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107. Tiered Approaches to Chromatographic Bioanalytical Method Performance Evaluation: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team

Author

Lowes, S., primary, Hucker, R., additional, Jemal, M., additional, Marini, J. C., additional, Rezende, V. M., additional, Shoup, R., additional, Singhal, P., additional, Timmerman, P., additional, Yoneyama, T., additional, Weng, N., additional, and Zimmer, D., additional

Published
2014
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111. Mutations in WNT1 cause different forms of bone fragility

Author

Keupp, K., Beleggia, F., Kayserili, H., Barnes, A., Steiner, M., Semler, O., Fischer, B., Yigit, G., Janda, C., Becker, J., Breer, S., Altunoglu, U., Grünhagen, J., Krawitz, P., Hecht, J., Schinke, T., Makareeva, E., Lausch, E., Cankaya, T., Caparrós-Martín, Jose, Lapunzina, P., Temtamy, S., Aglan, M., Zabel, B., Eysel, P., Koerber, F., Leikin, S., Garcia, K., Netzer, C., Schönau, E., Ruiz-Perez, V., Mundlos, S., Amling, M., Kornak, U., Marini, J., Wollnik, B., Keupp, K., Beleggia, F., Kayserili, H., Barnes, A., Steiner, M., Semler, O., Fischer, B., Yigit, G., Janda, C., Becker, J., Breer, S., Altunoglu, U., Grünhagen, J., Krawitz, P., Hecht, J., Schinke, T., Makareeva, E., Lausch, E., Cankaya, T., Caparrós-Martín, Jose, Lapunzina, P., Temtamy, S., Aglan, M., Zabel, B., Eysel, P., Koerber, F., Leikin, S., Garcia, K., Netzer, C., Schönau, E., Ruiz-Perez, V., Mundlos, S., Amling, M., Kornak, U., Marini, J., and Wollnik, B.

Abstract

We report that hypofunctional alleles of WNT1 cause autosomal-recessive osteogenesis imperfecta, a congenital disorder characterized by reduced bone mass and recurrent fractures. In consanguineous families, we identified five homozygous mutations in WNT1: one frameshift mutation, two missense mutations, one splice-site mutation, and one nonsense mutation. In addition, in a family affected by dominantly inherited early-onset osteoporosis, a heterozygous WNT1 missense mutation was identified in affected individuals. Initial functional analysis revealed that altered WNT1 proteins fail to activate canonical LRP5-mediated WNT-regulated ß-catenin signaling. Furthermore, osteoblasts cultured in vitro showed enhanced Wnt1 expression with advancing differentiation, indicating a role of WNT1 in osteoblast function and bone development. Our finding that homozygous and heterozygous variants in WNT1 predispose to low-bone-mass phenotypes might advance the development of more effective therapeutic strategies for congenital forms of bone fragility, as well as for common forms of age-related osteoporosis. © 2013 The American Society of Human Genetics.

Published
2013

113. Contributed papers to the 8th workshop on RF superconductivity - RF pulsed tests on Niobium and niobium based 3GHz superconducting cavities - Copper plasma sprayed niobium cavities

Author

Bienvenu, G., Thomas, C., Marini, J., Kerec, Hélène, Laboratoire de l'Accélérateur Linéaire (LAL), and Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[PHYS.PHYS.PHYS-INS-DET] Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det]
Published
1998

114. Tracheal gas insufflation: catheter effectiveness determined by expiratory flush volume

Author

Ravenscraft, S. A., Shapiro, R. S., Nahum, A., Burke, W. C., Adams, A. B., Nakos, G., and Marini, J. J.

Subjects
Male, Analysis of Variance, Dogs, Time Factors, Forced Expiratory Flow Rates, Trachea/*physiology, Animals, Intubation, Intratracheal/*instrumentation, Female, Respiration, Artificial, Catheterization, Insufflation/*instrumentation/methods
Abstract

Used adjunctively during mechanical ventilation, tracheal gas insufflation (TGI) improves CO2 elimination, principally by decreasing effective anatomic dead space. Continuing lung deflation at end- expiration raises the end-expiratory C02 concentration within the proximal airway, and could theoretically reduce the efficiency of a given catheter flow. To test this possibility, we designed a series of experiments that examined the influence of TGI delivery patterns on the efficiency of CO2 elimination. Using a gating device, catheter flow was delivered selectively during desired portions of expiration. Paralyzed, ventilated dogs were studied at short and extended inspiratory time fractions (TI/TT) with inspiratory tidal volume and ventilator frequency held constant. The expiratory flush volume, not the pattern of gas delivery, determined the observed decline in PaCO2, provided that the end-expiratory period was included in the catheter flush period. Despite continuing end-expiratory lung deflation (extended TI/TT), catheter effectiveness remained the same at matched expiratory flush volumes. To determine if enhanced distal mixing at the higher catheter flows required during the extended TI/TT (to match expiratory flush volume) masked a decrease in efficiency, we repeated the experiment with a tip-inverted catheter. We again found that matched catheter delivered expiratory volumes were similarly effective. With or without ongoing lung deflation, the volume of gas flushed during the expiratory period determined the effectiveness of TGI, provided that inspired minute ventilation remains unchanged and end-expiration is included in the catheter flush period. Am J Respir Crit Care Med

Published
1996

117. Tracheal gas insufflation augments CO2 clearance during mechanical ventilation

Author

Ravenscraft, S. A., Burke, W. C., Nahum, A., Adams, A. B., Nakos, G., Marcy, T. W., and Marini, J. J.

Subjects
Adult, Male, Respiratory Insufficiency/*therapy, Pulmonary Ventilation/physiology, Respiration/physiology, Tidal Volume/physiology, Lung/physiopathology, Respiratory Dead Space/physiology, Insufflation, Efficiency, Middle Aged, Functional Residual Capacity/physiology, Carbon Dioxide/analysis/*metabolism, Monitoring, Physiologic/methods, Oxygen/*administration & dosage, Pressure, Humans, Female, Intubation, Intratracheal/instrumentation/*methods, Pulmonary Gas Exchange/physiology, Positive-Pressure Respiration, Aged
Abstract

A technique that improves the efficiency of alveolar ventilation should decrease the pressure required and reduce the potential for lung injury during mechanical ventilation. Alveolar ventilation may be improved by replacing a portion of the anatomic dead space with fresh gas via an intratracheal catheter. We studied the effect of intratracheal gas insufflation as an adjunct to volume cycled ventilation in eight sedated, paralyzed patients with a variety of lung disorders. Continuous flows of 2, 4, and 6 L/min were delivered through a catheter positioned 1 or 10 cm above the carina. Carbon dioxide production, inspiratory minute ventilation, and peak and mean airway pressures did not change over the range of flows tested. PaCO2 and dead space volume/tidal volume decreased significantly as joint functions of catheter flow and position (p < 0.001). The highest catheter flow (6 L/min) and most distal catheter position (1 cm above the carina) were the most effective combination tested, averaging a 15% reduction in PaCO2 (range 9 to 23%). Certain characteristics of the expiratory capnogram were helpful in predicting the observed reduction in PaCO2. Tracheal gas insufflation may eventually prove a useful adjunct to a pressure-targeted strategy of ventilatory management (in either volume-cycled or pressure controlled modes), particularly when the total dead space is heavily influenced by its anatomic component. Am Rev Respir Dis

Published
1993

118. Effect of catheter flow direction on CO2 removal during tracheal gas insufflation in dogs

Author

Nahum, A., Ravenscraft, S. A., Nakos, G., Adams, A. B., Burke, W. C., and Marini, J. J.

Subjects
Male, Pulmonary Gas Exchange, Hemodynamics, Thorax/physiology, Equipment Design, Insufflation, Respiratory Dead Space, Respiration, Artificial, Dogs, Pressure, Tidal Volume, Animals, Trachea, Catheterization/instrumentation, Female, Lung Volume Measurements, Carbon Dioxide, Gases
Abstract

Tracheal gas insufflation (TGI) improves the efficiency of CO2 elimination by replacing CO2 in the anatomic dead space proximal to the catheter tip with fresh gas during expiration. Turbulence generated by gas exiting the catheter tip may also contribute to alveolar ventilation. To separate distal (turbulence-related) and proximal (washout of dead space) effects of TGI, we compared the efficacy of a straight and an inverted catheter during continuous and expiratory TGI in six mechanically ventilated dogs. We reasoned that the inverted catheter cannot improve CO2 elimination from more distal conducting airways. During continuous TGI with the straight catheter, arterial PCO2 (PaCO2) decreased significantly from baseline (without TGI) of 56 +/- 10 Torr to 38 +/- 8, 36 +/- 8, and 35 +/- 8 Torr at catheter flow rates (Vcath) of 5, 10, and 15 l/min, respectively. For the same conditions, PaCO2 was always higher (P < 0.001) with the inverted catheter (42 +/- 10, 41 +/- 10, and 41 +/- 10 Torr). PaCO2 was lower with the straight (40 +/- 9 Torr) than with the inverted catheter (44 +/- 10 Torr, P < 0.001) during TGI delivered only during expiration at a Vcath of 10 l/min. End-expiratory lung volume relative to baseline increased during continuous, but not during expiratory, TGI and was significantly greater with the straight than with the inverted catheter (P < 0.0001). Our data confirm that the primary mechanism of TGI is expiratory washout of the proximal anatomic dead space but also suggest a minor contribution of turbulence beyond the tip of the straight catheter. J Appl Physiol

Published
1993

126. GEOS-C altimeter attitude bias error correction

Author

Marini, J. W

Subjects
Spacecraft Instrumentation
Abstract

A pulse-limited split-gate-tracking radar altimeter was flown on Skylab and will be used aboard GEOS-C. If such an altimeter were to employ a hypothetical isotropic antenna, the altimeter output would be independent of spacecraft orientation. To reduce power requirements the gain of the altimeter antenna proposed is increased to the point where its beamwidth is only a few degrees. The gain of the antenna consequently varies somewhat over the pulse-limited illuminated region of the ocean below the altimeter, and the altimeter output varies with antenna orientation. The error introduced into the altimeter data is modeled empirically, but close agreements with the expected errors was not realized. The attitude error effects expected with the GEOS-C altimeter are modelled using a form suggested by an analytical derivation. The treatment is restricted to the case of a relatively smooth sea, where the height of the ocean waves are small relative to the spatial length (pulse duration times speed of light) of the transmitted pulse.

Published
1974

127. Doppler factors in satellite-to-satellite tracking

Author

Marini, J. W

Subjects
Space Sciences
Abstract

The Doppler factors occurring in range rate satellite-to-satellite tracking measurements are derived with special relativistic effects included. The error resulting from the use of simplified expressions for these factors is discussed.

Published
1974

128. Error analysis for relay type satellite-aided search and rescue systems

Author

Marini, J. W

Subjects
Space Communications, Spacecraft Communications, Command And Tracking
Abstract

An analysis is made of the errors in the determination of the position of an emergency transmitter in a satellite-aided search and rescue system. The satellite is assumed to be at a height of 820 km in a near-circular near polar orbit. Short data spans of four minutes or less are used. The error sources considered are measurement noise, transmitter frequency drift, ionospheric effects, and error in the assumed height of the transmitter. The errors are calculated for several different transmitter positions, data rates, and data spans. The only transmitter frequency used was 406 MHz, but the result can be scaled to different frequencies.

Published
1979

129. Ambiguity resolution for satellite Doppler positioning systems

Author

Argentiero, P and Marini, J

Subjects
Aircraft Communications And Navigation
Abstract

The implementation of satellite-based Doppler positioning systems frequently requires the recovery of transmitter position from a single pass of Doppler data. The least-squares approach to the problem yields conjugate solutions on either side of the satellite subtrack. It is important to develop a procedure for choosing the proper solution which is correct in a high percentage of cases. A test for ambiguity resolution which is the most powerful in the sense that it maximizes the probability of a correct decision is derived. When systematic error sources are properly included in the least-squares reduction process to yield an optimal solution the test reduces to choosing the solution which provides the smaller valuation of the least-squares loss function. When systematic error sources are ignored in the least-squares reduction, the most powerful test is a quadratic form comparison with the weighting matrix of the quadratic form obtained by computing the pseudoinverse of a reduced-rank square matrix. A formula for computing the power of the most powerful test is provided. Numerical examples are included in which the power of the test is computed for situations that are relevant to the design of a satellite-aided search and rescue system.

Published
1979

130. Ambiguity resolution for satellite Doppler positioning systems

Author

Argentiero, P. D and Marini, J. W

Subjects
Launch Vehicles And Space Vehicles
Abstract

A test for ambiguity resolution was derived which was the most powerful in the sense that it maximized the probability of a correct decision. When systematic error sources were properly included in the least squares reduction process to yield an optimal solution, the test reduced to choosing the solution which provided the smaller valuation of the least squares loss function. When systematic error sources were ignored in the least squares reduction, the most powerful test was a quadratic form comparison with the weighting matrix of the quadratic form obtained by computing the pseudo-inverse of a reduced rank square matrix. A formula is presented for computing the power of the most powerful test. A numerical example is included in which the power of the test is computed for a situation which may occur during an actual satellite aided search and rescue mission.

Published
1977

131. Error analysis for relay type satellite-aided search and rescue systems

Author

Marini, J. W

Subjects
Astronautics (General)
Abstract

An analysis was made of the errors in the determination of the position of an emergency transmitter in a satellite aided search and rescue system. The satellite was assumed to be at a height of 820 km in a near circular near polar orbit. Short data spans of four minutes or less were used. The error sources considered were measurement noise, transmitter frequency drift, ionospheric effects and error in the assumed height of the transmitter. The errors were calculated for several different transmitter positions, data rates and data spans. The only transmitter frequency used was 406 MHz, but the results can be scaled to different frequencies. In a typical case, in which four Doppler measurements were taken over a span of two minutes, the position error was about 1.2 km.

Published
1977

134. Correction of satellite tracking data for an arbitrary tropospheric profile.

Author

Marini, J. W

Subjects
Communications
Abstract

A procedure is given for deriving elevation-error and range-error correction equations in a form suitable for use in the rapid processing of satellite tracking data. The refractivity of the troposphere is assumed to have spherical symmetry, but may have any given profile that does not depart greatly from standard. When the procedure was tested for numerical accuracy by application to an exponential profile, the corrections calculated agreed with those obtained by ray tracing to 0.3% or better over a range of surface refractivity from 200 to 450 and a range of radiowave arrival angles from horizontal to vertical.

Published
1972

138. Apollo 6, 7, and 8 blackout test results

Author

Hager, F. W and Marini, J. W

Subjects
Communications
Abstract

S band communication blackout measurements during reentry phases of Apollo 6, 7, and 8 flights

Published
1969

142. Correction of laser range tracking data for atmospheric refraction at elevations above 10 degrees

Author

Marini, J. W and Murray, C. W., Jr

Subjects
Masers
Abstract

A formula for correcting laser measurements of satellite range for the effect of atmospheric refraction is given. The corrections apply above 10 deg elevation to satellites whose heights exceed 70 km. The meteorological measurements required are the temperature, pressure, and relative humidity of the air at the laser site at the time of satellite pass. The accuracy of the formula was tested by comparison with corrections obtained by ray-tracing radiosonde profiles. The standard deviation of the difference between the refractive retardation given by the formula and that calculated by ray-tracing was less than about 0.04% of the retardation or about 0.5 cm at 10 deg elevation, decreasing to 0.04 cm near zenith.

Published
1973

143. Tropospheric range-rate tracking data correction

Author

Marini, J. W

Subjects
Space Sciences
Abstract

A formula for correcting the tropospheric error in range-rate satellite tracking data is given. The formula is based on the method which was used to obtain corrections for elevation-angle and range data. In addition, an improved method is given for calculating some of the parameters required in the correction formulas.

Published
1972

146. Rehabilitation of children and infants with osteogenesis imperfecta. A program for ambulation

Author

Lynn Gerber, Binder H, Weintrob J, Dk, Grange, Shapiro J, Fromherz W, Berry R, Conway A, Nason S, and Marini J

Subjects
Tibial Fractures, Casts, Surgical, Fracture Fixation, Internal, Braces, Child, Preschool, Incidence, Humans, Infant, Osteogenesis Imperfecta, Child, Femoral Fractures, Exercise Therapy
Abstract

Management of children and infants with osteogenesis imperfecta (OI) poses difficult decisions for pediatricians, orthopedists, and physiatrists. These children are frequently frail with disabling bone and joint deformities and fractures. In an eight-year cumulative management of 12 children with OI, a comprehensive program included strengthening exercises to the pelvic girdle and lower extremity muscles, in addition to pool exercises and molded seating to support upright posture. Long leg braces were fitted when the children were able to sit unsupported. All 12 were fitted with braces; nine were functional ambulators, and three were home ambulators. Six children required femoral plating or rodding, two of whom subsequently had the metal removed. Lower extremity fractures averaged one and one-half per year prior to bracing for nine children who had fractures. There was 0.83 fracture per year for the ten children who had fractures after bracing. The degree of femoral bowing increased in four, decreased in four, and remained unchanged in four, while the degree of tibial bowing increased in two, decreased in nine, and remained unchanged in one during the observation period. A comprehensive rehabilitation program and long leg bracing with surgical operations on the femur result in a high level of functional activity for children with OI with an acceptable level of risk for fracture.

Published
1990

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