The number of new X-ray crystallography-based submissions to the Protein Data Bank appears to be at the beginning of a decline, perhaps signalling an end to the era of the dominance of X-ray crystallography within structural biology. This letter, from the viewpoint of a young structural biologist, applies the Copernican method to the life expectancy of crystallography and asks whether the technique is still the mainstay of structural biology. A study of the rate of Protein Data Bank depositions allows a more nuanced analysis of the fortunes of macromolecular X-ray crystallography and shows that cryo-electron microscopy might now be outcompeting crystallography for new labour and talent, perhaps heralding a change in the landscape of the field.

Maurice Jackson of Proven and Probable speaks with Andy Schectman, president of Miles Franklin Precious Metals Investments, about the present situation with physical precious metals.

The recent recession has prompted the adoption of 'return to growth' policies but the tools used to assess growth often have a narrow economic focus. A new report has assessed current macro-economic models and suggests they need to incorporate the impact that environmental factors can have on the economy, and vice versa, and recommends they should consider limits on resource and material consumption.

Here's how to capture gorgeous close-up photos in any scenario, with nothing but your smartphone and an affordable lens attachment.

Photographer Chris Perani painstakingly combines thousands of exposures to create each individual image.

The International Garden Photographer of the Year honors 16 photographers for their macro images of plants and animals.

'Coral Colors' showcases the psychedelic beauty of marine invertebrates.

Vibrations resistant Non-telecentric Macro Lens with a 16-mm-dia. simple mechanism.(3Z4S-LE VS-MC Series (φ16 Straight lens-barrel Type))

Tanya Menon, associate professor at Fisher College of Management, Ohio State University, explains how to recognize if your management style is too hands off. She's the co-author of "Stop Spending, Start Managing: Strategies to Transform Wasteful Habits."

Spot gold markets remained shut due to the lockdown to prevent the spread of coronavirus, according to HDFC Securities.

Don Komarechka is back on the show. This time he tells us about macro photography and about his latest book. The Kickstarter for it is almost finished. [sc:podlovebutton] Links: Kickstarter: Macro Photography: The Universe at our Feet by Don Komarechka Podcast: Photo Geek Weekly Homepage: Don Komarechka Photography SPONSOR: HoneyBook. Get 50% off with code … Continue reading "871 Frozen-UV-Macro-Stereo-Photography"

The post 871 Frozen-UV-Macro-Stereo-Photography appeared first on PHOTOGRAPHY TIPS FROM THE TOP FLOOR.

A library of macrocyclic compounds of the formula (I) where part (A) is a bivalent radical, a —(CH2)y— bivalent radical or a covalent bond;where part (B) is a bivalent radical, a —(CH2)z— bivalent radical, or a covalent bond;where part (C) is a bivalent radical, a —(CH2)t— bivalent radical, or a covalent bond; andwhere part (T) is a —Y-L-Z— radical wherein Y is CH2 or CO, Z is NH or O and L is a bivalent radical. These compounds are useful for carrying out screening assays or as intermediates for the synthesis of other compounds of pharmaceutical interest. A process for the preparation of these compounds in a combinatorial manner, is also disclosed.

A method is provided for providing consistent logical code across specific programming languages. The method incorporates preprocessor macros in a source computer program code to generate a program control flow. The preprocessor macros can be used to describe program control flow in the source programming language for execution in the source computer program code. The preprocessor macros can also be used to generate control flow objects representing the control flow, which converts the source computer program code into a general language representation. The general language representation when executed is used to output computer programming code in specific programming languages representing the same logical code as that of the source computer program code.

The present invention relates to a process for preparing cyclic compounds having at least eight carbon atoms and at least one keto group, to the cyclic compounds obtained by this process and to the use thereof, in particular as fragrance or for providing a fragrance.

The invention describes new structures of the nucleotide conjugates (nuc-macromolecules) comprising at lease one nucleotide moiety coupled to at least one macromolecular compound via a short linker. These conjugates can be used as substrates for various kinds of polymerizing enzymes in the enzymatic synthesis of nucleic acids. In particular, these compounds can be used for labeling nucleic acids.

The present invention aims to simulate a response more similar to a actual machine while inhibiting load increase in analog operation. Program configuration of the present invention is a component of a simulation program for circuit design, which is executed by a computer. The computer includes an operation portion, a storage portion, a manipulation portion, and a display portion, so that the computer exerts a function of a circuit design simulator, and as a macro model of an operational amplifier for use in the circuit design simulator, enabling the computer to act by simulating a response of the operational amplifier on the circuit design simulator. The macro model of the operational amplifier includes a control portion (LMT1) for generating output exception in the event of input exception or power supply exception of the operational amplifier.

An improved polycondensation method for bio-based polyesters synthesized from pre-formed macromers and the corresponding compositions, which are useful for producing binder polymers for imaging applications such as emulsion-aggregation (EA) toner.

The present invention discloses metal (III) complex of a biuret-amide based macrocyclic ligand as green catalysts that exhibit both excellent reactivity for the activation of H2O2 and high stability at low pH and high ionic strength. The invention also provides macrocyclic biuret amide based ligand for designing of functional peroxidase mimics. Further, the present invention discloses synthesis of said metal (III) complex of a biuret-amide based macrocyclic ligand.

Disclosed is a spectrofluorimetrically detectable luminescent composition consisting essentially of at least one energy transfer acceptor lanthanide(III) complex having an emission spectrum maximum in the range from 300 to 2000 nanometers and a luminescence-enhancing amount of at least one energy transfer donor selected from the group consisting of a fluorophore, a lumiphore, an organic compound, a salt of an organic ion, a metal ion, a metal ion complex, or a combination thereof. Such energy transfer donor enhances the luminescence of at least one energy transfer acceptor lanthanide(III) complex, with the conditions that the emission spectrum of any energy transfer donor differs from that of its energy transfer acceptor lanthanide(III) complex; and such energy transfer donor can be dissolved to form a unitary solution in a solvent having an evaporation rate at least as great as that of water.

Methods and systems are provided for prioritizing carriers in femtocell frequency-hopping pilot beacons. A femtocell receives registration requests from a number of mobile devices requesting to hand off service from a macro-network carrier to the femtocell. The femtocell identifies the macro-network carrier that each mobile device has handed off from. The femtocell then uses that information to prioritize future broadcasts of its frequency-hopping pilot beacon on those macro-network carriers on which the most mobile devices have handed off from. The prioritization could take the form of broadcasting more often on the higher priority one or more carriers per cycle, or broadcasting for a longer continuous period of time on the higher priority one or more carriers per cycle.

The invention relates to a catalytic reactor including: at least one first architecture/microstructure including a ceramic and/or metal cellular architecture having a pore size of 2 to 80 ppi and a macroporosity of more than 85%, and a microstructure having a grain size of 100 nm to 5 microns, and skeleton densification of more than 95%, and a catalytic layer; and at least one second architecture/microstructure including a spherical or cylindrical architecture having a pore size of 0.1 to 100 μm and a macroporosity of less than 60%, and a microstructure having a grain size of 20 nm to 10 μm and a skeleton densification of 20% to 90%, and a catalytic layer; the first and second architecture/microstructure being stacked inside said reactor.

In a wireless network, plural downlink signals from plural base stations are transmitted to a terminal. The plural downlink signals all carry the same information to the terminal. The terminal provides feedback on the downlink channels. The feedback provides information on the taps of the channels. The amount of information fed back is constrained. Based on the feedback, transmission parameters of the downlink signals are adjusted. The process of transmitting, providing feedback, and adjusting the parameters continue so that the energy of the downlink signal is enhanced at the terminal location and suppressed elsewhere. Beam forming can be used to further suppress the energy signature at locations other than the terminal location.

The unpredictable resurgence of vinyl has rekindled an interest in physical sonic structures. Gilles Azzaro’s “Macrogroove” realises the idea of a three-dimensional sonogram. It is a 3D printed ‘audio coding’, which is played by a laser beam, scanning the form →

Looking for someone to write a VBA macro for Outlook involving searching for text within a table and deleting the table if that match is found within it; also detecting if it's being run a received message (as opposed to an open composition window) and, if so, triggering 'edit message' beforehand.

In 2017, a team from Northeastern University released Turnstile, a framework for implementing propositionally typed languages in Racket; cf. naasking's story Type Systems as Macros. The system was really nice because it allowed type systems to be expressed in a manner similar to the way theoretical PL researchers would in a paper, and because it hooked into Racket's clean compiler backend.

Now Stephen Chang, one of that team, together with new coauthors Michael Ballantyne, Usamilo Turner and William Bowman, have released a rewrite that they call Turnstile+, together with a POPL article, Dependent Type Systems as Macros. From that article's introduction:

Turnstile+ represents a major research leap over its predecessor. Specifically, we solve the major challenges necessary to implement dependent types and their accompanying DSLs and extensions (which Turnstile could not support), while retaining the original abilities of Turnstile. For example, one considerable obstacle was the separation between the macro expansion phase and a program’s runtime phase. Since dependently typed languages may evaluate expressions while type checking, checking dependent types with macros requires new macrology design patterns and abstractions for interleaving expansion, type checking, and evaluation. The following summarizes our key innovations.

• Turnstile+ demands a radically different API for implementing a language’s types. It must be straightforward yet expressive enough to represent a range of constructs from base types, to binding forms like Π-types, to datatype definition forms for indexed inductive type families.
• Turnstile+ includes an API for defining type-level computation, which we dub normalization by macro expansion. A programmer writes a reduction rule using syntax resembling familiar on-paper notation, and Turnstile+ generates a macro definition that performs the reduction during macro expansion. This allows easily implementing modular type-level evaluation.
• Turnstile+’s new type API adds a generic type operation interface, enabling modular implementation of features such as error messages, pattern matching, and resugaring. This is particularly important for implementing tools like tactic systems that inspect intermediate type-checking steps and construct partial terms.
• Turnstile+’s core type checking infrastructure requires an overhaul, specifically with first-class type environments, in order to accommodate features like dependent binding structures of the shape[x:τ]...,i.e., telescopes [de Bruijn 1991; McBride 2000].
• Relatedly, Turnstile+’s inference-rule syntax is extended so that operations over telescopes, or premises with references to telescopes, operate as folds instead of as maps

The code is available at https://github.com/stchang/macrotypes.

17 June 2019

Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled.

Saverio Cinti
Nov 1, 2005; 46:2347-2355
Research Articles

Systemic infection and proliferation of intracellular pathogens require the biogenesis of a growth-stimulating compartment. The gastrointestinal pathogen Salmonella enterica commonly forms highly dynamic and extensive tubular membrane compartments built from Salmonella-modified membranes (SMMs) in diverse host cells. Although the general mechanism involved in the formation of replication-permissive compartments of S. enterica is well researched, much less is known regarding specific adaptations to different host cell types. Using an affinity-based proteome approach, we explored the composition of SMMs in murine macrophages. The systematic characterization provides a broader landscape of host players to the maturation of Salmonella-containing compartments and reveals core host elements targeted by Salmonella in macrophages as well as epithelial cells. However, we also identified subtle host specific adaptations. Some of these observations, such as the differential involvement of the COPII system, Rab GTPases 2A, 8B, 11 and ER transport proteins Sec61 and Sec22B may explain cell line-dependent variations in the pathophysiology of Salmonella infections. In summary, our system-wide approach demonstrates a hitherto underappreciated impact of the host cell type in the formation of intracellular compartments by Salmonella.

Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled.

Rationale: Currently available imaging techniques have limited specificity for the detection of active myocardial inflammation. Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-N,N',N''-triacetic acid conjugated folate (¹⁸F-FOL) is a positron emission tomography (PET) tracer targeting folate receptor β (FR-β) that is expressed on activated macrophages at sites of inflammation. We evaluated ¹⁸F-FOL PET for the detection of myocardial inflammation in rats with autoimmune myocarditis and studied expression of FR-β in human cardiac sarcoidosis specimens. Methods: Myocarditis was induced by immunizing rats (n = 18) with porcine cardiac myosin in complete Freund’s adjuvant. Control rats (n = 6) were injected with Freund’s adjuvant alone. ¹⁸F-FOL was intravenously injected followed by imaging with a small animal PET/computed tomography (CT) scanner and autoradiography. Contrast-enhanced high-resolution CT or 2-deoxy-2-¹⁸F-fluoro-D-glucose (¹⁸F-FDG) PET images were used for co-registration. Rat tissue sections and myocardial autopsy samples of 6 patients with cardiac sarcoidosis were studied for macrophages and FR-β. Results: The myocardium of 10 out of 18 immunized rats showed focal macrophage-rich inflammatory lesions with FR-β expression occurring mainly in M1-polarized macrophages. PET images showed focal myocardial ¹⁸F-FOL uptake co-localizing with inflammatory lesions (SUVmean, 2.1 ± 1.1), whereas uptake in the remote myocardium of immunized rats and controls was low (SUVmean, 0.4 ± 0.2 and 0.4 ± 0.1, respectively; P < 0.01). Ex vivo autoradiography of tissue sections confirmed uptake of ¹⁸F-FOL in myocardial inflammatory lesions. Uptake of ¹⁸F-FOL to inflamed myocardium was efficiently blocked by a non-labeled FR-β ligand folate glucosamine in vivo. The myocardium of patients with cardiac sarcoidosis showed many FR-β-positive macrophages in inflammatory lesions. Conclusion: In a rat model of autoimmune myocarditis, ¹⁸F-FOL shows specific uptake in inflamed myocardium containing macrophages expressing FR-β, which were also present in human cardiac sarcoid lesions. Imaging of FR-β expression is a potential approach for the detection of active myocardial inflammation.

Systemic infection and proliferation of intracellular pathogens require the biogenesis of a growth-stimulating compartment. The gastrointestinal pathogen Salmonella enterica commonly forms highly dynamic and extensive tubular membrane compartments built from Salmonella-modified membranes (SMMs) in diverse host cells. Although the general mechanism involved in the formation of replication-permissive compartments of S. enterica is well researched, much less is known regarding specific adaptations to different host cell types. Using an affinity-based proteome approach, we explored the composition of SMMs in murine macrophages. The systematic characterization provides a broader landscape of host players to the maturation of Salmonella-containing compartments and reveals core host elements targeted by Salmonella in macrophages as well as epithelial cells. However, we also identified subtle host specific adaptations. Some of these observations, such as the differential involvement of the COPII system, Rab GTPases 2A, 8B, 11 and ER transport proteins Sec61 and Sec22B may explain cell line-dependent variations in the pathophysiology of Salmonella infections. In summary, our system-wide approach demonstrates a hitherto underappreciated impact of the host cell type in the formation of intracellular compartments by Salmonella.

17 June 2019

Phospholipases A₂ (PLA₂s) catalyze hydrolysis of the sn-2 substituent from glycerophospholipids to yield a free fatty acid (i.e., arachidonic acid), which can be metabolized to pro- or anti-inflammatory eicosanoids. Macrophages modulate inflammatory responses and are affected by Ca²⁺-independent phospholipase A₂ (PLA₂)β (iPLA₂β). Here, we assessed the link between iPLA₂β-derived lipids (iDLs) and macrophage polarization. Macrophages from WT and KO (iPLA₂β–/–) mice were classically M1 pro-inflammatory phenotype activated or alternatively M2 anti-inflammatory phenotype activated, and eicosanoid production was determined by ultra-performance LC ESI-MS/MS. As a genotypic control, we performed similar analyses on macrophages from RIP.iPLA₂β.Tg mice with selective iPLA₂β overexpression in β-cells. Compared with WT, generation of select pro-inflammatory prostaglandins (PGs) was lower in iPLA₂β^–/–, and that of a specialized pro-resolving lipid mediator (SPM), resolvin D2, was higher; both changes are consistent with the M2 phenotype. Conversely, macrophages from RIP.iPLA₂β.Tg mice exhibited an opposite landscape, one associated with the M1 phenotype: namely, increased production of pro-inflammatory eicosanoids (6-keto PGF₁α, PGE₂, leukotriene B₄) and decreased ability to generate resolvin D2. These changes were not linked with secretory PLA₂ or cytosolic PLA₂α or with leakage of the transgene. Thus, we report previously unidentified links between select iPLA₂β-derived eicosanoids, an SPM, and macrophage polarization. Importantly, our findings reveal for the first time that β-cell iPLA₂β-derived signaling can predispose macrophage responses. These findings suggest that iDLs play critical roles in macrophage polarization, and we posit that they could be targeted therapeutically to counter inflammation-based disorders.

Pyruvate kinase M2 (PKM2) links metabolic and inflammatory dysfunction in atherosclerotic coronary artery disease; however, its role in oxidized LDL (Ox-LDL)-induced macrophage foam cell formation and inflammation is unknown and therefore was studied. In recombinant mouse granulocyte-macrophage colony-stimulating factor-differentiated murine bone marrow-derived macrophages, early (1–6 h) Ox-LDL treatment induced PKM2 tyrosine 105 phosphorylation and promotes its nuclear localization. PKM2 regulates aerobic glycolysis and inflammation because PKM2 shRNA or Shikonin abrogated Ox-LDL-induced hypoxia-inducible factor-1α target genes lactate dehydrogenase, glucose transporter member 1, interleukin 1β (IL-1β) mRNA expression, lactate, and secretory IL-1β production. PKM2 inhibition significantly increased Ox-LDL-induced ABCA1 and ABCG1 protein expression and NBD-cholesterol efflux to apoA1 and HDL. PKM2 shRNA significantly inhibited Ox-LDL-induced CD36, FASN protein expression, DiI-Ox-LDL binding and uptake, and cellular total cholesterol, free cholesterol, and cholesteryl ester content. Therefore, PKM2 regulates lipid uptake and efflux. DASA-58, a PKM2 activator, downregulated LXR-α, ABCA1, and ABCG1, and augmented FASN and CD36 protein expression. Peritoneal macrophages showed similar results. Ox-LDL induced PKM2- SREBP-1 interaction and FASN expression in a PKM2-dependent manner. Therefore, this study suggests a role for PKM2 in Ox-LDL-induced aerobic glycolysis, inflammation, and macrophage foam cell formation.

Endocrine cells of the pancreatic islet interact with their microenvironment to maintain tissue homeostasis. Communication with local macrophages is particularly important in this context, but the homeostatic functions of human islet macrophages are not known. Here we show that the human islet contains macrophages in perivascular regions that are the main local source of the anti-inflammatory cytokine Il-10 and the metalloproteinase MMP9. Macrophage production and secretion of these homeostatic factors is controlled by endogenous purinergic signals. In obese and diabetic states, macrophage expression of purinergic receptors, MMP9, and Il-10 is reduced. We propose that in those states exacerbated beta cell activity due to increased insulin demand and increased cell death produces high levels of ATP that downregulate purinergic receptor expression. Loss of ATP sensing in macrophages may reduce their secretory capacity.

Mobilization of hematopoietic stem/progenitor cells (HSPCs) from the bone marrow (BM) is impaired in diabetes. Excess oncostatin M (OSM) produced by M1 macrophages in the diabetic BM signals through p66Shc to induce Cxcl12 in stromal cells and retain HSPCs. BM adipocytes are another source of CXCL12 that blunts mobilization. We tested a strategy of pharmacologic macrophage reprogramming to rescue HSPC mobilization. In vitro, PPAR- activation with pioglitazone switched macrophages from M1 to M2, reduced Osm expression, and prevented transcellular induction of Cxcl12. In diabetic mice, pioglitazone treatment downregulated Osm, p66Shc and Cxcl12 in the hematopoietic BM, restored the effects of granulocyte-colony stimulation factor (G-CSF), and partially rescued HSPC mobilization, but it increased BM adipocytes. Osm deletion recapitulated the effects of pioglitazone on adipogenesis, which was p66Shc-independent, and double knockout of Osm and p66Shc completely rescued HSPC mobilization. In the absence of OSM, BM adipocytes produced less CXCL12, being arguably devoid of HSPC-retaining activity, whereas pioglitazone failed to downregulate Cxcl12 in BM adipocytes. In diabetic patients under pioglitazone therapy, HSPC mobilization after G-CSF was partially rescued. In summary, pioglitazone reprogrammed BM macrophages and suppressed OSM signaling, but sustained Cxcl12 expression by BM adipocytes could limit full recovery of HSPC mobilization.

Andrew S. Kimball
Sep 1, 2017; 66:2459-2471
Immunology and Transplantation

Michael J. Fowler
Apr 1, 2008; 26:77-82
Diabetes Foundation

Ronald Klein
Feb 1, 1995; 18:258-268
Kelly West Lecture 1994

OBJECTIVE

This study aims to evaluate the association of energy and macronutrient intake at dinner versus breakfast with disease-specific and all-cause mortality in people with diabetes.

OBJECTIVE

To evaluate whether high glucose levels in the normoglycemic range and higher have a causal genetic effect on risk of retinopathy, neuropathy, nephropathy, chronic kidney disease (CKD), peripheral arterial disease (PAD), and myocardial infarction (MI; positive control) in the general population.

Michael J. Fowler
Apr 1, 2008; 26:77-82
Diabetes Foundation

Spanish translation of "Pillar 3 disclosure requirements - updated framework", December 2018

BIS Bulletin No 7, April 2020. Past epidemics had long-lasting effects on economies through illness and the loss of lives, while Covid-19 is marked by widespread containment measures and relatively lower fatalities among young people. The short-term costs of Covid-19 will probably dwarf those of past epidemics, due to the unprecedented and synchronised global sudden stop in economic activity induced by containment measures. The current estimated impact on global GDP growth for 2020 is around -4%, with substantial downside risks if containment policies are prolonged. Output losses are larger for major economies.