bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Efficacy and Safety of the Glucagon Receptor Antagonist LY2409021 in Patients With Type 2 Diabetes: 12- and 24-Week Phase 2 Studies
Authors: Kazda Christof M. , Ding Ying , Kelly Ronan P. , Garhyan Parag , Shi Chunxue , Lim Chay Ngee , Fu Haoda , Watson David E. , Lewin Andrew J. , Landschulz William H. , Deeg Mark A. , Moller David E. , Hardy Thomas A. 
Published: January 2016

OBJECTIVE
Type 2 diabetes pathophysiology is characterized by dysregulated glucagon secretion. LY2409021, a potent, selective small-molecule glucagon receptor antagonist that lowers glucose was evaluated for efficacy and safety in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS
The efficacy (HbA1c and glucose) and safety (serum aminotransferase) of once-daily oral administration of LY2409021 was assessed in two double-blind studies. Phase 2a study patients were randomized to 10, 30, or 60 mg of LY2409021 or placebo for 12 weeks. Phase 2b study patients were randomized to 2.5, 10, or 20 mg LY2409021 or placebo for 24 weeks.

RESULTS
LY2409021 produced reductions in HbA1c that were significantly different from placebo over both 12 and 24 weeks. After 12 weeks, least squares (LS) mean change from baseline in HbA1c was –0.83% (10 mg), –0.65% (30 mg), and –0.66% (60 mg) (all P &lt; 0.05) vs. placebo, 0.11%. After 24 weeks, LS mean change from baseline in HbA1c was –0.45% (2.5 mg), –0.78% (10 mg, P &lt; 0.05), –0.92% (20 mg, P &lt; 0.05), and –0.15% with placebo. Increases in serum aminotransferase, fasting glucagon, and total fasting glucagon-like peptide-1 (GLP-1) were observed; levels returned to baseline after drug washout. Fasting glucose was also lowered with LY2409021 at doses associated with only modest increases in aminotransferases (mean increase in alanine aminotransferase [ALT] ≤10 units/L). The incidence of hypoglycemia in the LY2409021 groups was not statistically different from placebo.

CONCLUSIONS
In patients with type 2 diabetes, glucagon receptor antagonist treatment significantly lowered HbA1c and glucose levels with good overall tolerability and a low risk for hypoglycemia. Modest, reversible increases in serum aminotransferases were observed.
A1C Combined With Glycated Albumin Improves Detection of Prediabetes in Africans: The Africans in America Study
Authors: Sumner Anne E. , Duong Michelle T. , Aldana Paola C. , Ricks Madia , Tulloch-Reid Marshall K. , Lozier Jay N. , Chung Stephanie T. , Sacks David B. 
Published: January 2016

OBJECTIVE
Slowing the diabetes epidemic in Africa requires improved detection of prediabetes. A1C, a form of glycated hemoglobin A, is recommended for diagnosing prediabetes. The glycated proteins, fructosamine and glycated albumin (GA), are hemoglobin-independent alternatives to A1C, but their efficacy in Africans is unknown. Our goals were to determine the ability of A1C, fructosamine, and GA to detect prediabetes in U.S.-based Africans and the value of combining A1C with either fructosamine or GA.

RESEARCH DESIGN AND METHODS
Oral glucose tolerance tests (OGTT) were performed in 217 self-identified healthy African immigrants (69% male, age 39 ± 10 years [mean ± SD], BMI 27.6 ± 4.5 kg/m2). A1C, fructosamine, and GA were measured. Prediabetes was diagnosed by American Diabetes Association criteria for glucose obtained from a 2-h OGTT. The thresholds to diagnose prediabetes by A1C, fructosamine, and GA were the cutoff at the upper tertile for each variable: ≥5.7% (39 mmol/mol) (range 4.2–6.6% [22.4–48.6 mmol/mol]), ≥230 µmol/L (range 161–269 µmol/L), and ≥13.35% (range 10.20–16.07%), respectively.

RESULTS
Prediabetes occurred in 34% (74 of 217). The diagnostic sensitivities of A1C, fructosamine, and GA were 50%, 41%, and 42%, respectively. The P values for comparison with A1C were both &gt;0.3. Combining A1C with either fructosamine or GA increased sensitivities. However, the sensitivity of A1C combined with fructosamine was not better than for A1C alone (72% vs. 50%, P = 0.172). In contrast, the sensitivity of A1C combined with GA was higher than for A1C alone (78% vs. 50%, P &lt; 0.001).

CONCLUSIONS
As individual tests, A1C, fructosamine, and GA detected ≤50% of Africans with prediabetes. However, combining A1C with GA made it possible to identify nearly 80% of Africans with prediabetes.
Natriuretic Peptide and High-Sensitivity Troponin for Cardiovascular Risk Prediction in Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Gori Mauro , Gupta Deepak K. , Claggett Brian , Selvin Elizabeth , Folsom Aaron R. , Matsushita Kunihiro , Bello Natalie A. , Cheng Susan , Shah Amil , Skali Hicham , Vardeny Orly , Ni Hanyu , Ballantyne Christie M. , Astor Brad C. , Klein Barbara E. , Aguilar David , Solomon Scott D. 
Published: January 2016

OBJECTIVE
Cardiovascular disease (CVD) is the major cause of morbidity and mortality in diabetes; yet, heterogeneity in CVD risk has been suggested in diabetes, providing a compelling rationale for improving diabetes risk stratification. We hypothesized that N-terminal prohormone brain natriuretic peptide (NTproBNP) and high-sensitivity troponin T may enhance CVD risk stratification beyond commonly used markers of risk and that CVD risk is heterogeneous in diabetes.

RESEARCH DESIGN AND METHODS
Among 8,402 participants without prevalent CVD at visit 4 (1996–1998) of the Atherosclerosis Risk in Communities (ARIC) study there were 1,510 subjects with diabetes (mean age 63 years, 52% women, 31% African American, and 60% hypertensive).

RESULTS
Over a median follow-up of 13.1 years, there were 540 incident fatal/nonfatal CVD events (coronary heart disease, heart failure, and stroke). Both troponin T ≥14 ng/L (hazard ratio [HR] 1.96 [95% CI 1.57–2.46]) and NTproBNP &gt;125 pg/mL (1.61 [1.29–1.99]) were independent predictors of incident CVD events at multivariable Cox proportional hazard models. Addition of circulating cardiac biomarkers to traditional risk factors, abnormal electrocardiogram (ECG), and conventional markers of diabetes complications including retinopathy, nephropathy, and peripheral arterial disease significantly improved CVD risk prediction (net reclassification index 0.16 [95% CI 0.07–0.22]). Compared with individuals without diabetes, subjects with diabetes had 1.6-fold higher adjusted risk of incident CVD. However, participants with diabetes with normal cardiac biomarkers and no conventional complications/abnormal ECG (n = 725 [48%]) were at low risk (HR 1.12 [95% CI 0.95–1.31]), while those with abnormal cardiac biomarkers, alone (n = 186 [12%]) or in combination with conventional complications/abnormal ECG (n = 243 [16%]), were at greater risk (1.99 [1.59–2.50] and 2.80 [2.34–3.35], respectively).

CONCLUSIONS
Abnormal levels of NTproBNP and troponin T may help to distinguish individuals with high diabetes risk from those with low diabetes risk, providing incremental risk prediction beyond commonly used markers of risk.
Effect of Long-Acting Insulin Analogs on the Risk of Cancer: A Systematic Review of Observational Studies
Authors: Wu Jennifer W. , Filion Kristian B. , Azoulay Laurent , Doll Margaret K. , Suissa Samy 
Published: January 2016

OBJECTIVE
Observational studies examining the association between long-acting insulin analogs and cancer incidence have produced inconsistent results. We conducted a systematic review of these studies, focusing on their methodological strengths and weaknesses.

RESEARCH DESIGN AND METHODS
We systematically searched MEDLINE and EMBASE from 2000 to 2014 to identify all observational studies evaluating the relationship between the long-acting insulin analogs and the risk of any and site-specific cancers (breast, colorectal, prostate). We included cohort and case-control studies published in English on insulin glargine and detemir and any cancer incidence among patients with type 1 or 2 diabetes. The methodological assessment involved the inclusion of prevalent users, inclusion of lag periods, time-related biases, and duration of follow-up between insulin initiation and cancer incidence.

RESULTS
A total of 16 cohort and 3 case-control studies met our inclusion criteria. All studies evaluated insulin glargine, and four studies also examined insulin detemir. Follow-up ranged from 0.9 to 7.0 years. Thirteen of 15 studies reported no association between insulin glargine and detemir and any cancer. Four of 13 studies reported an increased risk of breast cancer with insulin glargine. In the quality assessment, 7 studies included prevalent users, 11 did not consider a lag period, 6 had time-related biases, and 16 had short (&lt;5 years) follow-up.

CONCLUSIONS
The observational studies examining the risk of cancer associated with long-acting insulin analogs have important methodological shortcomings that limit the conclusions that can be drawn. Thus, uncertainty remains, particularly for breast cancer risk.
Quantification of vanadium precipitates in HSLA steel by synchrotron X-ray absorption spectroscopy (XAS)
Authors: Suwanpinij Piyada , Dickert Hans Henning , Thammajak Nirawat , Srichareonchai Prasonk 
Published: January 2016

AbstractThis study demonstrates how the synchrotron X-ray absorption spectroscopy can be applied for the quantification of precipitation in high strength low alloyed steel. The fraction of vanadium in different forms of compounds, as well as in the solid solution, was measured using a linear combination fit of the spectral weights. The technique confirms substantial enhancement of precipitation by lowering the cooling rate. A significant fraction of vanadium atoms of over 0.6 remained in the solid solution when the cooling rate was as high as 60 K × s−1. In contrast, the precipitation of vanadium was almost completed by decreasing the cooling rate to 0.1 K × s−1. The results corresponded to the proof by scanning transmission electron microscopy.
Optimization of the wear behavior of uncoated, TiN and AlTiN coated cold work tool steel 1.2379 using response surface methodology
Authors: Bülbül Ali Emrah , Dilipak Hakan , Sarıkaya Murat , Yılmaz Volkan 
Published: January 2016

AbstractIn this study, the wear behavior of uncoated, TiN and AlTiN coated cold work tool steel 1.2379 which is widely used in the mold industry was investigated experimentally. Heat treatment was applied to the specimens, then TiN and AlTiN PVD coating process was performed. The wear tests were carried out at 0.5 m × s−1 sliding speed, 5, 10 and 15 N loads and 120 m sliding distance by using reciprocating abrasion device. The microhardness was measured and metallographic tests of the samples were investigated by SEM and EDS analysis. In order to examine the effect of process parameters on wear results, a statistical method such as analysis of variance (ANOVA) was employed. A mathematical model was created by using regression analysis based on both linear model and quadratic model for predicted wear value. Process parameters were optimized using response surface methodology with desirability function analysis. It is observed that the uncoated specimens worn approximately two times more than AlTiN coated and one time more than TiN coated. In the SEM images and EDS analysis, it is seen that the coating is spread uniformly on the materials.
Structural design of vehicle components using gravitational search and charged system search algorithms
Authors: Yildiz Betul Sultan , Lekesiz Huseyin , Yildiz Ali Riza 
Published: January 2016

Abstract
The fuel and cost efficiency in automotive industry is related to the designing of light-weight vehicle components. Main aim of this paper is to show effectiveness of two new optimization algorithms in solving structural design optimization problems. The gravitational search algorithm (GSA) and charged system search algorithm (CSS) are applied to the optimum design of a vehicle component. The results show that both GSA and CSS have a better search capability than the genetic algorithms to find optimum solutions.
Deep micro-hole drilling of Hardox 500 by electro-discharge machining
Authors: Yılmaz Volkan 
Published: January 2016

Abstract
In this study, micro-size drillability of Hardox 500 was investigated by the electro-discharge machining (EDM) method. For this purpose, holes were drilled by using different machining parameters (discharge current, electrode rotational speed, dielectric spray pressure) and the effect of these parameters on machining performance and hole profile was specified. At the end of the tests, it was detected that discharge current and electrode rotational speed increased material removal rate (MRR), electrode wear rate (EWR) and hole dimensional error (DE) whereas dielectric spray pressure increased the MRR values and decreased the EWR and DE values.
Experimental study of FLD0 for aluminum alloy using digital image correlation with modified ISO method
Authors: Li Junrui , Xu Wan , Xie Xin , Siebert Thorsten , Yang Lianxiang 
Published: January 2016

AbstractA new material's forming limit diagram (FLD) must be obtained before it can be used for stampings. Compared to conventional methods, the ISO method with a digital image correlation system provides an efficient way to conduct these tests. However the ISO method is position dependent, so the evaluation procedure for aluminum alloy will be seriously affected by the multiple necking strain distribution, resulting in much error. In this paper, a modified ISO method, which can be used for the evaluation of the aluminum alloy FLD, is proposed, and errors resulting from multiple necking were eliminated through detection of the major necking area. An FLD evaluation software was also programmed. An FLD0 punch test was conducted to verify the new modified ISO method. Through comparison of the results with the accepted value, the FLD0 value evaluated from the modified method was determined to be much more accurate than the standard method.
Fe–N and Fe–N–C phase equilibria above 853 K studied by nitriding/nitrocarburising and secondary annealing
Authors: Woehrle Thomas , Cinaroglu Havva , Leineweber Andreas , Mittemeijer Eric Jan 
Published: January 2016

AbstractCompound-layer microstructures obtained by gaseous nitriding and nitrocarburising treatments of α-Fe and Fe–N alloy and by subsequent treatments were analysed to obtain new information on the metastable Fe–N and Fe–N–C systems above 853 K at 1 atm. In the case of the binary Fe–N system, invariant temperatures and phase boundaries agree well with the literature data, only the γ/γ + γ' and the γ/γ + ∊ boundaries as determined in the present work by means of electron probe microanalysis are located at N contents up to 1 at.% lower than reported in previous works. In the case of the ternary Fe–N–C system, the invariant eutectoid reaction was found to occur in the range 853 K – 863 K, whereas the invariant transition reaction was found to occur in the range 868 K – 873 K. The obtained data were used to draw isothermal sections of the Fe–N–C system for 853 K and 893 K. The determined temperatures for the invariant eutectoid and transition reactions as well as the extent of the ternary ∊-phase field were compared with phase diagrams calculated on the basis of different thermodynamic descriptions of the Fe–N–C system.
Effect of deposition parameters on the crystal orientation and growth of Ag nanowires
Authors: Mehmood Tahir , Mukhtar Aiman , Wang Honghong , Khan Babar Shahzad 
Published: January 2016

AbstractAg nanowires deposited at –0.1 V to –0.6 V are single-crystals along [110] direction, and are polycrystalline when deposited at –1.0 V. The large critical nucleus and slow nucleation rate at low potentials could be responsible for the growth of single-crystal. The polycrystalline growth can be related to the small critical nuclei and fast nucleation rate at high potentials. At –0.2 V and different temperatures (15 °C to 60 °C), the preferred growth plane is (220).
A family with pheochromocytoma-paraganglioma inherited tumour syndrome
Authors: Zschieschang P. , Prasad V. , Moskopp D. , Knie B. , Plotkin M. 
Published: January 2016

SummaryAim: Hereditary pheochromocytoma-paraganglioma syndromes are characterized by multiple pheochromocytomas (PCC) and paragangliomas (PGLs), inherited in an autosomal dominant manner. Early detection and removal of tumours may prevent or minimize complications related to mass effects and malignant transformation. Having confirmed the diagnosis, it is important to localize the tumours and reveal their extent preoperatively. This study aimed to introduce 18F-DOPA PET/CT as a highly sensitive noninvasive diagnostic tool for early detection of mass lesions in patients with pheochromocytoma-paraganglioma inherited tumour syndrome and to report about its impact on patient management. Patients, methods: We are currently supervising one of the largest documented families in Germany with genetically determined SDHD gene mutation. We performed 18F-DOPA PET/CT in order to detect tumours in asymptomatic gene carriers and enable subsequent surgical therapy. Results: In seven patients undergoing 12 18F-DOPA PET/CT scans 17 lesions have been detected. Three of these lesions, located in the head and neck region, have had no morphologic correlate in CT and one had also no morphologic correlate in MRI. Of the six histologically analyzed lesions five have been tumors (PGL or PCC) and one has been a nodular hyperplasia. This means the 18F-DOPA PET/CT scan in our study group had a sensitivity of 83%. 18F-DOPA PET/CT investigations lead to change in the management in 5/7 studied patients (70%). Conclusion: The benefits of PET/ CT in detection of pheochromocytoma and paraganglioma are well documented, but we are the first to use this technique for screening of a rare hereditary disease (estimated prevalence 0.3/100 000).
MULTIPLE CARBON MONOXIDE SNOW LINES IN DISKS SCULPTED BY RADIAL DRIFT
Authors: Cleeves L. Ilsedore 
Published: January 2016

ABSTRACT
Observations of protoplanetary disks suggest that the gas and dust follow significantly different radial distributions. This finding can be theoretically explained by a combination of radial drift and gas drag of intermediate-sized dust grains. Using a simple parametric model to approximate the different distributions of the gas and dust components, we calculate and examine the impact of radial drift on the global dust temperature structure. We find that the removal of large grains beyond the “truncation radius” allows this region to become significantly warmer from reprocessed stellar radiation shining down from the disk upper layers, increasing the outer disk temperature by ∼10%–30%. This change is sufficient to raise the local temperature to a value exceeding the CO desorption temperature. These findings imply that the disk density structures induced by radial drift are able to create multiple CO snow lines. The inner disk CO is in the gas phase, freezing out near the classical snow line at

. Moving outward, the CO sublimates once again beyond the truncation radius (80 AU in our models) and subsequently re-freezes out at sufficiently large stellar distances beyond

. We find that thermal desorption of CO in the outer disk becomes competitive with external UV photodesorption and that this additional transition from solid state CO to the gas phase has significant implications for the C/O ratio in the outer disk.
Protection against Lethal Vaccinia Virus Infection in Mice using an siRNA Targeting the A5R Gene
Authors: Seo Dongjoon , Kim Na Young , Lee Jin Ah , Han Kang Rok , Hur Gyeung Haeng , Yang Jai Myung , Shin Sungho 
Published: January 2016

Background Although the World Health Organization has declared the eradication of smallpox in 1980, the fear of its potential use in bioterrorism has become a reality. Since the effectiveness of current vaccines and antiviral drugs is limited, development of new therapeutic strategies is needed. In this study, we investigated small interfering RNA (siRNA) as a therapeutic approach for preventing and treating smallpox infection. Methods Eight siRNA sequences were designed and evaluated for antiviral activity against vaccinia virus (VACV) in vitro and in vivo. Results Of eight siRNAs, A5R1 siRNA targeted the A5R gene and reduced VACV replication in cell culture by up to 85% at 100 nM concentration without inducing cytotoxicity. A prolonged prophylactic as well as therapeutic effect of siRNA was observed. In addition, real-time PCR analysis showed that A5R1 siRNA can especially reduce the target mRNA. Finally, intraperitoneal delivery of A5R1 siRNA in Balb/c mice significantly protected these animals from lethal challenge with VACV. Conclusions This study suggests the potential of A5R1 siRNA as a therapeutic antiviral agent against smallpox.
J’ai besoin de mon père
Authors: Mugnier Jean-Paul 
Published: January 2016

Cet article s’articule autour d’une seule idée déclinée en deux temps : le lien père/fils, d’une certaine façon, toujours un lien d’adoption. Ainsi, nombreux sont les patients que nous rencontrons qui nous disent, souvent à l’âge adulte, combien ils ont souffert de ne pas s’être sentis reconnus par leur père. Dans cette perspective, l’un des objectifs sera de permettre cette reconnaissance du fils par le père et, lorsque ce n’est pas possible, de permettre enfin au fils d’adopter son père.
Réflexions sur les fonctions du père dans les familles d’aujourd’hui
Authors: De Neuter Patrick 
Published: January 2016

Au cours de ces derniers siècles, la place du père et ses fonctions ont subi d’importantes modifications. L’auteur examine les particularités de certaines d’entre elles et insiste sur les différents agents qui assument aujourd’hui les fonctions dites paternelles : la mère notamment, et bien d’autres encore. C’est pourquoi il propose d’appeler ces fonctions dites paternelles, « fonctions tierces symboligènes ».
Le panier à salade
Authors: Gutton Philippe 
Published: January 2016

Dans un panier à salade de la police, le père et le fils vivent sous le masque d’un conflit œdipien l’intime-extime de la fonction symbolique symbolisante paternelle. Le matériel est issu de trois romans de Patrick Modiano : Les boulevards de ceinture (1972), Dora Bruder (1997), Un pedigree (2005).
Cryptococcus gattii Capsule Blocks Surface Recognition Required for Dendritic Cell Maturation Independent of Internalization and Antigen Processing
Authors: Huston Shaunna M. , Ngamskulrungroj Popchai , Xiang Richard F. , Ogbomo Henry , Stack Danuta , Li Shu Shun , Timm-McCann Martina , Kyei Stephen K. , Oykhman Paul , Kwon-Chung Kyung J. , Mody Christopher H. 
Published: January 2016

Abstract
Cryptococcus gattii is an emerging fungal pathogen on the west coast of Canada and the United States that causes a potentially fatal infection in otherwise healthy individuals. In previous investigations of the mechanisms by which C. gattii might subvert cell-mediated immunity, we found that C. gattii failed to induce dendritic cell (DC) maturation, leading to defective T cell responses. However, the virulence factor and the mechanisms of evasion of DC maturation remain unknown. The cryptococcal polysaccharide capsule is a leading candidate because of its antiphagocytic properties. Consequently, we asked if the capsule of C. gattii was involved in evasion of DC maturation. We constructed an acapsular strain of C. gattii through CAP59 gene deletion by homologous integration. Encapsulated C. gattii failed to induce human monocyte-derived DC maturation and T cell proliferation, whereas the acapsular mutant induced both processes. Surprisingly, encapsulation impaired DC maturation independent of its effect on phagocytosis. Indeed, DC maturation required extracellular receptor signaling that was dependent on TNF-α and p38 MAPK, but not ERK activation, and the cryptococcal capsule blocked this extracellular recognition. Although the capsule impaired phagocytosis that led to pH-dependent serine-, threonine-, and cysteine-sensitive protease-dependent Ag processing, it was insufficient to impair T cell responses. In summary, C. gattii affects two independent processes, leading to DC maturation and Ag processing. The polysaccharide capsule masked extracellular detection and reduced phagocytosis that was required for DC maturation and Ag processing, respectively. However, the T cell response was fully restored by inducing DC maturation.