Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Engineering Library- R857.O6B54 2016

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Engineering Library- QA76.76.E95A395 2016

For my job, I regularly need to do the same or very similar search queries in Outlook.

Some queries are a bit more complex so redoing them each time is a bit cumbersome.

Is there a way to save my Search queries so I can reuse them later rather than needing to redo them each time?

Health: Dr. Joel Fuhrman, Nutritional and Natural Methods

Strength training has many benefits for health and longevity. Now many older Angelenos are seeking out a method called slow motion strength training to protect their joints and heal injuries.

Protein engineering is a powerful biotechnological process that focuses on creating new enzymes or proteins and improving the functions of existing ones by manipulating their natural macromolecular architecture.1?

I don't want to get hosed buying a pretty label and sales pitch on the bottle. I don't mind buying more than one bottle to get a better price. I don't know what "should be" in good mayo but you do, that's why I came here for guidance. I know we all hate Amazon, plz go to the next question rather than telling me Bezos blows; I am aware.

Initially thought of this in the context of a camping trip, but now also wondering about home safety purposes. What's the latest on ensuring that water is drinkable/potable and won't kill you?

•Iodine, sure, but what are the limitations? How much water per tablet can it purify?

•Boiling? To what temperature, for how long? Which types of microbe is it effective against?

•I know next to nothing about filters/osmosis.

•As far as I know, basically all of the above are for bacteria only. Which is good and all, but what if the water has chemical toxins instead of just biological? (Unlikely for a camping trip, I know, but somewhat more plausible when it comes to, say, well-water for a house.) Is there anything that works then? How to even tell if this is the case?

Desde su formación en un pequeño garage hasta el Latin Grammy a Mejor Álbum de Música Latina para Niños, la Filarmónica conmemora su larga trayectoria

In casestudies in de literatuur of uit het werkveld lezen we vaak over de grote meerwaarde die neuromarketing biedt aan marketinggerichte projecten.  Maar wat is de realiteit? Wat zijn de effectieve mogelijkheden? Wat is het verschil tussen de verwachte potentie van neuromarketing en de daadwerkelijke mogelijkheden, uitdagingen en beperkingen ervan in de praktijk. En, wat […]

James Gaffigan guest conducts Wagner, Mozart and Barber; pianist Hélène Grimaud plays Beethoven.

Censorship is antithetical to the scientific method because it requires free speech and open debate and skepticism Continue reading →

Discover simple yet effective methods to remove coffee and tea stains from mugs, maintaining their shine and cleanliness. Our article offers practical steps and household products you can use, helping you enjoy your beverages stain-free. Goodbye, stubborn stains!

The post The Best Way to Remove Coffee and Tea Stains from Mugs: Foolproof Methods Revealed appeared first on Unclutterer.

Nonphotochemical quenching (NPQ) is a mechanism of regulating light harvesting that protects the photosynthetic apparatus from photodamage by dissipating excess absorbed excitation energy as heat. In higher plants, the major light-harvesting antenna complex (LHCII) of photosystem (PS) II is directly involved in NPQ. The aggregation of LHCII is proposed to be involved in quenching. However, the lack of success in isolating native LHCII aggregates has limited the direct interrogation of this process. The isolation of LHCII in its native state from thylakoid membranes has been problematic because of the use of detergent, which tends to dissociate loosely bound proteins, and the abundance of pigment–protein complexes (e.g. PSI and PSII) embedded in the photosynthetic membrane, which hinders the preparation of aggregated LHCII. Here, we used a novel purification method employing detergent and amphipols to entrap LHCII in its natural states. To enrich the photosynthetic membrane with the major LHCII, we used Arabidopsis thaliana plants lacking the PSII minor antenna complexes (NoM), treated with lincomycin to inhibit the synthesis of PSI and PSII core proteins. Using sucrose density gradients, we succeeded in isolating the trimeric and aggregated forms of LHCII antenna. Violaxanthin- and zeaxanthin-enriched complexes were investigated in dark-adapted, NPQ, and dark recovery states. Zeaxanthin-enriched antenna complexes showed the greatest amount of aggregated LHCII. Notably, the amount of aggregated LHCII decreased upon relaxation of NPQ. Employing this novel preparative method, we obtained a direct evidence for the role of in vivo LHCII aggregation in NPQ.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that plays a key role in controlling transepithelial fluid movement. Excessive activation results in intestinal fluid loss during secretory diarrheas, whereas CFTR mutations underlie cystic fibrosis (CF). Anion permeability depends both on how well CFTR channels work (permeation/gating) and on how many are present at the membrane. Recently, treatments with two drug classes targeting CFTR—one boosting ion-channel function (potentiators) and the other increasing plasma membrane density (correctors)—have provided significant health benefits to CF patients. Here, we present an image-based fluorescence assay that can rapidly and simultaneously estimate both CFTR ion-channel function and the protein's proximity to the membrane. We monitor F508del-CFTR, the most common CF-causing variant, and confirm rescue by low temperature, CFTR-targeting drugs and second-site revertant mutation R1070W. In addition, we characterize a panel of 62 CF-causing mutations. Our measurements correlate well with published data (electrophysiology and biochemistry), further confirming validity of the assay. Finally, we profile effects of acute treatment with approved potentiator drug VX-770 on the rare-mutation panel. Mapping the potentiation profile on CFTR structures raises mechanistic hypotheses on drug action, suggesting that VX-770 might allow an open-channel conformation with an alternative arrangement of domain interfaces. The assay is a valuable tool for investigation of CFTR molecular mechanisms, allowing accurate inferences on gating/permeation. In addition, by providing a two-dimensional characterization of the CFTR protein, it could better inform development of single-drug and precision therapies addressing the root cause of CF disease.

In their comment (1) on our publication (2), the authors make two points: (i) they raise concerns about the possible effect of residual NONOate in our study, and (ii) they promote nitrosylcobalamin (NOCbl) supplied by their own company. Both points lack merit for the following reasons. The authors make the astonishing claim that the spectra of nitric oxide (NO•) and cobalamins overlap. Unlike NO•, cobalamin absorbs in the visible region, permitting unequivocal spectral assignment of NOCbl as reported (3). We demonstrated that whereas NOCbl is highly unstable in solution, it is stabilized by the B12 trafficking protein CblC. So even if present, residual NONOate (which is unstable at neutral pH and is removed during the work-up (3)) could not account for the observed difference.The authors then misrepresent our synthetic method, claiming that anaerobic conditions were used to generate nitrocobalamin (NO2Cbl), which results in the transient formation of NOCbl. We synthesized NO2Cbl aerobically using nitrite as described (4); NOCbl is not an intermediate in this ligand exchange reaction. The aerobic instability of NOCbl has been rigorously described by inorganic chemists (3, 5) and raises obvious questions about its purported biological effects as exemplified by the authors' own 2003 JBC publication, which was later withdrawn.As to promoting NOCbl from their company, the authors refer to a synthetic route from a mixture of NO• gas and aquocobalamin. The authors' method (6) has been described as “dubious” by chemists (5). Whereas DEAE NONOate used in our method is widely known as an NO• donor,...

After a thorough read of this paper (1), we wish to clarify that the authors' anaerobic method of synthesis for the production of nitrocobalamin results in the transient formation of nitrosylcobalamin, an unstable intermediate upon exposure to air. We concur that the authors' method results in the production of nitrocobalamin based on the UV-visible data as shown. The authors' adapted anaerobic method consists of mixing hydroxocobalamin hydrochloride with diethylamine NONOate diethylammonium salt in aqueous solution. Of concern, the UV spectrum of nitric oxide overlaps that of all cobalamin species under anaerobic conditions, making any assignments of the binding of nitric oxide to hydroxocobalamin suspect (2). Additionally, the use of acetone to precipitate the authors' product causes precipitation of diethylamine NONOate, resulting in an impure product. As a result, its utility for drawing experimental conclusions is faulty.The product from the authors' anaerobic synthetic method has not been assessed for purity, and the synthetic method itself has not been validated using a stability-indicating method as required by the International Conference on Harmonization (ICH) (ICH Q2B, Validation of Analytical Procedures) methodology, which is a hallmark for analytical characterization. Our nitrosylcobalamin synthesis involves reacting nitric oxide gas with hydroxocobalamin acetate as a heterogeneous mixture in a non-electron-donating solvent followed by rotary evaporation. Our nitrosylcobalamin product is stable in air, releases nitric oxide gas in situ (3), and meets ICH stability guidelines (4). Additionally, our nitrosylcobalamin product demonstrates biological activity, which has not been observed for nitrocobalamin (3, 5).

William M. Old
Oct 1, 2005; 4:1487-1502
Research

Jennifer L. Macdonald
May 1, 2005; 46:1061-1067
Methods

M. Burstein
Nov 1, 1970; 11:583-595
Articles

Ran Gu and Bing Gao
Math. Comp. 93 (), 2837-2860.
Abstract, references and article information

Zhaohui Fu, Tao Tang and Jiang Yang
Math. Comp. 93 (), 2745-2767.
Abstract, references and article information

Katherine Baker, Lehel Banjai and Mariya Ptashnyk
Math. Comp. 93 (), 2711-2743.
Abstract, references and article information

Constantin Carle and Marlis Hochbruck
Math. Comp. 93 (), 2611-2641.
Abstract, references and article information

Buyang Li, Zongze Yang and Zhi Zhou
Math. Comp. 93 (), 2557-2586.
Abstract, references and article information

R. Gibara and D. Kinzebulatov
St. Petersburg Math. J. 35 (), 445-460.
Abstract, references and article information

TNF is a highly pro-inflammatory cytokine that contributes not only to the regulation of immune responses but also to the development of severe inflammatory diseases. TNF is synthesized as a transmembrane protein, which is further matured via proteolytic cleavage by metalloproteases such as ADAM17, a process known as shedding. At present, TNF is mainly detected by measuring the precursor or the mature cytokine of bulk cell populations by techniques such as ELISA or immunoblotting. However, these methods do not provide information on the exact timing and extent of TNF cleavage at single-cell resolution and they do not allow the live visualization of shedding events. Here, we generated C-tag TNF as a genetically encoded reporter to study TNF shedding at the single-cell level. The functionality of the C-tag TNF reporter is based on the exposure of a cryptic epitope on the C terminus of the transmembrane portion of pro-TNF on cleavage. In both denatured and nondenatured samples, this epitope can be detected by a nanobody in a highly sensitive and specific manner only upon TNF shedding. As such, C-tag TNF can successfully be used for the detection of TNF cleavage in flow cytometry and live-cell imaging applications. We furthermore demonstrate its applicability in a forward genetic screen geared toward the identification of genetic regulators of TNF maturation. In summary, the C-tag TNF reporter can be employed to gain novel insights into the complex regulation of ADAM-dependent TNF shedding.

The dimeric ectonucleotidase CD73 catalyzes the hydrolysis of AMP at the cell surface to form adenosine, a potent suppressor of the immune response. Blocking CD73 activity in the tumor microenvironment can have a beneficial effect on tumor eradication and is a promising approach for cancer therapy. Biparatopic antibodies binding different regions of CD73 may be a means to antagonize its enzymatic activity. A panel of biparatopic antibodies representing the pairwise combination of 11 parental monoclonal antibodies against CD73 was generated by Fab-arm exchange. Nine variants vastly exceeded the potency of their parental antibodies with ≥90% inhibition of activity and subnanomolar EC50 values. Pairing the Fabs of parents with nonoverlapping epitopes was both sufficient and necessary whereas monovalent antibodies were poor inhibitors. Some parental antibodies yielded potent biparatopics with multiple partners, one of which (TB19) producing the most potent. The structure of the TB19 Fab with CD73 reveals that it blocks alignment of the N- and C-terminal CD73 domains necessary for catalysis. A separate structure of CD73 with a Fab (TB38) which complements TB19 in a particularly potent biparatopic shows its binding to a nonoverlapping site on the CD73 N-terminal domain. Structural modeling demonstrates a TB19/TB38 biparatopic antibody would be unable to bind the CD73 dimer in a bivalent manner, implicating crosslinking of separate CD73 dimers in its mechanism of action. This ability of a biparatopic antibody to both crosslink CD73 dimers and fix them in an inactive conformation thus represents a highly effective mechanism for the inhibition of CD73 activity.