摘要:
The present invention provides methods and compositions comprising a population of alphavirus replicon particles comprising two or more isolated nucleic acids selected from 1) an isolated nucleic acid encoding an env gene product or an immunogenic fragment thereof of a human immunodeficiency virus, 2) an isolated nucleic acid encoding a gag gene product or an immunogenic fragment thereof of a human immunodeficiency virus, wherein the gag gene product or immunogenic fragment thereof is modified to inhibit formation of virus-like particles containing the gag gene product or the immunogenic fragment thereof and their release from a cell, and 3) an isolated nucleic acid encoding a pol gene product or an immunogenic fragment thereof of a human immunodeficiency virus, wherein the pol gene product or immunogenic fragment thereof is modified to inhibit protease, integrase, RNase H and/or reverse transcriptase activity, and wherein the nucleic acids are each contained within a separate alphavirus replicon particle.
摘要:
The present invention provides methods and compositions comprising a population of alphavirus replicon particles comprising two or more isolated nucleic acids selected from 1) an isolated nucleic acid encoding an env gene product or an immunogenic fragment thereof of a human immunodeficiency virus, 2) an isolated nucleic acid encoding a g&agr;g gene product or an immunogenic fragment thereof of a human immunodeficiency virus, wherein the g&agr;g gene product or immunogenic fragment thereof is modified to inhibit formation of virus-like particles containing the g&agr;g gene product or the immunogenic fragment thereof and their release from a cell, and 3) an isolated nucleic acid encoding a pol gene product or an immunogenic fragment thereof of a human immunodeficiency virus, wherein the pol gene product or immunogenic fragment thereof is modified to inhibit protease, integrase, RNase H and/or reverse transcriptase activity, and wherein the nucleic acids are each contained within a separate alphavirus replicon particle.
摘要:
The present invention provides immunogenic compositions and methods that may be used to administer safer (i.e., attenuated) alphavirus vectors (such as alphavirus vectors comprising a VEE virion shell) that retain improved immunogenicity as compared with other attenuated alphaviruses (e.g., the VEE 3014 mutant, described below). In particular embodiments of the invention, the alphavirus vector comprises VEE structural proteins comprising an attenuating mutation in the E1 glycoprotein. In other particular embodiments, the attenuating mutation is in the fusogenic region of the E1 glycoprotein. The present invention enables administration of lower dosages of a safer (i.e., attenuated) virus and, thus, can further reduce manufacturing costs. The present inventors have found that immunogenicity of alphavirus vectors may be influenced by a number of factors including species, site and route of administration.
摘要:
A method of maintaining a desired downhole pressure during a drilling operation can include measuring a parameter with a sensor, communicating actual parameter values from the sensor to a predictive device, training the predictive device to output predicted parameter values in response to input of the actual parameter values, and outputting the predicted parameter values from the predictive device when the predictive device ceases receiving the actual parameter values. A well drilling system can include a predictive device which outputs predicted parameter values in response to input of actual parameter values to the predictive device. The predictive device continues to output the predicted parameter values, even when the predictive device fails to receive valid actual parameter values. Another well drilling system includes a data validator which communicates valid actual parameter values to the predictive device, but does not communicate invalid actual parameter values to the predictive device.
摘要:
A well drilling method can include detecting a drilling event by comparing a parameter signature generated during drilling to an event signature indicative of the drilling event, and automatically controlling a drilling operation in response to at least a partial match resulting from comparing the parameter signature to the event signature. A well drilling system can include a control system which compares a parameter signature for a drilling operation to an event signature indicative of a drilling event, and a controller which controls the drilling operation automatically in response to the drilling event being indicated by at least a partial match between the parameter signature and the event signature.
摘要:
A gas supply system is disclosed. The gas supply system includes a housing, a spool, a gas tube, at least one opening, a retract mechanism and a holding member. The spool is configured within the housing. The gas tube is retractably wound on the spool and includes a first end portion and a second end portion capable of being connected to a gas supply and a nasal cannula respectively. The at least one opening is configured on the housing for enabling at least one of the first end portion and the second end portion of the gas tube to extend out of the housing. The retract mechanism is configured in the housing and is capable of retracting a portion of the gas tube extended out of the housing. The holding member extends from the housing and enables the gas supply system to be removably mounted on a supporting member.
摘要:
A method of controlling pressure in a wellbore can include determining a real time wellbore pressure PwbRT1 at a pressure sensor in the wellbore, calculating hydrostatic pressure Ph1 at the pressure sensor, determining a real time annulus pressure PaRT, calculating friction pressure Pf due at least to circulation of the fluid through the wellbore and depth in the wellbore, calculating a friction pressure correction factor CFPf1 equal to (PwbRT1−Ph1−PaRT)/Pf, and controlling operation of a pressure control device, based on the friction pressure correction factor CFPf1. The method can further include determining a desired wellbore pressure PwbD1 at the pressure sensor, calculating an annulus pressure setpoint PaSP1 equal to PwbD1−Ph1−(Pf*CFPf1), and adjusting the pressure control device as needed to maintain PaRT equal to PaSP1.
摘要:
Well pressure control is integrated in real time with geomechanics determinations made during drilling. A well drilling method includes updating determinations of properties of a formation surrounding a wellbore in real time as the wellbore is being drilled; and controlling wellbore pressure in real time as the wellbore is being drilled, in response to the updated determinations of the formation properties. Another well drilling method includes obtaining sensor measurements in a well drilling system in real time as a wellbore is being drilled; transmitting the sensor measurements to a control system in real time; the control system determining in real time properties of a formation surrounding the wellbore based on the sensor measurements, and the control system transmitting in real time a pressure setpoint to a controller; and the controller controlling operation of at least one flow control device, thereby influencing a well pressure toward the pressure setpoint.
摘要:
A method of maintaining a desired downhole pressure during a drilling operation can include measuring a parameter with a sensor, communicating actual parameter values from the sensor to a predictive device, training the predictive device to output predicted parameter values in response to input of the actual parameter values, and outputting the predicted parameter values from the predictive device when the predictive device ceases receiving the actual parameter values. A well drilling system can include a predictive device which outputs predicted parameter values in response to input of actual parameter values to the predictive device. The predictive device continues to output the predicted parameter values, even when the predictive device fails to receive valid actual parameter values. Another well drilling system includes a data validator which communicates valid actual parameter values to the predictive device, but does not communicate invalid actual parameter values to the predictive device.