bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated Network Analysis Identifies Fight-Club Nodes as a Class of Hubs Encompassing Key Putative Switch Genes That Induce Major Transcriptome Reprogramming during Grapevine Development
Authors: Palumbo Maria Concetta , Zenoni Sara , Fasoli Marianna , Massonnet Mélanie , Farina Lorenzo , Castiglione Filippo , Pezzotti Mario , Paci Paola 
Published: December 2014

AbstractWe developed an approach that integrates different network-based methods to analyze the correlation network arising from large-scale gene expression data. By studying grapevine (Vitis vinifera) and tomato (Solanum lycopersicum) gene expression atlases and a grapevine berry transcriptomic data set during the transition from immature to mature growth, we identified a category named “fight-club hubs” characterized by a marked negative correlation with the expression profiles of neighboring genes in the network. A special subset named “switch genes” was identified, with the additional property of many significant negative correlations outside their own group in the network. Switch genes are involved in multiple processes and include transcription factors that may be considered master regulators of the previously reported transcriptome remodeling that marks the developmental shift from immature to mature growth. All switch genes, expressed at low levels in vegetative/green tissues, showed a significant increase in mature/woody organs, suggesting a potential regulatory role during the developmental transition. Finally, our analysis of tomato gene expression data sets showed that wild-type switch genes are downregulated in ripening-deficient mutants. The identification of known master regulators of tomato fruit maturation suggests our method is suitable for the detection of key regulators of organ development in different fleshy fruit crops.
Unsupervised home use of an overnight closed‐loop system over 3–4 weeks: a pooled analysis of randomized controlled studies in adults and adolescents with type 1 diabetes
Authors: Thabit H. , Elleri D. , Leelarathna L. , Allen J. M. , Lubina‐Solomon A. , Stadler M. , Walkinshaw E. , Iqbal A. , Choudhary P. , Wilinska M. E. , Barnard K. D. , Heller S. R. , Amiel S. A. , Evans M. L. , Dunger D. B. , Hovorka R. 
Published: December 2014

AimsTo compare overnight closed‐loop and sensor‐augmented pump therapy in patients with type 1 diabetes by combining data collected during free‐living unsupervised randomized crossover home studies.MethodsA total of 40 participants with type 1 diabetes, of whom 24 were adults [mean ± standard deviation (s.d.) age 43 ± 12 years and glycated haemoglobin (HbA1c) 8.0 ± 0.9%] and 16 were adolescents (mean ± s.d. age 15.6 ± 3.6 years and HbA1c 8.1 ± 0.8%), underwent two periods of sensor‐augmented pump therapy in the home setting, in combination with or without an overnight closed‐loop insulin delivery system that uses a model predictive control algorithm to direct insulin delivery. The order of the two interventions was random; each period lasted 4 weeks in adults and 3 weeks in adolescents. The primary outcome was time during which sensor glucose readings were in the target range of 3.9–8.0 mmol/l.ResultsThe proportion of time when sensor glucose was in the target range (3.9–8.0 mmol/l) overnight (between 24:00 and 08:00 hours) was 18.5% greater during closed‐loop insulin delivery than during sensor‐augmented therapy (p < 0.001). Closed‐loop therapy significantly reduced mean overnight glucose levels by 0.9 mmol/l (p < 0.001), with no difference in glycaemic variability, as measured by the standard deviation of sensor glucose. Time spent above the target range was reduced (p = 0.001), as was time spent in hypoglycaemia (<3.9 mmol/l; p = 0.014) during closed‐loop therapy. Lower mean overnight glucose levels during closed‐loop therapy were brought about by increased overnight insulin delivery (p < 0.001) without changes to the total daily delivery (p = 0.84).ConclusionOvernight closed‐loop insulin therapy at home in adults and adolescents with type 1 diabetes is feasible, showing improvements in glucose control and reducing the risk of nocturnal hypoglycaemia.
Non‐dominated “trade‐off” solutions in television scheduling optimization
Authors: Lupo Toni 
Published: December 2014

AbstractThe main approaches for the television scheduling design are commonly based on the ratings or revenues maximization objective, and thus, only a single optimal solution can be obtained, corresponding to the best result for the considered objective. Therefore, these approaches lead up to the alternative solutions loss which, even if less effective from the ratings or revenues maximization viewpoint, may be more suitable for the decision maker because of better compromise in relation to factors influencing the decision process. Specifically, such a compromise could be achieved through a suitable “trade‐off” between these factors, with reference to the decision context in which the decision maker has to operate. The present study concerns the development of a multi‐objective approach for the television scheduling design in which ratings and costs are the considered objectives to optimize, because these are the main factors influencing the decision process. In particular, an integer mathematical programming model is formulated and solved, considering as input data forecasted values of show‐parts ratings and costs obtained by a suitable forecast engine. Finally, in order to show the employment of the proposed approach, a case study concerning the television scheduling optimization for an Italian TV channel is conducted with detailed practical considerations.
SPATIAL ADMINISTRATIVE STRUCTURE AND INTRA‐METROPOLITAN TAX COMPETITION
Authors: Kauder Björn 
Published: December 2014

ABSTRACTI investigate whether the spatial administrative structure of agglomerations is associated with local business tax rates in core cities of agglomerations. Using data for German municipalities, I define agglomerations based on distances and based on cumulative population densities. The results show that the population share of the core in its agglomeration is positively associated and the number of surrounding municipalities is negatively associated with the tax rate of the core. When municipalities consolidate, the core has the opportunity to increase the tax rate.
Synergistic antibacterial activity of the combination of the alkaloid sanguinarine with EDTA and the antibiotic streptomycin against multidrug resistant bacteria
Authors: Hamoud Razan , Reichling Jürgen , Wink Michael 
Published: December 2014

Abstract

Objectives
Drug combinations consisting of the DNA intercalating benzophenanthridine alkaloid sanguinarine, the chelator EDTA with the antibiotic streptomycin were tested against several Gram-positive and Gram-negative bacteria, including multi-resistant clinical isolates.

Methods
Microdilution, checkerboard and time kill curve methods were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of combinations.

Key findings
Sanguinarine demonstrated a strong activity against Gram-positive and Gram-negative bacteria (minimum inhibitory concentrations, MIC = 0.5–128 μg/ml), while streptomycin was active against Gram-negative strains (MIC = 2–128 μg/ml). EDTA showed only bacteriostatic activity. Indifference to synergistic activity was seen in the two-drug combinations sanguinarine + EDTA and sanguinarine + streptomycin (fractional inhibitory concentration index = 0.1–1.5), while the three-drug combination of sanguinarine + EDTA + streptomycin showed synergistic activity against almost all the strains (except methicillin-resistant Staphylococcus aureus), as well as a strong reduction in the effective doses (dose reduction index = 2–16 times) of sanguinarine, EDTA and streptomycin. In time kill studies, a substantial synergistic interaction of the three-drug combination was detected against Escherichia coli and Klebsiella pneumoniae.

Conclusions
The combination of drugs, which interfere with different molecular targets, can be an important strategy to combat multidrug resistant bacteria.
Immunoproteomic characterisation of M
ycoplasma mycoides subspecies capri by mass spectrometry analysis of two-dimensional electrophoresis spots and western blot
Authors: Churchward Colin P , Rosales Rubén S , Gielbert Adriana , Domínguez Mercedes , Nicholas Robin A J , Ayling Roger D 
Published: December 2014

Abstract

Objectives
M ycoplasma mycoides subspecies capri is one of the causative agents of contagious agalactia in goats. The disease is characterised by mastitis, pneumonia, arthritis, keratitis and in acute cases septicaemia. No vaccine is currently available that has been demonstrated to prevent disease.

Methods
This study used two-dimensional electrophoresis to separate proteins from whole-cell preparations and tandem mass spectrometry to identify them.

Key findings
In total, 145 spots were successfully identified corresponding to 74 protein identities. Twenty of these proteins were found to be immunogenic by western blot analysis using a pooled serum sample from experimentally infected goats.

Conclusions
Six proteins were found to have a less than 95% amino acid similarity to a closely related Mycoplasma species showing that they warrant further evaluation in development of diagnostic tests. These proteins were a dihydrolipoamide acetyltransferase component of the pyruvate dehydrogenase complex, phosphoglycerate kinase, pyrimidine-nucleoside phosphorylase, 30S ribosomal protein S6, ribulose-phosphate 3-epimerase and D-lactate dehydrogenase.
Particulate inorganic adjuvants: recent developments and future outlook
Authors: Maughan Charlotte N , Preston Stephen G , Williams Gareth R 
Published: December 2014

Abstract

Objectives
To review the state of the art and assess future potential in the use of inorganic particulates as vaccine adjuvants.

Key findings
An adjuvant is an entity added to a vaccine formulation to ensure that robust immunity to the antigen is inculcated. The inclusion of an adjuvant is typically vital for the efficacy of vaccines using inactivated organisms, subunit and DNA antigens. With increasing research efforts being focused on subunit and DNA antigens because of their improved safety profiles, the development of appropriate adjuvants is becoming ever more crucial. Despite this, very few adjuvants are licensed for use in humans (four by the FDA, five by the European Medicines Agency). The most widely used adjuvant, alum, has been used for nearly 90 years, yet its mechanism of action remains poorly understood. In addition, while alum produces a powerful antibody Th2 response, it does not provoke the cellular immune response required for the elimination of intracellular infections or cancers. New adjuvants are therefore needed, and inorganic systems have attracted much attention in this regard.

Summary
In this review, the inorganic adjuvants currently in use are considered, and the efforts made to date to understand their mechanisms of action are summarised. We then move on to survey the literature on inorganic particulate adjuvants, focusing on the most interesting recent developments in this area and their future potential.
Language‐Games and Relativism: On Cora Diamond's Reading of Peter Winch
Authors: Ahlskog Jonas , Lagerspetz Olli 
Published: December 2014

AbstractWe will look critically at three essays by Cora Diamond concerning Peter Winch's views on the possibility of communication and criticism between language‐games. We briefly present our understanding of Winch's approach to philosophy. Then, we argue that Diamond misidentifies Winch's views, taking them to imply language‐game relativism or linguistic idealism. When she does raise valid criticisms against language‐game relativism, her critical points mainly coincide with things that Winch has already stressed in his own work. That leaves us with the question what their real disagreement amounts to. Finally, we suggest that at the bottom of Diamond's objections lies her failure to appreciate Winch's insights about the place of logic in human intercourse.
Subtherapeutic ganciclovir (GCV) levels and GCV‐resistant cytomegalovirus in lung transplant recipients
Authors: Gagermeier J.P. , Rusinak J.D. , Lurain N.S. , Alex C.G. , Dilling D.F. , Wigfield C.H. , Love R.B. 
Published: December 2014

AbstractBackgroundCytomegalovirus (CMV) infection results in significant morbidity and mortality in lung transplant recipients. Ganciclovir (GCV) has dramatically reduced complications caused by CMV infections. Unfortunately, GCV resistance is identified in 5–10% of CMV‐infected patients. Mismatched CMV status and ongoing replication due to immunosuppression are risk factors for drug resistance. Whether subtherapeutic GCV levels contribute to resistance remains unknown.MethodsA retrospective review was conducted in all 51 patients who underwent lung transplantation between March 2007 and June 2008 at Loyola University Medical Center. GCV resistance and outcome data of CMV‐infected patients were analyzed to identify variables that may contribute to suboptimal response to CMV infection.ResultsDuring the 16‐month period, CMV infection was identified in 21 of 51 lung transplant recipients. Ten of 21 patients (47.6%) had CMV infection with early response to GCV, and 11 patients (52.4%) had CMV infection with suboptimal response to GCV. GCV levels were obtained in the 11 CMV‐infected patients with suboptimal response. In 6 patients, GCV levels were therapeutic; all 6 had delayed response to GCV. In 5 patients, GCV levels were subtherapeutic; each had persistent suboptimal response to GCV. Genotyping documented GCV‐resistant (GCV‐R) CMV in all 5 patients. Cystic fibrosis as the diagnosis requiring lung transplantation was associated with GCV‐R CMV infection (P = 0.01).ConclusionIn our lung transplant recipient cohort, GCV levels were subtherapeutic in all patients with persistent suboptimal response to GCV, each of whom had GCV‐R CMV infection. In contrast, GCV levels were therapeutic in CMV‐infected patients with delayed GCV response.
Storage of RBCs results in an increased susceptibility for complement‐mediated degradation
Authors: Kamhieh‐Milz J. , Bartl B. , Sterzer V. , Kamhieh‐Milz S. , Salama A. 
Published: December 2014

SUMMARYObjectiveThe objective of this study was to elucidate whether complement activation occurs during the storage of RBCs in newly formulated PAGGS‐M storage medium.BackgroundThe reason for red blood cell (RBC) storage lesions is not yet fully understood. The contribution of complement to RBC storage lesion has not been extensively characterised.Study design and methodsWe investigated the surface expression of CD35, CD55, CD59 and CD47, as well as deposition of C3d, using flow cytometry over a storage period of up to 42 days on a weekly basis. C3d and the immunoglobulins IgG, IgM and IgA were additionally investigated via the direct antiglobulin test (DAT). The effect of contact with homologous serum for 30 min at 37 °C was also performed for C3d and CD35 and is subsequently termed as a ‘transfusion simulation (TS)’.ResultsA weak but significant increase of C3d was observed prior to TS (anova P = 0·0103), whereas a stronger increase from 74·0 ± 12·4 to 101·2 ± 9·7 was observed post‐TS (anova; P < 0·0001). These findings were confirmed by the DAT. CD35, CD55 and CD47 demonstrated a decrease in their expression over storage time (anova; P < 0·0001 each). The majority of changes occurred following 14 days. There was neither a decrease of CD59 observed nor an increase of IgG, IgM and IgA.ConclusionRBCs are becoming increasingly susceptible to spontaneous complement deposition following TS, which might be associated with the decrease of C35 and CD55 by proteolytic cleavage and vesiculation during storage. As the impact of storage lesions is rather controversial, institutions involved in blood collection and administration of blood products should focus on carrying out research on the prevention of storage lesions.
Targeting CD20+ Aggressive B-cell Non–Hodgkin Lymphoma by Anti-CD20 CAR mRNA-Modified Expanded Natural Killer Cells In Vitro and in NSG Mice
Authors: Chu Yaya , Hochberg Jessica , Yahr Ashlin , Ayello Janet , van de Ven Carmella , Barth Matthew , Czuczman Myron , Cairo Mitchell S. 
Published: December 2014

Abstract
The prognosis is very dismal for patients with relapsed CD20+ B-cell non-Hodgkin lymphoma (B-NHL). Facilitating the development of alternative novel therapeutic strategies is required to improve outcomes in patients with recurrent/refractory CD20+ B-NHL. In this study, we investigated functional activities of anti-CD20 CAR-modified, expanded peripheral blood NK cells (exPBNK) following mRNA nucleofection against CD20+ B-NHL in vitro and in vivo. CAR+ exPBNK had significantly enhanced in vitro cytotoxicity, compared with CAR− exPBNK against CD20+ Ramos (P &lt; 0.05), Daudi, Raji, and two rituximab-resistant cell lines, Raji-2R and Raji-4RH (P &lt; 0.001). As expected, there was no significant difference against CD20− RS4;11 and Jurkat cells. CD107a degranulation and intracellular IFNγ production were also enhanced in CAR+ exPBNK in response to CD20+ B-NHL–specific stimulation. In Raji-Luc and Raji-2R-Luc xenografted NOD/SCID/γ-chain−/− (NSG) mice, the luciferase signals measured in the CAR+ exPBNK-treated group were significantly reduced, compared with the signals measured in the untreated mice and in mice treated with the CAR− exPBNK. Furthermore, the CAR exPBNK-treated mice had significantly extended survival time (P &lt; 0.001) and reduced tumor size, compared with those of the untreated and the CAR− exPBNK-treated mice (P &lt; 0.05). These preclinical data suggest that ex vivo–exPBNK modified with anti-CD20 CAR may have therapeutic potential for treating patients with poor-risk CD20+ hematologic malignancies. Cancer Immunol Res; 3(4); 333–44. ©2014 AACR.
Extracellular matrix protein 1 regulates cell proliferation and trastuzumab resistance through activation of epidermal growth factor signaling
Authors: Lee Kyung-min , Nam Keesoo , Oh Sunhwa , Lim Juyeon , Kim Young-Pil , Lee Jong Won , Yu Jong-Han , Ahn Sei-Hyun , Kim Sung-Bae , Noh Dong-Young , Lee Taehoon , Shin Incheol 
Published: December 2014

Abstract
Introduction
Extracellular matrix protein 1 (ECM1) is a secreted glycoprotein with putative functions in cell proliferation, angiogenesis and differentiation. Expression of ECM1 in several types of carcinoma suggests that it may promote tumor development. In this study, we investigated the role of ECM1 in oncogenic cell signaling in breast cancer, and potential mechanisms for its effects.

Methods
In order to find out the functional role of ECM1, we used the recombinant human ECM1 and viral transduction systems which stably regulated the expression level of ECM1. We examined the effect of ECM1 on cell proliferation and cell signaling in vitro and in vivo. Moreover, tissues and sera of patients with breast cancer were used to confirm the effect of ECM1.

Results
ECM1 protein was increased in trastuzumab-resistant (TR) cells, in association with trastuzumab resistance and cell proliferation. Through physical interaction with epidermal growth factor receptor (EGFR), ECM1 potentiated the phosphorylation of EGFR and extracellular signal-regulated kinase upon EGF treatment. Moreover, ECM1-induced galectin-3 cleavage through upregulation of matrix metalloproteinase 9 not only improved mucin 1 expression, but also increased EGFR and human epidermal growth factor receptor 3 protein stability as a secondary signaling.

Conclusions
ECM1 has important roles in both cancer development and trastuzumab resistance in breast cancer through activation of EGFR signaling.
Concentrations of bone morphogenetic protein-15 (BMP-15) and growth differentiation factor-9 (GDF-9) in follicular cysts, mono - and polyoocyte follicles in gilts
Authors: Stankiewicz Tomasz , Błaszczyk Barbara 
Published: December 2014

Abstract
The objective of the study was to determine the concentration of BMP-15 and GDF-9 in the fluid of follicular cysts and ovarian follicles, and to compare their concentrations in mono- and polyoocyte follicles in gilts. The study involved two experiments conducted on the ovaries collected post-slaughter from gilts (7-8 months old). The first experiment covered 31 follicular single cyst gilts (15-25 mm in diameter) and 41 gilts without cysts. Follicular fluid from follicles of 8-10 mm in diameter (n=41) and 5-8 mm in diameter (n=41), and cystic fluid (n=31) were collected for analysis. The second experiment involved collecting follicular fluid from poly- (n=19) and monooocyte (n=22) follicles. The concentration of BMP-15 and GDF-9 was then determined in the samples using specimen-specific ELISA kits. The differences in the concentration of these factors were calculated by means of analysis of variance and a posthoc test. Duncan’s multiple range test was used to verify the significance of differences at P<0.05 and P<0.01. In addition, correlations between the factors were calculated. BMP-15 and GDF-9 levels in the cystic fluid were significantly higher than those in the follicular fluid (P<0.01). However, no differences were observed between various size follicles or between mono- and polyoocyte follicles. BMP-15 and GDF-9 concentrations were found to be positively correlated (P<0.01). Differences in BMP-15 and GDF-9 concentrations in ovarian follicles and follicular cysts, as evidenced by our study, indicate that these factors may be related to folliculogenesis disorders in gilts. What is more, the number of oocytes in ovarian follicles does not influence the intrafollicular concentration of BMP-15 and GDF-9.
Microbiological evaluation of antibacterial potentiality of some edible plant extracts against multidrug resistant (MDR) human pathogens
Authors: El-Sayed Mohamed Helal , Refaat Bahgat Mohamed , Sharaf Mohamed Hamed 
Published: December 2014

Antimicrobial resistance is a subject of great concern in public health and also in the designing of strategies for current therapeutic protocols all over the world. Plants used for traditional medicine contain a wide range of substances which can be used to treat various infectious diseases. Hence, antibacterial activities of aqueous extracts of 10 plant species were studied against 25 multidrug resistant (MDR) clinical isolates using the agar well diffusion method. The most resistant organisms were Acinetobacter baumanii (A. baumanii) (resistant to 16 different antibiotics), Enterococcus faecium (E. faecium) (resistant to 15 different antibiotics), Pseudomonas aeruginosa (P. aeruginosa) (resistant to 15 antibiotics), Gemella morbillorum (G. morbillorum) (resistant to 14 different antibiotics), Enterobacter cloacae (E. cloacae) (resistant to 13 different antibiotics) respectively. Among the tested plant extracts, only extracts of Allium cepa, Allium sativum, Foeniculum vulgare, Matricaria chmomilla, Salvia offcinalis and Thymus Vulgaris showed strong antibacterial activity against MDR isolates with inhibition zones ranging from 8.33 to 26 mm. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the most active plant extracts; Allium cepa and Foeniculum vulgare were ranged from 0.062 to 0.25 mg/ml and 0.031 to 0.125 mg/ml, respectively. Foeniculum vulgare extract was bactericidal for all bacteria while Allium cepa extract was bacteriostatic. Hence, the discovered compounds from these plants can use as templates for the development of new antibacterial agents.DOI: http://dx.doi.org/10.3329/icpj.v4i1.21162 International Current Pharmaceutical Journal, December 2014, 4(1): 336-339