trolling

DUAL RAMP ACTUATOR CONTROLLING A TWO CLUTCH SYSTEM FOR A DRIVELINE

A ball ramp actuator assembly including a control ring, an activation ring including a first section and a second section, two circumferential plate grooves formed between the control ring and the sections of the activation ring which contain rolling elements, two clutches, a gear and an actuator. The first and second sections are splined together allowing for axial movement. The first clutch is connected to the first section of the activation ring and a second clutch is connected to the second section of the activation ring. The rotation of a section of the activation ring axially in one direction allows the corresponding plate groove to expand and apply a load to the corresponding clutch while the other section of the activation ring remains inactive and rotation in the opposite direction activates the other clutch respectively.




trolling

Method of controlling drainage of wash water remaining in a washing machine

Disclosed herein is a method of controlling drainage of wash water remaining in a washing machine. The method includes draining wash water from a tub to an outside of the washing machine, supplying wash water into the washing machine after the draining wash water, and re-draining the wash water to the outside of the washing machine after the supplying wash water.




trolling

SYSTEM AND METHOD FOR CONTROLLING A VOLTAGE CONTROLLED OSCILLATOR

An electrical circuit includes: at least one inductor, at least one varactor, and at least two transistors, all of which electrically arranged to form a voltage controlled oscillator (VCO) having an oscillation frequency; wherein the at least two transistors includes a first transistor and a second transistor; wherein the first transistor has a first bulk terminal and a first parasitic diode disposed between the first bulk terminal and the first transistor; wherein the second transistor has a second bulk terminal and a second parasitic diode disposed between the second bulk terminal and the second transistor; wherein application of a first control voltage to the first bulk terminal, application of a second control voltage to the second bulk terminal, or application of first and second control voltages to the first and second bulk terminals, respectively, is effective to change the oscillation frequency of the VCO.




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SYSTEMS AND METHODS FOR CONTROLLING A PLURALITY OF POWER SEMICONDUCTOR DEVICES

A power conversion system may include a plurality of power devices and a sensor operably coupled to at least one of the plurality of power devices and configured to detect a voltage, current, or electromagnetic signature signal associated with the plurality of power devices. The power converter may also include circuitry operably coupled to the plurality of power devices and the sensor. The circuitry may send a respective gate signal to each respective power device of the plurality of power devices, such that each respective gate signal is delayed by a respective compensation delay that is determined for the respective power device based on a respective time delay of the respective power device and a maximum time delay of the plurality of power devices.




trolling

Method for controlling the local characteristics of a non-woven textile and related installation

A crosslapper receives a card web and folds it into a lap intended to be needle-punched or consolidated by other ways. The web includes zones which are more condensed, having a spectrum of orientation of fibers with a component parallel to the width of the web, alternating with less condensed zones having a longitudinal unidirectional spectrum of orientations. The zones which are less condensed are used to form the edge zones of the lap. The result is that the lap has different respective spectra of orientation which pre-compensate for the unwanted changes produced by the needle-punching or other consolidation which follows. A needle-punched lap is obtained having a uniform MD/CD ratio (relationship between longitudinal and respectively transverse tensile strengths) or having a sought profile of the MD/CD ratio across the width of the lap.




trolling

REFRIGERATOR AND METHOD FOR CONTROLLING THE SAME

A method for controlling a refrigerator may comprise controlling at least one of a temperature and humidity of at least one storage area of the refrigerator based on first storage information, receiving, from a second refrigerator different from the refrigerator, second storage information of the second refrigerator, and controlling at least one of the temperature and the humidity of the at least one storage area of the refrigerator based on the received second storage information.




trolling

APPARATUS, METHOD AND COMPUTER PROGRAM FOR CONTROLLING FUNCTIONS OF A VEHICLE

Apparatuses, methods and computer programs for controlling functions of a vehicle. The apparatus for an information system of a vehicle includes a communication module for communication with a mobile device and a control module for controlling the communication module. The control module obtains a key signal and information about a user profile from the mobile device via the communication module. The user profile includes user settings for functions of the vehicle. The information about the user profile includes data about at least one subset of the user settings. The control module controls a locked state of the vehicle based on the key signal and controls at least one subset of the functions of the vehicle based on the information about the user profile.




trolling

METHOD AND BURNER USING THE CURIE EFFECT FOR CONTROLLING REACTANT VELOCITY FOR OPERATION IN PRE-HEATED AND NON-PRE-HEATED MODES

Methods, burner, apparatuses, and systems are provided for controlling a velocity of a jet of gas exiting a burner when the gas is heated or not and at a corresponding second higher temperature or lower first temperature. Through the use of a temperature-sensitive magnetic valve, the flow of a gas can be redirected to maintain velocity of the gas as delivered to a combustion chamber based on the temperature of the gas. The temperature-sensitive magnetic valve can redirect flow of the gas based on the magnetic state of a ferromagnetic material. The state of the temperature-sensitive magnetic valve changes based on the temperature of the gas to maintain the velocity of the gas delivered through an outlet of the burner to the combustion chamber. Thus, heated gases and standard temperature gases can be delivered at approximately equal velocities thus maintaining flame size and shape.




trolling

SEALPOT AND METHOD FOR CONTROLLING A SOLIDS FLOW RATE THERETHROUGH

A sealpot for a combustion power plant includes a downcomer standpipe which receives solids of the combustion power plant, a bed including a first end and a second opposite end, the first end connected to the downcomer standpipe, a discharge standpipe disposed at the second opposite end of the bed, and an orifice plate disposed between the bed and the discharge standpipe separating the discharge standpipe from the bed. The orifice plate includes apertures disposed at a height above the bed which allow transport of fluidized solids and gas through the orifice plate.




trolling

DEVICE FOR CONTROLLING THE COMBUSTION OF A BURNER

Described is a device (11) for controlling the combustion of a burner (1), comprising: •first means (12) for measuring the fuel flow rate (Vg); •second means 13 for measuring the flow rate of the comburent (Va) •first operator means (14) for controlling the opening of an inlet valve (5) as a function of the quantity of fuel to be supplied to the burner (1); •second operator means (15) for controlling the comburent flow regulator means (8) as a function of the quantity of comburent to be supplied to the burner (1); According to this invention, the device (11) comprises a unit (16) for controlling the first operator means (14) and the second operator means (15) as a function of the values measured by the first measuring means (12) and by the second measuring means (13).




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METHOD AND APPARATUS FOR DETECTING TIGHTNESS OF A PICK-UP HEAD, METHOD FOR CONTROLLING THE MOVING OF THE PICK-UP HEAD

A method and apparatus for detecting tightness of a pick-up head, and a method and apparatus for controlling the moving of the pick-up head are disclosed. The method for detecting the tightness of the pick-up head includes moving the pick-up head to an inner area of the disc reading device when then disc reading device is powered on, moving the pick-up head to an outer area of the disc reading device within a predetermined time period, moving the pick-up head from the outer area of the disc reading device to the inner area at a constant speed by a first fixed force, and recording the moving duration for moving the pick-up head from the outer area of the disc reading device to the inner area at the constant speed.




trolling

RECORDING CONTROL APPARATUS AND METHOD, DRIVE CONTROLLING CONTROLLER AND METHOD, RECORDING MEDIUM, AND PROGRAM

The present technology relates to a recording control apparatus, a recording control method, a drive controlling controller, a drive controlling method, a recording medium, and a program capable of reading information more reliably. A manager generates DMSs as management information for managing user data areas and spare areas of an optical disc. Further, the manager records the generated DMS in a DMA area of DS0 of the optical disc, and, in addition, records the generated DMS in a DMA mirror area of the DS1 surface of the optical disc. As described above, since DMSs as management information are recorded in the different areas of the optical disc, even if DMS cannot be read from one area, DMS can be read from the other area. The present technology is applicable to a recording and reproducing apparatus.




trolling

Method and apparatus for controlling a movable barrier system

In one embodiment, a method conducted by a movable barrier gateway device is disclosed for controlling a movable barrier, comprising receiving, by a communication interface, a remote command from a remote control device to move the movable barrier, the remote command sent over a network, delaying transmission of a signal to a movable barrier controller to move the movable barrier, by a processor, for a predetermined time period after the remote command is received, detecting movement of the movable barrier within the predetermined time period by a barrier movement detector, and ignoring the remote command by the processor in response to detecting movement of the movable barrier within the predetermined time period.




trolling

Apparatus for controlling slats of sash

An adjusting apparatus is provided in a sash to turn slats automatically while the sash is being opened. The adjusting apparatus includes a plurality of first engaging members, a driven unit, and a driving unit. The first engaging members are connected to the slats respectively. The driven unit is connected to the frame of the sash for reciprocation, and has a second engaging member, wherein all the first engaging members are engaged with the second engaging member. The driving unit is connected to the carrier and the driven unit respectively to drive the driven unit to move while the sash is being opened. The first engaging members are turned by the second engaging member when the driven unit is moved by the driving unit to turn the slats from the first position to the second position.




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CONTROLLING CONTENT MODIFICATIONS BY ENFORCING ONE OR MORE CONSTRAINT LINKS

Embodiments of the present disclosure include systems and methods for controlling modification of a data file that is accessed by multiple components of an application platform. The method for controlling modification of a data file includes: preparing a link constraint data that includes information of a data file and a component of an application platform, the component being associated with the data file; preparing an alert data that includes information of the data file and a person having a permission to modify the data file; responsive to an attempt of a user to modify the data file, retrieving the information of the component from the link constraint data and the information of the person from the alert data; and sending a notice of the attempt to at least one of the person and the user.




trolling

COMPRESSED-AIR DRYING DEVICE, METHOD FOR CONTROLLING COMPRESSED-AIR DRYING DEVICE, AND VEHICLE

A compressed air drying device that dries compressed air discharged from a compressor includes a dryer and a controller. The dryer includes a drying container, which is filled with a desiccant, and a discharge valve arranged in a discharge port that discharges drainage produced by regeneration of the desiccant. The controller obtains an ambient temperature and controls opening and closing of the discharge valve. When the ambient temperature is a temperature at which freezing occurs, the controller moves the compressed air, which is discharged from the compressor and heated, into the dryer and restricts opening of the discharge valve.




trolling

CARBON DIOXIDE SEPARATION AND CAPTURE APPARATUS AND METHOD OF CONTROLLING OPERATION OF CARBON DIOXIDE SEPARATION AND CAPTURE APPARATUS

A carbon dioxide separation and capture apparatus includes an absorption tower configured to cause an absorbing liquid to absorb a carbon dioxide gas contained in a process gas and a regeneration tower configured to cause the absorbing liquid from the absorption tower to release the carbon dioxide gas. The carbon dioxide separation and capture apparatus further includes an inlet concentration meter configured to measure concentration of an acid component in the process gas supplied to the absorption tower and an outlet concentration meter configured to measure concentration of the acid component in the process gas discharged from the absorption tower. Also included in the carbon dioxide separation and capture apparatus are a supplementary absorbing liquid supply mechanism configured to supply a supplementary absorbing liquid to the main unit and a controller configured to control an amount of the supplementary absorbing liquid supplied to the main unit by the supplementary absorbing liquid supply mechanism based on the concentrations of the acid component measured at the inlet concentration meter and the outlet concentration meter.




trolling

Method and apparatus for controlling odors

Methods and apparatus for controlling odors in an enclosed space, such as a pit latrine, include providing an oxidizer, such as a catalytic heater and an optional mechanical ventilation unit, such as an inline fan, both flow connected to a vault (pit) of the latrine. The heater is also connected to a source of fuel, for example, propane. Fresh air is drawn through vents in the latrine housing and thereafter through toilets in the latrine and through the vault, providing oxygen for the reaction. The fan and/or oxidation process draws both fresh air and accompanying odorous compounds directly from the latrine and into the oxidizer wherein the odorous components are substantially destroyed.




trolling

Method for controlling automatic head care system and automatic hair washing system, and automatic head care system

Provided is an automatic head care system and an automatic hair washing system for caring a person's head in a safe and effective manner without applying a straining force on the person's neck. In order to achieve the object, the following steps are performed in turn: a head receiving step in which a pair of arms 114L, 114R are placed at positions for receiving a person's head 10 on a suppotring body 112; a water washing step in which water ejected from a plurality of nozzles 110 is poured to the head 10 while the pair of arms 114L, 114R are swung; a shampoo step in which washing liquid ejected from the plurality of nozzles 110 is poured to the head 10 while the pair of arms 114L, 114R are swung; and a head care step in which the head 10 is cared by performing the push-rotating of the pair of arms 114L, 114R in the direction of approaching the head 10 so as to bring the plurality of contacts 109 into contact with the head 10 and by swinging the pair of arms 114L, 114R while moving the plurality of contacts 109.




trolling

RADAR APPARATUS AND CONTROLLING METHOD THEREOF

A vehicle-mounted radar apparatus includes transmission antenna members and a transmitting section provided with an oscillator and phase shifters, a controller controlling the phase shifter, a reception antenna member, and a receiving section. The oscillator generates radio waves for the radar waves transmitted from the transmission antenna. Each phase shifters changes a phase of the radio waves generated and supplies the phase-shifted radio waves to a corresponding one of the transmission antenna members. The reception antenna member receives reflected waves of the radar waves. The receiving section generates a reception signal including the reflected waves. For the noise reduction process, the controller controls the phase control, so that, of the received signals generated at the receiving section, a first leak component which is from reflected waves from objects other than a target object is subtracted from a second leak component leaking from the transmitting section to the receiving section.




trolling

CONTROLLING VALVE OPERATION USING PRESSURE

A valve body has a piston that slides within the body through four successive positions. The piston has a head, and an upper and lower skirt, with a port in the upper skirt. In the first position, a bias force urges the piston to the first of four positions, in which the piston port is closed. In a second position, the piston port aligns with a low pressure port in the valve body, when a low pressure supply of water is connected. In a third position, greater pressure again closes the piston port. In a fourth position, at a still greater pressure, the piston port aligns with a high pressure port in the valve body. The bias force or a location of the piston port can be varied for valves along a supply line, whereby varying supply pressure opens different valves, thereby enabling addressing of valves according to supply pressure.




trolling

Method and device for controlling effective heat transfer in a solid gas storage system

A method for controlling the effective heat transfer from a storage unit (1). During gas release from storage material (3) in the storage unit the storage material is heated by a heater (2). During re-saturation of the storage material (3) with gas the heater is off. Controlling of the effective heat transfer from the storage unit (1) is performed, during gas release, by ceasing convection of a convection gas and, during re-saturation, by performing or enabling convection of a convection gas to cool the storage unit (1).




trolling

Methods for controlling crystal growth, crystallization, structures and phases in materials and systems

This invention relates to novel methods for affecting, controlling and/or directing various crystal formation, structure formation or phase formation/phase change reaction pathways or systems by exposing one or more components in a holoreaction system to at least one spectral energy pattern. In a first aspect of the invention, at least one spectral energy pattern can be applied to a crystallization reaction system. In a second aspect of the invention, at least one spectral energy conditioning pattern can be applied to a conditioning reaction system. The spectral energy conditioning pattern can, for example, be applied at a separate location from the reaction vessel (e.g., in a conditioning reaction vessel) or can be applied in (or to) the reaction vessel, but prior to other (or all) crystallization reaction system participants being introduced into the reaction vessel.




trolling

Technologies for controlling degradation of sensing circuits

Technologies for controlling degradation of a sensor mote including detecting a trigger event and initiating degradation of at least a portion of the sensor mote in response to the trigger event. The trigger event may be embodied as any type of event detectable by the sensor mote such as a trigger signal, particular sensed data, expiration of a reference time period, completion of a task, and so forth. The sensor mote may imitate the degradation by, for example, controlling a valve to release a chemical stored in the sensor mote or allow a substance into the sensor mote.




trolling

PROCESS FOR CONTROLLING, UNDER VOID, A JET OF PARTICLES WITH AN AERODYNAMIC LENS AND ASSOCIATED AERODYNAMIC LENS

The invention relates to a method for controlling the divergence of a jet of particles in vacuo with an aerodynamic lens, the aerodynamic lens including at least one chamber; a diaphragm, a so-called inlet diaphragm, intended to form an inlet of the aerodynamic lens for a jet of particles, the inlet diaphragm having a given diameter (d1); and another diaphragm, a so-called outlet diaphragm, intended to form an outlet of the aerodynamic lens for this jet of particles; the method including: a step for generating the jet of particles from the inlet to the outlet, in vacuo, of the aerodynamic lens; and a step for adjusting the diameter (ds) of the outlet diaphragm for controlling the divergence of the jet of particles.




trolling

Method for controlling and optimizing the manufacture of gasoline blendstocks for blending with an alcohol as an oxygenate

A method for manufacturing an oxygenated gasoline-blend by blending a hydrocarbon Basestock for Oxygenate Blending (BOB) with an alcohol such as ethanol to a required octane specification first blends the BOB to an octane number, (RON+MON)/2 based on the octane sensitivity (RON−MON) of the BOB and the proportion of alcohol to be added to the BOB, such that when the BOB is blended with the specification proportion of alcohol to form the oxygenated gasoline blend, this blend will have the required octane specification. The blending of the BOB with the alcohol will typically be done at a location remote from that where the BOB is blended, e.g. at the product distribution terminal after being transported from the refinery by pipeline or tank car.




trolling

Device and method for controlling the conversion of biomass to biofuel

Embodiments presented herein describe an apparatus and method to control the conversion of carbonaceous materials, particularly biomass and those biomass resources, into a high performance solid fuel. This method, and the apparatus described as the means to accomplish this method, provides a process having a control system that enables the system to produce a fuel of uniform quality, even with a change in biomass supply.




trolling

Methods and apparatus for controlling moisture in plant oils and liquid biofuels

The moisture absorption capacity of biofuels can be more or less 10 times that of fossil diesel oil, causing biofuels to form acids that induce metal corrosion and form deposits in the fuel tank and pipe lines. Methods for removing moisture from stored biofuels and plant oils are described wherein glycerol is used as a solvent to extract the moisture from the bioliquid or oil, comprising the steps of placing the biofuel or oil in fluid contact with glycerol, incubating for a time, and then removing the glycerol. A cellulous ester dialysis or other semi-permeable membrane may be used to prevent the glycerol from contaminating the biofuel while allowing moisture to pass. Crude glycerol produced as a byproduct of biodiesel production may be used in the method of the disclosed invention with good result. Preferred embodiments of apparatus that employ the method of the subject invention are described.




trolling

METHOD OF CONTROLLING VELOCITY OF A HYDRAULIC ACTUATOR IN OVER-CENTER LINKAGE SYSTEMS

An electro-hydraulic actuation system includes a regeneration valve in fluid communication with a first fluid chamber and a second fluid chamber of a hydraulic actuator, and a dump valve is in fluid communication with the second fluid chamber and a fluid reservoir. A pump provides a flow of fluid to the first and second fluid chambers, a displacement of the pump controlling a velocity of the actuator during motion in the retraction and extension directions. An electric motor drives the pump, and a controller controls a state of the regeneration valve and the dump valve. At least one feedback device senses a system condition and provides a respective feedback signal indicative of the sensed system condition to the controller, the controller responsive to the feedback signal to determine an occurrence of an over-center load condition and control a state of the regeneration valve and the dump valve in response to the occurrence to maintain the velocity of the actuator.




trolling

tjcgttb whoisspirituallycontrollingted 62

TedISTed - Many of these Videos Are NOW In Bundle Files To DownLoad from TedISTheOneGod.Net AND IN MultiGigaByteSite From and THIS NOW From Ted WHO IS Ted AND Ted! WHO IS Ted AND Other Names And Titles And Autherities And Many Other Things Since Existence....

This item belongs to: movies/opensource_movies.

This item has files of the following types: Metadata




trolling

'Abusive, controlling and threatening' NT man jailed for fatal assault against ex-partner

Katherine man Lorenzo Deegan is sentenced to 10 years by the Northern Territory Supreme Court after fatally assaulting his ex-partner while on parole.



  • Law
  • Crime and Justice
  • Courts and Trials
  • Prisons and Punishment
  • Community and Society

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Power company trials solar, batteries and controlling home air conditioning to manage regional grid

A power company is remotely turning home air conditioners off in a trial to manage peak electricity demand, but will consumers hand over the remote control?





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TROLLING PHYSICS

TROLLING PHYSICS Existed in comics way before the internet




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People Are Trolling the Shit Out of Donald Trump After His St. Patrick's Day Tweet

Donald Trump's kept it pretty low key on Twitter in recent days. That didn't stop him from penning a little St. Paddy's Day sentiment though. If only he'd spell checked before sending it off though. Then again, would we expect anything less than this from the guy with a wide-reaching, well-developed reputation already for spelling shit in his own language incorrectly?

Yeah, yeah, we know. Here are some Trump Memes to smooth it over.




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Internet Had a Dangerous Amount of Fun Trolling Pic of Trump, Melania And Ivanka With The Pope

Just when we thought we'd never get anything better than Donald Trump grasping that orb, we get this dark-humored, delightfully awkward pic that just oozes cringe. Naturally, people were ready to flood Twitter with some entertaining captions. 




trolling

Celtic hero Chris Sutton bites back at Robbie Savage trolling as Hoops leapfrog Rangers



Celtic legend Chris Sutton has bitten back Robbie Savage on Twitter, as the Hoops finished the week top of the Scottish Premiership table, after Rangers’ 1-1 draw against Hearts.




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Molecular Basis of the Mechanisms Controlling MASTL [Research]

The human MASTL (Microtubule-associated serine/threonine kinase-like) gene encodes an essential protein in the cell cycle. MASTL is a key factor preventing early dephosphorylation of M-phase targets of Cdk1/CycB. Little is known about the mechanism of MASTL activation and regulation. MASTL contains a non-conserved insertion of 550 residues within its activation loop, splitting the kinase domain, and making it unique. Here, we show that this non-conserved middle region (NCMR) of the protein is crucial for target specificity and activity. We performed a phosphoproteomic assay with different MASTL constructs identifying key phosphorylation sites for its activation and determining whether they arise from autophosphorylation or exogenous kinases, thus generating an activation model. Hydrogen/deuterium exchange data complements this analysis revealing that the C-lobe in full-length MASTL forms a stable structure, whereas the N-lobe is dynamic and the NCMR and C-tail contain few localized regions with higher-order structure. Our results indicate that truncated versions of MASTL conserving a cryptic C-Lobe in the NCMR, display catalytic activity and different targets, thus establishing a possible link with truncated mutations observed in cancer-related databases.




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Strolling Through a World of Flowers

Spring has arrived. While some of us may have an opportunity to carefully step outside and view blossoms in our own neighborhood, others may not. Wherever you are, you can take a virtual stroll among the shoots and blossoms planted among the collections of the Prints & Photographs Division. Many images of gardens can be […]




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Supervisor Controlling Officer - Static Data, Auditing and Reporting

Application deadline: 17 May 2020 | Banking Settlements Centre | Location: Basel, Switzerland




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~$CPIL$378388$title$textbox$Zoetis accepting research grant proposals on controlling parasitic disease$/CPIL$~




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Controlling The Kernel - Its All About DRM




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Study of Tin Whisker Inhibiting Systems, Controlling the Copper Substrate Roughness and Controlling the Tin Deposit Crystal Structure

Presentation by George Milad of Uyemura International Corporation




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Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance

ABSTRACT

The protozoan parasites that cause malaria infect a wide variety of vertebrate hosts, including birds, reptiles, and mammals, and the evolutionary pressures inherent to the host-parasite relationship have profoundly shaped the genomes of both host and parasite. Here, we report that these selective pressures have resulted in unexpected alterations to one of the most basic aspects of eukaryotic biology, the maintenance of genome integrity through DNA repair. Malaria parasites that infect humans continuously generate genetic diversity within their antigen-encoding gene families through frequent ectopic recombination between gene family members, a process that is a crucial feature of the persistence of malaria globally. The continuous generation of antigen diversity ensures that different parasite isolates are antigenically distinct, thus preventing extensive cross-reactive immunity and enabling parasites to maintain stable transmission within human populations. However, the molecular basis of the recombination between gene family members is not well understood. Through computational analyses of the antigen-encoding, multicopy gene families of different Plasmodium species, we report the unexpected observation that malaria parasites that infect rodents do not display the same degree of antigen diversity as observed in Plasmodium falciparum and appear to undergo significantly less ectopic recombination. Using comparative genomics, we also identify key molecular components of the diversification process, thus shedding new light on how malaria parasites balance the maintenance of genome integrity with the requirement for continuous genetic diversification.

IMPORTANCE Malaria remains one of the most prevalent and deadly infectious diseases of the developing world, causing approximately 228 million clinical cases and nearly half a million deaths annually. The disease is caused by protozoan parasites of the genus Plasmodium, and of the five species capable of infecting humans, infections with P. falciparum are the most severe. In addition to the parasites that infect people, there are hundreds of additional species that infect birds, reptiles, and other mammals, each exquisitely evolved to meet the specific challenges inherent to survival within their respective hosts. By comparing the unique strategies that each species has evolved, key insights into host-parasite interactions can be gained, including discoveries regarding the pathogenesis of human disease. Here, we describe the surprising observation that closely related parasites with different hosts have evolved remarkably different methods for repairing their genomes. This observation has important implications for the ability of parasites to maintain chronic infections and for the development of host immunity.




trolling

Sulfamoyl Heteroarylcarboxylic Acids as Promising Metallo-{beta}-Lactamase Inhibitors for Controlling Bacterial Carbapenem Resistance

ABSTRACT

Production of metallo-β-lactamases (MBLs), which hydrolyze carbapenems, is a cause of carbapenem resistance in Enterobacteriaceae. Development of effective inhibitors for MBLs is one approach to restore carbapenem efficacy in carbapenem-resistant Enterobacteriaceae (CRE). We report here that sulfamoyl heteroarylcarboxylic acids (SHCs) can competitively inhibit the globally spreading and clinically relevant MBLs (i.e., IMP-, NDM-, and VIM-type MBLs) at nanomolar to micromolar orders of magnitude. Addition of SHCs restored meropenem efficacy against 17/19 IMP-type and 7/14 NDM-type MBL-producing Enterobacteriaceae to satisfactory clinical levels. SHCs were also effective against IMP-type MBL-producing Acinetobacter spp. and engineered Escherichia coli strains overproducing individual minor MBLs (i.e., TMB-2, SPM-1, DIM-1, SIM-1, and KHM-1). However, SHCs were less effective against MBL-producing Pseudomonas aeruginosa. Combination therapy with meropenem and SHCs successfully cured mice infected with IMP-1-producing E. coli and dually NDM-1/VIM-1-producing Klebsiella pneumoniae clinical isolates. X-ray crystallographic analyses revealed the inhibition mode of SHCs against MBLs; the sulfamoyl group of SHCs coordinated to two zinc ions, and the carboxylate group coordinated to one zinc ion and bound to positively charged amino acids Lys224/Arg228 conserved in MBLs. Preclinical testing revealed that the SHCs showed low toxicity in cell lines and mice and high stability in human liver microsomes. Our results indicate that SHCs are promising lead compounds for inhibitors of MBLs to combat MBL-producing CRE.

IMPORTANCE Carbapenem antibiotics are the last resort for control of severe infectious diseases, bloodstream infections, and pneumonia caused by Gram-negative bacteria, including Enterobacteriaceae. However, carbapenem-resistant Enterobacteriaceae (CRE) strains have spread globally and are a critical concern in clinical settings because CRE infections are recognized as a leading cause of increased mortality among hospitalized patients. Most CRE produce certain kinds of serine carbapenemases (e.g., KPC- and GES-type β-lactamases) or metallo-β-lactamases (MBLs), which can hydrolyze carbapenems. Although effective MBL inhibitors are expected to restore carbapenem efficacy against MBL-producing CRE, no MBL inhibitor is currently clinically available. Here, we synthesized 2,5-diethyl-1-methyl-4-sulfamoylpyrrole-3-carboxylic acid (SPC), which is a potent inhibitor of MBLs. SPC is a remarkable lead compound for clinically useful MBL inhibitors and can potentially provide a considerable benefit to patients receiving treatment for lethal infectious diseases caused by MBL-producing CRE.




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The Role of Fnr Paralogs in Controlling Anaerobic Metabolism in the Diazotroph Paenibacillus polymyxa WLY78 [Environmental Microbiology]

Fnr is a transcriptional regulator that controls the expression of a variety of genes in response to oxygen limitation in bacteria. Genome sequencing revealed four genes (fnr1, fnr3, fnr5, and fnr7) coding for Fnr proteins in Paenibacillus polymyxa WLY78. Fnr1 and Fnr3 showed more similarity to each other than to Fnr5 and Fnr7. Also, Fnr1 and Fnr3 exhibited high similarity with Bacillus cereus Fnr and Bacillus subtilis Fnr in sequence and structures. Both the aerobically purified His-tagged Fnr1 and His-tagged Fnr3 in Escherichia coli could bind to the specific DNA promoter. Deletion analysis showed that the four fnr genes, especially fnr1 and fnr3, have significant impacts on growth and nitrogenase activity. Single deletion of fnr1 or fnr3 led to a 50% reduction in nitrogenase activity, and double deletion of fnr1 and fnr3 resulted to a 90% reduction in activity. Genome-wide transcription analysis showed that Fnr1 and Fnr3 indirectly activated expression of nif (nitrogen fixation) genes and Fe transport genes under anaerobic conditions. Fnr1 and Fnr3 inhibited expression of the genes involved in the aerobic respiratory chain and activated expression of genes responsible for anaerobic electron acceptor genes.

IMPORTANCE The members of the nitrogen-fixing Paenibacillus spp. have great potential to be used as a bacterial fertilizer in agriculture. However, the functions of the fnr gene(s) in nitrogen fixation and other metabolisms in Paenibacillus spp. are not known. Here, we found that in P. polymyxa WLY78, Fnr1 and Fnr3 were responsible for regulation of numerous genes in response to changes in oxygen levels, but Fnr5 and Fnr7 exhibited little effect. Fnr1 and Fnr3 indirectly or directly regulated many types of important metabolism, such as nitrogen fixation, Fe uptake, respiration, and electron transport. This study not only reveals the function of the fnr genes of P. polymyxa WLY78 in nitrogen fixation and other metabolisms but also will provide insight into the evolution and regulatory mechanisms of fnr in Paenibacillus.




trolling

Controlling quantumness: Simulations reveal details about how particles interact

A recent study has described new states that can be found in super-cold atom experiments, which could have applications for quantum technology.




trolling

Boston Dynamics creepy robot dog is patrolling parks to encourage social distancing

Boston Dynamics robot dog, known as Spot, is patroling Bishan-Ang Mo Kio Park in Singapore to help with social distancing practices during the coronavirus pandemic, the Singapore government announced.




trolling

Controlling quantumness: Simulations reveal details about how particles interact

A recent study at the Okinawa Institute of Science and Technology Graduate University has described new states that can be found in super-cold atom experiments, which could have applications for quantum technology.




trolling

Controlling angular dispersions in optical metasurfaces