bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel length back-calculation approach accounting for ontogenetic changes in the fish length – otolith size relationship during the early life of sprat (Sprattus sprattus)
Authors: Günther Claudia C. , Temming Axel , Baumann Hannes , Huwer Bastian , Möllmann Christian , Clemmesen Catriona , Herrmann Jens-Peter
Published: June 2012

An individual-based length back-calculation method was developed for juvenile Baltic sprat ( Sprattus sprattus ), accounting for ontogenetic changes in the relationship between fish length and otolith length. In sprat, metamorphosis from larvae to juveniles is characterized by the coincidence of low length growth, strong growth in body height, and maximal otolith growth. Consequently, the method identifies a point of metamorphosis for an individual as the otolith radius at maximum increment widths. By incorporating this information in our back-calculation method, estimated length growth for the early larval stage was more than 60% higher compared with the result of the biological intercept model. After minimal length growth during metamorphosis, we found the highest increase in length during the early juvenile stage. We thus located the strongest growth potential in the early juvenile stage, which is supposed to be critical in determining recruitment strength in Baltic sprat.
Natural stressors and disease risk: does the threat of predation increase amphibian susceptibility to ranavirus?
Authors: Haislip N.A. , Hoverman J.T. , Miller D.L. , Gray M.J.
Published: June 2012

Emerging infectious diseases have been identified as threats to biodiversity, yet our understanding of the factors contributing to host susceptibility to pathogens within natural populations remains limited. It has been proposed that species interactions within communities affect host susceptibility to pathogens, thereby contributing to disease emergence. In particular, predation risk is a common natural stressor that has been hypothesized to compromise immune function of prey through chronic stress responses possibly leading to increased susceptibility to pathogens. We examined whether predation risk experienced during the development of four larval anuran species increases susceptibility (mortality and infection) to ranaviruses, a group of viruses responsible for amphibian die-offs. Using controlled laboratory experiments, we exposed each species to a factorial combination of two virus treatments (no virus or virus) crossed with three predator-cue treatments (no predators, larval dragonflies, or adult water bugs). All four amphibian species reduced activity by 22%–48% following continuous exposure to predator cues. In addition, virus exposure significantly reduced survival by 17%–100% across all species. However, exposure to predator cues did not interact with the virus treatments to elevate mortality or viral load. Our results suggest that the expression of predator-induced plasticity in anuran larvae does not increase ranaviral disease risk.
CONNECTING CLOSED WORLD RESEARCH INFORMATION SYSTEMS THROUGH THE LINKED OPEN DATA WEB
Authors: JOERG BRIGITTE , RUIZ-RUBE IVAN , SICILIA MIGUEL-ANGEL , DVOŘÁK JAN , JEFFERY KEITH , HOELLRIGL THORSTEN , RASMUSSEN HENRIK S. , ENGFER ANDREAS , VESTDAM THOMAS , BARRIOCANAL ELENA GARCIA
Published: June 2012

Research Information Systems (RIS) play a critical role in the sharing of scientific information and provide researchers, professionals and decision makers with the required data for their activities. Existing RIS standards have proposed data models to represent the main entities for storage and exchange. These account for the needs of multiple stakeholders through a high flexibility based on a formal syntax and declared semantics, but for techno-historical reasons they assume the completeness of information within system boundaries. The distributed nature of research information across systems calls for a mechanism to link the local entities from the closed world of concrete RISs with other possibly underspecified entities exposed through other means, as for example, the Linked Open Data Web. By transformation of a relational model into an open graph model, differences between the two system paradigms are revealed. The main principles and techniques for exposing CERIF-driven relational data as linked data will be provided as a first step demonstrating effective RISs interconnection through the linked open data (LOD) Web.
A HYBRID SOFTWARE COST ESTIMATION APPROACH UTILIZING DECISION TREES AND FUZZY LOGIC
Authors: PAPATHEOCHAROUS EFI , ANDREOU ANDREAS S.
Published: June 2012

Software cost estimation (SCE) is one of the critical activities in software project management. During the past decades various models have been proposed for SCE. However, developing accurate and useful models is limited in practice despite the considerable financial gain they could offer to software stakeholders. Traditional techniques, such as regression, by-analogy and machine learning, face the difficulty of handling the dynamic nature of the software process and the problematic nature of the public data available. This paper addresses the issue of SCE proposing an alternative approach that combines robust decision tree structures with fuzzy logic. Fuzzy decision trees are generated using the CHAID and CART algorithms in a systematic manner, while development effort is treated as the dependent variable against two subsets of factors: The first contains selected attributes from the ISBSG, COCOMO and DESHARNAIS datasets and the second contains a subset of the available factors that can be measured early in the development cycle. The association rules obtained from the trees are then merged and defuzzified through a Fuzzy Implication System (FIS). The fuzzy framework is utilized to perform effort estimations. Experimental results indicate that the proposed approach is promising as it yields quite accurate estimations in most dataset cases considered. Finally, our evaluation suggests that accurate estimations may be produced, even when using only a small set of factors that can be measured early in the development cycle, thus increasing the practical value of the proposed cost model.
CROSSING INFORMATION AND WARPING POLYNOMIALS ABOUT THE TREFOIL KNOT
Authors: HIGA RYUJI , NAKANISHI YASUTAKA , SATOH SHIN , YAMAMOTO TAKUTO
Published: June 2012

We go along a knot diagram, and get a sequence of over- and under- crossing points. We will study which kinds of sequences are realized by diagrams of the trefoil knot. As an application, we will characterize the Shimizu warping polynomials for diagrams of the trefoil knot.
Dependence of Biasing Voltage and Illumination Power on the Built-in Electric Field of InGaP Solar Cells
Authors: Shu Gia-Wei , Yang Jun-Jie , Shu I-Jen , Shen Ji-Lin , Yang Min-De , Wu Chih-Hung , Huang Ying-Sheng
Published: June 2012

The electroreflectance spectra of InGaP solar cells at various biasing voltages and illumination levels were studied. The Franz–Keldysh oscillations were observed and the electric field at the junction of solar cells can be extracted. The measured electric field decreases with increasing biasing voltage and illumination level. The theoretical electric fields as a function of the biasing voltage and the photocurrent are calculated on the basis of the depletion approximation in the junction theory and the photovoltaic effect, respectively.
Investigation and Integration of Polycrystalline Silicon/TiN/SiON Gate Stack in Silicon on Thin Buried Oxide Complementary Metal Oxide Semiconductor Field Effect Transistors
Authors: Ishigaki Takashi , Tsuchiya Ryuta , Morita Yusuke , Sugii Nobuyuki , Kimura Shinichiro , Iwamatsu Toshiaki , Oda Hidekazu , Inoue Yasuo
Published: June 2012

We developed fully depleted silicon on thin buried oxide (SOTB) complementary metal oxide semiconductor field effect transistors (CMOSFETs) with a polycrystalline-silicon (poly-Si)/TiN/SiON gate stack. We investigated the flat-band voltage (V
fb) shift of the gate stack for the threshold voltage (V
th) symmetry of SOTB CMOSFETs. We found that the V
fb shift depended on both TiN thickness and thermal load. Thicker TiN above 15 nm is preferable for obtaining the midgap value of V
fb with considering the thermal budget of the SOTB process. We also integrated the gate stack into SOTB CMOSFETs, which showed that the V
th roll-off characteristics corresponded to the proper control of the effective work function by considering how the impurity-related work function modulation affects. Narrow channel characteristics of the TiN-gate SOTB CMOSFETs were also shown to be superior to fully silicided gate SOTB devices due to the less silicidation.
A Feasibility Study of Beam-Wave Interaction in 670 GHz Gyrotron for Radioactive Material Detection Application
Authors: Kumar Nitin , Singh Udaybir , Kumar Anil , Sinha Ashok K.
Published: June 2012

In this article, a feasibility study of 300 kW RF power generation with TE25,10(transverse electric) operating mode for 670 GHz gyrotron is presented. The beam-wave interaction computation and power growth at fundamental harmonic are carried out by using the particle-in-cell code MAGIC. The beam current, beam voltage and magnetic field at cavity center are optimized for the efficient beam-wave interaction, which are 14 A, 70 kV, and 26.34 T, respectively. The parametric analysis is also carried out to provide the flexibility in the actual fabrication of the device. It is found that more than 300 kW power generation is possible at TE25,10operating mode.
Single Etch-Pit Shape on Off-Angled 4H-SiC(0001) Si-Face Formed by Chlorine Trifluoride
Authors: Hatayama Tomoaki , Tamura Tetsuya , Yano Hiroshi , Fuyuki Takashi
Published: June 2012

The etch pit shape of an off-angled 4H-SiC Si-face formed by chlorine trifluoride (ClF3) in nitrogen (N2) ambient has been studied. One type of etch pit with a crooked hexagonal shape was formed at an etching temperature below 500 °C. The angle of the etch pit measured from a cross-sectional atomic force microscopy image was about 10° from the [112̄0] view. The dislocation type of the etch pit was discussed in relation to the etch pit shape and an electron-beam-induced current image.
MDM2 Overexpression Deregulates the Transcriptional Control of RB/E2F Leading to DNA Methyltransferase 3A Overexpression in Lung Cancer
Authors: Tang Yen-An , Lin Ruo-Kai , Tsai Yo-Ting , Hsu Han-Shui , Yang Yi-Chieh , Chen Chih-Yi , Wang Yi-Ching
Published: June 2012

Purpose: Overexpression of DNA 5′-cytosine-methyltransferase 3A (DNMT3A), which silences genes including tumor suppressor genes (TSG), is involved in many cancers. Therefore, we examined whether the transcriptional deregulation of RB/MDM2 pathway was responsible for DNMT3A overexpression and analyzed the therapeutic potential of MDM2 antagonist for reversing aberrant DNA methylation status in lung cancer.

Experimental Design: The regulation of DNMT3A expression and TSG methylation status by RB/MDM2 was assessed in cancer cell lines and patients. The effects of Nutlin-3, an MDM2 antagonist, on tumor growth in relation to DNMT3A expression and TSG methylation status were examined by xenograft model.

Results: We found that RB suppressed DNMT3A promoter activity and mRNA/protein expression through binding with E2F1 protein to the DNMT3A promoter, leading to the decrease of methylation level globally and TSG specifically. In addition, MDM2 dramatically induced DNMT3A expression by negative control over RB. In clinical study, MDM2 overexpression inversely correlated with RB expression, while positively associating with overexpression of DNMT3A in samples from patients with lung cancer. Patients with high MDM2 and low RB expression showed DNMT3A overexpression with promoter hypermethylation in TSGs. Treatment with Nutlin-3, an MDM2 antagonist, significantly suppressed tumor growth and reduced DNA methylation level of TSGs through downregulation of DNMT3A expression in xenograft studies.

Conclusions: This study provides the first cell, animal, and clinical evidence that DNMT3A is transcriptionally repressed, in part, by RB/E2F pathway and that the repression could be attenuated by MDM2 overexpression. MDM2 is a potent target for anticancer therapy to reverse aberrant epigenetic status in cancers. Clin Cancer Res; 18(16); 4325–33. ©2012 AACR.
Adenosine A
2B
Receptor Agonism Inhibits Neointimal Lesion Development After Arterial Injury in Apolipoprotein E–Deficient Mice
Authors: Bot Ilze , de Vries Henk , Korporaal Suzanne J. A. , Foks Amanda C. , Bot Martine , van Veldhoven Jacobus , ter Borg Mariëtte N. D. , van Santbrink Peter J. , van Berkel Theo J. C. , Kuiper Johan , Ijzerman Adriaan P.
Published: June 2012

Objective—

The A
2B
adenosine receptor (A
2B
R) is highly expressed in macrophages and vascular smooth muscle cells and has been established as an important regulator of inflammation and vascular adhesion. Recently, it has been demonstrated that A
2B
R deficiency enhances neointimal lesion formation after vascular injury. Therefore, we hypothesize that A
2B
R agonism protects against injury-induced intimal hyperplasia.

Methods and Results—

Apolipoprotein E–deficient mice were fed a Western-type diet for 1 week, after which the left common carotid artery was denuded. Mice were treated with the A
2B
receptor agonist BAY60-6583 or vehicle control for 18 days. Interestingly, lumen stenosis as defined by the neointima/lumen ratio was inhibited by treatment with the A
2B
receptor agonist, caused by reduced smooth muscle cell proliferation. Collagen content was significantly increased in the BAY60-6583–treated mice, whereas macrophage content remained unchanged. In vitro, vascular smooth muscle cell proliferation decreased dose dependently whereas collagen content of cultured smooth muscle cells was increased by BAY60-6583.

Conclusion—

Our data show that activation of the adenosine A
2B
receptor protects against vascular injury, while it also enhances plaque stability as indicated by increased collagen content. These outcomes thus point to A
2B
receptor agonism as a new therapeutic approach in the prevention of restenosis.
Making Waves or Treading Water? An Analysis of Charter Schools in New York State
Authors: Silverman Robert Mark
Published: June 2012

This article compares charter schools and other public schools in New York State. School Report Card (SRC) data measuring student, teacher, and school characteristics from the state’s 16 urban school districts with charter schools were examined. Descriptive and multivariate analysis was used. The findings suggest that there are more similarities in student outcomes between charter schools and other public schools than differences. Although charter schools had higher sixth- and eighth-grade math scores, outcomes were comparable along other measures. Systemic issues, such as poverty, suspensions, and poor attendance had relatively stronger effects on student performance regardless of school type.
Synthesis and phase behavior of chiral liquid crystalline polymeric networks derived from menthol
Authors: Jia Ying-Gang , Hu Jian-She , Li Dan , Meng Qing-Bao , Zhang Xia
Published: June 2012

The synthesis of new chiral monomer 4-(menthyloxyacetoxy- benzoyloxy)biphenyl-4′-(2-(undec-10-e noyloxy)ethoxy)benzoate (ML), crosslinking agent 4-(undec-10-enoyloxy)biphenyl-4′-(2-(undec-10-enoyloxy)ethoxy)benzoate (CA), and liquid crystal polymer networks (E1−E5) containing menthyl group is presented. Their chemical structures and phase behavior were characterized with Fourier transform infrared (FT-IR), proton nuclear magnetic resonance (1H-NMR), elemental analyses, polarizing optical microscopy, differential scanning calorimetry, thermogravimetric analysis (TGA), and X-ray diffraction. The selective reflection of light for ML was investigated with ultraviolet/visible/near infrared (UV/Visible/NIR). By inserting a flexible spacer between the mesogenic core and the terminal menthyl groups, MLcould form mesophase and show a chiral smectic C phase, cholesteric phase and cubic blue phase. CA displayed a smectic A phase and nematic phase. The polymer networks containing less than 12 mol% of the crosslinking units showed reversible cholesteric phase transition, wide mesophase temperature range, and excellent thermal stability. With increasing the content of crosslinking unit, the corresponding Tg increased, the Ti decreased, and the mesophase temperature range narrowed for E1−E5. TGA showed that the Td(5%) was greater than 330°C for E1−E5.
Multinodular Reticular Schwannoma in the Head and Neck Region
Authors: Lau Patrick P. L. , Yau Derek T. W. , Lau W. H. , Mak L. S. , Chan John K. C.
Published: June 2012

Reticular/microcystic schwannoma is a recently described morphologic variant of schwannoma that occurs predominantly in visceral organs, most commonly the gastrointestinal tract. This report describes a case occurring in the masticator space, accompanied by focal erosion of the orbital floor, clinically and radiologically worrisome for malignancy. The 26-year-old man presented with facial swelling for 3 month. The tumor shows a multinodular appearance, with dense lymphoplasmacytic infiltrates in the fibrous septa. The tumor nodules are composed of plump spindle cells disposed in a reticular pattern. The diagnosis is confirmed by strong positive staining for S100 protein. The differential diagnoses of reticular schwannoma in the soft tissues of head and neck region are different from those in the gastrointestinal tract.
The Development of a Modified Ketogenic Diet Program
Authors: Chatfield Beth
Published: June 2012

Developing and implementing the modified ketogenic diet (MKD), an alternative to the traditional ketogenic diet (KD), proved to be a clinical and family-centered care success for the outpatient and ultimately the inpatient program at Connecticut Children’s Medical Center. Initially introduced as an option in the outpatient program, the need for the MKD treatment was soon identified in the inpatient setting as well. To ensure consistent and appropriate care for the children receiving the MKD, an inpatient clinical pathway was developed and adopted as standard of care. This included the development of a standard MKD menu for the hospital. Use of the name modified ketogenic diet versus modified Atkins diet ® was adopted to differentiate it from the KD and avoid possible confusion regarding the diet for weight management. An observational study of Connecticut Children’s MKD outcomes demonstrates effectiveness similar to the KD diet. Out of 36 patients completing the MKD, 56% experienced ≤50% to 100% seizure reduction. Of this 56%, 17% were seizure free, and 39% had ³50% to 90% seizure reduction. Connecticut Children’s outcomes support the MKD as a viable nutrition option for pediatric patients with refractory epilepsy. Two case studies are presented to provide support and additional treatment modalities for use in clinical practice for registered dietitians initiating the MKD.
Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index: a prospective, multicenter GITMO study
Authors: Raimondi Roberto , Tosetto Alberto , Oneto Rosi , Cavazzina Riccardo , Rodeghiero Francesco , Bacigalupo Andrea , Fanin Renato , Rambaldi Alessandro , Bosi Alberto
Published: June 2012

The development of tools for the prediction of nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (HSCT) would offer a major guidance in the therapeutic decision. Recently, the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) has been associated with increased NRM risk in several retrospective studies, but its clinical utility has never been demonstrated prospectively in an adequately sized cohort. To this aim, we prospectively evaluated a consecutive cohort of 1937 patients receiving HSCT in Italy over 2 years. HCT-CI was strongly correlated with both 2-year NRM (14.7%, 21.3%, and 27.3% in patients having an HCT-CI score of 0, 1-2, and ≥ 3, respectively) and overall survival (56.4%, 54.5%, and 41.3%, respectively). There was an excellent calibration between the predicted and observed 2-year NRM in patients having an HCT-CI score of 0 and 1-2, whereas in the ≥ 3 group the predicted NRM overestimated the observed NRM (41% vs 27.3%). HCT-CI alone was the strongest predictor of NRM in patients with lymphoma, myelodysplastic syndrome, and acute myeloid leukemia in first remission (c-statistics 0.66, 064, and 0.59, respectively). We confirm the clinical utility of the HCT-CI score that could also identify patients at low NRM risk possibly benefiting from an HSCT-based treatment strategy.
Aragon workers’ health study – design and cohort description
Authors: Casasnovas José A , Alcaide Victor , Civeira Fernando , Guallar Eliseo , Ibañez Borja , Borreguero Jesús Jiménez , Laclaustra Martin , León Montserrat , Peñalvo José Luis , Ordovás José M , Pocovi Miguel , Sanz Ginés , Fuster Valentín
Published: June 2012

Background

Spain, a Mediterranean country with relatively low rates of coronary heart disease, has a high prevalence of traditional cardiovascular risk factors and is experiencing a severe epidemic of overweight/obesity. We designed the Aragon Workers’ Health Study (AWHS) to characterize the factors associated with metabolic abnormalities and subclinical atherosclerosis in a middle aged population in Spain free of clinical cardiovascular disease. The objective of this paper is to describe the study design, aims and baseline characteristics of participants in the AWHS.

Methods/Design

Longitudinal cohort study based on the annual health exams of 5,400 workers of a car assembly plant in Figueruelas (Zaragoza, Spain). Study participants were recruited during a standardized clinical exam in 2009–2010 (participation rate 95.6%). Study participants will undergo annual clinical exams and laboratory assays, and baseline and triennial collection of biological materials for biobanking and cardiovascular imaging exams (carotid, femoral and abdominal ultrasonography, coronary calcium score, and ankle-arm blood pressure index). Participants will be followed-up for 10 years.

Results

The average (SD) age, body mass index, and waist circumference were 49.3 (8.7) years, 27.7 (3.6) kg/m2 and 97.2 (9.9) cm, respectively, among males (N = 5,048), and 40.8 (11.6) years, 24.4 (3.8) kg/m2, and 81.9 (9.9) cm, among females (N = 351). The prevalence of overweight, obesity, current smoking, hypertension, hypercholesterolemia, and diabetes were 55.0, 23.1, 37.1, 40.3, 75.0, and 7.4%, respectively, among males, and 23.7, 8.3, 45.0, 12.1, 59.5, and 0.6%, respectively, among females. In the initial 587 study participants who completed all imaging exams (94.5% male), the prevalence of carotid plaque, femoral plaque, coronary calcium score >1 to 100, and coronary calcium score >100 was 30.3, 56.9, 27.0, and 8.8%, respectively. 67.7% of study participants had at least one plaque in the carotid or femoral arteries.

Discussion

Baseline data from the AWHS show a high prevalence of cardiovascular risk factors and of sublinical atherosclerosis. Follow-up of this cohort will allow the assessment of subclinical atherosclerosis progression and the link of disease progression to traditional and emergent risk factors.
Left atrial pathological degeneration assessed by integrated backscatter transesophageal echocardiography as a predictor of progression to persistent atrial fibrillation: Results from a prospective study of three-years follow-up
Authors: Kubota Tomoki , Kawasaki Masanori , Takasugi Nobuhiro , Imai Hajime , Ishihara Yoshiyuki , Okubo Munenori , Takahashi Shigekiyo , Sato Hironobu , Nishigaki Kazuhiko , Takemura Genzou , Minatoguchi Shinya
Published: June 2012

Background

It is recognized that one of the causes of atrial fibrillation (AF) is pathological degeneration of the left atrium (LA). However, prospective study that elucidated the relationship between the incidence of persistent AF and pathological degeneration has not been performed. The purpose of this study was to elucidate the usefulness of integrated backscatter (IBS) values for the prediction of progression from paroxysmal AF (PAF) to persistent AF.

Methods

We measured IBS values of the entire LA wall at 5 mm intervals (except the posterior wall) in 27 patients with paroxysmal AF and evaluated progression to persistent AF for three years. IBS values were acquired with transesophageal echocardiography (TEE) using a 4–7 MHz transducer. IBS values were calculated as the average power of the backscattered signal from regions of interest (ROI). Each IBS value was color-coded to construct three dimensional maps.

Results

Average IBS values of total voxels in color-coded maps in the persistent AF group were significantly greater than those in the non-persistent AF group (25.8 ± 5.0 dB vs. 17.4 ± 10.2 dB, p = 0.047), whereas there was no significant difference in LA diameter between the persistent AF and the non-persistent AF group. There was significant difference in persistent AF-free survival after the baseline measurements in the subjects stratified by IBS value (<20 dB versus ≥20 dB) (univariate Cox regression analysis: hazard ratio: 8.74, p =0.046).

Conclusion

Using IBS values measured by TEE, we can identify an increase in atrial degeneration that may predict the occurrence of persistent AF before LA dilation.
Identifying the sociodemographic determinants of subjective health complaints in a cross-sectional study of Greek adolescents
Authors: Petanidou Dimitra , Giannakopoulos George , Tzavara Chara , Dimitrakaki Christine , Ravens-Sieberer Ulricke , Kolaitis Gerasimos , Tountas Yannis
Published: June 2012

Background

Experience of common health symptoms without a clear physical or psychological cause, such as headache or dizziness, is often reported in adolescence. The present study attempted to investigate associations of self-reported subjective health complaints (SHC) with a number of sociodemographic factors of Greek adolescents.

Methods

Questionnaires were administered to a Greek nationwide random school-based sample of adolescents aged 12 to 18 years and their parents in 2003. Data from 922 adolescent-parent pairs were analyzed (response rate = 63%). Adolescents’ reported subjective health complaints were assessed for their association with a number of sociodemographic factors: age, sex, type of area of residence according to level of urbanization, immigration background, parental education and employment status, family socioeconomic status and perceived quality of financial resources (PQFR). Multiple linear regression analysis was used to assess the association of the aforementioned factors with subjective health complaints as the dependent variable.

Results

Most sociodemographic variables, apart from area of residence and immigration background, were independently associated with subjective health complaints in the univariate analyses. The multiple linear regression analysis, however, limited the factors that could predict adolescents’ subjective health complaints to four (age, sex, Family Affluence Scale score and perceived quality of financial resources). Some considerations regarding parental employment status and immigration background are highlighted.

Conclusions

Our study highlights the sociodemographic components of subjective health complaints in the Greek adolescent population. The need to include adolescent-specific measures when collecting information on adolescents’ social background is underlined. Identifying vulnerable adolescent populations could lead to effective health promoting and preventive interventions.
The make or buy debate: Considering the limitations of domestic production in Tanzania
Authors: Wilson Kinsley Rose , Kohler Jillian Clare , Ovtcharenko Natalia
Published: June 2012

Background

In order to ensure their population’s regular access to essential medicines, many least developed countries and developing countries are faced with the policy question of whether to import or manufacture drugs locally, in particular for life-saving antiretroviral medicines for HIV/AIDS patients. In order for domestic manufacturing to be viable and cost-effective, the local industry must be able to compete with international suppliers of medicines by producing sufficiently low cost ARVs.

Methods

This paper considers the ‘make-or-buy’ dilemma by using Tanzania as a case study. Key informant interviews, event-driven observation, and purposive sampling of documents were used to evaluate the case study. The case study focused on Tanzania’s imitation technology transfer agreement to locally manufacture a first-line ARV (3TC + d4T + NVP), reverse engineering the ARV.

Results

Tanzania is limited by weak political support for the use of TRIPS flexibilities, limited production capacity for ARVs and limited competitiveness in both domestic and regional markets. The Ministry of Health and Social Welfare encourages the use of flexibilities while others push for increased IP protection. Insufficient production capacity and lack of access to donor-financed tenders make it difficult to obtain economies of scale and provide competitive prices.

Conclusions

Within the “make-or-buy” context, it was determined that there are significant limitations in domestic manufacturing for developing countries. The case study highlights the difficulty of governments to make use of economies of scale and produce low-cost medicines, attract technology transfer, and utilize the flexibilities of the WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). The results demonstrate the importance of evaluating barriers to the use of TRIPS flexibilities and long-term planning across sectors in future technology transfer and manufacturing initiatives.
RACK1, a clue to the diagnosis of cutaneous melanomas in horses
Authors: Campagne Cécile , Julé Sophia , Bernex Florence , Estrada Mercedes , Aubin-Houzelstein Geneviève , Panthier Jean-Jacques , Egidy Giorgia
Published: June 2012

Background

Melanocytic proliferations are common in horses but the diagnosis of malignancy is not always straightforward. To improve diagnosis and prognosis, markers of malignancy are needed. Receptor for activated C kinase 1 (RACK1) protein may be such a marker. RACK1 was originally found to characterize malignant melanocytic lesions in the Melanoblastoma-bearing Libechov minipig (MeLiM) and, later, in human patients. Our purpose was to investigate the value of RACK1 in the classification of cutaneous melanocytic proliferations in horses.

Results

Using immunofluorescence, we report here that both MITF (Microphthalmia-associated transcription factor) and PAX3 (Paired box 3) allow the identification of melanocytic cells in horse skin samples. Importantly, RACK1 was detected in melanocytic lesions but not in healthy skin melanocytes. Finally, we found that RACK1 labeling can be used in horses to distinguish benign melanocytic tumors from melanomas. Indeed, RACK1 labeling appeared more informative to assess malignancy than individual histomorphological features.

Conclusions

This study confirms that horses provide an interesting model for melanoma genesis studies. It establishes MITF and PAX3 as markers of horse melanocytic cells. RACK1 emerges as an important marker of malignancy which may contribute to progress in the diagnosis of melanomas in both human and veterinary medicine.
A minimal ligand binding pocket within a network of correlated mutations identified by multiple sequence and structural analysis of G protein coupled receptors
Authors: Moitra Subhodeep , Tirupula Kalyan C , Klein-Seetharaman Judith , Langmead Christopher James
Published: June 2012

Background

G protein coupled receptors (GPCRs) are seven helical transmembrane proteins that function as signal transducers. They bind ligands in their extracellular and transmembrane regions and activate cognate G proteins at their intracellular surface at the other side of the membrane. The relay of allosteric communication between the ligand binding site and the distant G protein binding site is poorly understood. In this study, GREMLIN [1], a recently developed method that identifies networks of co-evolving residues from multiple sequence alignments, was used to identify those that may be involved in communicating the activation signal across the membrane. The GREMLIN-predicted long-range interactions between amino acids were analyzed with respect to the seven GPCR structures that have been crystallized at the time this study was undertaken.

Results

GREMLIN significantly enriches the edges containing residues that are part of the ligand binding pocket, when compared to a control distribution of edges drawn from a random graph. An analysis of these edges reveals a minimal GPCR binding pocket containing four residues (T1183.33, M2075.42, Y2686.51 and A2927.39). Additionally, of the ten residues predicted to have the most long-range interactions (A1173.32, A2726.55, E1133.28, H2115.46, S186EC2, A2927.39, E1223.37, G902.57, G1143.29 and M2075.42), nine are part of the ligand binding pocket.

Conclusions

We demonstrate the use of GREMLIN to reveal a network of statistically correlated and functionally important residues in class A GPCRs. GREMLIN identified that ligand binding pocket residues are extensively correlated with distal residues. An analysis of the GREMLIN edges across multiple structures suggests that there may be a minimal binding pocket common to the seven known GPCRs. Further, the activation of rhodopsin involves these long-range interactions between extracellular and intracellular domain residues mediated by the retinal domain.
Functional SNPs within the Intron 1 of the PROP1 Gene Contribute to Combined Growth Hormone Deficiency (CPHD)
Authors: Godi Michela , Mellone Simona , Tiradani Luigi , Marabese Rita , Bardelli Claudio , Salerno Mariacarolina , Prodam Flavia , Bellone Simonetta , Petri Antonella , Momigliano-Richiardi Patricia , Bona Gianni , Giordano Mara
Published: June 2012

Context:

Mutations within the PROP1 gene represent one of the main causes of familial combined pituitary hormone deficiency (CPHD). However, most of the cases are sporadic with an unknown genetic cause.

Objective:

The aim of this study was the search for low penetrance variations within and around a conserved regulatory element in the intron 1 of PROP1, contributing to a multifactorial form of the disease in sporadic patients.

Methods and Patients:

A fragment of 570 bp encompassing the conserved region was sequenced in 107 CPHD patients and 294 controls, and an association study was performed with the four identified variants, namely c.109+435G>A (rs73346254), c.109+463C>T (rs4498267), c.109+768C>G (rs4431364), and c.109+915_917ins/delTAG (rs148607624). The functional role of the associated polymorphisms was evaluated by luciferase reporter gene expression analyses and EMSA.

Results:

A statistically significant increased frequency was observed in the patients for rs73346254A (P = 5 × 10−4) and rs148607624delTAG (P = 0.01) alleles. Among all the possible allele combinations, only the haplotype bearing both risk alleles showed a significantly higher frequency in the patients vs. controls (P = 4.7 × 10−4) and conferred a carrier risk of 4.19 (P = 1.2 × 10−4). This haplotype determined a significant decrease of the luciferase activity in comparison with a basal promoter and the other allelic combinations in GH4C and MCF7 cells (P = 4.6 × 10−6; P = 5.5 × 10−4, respectively). The EMSA showed a differential affinity for nuclear proteins for the alternative alleles of the two associated variations.

Conclusions:

Variations with a functional significance conferring susceptibility to CPHD have been identified in the PROP1 gene, indicating a multifactorial origin of this disorder in sporadic cases.
Studios in the Street: Creative Community and Visual Arts
Authors: Widener Daniel
Published: June 2012

The visual arts played a critical role in the cultural awakening that began with the Second World War and flourished in the aftermath of the Watts riots. In searching for new means of expression rooted in and relevant to the communities from which they came, black artists based in Los Angeles pushed the parameters of consciously black art by offering a fundamental reevaluation of the meaning art could have in black lives. Much like avant-garde jazz musicians, visual artists developed a unique mixed-media language that combined themes of political insurgency, communitarian engagement, and familiar cultural tropes of migration, musical, spirituality, and family. Augmented by a cross-generic engagement with sound and text, this bricolage avoided the formal limits of realist representation while producing a culturally specific aesthetics that artists could take as emblematic of the black liberation movement’s broader critique of the limits of American society for what Duke Ellington had called “the sun-tanned tenth of the nation.”
After the Black Arts Movement
Authors: Taylor Clyde
Published: June 2012

This essay attempts to locate the historical significance of Black Arts as a potent, widely social modernism, unlike the café/salon confines of the Paris model. The Black Arts and Black Aesthetics movements were at the center of a rupture of misidentified blackness left over from the American Apartheid epoch. Vertiginously brilliant and highly self-conscious, the Black Arts core leadership held sharply defined notions of mission and success, sometimes undervaluing the impact of Black Aesthetics as its critical-theoretical ally in academe and the culture industry. That core did not always recognize personal, geographic, or gender variations of its shared revolts. In this century the fixed branding of this renovative movement has to be opened to creative streams it never envisioned, some of which it provoked and others it only shared in exciting, revolutionary, postcolonial times.
Why Spiral?
Authors: Siegel Jeanne
Published: June 2012

Spiral, founded in 1963 by Romare Bearden, Norman Lewis, and Charles Alston, was a group of black American artists in New York. This article, originally published in ARTnews in 1966, explores the attitudes of Spiral’s membership about civil rights, Negro art, the “Negro Image,” and the group’s purpose, with commentary from the members themselves.
From the Center: The Spiral Group, 1963–1966
Authors: Martin Courtney J.
Published: June 2012

Spiral, founded in 1963 by Romare Bearden, Norman Lewis, and Charles Alston, was a group of black American artists in New York. This group has been credited with fostering Bearden’s entry into collage, launching a debate around the political function of abstraction and figuration, and incubating the early careers of Emma Amos and others. This essay looks at how Spiral’s trip to the March on Washington and its only exhibition demonstrate a lack of aesthetic and social cohesion in the group’s main collective activities, making it a typical example of post-1945 art collectives.
The Art of Richard Mayhew
Authors: Hess Janet Berry
Published: June 2012

This article employs ten years of interviews with the African and Native American artist Richard Mayhew to examine Mayhew’s artistic narrative of cultural “spiritual” commitments and ideals, his alignment with community production and performance, and his advocacy of an aesthetic individualism that embraces the overriding challenge confronted by Spiral, an artistic alliance that represented African American artists in the March on Washington and that sought to formulate an ongoing artistic response to the civil rights movement.
Talking in Tongues: Personal Reflections on Kara Walker
Authors: Harris Michael D.
Published: June 2012

This essay is a personal meditation on Kara Walker’s work seven years after the author’s critical assessment of her work in the book Colored Pictures. Walker’s work is linked to African American cultural practices like signifyin’ and speaking in tongues and is found to have elusive and reflective qualities implicating the viewer as much as the artist’s own intentionality.
Novel Method of Producing Carbon Nanoparticles on Benzene/Water Interface with Femtosecond Laser Plasma Filament
Authors: Yatsuhashi Tomoyuki , Uchida Naoko , Nishikawa Kayo
Published: June 2012

The irradiation of NIR femtosecond laser pulses to a benzene/water bilayer dramatically enhanced the formation of carbon nanoparticles compared with that in neat benzene. The focusing-position-dependent chemistry and the oxidative mechanism of nanoparticle formation are discussed.
Control of Periodicity in Mesoporous Silica Films with Aligned Mesochannels Prepared by a Sol–Gel Process
Authors: Komoto Atsushi , Kubo Wataru , Miyata Hirokatsu
Published: June 2012

Periodicity of mesoporous silica films with aligned cylindrical pores formed on a substrate with a rubbing-treated polyimide through a sol–gel process can be finely controlled using nonionic surfactants with different alkyl chains. The degree of alignment increases with the alkyl-chain length of the surfactant due to increase in anisotropic hydrophobic interaction between the oriented polyimide chains and the alkyl groups, which is responsible for the alignment.
Development of an Instrument to Measure Medical Students' Attitudes Toward People with Disabilities
Authors: Symons Andrew B. , Fish Reva , McGuigan Denise , Fox Jeffery , Akl Elie A.
Published: June 2012

As curricula to improve medical students' attitudes toward people with disabilities are developed, instruments are needed to guide the process and evaluate effectiveness. The authors developed an instrument to measure medical students' attitudes toward people with disabilities. A pilot instrument with 30 items in four sections was administered to 342 medical students. Internal consistency reliability and factor analysis were conducted. The Cronbach's alpha coefficient was 0.857, indicating very good internal consistency. Five components were identified: comfort interacting with people with disabilities, working with people with disabilities in a clinical setting, negative impressions of self-concepts of people with disabilities, positive impressions of self-concepts of people with disabilities, and conditional comfort with people with disabilities. The instrument appears to have good psychometric properties and requires further validation.
Collectible Toys as Marketing Tools: Understanding Preschool Children's Responses to Foods Paired with Premiums
Authors: McAlister Anna R. , Cornwell T. Bettina
Published: June 2012

Concern over obesity finds policy makers struggling to understand marketing's role in food choice, but with a limited empirical base to inform them. Because food patterns established in childhood influence life-long patterns, toy premiums that may sway food preference are being questioned. The motivational pull of collectible toys is of particular interest in this discussion because repeated exposure to foods engendered by frequent purchases to obtain collectibles may establish food preference. Thus, Study 1 addresses the role of collectible toys as premiums accompanying food offerings. The authors show that these premiums influence children's attitudes toward both unhealthful and healthful meal offerings. In Study 2, a choice task reveals that a healthful meal is favored when it is paired with a collectible toy premium and the unhealthful meal is presented with no premium. Findings are discussed in terms of providing an evidence base for policy decisions.
Field Test of Circular Footings on Reinforced Granular Fill Layer Overlying a Clay Bed
Authors: Laman Mustafa , Yildiz Abdulazim , Ornek Murat , Demir Ahmet
Published: June 2012

The ultimate bearing capacity and settlement of a circular shallow rigid plate on compacted granular fill layer with and without geogrid reinforcement overlying on natural clay deposit exhibiting low bearing capacity and large settlement have been investigated. A total of 15 field tests were carried out using a circular model rigid plate with a diameter of 0.90 m. This study has been initially directed to evaluate the beneficial effects of the compacted granular fill layer on natural clay deposit for the shallow rigid plate performance. Then, the reinforcing effect of the top granular fill layer with horizontal layers of welded geogrid reinforcement on the bearing capacity and settlement has been studied. Parameters of the testing program include granular fill thickness, depth of first reinforcement, vertical spacing of reinforcement layers, and number of reinforcement layers. Bearing capacity ratio (BCR) and percentage reduction in settlement (PRS) were defined to evaluate improvement performance. Based on the test results, the effect of the granular fill and welded geogrid reinforcement on the bearing capacity and settlement are discussed. The results indicate that the use of granular fill layers over natural clay soils has considerable effects on the bearing capacity and settlement characteristics. The construction of granular fill layer with welded geogrid reinforcement over clay deposit helps in redistributing the applied load to a wider area. It has been observed that the use of welded geogrid reinforcement in granular fill layer provides additional improvement of bearing capacity and provides reduction in settlement of the rigid plate up to 80 and 60 %, respectively.
Prokaryotic Chaperones Support Yeast Prions and Thermotolerance and Define Disaggregation Machinery Interactions
Authors: Reidy Michael , Miot Marika , Masison Daniel C
Published: June 2012

Saccharomyces cerevisiae Hsp104 and Escherichia coli ClpB are Hsp100 family AAA+ chaperones that provide stress tolerance by cooperating with Hsp70 and Hsp40 to solubilize aggregated protein. Hsp104 also remodels amyloid in vitro and promotes propagation of amyloid prions in yeast, but ClpB does neither, leading to a view that Hsp104 evolved these activities. Although biochemical analyses identified disaggregation machinery components required for resolubilizing proteins, interactions among these components required for in vivo functions are not clearly defined. We express prokaryotic chaperones in yeast to address these issues and find ClpB supports both prion propagation and thermotolerance in yeast if it is modified to interact with yeast Hsp70 or if E. coli Hsp70 and its cognate nucleotide exchange factor (NEF) are present. Our findings show prion propagation and thermotolerance in yeast minimally require cooperation of species-specific Hsp100, Hsp70, and NEF with yeast Hsp40. The functions of this machinery in prion propagation were directed primarily by Hsp40 Sis1p, while thermotolerance relied mainly on Hsp40 Ydj1p. Our results define cooperative interactions among these components that are specific or interchangeable across life kingdoms and imply Hsp100 family disaggregases possess intrinsic amyloid remodeling activity.
Mapping Quantitative Trait Loci onto a Phylogenetic Tree
Authors: Broman Karl W , Kim Sungjin , Sen Śaunak , Ané Cécile , Payseur Bret A
Published: June 2012

Despite advances in genetic mapping of quantitative traits and in phylogenetic comparative approaches, these two perspectives are rarely combined. The joint consideration of multiple crosses among related taxa (whether species or strains) not only allows more precise mapping of the genetic loci (called quantitative trait loci, QTL) that contribute to important quantitative traits, but also offers the opportunity to identify the origin of a QTL allele on the phylogenetic tree that relates the taxa. We describe a formal method for combining multiple crosses to infer the location of a QTL on a tree. We further discuss experimental design issues for such endeavors, such as how many crosses are required and which sets of crosses are best. Finally, we explore the method’s performance in computer simulations, and we illustrate its use through application to a set of four mouse intercrosses among five inbred strains, with data on HDL cholesterol.