bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central metabolic responses to the overproduction of fatty acids in Escherichia coli based on 13C‐metabolic flux analysis
Authors: He Lian , Xiao Yi , Gebreselassie Nikodimos , Zhang Fuzhong , Antoniewicz Maciek R. , Tang Yinjie J. , Peng Lifeng 
Published: October 2013

ABSTRACTWe engineered a fatty acid overproducing Escherichia coli strain through overexpressing tesA (“pull”) and fadR (“push”) and knocking out fadE (“block”). This “pull‐push‐block” strategy yielded 0.17 g of fatty acids (C12–C18) per gram of glucose (equivalent to 48% of the maximum theoretical yield) in batch cultures during the exponential growth phase under aerobic conditions. Metabolic fluxes were determined for the engineered E. coli and its control strain using tracer ([1,2‐13C]glucose) experiments and 13C‐metabolic flux analysis. Cofactor (NADPH) and energy (ATP) balances were also investigated for both strains based on estimated fluxes. Compared to the control strain, fatty acid overproduction led to significant metabolic responses in the central metabolism: (1) Acetic acid secretion flux decreased 10‐fold; (2) Pentose phosphate pathway and Entner–Doudoroff pathway fluxes increased 1.5‐ and 2.0‐fold, respectively; (3) Biomass synthesis flux was reduced 1.9‐fold; (4) Anaplerotic phosphoenolpyruvate carboxylation flux decreased 1.7‐fold; (5) Transhydrogenation flux converting NADH to NADPH increased by 1.7‐fold. Real‐time quantitative RT‐PCR analysis revealed the engineered strain increased the transcription levels of pntA (encoding the membrane‐bound transhydrogenase) by 2.1‐fold and udhA (encoding the soluble transhydrogenase) by 1.4‐fold, which is in agreement with the increased transhydrogenation flux. Cofactor and energy balances analyses showed that the fatty acid overproducing E. coli consumed significantly higher cellular maintenance energy than the control strain. We discussed the strategies to future strain development and process improvements for fatty acid production in E. coli. Biotechnol. Bioeng. 2014;111: 575–585. © 2013 Wiley Periodicals, Inc.
Aggregates of α‐chymotrypsinogen anneal to access more stable states
Authors: Maurer Ronald W. , Hunter Alan K. , Robinson Anne S. , Roberts Christopher J. 
Published: October 2013

AbstractNon‐native protein aggregates present a variety of problems in fundamental and applied biochemistry and biotechnology, from quality and safety issues in pharmaceutical development to their association with a number of chronic diseases. The aggregated, often amyloid, protein state is often considered to be more thermodynamically and kinetically stable than (partially) unfolded or folded monomers except under highly denaturing conditions. However, evolution of the structure and stability of aggregated states has received much less attention. Here it is shown that under mildly‐denaturing conditions (elevated temperature or [urea]), where the native monomer (N) is slightly favored compared to the unfolded state (U), α‐chymotrypsinogen A (aCgn) non‐native aggregates undergo a structural relaxation or annealing process to reach even more stable states. The annealed aggregates are more resistant to dissociation than aggregates that do not undergo this relaxation process. Aggregates without annealing dissociate via linear chain depolymerization, and annealing is accelerated under conditions that promote slow dissociation (partially denaturing conditions). This is consistent with a free energy landscape with multiple barriers and local minima that allows for a kinetic competition between aggregate dissociation and structural relaxation to more stable aggregate states. This highlights added complexities for protein refolding or aggregate dissociation processes, and may explain why it is often difficult to completely recover monomeric protein from aggregates. Biotechnol. Biotechnol. Bioeng. 2014;111: 782–791. © 2013 Wiley Periodicals, Inc.
Deceleration‐stats save much time during phototrophic culture optimization
Authors: Hoekema Sebastiaan , Rinzema Arjen , Tramper Johannes , Wijffels René H. , Janssen Marcel 
Published: October 2013

ABSTRACTIn case of phototrophic cultures, photobioreactor costs contribute significantly to the total operating costs. Therefore one of the most important parameters to be determined is the maximum biomass production rate, if biomass or a biomass associated product is the desired product. This is traditionally determined in time consuming series of chemostat cultivations. The goal of this work is to assess the experimental time that can be saved by applying the deceleration stat (D‐stat) technique to assess the maximum biomass production rate of a phototrophic cultivation system, instead of a series of chemostat cultures. A mathematical model developed by Geider and co‐workers was adapted in order to describe the rate of photosynthesis as a function of the local light intensity. This is essential for the accurate description of biomass productivity in phototrophic cultures. The presented simulations demonstrate that D‐stat experiments executed in the absence of pseudo steady‐state (i.e., the arbitrary situation that the observed specific growth rate deviates <5% from the dilution rate) can still be used to accurately determine the maximum biomass productivity of the system. Moreover, this approach saves up to 94% of the time required to perform a series of chemostat experiments that has the same accuracy. In case more information on the properties of the system is required, the reduction in experimental time is reduced but still significant. Biotechnol. Bioeng. 2014;111: 792–802. © 2013 Wiley Periodicals, Inc.
A quantitative analysis of the polyamine in lung cancer patient fingernails by LC‐ESI‐MS/MS
Authors: Min Jun Zhe , Matsumoto Akihito , Li Gao , Jiang Ying‐Zi , Yu Hai‐fu , Todoroki Kenichiro , Inoue Koichi , Toyo'oka Toshimasa 
Published: October 2013

ABSTRACTA quantitative analysis of polyamines in lung cancer patient fingernails by the combination of 4‐(N,N‐dimethylaminosulfonyl)‐7‐fluoro‐2,1,3‐benzoxadiazole derivatives and liquid chromatography–electrospray ionization tandem mass spectrometry is described. The reaction of the reagent with eight kinds of polyamines, that is, N1‐acetylputrescine (N1‐actPUT), N8‐acetylspermidine, N1‐acetylspermine, 1,3‐diaminopropane, putrescine (PUT), cadaverine, spermidine and spermine (SPM) effectively occurs at 60 °C for 30 min. The detection limits (signal‐to‐noise ratio 5) were 5–100 fmol. A good linearity was achieved from the calibration curves, which was obtained by plotting the peak area ratios of the analytes relative to the internal standard (IS), that is, 1,6‐diaminohexane, vs the injected amounts of polyamines (r2 > 0.996), and the intra‐day and inter‐day assay precisions were <9.84%. Furthermore, the recoveries (%) of the polyamines spiked in the human fingernails were 89.14–110.64. The present method was applied to human fingernail samples from 17 lung cancer patients and 39 healthy volunteers. The polyamine concentration was different based on the gender, that is, the N1‐actPUT and PUT contents were 3.10 times and 2.56 times higher in healthy men than in women, respectively. Additionally, in the lung cancer patient group, as compared with the healthy volunteers, the concentrations of SPM had a statistically significant (p < 0.05) correlation. Therefore, because the proposed method provides a good mass accuracy and the trace detection of the polyamines in human fingernails, this analytical technique could be a noninvasive technique to assist in the diagnosis and assessment of disease activity in lung cancer patients. Copyright © 2013 John Wiley & Sons, Ltd.
Comparison of diabetes patients with “demyelinating” diabetic sensorimotor polyneuropathy to those diagnosed with CIDP
Authors: Dunnigan Samantha K. , Ebadi Hamid , Breiner Ari , Katzberg Hans D. , Lovblom Leif E. , Perkins Bruce A. , Bril Vera 
Published: October 2013

AbstractBackgroundWe have previously identified a subset of diabetic sensorimotor polyneuropathy (DSP) patients with probable demyelination related to poor glycemic control. We aimed to determine whether the clinical characteristics and electrodiagnostic classification of nerve injury in diabetes patients with “demyelinating” DSP (D‐DSP) differed from those diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) (CIDP + diabetes mellitus [DM]).MethodsD‐DSP (56) and CIDP + DM (67) subjects underwent clinical examination and nerve conduction studies (NCS), and were compared using analysis of variance, contingency tables, and Kruskal–Wallis analyses.ResultsOf the 123 subjects with a mean age of 60.5 ± 15.6 years and mean hemoglobin A1c (HbA1c) of 8.2 ± 2.2%, 54% had CIDP + DM and 46% had D‐DSP. CIDP + DM subjects were older (P = 0.0003), had shorter duration of diabetes (P = 0.005), and more severe neuropathy as indicated by Toronto Clinical Neuropathy Score (TCNS) (P = 0.003), deep tendon reflexes (P = 0.02), and vibration perception thresholds (VPT) (P = 0.01, P = 0.02). The mean HbA1c value for D‐DSP subjects (8.9 ± 2.3%) was higher than in CIDP + DM subjects (7.7 ± 2.0%, P = 0.02).ConclusionsThe clinical phenotype and electrophysiological profile of CIDP + DM patients is marked by more severe neuropathy and better glycemic control than in patients with D‐DSP. These findings indicate that these two conditions – despite similarities in their electrophysiological pattern of demyelination – likely differ in etiology.
Do Greenhouse Gas Emissions Affect Financial Performance? – an Empirical Examination of Australian Public Firms
Authors: Wang Lei , Li Steven , Gao Simon 
Published: October 2013

ABSTRACTPrevious studies that have attempted to relate corporate environmental performance to financial performance have generated conflicting results. This paper presents the findings of a study on the relationship between greenhouse gas (GHG) emissions and the financial performance of Australian corporations. Using multiple regression models and data from a sample of 69 Australian public companies, this paper finds a positive correlation between GHG emissions and corporate financial performance. By testing the statistical significance of GHG emission factors in determining company Tobin's q, this study finds that a stronger Tobin's q often correlates with higher GHG emissions across all industry sectors. This finding is contrary to evidence found in previous studies conducted in other countries. The positive correlation found in this study could be explained with reference to the unique economic structure and development of Australia, particularly its dominant mining industry. Copyright © 2013 John Wiley & Sons, Ltd and ERP Environment
Oncologists’ attitudes toward KRAS testing: a multisite study
Authors: Harris Julie N. , Liljestrand Petra , Alexander Gwen L. , Goddard Katrina A. B. , Kauffman Tia , Kolevska Tatjana , McCarty Catherine , O'Neill Suzanne , Pawloski Pamala , Rahm Alanna , Williams Andrew , Somkin Carol P. 
Published: October 2013

AbstractRecent discoveries promise increasingly to help oncologists individually tailor anticancer therapy to their patients’ molecular tumor characteristics. One such promising molecular diagnostic is Kirsten ras (KRAS) tumor mutation testing for metastatic colorectal cancer (mCRC) patients. In the current study, we examined how and why physicians adopt KRAS testing and how they subsequently utilize the information when discussing treatment strategies with patients. We conducted 34 semi‐structured in‐person or telephone interviews with oncologists from seven different health plans. Each interview was audiotaped, transcribed, and coded using qualitative research methods. Information and salient themes relating to the research questions were summarized for each interview. All of the oncologists in this study reported using the KRAS test at the time of the interview. Most appeared to have adopted the test rapidly, within 6 months of the publication of National Clinical Guidelines. Oncologists chose to administer the test at various time points, although the majority ordered the test at the time their patient was diagnosed with mCRC. While oncologists expressed a range of opinions about the KRAS test, there was a general consensus that the test was useful and provided benefits to mCRC patients. The rapid adoption and enthusiasm for KRAS suggests that these types of tests may be filling an important informational need for oncologists when making treatment decisions. Future research should focus on the informational needs of patients around this test and whether patients feel informed or confident with their physicians’ use of these tests to determine treatment access.
Small endometrial carcinoma 10 mm or less in diameter: clinicopathologic and histogenetic study of 131 cases for early detection and treatment
Authors: Hasumi Katsuhiko , Sugiyama Yuko , Sakamoto Kimihiko , Akiyama Futoshi 
Published: October 2013

AbstractNatural history and clinicopathologic features of early endometrial carcinoma are not evident. Its knowledge is essential to make up strategies for prevention, early detection, and treatment of endometrial carcinoma. Especially it is important to know pathways of endometrial carcinogenesis and frequency of endometrial carcinomas arising from endometrial hyperplasia. Clinicopathologically 131 patients with endometrial carcinoma measuring ≤10 mm in diameter (“small endometrial carcinoma”) were studied to get useful information for early diagnosis, treatment, and histogenesis. The entire endometrium of surgically removed uterus was step‐cut and examined. The patients were, on average, 5 years younger than the controls whose carcinomas measure >10 mm (P < 0.0001). Of the 131 patients, 20% were asymptomatic although only 5% of the controls were asymptomatic (P < 0.0001). Seventy‐six percent had the carcinomas located in the upper third section of the uterine corpus. Macroscopically 44% of the tumors were flat and 56% were elevated. Incidence of nodal and ovarian metastases were <1%. Forty percent of “small endometrial carcinomas” were associated with endometrial hyperplasia and 60% were not. It is logical to believe that there are two pathways of endometrial carcinogenesis: carcinomas occurring from hyperplasia (40%) and carcinomas occurring from normal endometrium (60%). As hyperplasia‐carcinoma sequence is not a main route, we cannot probably prevent carcinomas only by treatment of hyperplasia. Effort must be focused on detecting early de novo carcinomas. As most “small endometrial carcinomas” arise in the upper third of the corpus, careful endometrial sampling there is important for early detection.
Prognostic value of CtIP/RBBP8 expression in breast cancer
Authors: Soria‐Bretones Isabel , Sáez Carmen , Ruíz‐Borrego Manuel , Japón Miguel A. , Huertas Pablo 
Published: October 2013

AbstractCtIP/RBBP8 is a multifunctional protein involved in transcription, DNA replication, DNA repair by homologous recombination and the G1 and G2 checkpoints. Its multiple roles are controlled by its interaction with several specific factors, including the tumor suppressor proteins BRCA1 and retinoblastoma. Both its functions and interactors point to a putative oncogenic potential of CtIP/RBBP8 loss. However, CtIP/RBBP8 relevance in breast tumor appearance, development, and prognosis has yet to be established. We performed a retrospective analysis of CtIP/RBBP8 and RB1 levels by immunohistochemistry using 384 paraffin‐embedded breast cancer biopsies obtained during tumor removal surgery. We have observed that low or no expression of CtIP/RBBP8 correlates with high‐grade breast cancer and with nodal metastasis. Reduction on CtIP/RBBP8 is most common in hormone receptor (HR)‐negative, HER2‐positive, and basal‐like tumors. We observed lower levels of RB1 on those tumors with reduced CtIP/RBBP8 levels. On luminal tumors, decreased but not absence of CtIP/RBBP8 levels correlate with increased disease‐free survival when treated with a combination of hormone, radio, and chemo therapies.
Clinical and demographic characteristics associated with the receipt of chemotherapy treatment among 7951 elderly metastatic colon cancer patients
Authors: Reese Emily S. , Onukwugha Eberechukwu , Hanna Nader , Seal Brian S. , Mullins C. Daniel 
Published: October 2013

AbstractAmong older individuals diagnosed with metastatic colon cancer (mCC) there is limited evidence available that describes the characteristics associated with advancing to second‐ and subsequent lines of treatment with chemotherapy/biologics. Our objective was to describe the trends and lines of treatment received among elderly mCC patients. Elderly beneficiaries diagnosed with mCC from 2003 to 2007 were identified in the Surveillance, Epidemiology and End Results (SEER)‐Medicare dataset. Beneficiaries were followed up until death or censoring. Treatment lines were classified in combinations of chemotherapies and biologics. Modified Poisson regression was used to predict receipt of lines of treatment. Analyses controlled for age, race/ethnicity, gender, marital status, state buy‐in during diagnosis year, SEER‐registry site, Charlson comorbidity index (CCI), poor performance indicators, surgery of primary site, and surgery of regional/distal sites. Among 7951 Medicare beneficiaries identified with mCC, 3266 initiated therapy. Of these, 1440 advanced to second‐line treatment. Of these, 274 advanced to a subsequent‐line treatment. Surgeries of the primary tumor site and of the regional/distal sites and marital status were the most significant variables associated with advancing through second‐ and subsequent‐line treatments. Greater than 80 years of age, African American race, SEER‐registry area, less than 6 months state buy‐in assistance in mCC diagnosis year, and having poor performance indicators were inversely associated with receipt of second‐ or subsequent‐line treatments. Among elderly individuals diagnosed with mCC, we identified demographic, clinical, and regional factors associated with receipt of second‐ and subsequent‐line chemotherapy/biologics. Additional research is warranted to understand the role of physician versus patient preferences as well as geographic differences explaining why patients advance through lines of chemotherapy.
Risk and Protective Factors for Physical and Emotional Abuse Victimisation amongst Vulnerable Children in South Africa
Authors: Meinck Franziska , Cluver Lucie D. , Boyes Mark E. , Ndhlovu Lodrick D. 
Published: October 2013

Little is known about risk and protective factors for emotional and physical child abuse in South Africa. Existing research has focused largely on sexual abuse and relied on recollections of childhood abuse from university and high‐school students or data from criminal reports. The objective of this study was to establish risk and protective factors for severe physical and emotional abuse amongst a large cross‐sectional community sample of South African youth. Confidential self‐report questionnaires were completed by children aged 13–19 (n = 603, 47.9% female) with local interviewers in deprived areas of South Africa. Standardised measures of abuse, hypothesised risk factors and socio‐demographic variables were used. Factors associated with severe physical and emotional child abuse were experience of family conflict (p = 0.003), unequal food distribution (p < 0.014), inconsistent discipline (p = 0.012), number of caregiver changes (p = 0.022), living with a step‐parent (p = 0.034), caregiver disability (p = 0.004), food insecurity (p = 0.006), bullying (p < 0.001), acquired immunodeficiency syndrome (AIDS)‐related stigma (p < 0.001), sexual abuse (p = 0.003), school non‐attendance (p = 0.006) and non‐achievement (p = 0.015). These identified risk and protective factors at community, school, caregiver and household levels have the potential to affect the risk of abuse for children in South Africa, and may be valuable fields for future intervention efforts. Copyright © 2013 John Wiley & Sons, Ltd.‘The objective of this study was to establish risk and protective factors for severe physical and emotional abuse amongst a large cross‐sectional sample of South African youth’Key Practitioner MessagesRisk and protective factors for physical and emotional child abuse have not been thoroughly studied in South Africa.Risk and protective factors for child abuse in South Africa include poverty, AIDS‐related stigma, bullying, school non‐attendance and achievement, sexual abuse, caregiver disability, inconsistent discipline, family conflict and living with a step‐parent.Future research should focus on longitudinal data to establish causality and to examine the relationship between child abuse and caregiver AIDS sickness.
Young People's Experiences of Going Missing From Care: A Qualitative Investigation using Peer Researchers
Authors: Taylor Julie , Bradbury‐Jones Caroline , Hunter Helen , Sanford Kate , Rahilly Tom , Ibrahim Nayla 
Published: October 2013

Looked after children are significantly more likely than other children to go missing. They face significant risk of harm through, for example, exposure to alcohol, drugs and sexual victimisation. While research identifies some factors which may reduce the likelihood of looked after children going missing, it is recognised that a greater understanding of effective practice is needed. The aim of the study was to investigate young people's experiences of going missing from care and to identify the issues that contributed to them running away; trigger factors that prompted episodes of going missing; support received during or following instances where they went missing; and factors that might prevent future absconding. Research on children's experiences is often reported from the adult's perspective rather than allowing children to have a voice. We therefore recruited two young people to collaborate with the researchers as peer researchers. A qualitative study was undertaken using the Critical Incident Technique. Twenty‐eight young people with a history of running away were recruited from different locations in Scotland. They took part in six focus groups, which were held during May 2012. Data were analysed using a framework approach. Four themes were identified regarding reasons for running away: authority and power; friction; isolation; and environmental issues. Commonly cited consequences were being ‘grounded’ and having shoes removed (to prevent further running away). Young people were critical of a lack of support on return and a lack of boundaries. They stressed the importance of being heard, being treated with respect, being able to exercise autonomy and feeling that someone cares. Copyright © 2013 John Wiley & Sons, Ltd.Key Practitioner MessagesLooked after children are significantly more likely than other children to go missing.When missing, young people are exposed to significant risk of harm.Reasons for running away are: authority and power; friction; isolation; and environmental issues.Approaches to responding to young people who go missing should be supportive and facilitative rather than punitive.Being heard, being treated with respect, being able to exercise autonomy and feeling that someone cares are crucial preventative factors.‘Research on children's experiences is often reported from the adult's perspective’‘Young people were critical of a lack of support on return and a lack of boundaries’