Some minimisation algorithms in arithmetic invariant theory

We extend the work of Cremona, Fisher and Stoll on minimising genus one curves of degrees 2,3,4,5, to some of the other representations associated to genus one curves, as studied by Bhargava and Ho. Specifically we describe algorithms for minimising bidegree (2,2)-forms, 3 x 3 x 3 cubes and 2 x 2 x 2 x 2 hypercubes. We also prove a theorem relating the minimal discriminant to that of the Jacobian elliptic curve

Simultaneous miRNA and mRNA transcriptome profiling of human myoblasts reveals a novel set of myogenic differentiation-associated miRNAs and their target genes

Background: miRNA profiling performed in myogenic cells and biopsies from skeletal muscles has previously identified miRNAs involved in myogenesis. Results: Here, we have performed miRNA transcriptome profiling in human affinity-purified CD56+ myoblasts induced to differentiate in vitro. In total, we have identified 60 miRNAs differentially expressed during myogenic differentiation. Many were not known for being differentially expressed during myogenic differentiation. Of these, 14 (miR-23b, miR-28, miR-98, miR-103, miR-107, miR-193a, miR-210, miR-324-5p, miR-324-3p, miR-331, miR-374, miR-432, miR-502, and miR-660) were upregulated and 6 (miR-31, miR-451, miR-452, miR-565, miR-594 and miR-659) were downregulated. mRNA transcriptome profiling performed in parallel resulted in identification of 6,616 genes differentially expressed during myogenic differentiation. Conclusions: This simultaneous miRNA/mRNA transcriptome profiling allowed us to predict with high accuracy target genes of myogenesis-related microRNAs and to deduce their functions

Possibilities for Misinterpretation in ASV-Speciation Studies of Natural Waters

Die Probleme, die bei Speciesuntersuchungen von Spurenelementen mit Hilfe der Differentialpuls Anodic Stripping Voltammetrie auftreten, werden zu-sammenfassend dargestellt. Neben den bei der eigentlichen Bestimmung auftretenden Problemen, werden auch solche erwähnt, die mit der Probennahme sowie der Lagerung und Vorbehandlung der Proben in Zusammenhang stehen

Impact of concomitant aortic regurgitation on long-term outcome after surgical aortic valve replacement in patients with severe aortic stenosis

<p>Abstract</p> <p>Background</p> <p>Prognostic value of concomitant aprtic regurgitation (AR) in patients operated for severe aortic stenosis (AS) is not clarified. The aim of this study was to prospectively examine the impact of presence and severity of concomitant AR in patients operated for severe AS on long-term functional capacity, left ventricular (LV) function and mortality.</p> <p>Methods</p> <p>Study group consisted of 110 consecutive patients operated due to severe AS. The patients were divided into AS group (56 patients with AS without AR or with mild AR) and AS+AR group (54 patients with AS and moderate, severe or very severe AR). Follow-up included clinical examination, six minutes walk test (6MWT) and echocardiography 12 and 104 months after AVR.</p> <p>Results</p> <p>Patients in AS group had lower LV volume indices throughout the study than patients in AS+AR group. Patients in AS group did not have postoperative decrease in LV volume indices, whereas patients in AS+AR group experienced decrease in LV volume indices at 12 and 104 months. Unlike LV volume indices, LV mass index was significantly lower in both groups after 12 and 104 months as compared to preoperative values. Mean LVEF remained unchanged in both groups throughout the study. NYHA class was improved in both groups at 12 months, but at 104 months remained improved only in patients with AS. On the other hand, distance covered during 6MWT was longer at 104 months as compared to 12 months only in AS+AR group (p = 0,013), but patients in AS group walked longer at 12 months than patients in AS+AR group (p = 0,002). There were 30 deaths during study period, of which 13 (10 due to cardiovascular causes) in AS group and 17 (12 due to cardiovascular causes) in AS+AR group. Kaplan-Meier analysis showed that the survival probability was similar between the groups. Multivariate analysis identified diabetes mellitus (beta 1.78, p = 0.038) and LVEF < 45% (beta 1.92, p = 0.049) as the only independent predictor of long-term mortality.</p> <p>Conclusion</p> <p>Our data indicate that the preoperative presence and severity of concomitant AR has no influence on long-term postoperative outcome, LV function and functional capacity in patients undergoing AVR for severe AS.</p

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

The Involvement of RCAS1 in Creating a Suppressive Tumor Microenvironment in Patients with Salivary Gland Adenocarcinoma

The tumor microenvironment is the tissue that determines the growth and progression of the tumor as well as its ability to initiate metastases. The aim of the present study has been to evaluate the role of RCAS1 in creating the suppressive tumor microenvironment in cases of parotid adenocarcinoma. The tissue samples of salivary gland adenocarcinomas and their stroma and the palatine tonsils which constituted the reference tissue sample group were obtained during routine surgical procedures. The immunoreactivity of RCAS1, CD3, CD25, CD68, CD69, and Foxp3 antigens was then evaluated by using the immunohistochemistry method. The patient’s consent was obtained in each case. A statistically significantly higher RCAS1 immunoreactivity level was found in the adenocarcinoma tissue samples in comparison to that found in the stromal tissue samples. A statistically significantly higher RCAS1 immunoreactivity was also identified in the adenocarcinoma tissue samples derived from patients who had lymph node metastases in comparison to patients without such metastases. Additionally, we observed the presence of RCAS1-positive macrophages in the stromal tissue samples. The infiltration of CD68-positive cells was significantly stronger in the adenocarcinoma and stromal tissue slides than in the reference group tissue slides; moreover, the infiltration was a good deal more prominent in the stromal tissue than in the adenocarcinoma tissue. The CD68 immunoreactivity levels in both the tumor and stromal tissue samples were found to be significantly higher in those patients who had lymph node metastases than in the patients without such metastases. Additionally, the infiltration of CD3- and CD25-positive cells was more prominent in the reference tissue slides than in the adenocarcinoma and stromal tissue slides, and was stronger in the adenocarcinoma tissue than in the stromal tissue. Furthermore, the infiltration of Foxp3-positive cells was seen exclusively in the stroma whereas it was not even detected in the adenocarcinoma tissue. Lastly, the Foxp3-positive cell infiltration was more prominent in the stromal tissue than in the reference group tissue. The present study demonstrates that RCAS1 expression by both tumor cells and tumor-associated macrophages may participate in creating the immunosuppressive microenvironment in parotid gland adenocarcinoma, thus promoting tumor development as well as metastases

Whole Genome Sequencing and Evolutionary Analysis of Human Respiratory Syncytial Virus A and B from Milwaukee, WI 1998-2010

BACKGROUND: Respiratory Syncytial Virus (RSV) is the leading cause of lower respiratory-tract infections in infants and young children worldwide. Despite this, only six complete genome sequences of original strains have been previously published, the most recent of which dates back 35 and 26 years for RSV group A and group B respectively. METHODOLOGY/PRINCIPAL FINDINGS: We present a semi-automated sequencing method allowing for the sequencing of four RSV whole genomes simultaneously. We were able to sequence the complete coding sequences of 13 RSV A and 4 RSV B strains from Milwaukee collected from 1998-2010. Another 12 RSV A and 5 RSV B strains sequenced in this study cover the majority of the genome. All RSV A and RSV B sequences were analyzed by neighbor-joining, maximum parsimony and Bayesian phylogeny methods. Genetic diversity was high among RSV A viruses in Milwaukee including the circulation of multiple genotypes (GA1, GA2, GA5, GA7) with GA2 persisting throughout the 13 years of the study. However, RSV B genomes showed little variation with all belonging to the BA genotype. For RSV A, the same evolutionary patterns and clades were seen consistently across the whole genome including all intergenic, coding, and non-coding regions sequences. CONCLUSIONS/SIGNIFICANCE: The sequencing strategy presented in this work allows for RSV A and B genomes to be sequenced simultaneously in two working days and with a low cost. We have significantly increased the amount of genomic data that is available for both RSV A and B, providing the basic molecular characteristics of RSV strains circulating in Milwaukee over the last 13 years. This information can be used for comparative analysis with strains circulating in other communities around the world which should also help with the development of new strategies for control of RSV, specifically vaccine development and improvement of RSV diagnostics

Selective and Irreversible Inhibitors of Aphid Acetylcholinesterases: Steps Toward Human-Safe Insecticides

Aphids, among the most destructive insects to world agriculture, are mainly controlled by organophosphate insecticides that disable the catalytic serine residue of acetylcholinesterase (AChE). Because these agents also affect vertebrate AChEs, they are toxic to non-target species including humans and birds. We previously reported that a cysteine residue (Cys), found at the AChE active site in aphids and other insects but not mammals, might serve as a target for insect-selective pesticides. However, aphids have two different AChEs (termed AP and AO), and only AP-AChE carries the unique Cys. The absence of the active-site Cys in AO-AChE might raise concerns about the utility of targeting that residue. Herein we report the development of a methanethiosulfonate-containing small molecule that, at 6.0 µM, irreversibly inhibits 99% of all AChE activity extracted from the greenbug aphid (Schizaphis graminum) without any measurable inhibition of the human AChE. Reactivation studies using β-mercaptoethanol confirm that the irreversible inhibition resulted from the conjugation of the inhibitor to the unique Cys. These results suggest that AO-AChE does not contribute significantly to the overall AChE activity in aphids, thus offering new insight into the relative functional importance of the two insect AChEs. More importantly, by demonstrating that the Cys-targeting inhibitor can abolish AChE activity in aphids, we can conclude that the unique Cys may be a viable target for species-selective agents to control aphids without causing human toxicity and resistance problems