Structural basis of the chiral selectivity of Pseudomonas cepacia lipase

To investigate the enantioselectivity of Pseudomonas cepacia lipase, inhibition studies were performed with SC- and RC-(RP,SP)-1,2-dialkylcarbamoylglycero-3-O-p-nitrophenyl alkylphosphonates of different alkyl chain lengths. P. cepacia lipase was most rapidly inactivated by RC-(RP,SP)-1,2-dioctylcarbamoylglycero-3-O-p-nitrophenyl octylphosphonate (RC-trioctyl) with an inactivation half-time of 75 min, while that for the SC-(RP,SP)-1,2-dioctylcarbamoylglycero-3-O-p-nitrophenyl octyl-phosphonate (SC-trioctyl) compound was 530 min. X-ray structures were obtained of P. cepacia lipase after reaction with RC-trioctyl to 0.29-nm resolution at pH 4 and covalently modified with RC-(RP,SP)-1,2-dibutylcarbamoylglycero-3-O-p-nitrophenyl butyl-phosphonate (RC-tributyl) to 0.175-nm resolution at pH 8.5. The three-dimensional structures reveal that both triacylglycerol analogues had reacted with the active-site Ser87, forming a covalent complex. The bound phosphorus atom shows the same chirality (SP) in both complexes despite the use of a racemic (RP,SP) mixture at the phosphorus atom of the triacylglycerol analogues. In the structure of RC-tributyl-complexed P. cepacia lipase, the diacylglycerol moiety has been lost due to an aging reaction, and only the butyl phosphonate remains visible in the electron density. In the RC-trioctyl complex the complete inhibitor is clearly defined; it adopts a bent tuning fork conformation. Unambiguously, four binding pockets for the triacylglycerol could be detected: an oxyanion hole and three pockets which accommodate the sn-1, sn-2, and sn-3 fatty acid chains. Van der Waals’ interactions are the main forces that keep the radyl groups of the triacylglycerol analogue in position and, in addition, a hydrogen bond to the carbonyl oxygen of the sn-2 chain contributes to fixing the position of the inhibitor.

Data access and integration in the ISPIDER proteomics grid

Grid computing has great potential for supporting the integration of complex, fast changing biological data repositories to enable distributed data analysis. One scenario where Grid computing has such potential is provided by proteomics resources which are rapidly being developed with the emergence of affordable, reliable methods to study the proteome. The protein identifications arising from these methods derive from multiple repositories which need to be integrated to enable uniform access to them. A number of technologies exist which enable these resources to be accessed in a Grid environment, but the independent development of these resources means that significant data integration challenges, such as heterogeneity and schema evolution, have to be met. This paper presents an architecture which supports the combined use of Grid data access (OGSA-DAI), Grid distributed querying (OGSA-DQP) and data integration (AutoMed) software tools to support distributed data analysis. We discuss the application of this architecture for the integration of several autonomous proteomics data resources

Main Memory Implementations for Binary Grouping

An increasing number of applications depend on efficient storage and analysis features for XML data. Hence, query optimization and efficient evaluation techniques for the emerging XQuery standard become more and more important. Many XQuery queries require nested expressions. Unnesting them often introduces binary grouping. We introduce several algorithms implementing binary grouping and analyze their time and space complexity. Experiments demonstrate their performance

Treatment strategies for metastatic soft tissue sarcomas

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Photoemission spectra of Sr2CuO2Cl2{\rm Sr_2 Cu O_2 Cl_2}: a theoretical analysis

Recent angle resolved photoemission (ARPES) results for the insulating cuprate ${\rm Sr_2 Cu O_2 Cl_2}$ have provided the first experimental data which can be directly compared to the (theoretically) well--studied problem of a single hole propagating in an antiferromagnet. The ARPES results reported a small bandwidth, providing evidence for the existence of strong correlations in the cuprates. However, in the same experiment some discrepancies with the familiar 2D ${\rm t-J}$ model were also observed. Here we discuss a comparison between the ARPES results and the quasiparticle dispersion of both (i) the ${\rm t-t'-J}$ Hamiltonian and (ii) the three--band Hubbard model in the strong--coupling limit. Both model Hamiltonians show that the experimentally observed one--hole band structure can be approximately reproduced using reasonable values for ${\rm t'}$, or the direct oxygen hopping amplitude ${\rm t_{pp}}$.Comment: 11 pages, RevTex version 3.0, 3 postscript figures, LaTeX file and figures have been uuencoded

The oncological outcomes of isolated limb perfusion and neo-adjuvant radiotherapy in soft tissue sarcoma patients:A nationwide multicenter study

Introduction: Patients with locally extensive high-grade extremity soft tissue sarcomas (eSTS) are often presented in multidisciplinary teams to decide between ablative surgery (amputation) or limb-salvage surgery supplemented with either neo-adjuvant radiotherapy (RT) or induction isolated limb perfusion (ILP). In The Netherlands, ILP typically aims to reduce the size of tumors that would otherwise be considered irresectable, whereas neo-adjuvant RT aims mainly at improving local control and reducing morbidity of required marginal margins. This study presents a 15-year nationwide cohort to describe the oncological outcomes of both pre-operative treatment strategies. Methods: All consecutive patients with locally extensive primary high-grade eSTS surgically treated between 2000 and 2015 at five tertiary sarcoma centers that received neo-adjuvant ILP or RT were included. 169 patients met the inclusion criteria (89 ILP, 80 RT). Median follow-up was 7.3 years. Results: Limb salvage was achieved in 84% of cases in the ILP group (80% for patients with amputation indication) and 96% of cases in the RT group. 5-Year overall survival was 47% in the ILP group, 69% in the RT group. 5-Year local recurrence rate was 14% in the ILP group, 10% in the RT group. Distant metastasis rate was 55% in the ILP group, 36% in the RT group. Conclusion: We find oncological outcomes and limb salvage rates in line with existing literature for both treatment modalities. Whether the tumor was locally advanced with an indication for induction therapy to prevent amputation or morbid surgery appeared to be the main determinant in choosing between neo-adjuvant ILP or RT

A Step Beyond the Bounce: Bubble Dynamics in Quantum Phase Transitions

We study the dynamical evolution of a phase interface or bubble in the context of a \lambda \phi^4 + g \phi^6 scalar quantum field theory. We use a self-consistent mean-field approximation derived from a 2PI effective action to construct an initial value problem for the expectation value of the quantum field and two-point function. We solve the equations of motion numerically in (1+1)-dimensions and compare the results to the purely classical evolution. We find that the quantum fluctuations dress the classical profile, affecting both the early time expansion of the bubble and the behavior upon collision with a neighboring interface.Comment: 12 pages, multiple figure

Magnetization steps in Zn_(1-x)Mn_xO: Four largest exchange constants and single-ion anisotropy

Magnetization steps (MST's) from Mn pairs in several single crystals of Zn_(1-x)Mn_xO (0.0056<=x<=0.030, and in one powder (x=0.029), were observed. The largest two exchange constants, J1/kB=-18.2+/-0.5K and J1'/kB=-24.3+/-0.6K, were obtained from large peaks in the differential susceptibility, dM/dH, measured in pulsed magnetic fields, H, up to 500 kOe. These two largest J's are associated with the two inequivalent classes of nearest neighbors (NN's) in the wurtzite structure. The 29% difference between J1 and J1' is substantially larger than 13% in CdS:Mn, and 15% in CdSe:Mn. The pulsed-field data also indicate that, despite the direct contact between the samples and a superfluid-helium bath, substantial departures from thermal equilibrium occurred during the 7.4 ms pulse. The third- and fourth-largest J's were determined from the magnetization M at 20 mK, measured in dc magnetic fields H up to 90 kOe. Both field orientations H||c and H||[10-10] were studied. (The [10-10] direction is perpendicular to the c-axis, [0001].) By definition, neighbors which are not NN's are distant neighbors (DN's). The largest DN exchange constant (third-largest overall), has the value J/kB=-0.543+/-0.005K, and is associated with the DN at r=c. Because this is not the closest DN, this result implies that the J's do not decrease monotonically with the distance r. The second-largest DN exchange constant (fourth-largest overall), has the value J/kB=-0.080 K. It is associated with one of the two classes of neighbors that have a coordination number z=12, but the evidence is insufficient for a definite unique choice. The dependence of M on the direction of H gives D/kB=-0.039+/-0.008K, in fair agreement with -0.031 K from earlier EPR work.Comment: 12 pages, 10 figures. Submitted to PR

Adaptive Mesh Refinement for Characteristic Grids

I consider techniques for Berger-Oliger adaptive mesh refinement (AMR) when numerically solving partial differential equations with wave-like solutions, using characteristic (double-null) grids. Such AMR algorithms are naturally recursive, and the best-known past Berger-Oliger characteristic AMR algorithm, that of Pretorius & Lehner (J. Comp. Phys. 198 (2004), 10), recurses on individual "diamond" characteristic grid cells. This leads to the use of fine-grained memory management, with individual grid cells kept in 2-dimensional linked lists at each refinement level. This complicates the implementation and adds overhead in both space and time. Here I describe a Berger-Oliger characteristic AMR algorithm which instead recurses on null \emph{slices}. This algorithm is very similar to the usual Cauchy Berger-Oliger algorithm, and uses relatively coarse-grained memory management, allowing entire null slices to be stored in contiguous arrays in memory. The algorithm is very efficient in both space and time. I describe discretizations yielding both 2nd and 4th order global accuracy. My code implementing the algorithm described here is included in the electronic supplementary materials accompanying this paper, and is freely available to other researchers under the terms of the GNU general public license.Comment: 37 pages, 15 figures (40 eps figure files, 8 of them color; all are viewable ok in black-and-white), 1 mpeg movie, uses Springer-Verlag svjour3 document class, includes C++ source code. Changes from v1: revised in response to referee comments: many references added, new figure added to better explain the algorithm, other small changes, C++ code updated to latest versio