Metallochaperones Are Needed for Mycobacterium tuberculosis and Escherichia coli Nicotinamidase-Pyrazinamidase Activity.

Mycobacterium tuberculosis nicotinamidase-pyrazinamidase (PZAse) is a metalloenzyme that catalyzes conversion of nicotinamide-pyrazinamide to nicotinic acid-pyrazinoic acid. This study investigated whether a metallochaperone is required for optimal PZAse activity. M. tuberculosis and Escherichia coli PZAses (PZAse-MT and PZAse-EC, respectively) were inactivated by metal depletion (giving PZAse-MT-Apo and PZAse-EC-Apo). Reactivation with the E. coli metallochaperone ZnuA or Rv2059 (the M. tuberculosis analog) was measured. This was repeated following proteolytic and thermal treatment of ZnuA and Rv2059. The CDC1551 M. tuberculosis reference strain had the Rv2059 coding gene knocked out, and PZA susceptibility and the pyrazinoic acid (POA) efflux rate were measured. ZnuA (200 μM) achieved 65% PZAse-EC-Apo reactivation. Rv2059 (1 μM) and ZnuA (1 μM) achieved 69% and 34.3% PZAse-MT-Apo reactivation, respectively. Proteolytic treatment of ZnuA and Rv2059 and application of three (but not one) thermal shocks to ZnuA significantly reduced the capacity to reactivate PZAse-MT-Apo. An M. tuberculosis Rv2059 knockout strain was Wayne positive and susceptible to PZA and did not have a significantly different POA efflux rate than the reference strain, although a trend toward a lower efflux rate was observed after knockout. The metallochaperone Rv2059 restored the activity of metal-depleted PZAse in vitro Although Rv2059 is important in vitro, it seems to have a smaller effect on PZA susceptibility in vivo. It may be important to mechanisms of action and resistance to pyrazinamide in M. tuberculosis Further studies are needed for confirmation.IMPORTANCE Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis and remains one of the major causes of disease and death worldwide. Pyrazinamide is a key drug used in the treatment of tuberculosis, yet its mechanism of action is not fully understood, and testing strains of M. tuberculosis for pyrazinamide resistance is not easy with the tools that are presently available. The significance of the present research is that a metallochaperone-like protein may be crucial to pyrazinamide's mechanisms of action and of resistance. This may support the development of improved tools to detect pyrazinamide resistance, which would have significant implications for the clinical management of patients with tuberculosis: drug regimens that are appropriately tailored to the resistance profile of a patient's individual strain lead to better clinical outcomes, reduced onward transmission of infection, and reduction of the development of resistant strains that are more challenging and expensive to treat

NCI-MATCH Arms N & P: Phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss

Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771. Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint. Results: Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SD \u3e 6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SD \u3e 6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Gr ≥ 3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm. Conclusions: Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss

Position and force control with mass estimation for cooperative systems

[ES] La manipulación cooperativa de un objeto por dos o más brazos robóticos requiere controlar tanto el movimiento del objeto como las fuerzas ejercidas por los manipuladores. En términos de cinemática y estática, el enfoque elegido se basa en la denominada formulación simétrica. Se diseña un algoritmo de control que utiliza una modificación del método híbrido de torque computarizado basado en el Principio de Ortogonalización. Además, la masa del objeto se estima calculando la fuerza aplicada por cada efector final para sostener el objeto. El método propuesto es una extensión natural del esquema de control adaptativo previamente reportado para manipuladores geométricamente restringidos. La prueba de estabilidad se desarrolla utilizando la teoría de Lyapunov. Se presentan resultados experimentales.[EN] The cooperative manipulation of an object by two or more robotic arms requires controlling both the object’s movement and the forces exerted by the manipulators. In terms of kinematics and static, the chosen approach is based on the so–called symmetric formulation. A control algorithm using a modified hybrid computed–torque method based on the Principle of Orthogonalization is designed. In addition, the mass of the object is estimated by calculating the force applied by each end–effector to hold the object. The proposed method is a natural extension of an adaptive control scheme previously reported for geometrically restricted manipulators. The stability test is developed using Lyapunov’s theory. Experimental results are presented.Los autores agradecen a PRODEP (PROMEP) con el folio BUAP–811 y al proyecto PAPIIT IN117820.Sánchez-Sánchez, P.; Arteaga-Pérez, MA. (2020). Control de posición y fuerza con estimación de masa para sistemas cooperativos. Revista Iberoamericana de Automática e Informática industrial. 17(4):368-379. https://doi.org/10.4995/riai.2020.12432OJS368379174Arimoto, S. and Liu, Y. H. and Naniwa, T., 1993. Principle of Orthogonalization for Hybrid Control of Robot Arms. Proceedings of the IFAC 12th Triennial World Congress. Volume 26, Issue 2, Part 3, 335-340. Sidney, Australia. https://doi.org/10.1016/S1474-6670(17)48744-1Arimoto, S. and Liu, Y. H. and Naniwa, T., 1993. Model-Based Adaptive Hybrid Control for Geometrically Constrained Robots. Proceedings IEEE International Conference on Robotics and Automation. 618-623. Atlanta, GA, USA. https://doi.org/10.1109/ROBOT.1993.292047Dauchez, P. and Zapata, R., 1985. Co-ordinated control of two cooperative manipulators: the use of a kinematic model. Proceedings 15th Int. Symp. Industrial Robots. 641-648. Tokyo, Japan.Fujii, S. and Kurono, S., 1975. Coordinated computer control of a pair of manipulators. Proceedings 4th IFToMM World Congress, University of Newcastle upon Tyne. 411-417. England.Gudiño-Lau, J. and Arteaga-Pérez, M. A., 2003. Force Control with a Velocity Observer. Proc. European Control Conference (ECC 2003). 52-55. Cambridge, UK. https://doi.org/10.23919/ECC.2003.7086506Gudiño-Lau, J. and Arteaga-Pérez, M. A. and Muñoz, L. A. and Parra-Vega, V., 2004. On the control of cooperative robots without velocity measurements. IEEE Transactions on Control Systems Technology, 12 (4) 600-608. https://doi.org/10.23919/ECC.2003.10.1109/TCST.2004.824965Hayati, S., 1986. Hybrid position/force control of multi-arm cooperating robots. Proceedings of 1986 IEEE International Conference on Robotics and Automation. 82-89. San Francisco, CA, USA. https://doi.org/10.1109/ROBOT.1986.1087650Hwang, G. and Hashimoto, H. and Szemes, P. and Ando, N., 2005. An evaluation of grasp force control in single-master multi-slave tele-micromanipulation. Proceedings of the IEEE/RSJ International Conference on Intelligent Robots and Systems. 2179-2184. Alberta, Canada. https://doi.org/10.1109/IROS.2005.1545074Kelly, R. and Santibáñez, V., 2003. Control de Movimiento de Robots Manipuladores, Pearson Prentice-Hall, Madrid, España. ISBN-10: 8420538310 / ISBN-13: 9788420538310Khalil, H. K., 1996. Nonlinear Systems (2nd Ed), Prentice-Hall, Englewood Cliffs, New Jersey ISBN-10: 9332542031 / ISBN-13: 978-9332542037Khatib, O., 1987. A Unified Approach for Motion and Force Control of Robot Manipulators: The Operational Space Formulation. IEEE Journal of Robotics and Automation, Vol. 3(1), 43-53. https://doi.org/10.1109/JRA.1987.1087068Koivo, A. J. and Bekey, G. A., 1987. Report of the Workshop on Coordinated Multiple Robot Manipulators: Planning, Control and Applications. IEEE Transactions on Robotics and Automation (IEEE Trans Robot Autom), 4(1) 91-93. ISSN: 1042-296XMcClamroch, N. H., 1986. Singular systems of differential equations as dynamic models for constrained robot systems. Proceedings of 1986 IEEE International Conference on Robotics and Automation, San Francisco, CA, USA 21-28. https://doi.org/10.1109/ROBOT.1986.1087712McClamroch, H. and Wang, D., 1990. Linear feedback control of position and contact force for a nonlinear constrained mechanism. ASME Journal of Dynamic Systems, Measurement, and Control, Vol. 112(4), 640-645. https://doi.org/10.1115/1.2896189Murphey, T. D. and Horowitz, M., 2008. Adaptive cooperative manipulation with intermit- tent contact. Proc. IEEE International Conference on Robotics and Automation, Pasadena, California. USA 1483-1488. https://doi.org/10.1109/ROBOT.2008.4543411Nakano, E. and Ozaki, S. and Ishida, T. and Kato, I., 1974. Cooperational control of the anthropomorphous manipulator MELARM. Proceedings 4th Int. Symp. Industrial Ro- bots, 251-260. Tokyo, Japan.Naniwa, T. and Arimoto, S. and Parra-Vega, V., 1994. A model-based adaptive control scheme for coordinated control of multiple manipulators. Proceedings of the IEEE/RS- J/GI International Conference on Intelligent Robots and Systems, Munich, Germany 695-702. https://doi.org/10.1109/IROS.1994.407357Pliego-Jiménez, J. and Arteaga-Pérez, M., 2017. On the adaptive control of cooperative robots with time-variant holonomic constraints. International Journal of Adaptive Control and Signal Processing, 31(8) 1217-1231. https://doi.org/10.1002/acs.2758Rahman, S. M. M. and Ikeura, R., 2012. Weight-perception-based novel control for cooperative lifting of objects with a power assist robot by two humans. International Conference on Biomedical Robotics and Biomechatronics (BioRob), Rome, Italy 228-233. https://doi.org/10.1109/BioRob.2012.6290259Raibert, M. and Craig, J., 1981. Hybrid position/force control of manipulators. ASME Journal of Dynamic Systems, Measurement, and Control, Vol. 103(2), 126-133. https://doi.org/10.1115/1.3139652Rivera-Dueñas, J. C. and Arteaga-Pérez, M. A., 2013. Robot force control without dynamic model: Theory and experiments. Robotica, Vol. 31(1) 149-171. https://doi.org/10.1017/S026357471200015XRugthum, T. and Tao, G., 2014. An adaptive actuator failure compensation scheme for a cooperative manipulator system. Proc. American Control Conference, Portland, Oregon. USA 1951-1956. https://doi.org/10.1109/CDC.2015.7403208Sánchez-Sánchez, P. and Arteaga-Pérez, M. A., 2017. Improving force tracking control performance in cooperative robots. International Journal of Advanced Robotic Systems, 14(4) 1-15. https://doi.org/10.1177/1729881417708969Slotine, J. J. E. and Li, W., 1991. Applied Nonlinear Control. Prentice-Hall, Englewood Cliffs, New Jersey. ISBN-10: 0130408905 / ISBN-13: 978-0130408907Spong, M. W. and Hutchinson, S. and Vidyasagar, M., 2006. Robot Modeling and Control. John Wiley and Sons, USA. ISBN-10: 0471649902 / ISBN-13: 978-0471649908Tarn, T. J. and Bejczy, A. K. and Yun, X., 1988. New nonlinear control algorithms for multiple robot arms. IEEE Transactions on Aerospace and Electronic Systems, 24(5) 571-583. https://doi.org/10.1109/7.9685Uchiyama, M. and Iwasawa, N. and Hakomori, K., 1987. Hybrid position/force control for coordination of a two-arm robot. Proceedings of 1987 IEEE International Conference on Robotics and Automation, 1242-1247, Raleigh, NC, USA. https://doi.org/10.1109/ROBOT.1987.1087766Uchiyama, M. and Dauchez, P., 1988. A symmetric hybrid position/force control scheme for the coordination of two robots. Proceedings of 1988 IEEE International Conference on Robotics and Automation, 350-356, Philadelphia, PA, USA. https://doi.org/10.1109/ROBOT.1988.12073Uchiyama, M. and Dauchez, P., 1993. Symmetric kinematic formulation and non- master/slave coordinated control of two-arm robots. Journal Advanced Robotics. 7(4) 361-383. https://doi.org/10.1163/156855393X00221Yun-Hui, L. and Parra-Vega, V. and Arimoto, S., 1996. Decentralized Cooperation Control: Joint-Space Approaches for Holonomic Cooperations. Proc. IEEE International Conference on Robotics and Automation, Minneapolis, Minnesota 2420-2425. https://doi.org/10.1109/ROBOT.1996.50652

Improving the magnetic heating by disaggregating nanoparticles

Recently, potential applications of the magnetic heating for heterogeneous catalysis or organic synthesis have been reported. As these new applications are not limited by biocompatibility requirements, a wide range of possibilities for non-aqueous colloidal nanoparticles with enhanced magnetic properties is open. In this work, manganese and cobalt ferrite nanoparticles are synthesized by co-precipitation method with average particle size around 12 nm. The particles are either coated with tetramethylammonium hydroxide (TMAOH) and dispersed in water or with oleic acid (OA) and dispersed in hexane to produce aggregated or disaggregated nanoparticles, respectively. It is observed that the particle disaggregation improves significantly the heating efficiency from 12 to 96 W/g in the case of cobalt ferrite, and from 120 to 413 W/g for the manganese ferrite. The main responsible for this improvement is the reduction of hydrodynamic volume that allows a faster Brownian relaxation. This work also discusses the relevance of the size distribution

Cumarinas en especies del género seseli (fam. umbelliferae)

A survey of the coumarins from species of the genus Seseli (Fam. Umbelliferae) is reported.Se presenta una revisión de cumarinas en especies del género Seseli (Fam. Umbelliferae)

Size Segregation of Granular Matter in Silo Discharges

We present an experimental study of segregation of granular matter in a quasi-two dimensional silo emptying out of an orifice. Size separation is observed when multi-sized particles are used with the larger particles found in the center of the silo in the region of fastest flow. We use imaging to study the flow inside the silo and quantitatively measure the concentration profiles of bi-disperse beads as a function of position and time. The angle of the surface is given by the angle of repose of the particles, and the flow occurs in a few layers only near the top of this inclined surface. The flowing region becomes deeper near the center of the silo and is confined to a parabolic region centered at the orifice which is approximately described by the kinematic model. The experimental evidence suggests that the segregation occurs on the surface and not in the flow deep inside the silo where velocity gradients also are present. We report the time development of the concentrations of the bi-disperse particles as a function of size ratios, flow rate, and the ratio of initial mixture. The qualitative aspects of the observed phenomena may be explained by a void filling model of segregation.Comment: 6 pages, 10 figures (gif format), postscript version at http://physics.clarku.edu/~akudrolli/nls.htm

Performance of the HAWC Observatory and TeV Gamma-Ray Measurements of the Crab Nebula with Improved Extensive Air Shower Reconstruction Algorithms

The High-Altitude Water Cherenkov (HAWC) Gamma-Ray Observatory, located on the side of the Sierra Negra volcano in Mexico, has been fully operational since 2015. The HAWC collaboration has recently significantly improved their extensive air shower reconstruction algorithms, which has notably advanced the observatory performance. The energy resolution for primary gamma rays with energies below 1 TeV was improved by including a noise-suppression algorithm. Corrections have also been made to systematic errors in direction fitting related to the detector and shower plane inclinations, O ( 0 .° 1 ) biases in highly inclined showers, and enhancements to the core reconstruction. The angular resolution for gamma rays approaching the HAWC array from large zenith angles (\u3e37°) has improved by a factor of 4 at the highest energies (\u3e70 TeV) as compared to previous reconstructions. The inclusion of a lateral distribution function fit to the extensive air shower footprint on the array to separate gamma-ray primaries from cosmic-ray ones based on the resulting χ 2 values improved the background rejection performance at all inclinations. At large zenith angles, the improvement in significance is a factor of 4 compared to previous HAWC publications. These enhancements have been verified by observing the Crab Nebula, which is an overhead source for the HAWC Observatory. We show that the sensitivity to Crab-like point sources (E −2.63) with locations overhead to 30° zenith is comparable to or less than 10% of the Crab Nebula’s flux between 2 and 50 TeV. Thanks to these improvements, HAWC can now detect more sources, including the Galactic center