Alternative Mechanisms for Tn5 Transposition

Bacterial transposons are known to move to new genomic sites using either a replicative or a conservative mechanism. The behavior of transposon Tn5 is anomalous. In vitro studies indicate that it uses a conservative mechanism while in vivo results point to a replicative mechanism. To explain this anomaly, a model is presented in which the two mechanisms are not independent—as widely believed—but could represent alternate outcomes of a common transpositional pathway

Boolean Dynamics with Random Couplings

This paper reviews a class of generic dissipative dynamical systems called N-K models. In these models, the dynamics of N elements, defined as Boolean variables, develop step by step, clocked by a discrete time variable. Each of the N Boolean elements at a given time is given a value which depends upon K elements in the previous time step. We review the work of many authors on the behavior of the models, looking particularly at the structure and lengths of their cycles, the sizes of their basins of attraction, and the flow of information through the systems. In the limit of infinite N, there is a phase transition between a chaotic and an ordered phase, with a critical phase in between. We argue that the behavior of this system depends significantly on the topology of the network connections. If the elements are placed upon a lattice with dimension d, the system shows correlations related to the standard percolation or directed percolation phase transition on such a lattice. On the other hand, a very different behavior is seen in the Kauffman net in which all spins are equally likely to be coupled to a given spin. In this situation, coupling loops are mostly suppressed, and the behavior of the system is much more like that of a mean field theory. We also describe possible applications of the models to, for example, genetic networks, cell differentiation, evolution, democracy in social systems and neural networks.Comment: 69 pages, 16 figures, Submitted to Springer Applied Mathematical Sciences Serie

Improved Measurements of Partial Rate Asymmetry in B -> h h Decays

We report improved measurements of the partial rate asymmetry (Acp) in B -> h h decays with 140fb^-1 of data collected with the Belle detector at the KEKB e+e- collider. Here h stands for a charged or neutral pion or kaon and in total five decay modes are included: K-+ pi+-, K0s pi-+, K-+ pi0, pi-+ pi0 and K0s pi0. The flavor of the last decay mode is determined from the accompanying B meson. Using a data sample 4.7 times larger than that of our previous measurement, we find Acp(K-+ pi+-) -0.088+-0.035+-0.013, 2.4 sigma from zero. Results for other decay modes are also presented.Comment: 9 pages, 1 figur

Search for CP violation in the decay B0->D*+-D-+

We report a search for CP-violating asymmetry in B0 -> D*+- D-+ decays. The analysis employs two methods of B0 reconstruction: full and partial. In the full reconstruction method all daughter particles of the B0 are required to be detected; the partial reconstruction technique requires a fully reconstructed D- and only a slow pion from the D*+ -> D0 pi_slow+ decay. From a fit to the distribution of the time interval corresponding to the distance between two B meson decay points we calculate the CP-violating parameters and find the significance of nonzero CP asymmetry to be 2.7 standard deviations.Comment: 4 pages, 3 figure

Studies of the Decay B+- -> D_CP K+-

We report studies of the decay B+- -> D_CP K+-, where D_CP denotes neutral D mesons that decay to CP eigenstates. The analysis is based on a 29.1/fb data sample of collected at the \Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e+ e- storage ring. Ratios of branching fractions of Cabibbo-suppressed to Cabibbo-favored processes involving D_CP are determined to be B(B- -> D_1 K-)/B(B- -> D_1 pi-)=0.125 +- 0.036 +- 0.010 and B(B- -> D_2 K-)/B(B- -> D_2 pi-)=0.119 +- 0.028 +- 0.006, where indices 1 and 2 represent the CP=+1 and CP=-1 eigenstates of the D0 - anti D0 system, respectively. We also extract the partial rate asymmetries for B+- -> D_CP K+-, finding A_1 = 0.29 +- 0.26 +- 0.05 and A_2 = -0.22 +- 0.24 +- 0.04.Comment: 10 pages, 2 figures, submitted to Physical Review Letter

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies

To study the substrate specificity of enzymes, we use the amidohydrolase and enolase superfamilies as model systems; members of these superfamilies share a common TIM barrel fold and catalyze a wide range of chemical reactions. Here, we describe a collaboration between the Enzyme Specificity Consortium (ENSPEC) and the New York SGX Research Center for Structural Genomics (NYSGXRC) that aims to maximize the structural coverage of the amidohydrolase and enolase superfamilies. Using sequence- and structure-based protein comparisons, we first selected 535 target proteins from a variety of genomes for high-throughput structure determination by X-ray crystallography; 63 of these targets were not previously annotated as superfamily members. To date, 20 unique amidohydrolase and 41 unique enolase structures have been determined, increasing the fraction of sequences in the two superfamilies that can be modeled based on at least 30% sequence identity from 45% to 73%. We present case studies of proteins related to uronate isomerase (an amidohydrolase superfamily member) and mandelate racemase (an enolase superfamily member), to illustrate how this structure-focused approach can be used to generate hypotheses about sequence–structure–function relationships

The expression of TGFβ1 mRNA in the early stage of the midpalatal suture cartilage expansion

INTRODUCTION: The application of an orthodontic expansion force induces bone formation at the midpalatal suture because of cell proliferation and differentiation. Expansion forces may stimulate the production of osteoinductive cytokines, such as transforming growth factor β1 (TGFβ1), in the progenitor cells. OBJECTIVES: This study determined the role of TGFβ1 in the early stage of midpalatal suture cartilage expansion. METHODS: A rectangular orthodontic appliance was placed between the right and left upper molars of 4-week-old rats. The initial expansion force was 50 g. Animals in the control and experimental groups were sacrified on days 0, 2, and 5 and 6 µmm thick sections were prepared for an in situ hybridization technique. RESULTS: Two days after the application of force, prechondroblastic and undifferentiated mesenchymal cells distributed along the inner side of the cartilaginous tissue had high levels of TGFβ1 transcription. On day 5, the TGFβ1 transcription was found in osteocytes and osteoblastic cells on the surface of newly formed bone. Immunohistochemistry using Osteocalcin-Pro (OC-Pro) confirmed osteoblastic activity. Conclusions: Results suggest that the expansion of midpalatal suture cartilage induces differentiation of osteochondroprogenitor cells into osteoblasts after stimulation by cytokine productio

Construction of large-volume tissue mimics with 3D functional vascular networks

We used indirect stereolithography (SL) to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture.ope