Path methods for strong shift equivalence of positive matrices

In the early 1990's, Kim and Roush developed path methods for establishing strong shift equivalence (SSE) of positive matrices over a dense subring U of the real numbers R. This paper gives a detailed, unified and generalized presentation of these path methods. New arguments which address arbitrary dense subrings U of R are used to show that for any dense subring U of R, positive matrices over U which have just one nonzero eigenvalue and which are strong shift equivalent over U must be strong shift equivalent over U_+. In addition, we show positive real matrices on a path of shift equivalent positive real matrices are SSE over R_+; positive rational matrices which are SSE over R_+ must be SSE over Q_+; and for any dense subring U of R, within the set of positive matrices over U which are conjugate over U to a given matrix, there are only finitely many SSE-U_+ classes.Comment: This version adds a 3-part program for studying SEE over the reals. One part is handled by the arxiv post "Strong shift equivalence and algebraic K-theory". This version is the author version of the paper published in the Kim memorial volume. From that, my short lifestory of Kim (and more) is on my web page http://www.math.umd.edu/~mboyle/papers/index.htm

Challenges in Estimating Insecticide Selection Pressures from Mosquito Field Data

Insecticide resistance has the potential to compromise the enormous effort put into the control of dengue and malaria vector populations. It is therefore important to quantify the amount of selection acting on resistance alleles, their contributions to fitness in heterozygotes (dominance) and their initial frequencies, as a means to predict the rate of spread of resistance in natural populations. We investigate practical problems of obtaining such estimates, with particular emphasis on Mexican populations of the dengue vector Aedes aegypti. Selection and dominance coefficients can be estimated by fitting genetic models to field data using maximum likelihood (ML) methodology. This methodology, although widely used, makes many assumptions so we investigated how well such models perform when data are sparse or when spatial and temporal heterogeneity occur. As expected, ML methodologies reliably estimated selection and dominance coefficients under idealised conditions but it was difficult to recover the true values when datasets were sparse during the time that resistance alleles increased in frequency, or when spatial and temporal heterogeneity occurred. We analysed published data on pyrethroid resistance in Mexico that consists of the frequency of a Ile1,016 mutation. The estimates for selection coefficient and initial allele frequency on the field dataset were in the expected range, dominance coefficient points to incomplete dominance as observed in the laboratory, although these estimates are accompanied by strong caveats about possible impact of spatial and temporal heterogeneity in selection

Sensitization of spinal cord nociceptive neurons with a conjugate of substance P and cholera toxin

<p>Abstract</p> <p>Background</p> <p>Several investigators have coupled toxins to neuropeptides for the purpose of lesioning specific neurons in the central nervous system. By producing deficits in function these toxin conjugates have yielded valuable information about the role of these cells. In an effort to specifically stimulate cells rather than kill them we have conjugated the neuropeptide substance P to the catalytic subunit of cholera toxin (SP-CTA). This conjugate should be taken up selectively by neurokinin receptor expressing neurons resulting in enhanced adenylate cyclase activity and neuronal firing.</p> <p>Results</p> <p>The conjugate SP-CTA stimulates adenylate cyclase in cultured cells that are transfected with either the NK1 or NK2 receptor, but not the NK3 receptor. We further demonstrate that intrathecal injection of SP-CTA in rats induces the phosphorylation of the transcription factor cyclic AMP response element binding protein (CREB) and also enhances the expression of the immediate early gene c-Fos. Behaviorally, low doses of SP-CTA (1 μg) injected intrathecally produce thermal hyperalgesia. At higher doses (10 μg) peripheral sensitivity is suppressed suggesting that descending inhibitory pathways may be activated by the SP-CTA induced sensitization of spinal cord neurons.</p> <p>Conclusion</p> <p>The finding that stimulation of adenylate cyclase in neurokinin receptor expressing neurons in the spinal cord produces thermal hyperalgesia is consistent with the known actions of these neurons. These data demonstrate that cholera toxin can be targeted to specific cell types by coupling the catalytic subunit to a peptide agonist for a g-protein coupled receptor. Furthermore, these results demonstrate that SP-CTA can be used as a tool to study sensitization of central neurons in vivo in the absence of an injury.</p

An individual-based model of the evolution of pesticide resistance in heterogeneous environments : Control of meligethes aeneus population in oilseed rape crops

Copyright: © 2014 Stratonovitch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Preventing a pest population from damaging an agricultural crop and, at the same time, preventing the development of pesticide resistance is a major challenge in crop protection. Understanding how farming practices and environmental factors interact with pest characteristics to influence the spread of resistance is a difficult and complex task. It is extremely challenging to investigate such interactions experimentally at realistic spatial and temporal scales. Mathematical modelling and computer simulation have, therefore, been used to analyse resistance evolution and to evaluate potential resistance management tactics. Of the many modelling approaches available, individual-based modelling of a pest population offers most flexibility to include and analyse numerous factors and their interactions. Here, a pollen beetle (Meligethes aeneus) population was modelled as an aggregate of individual insects inhabiting a spatially heterogeneous landscape. The development of the pest and host crop (oilseed rape) was driven by climatic variables. The agricultural land of the landscape was managed by farmers applying a specific rotation and crop protection strategy. The evolution of a single resistance allele to the pyrethroid lambda cyhalothrin was analysed for different combinations of crop management practices and for a recessive, intermediate and dominant resistance allele. While the spread of a recessive resistance allele was severely constrained, intermediate or dominant resistance alleles showed a similar response to the management regime imposed. Calendar treatments applied irrespective of pest density accelerated the development of resistance compared to ones applied in response to prescribed pest density thresholds. A greater proportion of springs own oilseed rape was also found to increase the speed of resistance as it increased the period of insecticide exposure. Our study demonstrates the flexibility and power of an individual-based model to simulate how farming practices affect pest population dynamics, and the consequent impact of different control strategies on the risk and speed of resistance development.Peer reviewe

Critical Perspective: Named Reactions Discovered and Developed by Women

Named organic reactions. As chemists, we’re all familiar with them: who can forget the Diels−Alder reaction? But how much do we know about the people behind the names? For example, can you identify a reaction named for a woman? How about a reaction discovered or developed by a woman but named for her male adviser? Our attempts to answer these simple questions started us on the journey that led to this Account. We introduce you to four reactions named for women and nine reactions discovered or developed by women. Using information obtained from the literature and, whenever possible, through interviews with the chemists themselves, their associates, and their advisers, we paint a more detailed picture of these remarkable women and their outstanding accomplishments. Some of the women you meet in this Account include Irma Goldberg, the only woman unambiguously recognized with her own named reaction. Gertrude Maud Robinson, the wife of Robert Robinson, who collaborated with him on several projects including the Piloty−Robinson pyrrole synthesis. Elizabeth Hardy, the Bryn Mawr graduate student who discovered the Cope rearrangement. Dorothee Felix, a critical member of Albert Eschenmoser’s research lab for over forty years who helped develop both the Eschenmoser−Claisen rearrangement and the Eschenmoser−Tanabe fragmentation. Jennifer Loebach, the University of Illinois undergraduate who was part of the team in Eric Jacobsen’s lab that discovered the Jacobsen−Katsuki epoxidation. Keiko Noda, a graduate student in Tsutomu Katsuki’s lab who also played a key role in the development of the Jacobsen−Katsuki epoxidation. Lydia McKinstry, a postdoc in Andrew Myers’s lab who helped develop the Myers asymmetric alkylation. Rosa Lockwood, a graduate student at Boston College whose sole publication is the discovery of the Nicholas reaction. Kaori Ando, a successful professor in Japan who helped develop the Roush asymmetric alkylation as a postdoc at MIT. Bianka Tchoubar, a critically important member of the organic chemistry community in France who developed the Tiffeneau−Demjanov rearrangement. The accomplishments of the women in this Account illustrate the key roles women have played in the discovery and development of reactions used daily by organic chemists around the world. These pioneering chemists represent the vanguard of women in the field, and we are confident that many more of the growing number of current and future female organic chemists will be recognized with their own named reactions

Disruption of a GATA4/Ankrd1 Signaling Axis in Cardiomyocytes Leads to Sarcomere Disarray: Implications for Anthracycline Cardiomyopathy

Doxorubicin (Adriamycin) is an effective anti-cancer drug, but its clinical usage is limited by a dose-dependent cardiotoxicity characterized by widespread sarcomere disarray and loss of myofilaments. Cardiac ankyrin repeat protein (CARP, ANKRD1) is a transcriptional regulatory protein that is extremely susceptible to doxorubicin; however, the mechanism(s) of doxorubicin-induced CARP depletion and its specific role in cardiomyocytes have not been completely defined. We report that doxorubicin treatment in cardiomyocytes resulted in inhibition of CARP transcription, depletion of CARP protein levels, inhibition of myofilament gene transcription, and marked sarcomere disarray. Knockdown of CARP with small interfering RNA (siRNA) similarly inhibited myofilament gene transcription and disrupted cardiomyocyte sarcomere structure. Adenoviral overexpression of CARP, however, was unable to rescue the doxorubicin-induced sarcomere disarray phenotype. Doxorubicin also induced depletion of the cardiac transcription factor GATA4 in cardiomyocytes. CARP expression is regulated in part by GATA4, prompting us to examine the relationship between GATA4 and CARP in cardiomyocytes. We show in co-transfection experiments that GATA4 operates upstream of CARP by activating the proximal CARP promoter. GATA4-siRNA knockdown in cardiomyocytes inhibited CARP expression and myofilament gene transcription, and induced extensive sarcomere disarray. Adenoviral overexpression of GATA4 (AdV-GATA4) in cardiomyocytes prior to doxorubicin exposure maintained GATA4 levels, modestly restored CARP levels, and attenuated sarcomere disarray. Interestingly, siRNA-mediated depletion of CARP completely abolished the Adv-GATA4 rescue of the doxorubicin-induced sarcomere phenotype. These data demonstrate co-dependent roles for GATA4 and CARP in regulating sarcomere gene expression and maintaining sarcomeric organization in cardiomyocytes in culture. The data further suggests that concurrent depletion of GATA4 and CARP in cardiomyocytes by doxorubicin contributes in large part to myofibrillar disarray and the overall pathophysiology of anthracycline cardiomyopathy