the literature to analyze the overall complication rates and safety of this flap. In our clinical series of 10 patients undergoing reconstruction with the flap, one necrosis of the distal half of the flap and one necrosis of a skin graft occurred. Our review of the literature identified 192 patients undergoing reconstruction with distally pedicled peroneus brevis flaps. The overall complication rate was 41.6%. Typical indications, complications, advantages and disadvantages to alternatives are discussed. The distally pedicled peroneus brevis flap is an interesting option for soft tissue coverage in the distal lower leg. The donor site can always be closed primarily, the anatomy is constant and complication rates are comparable to alternatives in this region like the distally based sural fasciocutaneous flap. © 2013 Wiley Periodicals, Inc. Microsurgery 34:203–208, 2014.
Digital subtraction angiography in selection of the vascularized greater trochanter bone grafting for treatment of osteonecrosis of femoral head
Authors: Zhao Dewei , Xiaobing Yu , Wang Tienan , Wang Benjie , Liu Baoyi , Fengde Tian , Fu Weimin , Huang Shibo , Qiu Xing
Published: October 2013

The aim of this report is to present our experience on the use of the digital subtraction angiography (DSA) in selection of the vascularized greater trochanter bone grafting for the treatment of the osteonecrosis of femoral head (ONFH) in early stages. Between January 2005 and June 2007, DSA was used to evaluate the blood perfusion of the early stages ONFH in 32 patients (45 hips). There were 18 males and 14 females with an average age of 30 years old. Twenty‐one hips were in ARCO stage I, and 24 in ARCO stage II. The arterial blood supply insufficiency was found in 22 hips by DSA, and the venous stasis in 23 hips. The hips with artery blood supply insufficiency received the vascularized greater trochanter bone grafting, and the hips with the venous stasis received the core decompression. All of patients were followed‐up with an average of 4.8 years (ranging 2.4–6.6 years). The preoperative Harris Hip score (HHS) in the patients with arterial blood supply insufficiency was 48.18 ± 7.81 and the postoperative HHS was 93.27 ± 3.03. The preoperative HHS in the patients with venous stasis was 44.04 ± 6.40, and the postoperative HHS 92.65 ± 2.93. The postoperative DSA showed an improved perfusion of the femoral head in 44 hips. Our experience showed that DSA would help to select the appropriate procedure for treatment of ONFH in the early stage. © 2013 Wiley Periodicals, Inc. Microsurgery 33:656–659, 2013.
A segmented and weighted Adomian decomposition algorithm for boundary value problem of nonlinear groundwater equation
Authors: Yun Yin‐shan , Chaolu Temuer , Duan Jun‐sheng
Published: October 2013

Based on Adomian decomposition method, a new algorithm for solving boundary value problem (BVP) of nonlinear partial differential equations on the rectangular area is proposed. The solutions obtained by the method precisely satisfy all boundary conditions, except the small pieces near the four corners of the rectangular area. A theorem on the boundary error is given. Hence, the Adomian decomposition method is more efficiently applied to BVPs for partial differential equations. Segmented and weighted analytical solutions with a high accuracy for the BVP of nonlinear groundwater equations on a rectangular area are obtained by the present algorithm. Copyright © 2013 John Wiley & Sons, Ltd.
Conservative‐dissipative approximation schemes for a generalized Kramers equation
Authors: Duong Manh Hong , Peletier Mark A. , Zimmer Johannes
Published: October 2013

We propose three new discrete variational schemes that capture the conservative‐dissipative structure of a generalized Kramers equation. The first two schemes are single‐step minimization schemes, whereas the third one combines a streaming and a minimization step. The cost functionals in the schemes are inspired by the rate functional in the Freidlin‐Wentzell theory of large deviations for the underlying stochastic system. We prove that all three schemes converge to the solution of the generalized Kramers equation. Copyright © 2013 John Wiley & Sons, Ltd.
Existence of positive solutions for nonlinear Kirchhoff type problems in with critical Sobolev exponent
Authors: Li Gongbao , Ye Hongyu
Published: October 2013

In this paper, we study the following nonlinear problem of Kirchhoff type with critical Sobolev exponent:
urn:x-wiley:01704214:media:mma3000:mma3000-math-0001 where a, b > 0 are constants. Under certain assumptions on the sign‐changing function f(x,u), we prove the existence of positive solutions by variational methods.

Our main results can be viewed as a partial extension of a recent result of He and Zou in [Journal of Differential Equations, 2012] concerning the existence of positive solutions to the nonlinear Kirchhoff problem
urn:x-wiley:01704214:media:mma3000:mma3000-math-0002 where ϵ > 0 is a parameter, V (x) is a positive continuous potential, and with 4 < p < 6 and satisfies the Ambrosetti–Rabinowitz type condition. Copyright © 2013 John Wiley & Sons, Ltd.
Cocoa flavonoid epicatechin protects pancreatic beta cell viability and function against oxidative stress
Authors: Martín María Ángeles , Fernández‐Millán Elisa , Ramos Sonia , Bravo Laura , Goya Luis
Published: October 2013

Scope

Diabetes mellitus is associated with reductions in glutathione, supporting the critical role of oxidative stress in its pathogenesis. Antioxidant food components such as flavonoids have a protective role against oxidative stress‐induced degenerative and age‐related diseases. Flavonoids such as epicatechin (EC) constitute an important part of the human diet; they can be found in green tea, grapes, and cocoa and possess multiple biological activities. This study investigates the chemo‐protective effect of EC against oxidative stress induced by tert‐butylhydroperoxide (t‐BOOH) on Ins‐1E pancreatic beta cells.

Methods and results

Cell viability, oxidative status, phosphorylated Jun kinase (p‐JNK) expression, and insulin secretion were evaluated. Ins‐1E cells treatment with 5–20 μM EC for 20 h evoked no cell damage and enhanced antioxidant enzymes and insulin secretion. Addition of 50 μM t‐BOOH for 2 h induced reactive oxygen species, p‐JNK, and carbonyl groups and decreased GSH and insulin secretion. Pretreatment of cells with EC prevented the t‐BOOH‐induced reactive oxygen species, carbonyl groups, p‐JNK expression and cell death, and recovered insulin secretion.

Conclusion

Ins‐1E cells treated with EC showed a remarkable recovery of cell viability and insulin secretion damaged by t‐BOOH, indicating that integrity of secreting and surviving machineries in the EC‐treated cells was notably protected against the oxidative insult.
The chemopreventive action of bromelain, from pineapple stem (Ananas comosusL.), on colon carcinogenesis is related to antiproliferative and proapoptotic effects
Authors: Romano Barbara , Fasolino Ines , Pagano Ester , Capasso Raffaele , Pace Simona , De Rosa Giuseppe , Milic Natasa , Orlando Pierangelo , Izzo Angelo A. , Borrelli Francesca
Published: October 2013

Scope

Colorectal cancer is an important health problem across the world. Here, we investigated the possible antiproliferative/proapoptotic effects of bromelain (from the pineapple stem Ananas comosus L., family Bromeliaceae) in a human colorectal carcinoma cell line and its potential chemopreventive effect in a murine model of colon cancer.

Methods and results

Proliferation and apoptosis were evaluated in human colon adenocarcinoma (Caco‐2) cells by the 3H‐thymidine incorporation assay and caspase 3/7 activity measurement, respectively. Extracellular signal‐related kinase (ERK) and Akt expression were evaluated by Western blot analysis, reactive oxygen species production by a fluorimetric method. In vivo, bromelain was evaluated using the azoxymethane murine model of colon carcinogenesis. Bromelain reduced cell proliferation and promoted apoptosis in Caco‐2 cells. The effect of bromelain was associated to downregulation of pERK1/2/total, ERK, and pAkt/Akt expression as well as to reduction of reactive oxygen species production. In vivo, bromelain reduced the development of aberrant crypt foci, polyps, and tumors induced by azoxymethane.

Conclusion

Bromelain exerts antiproliferative and proapoptotic effects in colorectal carcinoma cells and chemopreventive actions in colon carcinogenesis in vivo. Bromelain‐containing foods and/or bromelain itself may represent good candidates for colorectal cancer chemoprevention.
Sensitizing potential of enzymatically cross‐linked peanut proteins in a mouse model of peanut allergy
Authors: Radosavljevic Jelena , Nordlund Emilia , Mihajlovic Luka , Krstic Maja , Bohn Torsten , Buchert Johanna , Velickovic Tanja Cirkovic , Smit Joost
Published: October 2013

Scope

The cross‐linking of proteins by enzymes to form high‐molecular‐weight protein, aggregates can be used to tailor the technological or physiological functionality of food products. Aggregation of dietary proteins by food processing may promote allergic sensitization, but the effects of enzymatic cross‐linking of dietary proteins on the allergenic potential of food are not known. In this study, the bioavailability and the sensitizing or tolerizing potential of peanut proteins (PE) cross‐linked with microbial tyrosinase from Trichoderma reesei and mushroom tyrosinase from Agaricus bisporus, were investigated.

Methods and results

The impact of cross‐linking of PE on the in vitro bioavailability of fluorescein isothiocyanate‐labeled peanut proteins was tested in a Caco‐2 cell monolayer and by competitive ELISA. The in vivo allergenicity or capacity to induce oral tolerance in mice were measured by serum levels of PE‐specific antibodies and T cell cytokine production after exposure to PE and cross‐linked PE.

Conclusion

Enzymatic processing of peanut proteins by the two tyrosinases increased the bioavailability of major peanut allergen Ara h 2, but did not significantly change the allergenic or tolerizing properties of peanut. Enzymatic treatment of peanut proteins yielded cross‐linked proteins with preserved molecular and immunological features of peanut allergens.
Plant polyphenol induced cell death in human cancer cells involves mobilization of intracellular copper ions and reactive oxygen species generation: A mechanism for cancer chemopreventive action
Authors: Khan Husain Yar , Zubair Haseeb , Faisal Mohd , Ullah Mohd Fahad , Farhan Mohd , Sarkar Fazlul H. , Ahmad Aamir , Hadi Sheikh Mumtaz
Published: October 2013

Scope

Anticancer polyphenolic nutraceuticals from fruits, vegetables, and spices are generally recognized as antioxidants, but can be prooxidants in the presence of copper ions. We earlier proposed a mechanism for such activity of polyphenols and now we provide data in multiple cancer cell lines in support of our hypothesis.

Methods and results

Through multiple assays, we show that polyphenols luteolin, apigenin, epigallocatechin‐3‐gallate, and resveratrol are able to inhibit cell proliferation and induce apoptosis in different cancer cell lines. Such cell death is prevented to a significant extent by cuprous chelator neocuproine and reactive oxygen species scavengers. We also show that normal breast epithelial cells, cultured in a medium supplemented with copper, become sensitized to polyphenol‐induced growth inhibition.

Conclusion

Since the concentration of copper is significantly elevated in cancer cells, our results strengthen the idea that an important anticancer mechanism of plant polyphenols is mediated through intracellular copper mobilization and reactive oxygen species generation leading to cancer cell death. Moreover, this prooxidant chemopreventive mechanism appears to be a mechanism common to several polyphenols with diverse chemical structures and explains the preferential cytotoxicity of these compounds toward cancer cells.
Accumulation of promutagenic DNA adducts in the mouse distal colon after consumption of heme does not induce colonic neoplasms in the western diet model of spontaneous colorectal cancer
Authors: Winter Jean , Young Graeme P. , Hu Ying , Gratz Silvia W. , Conlon Michael A. , Le Leu Richard K.
Published: October 2013

Scope

Red meat is considered a risk factor for colorectal cancer (CRC). Heme is considered to promote colonic hyperproliferation and cell damage. Resistant starch (RS) is a food that ferments in the colon with studies demonstrating protective effects against CRC. By utilizing the western diet model of spontaneous CRC, we determined if feeding heme (as hemin chloride) equivalent to a high red meat diet would increase colonic DNA adducts and CRC and whether RS could abrogate such effects.

Methods and results

Four groups of mice: control, heme, RS and heme + RS were fed diets for 1 or 18 months. Colons were analyzed for apoptosis, proliferation, DNA adducts “8‐hydroxy‐2‐deoxyguanosine” and “O6‐methyl‐2‐deoxyguanosine” (O6MeG), and neoplasms. In the short term, heme increased cell proliferation (p < 0.05). Changes from 1 to 18 months showed increased cell proliferation (p < 0.01) and 8‐hydroxy‐2‐deoxyguanosine adducts (p < 0.05) in all groups, but only heme‐fed mice showed reduced apoptosis (p < 0.01) and increased O6MeG adducts (p < 0.01). The incidence of colon neoplasms was not different between any interventions.

Conclusion

We identified heme to increase proliferation in the short term, inhibit apoptosis over the long term, and increase O6MeG adducts in the colon over time although these changes did not affect colonic neoplasms within this mouse model.
GIAO/DFT studies on 1,2,4‐triazole‐5‐thiones and their propargyl derivatives
Authors: Phalgune Usha D. , Vanka Kumar , Rajamohanan P. R.
Published: October 2013

Density functional theory (DFT)/Becke–Lee–Yang–Parr (B3LYP) and gauge‐including atomic orbital (GIAO) calculations were performed on a number of 1,2,4‐triazole derivatives, and the optimized structural parameters were employed to ascertain the nature of their predominant tautomers. 13C and 15N NMR chemical shifts of 3‐substituted 1,2,4‐triazole‐5‐thiones and their propargylated derivatives were calculated via GIAO/DFT approach at the B3LYP level of theory with geometry optimization using a 6‐311++G** basis set. A good agreement between theoretical and experimental 13C and 15N NMR chemical shifts could be found for the systems investigated. The data generated were useful in predicting 15N chemical shifts of all the nitrogen atoms of the triazole ring, some of which could not be obtained in solution state 15N HMBC/HSQC NMR measurements. The energy profile computed for the dipropargylated derivatives was found to follow the product distribution profile of regioisomers formed during propargylation of 1,2,4‐triazole thiones. Copyright © 2013 John Wiley & Sons, Ltd.
1H and 13C NMR investigation of 20‐hydroxyecdysone dioxolane derivatives, a novel group of MDR modulator agents
Authors: Balázs Attila , Hunyadi Attila , Csábi József , Jedlinszki Nikoletta , Martins Ana , Simon András , Tóth Gábor
Published: October 2013

The synthesis, structure elucidation and the complete 1H and 13C signal assignment of a series of dioxolane derivatives of 20‐hydroxyecdysone, synthesized as novel modulators of multidrug resistance, are presented. The structures and NMR signal assignment were established by comprehensive one‐dimensional and two‐dimensional NMR spectroscopy supported by mass spectrometry. Copyright © 2013 John Wiley & Sons, Ltd.
1H and 13C NMR assignments of bioactive indeno[1,2‐b]indole‐10‐one derivatives
Authors: Al Chab Faten , Fenet Bernard , Le Borgne Marc , Jose Joachim , Pinaud Noël , Guillon Jean , Ettouati Laurent
Published: October 2013

The complete 1H and 13C assignments of eight bioactive indeno[1,2‐b]indole‐10‐one derivatives were accomplished by the combined use of one‐dimensional and two‐dimensional NMR experiments. Copyright © 2013 John Wiley & Sons, Ltd.
Polymeric adducts of rhodium(II) tetraacetate with aliphatic diamines: natural abundance 13C and 15N CPMAS NMR investigations
Authors: Jaźwiński Jarosław , Kamieński Bohdan , Sadlej Agnieszka
Published: October 2013

Complexation properties of dimeric rhodium(II) tetracarboxylates have been utilised in chemistry, spectroscopy and organic synthesis. Particularly, the combination of these rhodium salts with multifunctional ligands results in the formation of coordination polymers, and these are of interest because of their gas‐occlusion properties. In the present work, the polymeric adducts of rhodium(II) tetraacetate with flexible ligands exhibiting conformational variety, ethane‐1,2‐diamine, propane‐1,3‐diamine and their N,N′‐dimethyl‐ and N,N,N′,N′‐tetramethyl derivatives, have been investigated by means of elemental analysis, 13C CPMAS NMR, 15N CPMAS NMR and density functional theory modelling. Elemental analysis and NMR spectra indicated the axial coordination mode and regular structures of (1 : 1)n oligomeric chains in the case of adducts of ethane‐1,2‐diamine, N,N′‐dimethylethane‐1,2‐diamine N,N,N′,N′‐tetramethylethane‐1,2‐diamine and N,N,N′,N′‐tetramethylpropane‐1,3‐diamine. Propane‐1,3‐diamine and N,N′‐dimethylpropane‐1,3‐diamine tended to form heterogeneous materials, composed of oligomeric (1 : 1)n chains and the additive of dirhodium units containing equatorially bonded ligands. Experimental findings have been supported by density functional theory modelling of some hypothetical structures and gauge‐invariant atomic orbital calculations of NMR chemical shifts. Copyright © 2013 John Wiley & Sons, Ltd.
Mathematical Modeling of Carboxylated SB Latexes
Authors: Calvo Iñigo , Hester Ken , Leiza Jose R. , Asua José M.
Published: October 2013

A mathematical model for the seeded emulsion copolymerization of styrene, butadiene, and an acidic monomer has been developed. The outputs of the model include monomer conversion, copolymer composition, solids content, average particle size, 4‐PCH and 4‐VCH concentrations, overall molecular weight distribution, gel content, distance between crosslinking points, acid distribution between phases, and amount of inactive polymer in the aqueous phase and its composition. The parameters of the model have been estimated using pilot‐plant data and the model captures well the effect of the process variables on the latex characteristics.
Propagation of calibration errors in prospective motion correction using external tracking
Authors: Zahneisen Benjamin , Keating Brian , Ernst Thomas
Published: October 2013

Purpose

Prospective motion correction of MRI scans using an external tracking device (such as a camera) is becoming increasingly popular, especially for imaging of the head. In order for external tracking data to be transformed into the MR scanner reference frame, the pose (i.e., position and orientation) of the camera relative to the scanner—or cross‐calibration—must be accurate. In this study, we investigated how errors in cross‐calibration affect the accuracy of motion correction feedback in MRI.

Theory and Methods

An operator equation is derived describing how calibration errors relate to errors in applied motion compensation. By taking advantage of spherical symmetry and performing a Taylor approximation for small rotation angles, a closed form expression and upper limit for the residual tracking error is provided.

Results

Experiments confirmed theoretical predictions of a bilinear dependence of the residual rotational component on the calibration error and the motion performed, modulated by a sinusoidal dependence on the angle between the calibration error axis and motion axis. The residual translation error is bounded by the sum of the rotation angle multiplied by the translational calibration error plus the linear head displacement multiplied by the calibration error angle.

Conclusion

The results make it possible to calculate the required cross‐calibration accuracy for external tracking devices for a range of motions. Scans with smaller expected movements require less accuracy in cross‐calibration than scans involving larger movements. Typical clinical applications require that the calibration accuracy is substantially below 1 mm and 1°. Magn Reson Med 72:381–388, 2014. © 2013 Wiley Periodicals, Inc.
Development of an MRI phantom for diffusion‐weighted imaging with independent adjustment of apparent diffusion coefficient values and T2 relaxation times
Authors: Gatidis Sergios , Schmidt Holger , Martirosian Petros , Schwenzer Nina F.
Published: October 2013

Purpose

To design a phantom for diffusion‐weighted imaging (DWI) with defined apparent diffusion coefficients (ADC) and T2 relaxation times.

Methods

Varying concentrations of polyethylene glycol (PEG) were used for the adjustment of diffusivity. T2 relaxation times were tuned by adding of the MR contrast agent gadobutrol. Relaxation times and apparent diffusion coefficients were quantified using a multiecho spin echo sequence and an echo planar imaging (EPI) DWI sequence, respectively, on a 3T clinical scanner.

Results

Increasing concentrations of PEG led to a marked impairment of diffusivity accompanied by only moderate changes of T2 relaxation times. Adding gadobutrol to the PEG solutions allowed for adjustment of transverse relaxation times to predefined values. Thus, a broad range of defined ADC values and T2 relaxation times could be accurately achieved in the final phantom.

Conclusion

The proposed phantom allows for standardized in vitro studies of DWI methods and protocols. The obtained MR image contrasts are similar to a variety of biological tissues, which can contribute to optimization of imaging techniques with respect to specific clinical questions. Due to the simplicity of design and the accessibility of the contained compounds, this phantom may also serve as a tool for standardization and calibration. Magn Reson Med 72:459–463, 2014. © 2013 Wiley Periodicals, Inc.
Quantitative T2 mapping of the mouse heart by segmented MLEV phase‐cycled T2 preparation
Authors: Coolen Bram F. , Simonis Frank F.J. , Geelen Tessa , Moonen Rik P.M. , Arslan Fatih , Paulis Leonie E.M. , Nicolay Klaas , Strijkers Gustav J.
Published: October 2013

Purpose

A high‐quality, reproducible, multi‐slice T2‐mapping protocol for the mouse heart is presented.

Methods

A T2‐prepared sequence with composite 90° and 180° radiofrequency pulses in a segmented MLEV phase cycling scheme was developed. The T2‐mapping protocol was optimized using simulations and evaluated with phantoms.

Results

Repeatability for determination of myocardial T2 values was assessed in vivo in n = 5 healthy mice on 2 different days. The average baseline T2 of the left ventricular myocardium was 22.5 ± 1.7 ms. The repeatability coefficient for R2 = 1/T2 for measurements at different days was ΔR2 = 6.3 s−1. Subsequently, T2 mapping was applied in comparison to late‐gadolinium‐enhancement (LGE) imaging, to assess 1‐day‐old ischemia/reperfusion (IR) myocardial injury in n = 8 mice. T2 in the infarcts was significantly higher than in remote tissue, whereas remote tissue was not significantly different from baseline. Infarct sizes based on T2 versus LGE showed strong correlation. To assess the time‐course of T2 changes in the infarcts, T2 mapping was performed at day 1, 3, and 7 after IR injury in a separate group of mice (n = 16). T2 was highest at day 3, in agreement with the expected time course of edema formation and resolution after myocardial infarction.

Conclusion

T2 prepared imaging provides high quality reproducible T2 maps of healthy and diseased mouse myocardium. Magn Reson Med 72:409–417, 2014. © 2013 Wiley Periodicals, Inc.
Compressed sensing of spatial electron paramagnetic resonance imaging
Authors: Johnson David H. , Ahmad Rizwan , He Guanglong , Samouilov Alexandre , Zweier Jay L.
Published: October 2013

Purpose

To improve image quality and reduce data requirements for spatial electron paramagnetic resonance imaging (EPRI) by developing a novel reconstruction approach using compressed sensing (CS).

Methods

EPRI is posed as an optimization problem, which is solved using regularized least‐squares with sparsity promoting penalty terms, consisting of the l1 norms of the image itself and the total variation of the image. Pseudo‐random sampling was employed to facilitate recovery of the sparse signal. The reconstruction was compared with the traditional filtered back‐projection reconstruction for simulations, phantoms, isolated rat hearts, and mouse gastrointestinal (GI) tracts labeled with paramagnetic probes.

Results

A combination of pseudo‐random sampling and CS was able to generate high‐fidelity EPR images at high acceleration rates. For three‐dimensional (3D) phantom imaging, CS‐based EPRI showed little visual degradation at nine‐fold acceleration. In rat heart datasets, CS‐based EPRI produced high quality images with eight‐fold acceleration. A high resolution mouse GI tract reconstruction demonstrated a visual improvement in spatial resolution and a doubling in signal‐to‐noise ratio (SNR).

Conclusion

A novel 3D EPRI reconstruction using compressed sensing was developed and offers superior SNR and reduced artifacts from highly undersampled data. Magn Reson Med 72:893–901, 2014. © 2013 Wiley Periodicals, Inc.
Multiparametric optical and MR imaging demonstrate inhibition of tumor angiogenesis natural history by mural cell therapy
Authors: Faye Nathalie , Clément Olivier , Balvay Daniel , Fitoussi Victor , Pidial Laetitia , Sandoval Federico , Autret Gwennhael , Silvestre Jean Sébastien , Dean Carole Leré , Alison Marianne , Fournier Laure S.
Published: October 2013

Purpose

To determine whether functional imaging using MRI and fibered confocal fluorescence microscopy (FCFM) could be used to monitor cell therapy by mural progenitor cells (MPC).

Methods

Fifty mice bearing TC1 murine xenograft tumors were allocated into: control (n = 17), sham (phosphate buffer saline, n = 16), and MPC‐treated (MPC, n = 17) groups. MRI was performed before (D0) and 7 days (D7) after injection measuring tumor size, R2* under air, oxygen, and carbogen using blood oxygen level dependent (BOLD) and f (fraction linked to microcirculation), D* (perfusion related coefficient) and Dr (restricted diffusion coefficient) using diffusion‐weighted sequences based on the IVIM (intravoxel incoherent motion) method. FCFM was performed at D7 measuring “index leakage” (capillary permeability).

Results

Tumor growth was significantly slowed down in the MPC‐treated animals (P = 0.002) on D7. R2*air significantly decreased in controls between D0 and D7 (P = 0.03), reflecting a decrease in tumor oxygenation. ΔR2*O2CO2 significantly increased in controls between D0 and D7 (P = 0.01) reflecting loss of vessel response to carbogen. D* significantly decreased in controls between D0 and D7 (P = 0.03). Finally, “index leakage” was lower in the MPC‐treated tumors (P = 0,009).

Conclusion

Treatment by MPC resulted in slowing down of tumor growth, capillary permeability decrease, and stabilization of tumor angiogenesis. Magn Reson Med 72:841–849, 2014. © 2013 Wiley Periodicals, Inc.
Spiral tissue phase velocity mapping in a breath‐hold with non‐cartesian SENSE
Authors: Simpson Robin , Keegan Jennifer , Gatehouse Peter , Hansen Michael , Firmin David
Published: October 2013

Purpose

Tissue phase velocity mapping (TPVM) is capable of reproducibly measuring regional myocardial velocities. However acquisition durations of navigator gated techniques are long and unpredictable while current breath‐hold techniques have low temporal resolution. This study presents a spiral TPVM technique which acquires high resolution data within a clinically acceptable breath‐hold duration.

Methods

Ten healthy volunteers are scanned using a spiral sequence with temporal resolution of 24 ms and spatial resolution of 1.7 × 1.7 mm. Retrospective cardiac gating is used to acquire data over the entire cardiac cycle. The acquisition is accelerated by factors of 2 and 3 by use of non‐Cartesian SENSE implemented on the Gadgetron GPU system resulting in breath‐holds of 17 and 13 heartbeats, respectively. Systolic, early diastolic, and atrial systolic global and regional longitudinal, circumferential, and radial velocities are determined.

Results

Global and regional velocities agree well with those previously reported. The two acceleration factors show no significant differences for any quantitative parameter and the results also closely match previously acquired higher spatial resolution navigator‐gated data in the same subjects.

Conclusion

By using spiral trajectories and non‐Cartesian SENSE high resolution, TPVM data can be acquired within a clinically acceptable breath‐hold. Magn Reson Med 72:659–668, 2014. © 2013 Wiley Periodicals, Inc.
Protein expression profiling during wallerian degeneration after rat sciatic nerve injury
Authors: Li Meiyuan , Zhang Pingan , Guo Weimin , Li Huaiqin , Gu Xiaosong , Yao Dengbing
Published: October 2013

Introduction: Wallerian degeneration (WD) is an important area of research in modern neuroscience. Many protein expressions are regulated by differentially expressed genes in WD, but the precise mechanisms are elusive. Methods: In this study, we profiled differentially expressed proteins in WD after rat sciatic nerve injury using an antibody array. Results: Functional analysis positively identified cell proliferation, regulation of cell proliferation, and immune system processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed molecular networks related mainly to cytokine–cytokine receptor interaction, the mitogen‐activated proteinkinase (MAPK) signaling pathway, apoptosis, the toll‐like receptor (TLR) signaling pathway, and the Janus kinase (Jak) ‐ signal transducer and activator of transcription (STAT) signaling pathway. Interactions between these differential proteins were well established and regulated by the key factors transforming growth factor beta 1 (TGF‐β1), toll‐like receptor 4 (TLR4), Fas ligand (FasL), and 5′‐AMP‐activated protein kinase catalytic subunit alpha‐1 (PRKAA1). Conclusions: These results provide information related to functional analysis of differentially expressed genes during WD. Muscle Nerve 50: 73–78, 2014
Shifts in EMG spectral power during fatiguing dynamic contractions
Authors: Beck Travis W. , Stock Matt S. , Defreitas Jason M.
Published: October 2013

Introduction: We examined the etiology of the electromyographic (EMG) spectral shift during dynamic fatigue. Methods: Nineteen subjects (mean ± SD age = 22.4 ± 1.6 years) performed 50 consecutive maximal concentric isokinetic contractions of dominant leg extensors. Surface EMG signals were detected from the vastus lateralis, rectus femoris, and vastus medialis during each contraction, processed with a wavelet analysis, and the resulting spectra were decomposed with a nonparametric spectral decomposition procedure. Results: The results indicated that the decreases in EMG frequency during the 50 contractions were generally due to reductions in high‐frequency power and increases in low‐frequency power. In addition, the spectral shifts were most pronounced for the rectus femoris, followed by the vastus lateralis, and then the vastus medialis. Conclusions: The spectral decomposition procedure is much more sensitive for tracking dynamic fatigue than is EMG mean frequency or median frequency. Muscle Nerve 50: 95–102, 2014