bluuebunny/crossref_metadata_2025_split huggingface dataset:
Algorithms for optimizing cross-overs in DNA shuffling
Authors: He Lu , Friedman Alan M , Bailey-Kellogg Chris 
Published: March 2012

Abstract

Background
DNA shuffling generates combinatorial libraries of chimeric genes by stochastically recombining parent genes. The resulting libraries are subjected to large-scale genetic selection or screening to identify those chimeras with favorable properties (e.g., enhanced stability or enzymatic activity). While DNA shuffling has been applied quite successfully, it is limited by its homology-dependent, stochastic nature. Consequently, it is used only with parents of sufficient overall sequence identity, and provides no control over the resulting chimeric library.

Results
This paper presents efficient methods to extend the scope of DNA shuffling to handle significantly more diverse parents and to generate more predictable, optimized libraries. Our CODNS (cross-over optimization for DNA shuffling) approach employs polynomial-time dynamic programming algorithms to select codons for the parental amino acids, allowing for zero or a fixed number of conservative substitutions. We first present efficient algorithms to optimize the local sequence identity or the nearest-neighbor approximation of the change in free energy upon annealing, objectives that were previously optimized by computationally-expensive integer programming methods. We then present efficient algorithms for more powerful objectives that seek to localize and enhance the frequency of recombination by producing "runs" of common nucleotides either overall or according to the sequence diversity of the resulting chimeras. We demonstrate the effectiveness of CODNS in choosing codons and allocating substitutions to promote recombination between parents targeted in earlier studies: two GAR transformylases (41% amino acid sequence identity), two very distantly related DNA polymerases, Pol X and β (15%), and beta-lactamases of varying identity (26-47%).

Conclusions
Our methods provide the protein engineer with a new approach to DNA shuffling that supports substantially more diverse parents, is more deterministic, and generates more predictable and more diverse chimeric libraries.
Gravitational and magnetic field variations synergize to cause subtle variations in the global transcriptional state of Arabidopsis in vitro callus cultures
Authors: Manzano Ana I , van Loon Jack JWA , Christianen Peter CM , Gonzalez-Rubio Juana M , Medina F Javier , Herranz Raul 
Published: March 2012

AbstractBackgroundBiological systems respond to changes in both the Earth's magnetic and gravitational fields, but as experiments in space are expensive and infrequent, Earth-based simulation techniques are required. A high gradient magnetic field can be used to levitate biological material, thereby simulating microgravity and can also create environments with a reduced or an enhanced level of gravity (g), although special attention should be paid to the possible effects of the magnetic field (B) itself.ResultsUsing diamagnetic levitation, we exposedArabidopsis thaliana in vitrocallus cultures to five environments with different levels of effective gravity and magnetic field strengths. The environments included levitation, i.e. simulated μg* (close to 0g* atB= 10.1 T), intermediateg* (0.1g* atB= 14.7 T) and enhanced gravity levels (1.9g* atB= 14.7 T and 2g* atB= 10.1 T) plus an internal 1g* control (B= 16.5 T). The asterisk denotes the presence of the background magnetic field, as opposed to the effective gravity environments in the absence of an applied magnetic field, created using a Random Position Machine (simulated μg) and a Large Diameter Centrifuge (2g).Microarray analysis indicates that changes in the overall gene expression of cultured cells exposed to these unusual environments barely reach significance using an FDR algorithm. However, it was found that gravitational and magnetic fields produce synergistic variations in the steady state of the transcriptional profile of plants. Transcriptomic results confirm that high gradient magnetic fields (i.e. to create μg* and 2g* conditions) have a significant effect, mainly on structural, abiotic stress genes and secondary metabolism genes, but these subtle gravitational effects are only observable using clustering methodologies.ConclusionsA detailed microarray dataset analysis, based on clustering of similarly expressed genes (GEDI software), can detect underlying global-scale responses, which cannot be detected by means of individual gene expression techniques using raw or corrected p values (FDR). A subtle, but consistent, genome-scale response to hypogravity environments was found, which was opposite to the response in a hypergravity environment.
Phase I/IIa study of intratumoral/intracerebral or intravenous/intracerebral administration of Parvovirus H-1 (ParvOryx) in patients with progressive primary or recurrent glioblastoma multiforme: ParvOryx01 protocol
Authors: Geletneky Karsten , Huesing Johannes , Rommelaere Jean , Schlehofer Joerg R , Leuchs Barbara , Dahm Michael , Krebs Ottheinz , von Knebel Doeberitz Magnus , Huber Bernard , Hajda Jacek 
Published: March 2012

Abstract

Background
The treatment of patients with malignant brain tumors remains a major oncological problem. The median survival of patients with glioblastoma multiforme (GBM), the most malignant type, is only 15 months after initial diagnosis and even less after tumor recurrence. Improvements of standard treatment including surgery and radio-chemotherapy have not lead to major improvements. Therefore, alternative therapeutics such as oncolytic viruses that specifically target and destroy cancer cells are under investigation. Preclinical data of oncolytic parvovirus H-1 (H-1PV) infection of glioma cells demonstrated strong cytotoxic and oncosuppressing effects, leading to a phase I/IIa trial of H-1PV in patients with recurrent GBM (ParvOryx01). ParvOryx01 is the first trial with a replication competent oncolytic virus in Germany.

Methods
ParvOryx01 is an open, non-controlled, two groups, intra-group dose escalation, single center, phase I/IIa trial. 18 patients with recurrent GBM will be treated in 2 groups of 9 patients each. Treatment group 1 will first receive H-1PV by intratumoral injection and second by administration into the walls of the tumor cavity during tumor resection. In treatment group 2 the virus will initially be injected intravenously and afterwards, identical to group 1, into the surrounding brain tissue during tumor removal. Main eligibility criteria are: age of 18 years, unifocal recurrent GBM, amenable to complete or subtotal resection. Dose escalation will be based on the Continual Reassessment Method. The primary objective of the trial is local and systemic safety and tolerability and to determine the maximum tolerated dose (MTD). Secondary objectives are proof of concept (PoC) and Progression-free Survival (PFS) up to 6 months.

Discussion
This is the first trial with H-1PV in patients with recurrent GBM. The risks for the participants appear well predictable and justified. Furthermore, ParvOryx01 will be the first assessment of combined intratumoral and intravenous application of an oncolytic virus. Due to its study design the trial will not only generate data on the local effect of H-1PV but it will also investigate the penetration of H-1PV into the tumor after systemic delivery and obtain safety data from systemic delivery possibly supporting clinical trials with H-1PV in other, non-CNS malignancies.

Trial registration
ClinicalTrials.gov Identifier: NCT01301430
Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma
Authors: Todenhöfer Tilman , Wirths Stefan , von Weyhern Claus Hann , Heckl Stefan , Horger Marius , Hennenlotter Joerg , Stenzl Arnulf , Kanz Lothar , Schwentner Christian 
Published: March 2012

AbstractBackgroundRenal cell carcinoma can cause various paraneoplastic syndromes including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. We present the first case in the literature of severe paraneoplastic hypereosinophilia in a patient with renal cell carcinoma.Case presentationA 46 year-old patient patient with a history of significant weight loss, reduced general state of health and coughing underwent radical nephrectomy for metastasized renal cell carcinoma. Three weeks after surgery, the patient presented with excessive peripheral hypereosinophilia leading to profound neurological symptoms due to cerebral microinfarction. Systemic treatment with prednisolone, hydroxyurea, vincristine, cytarabine, temsirolimus and sunitinib led to reduction of peripheral eosinophils but could not prevent rapid disease progression of the patient. At time of severe leukocytosis, a considerable increase of cytokines associated with hypereosinophilia was measurable.ConclusionsParaneoplastic hypereosinophilia in patients with renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.
Antenatal magnesium individual participant data international collaboration: assessing the benefits for babies using the best level of evidence (AMICABLE)
Authors:   The AMICABLE Group
Published: March 2012

AbstractBackgroundThe primary aim of this study is to assess, using individual participant data (IPD) meta-analysis, the effects of administration of antenatal magnesium sulphate given to women at risk of preterm birth on important clinical outcomes for their child such as death and neurosensory disability. The secondary aim is to determine whether treatment effects differ depending on important pre-specified participant and treatment characteristics, such as reasons at risk of preterm birth, gestational age, or type, dose and mode of administration of magnesium sulphate.MethodsDesignThe Antenatal Magnesium Individual Participant Data (IPD) International Collaboration: assessing the benefits for babies using the best level of evidence (AMICABLE) Group will perform an IPD meta-analysis to answer these important clinical questions.Setting/TimelineThe AMICABLE Group was formed in 2009 with data collection commencing late 2010.Inclusion CriteriaFive trials involving a total 6,145 babies are eligible for inclusion in the IPD meta-analysis.Primary study outcomesFor the infants/children: Death or cerebral palsy. For the women: Any severe maternal outcome potentially related to treatment (death, respiratory arrest or cardiac arrest).DiscussionResults are expected to be publicly available in 2012.
Changing topographic Hox expression in blood vessels results in regionally distinct vessel wall remodeling
Authors: Pruett Nathanael D. , Hajdu Zoltan , Zhang Jing , Visconti Richard P. , Kern Michael J. , Wellik Deneen M. , Majesky Mark W. , Awgulewitsch Alexander 
Published: March 2012

Summary
The distinct topographic Hox expression patterns observed in vascular smooth muscle cells (VSMCs) of the adult cardiovascular system suggest that these transcriptional regulators are critical for maintaining region-specific physiological properties of blood vessels. To test this proposition, we expanded the vascular Hoxc11 expression domain normally restricted to the lower limbs by utilizing an innovative integrated tetracycline regulatory system and Transgelin promoter elements to induce Hoxc11 expression universally in VSMCs of transgenic mice. Ectopic Hoxc11 expression in carotid arteries, aortic arch and descending aorta resulted in drastic vessel wall remodeling involving elastic laminae fragmentation, medial smooth muscle cell loss, and intimal lesion formation. None of these alterations were observed upon induction of Hoxc11 transgene expression in the femoral artery, i.e. the natural Hoxc11 activity domain, although this vessel was greatly enlarged, comparable to the topographically restricted vascular changes seen in Hoxc11−/− mice. To begin defining Hoxc11-controlled pathways of vascular remodeling, we performed immunolabeling studies in conjunction with co-transfection and chromatin immunoprecipitation (ChIP) assays using mouse vascular smooth muscle (MOVAS) cells. The results suggest direct transcriptional control of two members of the matrix metalloproteinase (Mmp) family, including Mmp2 and Mmp9 that are known as key players in the inception and progression of vascular remodeling events. In summary, the severe vascular abnormalities resulting from the induced dysregulated expression of a Hox gene with regional vascular patterning functions suggest that proper Hox function and regulation is critical for maintaining vascular functional integrity.
The contribution of air breathing to aerobic scope and exercise performance in the banded knifefishGymnotus carapoL.
Authors: McKenzie David J. , Steffensen John F. , Taylor Edwin W. , Abe Augusto S. 
Published: March 2012

SUMMARYThe contribution of air breathing to aerobic metabolic scope and exercise performance was investigated in a teleost with bimodal respiration, the banded knifefish, submitted to a critical swimming speed (Ucrit) protocol at 30°C. Seven individuals (mean ± s.e.m. mass 89±7 g, total length 230±4 mm) achieved a Ucrit of 2.1±1 body lengths (BL) s–1 and an active metabolic rate (AMR) of 350±21 mg kg–1 h–1, with 38±6% derived from air breathing. All of the knifefish exhibited a significant increase in air-breathing frequency (fAB) with swimming speed. If denied access to air in normoxia, these individuals achieved a Ucrit of 2.0±0.2 BL s–1 and an AMR of 368±24 mg kg–1 h–1 by gill ventilation alone. In normoxia, therefore, the contribution of air breathing to scope and exercise was entirely facultative. In aquatic hypoxia (PO2=4 kPa) with access to normoxic air, the knifefish achieved a Ucrit of 2.0±0.1 BL s–1 and an AMR of 338±29 mg kg–1 h–1, similar to aquatic normoxia, but with 55±5% of AMR derived from air breathing. Indeed, fAB was higher than in normoxia at all swimming speeds, with a profound exponential increase during exercise. If the knifefish were denied access to air in hypoxia, Ucrit declined to 1.2±0.1 BL s–1 and AMR declined to 199±29 mg kg–1 h–1. Therefore, air breathing allowed the knifefish to avoid limitations to aerobic scope and exercise performance in aquatic hypoxia.
Blue-light-receptive cryptochrome is expressed in a sponge eye lacking neurons and opsin
Authors: Rivera Ajna S. , Ozturk Nuri , Fahey Bryony , Plachetzki David C. , Degnan Bernard M. , Sancar Aziz , Oakley Todd H. 
Published: March 2012

SUMMARY
Many larval sponges possess pigment ring eyes that apparently mediate phototactic swimming. Yet sponges are not known to possess nervous systems or opsin genes, so the unknown molecular components of sponge phototaxis must differ fundamentally from those in other animals, inspiring questions about how this sensory system functions. Here we present molecular and biochemical data on cryptochrome, a candidate gene for functional involvement in sponge pigment ring eyes. We report that Amphimedon queenslandica, a demosponge, possesses two cryptochrome/photolyase genes, Aq-Cry1 and Aq-Cry2. The mRNA of one gene (Aq-Cry2) is expressed in situ at the pigment ring eye. Additionally, we report that Aq-Cry2 lacks photolyase activity and contains a flavin-based co-factor that is responsive to wavelengths of light that also mediate larval photic behavior. These results suggest that Aq-Cry2 may act in the aneural, opsin-less phototaxic behavior of a sponge.
Adding ductus venosus blood flow as a categorical variable to the Combined and Integrated tests in Down's syndrome screening
Authors: Wald Nicholas J , Bestwick Jonathan P , Borrell Antoni 
Published: March 2012

Ductus venosus blood flow, expressed as a pulsatility index (DVPI) has been shown to improve the performance of the Combined and Integrated antenatal screening tests for Down's syndrome using previously published data. The use of ductus venosus blood flow as a categorical marker (reversed or absent end diastolic blood flow indicating a positive result) is less discriminatory but simpler, so is sometimes preferred over DVPI. For example, with the Integrated test the false-positive rate for a 90% detection rate was 1.5% as a categorical marker compared with 1.1% expressed as DVPI. We here provide the necessary algorithm and parameters for using ductus venosus blood flow as a categorical marker with the Combined and Integrated tests.
Overdiagnosis in the population-based service screening programme with mammography for women aged 40 to 49 years in Sweden
Authors: Hellquist Barbro Numan , Duffy Stephen W , Nyström Lennarth , Jonsson Håkan 
Published: March 2012

Objectives To estimate the level of overdiagnosis of all breast cancers and of invasive breast cancers in women aged 40–49 invited to the subsequent screening rounds in the Swedish service-screening programme 1986–2005. Methods To estimate the level of overdiagnosis in subsequent screening, the rate ratios (RR) of the breast cancer incidence in the study group (women in areas with screening in ages 40–49) and the control group (women in areas with no screening in ages 40–49) were calculated for all breast cancers and for invasive breast cancers. The RR estimates were adjusted for the prescreening difference in incidence between study and control group and for lead time. Results The prescreening incidence rate ratio was estimated at 0.92 (95% confidence interval [CI]: 0.88–0.97). The number of breast cancer cases and person-years were 6047 and 3.8 million, and 7790 and 5.2 million, in the study group and control group respectively during the study period. The RR estimate for all cancers was 1.01 (95% CI: 0.94–1.08) when adjusted for prescreening difference and a lead time of 1.2 years. The corresponding estimate for invasive breast cancers was 0.95 (95% CI: 0.88–1.02). Conclusions We found no significant overdiagnosis for women aged 40–49 in the Swedish service screening programme with mammography.
Influence of false-positive mammography results on subsequent screening: do physician recommendations buffer negative effects?
Authors: DeFrank Jessica T , Rimer Barbara K , Bowling J Michael , Earp Jo Anne , Breslau Erica S , Brewer Noel T 
Published: March 2012

Objective Cancer screening guidelines often include discussion about the unintended negative consequences of routine screening. This prospective study examined effects of false-positive mammography results on women's adherence to subsequent breast cancer screening and psychological well-being. We also assessed whether barriers to screening exacerbated the effects of false-positive results. Methods We conducted secondary analyses of data from telephone interviews and medical claims records for 2406 insured women. The primary outcome was adherence to screening guidelines, defined as adherent (10–14 months), delayed (15–34 months), or no subsequent mammogram on record. Results About 8% of women reported that their most recent screening mammograms produced false-positive results. In the absence of self-reported advice from their physicians to be screened, women were more likely to have no subsequent mammograms on record if they received false-positive results than if they received normal results (18% vs. 7%, OR = 3.17, 95% CI = 1.30, 7.70). Receipt of false-positive results was not associated with this outcome for women who said their physicians had advised regular screening in the past year (7% vs. 10%, OR = 0.74, 95% CI = 0.38, 1.45). False-positive results were associated with greater breast cancer worry ( P < .01), thinking more about the benefits of screening ( P < .001), and belief that abnormal test results do not mean women have cancer ( P < .01), regardless of physicians' screening recommendations. Conclusion False-positive mammography results, coupled with reports that women's physicians did not advise regular screening, could lead to non-adherence to future screening. Abnormal mammograms that do not result in cancer diagnoses are opportunities for physicians to stress the importance of regular screening.
Mammography screening and breast cancer mortality in Australia: an aggregate cohort study
Authors: Morrell Stephen , Taylor Richard , Roder David , Dobson Annette 
Published: March 2012

Background Evidence that mammography screening reduces breast cancer mortality derives from trials, with observational studies broadly supporting trial findings. The purpose of this study was to evaluate the national mammographic screening programme, BreastScreen Australia, using aggregate screening and breast cancer mortality data. Methods Breast cancer mortality from 1990 to 2004 in the whole Australian population was assessed in relation to screening exposure in the target of women aged 50–69 years. Population cohorts were defined by year of screening (and diagnosis), five-year age group at screening (and diagnosis), and local area of residence at screening (and diagnosis). Biennial screening data for BreastScreen Australia were related to cumulated mortality from breast cancer in an event analysis using Poisson regression, and in a time-to-event analysis using Cox proportional hazards regression. Results were adjusted for repeated measures and the potential effects of mammography outside BreastScreen Australia, regionality, and area socio-economic status. Results From the adjusted Poisson regression model, a 22% (95% CI:12–31%) reduction in six-year cumulated mortality from breast cancer was predicted for screening participation of approximately 60%, compared with no screening; 21% (95% CI:11–30%) for the most recently reported screening participation of 56%; and 25% (95% CI:15–35%) for the programme target of 70% biennial screening participation. Corresponding estimates from the Cox proportional hazard regression model were 30% (95% CI:17–41%), 28% (95% CI:16–38%) and 34% (95% CI:20–46%). Conclusions Despite data limitations, the results of this nationwide study are consistent with the trial evidence, and with results of other service studies of mammography screening. With sufficient participation, mammography screening substantially reduces mortality from breast cancer.
Dry self-sampling versus provider-sampling of cervicovaginal specimens for human papillomavirus detection in the Inuit population of Nunavik, Quebec
Authors: Cerigo Helen , Coutlée François , Franco Eduardo L , Brassard Paul 
Published: March 2012

Objective To assess the comparability of self-collected cervicovaginal samples and provider-collected cervical samples for the detection of human papillomavirus (HPV) DNA among Inuit women in Nunavik, Quebec, avoiding the use of liquid-based storage and transport of the self-collected samples. Methods Ninety-three women aged 18–69 years were recruited from a previously formed cohort on the natural history of HPV to this cross-sectional measurement study. This study utilized HPV DNA test results from 89 paired specimens collected by study participant and health provider with Dacron swabs. Samples were tested for 36 HPV types with the PGMY-primer PCR protocol and genotyping with the linear array method. Unweighted kappa statistics and McNemar tests were used to measure the agreement between sampling techniques. Results In the self-collected samples, 30 different HPV types were found, compared with 29 types found in the provider-collected samples. The prevalence of high-risk (HR) HPV was 38.2% in the self-collected samples and 28.1% in the provider-collected samples. The agreement between collection methods for the detection of HR-HPV DNA (85.4%) was good. HR-HPV and type-specific HPV 16/18 were as likely to be detected in the self-collected samples compared with the provider-obtained samples. Conclusions Women in this population were easily able to collect adequate cervicovaginal specimens for HPV testing. As self-sampling has a high recovery of HR-HPV and is comparable with provider-sampling, we conclude that self-sampling with dry storage and transport could be a good cervical cancer screening alternative for Inuit women in Nunavik who have traditionally avoided speculum examination.