bluuebunny/crossref_metadata_2025 huggingface dataset:
Point of care testing is appropriate for National Health Service health check
Authors: Jain Anjly , Persaud Jahm Want , Rao Nandini , Harvey Darren , Robertson Laura , Nirmal Lalit , Nirmal Divya , Thomas Michael , Mikhailidis Dimitri P , Nair Devaki R
Published: February 2011

Background

The Department of Health launched a cardiovascular disease risk assessment initiative with particular reference to reducing health inequalities in ethnic minorities. Collaboration between HEART UK, Royal Free Hampstead NHS Trust and Hindu Temples resulted in vascular screening in North London.

Methods

Subjects of South Asian origin were screened. A full lipid profile and glucose were measured using a point of care testing (POCT) Cholestech LDX analyser (LDX). Venous samples were analysed in our hospital laboratory.

Results

The results (215 men; 191 women) were divided into tertiles and Bland–Altman plots were used to assess agreement. At high-density lipoprotein cholesterol (HDL-C) concentrations <1.0 mmol/L the LDX underestimated values by −0.2 mmol/L ( P<0.0001). At HDL-C concentrations >1.3 mmol/L this bias disappeared. For total cholesterol the concentration-dependent negative bias was evident at concentrations of <4.1 mmol/L ( P < 0.0001). This bias was less evident at higher concentrations. A similar pattern was seen for low-density lipoprotein cholesterol. There were also small variations in glucose and triglyceride values. However, there was excellent agreement in calculated cardiovascular disease risk using kappa analysis for JBS2, QRISK2, ETHRISK and Framingham ( κ = 0.86, 0.92, 0.94 and 0.88, respectively). This was a high-risk population since 9.7–19.4% had a ≥20% 10-y probability of a vascular event depending on the risk engine and assay method used. The corresponding values for intermediate risk (11–19%) were 18.6–25.7%.

Conclusions

There was a minimum mismatch irrespective of the type of risk calculator used. POCT measurements are adequate for the National Health Service Health Check.
Utilization of dried blood spots within drug discovery: modification of a standard DiLab® AccuSampler® to facilitate automatic dried blood spot sampling
Authors: Clark G T , Giddens G , Burrows L , Strand C
Published: February 2011

The use of dried blood spots (DBS) in preclinical studies has seen an enormous increase over the past two years. Despite its positive impact on the 3Rs (reduce, replace and refine), its uptake in exploratory drug discovery has been limited due mainly to protracted method development time in bioanalysis but also the need for small volumes (<20 μL) to be sampled manually. Automatic blood sampling technology such as the DiLab® AccuSampler® is widely used in drug discovery to facilitate exploratory rodent-based pharmacokinetic and pharmacokinetic/pharmacodynamic studies with minimal animal handling. Propranolol was orally administered to a Han-Wistar rat attached to either a standard DiLab® AccuSampler® or a retrofitted unit designed to directly collect the DBS samples. In all, 50 or 20 μL blood samples were then collected via the standard or retrofitted unit, respectively, at six timepoints over a 7 h period. After drying and storage the DBS samples were analysed for propranolol via liquid chromatography-mass spectrometry. In this report we demonstrate that a standard DiLab® AccuSampler® can be easily retrofitted to facilitate automatic dried blood spot sampling and that time–concentration data generated from these samples are equivalent to that from manually spotted samples.
Agentenbasiertes Energiemanagement zur Spannungshaltung in Verteilnetzen
Authors: Wolter Martin , Hofmann Lutz
Published: February 2011

Heutzutage gehen Verteilnetzbetreiber neue Wege bei der Führung ihrer Netze. Hauptsächlich ist dies der steigenden Anzahl von Kleinerzeugern in ihren Netzen geschuldet. Darüber hinaus ist die Messtopologie unterbesetzt, so dass der Netzzustand nicht vollständig erfasst werden kann und unzulässige Systemzustände unentdeckt bleiben. Netzbetreiber, die intelligente Energiemanagementsysteme einsetzen, können sowohl einen globalen Optimierer als auch dezentrale Strukturen verwenden, um ihre Netzführung zu automatisieren. Letzterer Ansatz ist im Sinne des angestrebten plug´n´play-Verteilnetzes die bessere Variante.
Optimale Betriebsführung eines virtuellen Kraftwerks auf Basis von gasbetriebenen Mikro-Blockheizkraftwerken
Authors: Müller Christian , Rehkopf Andreas
Published: February 2011

Dieser Beitrag befasst sich mit der optimalen Betriebsführung eines virtuellen Kraftwerks auf Basis von Mikro-Blockheizkraftwerken. Dazu wird das Taktungsproblem der Anlagen als mathematische Zwei-Ebenen-Aufgabe der Spieltheorie formuliert. Es entsteht ein sog. Stackelberg-Spiel, für das die jeweiligen Zielfunktionen und Nebenbedingungen der beiden Ebenen herausgearbeitet werden. Schließlich erfolgt die Kopplung der Ebenen über die Lösungsmenge der unteren Ebene. Ein einfaches Beispiel der praktischen Anwendung wird aufgezeigt.
A Amazônia indígena de George Catlin: imagens e relatos de viagem desconhecidos
Authors: Porro Antonio
Published: February 2011

Este artigo apresenta e discute, pela primeira vez com vistas à etnologia e à etno-história do Brasil, as narrativas de viagem e os trabalhos do pintor norte-americano George Catlin (1796-1872) na Amazônia, em 1852, e a contribuição de suas memórias e pinturas para o conhecimento de grupos indígenas da época. Catlin ficara famoso, nos Estados Unidos, pelas centenas de retratos e imagens de aldeias indígenas do seu país, mas as suas viagens e trabalhos na América do Sul nunca receberam a mesma atenção; nos estudos brasileiros sobre artistas e naturalistas viajantes do século XIX ele não é sequer mencionado. Além da tradução de trechos relevantes das suas memórias de viagem, algumas de suas muitas pinturas de índios e paisagens amazônicas são aqui reproduzidas.
Aprendizagem de sinais vitais utilizando objetos educacionais digitais: opinião de estudantes de enfermagem
Authors: Cogo Ana Luísa Petersen , Silveira Denise Tolfo , Pedro Eva Néri Rubim , Tanaka Raquel Yurika , Catalan Vanessa Menezes
Published: February 2011

Estudo com o objetivo de conhecer as opiniões de estudantes de enfermagem quanto à prática pedagógica sobre sinais vitais fundamentada na aprendizagem baseada em problemas, apresentada na forma de objetos educacionais digitais. A pesquisa, na metodologia do estudo de caso qualitativo, contou com dez sujeitos. Os dados foram obtidos por meio de entrevistas semi-estruturadas analisadas pela técnica da análise temática. Identificou-se três categorias finais: a aprendizagem com o apoio da informática, a organização do trabalho em grupo e a avaliação do projeto de aprendizagem de sinais vitais. A atividade foi uma experiência nova para os alunos, considerada positiva pela facilitação do acesso aos conteúdos e da comunicação entre colegas, porém apontaram a falta da presença física do professor. O trabalho em grupo transcorreu, na sua maioria, de forma colaborativa. Constatou-se a importância de disponibilizar, a estudantes de enfermagem, atividades mediadas pelo computador associadas à metodologia da aprendizagem baseada em problemas.
Dubai Metro footbridge design
Authors: Smith David , Smith Tony , Chiarello Manuela , Ho Alan
Published: February 2011

The Dubai Metro light-rail scheme is a flagship project in the United Arab Emirates and the longest fully automated rail system in the world. The first line of the rail system was opened in September 2009 with a second line due for completion in 2010. These first two lines include 35 elevated stations along their combined 76 km length. This paper describes the design and construction of the steel truss footbridges developed as part of the station context planning work for all of the elevated stations. The footbridges are all fully enclosed, air-conditioned corridors with the widths of many dictated by the provision of automated walkways. A key aspect to the footbridge design concept was to develop a modular system that could be rapidly designed for scores of differing span arrangements to be suitable for each unique location. Several of the footbridge truss elements comprised structural hollow sections, and the new rules in Eurocode 3 were adopted to design many of the connections between such members. With simply supported spans up to 45 m long and external cladding creating irregular shaped cross-sections, wind tunnel testing was required to demonstrate aerodynamic stability of the footbridges. Several erection methods were also considered to minimise the installation time of completed footbridge spans over the major Dubai highways, and the pre-camber and deflection analysis associated with the methods adopted for lifting were also important aspects considered in the design. Other critical design issues resolved included the design of fillet-welded connections in place of full-strength full-penetration butt welds and the design of several special spans for connecting into non-standard stations and entrance structures.
Reliability of construction control of cable-stayed bridges
Authors: Su Cheng , Chen Zhaoshuan , Chen Zhihui
Published: February 2011

Deck elevations and cable tensions change throughout the construction process of a long-span cable-stayed bridge. Accordingly, geometric errors of deck elevations and tension errors in cables are frequently encountered. The tolerance values of such errors are of great concern to the construction control of cable-stayed bridges. In order to obtain reasonable tolerance errors of deck elevations and cable tensions, the randomness of geometric parameters, the material parameters and the loading parameters of the bridge during erection should be considered. This paper presents a novel reliability-based approach to determine the tolerance errors for different construction stages of a cable-stayed bridge. In the proposed approach, an improved response surface method based on finite-element analysis of segmental construction of the bridge girder is used to yield the failure probabilities of construction control under different erection errors. Reasonable tolerance errors are then obtained based on the acceptable failure probabilities. For engineering applications, the proposed method is further applied to the reliability analysis of the construction contort of the newly built Huangpu Bridge across the Pearl River in Guangzhou. The new approach is also applicable to the construction control of other types of bridges.
Recommendations for assessment Eurocodes for bridges
Authors: Hendy Chris R. , Sandberg Jessica , Shetty Navil K.
Published: February 2011

The new structural Eurocodes offer increased economy in design over most existing codes of practice. However, the assessment of existing structures is specifically outside the scope of the Eurocodes, so many of the benefits these new codes bring cannot be directly applied when reviewing old structures. This paper investigates the areas where the steel and concrete Eurocodes give increased resistances compared to existing codes and makes recommendations for sections that could be directly applied to the assessment of existing structures. Areas where the Eurocodes cannot be applied directly to existing structures are also identified, together with the reasons why, such as reliance on modern material and execution specifications. Recommendations are then made for how the Eurocode design rules could be modified for assessment situations, including the use of measured strengths and imperfections in calculation. Actions and the format for combining actions are also investigated and recommendations are made for modifications to these aspects for use in assessing bridges. Finally, an overall assessment of the scope of work required to produce an assessment suite of Eurocodes is made.
Middle Eastern archaeology
Authors: Roberts Gwilym
Published: February 2011

Following a brief description of the development of the ancient Middle Eastern civilisations and the vital roles played by engineers in their establishment, some of the more important archaeological structures of Mesopotamia and Egypt are described. This paper also gives shorter descriptions of other archaeological sites in the region, including some lesser known monuments. Frequent reference is made to the hydraulic works that made these civilisations possible, as well as to the building materials and construction techniques used in various structures. The paper concludes with appendices summarising the role these civilisations played in the development of writing and numerical practices and the actions practising engineers should take to help conserve the world's archaeological heritage.
The Woodhead dam on Table Mountain, Cape Town, South Africa
Authors: Murray Tony
Published: February 2011

The Woodhead dam was constructed between 1893 and 1897 on the ‘Back Table’ of the well-known landmark Table Mountain overlooking the city of Cape Town. At that time it was the main source of water supply to the city and was the largest dam of any consequence in southern Africa. It is still operational and, in 2008, was awarded international civil engineering landmark status by the American Society of Civil Engineers. This paper describes: the background to the water supply problems to Cape Town that led to construction of the dam; some details of the careers of John Gamble, the engineer who located the dam, and Scottish engineer Thomas Stewart, who became the first consulting engineer in South Africa; Stewart's design and construction of the dam, located on a mountain top with very difficult access; and brief details of subsequent measures taken to provide water to Cape Town.
Electrokinetic treatment on a tropical residual soil
Authors: Ahmad Kamarudin Bin , Taha Mohd. Raihan , Kassim Khairul Anuar
Published: February 2011

The results of shear box and consolidation tests on electrokinetically-treated tropical residual soil are presented. Injections of selected chemicals (calcium chloride, aluminium chloride and phosphoric acid) into the soil samples at the anodes or cathodes were carried out in cylindrical electrokinetic cells via applications of 30 V DC electrical potential for 168 h. Four different open-anode and open-cathode electrokinetic systems utilising different anolytes and catholytes were employed to treat the soil samples. The shear resistances of the treated soil utilising distilled water as the anolyte and 1·0 mol/l phosphoric acid as the catholyte was enhanced, whereas the treated soil near the cathode showed significant reduction in compressibility. Soil treated utilising the other chemicals showed no significant changes.
Field behaviour of stiffened deep cement mixing piles
Authors: Jamsawang Pittaya , Bergado Dennes T. , Voottipruex Panich
Published: February 2011

Full-scale pile load tests were performed on soft Bangkok clay improved by stiffened deep cement mixing (SDCM) piles and deep cement mixing (DCM) piles installed by jet-mixing to compare their performance. The SDCM pile is a DCM pile with a precast reinforced concrete core pile inserted in the middle. A series of full-scale tests consisting of axial compression, lateral and pullout interface between the concrete core pile and surrounding DCM material were performed. The length of the concrete core pile influenced both the ultimate axial bearing capacity and the settlement of the SDCM piles more than its section area. Furthermore, the section area of the concrete core pile affected both the lateral ultimate bearing capacity and the lateral displacements of SDCM piles significantly. Moreover, the SDCM piles with area ratio (Acore/ADCM) of 0·17 and length ratio (Lcore/LDCM) of 0·85 increased the axial and lateral ultimate bearing capacities so that they were as much as 2·2 and 15 times higher than the corresponding values of DCM piles, respectively. The flexural strength of the DCM pile obtained from the laboratory was 16% of its unconfined compressive strength whereas that obtained from full-scale lateral load tests was much lower at 4–7% of its unconfined compressive strength. The strength reduction factor, Rinter, at the interface between the concrete core pile and DCM pile in the field averaged 0·40, which agreed with the data from laboratory tests of 0·38–0·46.
Geometric parametric studies on reinforced soil gabion walls
Authors: Jayasree Parameswaran Kamala , Beena Krishnan Sulochana
Published: February 2011

Gabion-faced retaining walls are semi-rigid structures that can generally accommodate large lateral and vertical movements without excessive structural distress. Because of this feature, they offer technical and economical advantage over the conventional concrete gravity-retaining walls. A finite-element code developed for the analysis of gabion-faced reinforced earth walls was validated and used to study the behaviour of gabion-faced reinforced soil walls under self-weight loading. Deformation aspects are highlighted in this paper as the recent trends in the design of retaining walls is to incorporate serviceability conditions. The effects of varying the spacing of reinforcement, the length of reinforcement and width of facing were studied on walls of three different heights: 3 m (low-height walls), 6 m (medium-height walls) and 9 m (high walls). Studies were also conducted to understand the effect of strip loading on these walls. The results from the studies may be of direct use to the design engineers at site in fixing the dimensions of gabion-faced reinforced soil walls.
The role of Christianity in the development of European and Serbian medieval medicine
Authors: Antic Radisa
Published: February 2011

Being conceived in the name of Christianity, the Church quickly mastered all of Western Europe, including medicine, which was developed in monasteries at first and at universities later on. The first hospitals were built within monasteries, and were used to treat monks and the general population in later times. With the founding of the first universities, medicine claimed its place in the world next to law, philosophy, and theology. In its early days, it was studied only as a theoretical science, but soon practical classes on cadavers were added. Universities were completely ruled by the Church, which meant that the curriculum had to be pre-approved by the Church, even the diplomas were presented by a bishop in a religious ceremony. Development of Serbian medieval medicine was under the influence of Byzantine and Italian (mainly Salernian) medicine. The greatest role in transfer of medical knowledge from the Byzantine Empire belonged to Serbian and Byzantine monks, while Italian doctors working in Serbia were responsible for the transfer of the Western medical knowledge. Serbian monarchs quickly started founding hospitals, both in and out of their domains, with the most famous ones being within monasteries such as Hilandar, Studenica, Pantokrator, Visoki Decani, Sveti Arhangel, etc. In addition to those, there were two more hospitals not related to monasteries in Kotor and Belgrade, named after Stefan Lazarevic. This contribution of Christianity to European medicine created a basis for a sudden development of medical science in the Renaissance.
Famous medical doctors of Sombor in its history until the World War II
Authors: Kobilarov Aleksandar , Sakac Vladimir
Published: February 2011

Sombor is a town in the northwest of Backa, an area rich in culture. It was founded as a settlement in the 5th and the 6th centuries. There are many theories about the origins and name of the town. From the beginnings of the city and in the period when the town was under the Turks, the development of health care was poor. Especially during the period of the Turkish Empire, there was no cultural development in Serbian people. Educated doctors existed only in some western countries and the average lifetime of people in Sombor was 20-25 years. At the end of the 17th century, Sombor was freed from the Turks. Its first 'improvised' hospital with surgeons, Sombor obtained at the beginning of the 18th century. On February 17, 1749, Sombor became a free royal town. Dr. Petar Miloradovic arrived in 1770 as the first doctor. In 1778, the town got its first physician, Martin Peter Karl. The next city physician, Dr. Matthias Lotz introduced a new health code of conduct for the population, and Dr. Vasilije Maksimovic introduced new rules in the conduct and organization of health care workers. The second half of the 19th century was marked by two doctors of Sombor, a physician, Dr. Djordje Maksimovic, who was the main initiator of the construction of the first Sombor hospital in 1880, and Dr. Milan Jovanovic-Batut, who published a number of health-enlightenment magazines. Dr. Radivoj Simonovic came to Sombor in 1896. The doctors' influence to life and development of Sombor was very important, and without them Sombor would not be the town it is today.
Dr. Svetozar Markovic: The founder of the school hygiene in Serbia
Authors: Dimitrijevic Brana
Published: February 2011

Dr. Svetozar Markovic (1860-1916) graduated from the Medical School in Paris, France (1894) and was the founder of the schools hygiene in Serbia. He founded the Society for School Hygiene and People's Enlightenment (1906); he also established the Svetlost (1908), a periodical that was regularly published for six years, until the beginning of the World War I (1914). He was involved in introducing high standards in schools based on medical science, with a purpose of maintaining, and not ruining the health of students. He was a pioneer in this field of work.
Foreign medical help in Serbian liberation wars from 1912 until 1918
Authors: Petrovic Ilija
Published: February 2011

This work concerns involvement of the foreign medical missions during the Serbian Liberation Wars from 1912 until 1918, the work of their members immediately behind the front lines and in the back, healing of the wounded and the diseased, especially at the time of the great epidemics of typhoid fever, and also the efforts of numerous Serbian friends who collected the funds and material for equipping and sending of those missions. An American mission which came first to Serbia, soon after the beginning of the war operations and which was led by Dr. Edward Ryan, was specially mentioned. For many smaller of bigger missions, it is known that they acted in some of the Serbian war zones. A special attention was paid to the work of The Scottish Women's Hospital, its formation and means of funding, work in war conditions, attitudes towards wounded Serbs and posture during the Serbian retreat before the German, Austro-Hungarian and Bulgarian occupying armies. This text is largely the author's own view of his two books on medical assistance which the Serbs received from their friends from abroad (Medical Missions at Serbian Battlefields 1912-1918 and The Scottish Women with the Serbs 1914-1918). The first of these booklets contains a list with over 1350 names (of which, approximately 700 are the medical doctors), and the other 1230, were based on the author's personal inspection of the available literature and materials, significantly increased the official data of the Serbian Red Cross about the number of medical staff who reached Serbian battlefields: doubles them for the Balkan wars, while in the Great war they were at least five times greater.
An essay on giants of mankind
Authors: Kajtez Ilija
Published: February 2011

Great people are relentless in creation on the planet, exalted magicians of words, thoughts and deeds. An extraordinary man of excellence can bring immeasurable good to his race, faith, country or civilization. We should not forget that the man is a building block of creation and that sometimes he is not aware of how much of his creative zeal and fruitful energy is hidden in his spiritual flight and profound thoughts. Fortunately, the giants of the world (Aristotle, Hegel, Heidegger, Dostoevsky and Shakespeare) had timely recognized their gift and dedicated their valuable life to fertilize it. Nothing that God has given to the Man is without a reason. Nothing is given with the bad intention that gifts of spirit should die, unfertilized, overlaid and empty, when the person physically leaves this world. That exceptional value of the One is meant to be passed as the most precious gift on to new generations open to fruitful new knowledge. The Serbian race throughout its eventful and turbulent history and painful existence has delivered rich gifts of beauty, spirit, wisdom and struggle for freedom to the world heritage. Studenica is the place where St. Simeon Mirotocivi (the one who spreads peace) laid foundations of our state, and Saint Sava, the first light and dawn among the Serbs, christened our race for ever.
Personal traits and a sense of job-related stress in a military aviation crew
Authors: Cabarkapa Milanko , Korica Vesna , Rodjenkov Sanja
Published: February 2011

Background/Aim. Accelerated technological and organizational changes in numerous professions lead to increase in jobrelated stress. Since these changes are particularly common in military aviation, this study examined the way military aviation crew experiences job-related stress during a regular aviation drill, depending on particular social-demographic factors and personal traits. Methods. The modified Cooper questionnaire was used to examine the stress related factors at work. The questionnaire was adapted for the aviation crew in the army environment. Personal characteristics were examined using the NEO-PI-R personality inventory. The study included 50 examinees (37 pilots and 13 other crew members) employed in the Serbian Army. The studies were performed during routine physical examinations at the Institute for Aviation Medicine during the year 2007. Statistical analysis of the study results contained descriptive analysis, one-way analysis of variance and correlation analysis. Results. It was shown that army aviation crew works under high stress. The highest stress value had the intrinsic factor (AS = 40.94) and role in organisation (AS = 39.92), while the lowest one had the interpersonal relationship factor (AS = 29.98). The results also showed that some social-demographic variables (such as younger examinees, shorter working experience ) and neuroticism as a personality trait, were in correlation with job-related stress. Conclusion. Stress evaluation and certain personality characteristics examination can be used for the devalopment of the basic anti-stress programs and measures in order to achieve better psychological selection, adaptation career leadership and organization of military pilots and other crew members.
Extranodal marginal zone non Hodgkin's lymphoma of the lung: A ten-year experience
Authors: Milosevic Violeta , Bogdanovic Andrija , Jankovic Snezana , Perunicic-Jovanovic Maja , Mihaljevic Biljana
Published: February 2011

Background/Aim. Bronchus-associated lymphoid tissue (BALT) lymphoma is a rare subtype of low grade marginal zone B cell lymphoma representing 10% of all MALT lymphomas. The purpose of this study was to analyze the outcome of this group of patients comparing prognostic parameters and therapy modalities. Methods. A total of eight patients with BALT lymphoma had diagnosed between January 1998 - April 2008 at the Institute of Hematology, Clinical Center of Serbia, Belgrade, and they were included in this retrospective analysis. Results. Male/female ratio was 2/6, the median age was 64 years (range 37-67 years). Six patients had nonspecific respiratory symptoms and all of them had B symptoms. The patients were seronegative for HIV, HCV and HBsAg. Three patients had Sjogren's syndrome, rheumatoid arthritis and pulmonary tuberculosis, respectively. Seven patients were diagnosed by transbronchial biopsy and an open lung biopsy was done in one patient. Patohistological findings revealed lymphoma of marginal zone B cell lymphoma: CD20+/CD10-/CD5-/CyclinD1- /CD23-/IgM- with Ki-67+<20% of all cells. According to the Ferraro staging system, five patients had localized disease (CS I-IIE) and three had stage IVE; bulky tumor mass had 3 patients. All patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. Five patients received monochemotherapy with chlorambucil and 3 were treated with CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone). A complete response (CR) was achieved in 5 patients and a partial response (PR) in 3 of them, treated with chlorambucil monotherapy and CHOP regimen. All patients were alive during a median follow-up period of 49 months (range 6- 110 months). Three patients relapsed after monochemotherapy into the other extranodal localization. They were treated with CHOP regimen and remained in stable PR. Conclusion. BALT lymphoma tends to be localised disease at the time of diagnosis, responds well to monochemotherapy with chlorambucil and has a favourable prognosis.
Δ40 Isoform of p53 Controls β-Cell Proliferation and Glucose Homeostasis in Mice
Authors: Hinault Charlotte , Kawamori Dan , Liew Chong Wee , Maier Bernhard , Hu Jiang , Keller Susanna R. , Mirmira Raghavendra G. , Scrable Heidi , Kulkarni Rohit N.
Published: February 2011

OBJECTIVE

Investigating the dynamics of pancreatic β-cell mass is critical for developing strategies to treat both type 1 and type 2 diabetes. p53, a key regulator of the cell cycle and apoptosis, has mostly been a focus of investigation as a tumor suppressor. Although p53 alternative transcripts can modulate p53 activity, their functions are not fully understood. We hypothesized that β-cell proliferation and glucose homeostasis were controlled by Δ40p53, a p53 isoform lacking the transactivation domain of the full-length protein that modulates total p53 activity and regulates organ size and life span in mice.

RESEARCH DESIGN AND METHODS

We phenotyped metabolic parameters in Δ40p53 transgenic (p44tg) mice and used quantitative RT-PCR, Western blotting, and immunohistochemistry to examine β-cell proliferation.

RESULTS

Transgenic mice with an ectopic p53 gene encoding Δ40p53 developed hypoinsulinemia and glucose intolerance by 3 months of age, which worsened in older mice and led to overt diabetes and premature death from ∼14 months of age. Consistent with a dramatic decrease in β-cell mass and reduced β-cell proliferation, lower expression of cyclin D2 and pancreatic duodenal homeobox-1, two key regulators of proliferation, was observed, whereas expression of the cell cycle inhibitor p21, a p53 target gene, was increased.

CONCLUSIONS

These data indicate a significant and novel role for Δ40p53 in β-cell proliferation with implications for the development of age-dependent diabetes.
Epigenetic Changes in Mitochondrial Superoxide Dismutase in the Retina and the Development of Diabetic Retinopathy
Authors: Zhong Qing , Kowluru Renu A.
Published: February 2011

OBJECTIVE

To investigate the role of epigenetic regulation of the manganese superoxide dismutase gene (sod2) in the development of diabetic retinopathy and the metabolic memory phenomenon associated with its continued progression after hyperglycemia is terminated.

RESEARCH DESIGN AND METHODS

Streptozotocin-induced diabetic rats were maintained in poor glycemic control (PC, GHb ∼12%) or in good glycemic control (GC, GHb ∼7.0%) for 4 months, or were allowed to maintain PC for 2 months, followed by GC for 2 additional months (PC-Rev). For experimental galactosemia, a group of normal rats were fed a 30% galactose diet for 4 months or for 2 months, followed by a normal diet for 2 additional months. Trimethyl histone H4 lysine 20 (H4K20me3), acetyl histone H3 lysine 9 (H3K9), and nuclear transcriptional factor NF-κB p65 and p50 at the retinal sod2 promoter and enhancer were examined by chromatin immunoprecipitation.

RESULTS

Hyperglycemia (diabetes or galactosemia) increased H4K20me3, acetyl H3K9, and NF-κB p65 at the promoter and enhancer of retinal sod2, upregulated protein and gene expression of SUV420h2, and increased the interactions of acetyl H3K9 and NF-κB p65 to H4K20me3. Reversal of hyperglycemia failed to prevent increases in H4K20me3, acetyl H3K9, and NF-κB p65 at sod2, and sod2 and SUV420h2 continued to be abnormal. Silencing SUV420h2 by its small interfering RNA in retinal endothelial cells prevented a glucose-induced increase in H4K20me3 at the sod2 enhancer and a decrease in sod2 transcripts.

CONCLUSIONS

Increased H4K20me3 at sod2 contributes to its downregulation and is important in the development of diabetic retinopathy and in the metabolic memory phenomenon. Targeting epigenetic changes may serve as potential therapeutic targets to retard the development and progression of diabetic retinopathy.
A Comparative Evaluation of Amitriptyline and Duloxetine in Painful Diabetic Neuropathy
Authors: Kaur Harjot , Hota Debasish , Bhansali Anil , Dutta Pinaki , Bansal Dipika , Chakrabarti Amitava
Published: February 2011

OBJECTIVE

To compare the efficacy and safety of duloxetine and amitriptyline in painful diabetic neuropathy (PDN).

RESEARCH DESIGN AND METHODS

In this randomized, double-blind, cross-over, active-control trial, 58 patients received amitriptyline and duloxetine orally once daily at bedtime, each for 6 weeks with optional dose uptitration fortnightly. Single-blinded placebo washout was given for 2 weeks between the two treatments and a single-blinded placebo run-out phase of 4 weeks was given at the end of the treatment period. Pain relief was measured by the patient’s global assessment of efficacy, using a visual analog scale (0–100) as a primary end point, and overall improvement and adverse events were assessed as secondary outcome measures. Median pain score reductions of >50%, 25–50%, and <25% were considered good, moderate, and mild responses, respectively.

RESULTS

There was a significant improvement in pain with both treatments compared with their baseline values (P < 0.001 for both). Good, moderate, and mild pain relief was achieved in 55, 24, and 15% of patients, respectively, on amitriptyline and 59, 21, and 9% of patients, respectively, on duloxetine. There were no significant differences in various other outcome measures between the groups. Of the reported adverse events, dry mouth was significantly more common with amitriptyline than duloxetine (55 vs. 24%; P < 0.01). Although, numerically, more patients preferred duloxetine, overall this was not statistically significant (48 vs. 36%; P = 0.18).

CONCLUSIONS

Both duloxetine and amitriptyline demonstrated similar efficacy in PDN. A large, multicentric clinical trial in other populations could possibly demonstrate the superiority of either drug.
FaceBots: Steps Towards Enhanced Long-Term Human-Robot Interaction by Utilizing and Publishing Online Social Information
Authors: Mavridis Nikolaos , Petychakis Michael , Tsamakos Alexandros , Toulis Panos , Emami Shervin , Kazmi Wajahat , Datta Chandan , BenAbdelkader Chiraz , Tanoto Andry
Published: February 2011

The overarching goal of the FaceBots project is to support the achievement of sustainable long-term human-robot relationships through the creation of robots with face recognition and natural language capabilities, which exploit and publish online information, and especially social information available on Facebook, and which achieve two significant novelties. The underlying experimental hypothesis is that such relationships can be significantly enhanced if the human and the robot are gradually creating a pool of episodic memories that they can co-refer to (“shared memories”), and if they are both embedded in a social web of other humans and robots they mutually know (“shared friends”). We present a description of system architecture, as well as important concrete results regarding face recognition and transferability of training, with training and testing sets coming from either one or a combination of two sources: an onboard camera which can provide sequences of images, as well as facebook-derived photos. Furthermore, early interaction-related results are presented, and evaluation methodologies as well as interesting extensions are discussed.
Accuracy in Biological Information Technology Involves Enzymatic Quantum Processing and Entanglement of Decohered Isomers
Authors: Cooper Willis Grant
Published: February 2011

Genetic specificity information “seen by” the transcriptase is in terms of hydrogen bonded proton states, which initially are metastable amino (–NH2) and, consequently, are subjected to quantum uncertainty limits. This introduces a probability of arrangement, keto-amino → enol-imine, where product protons participate in coupled quantum oscillations at frequencies of ~ 1013 s−1 and are entangled. The enzymatic ket for the four G′-C′ coherent protons is │ψ > = α│+ − + − > + β│+ − − + > + γ│− + + − > + δ│− + − + >. Genetic specificities of superposition states are processed quantum mechanically, in an interval ∆t < < 10−13 s, causing an additional entanglement between coherent protons and transcriptase units. The input qubit at G-C sites causes base substitution, whereas coherent states within A-T sites cause deletion. Initially decohered enol and imine G′ and *C isomers are “entanglement-protected” and participate in Topal-Fresco substitution-replication which, in the 2nd round of growth, reintroduces the metastable keto-amino state. Since experimental lifetimes of metastable keto-amino states at 37 °C are ≥ ~3000 y, approximate quantum methods for small times, t < ~100 y, yield the probability, P(t), of keto-amino → enol-imine as Pρ(t) = ½ (γρ/ħ)2 t2. This approximation introduces a quantum Darwinian evolution model which (a) simulates incidence of cancer data and (b) implies insight into quantum information origins for evolutionary extinction.
An MILP-Based Cross-Layer Optimization for a Multi-Reader Arbitration in the UHF RFID System
Authors: Choi Jinchul , Lee Chaewoo
Published: February 2011

In RFID systems, the performance of each reader such as interrogation range and tag recognition rate may suffer from interferences from other readers. Since the reader interference can be mitigated by output signal power control, spectral and/or temporal separation among readers, the system performance depends on how to adapt the various reader arbitration metrics such as time, frequency, and output power to the system environment. However, complexity and difficulty of the optimization problem increase with respect to the variety of the arbitration metrics. Thus, most proposals in previous study have been suggested to primarily prevent the reader collision with consideration of one or two arbitration metrics. In this paper, we propose a novel cross-layer optimization design based on the concept of combining time division, frequency division, and power control not only to solve the reader interference problem, but also to achieve the multiple objectives such as minimum interrogation delay, maximum reader utilization, and energy efficiency. Based on the priority of the multiple objectives, our cross-layer design optimizes the system sequentially by means of the mixed-integer linear programming. In spite of the multi-stage optimization, the optimization design is formulated as a concise single mathematical form by properly assigning a weight to each objective. Numerical results demonstrate the effectiveness of the proposed optimization design.
Biodiversity assessment: State‐of‐the‐art techniques in phylogenomics and species identification
Authors: Steele P. Roxanne , Pires J. Chris
Published: February 2011

• Premise of the study: Biodiversity assessment is the first step in protecting the complete range of morphological and genetic diversity of species on Earth, and in reaching the goals of conservation biology. Assessment begins with identifying organisms that make up biological communities and understanding evolutionary histories. Scientific advancements in molecular sequencing can help clarify and provide support for identifications. Massively parallel DNA sequencing technologies are being used to sequence complete genomes of model organisms; however, this resource has not been fully used for species identifications. Animal researchers commonly use one mitochondrial region, and groups of plant scientists have proposed numerous combinations of two or three chloroplast markers as genomic identifiers. Yet, nearly as many studies have reported that the proposed regions are uninformative in some plant groups and at various taxonomic levels.

• Methods: We propose a combination of whole (or nearly whole) chloroplast genomes, mitochondrial genes, and nuclear repeat regions for both species identifications and phylogenetic analyses, obtained from a simple total DNA extraction and one run on massively parallel DNA sequencing machines.

• Key results: We have recovered both coding and noncoding sequences from multiple genetic sources, providing genomic information for comparisons within and between multiple taxonomic levels.

• Conclusions: In combination with morphological and other data, this abundance of genomic information will have a broad range of applications, including not only helping conservation biologists understand ecosystem biodiversity, but also understanding the evolutionary histories of organisms, mending damaged landscapes, and investigating interactions of plants with pollinators and pests.
Microsatellite marker development for Galax urceolata (Diapensiaceae)
Authors: Servick Stein V. , Soltis Pamela S. , Soltis Douglas E.
Published: February 2011

• Premise of the study: Microsatellite markers were developed for Galax urceolata to investigate genetic diversity, population structure, and polyploid origins (auto‐ vs. allopolyploid), and to estimate the minimum number of independent cytotype origins.

• Methods and Results: Ten primer sets have been developed, and preliminary study indicates that all loci are appropriate for population‐level genetic investigations. All loci are polymorphic with 6 to 46 alleles per locus. Expected heterozygosity ranges from 0.1007 to 0.6085.

• Conclusions: The microsatellite markers presented will facilitate analyses of polyploid origins, genetic diversity, geographic structure, and gene flow.
Isolation of compound microsatellite markers for the common Mediterranean shrub Smilax aspera (Smilacaceae)
Authors: Xu Xi‐hui , Wan Ying , Qi Zhe‐Chen , Qiu Ying‐xiong , Fu Cheng‐Xin
Published: February 2011

• Premise of the study: Microsatellite markers were developed for the common Mediterranean shrub Smilax aspera to study the population genetics of this species.

• Methods and Results: Using the compound microsatellite marker technique, a total of 14 pairs of primers were developed for S. aspera, of which 11 were polymorphic, and three were monomorphic. Levels of polymorphism in the 11 markers were checked in 43 individuals collected from two populations in Greece and Italy. The number of alleles per locus ranged from 10 to 26, with an average of 15.55 alleles per locus. All of these primers also could be amplified from a second species, S. hispida.

• Conclusions: These microsatellite markers can be used for future studies of genetic diversity in S. aspera, as well as in other related taxa, and will help us to improve our understanding of the microevolutionary processes of this species in the Mediterranean region.
Stat6 and c-Jun Mediate Th2 Cell-Specific IL-24 Gene Expression
Authors: Sahoo Anupama , Lee Choong-Gu , Jash Arijita , Son Jun-Seock , Kim Gicheon , Kwon Ho-Keun , So Jae-Seon , Im Sin-Hyeog
Published: February 2011

TCR signaling regulates multiple aspects of T cell function by controlling expression of various cytokine genes. IL-24 is a multifunctional cytokine belonging to the IL-10 family. It displays anticancer effects in diverse cancer cells and regulates immunopathology of psoriasis and rheumatoid arthritis. IL-24 also plays an important role in B cell differentiation. Mouse IL-24 gene is selectively expressed in activated Th2 cells upon TCR stimulation. However, the molecular mechanisms by which TCR stimulation induces IL-24 gene expression are still unclear. In this study, to elucidate the mechanism of Th2 cell-specific expression of IL-24, we identified a proximal promoter region (−157/+95bp) that plays critical role in activating the IL-24 gene in Th2 cells. This region has a Th2 cell-specific open chromatin structure along with permissive histone modifications. In vivo binding of Stat6 and AP-1 (c-Jun) to the IL-24 promoter locus in Th2 cells synergistically transactivated the IL-24 promoter. Stat6 and c-Jun proteins were found to physically cooperate with each other and upregulated IL-24 gene transcription. Knockdown of either Stat6 or c-Jun suppressed endogenous IL-24 gene expression in Th2 cells. In summary, TCR stimulation induces IL-24 expression in Th2 cells by the coordinate action of Stat6 and c-Jun transcription factors at the transcriptional level.
Contributions of Antinucleoprotein IgG to Heterosubtypic Immunity against Influenza Virus
Authors: LaMere Mark W. , Lam Ho-Tak , Moquin Amy , Haynes Laura , Lund Frances E. , Randall Troy D. , Kaminski Denise A.
Published: February 2011

Influenza A virus causes recurring seasonal epidemics and occasional influenza pandemics. Because of changes in envelope glycoprotein Ags, neutralizing Abs induced by inactivated vaccines provide limited cross-protection against new viral serotypes. However, prior influenza infection induces heterosubtypic immunity that accelerates viral clearance of a second strain, even if the external proteins are distinct. In mice, cross-protection can also be elicited by systemic immunization with the highly conserved internal nucleoprotein (NP). Both T lymphocytes and Ab contribute to such cross-protection. In this paper, we demonstrate that anti-NP IgG specifically promoted influenza virus clearance in mice by using a mechanism involving both FcRs and CD8+ cells. Furthermore, anti-NP IgG rescued poor heterosubtypic immunity in B cell-deficient mice, correlating with enhanced NP-specific CD8 T cell responses. Thus, Ab against this conserved Ag has potent antiviral activity both in naive and in influenza-immune subjects. Such antiviral activity was not seen when mice were vaccinated with another internal influenza protein, nonstructural 1. The high conservation of NP Ag and the known longevity of Ab responses suggest that anti-NP IgG may provide a critically needed component of a universal influenza vaccine.
Role of SLAM in NKT Cell Development Revealed by Transgenic Complementation in NOD Mice
Authors: Jordan Margaret A. , Fletcher Julie M. , Jose Roby , Chowdhury Shahead , Gerlach Nicole , Allison Janette , Baxter Alan G.
Published: February 2011

Allelic variation of SLAM expression on CD4+CD8+ thymocytes has been proposed to play a major role in NKT cell development. In this article, this hypothesis is tested by the production of subcongenic mouse strains and Slamf1 transgenic lines. The long isoform of the C57BL/6 allele of Slamf1 was transgenically expressed on CD4+CD8+ thymocytes under control of an hCD2 minigene. NOD.Nkrp1b.Tg(Slamf1)1 mice, which had a 2-fold increase in SLAM protein expression on CD4+CD8+ thymocytes, had a 2-fold increase in numbers of thymic NKT cells. The additional thymic NKT cells in NOD.Nkrp1b.Tg(Slamf1)1 mice were relatively immature, with a similar subset distribution to those of congenic NOD.Nkrp1b.Nkt1 and NOD.Nkrp1b.Slamf1 mice, which also express increased levels of SLAM on CD4+CD8+ thymocytes and produce larger numbers of NKT cells. Transgenic enhancement of SLAM expression also increased IL-4 and IL-17 production in response to TCR-mediated stimulation. Paradoxically, NOD.Nkrp1b.Tg(Slamf1)2 mice, which had a 7-fold increase in SLAM expression, showed no significant increase in NKT cells numbers; on the contrary, at high transgene copy number, SLAM expression levels correlated inversely with NKT cell numbers, consistent with a contribution to negative selection. These data confirm a role for SLAM in controlling NKT cell development and are consistent with a role in both positive and negative thymic selection of NKT cells.