mono

Monoclonal antibodies against GMF-B antigens, and uses therefor

The disclosure relates to anti-glial maturation factor beta (“GMF-B”) monoclonal antibodies (mAbs) and fragments thereof, as well as hybridoma lines that secrete antibodies or fragments. Therapeutic and diagnostic uses of such antibodies, including treatment and detection of cancer and dementia, and methods and kits for detecting cells or samples expressing GMF-B, including soluble GMF-B, are also encompassed.




mono

DNA replicon system for high-level rapid production of vaccines and monoclonal antibody therapeutics in plants

Plant viral vectors have great potential in rapid production of proteins, but no simple. Here a geminivirus-based system for high-yield and rapid production of oligomeric protein complexes, including virus-like particle (VLP) vaccines and monoclonal antibodies (mAbs) is described. In particular, a single vector that contains two non-competing replicons for transient expression in Nicotiana benthamiana leaves is described. The correct assembly of these subunit proteins into functional oligomeric structures (VLPs or full-size mAb) is also described. This system advances plant transient expression technology by eliminating the need for non-competing viruses, and thus, enhances the realistic commercial application of this technology for producing multiple-subunit protein complexes.




mono

Method of treatment of cancer using guanosine 3', 5' cyclic monophosphate (cyclic GMP)

A method of treating cancer through use of guanosine 3',5'-cyclic monophosphate (cyclic GMP). Cyclic GMP decreases the number of human breast cancer and prostate adenocarcinoma as well as small-cell and squamous lung cells in culture by 30% (1 μM), 84% (1 mM), 31% (1 μM), and 30% (1 μM), respectively. Cyclic GMP decreases DNA synthesis in human pancreatic, breast, and prostate adenocarcinomas as well as small-cell and squamous cell carcinomas of the lung at its 1 μM concentration by 51%, 54%, 56%, 50% and 52%, respectively. Cyclic GMP when infused for one week decreases the tumor volume of human pancreatic adenocarcinomas in athymic mice 95% compared to untreated animals with human pancreatic adenocarcinomas.




mono

Method for producing water-absorbing polymer particles by polymerizing droplets of a monomer solution

A process for producing water-absorbing polymer particles by polymerizing droplets of a monomer solution in a surrounding gas phase in a reaction chamber, wherein the monomer solution is metered into the reaction chamber via at least one bore, and the diameter is from 210 to 290 μm per bore and the metering rate is from 0.9 to 5 kg/h per bore.




mono

Ethylenically unsaturated polymerizable groups comprising polycarbosiloxane monomers

The present application relates to novel monomers comprising polycarbosiloxane monomers useful in certain specific embodiments in the manufacture of devices. More particularly, the present application relates to certain ethylenically unsaturated free radical polymerizable monomers comprising polycarbosiloxane monomers. Even more particularly, the present application pertains to monomers comprising polycarbosiloxane monomers which further comprise at least two ethylenically unsaturated free radical polymerizable groups.




mono

Bridged metallocene catalyst systems with switchable hydrogen and comonomer effects

The present invention provides polymerization processes utilizing an ansa-metallocene catalyst system for the production of olefin polymers. Polymers produced from the polymerization processes have properties that vary based upon the presence or the absence of hydrogen and/or comonomer in the polymerization process.




mono

Manufacturing method for monolithic ceramic electronic component

In a manufacturing method for a monolithic ceramic electronic component, a plurality of green chips arrayed in row and column directions which are obtained after cutting a mother block are spaced apart from each other and then tumbled, thereby uniformly making the side surface of each of the green chips an open surface. Thereafter, an adhesive is applied to the side surface. Then, by placing a side surface ceramic green sheet on an affixation elastic body, and pressing the side surface of the green chips against the side surface ceramic green sheet, the side surface ceramic green sheet is punched and stuck to the side surface.




mono

Nutritional products including monoglycerides and fatty acids

Disclosed are nutritional formulations including predigested fats that can be administered to preterm infants, infants, toddlers, and children for improving tolerance, digestion, and absorption of nutrients and for reducing the incidence of necrotizing enterocolitis, colic, and short bowel syndrome. The predigested fats include fatty acid-containing monoglycerides and/or a fatty acid component.




mono

Obtaining narrow line-width, full C-band tunability mirror for monolithic or hybrid integrated lasers

An apparatus comprising an optical medium, a power splitter coupled to the optical medium, a first delay line coupled to the power splitter such that the power splitter is positioned between the first delay line and the optical medium, a first comb reflector coupled to the first delay line such that the first delay line is positioned between the first comb reflector and the power splitter, and a second comb reflector coupled to the power splitter but not the first comb reflector and not the first delay line. A method comprising receiving an optical signal, splitting the optical signal into a first split optical signal and a second split optical signal, delaying the first split optical signal, tuning the delayed first split optical signal, tuning the second split optical signal, and delaying the tuned second split optical signal.




mono

Monoclonal thyroid stimulating or blocking antibodies, peptide sequences corresponding to their variable regions, and their uses in diagnostic, preventive and therapeutic medicine

Monoclonal antibodies (mAbs) having thyroid stimulating activity (TSAb), especially full or considerably agonistic activity, or thyroid blocking activity (TBAb), which are obtainable by genetic immunization of mice, or fragments (F(ab')2, Fab or Fv) or humanized forms of such monoclonal antibodies or single chain forms (SCA; scFv) of such fragments, which antibodies, or their fragments, compete with bovine TSH for epitopes of the human TSHr, compete with autoantibodies from sera from Graves' patients as well as with autoantibodies from sera from patients harboring blocking autoantibodies for epitopes of the human TSHr, bind to conformational epitopes of the human TSHr located in the first 281 amino acids of the human TSHr, and usually also bind to TSFR receptors (TSHr) from different animals. Various uses of such antibodies, or of peptides corresponding to variable regions of such antibodies, are also described and claimed.




mono

Flip-flops in a monolithic three-dimensional (3D) integrated circuit (IC) (3DIC) and related methods

Flip-flops in a monolithic three-dimensional (3D) integrated circuit (IC)(3DIC) and related method are disclosed. In one embodiment, a single clock source is provided for the 3DIC and distributed to elements within the 3DIC. Delay is provided to clock paths by selectively controllable flip-flops to help provide synchronous operation. In certain embodiments, 3D flip-flop are provided that include a master latch disposed in a first tier of a 3DIC. The master latch is configured to receive a flip-flop input and a clock input, the master latch configured to provide a master latch output. The 3D flip-flop also includes at least one slave latch disposed in at least one additional tier of the 3DIC, the at least one slave latch configured to provide a 3DIC flip-flop output. The 3D flip-flop also includes at least one monolithic intertier via (MIV) coupling the master latch output to an input of the slave latch.




mono

Method and apparatus for producing disilane through pyrolysis of monosilane

An apparatus for producing disilane through pyrolysis of monosilane, includes: a monosilane pyrolysis unit; a solid particle removal unit which removes solid particles generated in the pyrolysis unit; a condensing unit which liquefies and collects unreacted monosilane, and disilane and higher silanes with three (3) to seven (7) silicon atoms as pyrolysis products excluding hydrogen from a gas with the solid particles removed; a first separation unit which separates monosilane from a mixture of the liquefied unreacted monosilane, disilane and higher silanes; and a second separation unit which separates disilane and higher silanes from the mixture with the monosilane removed. In accordance with the present disclosure, disilane can be produced economically and efficiently with high purity through pyrolysis of monosilane.




mono

Monolithic optical coupling module based on total internal reflection surfaces

In one aspect, an optical device comprises a monolithic optical module which includes a first total internal reflection (TIR) surface, a second TIR surface adjacent the first TIR surface, and a first optical port aligned with the first internal optical beam dividing interface. An interface between the first TIR surface and the second TIR surface forms a first internal optical beam dividing interface. An exterior surface of the first TIR surface and an exterior surface of the second TIR surface form a generally V-shaped notch on the monolithic optical module. A first optical beam entering the monolithic optical module through the first optical port and incident on the first internal optical beam dividing interface is partially reflected by the first TIR surface to travel in a first direction as a second optical beam and partially reflected by the second TIR surface to travel in a second direction as a third optical beam. The second direction is generally opposite to the first direction.




mono

Method and apparatus for forming fine gauge and monofilament single and double-armed sutures

An apparatus for forming armed sutures has a swaging station for receiving, holding and swaging needles that are deposited therein. A linear motor drives a suture insertion gripper, which pulls suture from a supply reel and inserts a cut end thereof into a needle held in the swaging station. A ganged needle transfer assembly with a plurality of spaced needle gripper units carries needles along a line substantially at right angles to the suture line and transfers them to and from the swaging station and other needle processing stations. A precisor orients needles prior to placement in the swaging station and a pull test assembly tests armed sutures in both destructive and non-destructive modes. Both ends of the production line may be automated, e.g., by robots which load and offload needles prior to and after swaging, respectively. The apparatus is capable of forming double armed sutures by using a rotatable mount for the suture insertion gripper and a secondary, loop gripper. A suture transfer gripper extending up to the suture from a multi-tiered stack of slide tables. The suture transfer gripper cooperates with the suture insertion and loop grippers to hold the suture during cutting, insertion and transfer to the pull test apparatus and thereby protects the suture during processing.




mono

Dispersion medium comprising monocarboxylic esters for preparations of solids

The invention concerns a composition comprising as component (A): 10% to 97% by weight, based on the total weight of the composition, of one or more monocarboxylic esters of the general formula R1—CO—OR2, in which R1 is a saturated or unsaturated, branched or straight-chain, aliphatic group having 11 to 23 carbon atoms and R2 is a branched or straight-chain aliphatic group, a cycloaliphatic group or aromatic group having 1 to 13 carbon atoms, and the sum of the carbon atoms of the groups R1 and R2 is not more than 30, the monocarboxylic ester or esters possessing a boiling point of more than 250° C. under a standard pressure of 101.3 kPa, and as component (B): 3% to 90% by weight, based on the total weight of the composition, of one or more dispersants, the composition possessing a viscosity at 25° C. of less than 5000 mPas. The invention further concerns the use of the composition as a dispersion medium, millbases obtained from the composition, and the use of the millbases.




mono

Monorail vehicle apparatus with gravity-augmented contact load

Apparatus and method for gravity-augmented preload of drive wheels in a monorail vehicle travelling along a guide rail bearing and contact surfaces that are non-parallel with the gravity vector. The vehicle has a structure defining a pivot location against the bearing surface, as well as first and second assemblies for engaging the rail on the bearing and contact surfaces, respectively. The vehicle is mounted so its center of gravity is at a rear longitudinal offset rrl from the pivot location and a vertical offset rvert from the guide rail. A force and moment balance thus created in a normal load on a drive wheel engaged with the bearing surface at the pivot location, where the load value exceeds a standard normal load generated by the mass of the monorail vehicle alone.




mono

Monorail vehicle apparatus with gravity-controlled roll attitude and loading

Monorail vehicle that travels on a non-featured rail with substantial profile variation and controls roll attitude, lateral location, and loading through judicious placement of the vehicle's center of gravity without using springs or suspensions. The vehicle has a bogie for engaging the non-featured rail so the center of gravity has a lateral offset r1 from the rail centerline to produce a roll moment Nr determined by vehicle's mass and value of r1. The center of gravity also has a vertical offset r2. The bogie uses first and second assemblies for engaging the rail to produce a pair of surface normal reaction forces to thus control roll attitude and loading by the placement of the center of gravity, thereby enabling accurate alignment of the monorail vehicle.




mono

Coaxial passive radiation monomer

A coaxial passive radiation monomer apparatus is disclosed. In accordance with an aspect of the present disclosure, there is disclosed a dynamic speaker monomer combined with a passive radiator in a single unitary structure located in spatial proximity with respect to one another to thereby and further comprising an elastic material at the base of the speaker assembly for enhanced and optimized resonance frequencies for the active and passive components of the overall device.




mono

Lithographic printing plate precursor, lithographic printing plate platemaking method, and polymerizable monomer

There is provided a lithographic printing plate precursor that enables image recording using a laser and that provides an excellent scumming resistance and an excellent developability while maintaining a satisfactory printing durability. Also provided are a platemaking method, and a novel polymerizable monomer. A lithographic printing plate precursor has a support, and an image recording layer disposed thereon and containing a radical polymerization initiator and a polymerizable monomer that has a sulfonamide group and at least two ethylenically unsaturated groups; a lithographic printing plate platemaking method uses this lithographic printing plate precursor; and a polymerizable monomer has a sulfonamide group and at least two ethylenically unsaturated groups.




mono

Split ply tires and bead area monocomponents

An intermediate article of manufacture formed as a first stage bead area subassembly for a split ply pneumatic tire carcass is disclosed. The bead area subassembly has an annular bead core; a bead apex; a ply strip; and preferably a sidewall affixed to the ply strip. The subassembly is formed into a disk-shaped bead area monocomponent. The ply strip is wrapped about the bead core and the apex to form a ply turnup and both the ply strip and the ply turnup extend radially outwardly from the bead core. The bead area subassembly when formed into the disk-shaped bead area monocomponent is placed on an annular holder device. The combination of the bead area monocomponent on the holder device can be stacked for storage and latter assembly into a split ply carcass. Preferably, the ply turnup can be oriented extending inside or axially inward of the bead core on final assembly to form a split ply tire having axially inside turnups. In the preferred embodiment the ply strip is reinforced by radially extending ply cords.




mono

Monofilament line cutting tool

A monofilament line cutting tool is formed by sandwiching a cutting blade between first and second plastic sheets which are thermally bonded to one another. A monofilament line receiving slot in the plastic sheets extends to the blade whereby monofilament line bent into a U-shape may be placed in contact with the blade cutting edge. The plastic sheets are part of spool forming plastic sheet portions which are thermally bonded to one another and shaped into a spool. The plastic sheets forming the tool are selectively pivotable about a live hinge relative to the spool. The plastic sheets can be separated from one another for forming: a sphere generally around the cutting edge; a pair of elongate barrels extending parallel along each side of the monofilament line receiving slot and adjacent the cutting edge; or, a monofilament line receiving cavity extending to the blade cutting edge.




mono

Oxygen monolayer on a semiconductor

A Si or Ge semi-conductor substrate includes an oxygen monolayer on a surface thereof. The oxygen monolayer can be fractional or complete. A Si4+ or Ge4+ oxidation state of the surface of the Si or Ge substrate, respectively, resulting from the presence of the oxygen monolayer represents less than 50%, preferably less than 40% and more preferably less than 30% of the sum of Si1+, Si2+, Si3+ and Si4+ oxidation states or the sum of Ge1+, Ge2+, Ge3+ and Ge4+ oxidation states, respectively, as measured by XPS.




mono

Knitted component for an article of footwear including a full monofilament upper

An article of footwear including a full monofilament upper is described. The full monofilament upper incorporates a knitted component including a monofilament knit element. The monofilament knit element is formed by knitting with a monofilament strand. The monofilament knit element is formed of unitary knit construction with the remaining portions of the knitted component, including peripheral portions that are knit using a natural or synthetic twisted fiber yarn. An inlaid tensile element can extend through the knitted component, including portions of the monofilament knit element. The monofilament knit element may be knitted with a monofilament strand according to a variety of knit structures.




mono

Article of footwear including a monofilament knit element with peripheral knit portions

An article of footwear including a knitted component having a monofilament knit element with peripheral knit portions is described. The knitted component includes a monofilament knit element formed by knitting with a monofilament strand. The monofilament knit element is formed of unitary knit construction with the remaining portions of the knitted component, including peripheral portions that are knit using a natural or synthetic twisted fiber yarn. An inlaid tensile element can extend through the knitted component, including portions of the monofilament knit element. The monofilament knit element may be knitted with a monofilament strand according to a variety of knit structures.




mono

Article of footwear including a monofilament knit element with a fusible strand

An article of footwear including a full monofilament upper is described. The full monofilament upper incorporates a knitted component including a monofilament knit element. The monofilament knit element is formed by knitting with a monofilament strand. The monofilament knit element is formed of unitary knit construction with the remaining portions of the knitted component, including peripheral portions that are knit using a natural or synthetic twisted fiber yarn. An inlaid tensile element can extend through the knitted component, including portions of the monofilament knit element. The monofilament knit element may be knitted with a monofilament strand according to a variety of knit structures. A fusible strand may be knit with the monofilament knit element. Upon heating, the fusible strand can combine and surround the monofilament strand within the monofilament knit element.




mono

Article of footwear including a monofilament knit element with peripheral knit portions

An article of footwear including a knitted component having a monofilament knit element with peripheral knit portions is described. The knitted component includes a monofilament knit element formed by knitting with a monofilament strand. The monofilament knit element is formed of unitary knit construction with the remaining portions of the knitted component, including peripheral portions that are knit using a natural or synthetic twisted fiber yarn. An inlaid tensile element can extend through the knitted component, including portions of the monofilament knit element. The monofilament knit element may be knitted with a monofilament strand according to a variety of knit structures.




mono

EBOLA MONOCLONAL ANTIBODIES

The present disclosure provides antibodies, and antigen-binding fragments thereof that bind to EBOV glycoprotein. The present disclosure further provides hybridoma cell lines and methods for making and using the compositions provided herein.




mono

IMMUNE-STIMULATING MONOCLONAL ANTIBODIES AGAINST HUMAN INTERLEUKIN-2

The invention relates to a human Interleukin-2 (hIL-2) specific monoclonal antibody (mAb), or antigen binding fragment thereof, the binding of which to hIL-2 inhibits binding of hIL-2 to CD25 and the antibody is characterized by any of the parameters: the variable chain of the mAb comprises the amino acid sequence of SEQ ID NO 005 or SEQ ID NO 006; the binding to hIL-2 is characterized by a dissociation constant (KD)≦7.5 nmol/L; the binding to hIL-2 is characterized by an off-rate (Koff)≦1×10−4 s−1 and/or the antibody displays no measurable cross-reactivity to murine IL-2.




mono

Monoclonal Antibodies That Specifically Block Biological Activity Of A Tumor Antigen

This invention relates to novel monoclonal antibodies that specifically bind to the alpha-folate receptor. In some embodiments, the antibodies inhibit a biological activity of folate receptor-α (FR-α). The antibodies are useful in the treatment of certain cancers, particularly cancers that have increased cell surface expression of the alpha-folate receptor (“FR-α”), such as ovarian, breast, renal, colorectal, lung, endometrial, or brain cancer. The invention also relates to cells expressing the monoclonal antibodies, antibody derivatives, such as chimeric and humanized monoclonal antibodies, antibody fragments, and methods of detecting and treating cancer using the antibodies, derivatives, and fragments.




mono

Method for manufacturing monolithic ceramic electronic components

A ceramic green sheet laminate is produced by stacking ceramic green sheets, each including conductive films for forming first or second internal electrodes on a surface thereof. A first cutting step is performed in which the ceramic green sheet laminate is cut to form first and second end surfaces at which the first or second internal electrodes are exposed. A second cutting step is performed in which the ceramic green sheet laminate is cut to form first and second side surfaces at which the first and second internal electrodes are exposed. In the second cutting step, the ceramic green sheet laminate is pressed and cut by moving a cutting blade in a length direction or a width direction.




mono

Underdeck mid-cabin entry system for mono hull boat

An under deck mid cabin entry system for a mono hull boat including an entry console and exposed top and front surfaces. Front and top openings extend to the top edge of the front surface and collectively define a generally L shaped entryway. The entry console is disposed to the side of a center console and provides access to steps extending beneath the main deck. A top step is within the entry console proximate to the front surface and the steps curve towards a central beam of the boat and descend into the mid cabin such that a bottom step proximate to a floor of the mid cabin directs a user into a central area of the mid cabin and terminates to avoid obstructing movement in the central area.




mono

Associative thickener comprising acid monomer, associative monomer and nonionic monomer

As associative thickener obtainable by free radical polymerization, the preparation thereof and the use thereof in paper coating slips are described. The associative thickener is formed from (a) acid monomers selected from ethylenically unsaturated C3- to C8-carboxylic acids, (b) associative monomers of the general formula H2C═CR1—COO-(EO)n—(PO)m—R2, in which R1 is hydrogen or methyl, n is a number of at least two, m is a number from zero to 50, EO is an ethylene oxide group, PO is a propylene oxide group and R2 is a C8-C30-alkyl group or a C8-C30-alkaryl group, and (c) nonionic, copolymerizable monomers differing from a) and b), the reaction product having been reacted, after the polymerization, with initiators forming nonionic radicals.




mono

MONOLITHIC THERMOPLASTIC P-CLAMP WITH CUSHION AND LOCKING MECHANISM

A securing device for mechanical components that is comprised of the securing device is designed as a longitudinal plastic strip comprised of a first complementary tab and a second complementary tab. The first complementary tab and the second complementary tab interlock together and rest flush against one another in a manner that lines up the hole of the first complementary tab with the hole of the second complementary tab. The securing device may be surrounded by a cushion to improve the securing functionality of the device.




mono

DIAGNOSTIC OF CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML) BY FLOW CYTOMETRY

The present invention relates to an in vitro method of diagnosing chronic myelomonocytic leukemia (CMML) in a subject, said method comprising the steps of: a) Detecting a monocyte population in a biological sample from said subject; b) Quantifying the CD14+/CD16− monocytes in said biological sample; c) Comparing the value of step b) to a reference value; and d) Diagnosing CMML based on said comparison. Preferably, said detecting step a) is performed by an exclusion gating strategy by flow cytometry.




mono

MONOFUNCTIONAL AMINES AS ADHESION PRIMERS FOR CONDUCTIVE POLYMERS

The present invention relates to a process for producing an electrolytic capacitor, the process comprising process steps i) ii): i) providing a capacitor body (1) that comprises an electrode body (2) of an electrode material,a dielectric (3) which at least partially covers the surface of this electrode material, anda solid electrolyte (4) at least comprising an electrically conductive material which at least partially covers the dielectric surface; ii) applying a primer solution e) to the capacitor body (1), followed by an application of a solution or dispersion a) comprising a conjugated polymer b) and a solvent or dispersant d), followed by an at least partial removal of the solvent or dispersant d) for the formation of the polymeric outer layer (5) that is formed onto the capacitor body (1); wherein the primer solution e) comprises at least one monofunctional amine and at least one carboxylic acid.




mono

Acrylate-Terminated Urethane Polybutadienes From Low-Monomer 1:1 Monoadducts From Reactive Olefinic Compounds and Diisocyanates and Hydroxy-Terminated Polybutadienes for Liquid Optically Clear Adhesives (LOCAs)

The present invention relates to an optical clear resin and a method for producing a liquid optical clear photo-curable adhesive.




mono

Softube Monoment Bass synthesizer on sale for $75 USD

Plugin Boutique has announced a sale on the Monoment Bass by Softube, a software synthesizer designed to producing huge, solid bass tones with complex, organic overtones and focused effects. In the modern day, music production leans more heavily on bass than ever before. Although track counts can number a hundred or more, often the core […]

The post Softube Monoment Bass synthesizer on sale for $75 USD appeared first on rekkerd.org.




mono

monome’s alternative musical world: a hands-on creative expedition with norns and grid

It's a rarified way of making music - the ultra-minimal monome grid and norns open music platform. But what is it really about? We turn to reviewer Andreas Roman to find out.

The post monome’s alternative musical world: a hands-on creative expedition with norns and grid appeared first on CDM Create Digital Music.





mono

Disney Fans, There’s a Theme Park Version of Monopoly—And It’s Available Now

Its the perfect antidote to quarantine boredom. READ MORE...




mono

Charter Schools I: Preliminaries & Monopolies

Embed from Getty Images In November of 2016, president elect Trump selected Betsy DeVos as his Secretary of Education. While this appointment seems to have changed her mind about Common Core, DeVos has remained committed to expanding charter schools. Charter …




mono

Day 04 Shimonoseki to Mojiko Jun 2019

Wednesday 26th June 2019Dark clouds greeted me this morning as I woke up on my 40th birthday in Japan. Not a great start for me as I had planned to commemorate this special day with a crossisland expedition between Honshu Shimonoseki and Kyu




mono

Eduard Limonov, Russian author, dissident and longtime Kremlin irritant, dies at 77

The Russian dissident and author Eduard Limonov, who vocal opposition was a persistent thorn in the Kremlin's side, dies at 77.




mono

Firefighters remind Londoners to have working carbon monoxide alarms

Firefighters are warning Londoners to make sure they have a life-saving carbon monoxide (CO) alarm in Carbon Monoxide Awareness Week




mono

Dan Crenshaw defends Ricky Gervais’s Golden Globes monologue: ‘He’s illuminating their hypocrisy.’

The Republican congressman chastised entertainment culture for being "divisive."




mono

The Majestic Monolith can become The Citadel

The vast majority of web applications should start life as a Majestic Monolith: A single codebase that does everything the application needs to do. This is in contrast to a constellation of services, whether micro or macro, that tries to carve up the application into little islands each doing a piece of the overall work.… keep reading




mono

A neuroglobin-based high-affinity ligand trap reverses carbon monoxide-induced mitochondrial poisoning [Molecular Biophysics]

Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo. Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC–treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 μm) and nitric oxide (100 μm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 μm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning.




mono

Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase

Jorge H. Capdevila
Feb 1, 2000; 41:163-181
Reviews




mono

Structural basis of specific inhibition of extracellular activation of pro- or latent myostatin by the monoclonal antibody SRK-015 [Molecular Biophysics]

Myostatin (or growth/differentiation factor 8 (GDF8)) is a member of the transforming growth factor β superfamily of growth factors and negatively regulates skeletal muscle growth. Its dysregulation is implicated in muscle wasting diseases. SRK-015 is a clinical-stage mAb that prevents extracellular proteolytic activation of pro- and latent myostatin. Here we used integrated structural and biochemical approaches to elucidate the molecular mechanism of antibody-mediated neutralization of pro-myostatin activation. The crystal structure of pro-myostatin in complex with 29H4-16 Fab, a high-affinity variant of SRK-015, at 2.79 Å resolution revealed that the antibody binds to a conformational epitope in the arm region of the prodomain distant from the proteolytic cleavage sites. This epitope is highly sequence-divergent, having only limited similarity to other closely related members of the transforming growth factor β superfamily. Hydrogen/deuterium exchange MS experiments indicated that antibody binding induces conformational changes in pro- and latent myostatin that span the arm region, the loops contiguous to the protease cleavage sites, and the latency-associated structural elements. Moreover, negative-stain EM with full-length antibodies disclosed a stable, ring-like antigen–antibody structure in which the two Fab arms of a single antibody occupy the two arm regions of the prodomain in the pro- and latent myostatin homodimers, suggesting a 1:1 (antibody:myostatin homodimer) binding stoichiometry. These results suggest that SRK-015 binding stabilizes the latent conformation and limits the accessibility of protease cleavage sites within the prodomain. These findings shed light on approaches that specifically block the extracellular activation of growth factors by targeting their precursor forms.




mono

A neuroglobin-based high-affinity ligand trap reverses carbon monoxide-induced mitochondrial poisoning [Molecular Biophysics]

Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo. Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC–treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 μm) and nitric oxide (100 μm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 μm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning.