bluuebunny/crossref_metadata_2025 huggingface dataset:
Standardization of relative cerebral blood volume (rCBV) image maps for ease of both inter‐ and intrapatient comparisons
Authors: Bedekar Devyani , Jensen Todd , Schmainda Kathleen M.
Published: May 2010

Relative cerebral blood volume (rCBV) measured using dynamic susceptibility contrast MRI suffers from interpatient and interstudy variability for the same tissue type. Traditionally, when a more quantitative assessment of rCBV is required, as for comparison across studies and patients, the rCBV values are normalized to the rCBV in a reference region such as normal‐appearing white matter. However, this technique of normalization is subjective and time consuming and introduces user‐dependent variability. In this study, we demonstrate that a method called standardization, applied to rCBV maps, is an objective means of translating all rCBV values to a consistent scale. This approach reduces interpatient and interstudy variability for the same tissue type, thus enabling easy and accurate visual and quantitative comparison across studies. One caveat to this approach is that it is not appropriate for the evaluation of global changes in blood volume, since systematic differences are removed in the process of standardization. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Thoracic Aortic Aneurysms and Dissections: Endovascular Treatment
Authors: Baril Donald T. , Cho Jae S. , Chaer Rabih A. , Makaroun Michel S.
Published: May 2010

The treatment of thoracic aortic disease has changed radically with the advances made in endovascular therapy since the concept of thoracic endovascular aortic repair was first described 15 years ago. Currently, there is a diverse array of endografts that are commercially available to treat the thoracic aorta. Multiple studies, including industry‐sponsored and single‐institution reports, have demonstrated excellent outcomes of thoracic endovascular aortic repair for the treatment of thoracic aortic aneurysms, with less reported perioperative morbidity and mortality in comparison with conventional open repair. Additionally, similar outcomes have been demonstrated for the treatment of type B dissections. However, the technology remains relatively novel, and larger studies with longer term outcomes are necessary to more fully evaluate the role of endovascular therapy for the treatment of thoracic aortic disease. This review examines the currently available thoracic endografts, preoperative planning for thoracic endovascular aortic repair, and outcomes of thoracic endovascular aortic repair for the treatment of both thoracic aortic aneurysms and type B aortic dissections. Mt Sinai J Med 77:256–269, 2010. © 2010 Mount Sinai School of Medicine
Sports‐Related Injuries in the Young Female Athlete
Authors: Colvin Alexis C. , Lynn Abigail
Published: May 2010

The number of females participating in sports continues to increase. Adolescent and preadolescent females are at a risk injury to both their open growth plates as well as their joints. The purpose of this article is to review the common injuries seen with the most popular sports with females. Mt Sinai J Med 77:307–314, 2010. © 2010 Mount Sinai School of Medicine
Abdominal Aortic Aneurysms: Endovascular Repair
Authors: Jim Jeffrey , Sanchez Luis A.
Published: May 2010

Since its introduction 2 decades ago, endovascular repair of abdominal aortic aneurysms has continued to evolve, and many now consider it the optimal treatment modality for infrarenal abdominal aortic aneurysms. There are currently 5 commercially approved endografts, each with its unique design, and all can be utilized with excellent technical results. The endovascular repair is performed with radiographic guidance utilizing general, spinal, or local anesthesia. Endoleak is the most common complication and unique to the procedure. Routine postoperative surveillance imaging is essential to ensure long‐term success. Clinical trials have demonstrated lower perioperative mortality and morbidity for endovascular repair of abdominal aortic aneurysms compared with open repair. However, evidence for long‐term survival benefits is lacking. Furthermore, the benefits of endovascular repair in “high‐risk” patients remain unclear. Though there is a subset of patients who benefit from endovascular repair of abdominal aortic aneurysms, objective identification of this population remains a challenge. Practitioners currently recommend elective repair for aneurysms ≥ 5.5 cm in diameter and in selected patients with smaller aneurysms. Current studies are underway to evaluate the utility of endovascular repair in small aneurysms. Patients with ruptured aneurysms, due to the high morbidity and mortality associated with their management, may significantly benefit from endovascular repair. Although there is a lack of sufficient randomized controlled trial data, available evidence does support the use of endovascular repair for ruptured abdominal aortic aneurysms. Multiple newer endovascular devices are under clinical investigation to address the limitations of available devices. Ultimately, we may be able to treat the vast majority of patients with all types of abdominal and thoracoabdominal aortic aneurysms with endovascular devices. Mt Sinai J Med 77:238–249, 2010. © 2010 Mount Sinai School of Medicine
Visceral Artery Aneurysms: Review of Current Management Options
Authors: Sachdev‐Ost Ulka
Published: May 2010

Visceral artery aneurysms are relatively rare clinical entities, although their detection is rising due to an increased use of cross‐sectional imaging. Rupture is the most devastating complication, and is associated with a high morbidity and mortality. For this reason, elective repair is preferable in the appropriately chosen patient. In general, splenic artery aneurysms measuring 2 cm or larger and those found in women of childbearing age and in persons undergoing liver transplantation should be treated. Hepatic artery aneurysms 2 cm or larger and those that are multiple or nonatherosclerotic in nature should be repaired in the appropriate patient due to a higher risk of rupture. Endovascular coil embolization has excellent success rates and is the first‐line treatment for anatomically suitable splenic artery aneurysms and intrahepatic hepatic artery aneurysms. However, reperfusion is an important complication of endovascular management. Aneurysms involving the celiac, superior mesenteric, pancreaticoduodenal, gastroduodenal, and inferior mesenteric arteries, as well as visceral artery pseudoaneurysms, are unpredictable and should be repaired in the appropriate medical patient. These aneurysms are often amenable to ligation due to the presence of collateral circulation. Endovascular management is particularly useful in the treatment of pseudoaneurysms where comorbidities and previous surgery make open surgical repair less desirable. Mt Sinai J Med 77:296–303, 2010. © 2010 Mount Sinai School of Medicine
Ruptured Abdominal Aortic Aneurysms: Role of Endovascular Therapy
Authors: Cayne Neal S. , Veith Frank J.
Published: May 2010

Ruptured abdominal aortic aneurysms historically have high mortality rates. Despite improvements in many open surgical techniques and perioperative care, these mortality rates have not significantly changed. Some of the reasons for the high mortality rates include the excessive blood loss and hypothermia that occur during open operative repair. The blood loss and hypothermia, combined with resuscitative dilutional coagulopathy, can lead to an irreversible spiraling coagulopathy that ultimately ends in the patient's demise. The availability of endovascular approaches to treat abdominal aortic aneurysms in the early 1990s offered an opportunity to substantially alter the treatment outcomes of ruptured abdominal aortic aneurysms. Endovascular repair offers many advantages, including rapid aortic control under local anesthesia, as well as an opportunity to limit the hypothermia and blood loss that occur with an open abdomen. This article will review the endovascular management of ruptured abdominal aortic aneurysms and describe the endovascular techniques for safe and effective treatment. Mt Sinai J Med 77:250–255, 2010. © 2010 Mount Sinai School of Medicine
Intracranial Aneurysms: Endovascular Treatment
Authors: Moyle Henry , Patel Aman B.
Published: May 2010

The incidence of subarachnoid hemorrhage is estimated at 5 to 10 per 100,000 per year. In patients who survive the initial hemorrhage, the repeat hemorrhage rate is 15% to 20% in the first 2 weeks after presentation and is associated with devastating clinical outcomes even graver than the initial rupture. The current options for aneurysm treatment are surgical clipping and, since the mid‐1990s, neuroendovascular coil embolization. The former was at one time the gold standard of care, but consistent with the trend in modern medicine toward less‐invasive procedures, the latter has steadily gained prominence. Although there is still controversy as to its long‐term durability and safety, it is now the preferred procedure. This article describes the procedure's antecedents, rationale, and essential components. Mt Sinai J Med 77:279–285, 2010. © 2010 Mount Sinai School of Medicine
Deep Vein Thrombosis: Endovascular Management
Authors: Lookstein Robert A. , Giordano Christopher F.
Published: May 2010

Deep vein thrombosis is a condition that affects hundreds of thousands of patients each year. The major complications include pulmonary embolus with the potential for loss of life and post‐thrombotic syndrome with the potential for loss of function of the limb. Extensive clinical research over the last 40 years has improved the techniques to remove the thrombus from the affected limb and reduce the likelihood of developing post‐thrombotic syndrome. These treatments have included intravenous systemic thrombolysis, catheter‐directed thrombolysis, surgical thrombectomy, and most recently pharmacomechanical thrombectomy to rapidly fragment, lyse, and remove the thrombus from the affected limb. This last technique may finally transform the treatment of acute deep vein thrombus from strictly conservative medical therapy to a minimally invasive procedure that can remove the thrombus to improve the quality of life of millions of individuals suffering from the symptoms of deep vein thrombosis. Mt Sinai J Med 77:286–295, 2010. © 2010 Mount Sinai School of Medicine
Minimally Invasive Vein Surgery: Latest Options for Vein Disease
Authors: Elias Steven
Published: May 2010

The goal of treatment for venous disease is to decrease ambulatory venous hypertension. Various strategies are employed. These can be divided into exogenous and endogenous treatments. Exogenous methods concern those employed from the outside of the limb, such as compression and elevation. Endogenous modalities treat from inside the limb the underlying venous pathology due to venous valvular dysfunction or venous obstruction. Traditional endogenous procedures include stripping, ligation, and phlebectomy. All these procedures require incisions, anesthesia, and perhaps hospitalization, and involve significant discomfort. Newer minimally invasive vein surgery procedures now exist. These are all same‐day, outpatient procedures, usually involving local anesthesia. Most can be performed percutaneously without incisions. Patients ambulate the day of the procedure. Morbidity is less than 1%. This article summarizes the concept of minimally invasive vein surgery and summarizes new technologies to manage all forms of venous disease. Mt Sinai J Med 77:270–278, 2010. © 2010 Mount Sinai School of Medicine
Pore scale study of permeability and tortuosity for flow through particulate media using Lattice Boltzmann method
Authors: Ghassemi Ali , Pak Ali
Published: May 2010

In this paper, Lattice Boltzmann method (LBM) has been used to study the effects of permeability and tortuosity on flow through saturated particulate media and identify the relationships between permeability and tortuosity with other parameters such as particles diameter, grain specific surface, and porosity. LBM is a simple kinematic model that can incorporate the essential physics of microscopic and mesoscopic processes involved in flow through granular soils.

The obtained results indicate that the 2D LB model, due to its inherent theoretical advantages, is capable of demonstrating that the porosity and specific surface are the most influential parameters in determining the intrinsic permeability of granular media. The obtained results show that particles' size diameter has a two‐fold effect on the coefficient of permeability: one is through specific surface and the other is by tortuosity factor. Numerical study also reveals that tortuosity of granular soils decreases almost linearly with increasing the porosity. Copyright © 2010 John Wiley & Sons, Ltd.
C2‐symmetry dimethylated zirconocenes activated with triisobutyl aluminum as effective homogeneous catalysts for copolymerization of olefins
Authors: Bravaya N. M. , Panin A. N. , Faingol'd E. E. , Babkina O. N. , Razavi A.
Published: May 2010

We investigated the catalytic performance of both bridged unsubstituted [rac‐EtInd2ZrMe2, rac‐Me2SiInd2ZrMe2] and 2‐substituted [rac‐Et(2‐MeInd)2ZrMe2), rac‐Me2Si(2‐MeInd)2ZrMe2] dimethylbisindenylzirconocenes activated with triisobutyl aluminum (TIBA) as a single activator in (a) homopolymerizations of ethylene and propylene, (b) copolymerization of ethylene with propylene and hexene‐1, and (c) copolymerization of propylene with hexene‐1 (at AlTIBA/Zr = 100‐300 mol/mol). Unsubstituted catalysts were inactive in homopolymerizations of ethylene and propylene and copolymerization of propylene with hexene‐1 but exhibited high activity in copolymerizations of ethylene with propylene and hexene‐1. 2‐Substituted zirconocenes activated with TIBA were active in homopolymerizations of ethylene and propylene and exhibited high activity in copolymerization of ethylene with propylene and hexene‐1, and in copolymerization of propylene with hexene‐1. Comparative microstructural analysis of ethylene‐propylene copolymers prepared over rac‐Me2SiInd2ZrMe2 activated with TIBA or Me2NHPhB(C6F5)4 has shown that the copolymers formed upon activation with TIBA are statistical in nature with some tendency to alternation, whereas those with borate activated system show a tendency to formation of comonomer blocks. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2934–2941, 2010
Aluminum Burn Rate Modifiers Based on Reactive Nanocomposite Powders
Authors: Stamatis Demitrios , Jiang Xianjin , Beloni Ervin , Dreizin Edward L.
Published: May 2010

Aluminum powders have long been used as additives in propellants, pyrotechnics, and explosives. Aluminum has a high enthalpy of combustion but relatively low burn rate. Addition of reactive nanocomposite powders can increase the burn rate of aluminum and thus the overall reaction rate of the energetic formulation. Replacing only a small fraction of the fuel by a nanocomposite material can enhance the reaction rate with little change to the thermodynamic performance of the formulation. This research showed the feasibility of the above concept using nanocomposite powders prepared by arrested reactive milling (ARM), a scalable “top‐down” technique for manufacturing reactive nanomaterials. The nanocomposite materials used in this study were 2B+Ti, and Al‐rich thermites: 8Al+3CuO, and 8Al+MoO3. The reactive nanocomposite powders were added to micrometer‐sized aluminum powder and the mixture was aerosolized and burned in a constant volume chamber. The combustion atmosphere was varied using oxygen, nitrogen, and methane. The resulting pressure traces were recorded and processed to compare different types and amounts of modifiers. Additives of nanocomposite powders of 8Al+MoO3 and 2B+Ti to micrometer‐sized aluminum were found to be effective in increasing both the rate of pressure rise and maximum pressure in the respective constant volume explosion experiments. It was observed that 20 wt.‐% of additive resulted in the best combination of the achieved burn rate and pressure.
A transcriptional signature associated with the onset of benign prostate hyperplasia in a canine model
Authors: Gallardo‐Arrieta F. , Doll A. , Rigau M. , Mogas T. , Juanpere N. , García F. , Morote J. , Nuñez F. , Abal M. , Lloreta J. , Reventós J.
Published: May 2010

BACKGROUND

Benign prostatic hyperplasia (BPH) represents the most frequent proliferative abnormality of the human prostate. In spite of the well‐characterized architectural development of BPH, little is known about the cellular and molecular events that contribute to it.

METHODS

We have developed an animal model to evaluate the follow‐up of hormone‐induced BPH and the analysis of the gene expression associated with BPH. Immunohistochemistry on human patient samples validated the BPH‐related molecular alterations.

RESULTS

Canine specific Affymetrix microarray analysis performed on sequential biopsies obtained from a beagle dog dynamic model characterized a number of genes altered during the onset of BPH. In addition to the genes involved in calcification, matrix remodeling, detoxification, cell movement, and mucosa protection (MGP, MMP2, TIMP2, ITIH3, GST, MT2A, SULT1A1, FKBP1B, MUC1, STRBP, TFF3), the up‐regulation of TGFB3 and CLU indicated a complete adjustment of the transdifferentiation, senescence and apoptosis programs. The up‐regulation of Clusterin was validated by RT‐qPCR and immunohistochemistry, both in the dog dynamic model and in human samples, further confirming the suitability of the animal model for the study of the molecular alterations associated with BPH.

CONCLUSIONS

Transcriptome analysis performed on a dynamic animal model that accurately mimicked the human clinic, allowed us to characterize a gene expression pattern associated with the onset of BPH. Prostate 70: 1402–1412, 2010. © 2010 Wiley‐Liss, Inc.
Vitamin D pathway gene variants and prostate cancer prognosis
Authors: Holt Sarah K. , Kwon Erika M. , Koopmeiners Joseph S. , Lin Daniel W. , Feng Ziding , Ostrander Elaine A. , Peters Ulrike , Stanford Janet L.
Published: May 2010

BACKGROUND

Observational studies linking vitamin D deficiency with increased prostate cancer (PCa) mortality and the pleiotropic anticancer effects of vitamin D in malignant prostate cell lines have initiated trials examining potential therapeutic benefits of vitamin D metabolites. There have been some successes but efforts have been hindered by risk of inducing hypercalcemia. A limited number of studies have investigated associations between variants in vitamin D pathway genes with aggressive forms of PCa. Increased understanding of relevant germline genetic variation with disease outcome could aid in the development of vitamin‐D‐based therapies.

METHODS

We undertook a comprehensive analysis of 48 tagging single‐nucleotide polymorphisms (tagSNPs) in genes encoding for vitamin D receptor (VDR), vitamin D activating enzyme 1‐α‐hydroxylase (CYP27B1), and deactivating enzyme 24‐hydroxylase (CYP24A1) in a cohort of 1,294 Caucasian cases with an average of 8 years of follow‐up. Disease recurrence/progression and PCa‐specific mortality risks were estimated using adjusted Cox proportional hazards regression.

RESULTS

There were 139 cases with recurrence/progression events and 57 cases who died of PCa. Significantly altered risks of recurrence/progression were observed in relation to genotype for two VDR tagSNPs (rs6823 and rs2071358) and two CYP24A1 tagSNPs (rs927650 and rs2762939). Three VDR tagSNPs (rs3782905, rs7299460, and rs11168314), one CYP27B1 tagSNP (rs3782130), and five CYP24A1 tagSNPs (rs3787557, rs4809960, rs2296241, rs2585428, and rs6022999) significantly altered risks of PCa death.

CONCLUSIONS

Genetic variations in vitamin D pathway genes were found to alter both risk of recurrence/progression and PCa‐specific mortality. Prostate 70: 1448–1460, 2010. © 2010 Wiley‐Liss, Inc.
Glycemic control and prostate cancer progression: Results from the SEARCH database
Authors: Kim Howard S. , Presti Joseph C. , Aronson William J. , Terris Martha K. , Kane Christopher J. , Amling Christopher L. , Freedland Stephen J.
Published: May 2010

PURPOSE

Several studies have examined the association between diabetes mellitus (DM) and prostate cancer (PCa) risk and progression, however nearly all of these studies have compared diabetic versus non‐diabetic men. We sought to investigate the role of glycemic control, as measured by HbA1c, on PCa aggressiveness and prognosis in men with DM and PCa from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

METHODS

We identified 247 men in SEARCH with DM and a recorded HbA1c value within the 12 months prior to radical prostatectomy between 1988 and 2009. We divided these men into tertiles by HbA1c level. The associations between HbA1c tertiles and risk of adverse pathology and biochemical recurrence were tested using multivariate logistic regression and Cox proportional hazards models, respectively.

RESULTS

Median HbA1c level was 6.9. On multivariate analysis, HbA1c tertiles were predictive of pathological Gleason score (P‐trend = 0.001). Relative to the first tertile, men in the second (OR 4.68, P = 0.003) and third tertile (OR 6.60, P < 0.001) were more likely to have Gleason score ≥4 + 3. HbA1c tertiles were not associated with margin status, node status, extracapsular extension or seminal vesicle invasion (all P‐trend > 0.2). In the multivariate Cox proportional hazards model, increasing HbA1c tertiles were not significantly related to risk of biochemical recurrence (P‐trend = 0.56).

CONCLUSION

Men with higher HbA1c levels presented with more biologically aggressive prostate tumors at radical prostatectomy. Although risk of recurrence was unrelated to HbA1c levels, further studies are needed to better explore the importance of glycemic control on long‐term outcomes in diabetic men with PCa. Prostate 70: 1540–1546, 2010. © 2010 Wiley‐Liss, Inc.
The effect of estrogen supplementation on cell proliferation and expression of c‐kit positive cells in the rat prostate
Authors: Kusljic Snezana , Exintaris Betty
Published: May 2010

BACKGROUND

Benign prostatic hyperplasia (BPH) is associated with the proliferation of prostate tissue and an increase in smooth muscle tone. However, the way in which the hormonal environment affects cell proliferation and prostatic interstitial cells (PIC) responsible for the maintenance of the smooth muscle tone is not clear. The present study investigated the effect of estrogen supplementation on cell proliferation, androgen/estrogen ratio, and expression and/or distribution of PIC.

METHODS

Male Sprague–Dawley rats were anesthetized with isoflurane/oxygen breathing mixture and subcutaneously implanted with silastic capsules. These capsules were either empty or filled with a 10 or 20 mg of crystalline estrogen.

RESULTS

Estrogen exerted a potent effect on ventral prostate weight, which was manifested as a significant decrease between controls and the E10‐ and E20‐treated rats. Active cell proliferation detected as Ki67‐positive nuclei was observed in the stromal and epithelial cells of the ventral prostatic lobes from estrogen‐treated rats and controls. Estrogen supplementation caused a significant and dose‐dependent increase in prostatic estradiol and 5α‐dihydrotestosterone (DHT) concentration but the ratios of either DHT/E2 or E2/DHT were not significantly affected. PIC were observed in the region between the fibromuscular stroma and the glandular epithelium in all three experimental groups. E20‐treated rats showed a higher expression of PIC than controls and E10‐treated rats.

CONCLUSIONS

The present study provides novel information regarding the synergistic role of estrogens and androgens in the prostate: estrogen may prevent prostatic hyperplasia via mechanisms other than affecting cell proliferation or DHT/estrogen ratio. Prostate 70: 1555–1562, 2010. © 2010 Wiley‐Liss, Inc.
Selection of near‐native poses in CAPRI rounds 13‐19
Authors: Qin Sanbo , Zhou Huan‐Xiang
Published: May 2010

In CAPRI rounds 13–19, we submitted models that are of acceptable or higher quality for 6 of the total of 13 targets. This success builds on our record in previous CAPRI rounds. The docking problem can be divided into two steps. In the first, translational/rotational and conformational space is searched to generate a pool of docked poses; the success of this search step is measured by whether near‐native poses are included in the pool. In the second step, the pool is selected for near‐native poses. In our previous assessment of CAPRI results, we suggested that the search problem is largely solved; a remaining problem is to select near‐native poses. Our work in these new rounds of CAPRI was guided by this assessment. To solve the selection problem, we used an assortment of criteria on the interfaces of candidate poses. In one extreme, represented by T29, with very little known interface information, our criterion for top models was based on interface prediction. Poses in which the predicted interface residues occurred in interfaces were selected. Our model 1 for T29 was of medium quality. In the other extreme, represented by T40, with reliably known interface information, our selection was solely based on such information. Nine of the ten models submitted for T40 were of high (3 models), medium (4 models), and acceptable (2 models) quality. Our strategy of mixing predicted and known interface information appears to be widely applicable for the selection of near‐native poses. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Optimization of pyDock for the new CAPRI challenges: Docking of homology‐based models, domain–domain assembly and protein‐RNA binding
Authors: Pons Carles , Solernou Albert , Perez‐Cano Laura , Grosdidier Solène , Fernandez‐Recio Juan
Published: May 2010

We describe here our results in the last CAPRI edition. We have participated in all targets, both as predictors and as scorers, using our pyDock docking methodology. The new challenges (homology‐based modeling of the interacting subunits, domain–domain assembling, and protein‐RNA interactions) have pushed our computer tools to the limits and have encouraged us to devise new docking approaches. Overall, the results have been quite successful, in line with previous editions, especially considering the high difficulty of some of the targets. Our docking approaches succeeded in five targets as predictors or as scorers (T29, T34, T35, T41, and T42). Moreover, with the inclusion of available information on the residues expected to be involved in the interaction, our protocol would have also succeeded in two additional cases (T32 and T40). In the remaining targets (except T37), results were equally poor for most of the groups. We submitted the best model (in ligand RMSD) among scorers for the unbound‐bound target T29, the second best model among scorers for the protein‐RNA target T34, and the only correct model among predictors for the domain assembly target T35. In summary, our excellent results for the new proposed challenges in this CAPRI edition showed the limitations and applicability of our approaches and encouraged us to continue developing methodologies for automated biomolecular docking. Proteins 2010. © 2010 Wiley‐Liss, Inc.
The targets of CAPRI Rounds 13–19
Authors: Janin Joël
Published: May 2010

Seven rounds of CAPRI predictions with a total of 14 targets were held in the period June 2007–November 2009. In addition to protease/inhibitor complexes and complexes with G‐proteins, some of the targets displayed novel features presenting new challenges to the predictors: a complex with RNA, a leucine zipper to be built abinitio, and a human‐designed protein. Nine targets were unbound or required model building; the other five had a bound component. Thirteen were assessed, and the results show that the predictor and scorer groups submitted two‐ or three‐star (medium or high quality) models for eight of them, one‐star (acceptable) models for three but failed on the unbound RNA complex and another unbound target. Proteins 2010. © 2010 Wiley‐Liss, Inc.
A new reactive sputtering technique for the low temperature deposition of transparent light emitting ZnS:Mn thin films
Authors: Wakeham Steve , Thwaites Mike , Tsakonas Costas , Cranton Wayne , Ranson Robert , Boutaud Gabriel , Koutsogeorgis Demosthenes
Published: May 2010

The temperature sensitive nature of the substrates used in the flexible displays market necessitates a low temperature deposition technique for processing them. ZnS:Mn exhibiting high intensity photoluminescence (PL) and good crystallinity has been deposited onto Si wafers, glass microscope slides and polymeric substrates using a new reactive sputtering technology referred to as HiTUS. This technique enables very high deposition rates and requires no substrate heating. When incorporated as part of a complete EL device, as‐deposited ZnS:Mn films are seen to exhibit stable electroluminescence on Si, glass and planarised PET substrate materials. Post annealing of the devices on Si and glass at temperatures of up to 600 °C show that the HiTUS films perform better than equivalent ZnS:Mn films deposited using RF magnetron sputtering.
An index of local sensitivity to non‐ignorability for multivariate longitudinal mixed data with potential non‐random dropout
Authors: Mahabadi S. Eftekhari , Ganjali M.
Published: May 2010

Multivariate longitudinal data with mixed continuous and discrete responses with the possibility of non‐ignorable missingness are often common in follow‐up medical studies and their analysis needs to be developed. Standard methods of analysis based on the strong and the unverifiable assumption of missing at random (MAR) mechanism could be highly misleading. A way out of this problem is to start with methods that simultaneously allow modelling non‐ignorable mechanism, which includes somehow troubling computations that are often time consuming, then we can use a sensitivity analysis, in which one estimates models under a range of assumptions about non‐ignorability parameters to study the impact of these parameters on key inferences. A general index of sensitivity to non‐ignorability (ISNI) to measure sensitivity of key inferences in a neighborhood of MAR model without fitting a complicated not MAR (NMAR) model for univariate generalized linear models and for models used for univariate longitudinal normal and non‐Gaussian data with potentially NMAR dropout are well presented in the literature. In this paper we extend ISNI methodology to analyze multivariate longitudinal mixed data subject to non‐ignorable dropout in which the non‐ignorable dropout model could be dependent on the mixed responses. The approach is illustrated by analyzing a longitudinal data set in which the general substantive goal of the study is to better understand the relations between parental assessment of child's antisocial behavior and child's reading recognition skill. Copyright © 2010 John Wiley & Sons, Ltd.
Some drop‐the‐loser designs for monitoring multiple doses
Authors: Joshua Chen Y. H. , DeMets David L. , Gordon Lan K. K.
Published: May 2010

A scenario not uncommon at the end of a Phase II clinical development is that although choices are narrowed down to two to three doses, the project team cannot make a recommendation of one single dose for the Phase III confirmatory study based upon the available data. Several ‘drop‐the‐loser’ designs to monitor multiple doses of an experimental treatment compared with a control in a pivotal Phase III study are considered. Ineffective and/or toxic doses compared with the control may be dropped at the interim analyses as the study continues, and when the accumulated data have demonstrated convincing efficacy and an acceptable safety profile for one dose, the corresponding dose or the study may be stopped to make the experimental treatment available to patients. A decision to drop a toxic dose is usually based upon a comprehensive review of all the available safety data and also a risk/benefit assessment. For dropping ineffective doses, a non‐binding futility boundary may be used as guidance. The desired futility boundary can be derived by using an appropriate combination of risk level (i.e. error rate for accepting null hypothesis when the dose is truly efficacious) and spending strategy (dropping a dose aggressively in early analyses versus late). For establishing convincing evidence of the treatment efficacy, three methods for calculating the efficacy boundary are discussed: the Joint Monitoring (JM) approach, the Marginal Monitoring method with Bonferroni correction (MMB), and the Marginal Monitoring method with Adjustment for correlation (MMA). The JM approach requires intensive computation especially when there are several doses and multiple interim analyses. The marginal monitoring methods are computationally more attractive and also more flexible since each dose is monitored separately by its own alpha‐spending function. The JM and MMB methods control the false positive rate. The MMA method tends to protect the false positive rate and is more powerful than the Bonferroni‐based MMB method. The MMA method offers a practical and flexible solution when there are several doses and multiple interim looks. Copyright © 2010 John Wiley & Sons, Ltd.
Influence of limestone particle size on iron ore sinter properties and productivity
Authors: Umadevi T. , Bandopadhyay U.K. , Mahapatra P.C. , Prabhu M. , Ranjan Madhu
Published: May 2010

Iron ore fluxed sinter is the main ferrous burden of Jindal south west steel limited (JSWSL) blast furnaces. In sinter plant fluxes including limestone and dolomite are added to improve the sinter properties of iron ore and to provide an appropriate slag composition of the blast furnace. The raw material grain size affects the sinter process considerably because the sinter productivity and quality are strongly dependent on the green permeability of the bed, which is determined by the particle size distribution of the raw materials, the granulation effectiveness and by the sintering process itself. It is well‐known that in fluxed sinter, the size of limestone affects productivity and physical and metallurgical properties of the sinter. It is therefore necessary to understand the role of limestone particle size on sinter properties and productivity. In the present work laboratory sintering experiments have been carried out with different levels of limestone mean particle size (from 0.14 to 1.83mm) to understand the influence of limestone particle size on mineralogy, productivity, physical and metallurgical properties of the sinter. Sinter productivity increased with increasing limestone mean particle size due to improved sinter bed permeability. Sinter with limestone mean particle size of 1.25 to 1.52 mm yielded better sinter strength and lower RDI compared to sinter with smaller or larger limestone mean particle size. Higher sinter strength is due to better and uniform distribution of limestone particles, and better bed permeability enabled easy assimilation and effective distribution of calcium ferrite phases. The improvement in sinter RDI is due to change in mineralogy of the sinter compared to coarser and finer limestone mean particle size.
Decoded Calreticulin-Deficient Embryonic Stem Cell Transcriptome Resolves Latent Cardiophenotype
Authors: Faustino Randolph S. , Chiriac Anca , Niederlander Nicolas J. , Nelson Timothy J. , Behfar Atta , Mishra Prasanna K. , Macura Slobodan , Michalak Marek , Terzic Andre , Perez-Terzic Carmen
Published: May 2010

Genomic perturbations that challenge normal signaling at the pluripotent stage may trigger unforeseen ontogenic aberrancies. Anticipatory systems biology identification of transcriptome landscapes that underlie latent phenotypes would offer molecular diagnosis before the onset of symptoms. The purpose of this study was to assess the impact of calreticulin-deficient embryonic stem cell transcriptomes on molecular functions and physiological systems. Bioinformatic surveillance of calreticulin-null stem cells, a monogenic insult model, diagnosed a disruption in transcriptome dynamics, which re-prioritized essential cellular functions. Calreticulin-calibrated signaling axes were uncovered, and network-wide cartography of undifferentiated stem cell transcripts suggested cardiac manifestations. Calreticulin-deficient stem cell-derived cardiac cells verified disorganized sarcomerogenesis, mitochondrial paucity, and cytoarchitectural aberrations to validate calreticulin-dependent network forecasts. Furthermore, magnetic resonance imaging and histopathology detected a ventricular septal defect, revealing organogenic manifestation of calreticulin deletion. Thus, bioinformatic deciphering of a primordial calreticulin-deficient transcriptome decoded at the pluripotent stem cell stage a reconfigured multifunctional molecular registry to anticipate predifferentiation susceptibility toward abnormal cardiophenotype.
Tumor Necrosis Factor Receptors Support Murine Hematopoietic Progenitor Function in the Early Stages of Engraftment
Authors: Pearl-Yafe Michal , Mizrahi Keren , Stein Jerry , Yolcu Esma S. , Kaplan Ofer , Shirwan Haval , Yaniv Isaac , Askenasy Nadir
Published: May 2010

Tumor necrosis factor (TNF) family receptors/ligands are important participants in hematopoietic homeostasis, in particular as essential negative expansion regulators of differentiated clones. As a prominent injury cytokine, TNF-α has been traditionally considered to suppress donor hematopoietic stem and progenitor cell function after transplantation. We monitored the involvement of TNF receptors (TNF-R) 1 and 2 in murine hematopoietic cell engraftment and their inter-relationship with Fas. Transplantation of lineage-negative (lin−) bone marrow cells (BMC) from TNF receptor-deficient mice into wild-type recipients showed defective early engraftment and loss of durable hematopoietic contribution upon recovery of host hematopoiesis. Consistently, cells deficient in TNF receptors had reduced competitive capacity as compared to wild-type progenitors. The TNF receptors were acutely upregulated in bone marrow (BM)-homed donor cells (wild-type) early after transplantation, being expressed in 60%–75% of the donor cells after 6 days. Both TNF receptors were detected in fast cycling, early differentiating progenitors, and were ubiquitously expressed in the most primitive progenitors with long-term reconstituting potential (lin−c-kit+ stem cell antigen (SCA)-1+). BM-homed donor cells were insensitive to apoptosis induced by TNF-α and Fas-ligand and their combination, despite reciprocal inductive cross talk between the TNF and Fas receptors. The engraftment supporting effect of TNF-α is attributed to stimulation of progenitors through TNF-R1, which involves activation of the caspase cascade. This stimulatory effect was not observed for TNF-R2, and this receptor did not assume redundant stimulatory function in TNFR1-deficient cells. It is concluded that TNF-α plays a tropic role early after transplantation, which is essential to successful progenitor engraftment.
Glutathione‐S‐transferase in Nereis succinea (Polychaeta) and its induction by xeno‐estrogen
Authors: Ayoola James A. O. , García‐Alonso Javier , Hardege Jörg D.
Published: May 2010

The need to replace or at least to reduce the use of vertebrates in toxicity tests is a timely major concern in research and industry but to date, efforts made to minimize their use are still far from complete. Increasing demands for toxicity tests put considerable pressures upon the development of future fast and efficient test methods using invertebrates. In fact, to date, few studies provide links between biochemical and cellular effects of xeno‐estrogens in aquatic invertebrates. Glutathione‐S‐transferase (GST) activity, as a biomarker of stress exposure, was measured in the population of clamworms (Nereis succinea) from Cardiff Bay. In addition, we examined the effect of single exposure to nonylphenol (NP) on this enzymatic activity. Field study results showed a relationship between the worm's size, reproductive status, and GST activity from the field population. In addition, we show a significant increase in the GST activity at 100 μg/L NP with sex‐specific responses. The xeno‐estrogens, which could affect reproduction of nereid by interfering in normal endocrinological pathways, are eliminated through GST by conjugation with glutathione. This work shows for the first time that GST activity depends on sex and stage of the clamworms and also that the xeno‐estrogen NP induces its activity. This study supports the use of this species as a bioindicator of aquatic pollution and lays the foundation to causally link toxic exposure with reproductive output. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.
A new in vitro screening bioassay for the ecotoxicological evaluation of the estrogenic responses of environmental chemicals using roach (Rutilus rutilus) liver explant culture
Authors: Gerbron Marie , Geraudie Perrine , Rotchell Jeanette , Minier Christophe
Published: May 2010

There is growing evidence that many chemicals released in the environment are able to disturb the normal endocrinology of organisms affecting the structure and function of their reproductive system. This has prompted the scientific community to develop appropriate testing methods to identify active compounds and elucidate mechanisms of action. Of particular interest are in vitro screening methods that can document the effects of these endocrine disrupting compounds on fish. In this study, an in vitro bioassay was developed in the roach (Rutilus rutilus) for evaluating the estrogenicity or antiestrogenicity potency of environmental pollutants by measuring vitellogenin (VTG) induction in cultured liver explants. The cell viability was assessed by the measurement of nonspecific esterase activity using a fluorescein diacetate hydrolysis assay. Results showed that explants could be cultured for 72 h without any significant loss of activity. Dose‐dependent responses have been measured with estrogenic model compounds such as 17‐β‐estradiol (E2) and 17‐α‐ethynylestradiol (EE2) or antiestrogenic compounds such as tamoxifen. Lowest observable effective concentrations were 1 nM for E2, 1 nM for EE2, and 100 nM for tamoxifen, showing a good sensitivity of the test system. Estrogenicity of butyl 4‐hydroxybenzoate, 4‐nonylphenol, and bisphenol A was tested. bisphenol A (100 μM) or butylparaben induced a twofold increase in VTG production when compared with 100 nM E2, whereas this production was only 20% with 100 μM 4‐nonylphenol. Overall, this study shows that the bioassay could provide valuable information on endocrine disrupting chemicals including metabolites and mixtures of compounds. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.
ISTA 14—in‐situ accumulation of PAHs in low‐density polyethylene membranes in sediment
Authors: Devault Damien A. , Combe Matthieu , Gourlay‐Francé Catherine
Published: May 2010

The use of passive samplers for the assessment of organic contaminants has been extended to solid matrixes for the past decade. Passive sampling is usually applied to sediment in laboratory experiments involving significant upheaval, whereas in‐situ experiments remain rare. In this study, low‐density polyethylene (LDPE) strips were deployed within the sediments of a small river contaminated with polycyclic aromatic hydrocarbons (PAHs). LDPE strips were deployed in the 3‐cm depth sediment layer. Over a period of 36 days, LDPE strips were regularly retrieved and accumulated PAHs in LDPE were extracted and analyzed. Accumulations of hydrophobic contaminants in LDPE directly exposed in the sediment were observed. Accumulations in LDPE were observed for moderately hydrophobic PAHs with the highest concentrations in the sediment. Low accumulations were observed for more hydrophobic compounds, despite their presence in high concentrations in the sediment. This was explained by very low exchange rates and competitive interactions with particles in the sediment. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.
Hexavalent chromium‐induced multiple biomarker responses in liver and kidney of goldfish, Carassius auratus
Authors: Velma Venkatramreddy , Tchounwou Paul B.
Published: May 2010

Hexavalent chromium [Cr (VI)] is a constituent of chromite ore. Although it is known to have several industrial and technological applications, its release into the aquatic environment as a result of chemical spill or inadequate waste discharge may hamper the health of aquatic organisms. In this study, we have investigated the effects of Cr (VI) on multiple biomarkers responses in goldfish under subchronic exposure conditions. Laboratory‐acclimatized fish were exposed to 4.25 ppm and 8.57 ppm Cr (VI) for four weeks using a continuous flow‐through system. During exposure, fish samples were collected on a weekly basis and analyzed for multiple biomarkers including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), metallothionein (MT), and total protein in liver and kidney. Study results indicated that the CAT activity and total protein levels in Cr (VI) ‐ treated goldfish did not significantly differ (P > 0.05) from their respective controls during experimentation. However, highly significant up‐regulations (P < 0.05) of SOD, GPx, and MT expression in Cr (VI) ‐ treated goldfish were recorded at different exposure times depending on Cr (VI) concentration, test organ, and/or biomarker of interest. For example, significantly higher liver GPx levels were found at weeks 2 and 3 in the 4.25 ppm concentration, and at weeks 3 and 4 in the 8.57 ppm, while kidney GPx levels were significantly higher at weeks 1, 2 and 3 in the 4.25 ppm concentration, and at weeks 2, 3 and 4 in the 8.57 ppm concentration. In summary, Cr (VI)‐induced oxidative stress was characterized by statistically significant increases in SOD, GPx, and MT expression in goldfish tissues; with the kidney showing a relatively higher sensitivity to Cr (VI) toxicity compared with the liver. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2011.
Brominated diphenyl ether (BDE) levels in liver, adipose, and milk from adult and juvenile rats exposed by gavage to the DE‐71 technical mixture
Authors: Bondy G. S. , Gaertner D. , Cherry W. , MacLellan E. , Coady L. , Arnold D. L. , Doucet J. , Rowsell P. R.
Published: May 2010

Brominated diphenyl ethers (BDEs) are used as flame retardants in consumer products. Rodent studies indicate that the liver, thyroid, and nervous system of developing animals are targets of BDEs. To explore the relationship between exposure and health in developing animals, BDE accumulation in adult and juvenile rats was examined in conjunction with changes in liver weight and serum thyroxine (T4). Adult (F0) rats received the commercial BDE mixture DE‐71 by gavage at doses of 0.5, 5, and 25 mg kg−1 body weight (bw)/day for 21 weeks. F0 rats were mated and exposure continued throughout breeding, pregnancy, lactation, and postweaning until the pups (F1 generation) reached postnatal day (PND) 42. Milk was collected from lactating dams. Adipose and liver samples were collected from F0 and F1 males and females for BDE congener analysis. Congener prevalence in rat tissues mimicked congener prevalence in wildlife and humans. Tissue concentrations of all congeners except BDE‐153 were lower than would be expected based on dose proportionality, confirming that BDE‐153 has a high capacity for bioaccumulation. BDEs were transferred from maternal tissues to milk during lactation. Milk congener profiles differed from maternal tissue profiles indicating that degree of bromination and maternal sequestration influenced BDE transfer to milk. Female F1 rats accumulated more BDEs than F1 males, indicating that female rats were less able to metabolize and/or excrete BDEs. Significant effects on liver weight and serum T4 levels were observed in adults and juveniles in the middle and high dose groups, corresponding to BDE levels in the μg g−1 range. Although it remains to be determined how human liver and thyroid are affected by exposure to much lower BDE levels, the present study confirmed that gender and reproductive status influence BDE accumulation in tissues and BDE transfer to the neonate via milk. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2011.