bluuebunny/crossref_metadata_2025 huggingface dataset:
Socioeconomic Position, Co-Occurrence of Behavior-Related Risk Factors, and Coronary Heart Disease: the Finnish Public Sector Study
Authors: Kivimäki Mika , Lawlor Debbie A. , Smith George Davey , Kouvonen Anne , Virtanen Marianna , Elovainio Marko , Vahtera Jussi
Published: March 2007

Objectives. We examined the associations between socioeconomic position, co-occurrence of behavior-related risk factors, and the effect of these factors on the relative and absolute socioeconomic gradients in coronary heart disease.

Methods. We obtained the socioeconomic position of 9337 men and 39 255 women who were local government employees aged 17–65 years from employers’ records (the Public Sector Study, Finland). A questionnaire survey in 2000–2002 was used to collect data about smoking, heavy alcohol consumption, physical inactivity, obesity, and prevalence of coronary heart disease (myocardial infarction or angina diagnosed by a doctor).

Results. The age-adjusted odds of coronary heart disease were 2.1–2.2 times higher for low-income groups than high-income groups for both men and women, and adjustment for risk factors attenuated these associations by 13%–29%. There was no further attenuation with additional adjustment for the number of co-occurring risk factors, although socioeconomic disadvantage was associated with the co-occurrence of multiple risk factors. The absolute difference in coronary heart disease risk between socioeconomic groups could not be attributed to the measured risk factors.

Conclusions. Interventions to reduce adult behavior-related risk factors may not completely remove socioeconomic differences in relative or absolute coronary heart disease risk, although they would lessen these effects.
Race and the Politics of Polio
Authors: Rogers Naomi
Published: March 2007

The Tuskegee Institute opened a polio center in 1941, funded by the March of Dimes. The center’s founding was the result of a new visibility of Black polio survivors and the growing political embarrassment around the policy of the Georgia Warm Springs polio rehabilitation center, which Franklin Roosevelt had founded in the 1920s before he became president and which had maintained a Whites-only policy of admission. This policy, reflecting the ubiquitous norm of race-segregated health facilities of the era, was also sustained by a persuasive scientific argument about polio itself: that Blacks were not susceptible to the disease.

After a decade of civil rights activism, this notion of polio as a White disease was challenged, and Black health professionals, emboldened by a new integrationist epidemiology, demanded that in polio, as in American medicine at large, health care should be provided regardless of race, color, or creed.
Water purification: from ancient civilization to the XXI Century
Authors: Danil de Namor A.F.
Published: March 2007

Ancient civilization valued the vital role of water in human life. As reflected in the literature, environmental awareness led to early water treatments and these are briefly described in this paper. Thus the period prior to 500 BC to 1000 AD saw the use of naturally occurring materials for water purification, the building of aqueducts, and the introduction of the distillation process. This was followed by a dormant period of five centuries in which hardly any progress was made in water purification methodology. From the 17th to the 19th century, progress was made on filtration processes and the introduction of the microscope. In addition chemical methods for water disinfection by the use of chlorine and ozone were reported. These methods and their combination progressed significantly through the 20th century. However the problems associated with chemical contamination of ground water, from which, drinking water is mainly generated remained practically ignored for about five decades. It was in the late seventies that this was brought to light. Since then technologies for groundwater purification started to emerge but a lot remains to be done in this area of research. The crucial role of suitable analytical tools for any technological development which aim to remove toxic pollutants from water is acknowledged. Thus the need of re-visiting old methodology making use of the advantages resulting from the availability of advanced analytical techniques and the possibility of enriching naturally occurring materials by the introduction of supramolecular receptors for water decontamination purposes are emphasized.
Rainwater harvesting in ancient civilizations in Jordan
Authors: AbdelKhaleq R.A. , Alhaj Ahmed I.
Published: March 2007

One might think that locations of settlements through history depended on the existence of a nearby permanent water source. Wåhlin thinks that anthropologists and geographers seem to have missed that people in settlements in many parts of the Middle East were able to create for themselves a near-permanent water supply in places where nature was not kind enough to place a river or a spring. Several sites in Jordan provide examples of these creations. Despite an arid to semi-arid climate, several civilizations have started and flourished in these conditions. This paper summarizes the types of systems that people have used through history to develop reliable water supplies in this part of the world. Jawa was a settlement in northern Jordan during the Bronze Age that built an extensive hydraulic system. At Um El Jimal, a city in northern Jordan during the Byzantine era, deflection dams, canals and reservoirs provided a local water supply. Neabateans excelled in water management using cut-stone reservoirs in their capital, Petra, and their empire flourished more than 2500 years ago in what is now southern and central Jordan. Underground cisterns found in Umayyad desert castles in different parts of the country reveal similar activities during the Islamic era. Examining how water resources were managed long ago can provide relevant information in facing the water-resources challenges of today in arid lands.
A review of Ancient Roman water supply exploring techniques of pressure reduction
Authors: Monteleone M.C. , Yeung H. , Smith R.
Published: March 2007

The Ancient Roman water supply systems still leave us astonished when admiring the solidity of the ruins of aqueducts surviving around Europe. Some parts of these systems are still in use at present and prove the practical efficiency of Roman hydraulics in the principles acquired from the populations living in the different regions of the Empire. In Pompeii the urban water supply system stands as a clear example of the Roman planning of urban complex networks by using small water towers to serve a limited numbers of users. This allowed to control the derivations and their maintenance and operated a disconnection from the high pressure mains and the low pressure pipes, maintaining a fixed maximum height of water over the final points of discharge. Considering the techniques for pressure reduction as a method to control leakages, this paper examines the ancient Roman water supply system to deduce some applications to modern urban networks built in new housing establishments.
Aqueducts in the Hellenic area during the Roman period
Authors: Mavromati E. , Chryssaidis L.
Published: March 2007

Since their very beginnings, organized societies have been concerned with the preservation and improvement of their environment and natural resources as these were the basis of their wellbeing and survival. In pursuing this goal, many civilizations have constructed admirable technical and infrastructural works. To most of us, however, the society that stands out for its particular preoccupation and special widespread achievements in this field is the Roman Empire which actively demonstrated great interest for its cities and the providing for their everyday basic livelihood needs. The creation of most urban centres was combined with the construction of aqueducts, water supply and wastewater systems. During the Roman occupation period (200 BC–300 AD) of the Hellenic world, many cities within the region expanded and new urban centres were created. Substantial steps were taken to upgrade the urban landscape and to improve their living conditions. This was connected with water supply and wastewater systems, comprising aqueducts, water towers and underground pipe systems. The investigation of the criteria that determined engineers' design choices for aqueducts, methods and processes of construction, techniques and materials used - as these are revealed through the archaeological excavations and relics - testify to the environmental approach and the maintenance perception of the Roman period.
Potable water and sanitation in Tenochtitlan: Aztec culture
Authors: Becerril J.E. , Jiménez B.
Published: March 2007

A source of clean drinking water is essential, and the Aztecs were quite advanced in providing it. While London still drew its drinking water from the polluted Thames River as late as 1854, the Aztecs brought potable water to Tenochtitlán from springs on the mainland by means of the aqueduct built by Nezahualcoyotl between 1466 and 1478. A second aqueduct was constructed in 1,499–1,500 by the ruler Ahuizotl when the first aqueduct became inadequate. Although the Aztecs had no citywide drainage system, and much of the wastewater ended up in the lake surrounding the city, they had a system to handle human waste by means of privies in all public places and many private dwellings from which excrement was collected in canoes. The excrement was applied as fertilizer to chinampas (floating parcels of land) or sold in the market to be used for tanning animal hides. Urine was collected in pottery vessels to be used later as a mordant for dyeing cloth. The Tenochtitlán environment was obviously healthy for its time, especially in comparison to European cities. Public and personal hygiene contributed to minimize the incidence and severity of illnesses.
Overview of the history of water resources and irrigation management in the Near East region
Authors: Bazza M.
Published: March 2007

The Near East region extends from Turkey in the north to Somalia in the south and from Mauritania in the west to Afghanistan in the east. It is characterized by aridity and scarcity of water which explains its dependence on irrigation since ancestral times. The aim of this paper is to give a brief overview of the history of water management and irrigation developments in the region, based on remnants and bibliographical research, with a focus on ancient water management techniques and ingenious irrigated agriculture practices, including the use of non conventional water resources. The implications and impacts of these techniques on modern management of water resources and irrigated agriculture are also discussed.
Ancient water catchment techniques for proper management of Mediterranean ecosystems
Authors: Laureano P.
Published: March 2007

Traditional knowledge from the ancient techniques and practices of a territory passed on through the generations and used for water harvesting, soil management, use and protection of natural areas, rural architecture, and for organising urban centres. Today, traditional knowledge is in danger and its disappearance would not only cause the loss of people's capability to keep and pass on the artistic and natural heritage, but also the loss of an extraordinary source of knowledge and cultural diversity from which appropriate innovative solutions could be derived today and in the future. UNESCO launched a global programme for an inventory assigned to IPOGEA -Research Centre on Traditional and Local Knowledge. The project gathers and protects historical knowledge and promotes and certifies innovative practices based on the modern re-proposal of tradition as well. The main targets are the firms, the natural areas, and the historical centres which will be assigned quality trademarks and acknowledgements of international excellence in production or use of good practices and innovative solutions. Each technology, proposition and experience achieved will provide a spin-off on an international scale and each good practice will contribute to safeguarding the whole planet.
A voyage to Ancient Greek Harbours on board Limenoscope
Authors: Theodoulou T. , Memos C.
Published: March 2007

Limenoscope is a web based database aiming at promoting the cultural heritage regarding ancient Greek harbours and disseminate the relevant information equally to the general public and to researchers with an interest in that particular cognitive field. The scope of the project is the realization of a database, where one can search for concise information relevant to the historical role, the topography, the morphology, as well as the technical works and installations of ancient harbours in the Mediterranean and the Black Sea. The Database started off with the registration of harbours located in the Aegean Sea and Cyprus, dating from Archaic to Byzantine times. Special emphasis is laid on the bibliographical update of the data forms of the harbour sites, as well as on the related references in ancient literature. The database enables the locating of these sites on a general map, where photographs, plans etc. are also archived. The principles of the database structure are briefly presented along with an example, that of the harbour of Phalasarna, among the harbours registered therein.
The Water in the Royal Monastery of Santa Maria De Poblet, Tarragona, Spain
Authors: De la Peña J.L. , De la Peña M. , Salgot M. , Torcal Ll.
Published: March 2007

The history and water-related features in the Poblet Cistercian Monastery, located in Tarragona province, Spain are described. The study is undertaken with the main purpose of obtaining data for the establishment of an integrated water management system inside the walls of the abbey, which is suffering water scarcity due to increasing demands and the prevalent semiarid conditions.
Overview of Pharmacogenetics
Authors: Katz David A.
Published: March 2007

Pharmacogenetics is the study of relationships between genetic variation and inter‐individual differences with respect to drug response. As the field has matured over the past 15 years, a remarkable diversity of pathways, variation types, and mechanisms have been found to be relevant pharmacogenetic factors. Today, pharmacogenetics is becoming more important in pharmacology for target validation, lead optimization, and understanding of idiosyncratic toxicity. This unit provides an overview of the history of pharmacogenetics and current research applications in drug discovery, as well as a discussion of research quality issues relevant to human subjects research in the pharmacogenetics laboratory.
A Convenient Stereochemical Notation for P‐Chiral Nucleotide Analogs
Authors: Sobkowski Michal , Stawinski Jacek , Kraszewski Adam
Published: March 2007

The DP/LP convention is a stereochemical notation for P‐chiral nucleotide analogs and related compounds. In contrast to the absolute RP/SP notation, the DP/LP system is based on a geometrical relationship between substituents in a dinucleoside monophosphate skeleton. The DP/LP notation is a convenient alternative to the RP/SP notation for stereochemical correlation analysis of physical, chemical, and biological properties of nucleotide and oligonucleotide analogs bearing any type of tri‐ or tetra‐coordinated phosphorus moiety.
Maintenance and In Vitro Differentiation of Mouse Embryonic Stem Cells to Form Blood Vessels
Authors: Kappas Nicholas C. , Bautch Victoria L.
Published: March 2007

Embryonic stem (ES) cells, which are derived from developing mouse blastocysts, have the capacity to give rise to all cell types in the adult body. The ability of ES cells to do so has opened the door for novel experimental approaches in the field of developmental biology. Under appropriate culture conditions, ES cells will differentiate and form embryoid bodies (EBs). Upon attachment to a permissive surface, EBs continue a programmed differentiation, and many of the cells differentiated from the EBs reflect those found in the developing embryo and yolk sac, such as hematopoietic cells, endoderm, and endothelial cells. Endothelial cells that arise during ES cell differentiation have the potential to form primitive blood vessels, comparable to the vessels that first form in vivo. This unit describes protocols for maintaining ES cells and the subsequent differentiation of EBs. This unit also provides methods for analyzing vascular marker expression in differentiated ES cultures.
Induction of ES Cell–Derived Cartilage Formation
Authors: Kramer Jan , Schlenke Peter , Rohwedel Jürgen
Published: March 2007

This unit describes the protocols used for cultivation of murine embryonic stem (ES) cells and their differentiation into chondrogenic cell types in vitro. ES cells cultivated as cellular aggregates, so‐called embryoid bodies (EBs), differentiate spontaneously into chondrogenic cell types recapitulating cellular events of chondro‐ and osteogenesis. The undifferentiated ES cells differentiate into mesenchymal prechondrogenic cells in the EB outgrowths. These progenitor cells aggregate and form mesenchymal condensations. During further cultivation, these cells form cartilage nodules, show a phenotype typical for chondroblasts, and start to express marker molecules of cartilage tissue. Later, the chondrocytes become hypertrophic, and finally, marker molecules indicating bone formation can be detected in the nodules. This unit also contains protocols for characterization of the differentiated cells by immunostaining, mRNA‐in situ hybridization, electron microscopy, and RT‐PCR analysis.
Maximum‐Likelihood Analysis Using TREE‐PUZZLE
Authors: Schmidt Heiko A. , von Haeseler Arndt
Published: March 2007

TREE‐PUZZLE provides a means to analyze and reconstruct evolutionary relationships and trees based on quartets, i.e., groups of four sequences. Basic Protocol 1 explains how to reconstruct trees based on the maximum‐likelihood principle and quartet puzzling. Basic Protocol 2 discusses likelihood mapping, a method to visualize phylogenetic content in a multiple sequence alignment. Basic Protocol 3 explains how to compare tree topologies using different tests.
Assembling Genomic DNA Sequences with PHRAP
Authors: de la Bastide Melissa , McCombie W. Richard
Published: March 2007

The PHRAP assembly program provides rapid comparison, alignment, and assembly of large sets of DNA sequences. PHRAP compares sequences by searching for pairs of perfectly matching “words” or sequence regions that meet certain criteria. If a match is found, PHRAP then tries to extend the alignment into overlapping sections called contigs. PHRAP uses quality values produced by the PHRED basecaller to strike a balance between tolerance of discrepancies and prevention of stacking repeat sequences. The PHRAP assembly algorithm is generally used as part of the PHRED/PHRAP/Consed software suite for sequence analysis. This unit presents instructions for basic usage of the PHRAP assembler, including preparation of the input files (Support Protocols 1 and 2) and explanation of output files (Basic Protocols 1 and 2). Several command line options for changing the PHRAP assembly parameters are also discussed (Basic Protocol 3).
Hexamethylene diisocyanate crosslinking 2‐hydroxypropyltrimethyl ammonium chloride chitosan/poly(acrylonitrile) composite nanofiltration membrane
Authors: Huang Rui‐Hua , Chen Guo‐Hua , Sun Ming‐Kun , Gao Cong‐Jie
Published: March 2007

The effects of membrane preparation conditions on membrane properties were studied in detail. The results suggested that composite nanofiltration (NF) membrane from 2.0 wt % 2‐hydroxypropyltrimethyl ammonium chloride chitosan (HACC) vaporized for 2.5 h at 50°C, and then crosslinked for 9 h at 50°C with hexamethylene diisocyanate (HDI)/ethanol (0.45/50 wt/wt) were found to have optimal performance. The resultant membrane was called HACC/PAN [poly(acrylonitrile)] NF membrane. The characteristics of this membrane such as pure water permeability, molecular weight cut‐off, rejection of salts, and swelling were investigated. And its cut‐off molecular weight (MWCO) was ∼520 Da. At 25°C and 1.0 MPa, the permeability of water was 17.24 L/h m2 MPa. Swelling in water decreased and rejection of salts increased with increasing HDI concentration, indicating pore contraction and increase in hydrophobicity as well as pore tortuosity due to crosslinking. The order of rejection to different salt solutes followed the decreasing of CaCl2, MgCl2, NaCl, KCl, and Na2SO4, suggesting that this membrane was positively charged. The rejections to MgCl2 and CaCl2 were more than 0.90; therefore, this membrane can be used for hardness removal in water treatment process. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007.
Measuring fatigue in rheumatoid arthritis: A systematic review of scales in use
Authors: Hewlett S. , Hehir M. , Kirwan J. R.
Published: March 2007

Objective

Fatigue is an important outcome for patients with rheumatoid arthritis (RA). The purpose of this study was to identify the scales being used to measure RA fatigue, and to systematically examine the evidence for their validation.

Methods

Articles measuring fatigue in RA were sought using the terms RA and fatigue, and RA and tiredness, plus scale, questionnaire, inventory, and checklist. Index articles reporting identifiable RA fatigue data were examined for the fatigue scale used. Index and validation articles for each scale were reviewed for evidence supporting scale validation to measure RA fatigue using a standardized checklist of content, face, criterion, and construct validity, reliability, and sensitivity to change.

Results

A total of 61 index articles used 23 different fatigue scales to measure RA fatigue on 71 occasions. Seventeen scales had either no data on validation in RA or limited evidence. Reasonable evidence of validation was identified for 6 scales, each also having some evidence of sensitivity to change: ordinal scales, the Short Form 36 vitality subscale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, visual analog scales (VAS), the Profile of Mood States, and the RA‐specific Multidimensional Assessment of Fatigue scale (MAF). However, the 4 generic scales would benefit from further validation in patients with RA, the VAS requires standardization, and the MAF would benefit from further sensitivity data.

Conclusion

It was possible to identify evidence of reasonable validation for 6 of 23 scales being used to measure RA fatigue. Researchers and clinicians should select scales to measure RA fatigue carefully.
Computed tomography measurement of tophus volume: Comparison with physical measurement
Authors: Dalbeth Nicola , Clark Barnaby , Gregory Kate , Gamble Gregory D. , Doyle Anthony , McQueen Fiona M.
Published: March 2007

Objective

Computed tomography (CT) has high accuracy for tophus detection. This study assessed reliability of CT measurement of tophus volume and compared reproducibility of CT with physical measurement of tophus size.

Methods

Forty‐seven hand tophi were analyzed in 20 patients with gout. The longest tophus diameter was recorded by 2 independent observers. All patients proceeded to CT scanning of the hands on a Philips Brilliance scanner (0.8‐mm slices). Two independent observers measured tophus volume using the Surface Shaded Display 3‐dimensional function on the Philips CT workstation. Five patients underwent repeat physical and CT assessments within 1 week (18 observations). Inter‐ and intraobserver reproducibility were analyzed by limits of agreement and coefficients of variation.

Results

Of the 47 lesions identified as tophi on physical examination, 42 (89%) were also identified on CT. The mean (95% confidence interval [95% CI]) difference between observers for physical measurement was 0.45 mm (−4.07, 4.96) and for CT was 65.2 mm3 (−293.0, 423.3). The mean (95% CI) difference between visits for physical measurement was −0.72 mm (−5.47, 4.03) and for CT was −13.1 mm3 (−112.5, 86.3). There was no difference between coefficients of variation for inter‐ and intraobserver reproducibility for the 2 measurement techniques. For tophi identified by physical and CT assessment, there was good correlation between measurements (r = 0.91, P < 0.0001).

Conclusion

CT assessment of tophus volume is reliable and reproducible. However, physical measurement correlates well with CT and has equivalent reproducibility. These data support the use of physical measurement as a simple and reliable method to assess tophus size.
Work disability among two cohorts of women with recent‐onset rheumatoid arthritis: A survival analysis
Authors: Reisine S. , Fifield J. , Walsh S. , Dauser D.
Published: March 2007

Objective

To analyze factors associated with leaving employment among women with newly diagnosed rheumatoid arthritis (RA).

Methods

Women with RA were recruited from a national sample of rheumatologists in 1987 and 1998. Inclusion criteria were RA diagnosis <18 months earlier, age ≥18 years, and no other disabling health condition. The 1987 and 1998 cohorts comprised 48 and 91 women, respectively. Data were collected by telephone for 4 years. Survival analysis was conducted using Kaplan‐Meier curves and a proportional hazards generalized linear model to assess whether the time to stopping work differed between the cohorts and to identify baseline predictors and time‐varying covariates of leaving work.

Results

Most patients were age <50 years, married, had >12 years of education, and were white. Fifteen patients (31%) in the 1987 cohort and 24 patients (26%) in the 1998 cohort stopped working in the observation periods. Kaplan‐Meier survival curves for each cohort were not significantly different. Multivariate analyses demonstrated that married women (P = 0.03) and those with joint deformities (P = 0.00) were more likely to stop working. A significant flares by cohort interaction (P = 0.01) indicated that, in comparison with patients in the 1998 cohort, those in the 1987 cohort with <2 disease flares had the lowest risk of stopping work and those with ≥2 flares had the greatest risk.

Conclusion

Unexpectedly, the cumulative rate of stopping work among women in the 1998 study did not differ from that among women diagnosed >16 years earlier. However, disease flares greatly affected employment in the 1987 but not the 1998 cohort, possibly indicating that newer medications were effective in maintaining functional status among those with more severe disease activity, measured by number of flares, in the 1998 group.
Impact of health maintenance organizations and fee‐for‐service on health care utilization among people with systemic lupus erythematosus
Authors: Yelin Edward , Trupin Laura , Katz Patricia , Criswell Lindsey A. , Yazdany Jinoos , Gillis Joann , Panopalis Peter
Published: March 2007

Objective

To compare health care utilization in people with systemic lupus erythematosus (SLE) in health maintenance organizations (HMOs) and fee‐for‐service (FFS).

Methods

A structured survey was administered to a cohort of 982 people with SLE who were assembled between 2002 and early 2005. A total of 2,656 person‐years of observation were completed by the end of 2005. In each year, respondents reported their health care utilization and whether they had HMO or FFS coverage. We compared health care utilization of those in HMOs and FFS, with and without adjustment for socioeconomic, demographic, and health characteristics using repeated‐measures regression techniques.

Results

Compared with people with SLE who were in FFS, those in HMOs were younger (3.3 years), received a diagnosis at an earlier age (3.6 years), had slightly less disease activity (0.4 on a 10‐point scale), were more likely to be nonwhite (8.8%), were less likely to be below the poverty line (7.8%), and were less likely to have public insurance (29.7%). The 2 groups did not differ in other characteristics. On an unadjusted basis, subjects with SLE in HMOs had significantly fewer physician visits (3.1; 95% confidence interval [95% CI] 1.7, 4.5) and were less likely to report one or more outpatient surgical visits (6.3%; 95% CI 2.5, 10.0), and hospital admissions (5.5%; 95% CI 1.7, 9.3) than those in FFS. Adjustment reduced the differences in physician visits (2.3; 95% CI 1.1, 3.5), outpatient surgical rates (4.4%; 95% CI 0.6, 8.1), and hospital admission rates (4.0%, 95% CI 0.4, 7.7).

Conclusion

Subjects with SLE in HMOs utilized substantially less ambulatory care and were less likely to have outpatient surgery and hospital admissions than those in FFS; the effects were not completely explained by socioeconomic, demographic, and health characteristics.
Berechnung erdgedeckter Lagertanks nach Mang
Authors: Bußhaus Ludger
Published: March 2007

Erdgedeckte Lagertanks, die einzeln im gewachsenen Boden gelagert sind (“Grabenlagerung”) und eine Erdüberdeckung von mindestens 1000 mm aufweisen, können nach dem Verfahren von Windels [1] sehr wirtschaftlich dimensioniert werden. Dieses Verfahren wurde in [2] ausführlich beschrieben und um alle vorkommenden betrieblichen und Montage‐Lastfälle erweitert. Die übrigen erdgedeckten Lagertanks werden nach dem Verfahren von Mang [3] entsprechend den Vorgaben in [4] ausgelegt. Dieses Verfahren wird in diesem Beitrag erläutert.
Strategy for selecting and characterizing linker peptides for CBM9‐tagged fusion proteins expressed in Escherichia coli
Authors: Kavoosi Mojgan , Creagh A. Louise , Kilburn Douglas G. , Haynes Charles A.
Published: March 2007

The influence of linker design on fusion protein production and performance was evaluated when a family 9 carbohydrate‐binding module (CBM9) serves as the affinity tag for recombinant proteins expressed in Escherichia coli. Two bioinformatic strategies for linker design were applied: the first identifies naturally occurring linkers within the proteome of the host organism, the second involves screening peptidases and their known specificities using the bioinformatics software MEROPS™ to design an artificial linker resistant to proteolysis within the host. Linkers designed using these strategies were compared against traditional poly‐glycine linkers. Although widely used, glycine‐rich linkers were found by tandem MS data to be susceptible to hydrolysis by E. coli peptidases. The natural (PT)xP and MEROPS™‐designed S3N10 linkers were significantly more stable, indicating both strategies provide a useful approach to linker design. Factor Xa processing of the fusion proteins depended strongly on linker chemistry, with poly(G) and S3N10 linkers showing the fastest cleavage rates. Luminescence resonance energy transfer studies, used to measure average distance of separation between GFP and Tb(III) bound to a strong calcium‐binding site of CBM9, revealed that, for a given linker chemistry, the separation distance increases with increasing linker length. This increase was particularly large for poly(G) linkers, suggesting that this linker chemistry adopts a hydrated, extended configuration that makes it particularly susceptible to proteolysis. Differential scanning calorimetry studies on the PT linker series showed that fusion of CBM9 to GFP did not alter the Tm of GFP but did result in a destabilization, as seen by both a decrease in Tm and ΔHcal, of CBM9. The degree of destabilization increased with decreasing length of the (PT)xP linker such that ΔTm = −8.4°C for the single P linker. Biotechnol. Bioeng. 2007;98: 599–610. © 2007 Wiley Periodicals, Inc.
The novel MGC13096 protein is correlated with proliferation
Authors: Chen Qiu , Yan Chengqi , Yan Qingfeng , Feng Lifeng , Chen Jianping , Qian Kaixian
Published: March 2007

We report a functional characterisation of the novel protein MGC13096. MGC13096 over‐expression restrained proliferation of HEK293T cells. DNA/flow cytometry analysis showed that the over‐expression of MGC13096 severely delays cell cycle progression at S phase. Transcription factors such as activator protein‐1 (AP‐1), cAMP response element binding protein (CREB), nuclear factor of activated T cells (NFAT), NF‐κB, signal transducer and activator of transcription 1 (STAT1) took part in the process. Copyright © 2007 John Wiley & Sons, Ltd.
Pilot study to evaluate the safety and feasibility of intracoronary CD133+ and CD133− CD34+ cell therapy in patients with nonviable anterior myocardial infarction
Authors: Manginas Athanassios , Goussetis Evgenios , Koutelou Maria , Karatasakis George , Peristeri Ioulia , Theodorakos Athanassios , Leontiadis Evangelos , Plessas Nikolaos , Theodosaki Maria , Graphakos Stelios , Cokkinos Dennis V
Published: March 2007

Objectives: The long‐term effect of intracoronary infusion of progenitor cells in patients with chronic ischemic cardiomyopathy. Background: Bone marrow stem‐cell administration in patients with myocardial infarction improved myocardial performance and in some studies contributed to favorable left ventricular remodeling. Methods: We report on the results of a pilot, single center, controlled safety, and feasibility study, including 24 patients with old, nonviable anterior myocardial infarction. Twelve patients underwent intracoronary administration of selected CD133+ and CD133−CD34+ progenitor cells and 12 were followed up on medical therapy. Left ventricular volumes and ejection fraction, at rest and during low‐dose dobutamine, and myocardial viability, using TL‐201 reinjection scintigraphy, were analyzed at baseline and long‐term follow‐up. Results: Patients in the treatment group experienced a sustained decrease in left ventricular end‐diastolic and end‐systolic resting volumes (P = 0.008 and P = 0.002, respectively), as well as an improvement in global ejection fraction at rest [from (27.2 ± 6.8)% to (29.7 ± 7.3)%, P = 0.016]. Segmental anterior and apical wall perfusion, during TL‐201 reinjection, were similarly improved (P = 0.005 and P << 0.001, respectively). One patient developed restenosis at the cell delivery site and one progression of atherosclerosis. During 28.0 ± 8.7 months of clinical follow‐up, only one patient experienced deterioration of heart failure. In the control group, we observed stability in the perfusion defect and deterioration in end‐diastolic and end‐systolic volumes (P= 0.002 and P = 0.003, respectively) and a nonsignificant decrease in ejection fraction (P = 0.11). Conclusion: Intracoronary infusion of selected CD133+ and CD133−CD34+ progenitor cells to a previously infarcted and nonviable anterior wall is safe, and results in sustained improvement in segmental myocardial perfusion and in favorable left ventricular remodeling. © 2007 Wiley‐Liss, Inc.
Stent thrombosis with drug‐eluting stents: A re‐examination of the evidence
Authors: Kedia Gautam , Lee Michael S.
Published: March 2007

The excitement of drug‐eluting stents and their promise for reduced restenosis rates have been tempered by recent reports of stent thrombosis. The mechanism of stent thrombosis is multifactorial but appears to be related to delayed endothelialization and healing, late stent malapposition, and antiplatelet resistance. The most important risk factor appears to be the discontinuation of dual antiplatelet therapy. The data from clinical trials suggest that drug‐eluting stents are associated with increased incidence of death or myocardial infarction compared with bare metal stents at long‐term follow‐up, suggesting that the window of thrombotic risk with drug‐eluting stents may extend far beyond that for bare metal stents. Measures to possibly decrease the incidence of stent thrombosis include improvements in antiplatelet regimens and newer generation of drug‐eluting stents which have biodegradable polymers or are polymer‐free. In addition, percutaneous coronary intervention with bare metal stents in patients may be helpful in those known to be intolerant or noncompliant to antiplatelet therapy, have planned procedures or surgeries, or have overwhelming risks which may require discontinuation of dual antiplatelet therapy. © 2007 Wiley‐Liss, Inc.
Spontaneous Formation of Heteroligated PtII Complexes with Chelating Hemilabile Ligands
Authors: Ulmann Pirmin A. , Brown Aaron M. , Ovchinnikov Maxim V. , Mirkin Chad A. , DiPasquale Antonio G. , Rheingold Arnold L.
Published: March 2007

The spontaneous formation of the heteroligated complex [PtCl(κ2‐Ph2PCH2CH2SMe)(Ph2PCH2CH2SPh)]Cl (8 a) by a novel ligand rearrangement process has been observed. By using the weak‐link approach, the relative arrangement of the alkyl and aryl groups can be controlled by abstraction of chloride from 8 a to form the closed complex [Pt(κ2‐Ph2PCH2CH2SMe)(κ2‐Ph2PCH2CH2SPh)][BF4]2 (5) and reopening using halide ions to form semi‐open complexes [PtX(κ2‐Ph2PCH2CH2SMe)(Ph2PCH2CH2SPh)]BF4 (8 b; X=Cl−) and (8 c; X=I−). Analogous procedures using Ph2PCH2CH2SMe and 1,4‐(Ph2PCH2CH2S)2C6H4 lead to heteroligated bimetallic complexes 7 and 9, illustrating that this ligand rearrangement process can be used as a tool for the assembly of complementary metallosupramolecular structures.
Anti‐Nogo‐A antibody treatment enhances sprouting of corticospinal axons rostral to a unilateral cervical spinal cord lesion in adult macaque monkey
Authors: Freund Patrick , Wannier Thierry , Schmidlin Eric , Bloch Jocelyne , Mir Anis , Schwab Martin E. , Rouiller Eric M.
Published: March 2007

After injury, regrowth of axons in mammalian adult central nervous system is highly limited. However, in monkeys subjected to unilateral cervical lesion (C7–C8 level), neutralization of an important neurite outgrowth inhibitor, Nogo‐A, stimulated axonal sprouting caudal to the lesion, accompanied by enhanced functional recovery of manual dexterity, compared with lesioned monkeys treated with a control antibody (Freund et al. [2006] Nat. Med. 12:790–792). The present study aimed at comparing the same two groups of monkeys for axonal sprouting rostral to the cervical lesion. The corticospinal tract was labeled by injecting the anterograde tracer biotinylated dextran amine into the contralesional motor cortex. The corticospinal axons were interrupted at the level of the lesion, accompanied by retrograde axonal degeneration (axon dieback), reflected by the presence of terminal retraction bulbs. The number of terminal retraction bulbs was lower in anti‐Nogo‐A antibody treated monkeys, and, when present, they were found closer to the lesion than in control‐antibody treated monkeys. Compared with control antibody treated monkeys, the anti‐Nogo‐A antibody treated monkeys exhibited an increased cumulated axon arbor length and a higher number of axon arbors going in the medial direction from the white to the gray matter. Higher in the cervical cord (at C5 level), the anti‐Nogo‐A treatment enhanced the number of corticospinal fibers crossing the midline, suggesting axonal sprouting. Thus, the anti‐Nogo‐A antibody treatment enhanced axonal sprouting rostral to the cervical lesion; some of these fibers grew around the lesion and into the caudal spinal segments. These processes paralleled the observed improved functional recovery. J. Comp. Neurol. 502:644–659, 2007. © 2007 Wiley‐Liss, Inc.
Development of starburst cholinergic amacrine cells in the retina of Tupaia belangeri
Authors: Knabe Wolfgang , Washausen Stefan , Happel Nicole , Kuhn Hans‐Jürg
Published: March 2007

“Starburst” cholinergic amacrines specify the response of direction‐selective ganglion cells to image motion. Here, development of cholinergic amacrines was studied in the tree shrew Tupaia belangeri (Scandentia) by immunohistochemistry with antibodies against choline acetyltransferase (ChAT) and neurofilament proteins. Starburst amacrines expressed ChAT much earlier than previously thought. From embryonic day 34 (E34) onward, orthotopic and displaced subpopulations segregated from a single cluster of immunoreactive precursor cells. Orthotopic starburst amacrines rapidly took up positions in the inner nuclear layer. Displaced starburst amacrines were first arranged in a monocellular row in the inner plexiform layer, and, with a delay of 1 week, they descended to the ganglion cell layer. Conversely, dendritic stratification of displaced amacrines slightly preceded that of orthotopic ones. Starburst amacrines expressed the medium‐molecular‐weight neurofilament protein (NF‐M) from E34 to postnatal day 11 (P11) and coexpressed α‐internexin from E36.5 to P11. Consequently, neurofilaments composed of α‐internexin and NF‐M may stabilize developing dendrites of starburst amacrines. During the first 2 postnatal weeks, subpopulations of anti‐NF‐M‐labeled ganglion cells costratified with the preexisting dendritic strata of starburst amacrines in the ON sublamina, OFF sublamina, or both. Hence, anti‐NF‐M‐labeled ganglion cells may include direction‐selective ones. Thereafter, NF‐M and α‐internexin proteins disappeared from starburst amacrines, and NF‐M immunoreactivity was lost in the dendrites of ganglion cells. Our findings suggest that NF‐M and α‐internexin are important for starburst amacrines and ganglion cells to recognize each other and, thus, contribute to the formation of early developing retinal circuits in the inner plexiform layer. J. Comp. Neurol. 502:584–597, 2007. © 2007 Wiley‐Liss, Inc.
Asymmetric innervation of the habenula in zebrafish
Authors: Hendricks Michael , Jesuthasan Suresh
Published: March 2007

The habenular complex is a paired structure found in the diencephalon of all vertebrates, linking the forebrain and midbrain. Habenulae are asymmetrical and may contribute to lateralized behavior. Recent studies in zebrafish have characterized molecular pathways that give rise to the habenular asymmetry and the distinct projections of the left and right habenula to the midbrain. However, it is unclear whether there are asymmetries in habenula afferents from the forebrain. By lipophilic dye tracing, we find that axons innervating the habenula derive primarily from a region in the lateral diencephalon containing migrated neurons of the eminentia thalami (EmT). EmT neurons terminate in neuropils in both ipsilateral and contralateral habenula. These axons, together with axons from migrated neurons of the posterior tuberculum and pallial neurons, cross the midline via the habenular commissure. Subsets of pallial neurons terminate only in the medial right habenula, regardless of which side of the brain they originate from. These include an unusual type of forebrain projection: axons that cross the midline twice, at both the anterior and habenular commissures. Our data establish that there is asymmetric innervation of the habenula from the telencephalon, suggesting a mechanism by which habenula asymmetry might contribute to lateralized behavior. J. Comp. Neurol. 502:611–619, 2007. © 2007 Wiley‐Liss, Inc.
Elf5 is an epithelium‐specific, fibroblast growth factor–sensitive transcription factor in the embryonic lung
Authors: Metzger David E. , Xu Yan , Shannon John M.
Published: March 2007

Fibroblast growth factor (FGF) signaling has been shown to be essential for many aspects of normal lung development. To determine epithelial targets of FGF signaling, we cultured embryonic day (E) 11.5 mouse lungs for 24 hr in the presence or absence of the FGF receptor antagonist SU5402, which inhibited branching morphogenesis. Affymetrix gene chip analysis of treated and control epithelia identified several genes regulated by FGF signaling, including Elf5, a member of the Epithelial‐specific Ets family of transcription factors. SU5402 reduced Elf5 expression in mesenchyme‐free cultures of E12.5 epithelium, demonstrating that the inhibition was direct. In situ hybridization revealed that Elf5 had a dynamic pattern of expression during lung development. We found that expression of Elf5 was induced by FGF7 and FGF10, ligands that primarily bind FGFR2b. To further define the pathways by which FGFs activate Elf5 expression, we cultured E11.5 lung tips in the presence of compounds to inhibit FGF receptors (SU5402), PI3‐Kinase/Akt–mediated signaling (LY294002), and MAP Kinase/Erk‐mediated signaling (U0126). We found that SU5402 and LY294002 significantly reduced Elf5 expression, whereas U0126 had no effect. LY294002 also reduced Elf5 expression in cultures of purified epithelium. Finally, pAkt was coexpressed with Elf5 in the proximal epithelial airways of E17.5 lungs. These results demonstrate that Elf5 is an FGF‐sensitive transcription factor in the lung with a dynamic pattern of expression and that FGF regulation of Elf5 by means of FGFR2b occurs through the PI3‐Kinase/Akt pathway. Developmental Dynamics 236:1175–1192, 2007. © 2007 Wiley‐Liss, Inc.
Segmental border is defined by the key transcription factor Mesp2, by means of the suppression of notch activity
Authors: Saga Yumiko
Published: March 2007

Elaborate somite patterning is based upon dynamic gene regulation within the presomitic mesoderm (PSM), which is derived from the primitive streak and tail bud in the later stage mouse embryo. The Notch signaling pathway and its regulators are major components of most of the events required for temporally and spatially coordinated somite formation. The PSM can be subdivided into at least two domains, based upon transcriptional regulation and gene function. In the posterior PSM, the basic helix–loop–helix (bHLH) protein Hes7 plays a central role in generating a traveling wave of gene expression by negatively regulating the transcription of its target genes. This in turn may define the somite spacing and future segmental units. In the anterior PSM, cells begin to form segmental patterning by acquiring rostral or caudal identities of somite primordia and by defining the segmental border, which must be coupled with the segmentation clock. The link between the clock and segmental border formation is of fundamental importance during somitogenesis. During this process, Mesp2, another basic HLH protein, plays a critical role in the anterior PSM. In this review, I further clarify the dynamic processes leading to segmental border formation in the developing mouse embryo. Developmental Dynamics 236:1450–1455, 2007. © 2007 Wiley‐Liss, Inc.
Synthesis, Structures and Properties of Cluster Complexes [H3O(Ph3PO)3]2[Mo6Cl14] and [H(Ph3PO)2]2[Re6S6Br8]
Authors: Kozhomuratova Zhyldyz S. , Mironov Yuri V. , Shestopalov Michael A. , Drebushchak Irina V. , Moroz Nikolay K. , Naumov Dmitry Y. , Smolentsev Anton I. , Uskov Evgenii M. , Fedorov Vladimir E.
Published: March 2007

New cluster compounds [H3O(Ph3PO)3]2[Mo6Cl14] (I) and [H(Ph3PO)2]2[Re6S6Br8] (II) have been prepared by the reaction of a acetonitrile solution of triphenylphosphane oxide Ph3PO with octahedral cluster complexes of molybdenum (H3O)2Mo6Cl14·6H2O and rhenium K2Re6S6Br8, respectively, (with addition of several drops of HBr). The structures and properties of the products were studied by single‐crystalX‐ray diffraction and NMR and luminescence spectroscopic methods. The compounds studied are characterized by strong hydrogen bonds with O–O distances of 2.45–2.51 Å (I) and 2.34–2.41 Å (II); unusual H‐bonded cationic trimers, [H3O(Ph3PO)3]+, were found in compound I. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Inelastic seismic analysis of a building structure designed by argentine codes
Authors: Sonzogni Victorio E. , Cardona Alberto , Idelsohn Sergio R.
Published: March 2007

A reinforced concrete frame‐wall structure of a building designed in accordance to standard practice in Argentina was analysed by the procedures prescribed by current Argentine Codes. In addition, the inelastic step‐by‐step response of the structure to design spectrum‐compatible accelerograms was studied by means of a special element for inelastic dynamic analysis of reinforced concrete frames. Results obtained by the different methods of analysis are presented.