bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous model discrimination and parameter estimation in dynamic models of cellular systems
Authors: Rodriguez-Fernandez Maria , Rehberg Markus , Kremling Andreas , Banga Julio R 
Published: August 2013

Abstract

Background
Model development is a key task in systems biology, which typically starts from an initial model candidate and, involving an iterative cycle of hypotheses-driven model modifications, leads to new experimentation and subsequent model identification steps. The final product of this cycle is a satisfactory refined model of the biological phenomena under study. During such iterative model development, researchers frequently propose a set of model candidates from which the best alternative must be selected. Here we consider this problem of model selection and formulate it as a simultaneous model selection and parameter identification problem. More precisely, we consider a general mixed-integer nonlinear programming (MINLP) formulation for model selection and identification, with emphasis on dynamic models consisting of sets of either ODEs (ordinary differential equations) or DAEs (differential algebraic equations).

Results
We solved the MINLP formulation for model selection and identification using an algorithm based on Scatter Search (SS). We illustrate the capabilities and efficiency of the proposed strategy with a case study considering the KdpD/KdpE system regulating potassium homeostasis in Escherichia coli. The proposed approach resulted in a final model that presents a better fit to the in silico generated experimental data.

Conclusions
The presented MINLP-based optimization approach for nested-model selection and identification is a powerful methodology for model development in systems biology. This strategy can be used to perform model selection and parameter estimation in one single step, thus greatly reducing the number of experiments and computations of traditional modeling approaches.
Identification of genetic markers with synergistic survival effect in cancer
Authors: Louhimo Riku , Laakso Marko , Heikkinen Tuomas , Laitinen Susanna , Manninen Pekka , Rogojin Vladimir , Miettinen Minna , Blomqvist Carl , Liu Jianjun , Nevanlinna Heli , Hautaniemi Sampsa 
Published: August 2013

AbstractBackgroundCancers are complex diseases arising from accumulated genetic mutations that disrupt intracellular signaling networks. While several predisposing genetic mutations have been found, these individual mutations account only for a small fraction of cancer incidence and mortality. With large-scale measurement technologies, such as single nucleotide polymorphism (SNP) microarrays, it is now possible to identify combinatorial effects that have significant impact on cancer patient survival.ResultsThe identification of synergetic functioning SNPs on genome-scale is a computationally daunting task and requires advanced algorithms. We introduce a novel algorithm, Geninter, to identify SNPs that have synergetic effect on survival of cancer patients. Using a large breast cancer cohort we generate a simulator that allows assessing reliability and accuracy of Geninter and logrank test, which is a standard statistical method to integrate genetic and survival data.ConclusionsOur results show that Geninter outperforms the logrank test and is able to identify SNP-pairs with synergetic impact on survival.
Effects of multimerization on the temporal variability of protein complex abundance
Authors: Häkkinen Antti , Tran Huy , Yli-Harja Olli , Ingalls Brian , Ribeiro Andre S 
Published: August 2013

Abstract
We explore whether the process of multimerization can be used as a means to regulate noise in the abundance of functional protein complexes. Additionally, we analyze how this process affects the mean level of these functional units, response time of a gene, and temporal correlation between the numbers of expressed proteins and of the functional multimers. We show that, although multimerization increases noise by reducing the mean number of functional complexes it can reduce noise in comparison with a monomer, when abundance of the functional proteins are comparable. Alternatively, reduction in noise occurs if both monomeric and multimeric forms of the protein are functional. Moreover, we find that multimerization either increases the response time to external signals or decreases the correlation between number of functional complexes and protein production kinetics. Finally, we show that the results are in agreement with recent genome-wide assessments of cell-to-cell variability in protein numbers and of multimerization in essential and non-essential genes in Escherichia coli, and that the effects of multimerization are tangible at the level of genetic circuits.
Evaluation of physicochemical and antioxidant properties of sourwood and other Malaysian honeys: a comparison with manuka honey
Authors: Moniruzzaman Mohammed , Sulaiman Siti Amrah , Khalil Md Ibrahim , Gan Siew Hua 
Published: August 2013

Abstract

Background
The aim of the present study was to evaluate the physical, biochemical and antioxidant properties of four Malaysian monofloral types of honey (gelam, longan, rubber tree and sourwood honeys) compared to manuka honey.
Several physical parameters of honey, such as pH, moisture content, electrical conductivity (EC), total dissolved solids (TDS), color intensity, total sugar and sucrose content, were measured. A number of biochemical and antioxidant tests were performed to determine the antioxidant properties of the honey samples. Hydroxymethylfurfural (HMF) levels were determined using high performance liquid chromatography.

Results
The mean pH, moisture content, EC and TDS of Malaysian honey were 3.90 ± 0.12, 17.01 ± 3.07%, 0.59 ± 0.17 mS/cm and 294.87 ± 81.96 ppm, respectively. The mean color and HMF level was 102.07 ± 41.77 mm Pfund and 49.51 ± 0.12 mg/kg, respectively. Sourwood honey contained the highest contents of phenolics (580.03 ± 0.38 mggalic acid/kg) and flavonoids (156.82 ± 0.47 mgcatechin/kg) with high DPPH radical scavenging activity (59.26 ± 3.77%) as well as ferric reducing power [648.25 ± 0.90 μM Fe (II)/100 g]. Sourwood honey also exhibited the highest color intensity. Several strong positive correlations were observed amongst the different antioxidant parameters and the various antioxidant tests.

Conclusion
This is the first time that the antioxidant potential of both sourwood and rubber tree honeys have been reported. Our results indicated that Malaysian honey (specifically sourwood honey and longan honey) is a good source of antioxidants compared to Manuka honey.
Pathological assessments for the presence of hexanucleotide repeat expansions in C9ORF72 in Alzheimer’s disease
Authors: Davidson Yvonne S , Robinson Andrew C , Snowden Julie S , Mann David MA 
Published: August 2013

Abstract

Background
We have sought histological evidence, using TDP-43 and p62 immunohistochemistry, for the presence of expansions in C9ORF72 among 200 patients with pathologically confirmed AD.

Results
We noted TDP-43 pathological changes in hippocampus and temporal cortex in 45 (22.5%) of these patients, but did not detect any cases where p62 positive changes in hippocampus and cerebellum, considered pathognomic for C9ORF72 expansions, were present.

Conclusion
We conclude that expansions in C9ORF72 associated with AD are a rare occurrence, and in those instances in the literature where these have been reported, the presence of AD may in fact be coincidental and unrelated to the expansion.
Novel sorafenib analogues induce apoptosis through SHP-1 dependent STAT3 inactivation in human breast cancer cells
Authors: Liu Chun-Yu , Tseng Ling-Ming , Su Jung-Chen , Chang Kung-Chi , Chu Pei-Yi , Tai Wei-Tien , Shiau Chung-Wai , Chen Kuen-Feng 
Published: August 2013

Abstract
Introduction
Signal transducers and activators of transcription 3 (STAT3) signaling is constitutively activated in various cancers including breast cancer and has emerged as a novel potential anti-cancer target. STAT3 has been demonstrated to be a target of sorafenib, and a protein tyrosine phosphatase Src homology 2-domain containing tyrosine phosphatase 1 (SHP-1) has been demonstrated to downregulate p-STAT3 via its phosphatase activity. Here, we tested the efficacy of two sorafenib analogues, SC-1 and SC-43, in breast cancer cells and examined the drug mechanism.

Methods
Breast cancer cell lines were used for in vitro studies. Cell viability was examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was examined by flow cytometry and western blot. Signal transduction pathways in cells were assessed by western blot. In vivo efficacy of sorafenib, SC-1 and SC-43 was tested in xenografted nude mice.

Results
SC-1 and SC-43 induced more potent apoptosis than sorafenib, in association with downregulation of p-STAT3 and its downstream proteins cyclin D1 and survivin in a dose-dependent manner in breast cancer cell lines (HCC-1937, MDA-MB-468, MDA-MB-231, MDA-MB-453, SK-BR3, MCF-7). Overexpression of STAT3 in MDA-MB-468 cells protected the cells from apoptosis induced by sorafenib, SC-1 and SC-43. Moreover, SC-1 and SC-43 upregulated SHP-1 activity to a greater extent than sorafenib as measured by in vitro phosphatase assays. Knockdown of SHP-1 by siRNA reduced apoptosis induced by SC-1 and SC-43. Importantly, SC-1 and SC-43 showed more efficacious antitumor activity and p-STAT3 downregulation than sorafenib in MDA-MB-468 xenograft tumors.

Conclusions
Novel sorafenib analogues SC-1 and SC-43 induce apoptosis through SHP-1 dependent STAT3 inactivation and demonstrate greater potency than sorafenib in human breast cancer cells.
The Shock Index revisited – a fast guide to transfusion requirement? A retrospective analysis on 21,853 patients derived from the TraumaRegister DGU®
Authors: Mutschler Manuel , Nienaber Ulrike , Münzberg Matthias , Wölfl Christoph , Schoechl Herbert , Paffrath Thomas , Bouillon Bertil , Maegele Marc ,   The TraumaRegister DGU®
Published: August 2013

Abstract
Introduction
Isolated vital signs (for example, heart rate or systolic blood pressure) have been shown unreliable in the assessment of hypovolemic shock. In contrast, the Shock Index (SI), defined by the ratio of heart rate to systolic blood pressure, has been advocated to better risk-stratify patients for increased transfusion requirements and early mortality. Recently, our group has developed a novel and clinical reliable classification of hypovolemic shock based upon four classes of worsening base deficit (BD). The objective of this study was to correlate this classification to corresponding strata of SI for the rapid assessment of trauma patients in the absence of laboratory parameters.

Methods
Between 2002 and 2011, data for 21,853 adult trauma patients were retrieved from the TraumaRegister DGU® database and divided into four strata of worsening SI at emergency department arrival (group I, SI <0.6; group II, SI ≥0.6 to <1.0; group III, SI ≥1.0 to <1.4; and group IV, SI ≥1.4) and were assessed for demographics, injury characteristics, transfusion requirements, fluid resuscitation and outcomes. The four strata of worsening SI were compared with our recently suggested BD-based classification of hypovolemic shock.

Results
Worsening of SI was associated with increasing injury severity scores from 19.3 (± 12) in group I to 37.3 (± 16.8) in group IV, while mortality increased from 10.9% to 39.8%. Increments in SI paralleled increasing fluid resuscitation, vasopressor use and decreasing hemoglobin, platelet counts and Quick’s values. The number of blood units transfused increased from 1.0 (± 4.8) in group I to 21.4 (± 26.2) in group IV patients. Of patients, 31% in group III and 57% in group IV required ≥10 blood units until ICU admission. The four strata of SI discriminated transfusion requirements and massive transfusion rates equally with our recently introduced BD-based classification of hypovolemic shock.

Conclusion
SI upon emergency department arrival may be considered a clinical indicator of hypovolemic shock in respect to transfusion requirements, hemostatic resuscitation and mortality. The four SI groups have been shown to equal our recently suggested BD-based classification. In daily clinical practice, SI may be used to assess the presence of hypovolemic shock if point-of-care testing technology is not available.
Social Behavior and Characteristics of Autism Spectrum Disorder in Angelman, Cornelia de Lange, and Cri du Chat Syndromes
Authors: Moss Joanna , Howlin Patricia , Hastings Richard Patrick , Beaumont Sarah , Griffith Gemma M. , Petty Jane , Tunnicliffe Penny , Yates Rachel , Villa Darrelle , Oliver Chris 
Published: August 2013

Abstract
We evaluated autism spectrum disorder (ASD) characteristics and social behavior in Angelman (AS; n  =  19; mean age  = 10.35 years), Cornelia de Lange (CdLS; n  =  15; mean age  = 12.40 years), and Cri du Chat (CdCS, also known as 5 p-syndrome; n  =  19; mean age  =  8.80 years) syndromes. The proportion of individuals meeting the ASD cutoff on the Social Communication Questionnaire was significantly higher in the AS and CdLS groups than in the CdCS group (p &lt; .01). The groups demonstrated divergent social behavior profiles during social conditions in which adult availability, adult familiarity, and social demand were manipulated. Social enjoyment was significantly heightened in AS, whereas social approaches were heightened in individuals with CdCS. Social motivation, social communication, and enjoyment were significantly lower in CdLS. The findings highlight the importance of detailed observation when evaluating ASD and social behavior in genetic syndromes.
Long-term Impact of Parental Well-Being on Adult Outcomes and Dementia Status in Individuals With Down Syndrome
Authors: Esbensen Anna J. , Mailick Marsha R. , Silverman Wayne 
Published: August 2013

Abstract
Parental characteristics were significant predictors of health, functional abilities, and behavior problems in adults with Down syndrome (n  =  75) over a 22-year time span, controlling for initial levels and earlier changes in these outcomes. Lower levels of behavior problems were predicted by improvements in maternal depressive symptoms. Higher levels of functional abilities were predicted by prior measures of and improvements in maternal depressive symptoms. Better health was predicted by prior measures of maternal depressive symptoms, paternal positive psychological well-being, relationship quality between fathers and their adult children, and improvements in maternal positive psychological well-being. Dementia status was also predicted by parental characteristics. The study suggests the importance of the family context for healthy aging in adults with Down syndrome.
Accuracy of Self-Reported Cervical and Breast Cancer Screening by Women With Intellectual Disability
Authors: Son Esther , Parish Susan L. , Swaine Jamie G. , Luken Karen 
Published: August 2013

AbstractThis study examines the accuracy of self-report of cervical and breast cancer screening by women with intellectual disability (n  =  155). Data from face-to-face interviews and medical records were analyzed. Total agreement, sensitivity, specificity, positive predictive value and negative predictive value were calculated. Total agreement between self-report and medical record on receipt of both procedures was 75% for Pap test and 87% for mammography. Self-reported Pap tests and mammography showed &gt;90% sensitivity, but specificity was low for both procedures (41% for Pap test, 30% for mammogram), indicating overreporting of receipt of Pap tests and mammography similar to women without disabilities. Clinicians and researchers are cautioned to corroborate self-reported data with other sources for patients and research participants with intellectual disability.
Multiplex Picodroplet Digital PCR to Detect KRAS Mutations in Circulating DNA from the Plasma of Colorectal Cancer Patients
Authors: Taly Valerie , Pekin Deniz , Benhaim Leonor , Kotsopoulos Steve K , Le Corre Delphine , Li Xinyu , Atochin Ivan , Link Darren R , Griffiths Andrew D , Pallier Karine , Blons Hélène , Bouché Olivier , Landi Bruno , Hutchison J Brian , Laurent-Puig Pierre 
Published: August 2013

BACKGROUND
Multiplex digital PCR (dPCR) enables noninvasive and sensitive detection of circulating tumor DNA with performance unachievable by current molecular-detection approaches. Furthermore, picodroplet dPCR facilitates simultaneous screening for multiple mutations from the same sample.

METHODS
We investigated the utility of multiplex dPCR to screen for the 7 most common mutations in codons 12 and 13 of the KRAS (Kirsten rat sarcoma viral oncogene homolog) oncogene from plasma samples of patients with metastatic colorectal cancer. Fifty plasma samples were tested from patients for whom the primary tumor biopsy tissue DNA had been characterized by quantitative PCR.

RESULTS
Tumor characterization revealed that 19 patient tumors had KRAS mutations. Multiplex dPCR analysis of the plasma DNA prepared from these samples identified 14 samples that matched the mutation identified in the tumor, 1 sample contained a different KRAS mutation, and 4 samples had no detectable mutation. Among the tumor samples that were wild type for KRAS, 2 KRAS mutations were identified in the corresponding plasma samples. Duplex dPCR (i.e., wild-type and single-mutation assay) was also used to analyze plasma samples from patients with KRAS-mutated tumors and 5 samples expected to contain the BRAF (v-raf murine sarcoma viral oncogene homolog B) V600E mutation. The results for the duplex analysis matched those for the multiplex analysis for KRAS-mutated samples and, owing to its higher sensitivity, enabled detection of 2 additional samples with low levels of KRAS-mutated DNA. All 5 samples with BRAF mutations were detected.

CONCLUSIONS
This work demonstrates the clinical utility of multiplex dPCR to screen for multiple mutations simultaneously with a sensitivity sufficient to detect mutations in circulating DNA obtained by noninvasive blood collection.
Investment, Dynamic Consistency and the Sectoral Regulator’s Objective
Authors: Brito Duarte , Pereira Pedro , Vareda João 
Published: August 2013

Abstract
This article explores the possibility of distorting the regulator’s objective function as a way of overcoming the dynamic consistency problem of regulatory policy toward investment. We derive general conditions under which having the legislator distort the regulator’s objective function away from social welfare allows increasing the range of parameter values for which it is possible to induce socially desirable investment. In particular, we show that when the regulator cannot commit to a regulatory policy, the legislator should give a relatively higher weight to the incumbent’s profit in the regulator’s objective function, if the incumbent invests, and a relatively higher weight to consumer surplus, if the incumbent does not invest.
Political Parties, Candidate Selection, and Quality of Government
Authors: Aragón Fernando M. 
Published: August 2013

Abstract
This article explores empirically the relation between political parties’ institutions and quality of government. I focus on procedures used to nominate presidential candidates given the importance of candidate selection in party politics. Using a panel dataset of Latin American countries, I find robust evidence of a positive relation between the use of democratic procedures, such as primaries, and quality of government. To shed light on the mechanism, I examine why parties use primaries. I find evidence suggestive that the results are mostly driven by the increase in political competition and candidates’ pre-electoral incentives.
Silver nanoparticles induce cytotoxicity, but not cell transformation or genotoxicity on Balb3T3 mouse fibroblasts
Authors: Broggi Francesca , Ponti Jessica , Giudetti Guido , Franchini Fabio , Stone Vicki , García César Pascual , Rossi François 
Published: August 2013

AbstractSilver nanoparticles (Ag NPs) are one of the most common nanomaterials present in nanotechnology-based products. Here, the physical chemical properties of Ag NPs suspensions of 44 nm, 84 nm and 100 nm sizes synthesized in our laboratory were characterized. The NM-300 material (average size of 17 nm), supplied by the Joint Research Centre Nanomaterials Repository was also included in the present study. The Ag NPs potential cytotoxicity was tested on the Balb3T3 cell line by the Colony Forming Efficiency assay, while their potential morphological neoplastic transformation and genotoxicity were tested by the Cell Transformation Assay and the micronucleus test, respectively. After 24 h of exposure, NM-300 showed cytotoxicity with an IC50 of 8 µM (corresponding to 0.88 µg/mL) while for the other nanomaterials tested, values of IC50 were higher than 10 µM (1.10 µg/mL). After 72 h of exposure, Ag NPs showed size-dependent cytotoxic effect with IC50 values of 1.5 µM (1.16 µg/mL) for NM-300, 1.7 µM (1.19 µg/mL) for Ag 44 nm, 1.9 µM (0.21 µg/mL) for Ag 84 nm and 3.2 µM (0.35 µg/mL) for Ag 100 nm. None of the Ag NPs tested was able to induce either morphological neoplastic transformation or micronuclei formation.
Vitamin D, adipose tissue, and obesity
Authors: Marcotorchino Julie , Tourniaire Franck , Landrier Jean-François 
Published: August 2013

Abstract
Epidemiological studies have shown a link between vitamin D deficiency and numerous pathologies such as cancers, immunity diseases, cardiovascular diseases, hypertension, type 2 diabetes, and obesity. Recent studies in vitro and in animal models demonstrated an impact of vitamin D on adipose tissue and adipocyte biology. Such observations are of particular interest and provide mechanistic explanations on the relationship between vitamin D deficiency and obesity.
Adipose tissue inflammation and metabolic dysfunction: a clinical perspective
Authors: Tam Charmaine S. , Redman Leanne M. 
Published: August 2013

Abstract
Obesity is characterized by a state of chronic low-grade inflammation due to increased immune cells, specifically infiltrated macrophages into adipose tissue, which in turn secrete a range of proinflammatory mediators. This nonselective low-grade inflammation of adipose tissue is systemic in nature and can impair insulin signaling pathways, thus, increasing the risk of developing insulin resistance and type 2 diabetes. The aim of this review is to provide an update on clinical studies examining the role of adipose tissue in the development of obesity-associated complications in humans. We will discuss adipose tissue inflammation during different scenarios of energy imbalance and metabolic dysfunction including obesity and overfeeding, weight loss by calorie restriction or bariatric surgery, and conditions of insulin resistance (diabetes, polycystic ovarian syndrome).