bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extraction of elementary rate constants from global network analysis of E. coli central metabolism
Authors: Zhao Jiao , Ridgway Douglas , Broderick Gordon , Kovalenko Andriy , Ellison Michael 
Published: May 2008

Abstract

Background
As computational performance steadily increases, so does interest in extending one-particle-per-molecule models to larger physiological problems. Such models however require elementary rate constants to calculate time-dependent rate coefficients under physiological conditions. Unfortunately, even when in vivo kinetic data is available, it is often in the form of aggregated rate laws (ARL) that do not specify the required elementary rate constants corresponding to mass-action rate laws (MRL). There is therefore a need to develop a method which is capable of automatically transforming ARL kinetic information into more detailed MRL rate constants.

Results
By incorporating proteomic data related to enzyme abundance into an MRL modelling framework, here we present an efficient method operating at a global network level for extracting elementary rate constants from experiment-based aggregated rate law (ARL) models. The method combines two techniques that can be used to overcome the difficult properties in parameterization. The first, a hybrid MRL/ARL modelling technique, is used to divide the parameter estimation problem into sub-problems, so that the parameters of the mass action rate laws for each enzyme are estimated in separate steps. This reduces the number of parameters that have to be optimized simultaneously. The second, a hybrid algebraic-numerical simulation and optimization approach, is used to render some rate constants identifiable, as well as to greatly narrow the bounds of the other rate constants that remain unidentifiable. This is done by incorporating equality constraints derived from the King-Altman and Cleland method into the simulated annealing algorithm. We apply these two techniques to estimate the rate constants of a model of E. coli glycolytic pathways. The simulation and statistical results show that our innovative method performs well in dealing with the issues of high computation cost, stiffness, local minima and uncertainty inherent with large-scale non-convex nonlinear MRL models.

Conclusion
In short, this new hybrid method can ensure the proper solution of a challenging parameter estimation problem of nonlinear dynamic MRL systems, while keeping the computational effort reasonable. Moreover, the work provides us with some optimism that physiological models at the particle scale can be rooted on a firm foundation of parameters generated in the macroscopic regime on an experimental basis. Thus, the proposed method should have applications to multi-scale modelling of the real biological systems allowing for enzyme intermediates, stochastic and spatial effects inside a cell.
Metabolic regulation analysis of an ethanologenic Escherichia coli strain based on RT-PCR and enzymatic activities
Authors: Orencio-Trejo Montserrat , Flores Noemí , Escalante Adelfo , Hernández-Chávez Georgina , Bolívar Francisco , Gosset Guillermo , Martinez Alfredo 
Published: May 2008

Abstract

Background
A metabolic regulation study was performed, based upon measurements of enzymatic activities, fermentation performance, and RT-PCR analysis of pathways related to central carbon metabolism, in an ethanologenic Escherichia coli strain (CCE14) derived from lineage C. In comparison with previous engineered strains, this E coli derivative has a higher ethanol production rate in mineral medium, as a result of the elevated heterologous expression of the chromosomally integrated genes encoding PDC
Zm
and ADH
Zm
(pyruvate decarboxylase and alcohol dehydrogenase from Zymomonas mobilis). It is suggested that this behavior might be due to lineage differences between E. coli W and C.

Results
This study demonstrated that the glycolytic flux is controlled, in this case, by reactions outside glycolysis, i.e., the fermentative pathways. Changes in ethanol production rate in this ethanologenic strain result in low organic acid production rates, and high glycolytic and ethanologenic fluxes, that correlate with enhanced transcription and enzymatic activity levels of PDC
Zm
and ADH
Zm
. Furthermore, a higher ethanol yield (90% of the theoretical) in glucose-mineral media was obtained with CCE14 in comparison with previous engineered E. coli strains, such as KO11, that produces a 70% yield under the same conditions.

Conclusion
Results suggest that a higher ethanol formation rate, caused by ahigher PDC
Zm
and ADH
Zm
activities induces a metabolic state that cells compensate through enhanced glucose transport, ATP synthesis, and NAD-NADH+H turnover rates. These results show that glycolytic enzymatic activities, present in E. coli W and C under fermentative conditions, are sufficient to contend with increases in glucose consumption and product formation rates.
Salicylates Increase Insulin Secretion in Healthy Obese Subjects
Authors: Fernández-Real José-Manuel , López-Bermejo Abel , Ropero Ana-Belén , Piquer Sandra , Nadal Angel , Bassols Judit , Casamitjana Roser , Gomis Ramón , Arnaiz Eva , Pérez Iñaki , Ricart Wifredo 
Published: May 2008

AbstractContext: Conflicting results on the effects of salicylates on glucose tolerance in subjects with normal glucose tolerance or type 2 diabetes have been reported.Objective: The objective of the study was to investigate the effects of a salicylate derivative (triflusal) on insulin sensitivity and insulin secretion.Design, Setting, and Participants: This was a double-blind, randomized, crossover study with three treatment periods corresponding to two dose levels of triflusal and placebo in healthy obese subjects.Main Outcome Measures: Insulin sensitivity and insulin secretion, evaluated through frequently sampled iv glucose tolerance test that was performed after each treatment period, were measured. Insulin secretion was also evaluated in vitro in mice and human islets of Langerhans.Results: The administration of triflusal led to decreased fasting serum glucose concentration in the study subjects. Insulin sensitivity did not significantly change after each treatment period. Insulin secretion, however, significantly increased in a dose-dependent fashion after each triflusal treatment period. The administration of 800 μm of the main triflusal metabolite to whole mice islets of Langerhans led to a sustained increase in intracellular calcium concentration level. This was followed by a significantly increase in insulin secretion. In human islets, 200 μm of 2-hydroxy-4-trifluoromethylbenzoic acid was sufficient to increase insulin release.Conclusions: The administration of a salicylate compound led to lowering of serum glucose concentration. We suggest that this effect was mediated through increased insulin secretion induced by salicylate directly on the β-cell.
Effects of Intrabrachial Metacholine Infusion on Muscle Capillary Recruitment and Forearm Glucose Uptake during Physiological Hyperinsulinemia in Obese, Insulin-Resistant Individuals
Authors: Murdolo Giuseppe , Sjöstrand Mikaela , Strindberg Lena , Gudbjörnsdóttir Soffia , Lind Lars , Lönnroth Peter , Jansson Per-Anders 
Published: May 2008

Abstract
Context: Impairment of insulin-mediated capillary recruitment in skeletal muscle contributes to a hampered glucose uptake in obesity.
Objective: The objective of this study was to evaluate whether metacholine (MCh), a nitric oxide vasodilator, potentiates muscle capillary recruitment and forearm glucose uptake (FGU) during physiological hyperinsulinemia.
Design: The double-forearm technique [i.e. infused vs. control (Ctrl) forearm] was combined with im microdialysis during an oral glucose tolerance test in 15 nondiabetic, obese subjects divided into a group of insulin-resistant (IR) (n = 7) and insulin-sensitive (n = 8) individuals.
Results: After the oral glucose tolerance test, forearm blood flow in the Ctrl forearm was unchanged, whereas it increased about 3-fold (P &lt; 0.0001 vs. baseline) in response to MCh. Capillary permeability surface area product for glucose (PSglu) (capillary recruitment), FGU, and interstitial insulin concentrations increased significantly over time (P &lt; 0.001) in both forearms. Compared with insulin-sensitive, the IR subjects exhibited lower PSglu (P &lt; 0.001) and FGU (P &lt; 0.01) in the Ctrl arm, whereas this difference was insignificant in the MCh arm despite the blunted forearm blood flow increase. Moreover, in IR individuals MCh significantly (P &lt; 0.05) ameliorated the delayed onset of insulin action, i.e. the FGU response to hyperinsulinemia. Finally, we found PSglu to be a strong and independent predictor of FGU response (adjusted R2 0.72; P &lt; 0.0001).
Conclusions: MCh-induced vasodilation may improve the microvascular and metabolic responses to physiological hyperinsulinemia in obese, IR individuals. Further studies are required to unravel whether stimulation of nitric oxide production in skeletal muscle may represent an attractive therapeutic approach to bypassing cellular resistance to glucose disposal.
Comparison of Single and Combined Treatment with Exenatide and Metformin on Menstrual Cyclicity in Overweight Women with Polycystic Ovary Syndrome
Authors: Elkind-Hirsch Karen , Marrioneaux Ory , Bhushan Madhu , Vernor Denise , Bhushan Rajat 
Published: May 2008

Abstract
Context: Insulin resistance and obesity are common features of the polycystic ovary syndrome (PCOS). Weight loss and use of insulin-lowering drugs have been shown to improve both reproductive and metabolic aspects of PCOS.
Objective: We evaluated exenatide (EX) and metformin (MET), alone and in combination (COM), on menstrual cyclicity, hormonal parameters, metabolic profiles, and inflammatory markers in overweight, insulin-resistant women with PCOS.
Design, Setting, and Participants: Sixty overweight oligoovulatory women with PCOS (body mass index &gt; 27; 18–40 yr) were randomized to one of three treatment groups: MET [1000 mg twice daily (BID)], EX (10 μg BID), or COM (MET 1000 mg BID, EX 10 μg BID) for 24 wk. The primary outcome was menstrual frequency; secondary outcome measures included changes in ovulation rate, insulin action, anthropometric measures, androgen levels, and inflammatory markers.
Results: Forty-two (70%) patients completed the study. COM therapy was superior to EX or MET monotherapy in improving menstrual cyclicity, ovulation rate, free androgen index, and insulin sensitivity measures and reducing weight and abdominal fat. Both EX arms were more effective in promoting weight loss than MET (P = 0.003).
Conclusions: COM appears better than either EX or MET alone on menstrual cycle frequency and hormonal and metabolic derangements. A marked decrease in central adiposity could partly explain the improvements in reproductive function, insulin-glucose parameters, and adiponectin observed in these overweight women with PCOS treated with COM therapy. Larger trials of longer duration are warranted to assess the long-term efficacy and safety of combined EX-MET therapy in overweight women with PCOS.
Synthesis of Unnatural Mono- and Oligosaccharides of Farnesol, Geraniol, and (S)-Perillyl Alcohol by Biocatalytic Glycosylations
Authors: Shimoda Kei , Sakamoto Sou , Nakajima Nobuyoshi , Hamada Hatsuyuki , Hamada Hiroki 
Published: May 2008

Abstract
Farnesol and geraniol were glucosylated to the corresponding unnatural β-glucosides, which were two new biotransformation products, by cultured plant cells of Eucalyptus perriniana, Strophanthus gratus, and Phytolacca americana. Cultured E. perriniana cells glycosylated (S)-perillyl alcohol to two β-glycosides, i.e., β-glucoside and unnatural β-gentiobioside, whereas only perillyl β-glucoside was produced by S. gratus and P. americana. Perillyl β-glucoside was further converted into two unnatural β-maltooligosaccharides, i.e., β-maltoside and β-maltotrioside, by cyclodextrin glucanotransferase.
Observations of Domain Structure and Ferroelectricity in Bi(Ni0.5Ti0.5)O3 Ceramics Fabricated by High-pressure Sintering
Authors: Kitada Kazuya , Kobune Masafumi , Adachi Wataru , Yazawa Tetsuo , Saitoh Hiroyuki , Aoki Katsutoshi , Mizuki Jun’ichiro , Ishikawa Kenya , Hiranaga Yoshiomi , Cho Yasuo 
Published: May 2008

Abstract
Bi(Ni0.5Ti0.5)O3 (BNT) ceramics with a perovskite structure, which were almost impossible to fabricate under atmospheric pressure, were synthesized at a high pressure of 6 GPa using a multianvil-type high-pressure apparatus. It was confirmed that the synthesized samples had a multidomain structure and ferroelectricity on the basis of scanning nonlinear dielectric microscopy (SNDM) and polarization–electric field (P–E) hysteresis loop measurements.
PEG-b-polyamine Stabilized Bionanoparticles for Nanodiagnostics and Nanotherapy
Authors: Nagasaki Yukio 
Published: May 2008

Abstract
Poly(ethylene glycol)-b-poly(2-(N,N-dimethylamino)ethyl methacrylate) block copolymers possessing a reactive group at the PEG chain end (R-PEG-b-PAMA) was synthesized by two different polymerization techniques. Using R-PEG-b-PAMA block copolymer thus obtained, gold nanoparticles (GNPs) were prepared. The PEG-b-PAMA worked as not only reducing agent of aurate ions but also coordination on the obtained nanoparticle surface. The obtained GNP had controlled sizes and narrow size distributions. It is also showed extremely high dispersion stability due to the PEG tethering chains on the surface. The same strategy could be applicable to other nanoparticles such as semiconductor quantum dot and inorganic porous nanoparticles. Using PEGylated GNPs thus prepared, several applications such as molecular recognitions, siRNA release and enzyme immobilizations were carried out. The functionalities of these materials are described in this review.
Quantitative Spin-trapping ESR Investigation on Reaction of Hydroxyl Radical and Selected Scavengers by a Newly Developed Flow-injection ESR System
Authors: Komatsu-Watanabe Rushiru , Sakurai Yasuhiro , Morimoto Chie , Sakamoto Shunji , Kanaori Kenji , Tajima Kunihiko 
Published: May 2008

Abstract
A new flow-injection ESR system (FI-ESR) special for the quantitative spin-trapping ESR measurements is developed to estimate the second-order rate constants (ks) of the reaction between hydroxyl radical and selected scavengers, glycine, mannitol, and 4-hydroxycoumaric acid. The ks values of these scavengers show reasonable agreement with those evaluated by pulse radiolysis method.
Perceptions of childhood immunization in a minority community: qualitative study
Authors: Henderson Lesley , Millett Christopher , Thorogood Nicki 
Published: May 2008

Summary Objective To assess reasons for low uptake of immunization amongst orthodox Jewish families. Design Qualitative interviews with 25 orthodox Jewish mothers and 10 local health care workers. Setting The orthodox Jewish community in North East London. Main outcome measures Identification of views on immunization in the orthodox Jewish community. Results In a community assumed to be relatively insulated from direct media influence, word of mouth is nevertheless a potent source of rumours about vaccination dangers. The origins of these may lie in media scares that contribute to anxieties about MMR. At the same time, close community cohesion leads to a sense of relative safety in relation to tuberculosis, with consequent low rates of BCG uptake. Thus low uptake of different immunizations arises from enhanced feelings of both safety and danger. Low uptake was not found to be due to the practical difficulties associated with large families, or to perceived insensitive cultural practices of health care providers. Conclusions The views and practices of members of this community are not homogeneous and may change over time. It is important that assumptions concerning the role of religious beliefs do not act as an obstacle for providing clear messages concerning immunization, and community norms may be challenged by explicitly using its social networks to communicate more positive messages about immunization. The study provides a useful example of how social networks may reinforce or challenge misinformation about health and risk and the complex nature of decision making about children's health.
‘Surgical’ causes of benign intracranial hypertension
Authors: Bodkin Peter Alwyn , Hassan Md Faizul , Kane Philip John , Brady Nick , Whittle Ian Roger 
Published: May 2008

Summary Benign intracranial hypertension is a clinical diagnosis linked to a number of medical and surgical disorders. A common aetiology has not yet been established. It would seem, however, that many, if not all, of these cases can be related to some degree of cerebral venous outflow obstruction. We present here a series of patients with extraluminal compression of the cerebral venous sinuses that has been amenable to surgical resection. These ‘surgical’ causes of BIH illustrate an important subset of the disease and inform us about the possible pathophysiological principles underlying the disorder.
Atypical Anaphylactic Reaction to Patent Blue During Sentinel Lymph Node Biopsy for Breast Cancer
Authors: Lanitis Sophocles , Filippakis George , Sidhu Virinder , Mufti Ragheed AL , Lee Tak H , Hadjiminas Dimitri J 
Published: May 2008

INTRODUCTION We present an unusual case of severe anaphylaxis to Patent Blue dye with atypical clinical features during sentinel lymph node biopsy (SLNB). The medical personnel involved with sentinel node biopsies should be alert, and familiar with this unusual entity. We also present current data from the literature. CASE REPORT During a wide local excision for primary breast cancer and SLNB, and early during the operation, the patient became severely tachycardic and hypotensive without any signs of urticaria, rash, oedema, or bronchospasm. Resuscitation required the addition of noradrenaline infusion followed by an overnight admission to the intensive care unit. Raised serum tryptase levels supported the diagnosis of anaphylactic shock while skin tests showed a severe reaction to Patent Blue dye. CONCLUSIONS Severe, life-threatening anaphylaxis to Patent Blue dye may present without obvious previous exposure to the dye and without the cardinal signs of oedema, urticaria and bronchospasm making the diagnosis and management of such cases challenging. Correct diagnosis and identification of the causative factor is important and requires a specific set of laboratory tests that are not commonly requested in every-day medical practice. It is not clear from the literature whether the condition is common enough to justify pre-operative prophylactic or diagnostic measures.
Biopsy for Malignant Melanoma – Are We Following the Guidelines?
Authors: Tadiparthi S , Panchani S , Iqbal A 
Published: May 2008

INTRODUCTIONGuidelines for suspected malignant melanoma recommend a prompt, full-thickness excision biopsy allowing diagnosis and assessment of the Breslow thickness. Incisional biopsy is acceptable only for extensive facial lentigo maligna or acral melanoma. Punch, shave and other types of biopsies do not allow pathological staging and are, therefore, not recommended.PATIENTS AND METHODSA total of 100 referrals for histology-proven malignant melanoma were assessed retrospectively over a 1-year period (2005).RESULTSOf the 100 patients included in this study, 52 were male and 48 female. Ages ranged from 18–91 years, with a mean of 63 years. Origin of referrals was: dermatology, 63%; general practitioner (GP), 33%; and other sources in the remaining 4% of cases. Malignant melanoma was suspected in 84% and a benign lesion in remaining 16% of patients. However, only 56% of the patients were seen in our unit within 14 days of the referral as per the 2-week cancer rule. In these 100 patients, various types of biopsy were performed: 50 were referred without biopsy, 17 excision, 20 punch, 3 shave, 1 curettage, and 1 incisional biopsy. The type of biopsy was not recorded in the remaining 3 patients. Of the GP group, 48% were referred without biopsy, 12% had excision and 3% had incisional biopsies. The remaining 30% were punch, shave biopsies, and even curettage, inconsistent with current recommendations. Of the dermatology group, 54% were referred without biopsy, 21% underwent excision biopsy and 22% were punch biopsies. In total, 20 punch biopsies were performed, of which 7 were for lesions on the face ranging from 1.7–25 mm in size. The remaining punch biopsies were for lesions on the trunk or limbs (4–50 mm). Of the 20 punch biopsies performed, Breslow thickness was available in only 9 cases (45%). Sixteen of the punch biopsies were done when malignant melanoma was suspected and lesion otherwise was suitable for excisional biopsy. In the GP group, 3 shave biopsies and 1 curettage were performed, of which malignant melanoma was clinically suspected in one patient. The Breslow thickness was not obtained from any of the shave biopsies or curettage cases. Of the 17 excision biopsies performed, 3 were incompletely excised (2 by dermatology and 1 by GP).CONCLUSIONSA significant proportion of biopsies are inappropriate and inconsistent with the malignant melanoma guidelines. Punch biopsies are performed even when malignant melanoma is clinically suspected and excision biopsy is feasible. Only a small proportion of patients appear to be seen on an urgent basis within 14 days of referral. Such factors can lead to a delay in diagnosis, subsequent definitive treatment and adversely affect patient outcome. This study identifies a need to provide feedback and education to sources of malignant melanoma referrals.
Self-Assessment of Technical Skill in Surgery: The Need for Expert Feedback
Authors: Pandey VA , Wolfe JHN , Black SA , Cairols M , Liapis CD , Bergqvist D 
Published: May 2008

INTRODUCTION Technical skill has been formally assessed in the Fellow of the European Board of Vascular Surgery Examinations (FEBVS) since 2002. The aim of this study was to examine the relationship between expert assessment and trainee self-assessment. MATERIALS AND METHODS Forty-two examination candidates performed a saphenofemoral junction (SFJ) ligation and an anterior tibial anastomosis on a synthetic simulation. Each candidate was rated by two examiners using a validated rating scale for their generic surgical skill for both procedures. Candidates then anonymously rated their own performance using the same scale. Parametric tests were used in the statistical analysis; a P-value <0.05 was considered significant. RESULTS The maximum mark in each assessment was 40; 24 was considered a competent score. The interobserver correlation for examiners marks were high (SFJ ligation, α = 0.68; distal anastomosis, α = 0.76). Examiners' marks were averaged. The mean examiner score for the SFJ ligation station was 27.8 (SD = 4.1) with 36 candidates (85.8%) attaining a competent score. The mean self-assessment score for this station was 30.7 (SD = 4.66). The mean examiners' marks for the distal anastomosis station was 29.2 (SD = 4.2); 39 candidates (92.8%) attained a competent score. The mean self-assessment score was 32.1 (SD = 4.0). There was no correlation between examiner and self-assessment scores in either station (Pearson's correlation coefficient: SFJ, r = 0.045, P = NS); distal anastomosis, r = 0.089, P = NS). Bland and Altman plots assessed the agreement between examiner and self-assessment. These showed candidates marked themselves higher than examiners with a mean difference of 2.9 marks in each station. CONCLUSIONS Candidates' self-assessment and expert independent assessment correlate poorly. Trainees overestimate their ability according to independent assessment; regular technical feedback during training is, therefore, essential.