bluuebunny/crossref_metadata_2025 huggingface dataset:
NKX2-5GFP/w Human Embryonic Stem Cells Permit the Identification of Human Cardiac Progenitor Cells and Cardiomyocytes
Authors: Elliott David
Published: March 2012

Differentiation of human embryonic stem cells (hESCs) into cardiac progenitors is a powerful approach to dissect the molecular control of early human cardiogenesis. Cardiomyocytes can be derived from hESCs via the formation of embryoid bodies (EBs), which are cellular aggregates containing derivatives of all three germ layers that arise from differentiating hESCs. In order to identify, purify and characterize emerging cardiac progenitor cells (hESC-CPCs), we engineered a hESC line, NKX2-5GFP/w, in which GFP replaced the coding region of the conserved cardiac transcription factor NKX2-5. Using this line we have optimized a protocol for the differentiation of hESC-CPCs and cardiomyocytes (hESC-CMs) from hESCs in a 96-well plate format in serum free, chemically defined media that enables the precise and reproducible manipulation of differentiation conditions. EBs are formed by centrifugation (spin EBs). The combination of Activin A, bone morphogenetic protein 4 (BMP4), vascular endothelial growth factor (VEGF) and WNT 3a drives mesoderm formation until day three. Subsequently, the cytokine cocktail is replaced with media without growth factors and the EBs endogenous signaling networks control the specification of cardiovascular progenitors. Contractile foci are found in almost all EBs and all beating areas are GFP positive. Flow cytometric analysis for GFP demonstrates that up to 30 % of cells within the EB are NKX2-5 positive. The production of GFP+ cells is temporally restricted to day six and day nine of EB differentiation; after this time no further cardiac cells are specified. Electrophysiological studies show that the GFP+ CMs have a fetal phenotype. Expression analysis supports this finding demonstrating that NKX2-5+ hESC-CPCs and CMs constitute developmentally distinct populations with both having gene expression profiles closer to fetal heart than adult heart. Clonal analysis demonstrates that NKX2-5+ cells are capable of giving rise to the three major lineages in the heart, namely cardiomyocytes, smooth muscle and endothelium. Together, these data demonstrate that NKX2-5GFP/w hESC lines facilitate the identification, isolation and culture of human cardiovascular progenitors.

David A Elliott1*, Stefan R Braam2, Louise Lagerqvist3, Katerina Koutsis1, Rob Jenny1, Magdaline Costa1, Elizabeth Ng1, Tanya Hatzistavrou1, Rhys JP Skelton, Claire E Hirst1, Cissy Yu1, Ouda Khammy4, Xuleing Li1, Sue Mei Lim1, Richard P Davis2, Adam L Goulburn1, Robert Passier2, John M Haynes3, Colin W Pouton3, David M Kaye4, Christine L Mummery2, Andrew G Elefanty1 and Edouard G Stanley1.

1 Monash Immunology and Stem Cell Laboratories, Monash University, Victoria, 3800, Australia
2 Department of Anatomy and Embryology, Leiden University Medical Centre, Leiden, The Netherlands
3 Monash Institute of Pharmaceutical Science, Monash University, Parkville, Victoria 3052, Australia
4 Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, 3004, Australia
Prospective Isolation of Therapeutically Relevant Human Embryonic Stem Cell-derived Cardiovascular Progenitors
Authors: Ardehali Reza , Weissman Irving
Published: March 2012

Cardiomyocytes derived from human embryonic stem cells (hESCs) are promising candidates to regenerate myocardium as a treatment for heart disease. However, this application is limited because of the inability to prospectively identify a pure population of cardiovascular progenitors (CVPs) that is devoid of residual, undifferentiated cells capable of teratoma formation. Furthermore, the potential of hESC-derived cardiovascular lineage cells to functionally couple to human myocardium remains unknown. The purpose of the current study was to test the hypotheses that (i) CVPs derived from hESCs can be isolated based on a set of distinct surface markers and (ii) they can functionally integrate into the human fetal heart. We screened a large panel of monoclonal antibodies to prospectively identify early cardiovascular precursors that emerge from differentiating hESCs based on the expression of surface markers. We discovered four surface markers that highly enrich for CVPs: receptor tyrosine kinase-like orphan receptor family, ROR2, aminopeptidase-N, CD13, kinase insert domain protein receptor, KDR, and platelet-derived growth factor-α, PDGFRα. This quadruple positive population, or QP, gave rise to cardiomyocytes, endothelial cells, and vascular smooth muscle cells in vitro. We observed rare clusters of ROR2+ cells and diffuse expression of KDR and PDGFRα in first trimester human fetal hearts. Upon delivery of the QP cells into murine hearts, they developed into mature cardiomyocytes and endothelial cells, but failed to functionally integrate. While no teratomas were observed in the animals transplanted with QP cells, one out of the seven mice transplanted with the quadruple-negative cells developed teratoma in the heart. In contrast to traditional murine heart models for cell transplantation, delivery of the QP cells into human fetal hearts, heterotopically transplanted into rat’s abdomen, resulted in structural and functional integration of hESC-derived CVPs into human hearts. Taken together, we have shown for the first time that CVPs, defined by four novel surface markers, can structurally and functionally integrate into the electrical syncytia of a human fetal heart upon transplantation.
Professional guidelines and approaches to the ethical oversight of stem cell research
Authors: Sugarman Jeremy
Published: March 2012

The extraordinary excitement over the scientific, medical, and financial possibilities of stem cell research has been accompanied by ethical concerns. As a consequence, professional groups have developed approaches to addressing these concerns across the continuum of stem cell research, from bench to bedside and to publication. Prominent approaches that have received considerable traction include those developed by the National Academy of Sciences, the International Society for Stem Cell Research, and the Hinxton Group. Understanding and implementing such approaches promises to mitigate some of the ethical issues related to stem cell research.
International stem cell policies
Authors: Matthews Kirstin
Published: March 2012

After the first isolation of human embryonic stem cells was reported in 1998, many countries reviewed their national policies regarding human embryo research. During this process, several countries amended current policies or created new policies to specifically address human embryonic stem cell research. These policies can be classified in three broad categories: restrictive, permissive with limits, or permissive. Over this 13 year period, there has been a global trend to transition policies from restrictive to more permissive. These shifts have occurred due to the efforts of scientists who have advocated for policy harmonization. While countries still possess a range of policies, this attempt towards harmonization has had a positive impact on the field by improving the quality and quantity of international scientific collaborations. This talk will review national stem cell policies, describe how international collaborations have been fostered under such policies, and discuss the impact of these international collaborations in the field of stem cell research.
Conceptual and practical considerations for material and data sharing in stem cell research
Authors: Kato Kazuto
Published: March 2012

Rapid development in the stem cell field, particularly in the field of pluripotent stem cells, resulted in the establishment of many cell lines, including those of ES cells and iPS cells. Some cell lines were made with the help of public funding while others with private money. The way stem cells are used also varies depending on the purpose of the types of research or medical applications. Regardless of the source of funding or the way cells are used, one important question is how to decide policies for sharing materials and data.

On one hand, to accelerate innovation and commercialization, one may need to admit that obtaining IPs and not sharing research materials and data need to be prioritized for researchers and companies. On the other hand, to facilitate overall research activities and speed up medical innovation, one can say that sharing materials and data should be encouraged by researchers and even by the business sector.

Regarding the latter view, we can learn some lessons from genome research areas, where notions of equity, justice and benefit sharing have been emphasized throughout the history of the field. One well-known example is Bermuda principle formulated in 1996. The principle declared that genome sequence data in the Human Genome Project (HGP) should be released into the public domain as soon as data is produced. One reason behind the principle was to emphasize that human genome data should not be privately owned by a few, but needs to be utilized by all of the researchers around the world. Another reason is a kind of moral consideration – human genome research should give benefit to the people of the society where advanced biomedical science cannot be conducted. The concept has been inherited in many subsequent research activities and has become a basic norm for genome research areas. I would like to argue that stem cell research community needs to learn the same notion of sharing and to pay attention to the concept of global equity and benefit sharing. Moreover, to actually facilitate sharing of materials and data, various points need to be considered. For example, informed consent that enables sharing of cells and data should be obtained. I will talk about conceptual reasoning as well as practical points to facilitate material and data sharing in the stem cell field.
Secreted Noncoding RNAs and Therapeutic Neural Stem Cell Plasticity
Authors: Pluchino Stefano
Published: March 2012

Compelling evidence exists that somatic stem cell-based therapies protect the central nervous system (CNS) from chronic inflammation-driven degeneration, such as that occurring in experimental autoimmune encephalomyelitis (EAE), multiple sclerosis (MS) and cerebral ischemic/hemorrhagic stroke. However, while it was first assumed that stem cells may act through direct replacement of lost/damaged cells, it has now become clear that they are able to protect the damaged nervous system through a number of ‘bystander’ mechanisms other than cell replacement. In immune-mediated experimental demyelination and stroke – both in rodents and non-human primates – others and we have shown that transplanted neural stem/precursor cells (NPCs) possess a constitutive and inducible ability to mediate efficient ‘bystander’ myelin repair and axonal rescue. Yet a comprehensive understanding of the multiple mechanisms by which NPCs exert their therapeutic impact is lacking. We envisage that the remarkable therapeutic plasticity of NPCs results from their capacity to engage highly sophisticated programmes of horizontal cell-to-cell communication at the level of the (micro) environment and we attribute a key role to the transfer of secreted membrane vesicles (MVs) from (donor) NPCs to (recipient) neighbouring cells. We are starting to define whether this form of communication is biologically relevant for NPCs, and look forward to establishing whether it is associated to cell-to-cell trafficking of non-coding RNAs (ncRNAs), and indeed on elucidating its molecular signature and therapeutic significance for MS. We believe that the true innovation of this approach relies in its unique peculiarity to look into an innate cellular mechanism with the visionary focus of translating the knowledge of basal stem cell functions into innovative high-impact clinical therapeutics for MS.
Subependymal zone stem cells and progenitor migration to brain injuries: a critical analysis
Authors: Szele Francis
Published: March 2012

Adult neurogenesis in mammals was rediscovered over twenty years ago and has generated a huge amount of interest as a developmental biology system to study stem cells, proliferation, fate determination and migration. It has also raised hope that these cells may be harnessed to help repair brain injury and disease. Indeed subependymal zone (SEZ) progenitors actively migrate to brain injuries and help replace dead cells and provide protective trophic support. Whereas human neurogenesis after infancy is quite minimal it seems to increase after most degenerative brain diseases. I will argue that more post mortem examination of human neurogenesis is needed. I will also present data from my laboratory that has shown the epidermal growth factor receptor and galectin-3 both modulate migration of SEZ cells. These and other molecular mechanisms may be manipulated to increase the reparative response. We are examining SEZ migration with 2-Photon time-lapse microscopy a technique which allows high temporal spatial resolution of dynamic events. This is helping us discern the natural history of these fascinating tissue specific stem and progenitor cells. We believe this is essential for the field to develop their potential clinical use.
Establishing a Legal Foundation for Public Oversight of Clinical Trials
Authors: Frankel Mark
Published: March 2012

Public (government) oversight reflects the way society perceives and responds to risk, which is intrinsic to the conduct of experimental research. Such oversight typically takes the form of regulation, which combines organizations, rules and sanctions intended to produce desired behaviors in support of clear objectives. Ensuring a rigorous clinical trial process that also offers proper protections of research subjects requires a legal framework that features the following qualities: (1) must act, and be seen to act, in the public interest; (2) comprised of clear and explicit objectives and requirements; (3) fairness in its application and enforcement; (4) based on dialogue among regulators, the regulated community, and the beneficiaries of regulation; (5) sustains public confidence and trust; and (6) is more likely than other options to achieve its goals. While these features will be applied to stem cell clinical trials, they are also relevant in other areas where science and technology are perceived as posing risks to individuals and/or the larger society.
What We Need in the GCC States to Catch-up with Evolving Stem Cell and Regenerative Medicine Research
Authors: Al Othman Saleh Fahed
Published: March 2012

Every year we witness the introduction of new drugs and medical technologies that improve the health and lives of individuals around the world. Stem cell research holds an awesome potential for restructuring the way we practise medicine. One day, stem cell researches will dramatically alter the way we treat diseases.

Since the first human ES cell lines were derived more than a decade ago, hundreds have been created worldwide, including lines suitable for clinical application. As such, it involves questions of ethics that are commonly raised in research, such as preserving research integrity and the use of human tissue and animals in research. Moreover, there is much to be investigated about the specific characteristics of stem cells and about the efficacy and safety of the new drugs based on this type of cells, both embryonic and adult stem cells, for several therapeutic indications.

The current reality is that, although extensive researches are ongoing and encouraging partial results are being achieved, there is still much to do in the GCC states to orchestrate the stem cell and regenerative medicine research.
Attachment of Embryonic Stem Cells-derived Cardiomyocytes in Cultispher-S Microcarriers by using Spinner flask
Authors: Akasha Abdulrhaman Ahmed
Published: March 2012

Embryonic Stem cells have the ability to differentiate under in vitro conditions into cardiomyocytes. A transgenic α-myosin heavy chain (α-MHC+) ES cell line was generated, exhibiting puromycin resistance and expressing enhanced green fluorescent protein (EGFP) under control of the α-MHC+ promoter. A puromycin-resistant, EGFP-positive α-MHC+ cardiomyocyte population was isolated with over 92 percent purity.

The cultivation of these cardiomyocytes, in macroporous gelatine microsphere beads in a spinner flask bioreactor has been studied. The average number of cultivated cells per microsphere was optimised after we specified the most suitable agitation conditions and the optimal time frames of cultivation. Our study shows that 80 percent of microspheres were colonised by cardiomyocytes under optimal conditions. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to show that the population of the beads was not limited to the microcarrier surface, but some cells invaded the inner surfaces of the microspheres as well.

The present findings demonstrate the successful culture of α-MHC+ cardiomyocytes in macroporous biodegradable microcarriers while maintaining the typical morphological and electrophysiological properties of cardiomyocytes. Our perspective significantly improves survival of grafted cardiomyocytes and thus helps to overcome current limitations of cell replacement approaches
Gene Expression Profiling of Embryonic Human Neural Stem Cells and Dopaminergic Neurons from Adult Human Substantia Nigra
Authors: Marei Hany , Althani Asma , Afifi Nahla , Michetti Fabricio , Pescatori Mario , Pallini Roberto , Casalbore Patricia , Cenciarelli Carlo , Schwartz Philip , Ahmed Abd-Elmaksoud
Published: March 2012

Neural stem cells (NSC) with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat neurodegenerative insults such as Parkinson's disease. We used Agilent's and Illumina Whole Human Genome Oligonucleotide Microarray to compare the genomic profiles of human embryonic NSC at a single time point in culture, and a multicellular tissue from postmortem adult substantia nigra (SN) which are rich in dopaminergic (DA) neurons. We identified 13525 up-regulated genes in both cell types of which 3737 (27.6%) genes were up-regulated in the hENSC, 4116 (30.4%) genes were up-regulated in the human substantia nigra dopaminergic cells, and 5672 (41.93%) were significantly up-regulated in both cell population. Careful analysis of the data that emerged using DAVID has permitted us to distinguish several genes and pathways that are involved in dopaminergic (DA) differentiation, and to identify the crucial signaling pathways that direct the process of differentiation.

The set of genes expressed more highly at hENSC is enriched in molecules known or predicted to be involved in the M phase of the mitotic cell cycle. On the other hand, the genes enriched in SN cells include a different set of functional categories, namely synaptic transmission, central nervous system development, structural constituents of the myelin sheath, the internode region of axons, myelination, cell projection, cell somata, ion transport, and the voltage-gated ion channel complex. Our results were also compared with data from various databases, and between different types of arrays, Agilent versus Illumina. This approach has allowed us to confirm the consistency of our obtained results for a large number of genes that delineate the phenotypical differences of embryonic NSCs, and SN cells.
Mechanotransduction Modulates the Effect of Mechanical Forces (fluid shear stress and cyclic strain) on Embryonic Stem Cell Differentiation toward Vascular Endothelial and Smooth Muscle Cells
Authors: Nikmanesh Maria , Shi Zhong-Dong , Tarbell John
Published: March 2012

It has been shown that shear stress plays a critical role in promoting endothelial cell (EC) differentiation from embryonic stem cell (ESC)-derived ECs. However, the underlying mechanisms mediating shear stress effects in this process have yet to be investigated. It has been reported that the glycocalyx component heparan sulfate proteoglycan (HSPG) mediates shear stress mechanotransduction in mature EC.

In this study, we investigated whether cell surface HSPG plays a role in shear stress modulation of EC phenotype. ESC-derived EC were subjected to shear stress (5 dyn/cm(2) ) for 8h with or without heparinase III (Hep III) that digests heparan sulfate. Immunostaining showed that ESC-derived EC surfaces contain abundant HSPG, which could be cleaved by Hep III. We observed that shear stress significantly increased the expression of vascular EC-specific marker genes (vWF, VE-cadherin, PECAM-1. The effect of shear stress on expression of tight junction protein genes (ZO-1, OCLD, CLD5) was also evaluated. Shear stress increased the expression of ZO-1 and CLD5, while it did not alter the expression of OCLD. Shear stress increased expression of vasodilatory genes (eNOS, COX-2), while it decreased the expression of the vasoconstrictive gene ET1. After reduction of HSPG with Hep III, the shear stress-induced expression of vWF, VE-cadherin, ZO-1, eNOS, and COX-2, were abolished, suggesting that shear stress-induced expression of these genes depends on HSPG. These findings indicate for the first time that HSPG is a mechanosensor mediating shear stress-induced EC differentiation from ESC-derived EC cells.
Comprehensive Transcriptome and Proteome Analysis of Human Embryonic Stem Cells Differentiation to Neural Cells
Authors: Salekdeh Ghasem Hosseini
Published: March 2012

Human embryonic stem cells (hESCs) are pluripotent cells capable of differentiating into other cell lineages in vivo. Global gene expression analysis of hESCs that differentiate into neural cells would help to further define the molecular mechanisms involved in neurogenesis in humans. We performed a comprehensive transcriptome and proteome analysis of hESC differentiation at three different stages: early neural differentiation, neural ectoderm and differentiated neurons. We identified and validated time-dependent gene expression patterns and showed that the gene expression patterns reflect early ESC differentiation. Sets of genes are induced in primary ectodermal lineages and then in differentiated neurons, constituting consecutive waves of known and novel genes. Pathway analysis revealed dynamic expression patterns of members of several signaling pathways, including NOTCH, mTOR and Toll like receptors (TLR), during neural differentiation. Owing to comparative proteomics and transcriptomics analyses, novel genes involved in proliferation of rosette cells, fate specification and neural differentiation were identified. Functional analysis with RNAi figured up that suppression of a protein involved in mRNA processing, MAGOHB, enhanced the neural differentiation of hESCs. Collectively, these results enhance our understanding of the molecular dynamics underlying neural commitment and differentiation.
Solution of Wave Equation in Radial Form by VIM
Authors: Aminikhah Hossein
Published: March 2012

An analytic approximation to the solution of wave equation is studied. Wave equation is in radial form with indicated initial and boundary conditions, by variational iteration method it has been used to derive this approximation and some examples are presented to show the simplicity and efficiency of the method.
Effect of Topical Application of Different Substances on Fibroplasia in Cutaneous Surgical Wounds
Authors: Abreu Andreza Miranda , Oliveira Dhelfeson Willya Douglas , Marinho Sandra Aparecida , Lima Nádia Lages , de Miranda João Luiz , Verli Flaviana Dornela
Published: March 2012

Background. Fibroblasts on the edges of a surgical wound are induced to synthesize collagen during the healing process which is known as fibroplasia.Objective. The aim of this study was to determine the effect of the application of different substances on fibroplasia of cutaneous surgical wounds on rats.Materials and Methods. 48Wistarrats were divided into three groups. A surgical wound 1 cm in diameter and 1  mm in depth was created on the dorsum of each animal. The surgical wounds were submitted to the topical application of an alcoholic extract of 30% propolis, 70% alcohol, or 0.001% dexamethasone in a cream base every 12 hours. The animals were sacrificed three, seven, 14, and 28 days postoperatively. The specimens were histologically processed and stained with Masson’s trichrome. The assessment of fibroplasia was performed using a scoring system: (1) 5 to 25% collagen deposition; (2) 26 to 50% collagen deposition; (3) 51 to 75% collagen deposition; (4) more than 75% collagen deposition.Results. There were statistically significant differences in collagen deposition between the substances at all postoperative evaluation times.Conclusion. Propolis and alcohol promoted greater collagen deposition in surgical wounds than dexamethasone.
Elemental Studies of Soil and Food Flour for Risk Assessment of Highway Pollution Using Particle-Induced X-Ray Emission (PIXE) Spectrometry
Authors: Asubiojo O. I. , Adebiyi F. M. , Obiajunwa E. I. , Ajao J. A.
Published: March 2012

The study investigated potential toxic elements in soils and food flours for highway pollution using PIXE spectrometry. The contaminated soils and cassava food flours contained higher levels of the elements than their control samples, while comparison with their standard permissible limits followed similar trend which was attributable to anthropogenic influences. These were corroborated by their elevated Enrichment factor, Pollution index and Geoaccumulation index values for the elements, suggesting significant anthropogenically—derived contaminations of the soils. T-test value (0.038) for the elemental composition of the contaminated soils & cassava flours was significant due to considerable higher concentrations of the elements in the soils than the cassava flours. Cross plot analysis result for the contaminated soils and cassava fours showed moderate positive correlation (R2 = 0.426), indicating inter-element relationship between them. Cluster analysis results for the analyzed elements in the contaminated soil samples indicated that Mn, Fe, V, Cr, Zn, Cl, Ti and S showed closest inter-element clustering and was corroborated by the results of Pearson correlation matrices, while inter-element clustering in the food flour followed the same trend and was also supported by their results of Pearson correlation matrices, validating that the soils and cassava flours were contaminated via similar sources.
Perceptions and Practices: A Survey of Professional Engineers and Architects
Authors: Cunningham Don , Stewart Jill
Published: March 2012

This descriptive cross-sectional research study examines perceptions of time spent by architects and professional engineers on reading, writing, and evaluating various information products, as well as their perspectives of specific quality characteristics and the relative significance in meeting work goals. Professional engineers and architects were surveyed at seminars held at eight locations in seven states. Descriptive statistics were then used to investigate perceptions and relationships. Findings indicate architects and professional engineers spend the most amount of time reading correspondence and the least amount of time reading management reports. Respondents considered correspondence to be the most important reading activity. Participants also spend the most amount of time writing correspondence, closely followed by nearly equal time spent writing and editing technical reports and proposals. Finally, participants rated organization, comprehensiveness, and accuracy as the most important aspects while indicating mechanical issues such as grammar and spelling as the least important aspects of technical documents.
Medial Approach to the Sciatic Nerve at the Popliteal Fossa in the Supine Position with Ultrasound Guidance and Nerve Stimulator
Authors: Yanaru Tomoaki , Shigematsu Kenji , Higa Kazuo , Nakamori Erisa , Nitahara Keiichi
Published: March 2012

Ultrasound guided sciatic nerve block (SNB) at the popliteal fossa is performed with the lateral approach in the supine position or with the lateral or posterior approach in the prone position. When the sciatic nerve (SN) is blocked with the lateral approach in the supine position, the lower limb must be sufficiently elevated to enable adequate space around the knee joint for transducer application. When the SN is blocked in the prone position, the patients’ position needs to be changed. We report a medial approach to the SNB at the popliteal fossa in the supine position with ultrasound guidance. Ten patients scheduled for elective knee or foot surgery participated in this study. Patients were placed in the supine position, with the hip and knee on the operated side flexed and the thigh externally rotated at approximately 45 degrees. A block needle was inserted in-plane with the transducer toward the SN bifurcation from the medial side of the thigh. The block performance time for SNB was  min (1.3–3.1 min). All blocks were effective. Our medial approach to the SN in the supine position with ultrasound guidance does not require elevation of the patient’s lower limb or a change in the patient’s position.
The Association between EEG Abnormality and Behavioral Disorder: Developmental Delay in Phenylketonuria
Authors: Karimzadeh Parvaneh , Alaee Mohammad Reza , Zarafshan Hadi
Published: March 2012

Background. Brain defect leading to developmental delay is one of the clinical manifestations of phenylketonuria. The aim of this study was to evaluate the association between EEG abnormality and developmental delay/behavioral disorders in phenylketonuria. Patients and Methods. 105 phenylketonuria patients, who were diagnosed through newborn screening tests or during follow-up evaluation, were enrolled. Patients who were seizure-free for at least six months before the study were included. The developmental score were evaluated by the ASQ questionnaire (age-stage questionnaire) and the test of child symptom inventory-4 (CSI-4), respectively. Results. 55 patients had a history of seizure more than 6 months before the study. Seventy had abnormal EEG (cases) and 35 had normal EEG (controls). There was no significant difference between mean phenylalanine levels in the abnormal and normal EEG groups at the time of diagnosis, after six months and at our evaluation. Distribution of DQ level in the abnormal and normal EEG groups revealed a significant difference. An abnormal EEG was associated with a higher percentage of low DQ levels. Conclusion. Paroxysmal epileptic discharges in PKU patients are important. Treatment of these EEG abnormalities may affect developmental scores or may lead to correction of some behavioral disorders in patients.
A web-based application to simulate alternatives for sustainable forest management: SIMANFOR
Authors: Bravo F. , Rodriguez F. , Ordóñez C.
Published: March 2012

Growth and yield models at different scales are useful tools for forest stakeholders. Adequate simulation of forest stand conditions after different silvicultural scenarios allows stakeholders to adopt appropriate actions to maintain forest integrity while forest products and services are obtained to benefit society as a whole. SIMANFOR is a platform to simulate sustainable forest management alternatives, integrating different modules to manage forest inventories, simulate and project stand conditions and maintain systems security and integrity. SIMANFOR output is compatible with an Office environment (Microsoft or Open), allowing users to exchange data and files between SIMANFOR and their own software. New developments are being planned under a web 2.0 environment to take advantage of user input to improve SIMANFOR in the future.
The round wood market in Greece: An empirical approach
Authors: Zafeiriou E. , Arabatzis G. , Koutroumanidis Th.
Published: March 2012

The present study aims to determine the factors affecting the producer price of the industrial round wood. The factors examined as determinants of the producer price are the volume of domestic production, imports and exports of the industrial round wood in Greece. As a proxy for the producer price, the round wood of long length (> 2m) price is employed. For the achievement of the aforementioned objective, Johansen cointegration technique was implemented. The results confirmed the existence of a sole long-run relationship between the variables studied while the estimation of the vector error correction model indicated a statistically significant speed in the long-term equilibrium. The implementation of the Granger causality test has shown that the producer’s price is affected by the imported volume while the domestic production is determined by the volume of exports. Finally, the producer prices are determined by the exports and the imports of the Greek wood sector and vice versa. All the aforementioned results are consistent with the classic supply-demand economic theory.
Multi-functional approach in forest landscape management planning: an application in Southern Italy
Authors: Paletto A. , Ferretti F. , Cantiani P. , De Meo I.
Published: March 2012

Forest Landscape Management Plan (FLMP) is intended to have an intermediate role between forest management plans on a regional level and forest management on a unit level. FLMP addresses long-term management issues, with special attention to social and environmental functions, normally not meticulously considered when working on a single forest property level. This paper presents a method to evaluate forest multifunctionality, in order to define management guidelines and support forest planning. A FLMP was conducted in a district of the Basilicata region (Italy). A total of 92 inventory plots comprising the main forest types: i) turkey oak, Hungarian oak, and sessile oak forests (Quercus cerris L. dominant), ii) downy oak forests (Quercus pubescens Willd. dominant), iii) Mediterranean evergreen oak forests (Quercus ilex L. dominant), were considered. Technicians evaluated the multifunctionality of each area by estimating — in the context of an Index of Importance of Function (I) — the capacity of each forest to fulfil different functions. The index was successively aggregated according to forest type and forest system (high forest and coppice). The results showed that the higher level of multifunctionality was found in the high forests. According to the synthetic indicators of multifunctionality, the turkey oak forests obtained the highest values among all forest types. The last part of the paper illustrates an approach to multi-functional forest management, analysing how different silvicultural systems are able to fulfil the main forest functions. This method, as shown in the results, seems to provide a useful support for technicians to evaluate multifunctionality related to forest types and different silvicultural treatments.
Public perception on forestry issues in the Region of Valencia
Authors: Fabra-Crespo M. , Mola-Yudego B. , Gritten D. , Rojas-Briales E.
Published: March 2012

Are the policies designed by decision-makers differing from society’s wishes and preferences? The present paperanalyzes the divergences between forest policy and public opinion in the Region of Valencia (Comunidad Valenciana)in Eastern Spain. The data is based on an extensive telephone survey of the general public on their perception of forestryissues. The issues studied include attitudes regarding forest fires, silvicultural treatments, the externalities producedby forest owners, and the state forest service’s role related to these issues. In total, the answers of 823 respondentswere analyzed using classification trees. The results of the analysis showed a large divergence between the desires,preferences and priorities of society, on the one hand, and the policies implemented by the regional government, onthe other. The study concludes that communication strategies concerning sustainable forest management need to befurther developed by the responsible authorities, with the input of the research community.
Biomass expansion factors for Eucalyptus globulus stands in Portugal
Authors: Soares P. , Tomé M.
Published: March 2012

One of several procedures for estimating carbon stocks in forests is the estimation of tree or stand biomass based on forest inventory data. The two approaches normally used to convert field measurements of trees to stand biomass values are allometric biomass equations and biomass expansion factors (BEFs). BEFs are used in published National Forest Inventory results in which biomass is not estimated or as a complement of growth models that do not include biomass predictions. In this paper, the effectiveness of BEFs for estimating total stand biomass in Portuguese Eucalyptus globulus plantations was analyzed. Here, BEF is defined as the ratio of total stand biomass (aboveground biomass plus root biomass) to stand volume with bark. To calculate total biomass, an equation was developed to estimate root biomass as a function of aboveground biomass. Changes of BEF with stand variables were analyzed. Strong relationships were observed between BEF and stand age, stand basal area, stand volume and dominant height. Consequently, an equation to predict BEF as a function of stand variables was fitted, and dominant height was selected as the predictor stand variable. Estimates of total stand biomass based on individual tree allometric equations were compared with estimates obtained with a constant BEF (0.77), used in the Portuguese National Inventory Report on Greenhouse Gases, and with estimates obtained using the dominant height-dependent BEF equation developed in this work. The BEF prediction model proposed in this work may be used to improve E. globulus Portuguese biomass estimates when tree allometric equations cannot be used.
Forest road and fuelbreak siting with respect to reference fire intensities
Authors: Eastaugh C.S. , Molina D.M.
Published: March 2012

Forest roads and permanent fuelbreaks are an important part of fire suppression infrastructure, but due to maintenance and environmental costs many forest agencies seek to reduce the extent of these networks. The question of which roads should be retained or where fuelbreaks should be established is contentious, and few quantified methods exist to aid management decisions. This study uses GIS procedures and develops a metric for road network vulnerability, which may be used to determine the relative effectiveness of a road network or a particular fuelbreak as a fire control line. The method constructs ‘reference fire’ intensities, and compares the fire intensity at roadsides or fuelbreaks with the overall forest average. In the case study area in Victoria’s Central Highlands (southeast Australia), average fire intensities on the forest road network are found to closely match the forest average, indicating that roads in their current locations are not skewed towards more dangerous parts of the forest. The fuelbreak network however is likely to face fire intensities substantially greater than those in the average forest area.
Selected Common Diagnostic Problems in Urologic Pathology: Perspectives From a Large Consult Service in Genitourinary Pathology
Authors: Brimo Fadi , Epstein Jonathan I.
Published: March 2012

Context.—Several common differential diagnoses are encountered in urologic pathology, frequently causing patient referrals for a second opinion.

Objectives.—To review 3 common differential diagnoses encountered in a large consultation service in genitourinary pathology, including partial atrophy versus prostatic acinar adenocarcinoma, oncocytoma versus chromophobe renal cell carcinoma, and urothelial carcinoma in situ versus normal urothelium and reactive atypia. We will discuss the detailed, morphologically distinctive features and the usefulness of immunohistochemistry.

Data Sources.—Personal experience and review of the current literature.

Conclusions.—Careful morphologic assessment and awareness of diagnostic pitfalls are fundamental in reaching a definitive diagnosis in most cases. Immunohistochemistry is useful but should be used only in conjunction with the morphologic impression.
Emerging Critical Role of Molecular Testing in Diagnostic Genitourinary Pathology
Authors: Netto George J. , Cheng Liang
Published: March 2012

Context.—The unprecedented advances in cancer genetics and genomics are rapidly affecting clinical management and diagnostics in solid tumor oncology. Molecular diagnostics is now an integral part of routine clinical management in patients with lung, colon, and breast cancer. In sharp contrast, molecular biomarkers have been largely excluded from current management algorithms of urologic malignancies.

Objective.—To discuss promising candidate biomarkers that may soon make their transition to the realm of clinical management of genitourologic malignancies. The need for new treatment alternatives that can improve upon the modest outcome so far in patients with several types of urologic cancer is evident. Well-validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management are lacking. Identifying robust predictive biomarkers that will stratify response to emerging targeted therapeutics is another crucially needed development. A compiled review of salient studies addressing the topic could be helpful in focusing future efforts.

Data Sources.—A PubMed (US National Library of Medicine) search for published studies with the following search terms was conducted: molecular, prognostic, targeted therapy, genomics, theranostics and urinary bladder cancer, prostate adenocarcinoma, and renal cell carcinoma. Articles with large cohorts and multivariate analyses were given preference.

Conclusions.—Our recent understanding of the complex molecular alterations involved in the development and progression of urologic malignancies is yielding novel diagnostic and prognostic molecular tools and opening the doors for experimental targeted therapies for these prevalent, frequently lethal solid tumors.
Role of Immunohistochemistry in Diagnosing Renal Neoplasms: When Is It Really Useful?
Authors: Shen Steven S. , Truong Luan D. , Scarpelli Marina , Lopez-Beltran Antonio
Published: March 2012

Context.—With the refinement of molecular and histologic classifications of renal neoplasms and the availability of more-effective molecular targeted therapy for specific renal neoplasms, immunohistochemical techniques will play an increasingly important role in the diagnosis of renal neoplasm. During the past few decades, many markers have been evaluated for their role in the diagnosis, prognosis, and prediction of treatment for renal neoplasms. The number of useful markers in our routine practice continues to increase. The challenge will be to choose among them and to decide in which situations immunohistochemistry will be truly useful.

Objectives.—To review the diagnostic utility of molecular markers for renal neoplasms and common diagnostic scenarios that call for immunohistochemistry in routine practice.

Data Sources.—This review is based on published literature and personal experience.

Conclusions.—Some of the most important and useful markers for the diagnosis of renal neoplasm include cytokeratins, vimentin, PAX2, PAX8, RCC marker, CD10, E-cadherin, kidney-specific cadherin, parvalbumin, claudin-7, claudin-8, α-methylacyl coenzyme A racemase, CD117, TFE3, thrombomodulin, uroplakin III, p63, CD57, and carbonic anhydrase IX. Each marker has its diagnostic role in a specific diagnostic setting. The common diagnostic situations that call for immunohistochemical staining are differential diagnoses of renal versus nonrenal neoplasms, histologic subtyping of renal cell carcinoma, diagnosis of rare primary renal neoplasms, diagnosis of renal neoplasms in small core-biopsy specimens, diagnosis of possible metastatic renal carcinomas, and less frequently, molecular prognostication.
Spectrum of Preneoplastic and Neoplastic Cystic Lesions of the Kidney
Authors: Chen Ying-Bei , Tickoo Satish K.
Published: March 2012

Context.—Cystic lesions of the kidney may be accompanied by a range of neoplasms with distinct prognoses and future risks of developing additional tumors. In addition, some renal tumors, with or without accompanying renal cysts, may show a prominent cystic component. In the adult population, neoplasms occurring in a background of renal cystic diseases and cystic renal neoplasms often pose diagnostic challenges because of their many overlapping features.

Objective.—To review the clinicopathologic characteristics of common entities in the spectrum of neoplastic and potential preneoplastic cystic lesions encountered in adults, with an emphasis on renal cystic diseases associated with tumor development and on renal neoplasms with predominantly cystic morphology.

Data Sources.—The relevant English-language literature was reviewed, accompanied by the authors' experience at their practicing institution.

Conclusions.—The presence of multiple renal cysts, both acquired and syndromic, can be associated with a variety of renal tumors. The morphology of the cysts and associated tumor types can help predict the genetic or acquired basis of the lesions, and particularly in specimens with no accompanying pertinent clinical history, such potential associations should be suggested in surgical pathology reports.
Phosphine‐Catalyzed [3+2] and [4+3] Annulation Reactions of C,N‐Cyclic Azomethine Imines with Allenoates
Authors: Jing Chengfeng , Na Risong , Wang Bo , Liu Honglei , Zhang Lei , Liu Jun , Wang Min , Zhong Jiangchun , Kwon Ohyun , Guo Hongchao
Published: March 2012

Phosphine‐catalyzed [3+2] and [4+3] annulation reactions of C,N‐cyclic azomethine imines with allenoates have been developed to give a variety of pharmaceutically attractive tetrahydroisoquinoline derivatives in moderate to excellent yields. The two distinct reaction pathways, [3+2] and [4+3] cyclization, depend on the nature of the nucleophilic phosphine and the allenoate. Generally, for α‐alkylallenoates, the reactions always proceed with [3+2] cyclization as the major pathway no matter what phosphine was used; for α‐ArCH2‐substituted allenoates, the reaction pathway was controlled by the phosphine catalyst used.
Click Functionalization of Gold Nanoparticles Using the Very Efficient Catalyst Copper(I) (Hexabenzyl)tris(2‐aminoethyl)‐ amine Bromide
Authors: Zhao Pengxiang , Grillaud Maxime , Salmon Lionel , Ruiz Jaime , Astruc Didier
Published: March 2012

Whereas previous “click” functionalization (Huisgen‐type copper‐catalyzed alkyne‐azide cycloaddition, CuAAC) of various gold nanoparticles (AuNP) had systematically proven to be very difficult, tedious, providing low yields with the use of high amounts of copper sulfate+sodium ascorbate – the classic Sharpless catalyst, the new catalyst copper(I) (hexabenzyl)tris(2‐aminoethyl)amine bromide, {[Cu(I)(Hexabenzyl)Tren]Br} is shown here to be very efficient for the introduction of a large variety of organic, organometallic, dendronic and polymeric molecular fragments of various sizes, topologies and hydrophilicities. Indeed, 0.1–0.15 equiv. of this catalyst in toluene was used in each reaction under ambient conditions for 8 to 48 h with good yields without AuNP aggregation. The new functional AuNP have been characterized by 1H NMR, IR and UV‐vis. (plasmon band) spectroscopy, cyclic voltammetry (CV), dynamic light scattering (DLS) and transmission electron microscopy (TEM).