text:
biopolyverse
A general molecular and cellular biology site
Bioorthogonal Chemistry and Recognition
tags: Molecular Recognition, Orthogonality
This post further extends some themes raised in previous posts, concerning xenorecognition and its corresponding biological repertoires in relation to bioorthogonality (first noted in the context of the possibility of 'weird life' in a shadow biosphere on Earth, and further considered later in the context of the recognition of xenobiotics). Previously, the concept of true biological orthogonality was posed as a hypothetical state of complete 'invisibility' of a chemical entity and a biological system with respect to each other. Here, we are concerned with an artificial application of growing importance, where orthogonality refers to the specificity of chemical reactions of interest. This particular topic, noted briefly in earlier posts (see 30 May 2012), is thus further developed as the theme of this post. At the same time, it should be noted that it is not the intention to provide extensive chemical detail, for which many excellent sources are already available. Primarily, this post provides an overview with some additional views which are relevant to xenobiotic molecular recognition and the general concept of orthogonality in biology. .
Chemistry and Life
Curious parallels and contrasts can be made between the modern concept of chemical bioorthogonality and non-scientific (pre-molecular) notions regarding the nature of life. In early times it seemed self-evident that living things were so fundamentally different from non-living matter that life must be constituted of radically different stuff, whatever that might be. This supposition was frequently interlinked with the doctrine of vitalism, or the need for a 'vital spark' to animate anything that can be called 'alive'. Nevertheless, the old belief in the 'otherness' of life would result in 'bioorthogonality' (in a literal sense) following on as a natural corollary. This statement carries the assumption that the supposed living stuff would not only be distinct from non-living matter, but also would remain aloof from it. By this reasoning, any conventional inorganic reaction (insofar as they were known in earlier times) would fail to impact on a living organism.
But this viewpoint could be shot down very rapidly even in the earliest of times, with just a little thought. A great many natural substances can burn, damage or kill a living organism, ranging from acids and alkalis to toxic metals. For example, natural deposits of arsenic or mercury ores could easily be prepared and administered as poisons – the point being that such deadly agents come from the non-living world, irrespective of their chemical natures. Therefore, the lifeless material world can obviously impact dramatically on 'life-stuff', and 'extreme bioorthogonality' (the belief in the complete independence of life from non-living matter) could never have been a tenable proposition. (This might seem obvious as well from the need take in water and air, but these facts might be more easily rationalized away than the dramatic action of inorganic poisons).
But having conceded this, to many early thinkers it still seemed 'obvious' that living things, though influenced by the non-living world, could not be made of the same stuff. It was well known from observing the effects of combustion that carbon was present in anything alive, and as a primordial discipline of chemistry gradually emerged from nonscientific alchemy, it became clear that many pure materials could be obtained from specific living sources. These were accordingly viewed as 'organic' in the literal sense, but such products were held to be special by virtue of their origins within things that (at least before their demise) possessed the mysterious property of life. Clearly it was possible to influence a living organism with the products of another. Any number of natural medicines or poisons from (mainly) plants and (less commonly) animals could easily make this point. Yet a pre-modern 'bio-philosopher' could simply claim that all such products were made by life, and thus possessed the enigmatic 'organic' quality which set them apart from everything else. True, the above-noted action of many never-living materials proved that inorganic matter could modulate life, but apparently in a crude and battering-ram sort of way.
This mental picture of organic material as partitioned from everything else received its first major challenge when the German chemist Friedrich Wöhler prepared urea in the laboratory in 1828, without any recourse to the urine of animals. (Urea, of course, derives its name from the excretory source from which it was first isolated, and it therefore stood as a classic organic substance 'impossible' to synthesize, at least until Wöhler showed otherwise). Since that time, the science of organic chemistry has seen a series of increasingly intricate synthetic triumphs, where all manner of complex natural compounds have yielded to the ingenuity of synthetic chemists. Obviously, all notions of the 'special' nature of organic compounds and their dependence on a 'life-force' have long since been consigned to the proverbial trash-can of history. We retain, though, an echo of this through the retention of the word 'organic' in reference to covalent carbon compounds in general, whether or not they derive from living biosystems.
The demolition of the special status of the chemistry of life, and its integration with chemistry in general, might seem at first glance to remove the possibility of 'orthogonality' from biology. If life is, in essence, nothing more than souped-up chemistry, how could it stand aside in any aspect from general chemical reactivity? Would not the incredible complexity of living organisms demand an equally complex repertoire of chemical reactions? And if the latter was true, would not virtually any chemical reaction engineered by humans already have its biological counterpart? Clearly, were that to be the case, then the concept of a 'bioorthogonal' chemical reaction would be illusory, since any reaction component would be able to find a biological target with which to react. Nevertheless, this supposition is emphatically not the case at all; it is demonstrably incorrect.
It is undeniable and obvious fact that life is a phenomenon of consummate complexity (often described as the most complex known system in the universe, with the emergence of intelligence at its apex). Yet while an enormous number of distinct chemical transactions exist across the biosphere, the vast majority of these are catalyzed by protein enzymes composed of a relatively small 'alphabet' of amino acids (usually the canonical 20) linked together by peptide bonds in highly specific sequences. Many such reactions have an absolute requirement for additional cofactors as well as the relevant protein enzymes, in the way of metal ions, small organic compounds (vitamins) or metal-sulfur clusters. Even so, a 'take home message' from biology is that incredible complexity can emerge from combinations and permutations of a relatively small set of building blocks.
A corollary of this biological insight is that it should not be surprising to find that there are many precedents for chemical reactions which have no known biological parallels, although an important caveat here is the need to add the qualifier "under normal physiological conditions". It is obvious that chemistry only operating under conditions of temperature and pressure far removed from those tolerated by life cannot be applicable within living systems. Nevertheless, even after this restriction is enforced, chemical candidates for non-biological reaction status still remain. A pair of such interacting chemical groups could thus potentially 'only have eyes for each other', in a metaphorical sense, as long as they did not react with the plethora of functional groups commonly encountered in biological systems. This notion is shown schematically in the Figure below:
Figure 1: Depiction of a bioorthogonal reaction pair, in the presence of examples of common biological functional groups (not exhaustive), which do not interact with the participating non-biological groups. Geometric shapes represent any biological molecules to which the bioorthogonal groups have been appended in vitro, prior to introduction to the intracellular environment.
Many applications of bioorthogonal reactions have been envisaged, such as specific labeling of biocomponents and tracing of the intracellular traffic of specific molecules. But for such systems to work in practice, bioorthogonality of the reactions is necessary but not sufficient: the reactions must also be highly efficient under intracellular conditions. The required reaction properties of high yield and product specificity are satisfied by a class of reactions termed 'click chemistry', envisaged as 'spring loaded' to rapidly and efficiently proceed down a specific reaction pathway. Some such reactions require catalysis to operate under normal ambient conditions, but this need can be obviated within certain molecular arrangements. A classic case of this is the reaction between alkynes (bearing a carbon-carbon triple bond) and the dipolar azide group. While this reaction involving a linear alkyne group requires a cuprous ion (Cu[1]) catalyst to work well at normal temperatures and pressures, if the triple bond is placed under strain within a cyclic structure (an eight-membered cyclooctyne ring) then the reaction is greatly accelerated. These observations are presented in the following Figure:
Figure 2: Alkyne-azide bioorthogonal reaction pairs, for (A) both linear-alkynes (Cu[1]-catalyzed) or (B) strained-alkyne octyl ring (uncatalyzed).
But the rate at which any intermolecular chemical reactions proceed is necessarily driven by the respective concentrations of reactants. Within the intracellular environment, the total concentration of solutes (all macromolecules and small molecules included) is very high, and at relatively low concentrations, even highly self-reactive and bioorthogonal groups may have slow kinetics of interaction. A useful approach which solves this issue is to engineer the reaction process such that a pair of bioorthogonal participants are brought into close spatial proximities with respect to each other, as a direct consequence of the targeting strategy. This is illustrated in the Figure below:
Figure 3: Bioorthogonal click reaction engendered through spatial proximity produced through the targeting choice. Two related proteins (1 and 2) are depicted with two proximal sites (in principal, either for natural ligands, or sites for which artificial ligands can be designed). If two such ligands equipped with mutually interactive bioorthogonal click groups are introduced into the intracellular environment, then only Protein 1 can bind the correct pair such that desired labeling product is formed.
Spatial proximity for promotion of specific reactions can be engineered in other ways, most notably via nucleic acid templating, a very large field beyond the scope of this post. But having given this very brief taste of how bioorthogonal reactions are practically engineered, let us move on to some general issues of the nature of chemical bioorthogonality.
Chemically Possible Bio-reactions
Chemical reactions that are ascribed as bioorthogonal could in principle be compromised in two broad ways: by the discovery of biocatalysts capable of accelerating the reaction between the 'orthogonal' pair of chemical groups, or capable of promoting reactivity between either (or both) of the foreign functional groups and one or more host molecules. Either possibility would require recognition by an enzyme of at least one of the 'foreign' functional groups.
Here it is appropriate to reiterate a point noted in a previous post, to the effect that orthogonality in biological systems is a relative concept. This referred to the observation that while a xenobiotic compound might be completely orthogonal within an isolated biological system, that status certainly is not necessarily the case within the biosphere as a whole. With respect to the potential biorthogonality of chemical reactions, a particular contrast can be drawn between the relatively limited repertoire of most eukaryotes in comparison with the astonishing catalytic diversity of the prokaryotic world. A good example of this is the observation that the complex core structure of Vitamin B12, an essential nutritional cofactor for many (although not all) multicellular eukaryotes, is made solely by prokaryotes.
If a pair of inter-reacting functional groups attained 'pan-biospheric bioorthogonality', then all known biological systems would necessarily lack this kind of chemical functionality. But the absence of a reaction from biology certainly does not mean that it could never exist. A case in point also noted in the same previous post has been the apparent extremely rapid evolution of the bacterial enzyme phosphotriesterase. In fact, such apparent large jumps in an imaginary 'catalytic space' are not necessarily difficult in terms of the parallel evolutionary moves within protein sequences. A recent demonstration of this comes from the artificial adaptation of a specific cytochrome P450 enzyme (one of a large class involved with xenobiotic recognition and modification) from its normal catalytic transfer mechanism into one involving a hitherto non-biological process. The adapted cytochromes in this case were selected from a relatively small set of artificial enzyme variants.
Another useful precedent is that of the catalysis of the Diels-Alder reaction, a chemical cycloaddition of great importance in synthetic chemistry. By rational design and directed evolutionary approaches, both protein enzymes (catalytic antibodies) and ribozymes have been derived which are capable of catalyzing this reaction, albeit not with very high efficiency. Yet although there is suggestive evidence from certain biosynthetic pathways, there is as at present no definitive evidence that a natural precedent exists for this particular catalytic activity. While this is a significant evolutionary question, the artificial generation of the specific catalytic activity in diverse macromolecular frameworks already shows its inherent biological feasibility.
So, with these precedents in mind, the assignation of a reaction process as 'bioorthogonal' should always be defined with specific limits of space and time. Spatially, in the sense that the orthogonality of a reactive pair can be assigned for a specific cell type, whole organism, phylogenetic group, or even the entire existing biosphere ('pan-bioorthogonality' once more). Temporally, in the sense that a 'hole' in biological rendition of a chemical reaction may be plugged through evolution (either natural or artificial), where the required time can be surprisingly short in at least some instances. Of course, the evolution of other challenges might require more fundamental protein adaptation. A specific example can be found from the above Figure 2A (showing the Cu(1) catalyzed linear alkyne-azide cycloaddition reaction), if an enzyme evolved which could accomplish both catalysis (possibly via a copper ion itself bound near the reactive site, or through some other cofactor) and engendering spatial proximity (through binding of reactants within an active-site pocket). This is portrayed below:
Figure 4: Schematic depiction of a hypothetical protein catalyst for an alkyne-azide cycloaddition reaction.
In fact, the alkyne ('acetylenic') triple bond is not at all absent from biological systems, being found in metabolic products of diverse organisms, ranging from prokaryotes to plants and certain animal lineages. Organic azides, on the other hand, are believed to be totally absent from known biosystems. Thus, although the hypothetical catalysis of Fig. 4 might be artificially engineered, in the absence of biological azides, its prospects for arising naturally would be remote. So any theoretical threat to the bioorthogonality of such reactions as a pair is most unlikely to be realized by natural agency. In principle, though, if organic azides were artificially introduced into specific cells synthesizing certain natural products bearing strained acetylenic bonds in ring structures (members of the enediyne natural product family), then an azide-associated reaction with the enediyne product could occur. In such circumstances, the resulting cycloaddition reaction, deriving from a natural host product and a non-biological reactant, would lack complete orthogonality.
Levels of Orthogonality
It should be kept in mind that the above considerations regarding bioorthogonality are at the level of chemical reactions, which is a distinct concept from biorthogonality at the level of molecular recognition of initial reactive groups or the products by xenobiotic recognition systems. Certainly these two categories have regions of overlap, as when a natural enzyme must bind (show molecular recognition for) a substrate as well as enact a catalytic change upon it. But binding per se is not necessarily linked with catalysis, as demonstrated by a vast array of ligand / receptor interactions, as well as antibodies and their cognate antigens. It was in fact noted in a previous post that the physiological action of some xenobiotics arises from non-covalent interactions with normal host receptors, with concomitant aberrant signaling induction.
Nevertheless, in terms of recognition of xenobiotics by natural defense mechanisms, binding and catalysis are usually linked, since catalytic modification of foreign compounds is an important part of detoxification processes (as discussed in another previous post. In any case, if we return to the example of Fig. 2, then assignment of the reaction as essentially bioorthogonal is acknowledged (with the above caveat of rare possible acetylenic host product interactions). Yet orthogonality may not necessarily exist at the level of recognition of either the reactants or the product(s) in terms of xenobiotic recognition, even in the same host organism. And at both reactant and product levels, recognition precedents exist for the components within Fig. 2.
In some organisms, alkyne groups are produced and recognized through biosynthetic machinery, as noted above for metabolites such as the enediynes. But more generally, substituted alkynes are clearly interactive with specific cytochrome P450 enzymes (important for xenobiotic processing, also noted above). In fact, certain compounds with carbon-carbon triple bonds have been well-characterized as P450 inhibitors, through the formation of covalent adducts. The action of a P450 enzyme on a simple substituted alkyne, propargyl alcohol, has been found to be responsible for converting it into the toxic propiolaldehyde, another example of the self-activation of a deleterious effect of a xenobiotic (this general phenomenon was discussed by way of an analogy to autoimmunity in a previous post).
While the azide functional group appears to be absent from biology, it can certainly have profound physiological consequences when artificially introduced as a moiety in certain molecular contexts. Probably the best-known example of this is the compound AZT (3'-azido-3'deoxythymidine), formerly used as a mainstay of treatment for HIV patients, although now superseded by more effective drugs. A major limitation of AZT was its tendency to produce often serious side-effects in certain patients. While 'off-target' activities are a bane to patients and clinicians, for the present purposes they help make the point that azido-compounds are far from orthogonal when introduced into complex (human) biosystems. Side-effects do not arise randomly; they result from unwanted interactions of drugs with otherwise-irrelevant specific host structures. Such interactions themselves surely provide a back-up demonstration of 'non-bioorthogonality' at the level of molecular recognition.
In addition, AZT is known to be recognized and metabolized by P450 enzymes. The final component of the reactions of Fig. 2, the 1,2,3-triazole group, is likewise recognized in a variety of biological contexts, including P450 enzymes as well. The 1.2.3-triazole isomer is also a central moiety of a variety of drug candidates for a wide range of potential targets.
All of these pieces of information are proffered as evidence that each functional group involved as reactants or products in a well-known bioorthogonal reaction are not at all orthogonal at the level of molecular recognition within an entire complex multicellular organism (where xenobiotic processing enzymes are expressed), as opposed to an isolated single cellular system. But the mutual interaction of bioorthogonal chemical components (such as azides and alkyne groups) and their avoidance of interaction with host functional groups in the vast majority of cases classifies the chemical reaction itself as bioorthogonal in almost all useful contexts.
The correlation of reactivity per se and orthogonality was considered in a previous post, where the remarkable fact was noted that highly unreactive compounds (such as saturated fluorocarbons) and even inert gases cannot be considered to be bioorthogonal, through their potent effects in inducing anesthesia. Therefore, even the complete preclusion of possible covalent bond formation does not necessarily exclude a chemical agent from the capability of strongly perturbing a biological system, the complete antithesis of a generalized notion of bioorthogonality. At the level of designing bioorthogonal chemical reactions, on the other hand, covalent bond formation is of central and defining importance. And new bioorthogonal reactions are being actively sought and found.
To finish up, a biopoly(verse) comment on an ideal biorthogonal reactive situation:
Make a molecule to enter a cell
Yet trigger no metaphorical bell
(Meaning bio-inert –
And thus causing no hurt)
While reacting with designed targets well.
References & Details
(In order of citation, giving some key references where appropriate, but not an exhaustive coverage of the literature).
'…….it is not the intention to provide extensive chemical detail, for which many excellent sources are already available.' Some reviews from the lab of a major pioneer of bioorthogonal chemistry (and related areas of click chemistry), Carolyn Bertozzi, are very useful. See Sletten & Bertozzi 2009; Jewett & Bertozzi 2010. For another good recent review, see Best 2009.
'…..Friedrich Wöhler prepared urea in the laboratory in 1828…..' This occurred serendipitously while he was attempting to make ammonium cyanate (the ammonium salt of cyanic acid), which can undergo a conversion rearrangement from an ionic salt to a simple covalent organic compound:
A good source of further information is the relevant site from the Chemical Heritage Foundation. Here, a quote from Wöhler states," the ammonium salt of cyanic acid is urea". Of course, this is not literally correct as such, since the compounds have the same atomic compositions but very distinct structures and bonding states. But this discovery helped to frame the concept of chemical isomers, as coined by the Swedish chemist Berzelius, a contemporary of Wöhler.
'………chemistry only operating under conditions of temperature and pressure far removed from those tolerated by life cannot be applicable within living systems.' An example of this with a biological reply is the artificial Haber process for the reaction of atmospheric nitrogen with hydrogen to form ammonia, which requires both catalysts and high temperatures. But natural evolution has found a way to 'fix' nitrogen using specific enzymes (nitrogenases) and essential metal (typically iron and molybdenum, but sometimes vanadium) – sulfur clusters (See Hu and Ribbe 2011 for a recent review). For details on the Haber process itself, see Modak 2002.
'………a class of reactions termed 'click chemistry'…..' For reviews on this topic, See Kolb et al. 2001; Best 2009.
'……if the triple bond is placed under strain within a cyclic structure (an eight-membered cyclooctyne ring)……' The smaller the ring group, the more strain that is placed on the normally linear alkyne bond, and in fact an eight-membered ring is the smallest that is stable while retaining a carbon-carbon triple bond under normal conditions.
' Spatial proximity for promotion of specific reactions can be engineered in other ways, most notably via nucleic acid templating…..' For a review, see Li & Liu 2004.
'……the complex core structure of Vitamin B12, an essential nutritional cofactor for many (although not all) multicellular eukaryotes, is made solely by prokaryotes.' And this also demonstrates but one aspect of the dependence of 'higher' multicellular organisms upon the activities of prokaryotes. For details on Vitamin B12 biosynthesis, see Martens et al. 2002.
'…..the artificial adaptation of a specific cytochrome P450 enzyme ………. from its normal catalytic transfer mechanism into one involving a hitherto non-biological process.' For the recent paper, see Coelho et al. 2013. Their work resulted in the normal oxene transfer (equivalent of atomic oxygen) mechanism of the P450 enzyme of interest converted into an isoelectronic (but non-biological) carbene (equivalent to a substituted methylene) transfer.
'…….the Diels-Alder reaction a chemical cycloaddition reaction of great importance…..' The eponymous title of this reaction (named for the two German chemists who originated it) has also lent itself towards the naming of the insecticides Dieldrin and Aldrin. '…..both protein enzymes (catalytic antibodies) and ribozymes have been derived which are capable of catalyzing this [Diels-Alder] reaction.' For catalytic antibody Diels-Alderase, see Heine et al. 1998; for an example of ribozyme Diels-Alderase work see Agresti et al. 2005. '…..there is at present no definitive evidence that a natural precedent exists for this particular catalytic activity [Diels-Alderases]….' See Kim et al. 2012.
'……alkyne ('acetylenic') triple bond is not at all absent from biological systems, being found in metabolic products of diverse organisms……' A note on terminology: strictly speaking, an 'alkyne' would only refer to a hydrocarbon containing at least one carbon-carbon triple bond. Here it denotes substituted alkynes, where one or both of the hydrogen atoms of an acetylene (C2H2) are replaced by other chemical groups, which could be as large as a protein molecule, or which could join cyclicly to form ring structures. Triple-bonded carbons within larger molecules are also often referred as 'acetylenic' after the prototypical alkyne molecule. For a good review of natural molecules containing such alkyne groups, see Minto & Blacklock 2008.
' Organic azides, on the hand, are believed to be totally absent from known biosystems.' See Sletten & Bertozzi 2009.
'……….if organic azides were artificially introduced into specific cells synthesizing certain natural products ….. (members of the enediyne natural product family), then an azide-associated reaction with the enediyne product could occur.' The natural enediynes have 9- or 10-membered ring structures, less strained then cyclooctynes (as in Fig. 2 above), but still significantly strained relative to a linear alkyne. See Kim at al. 1993 for the structure of an enediyne antibiotic when complexed with its specific carrier protein.
'……….. the resulting cycloaddition reaction, deriving from a natural host product and a non-biological reactant, would lack complete orthogonality.' This hypothetical example is another illustration of how bioorthogonality may exist within a specific closed and defined biosystem, but not necessarily for the biosphere as a whole.
'……alkyne groups are recognized through biosynthetic machinery……' See Van Lanen & Shen 2008.
'……certain compounds with carbon-carbon triple bonds have been well-characterized as P450 inhibitors….' See Lin et al. 2011.
'…..the best-known example of this is the compound AZT (3'-azido-3'deoxythymidine)…..' AZT is a nucleoside analog, in common with numerous other antiviral compounds, aimed at impeding the function of virally-encoded polymerases.
'…..limitation of AZT was its tendency to produce often serious side-effects…..' One such side-target of AZT is human mitochondrial RNA polymerase II; see Arnold et al. 2012.
'…..1,2,3-triazole group, is likewise recognized in a variety of biological contexts, including P450 enzymes….' See Conner et al. 2012.
'……1.2.3-triazole isomer is also a central moiety of a variety of drug candidates……' For example, See Röhrig et al. 2012 (a dioxygenase target in cancer contexts), Manohar et al. 2011 (malaria), and Jordão et al. 2009; Jordão et al. 2011 (antiviral).
'…….new bioorthogonal reactions are being actively sought and found.' As an example, see Sletten and Bertozzi 2011.
Next post: April.
from → Bioorthogonality, Molecular Discovery
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1953 – A Real 'Annus Mirabilis' →
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Incredible points. Great arguments. Keep up the great morale.
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Pomegranate raita is a flavourful raita filled with the crunchiness of pomegranate kernels.
In a mixing bowl whisk thick curds, add pomegranate kernels, black salt, roasted cumin powder,salt and sugar and mix well.
Mix well, check the flavour of raita and transfer to a serving bowl. Garnish with pomegranate kernels , mint leaves and serve chilled with pulav, biryanis etc.
Add finely chopped fresh mint leaves just before serving because mint leaves turn black and also lose their flavour if chopped in advance.
Always use fresh curds to prepare raita.


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Geltor Announces Series A Funding from Cultivian Sandbox Ventures
October 25, 2018 07:30 ET | Source: Geltor
Bio-design company launches its Designer Collagen business globally for the beauty, nutraceutical, and food and beverage industries
SAN LEANDRO, Calif. , Oct. 25, 2018 (GLOBE NEWSWIRE) -- Geltor, the bio-design company behind Designer Collagen, today announced $18.2 million in Series A financing, led by Cultivian Sandbox Ventures. The round includes investment from GELITA, the leading global supplier of collagen proteins, and ADM Ventures, the venture investing arm of global food and feed ingredient provider, Archer Daniels Midland Company – alongside investment from Cavallo Ventures and Box Group.
The consumer product industry is at an inflection point where the demand for collagen is surging, as is the consideration for what consumers are putting on their skin and in their bodies. Many people don't realize that the collagen found in consumer products today is sourced from the skin and bones of livestock, raising ethical concerns from consumers and contributing to the growing threat of climate change.
Geltor has developed a proprietary bio-design platform where high-value proteins can be produced on a global scale. By combining biology, protein optimization, and fermentation, the company is able to produce naturally occurring and previously untapped types of collagen – precisely targeting the ideal protein type, rather than sourcing it from the low-grade availability of animal waste. This process also gives Geltor's products an advantage over other commercially available animal proteins, since they're bio-designed for strength, firmness, and flexibility for optimum performance in consumer products.
"The industry standard for proteins right now is to use factory-farm waste to mimic the process our bodies make naturally. This method works at a base level, but it's harmful to animals, the environment, and it doesn't leverage the true power or benefits of collagen," said CEO of Geltor, Alexander Lorestani. "Geltor's Designer Collagens deliver better functionality for consumers, a robust supply chain for businesses, and a sustainable alternative for our planet. They're proteins we can be proud of, and I'm so excited to see the world's biggest consumer companies choosing Geltor as their sustainable protein partner."
The company's flagship consumer product, N-Collage, is a bio-designed, clinically-tested collagen that delivers superior cellular regeneration, protection and derma-collagen synthesis. It's the first-ever 100 percent vegan collagen technology engineered for unparalleled skincare performance, is Certified Halal, and the winner of the 2018 CEW Beauty "Innovation of the Year" award.
"At Cultivian Sandbox, we focus on identifying companies reinventing the food and agriculture industry with technology, and Geltor is doing just that," said Dan Phillips, Managing Director at Cultivian Sandbox Ventures. "With a team of experienced and passionate PhD scientists behind it, and a unique, science-first approach, the company is pioneering a new industry standard for protein creation and we're excited to be their partner on this journey."
This latest funding round will allow the company to continue its mission of creating new, category-defining ingredients, expanding its product offering of 100 percent animal and GMO-free proteins. It also takes the company's raised funding to $23 million to date. For more information, visit www.geltor.com.
About Geltor
Geltor is a bio-design company creating high-value designer proteins, starting with collagen. Its proteins are 100 percent animal-and GMO-free, and are cultivated using a sustainable fermentation process. Geltor's Designer Collagen products provide unprecedented functionality and benefits for consumers, while producing less waste and consuming fewer natural resources than the current process sourced from animal waste. Geltor was founded in 2015 by Alexander Lorestani and Nick Ouzounov and is based in San Leandro, Calif. For more information, visit www.geltor.com.
Meredith Klee for Geltor
geltor@highwirepr.com
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If you're a Photoshop Elements user, you may appreciate these free tutorials. If you're thinking about purchasing the graphics editing software, Adobe is currently offering $40 USD off in rebates, which brings the cost down to $59.99 USD for Photoshop Elements version 9.
As always, Photoshop tutorials for making minis are still accessible on my blog. The link "Photoshop Tutorial" is permanently located below the header.
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HMS Frolic (1872)
Name Frolic (1872) Explanation
Type Gunvessel
Launched 29 February 1872
Hull Composite
Propulsion Screw
Builders measure 462 tons
Displacement 610 tons
Guns 4
Class Frolic
Note 1888 drillship.
1893 = WV.30, Coastguard.
1897 = WV.41
- 20 April 1876 Commanded (from commissioning at Sheerness) by Commander Claude Edward Buckle, China
- 30 December 1878 Commanded (from commissioning at Honk Kong) by Commander Arthur Edward Dupuis, China
- 7 August 1880 Commanded (until paying off at Chatham) by Commander Stuart Hamilton Rickman, China
- 19 May 1884 Commanded (from commissioning at Sheerness) by Commander Arthur William Moore, West coast of Africa
- 11 May 1887 Commanded (until paying off at Sheerness) by Commander Alfred Arthur Chase Parr, West coast of Africa, then (December 1885) south-east coast of America, relieving Algerine
28 June 1887 Condemned as unfil for further service whllst being brought forward for service on the west coast of Africa
May 1888 Headquarters and Drill Ship of the Royal Navy Artillery Volunteers, off Somerset House, London. Officer in charge: Thomas Patter, pensioned Chief Gunner, R.N.
August 1892 Towed to Sheerness for conversion by a private contractor to a Coastguard watch vessel after disbanding of the Royal Navy Artillery Volunteers
July 1893 Stationed as Coastguard watch vessel on the Roach River station, Essex
Th 18 January 1877 Our Hongkong Correspondent writes under date the 14th of December last:—
"Her Majesty's ships of war in harbour are the Audacious (flag-ship of Vice-Admiral Ryder), Fly, Growler, Nassau, Ringdove and Vigilant. The orders for the Ringdove to leave here on the 16th of December for England have been countermanded. She will now probably be paid off here, thoroughly repaired by the Naval-yard authorities and re-commissioned with the crew of the Lapwing, her present officers and crew returning to England in the troopship Himalaya. By last advances of the 30th of November, the Charybdis, Frolic, and Mosquito remained by the Lapwing at Chan-shan-tan Island. The weather continued fine, but the chances of getting her afloat were very much against her. The Curlew at Tien-tsin, remains there for the winter. The Growler, after a thorough repair to het boilers, has completed her stores, and proceeds to Amoy in the place of the Fly, ordered to remain in Hongkong.
Tu 27 November 1877 The Euphrates left Port Said on the 24th inst. for Malta and Portsmouth. Letters have been received from Commodore Sullivan, in the Active, in Simon's Bay, up to the 29th of October. The Industry would convey Mr. Stanley , the explorer, and his followers to Zanzibar. Letters have been received from Admiral Ryder, in the Audacious, at Hongkong, up to the 11th ult.; he would there await the arrival of his successor. The Sheldrake had returned from Ichang to Hankow. The Lily had gone from Nagasaki to Chinkiang. The Midge left on the 24th of September for Tientsin, where she will winter. The Frolic was still in dock at Shanghai, after collision. The Growler was ordered from the Dindings up to Hongkong, where she will be docked. The Vigilant had been docked. The health of the Squadron was satisfactory.


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The 8 Most Popular Salwar Suit Styles for 2022
When it comes to Indian ethnic wear, few outfits can beat the style and elegance of a salwar suit. Women of all ages adore wearing salwar suits to parties, work, wedding attire, and daily wear. A typical salwar suit will have a kameez of a certain length paired with a salwar or pants in a loose or close-fitting style. It's unquestionably one of the most comfortable and attractive ethnic clothing for women of all ages and body types.
To complete the look, most salwars come with beautiful dupattas. The popularity of Indian salwar kameezfes stems from their continual development in design ever since they were worn. There are a plethora of salwar suit designs to select from, so you'll be able to find something for every woman and each occasion. Only a few other Indian costumes come close to matching these features.
You Ought to Have These 8 Styles in Your Wardrobe
There are many beautiful, designer salwar kameez available on the market if you're seeking one for yourself or to gift it to someone. The most well-known salwar kameez style comes in a variety of fabrics, colors, and sizes. Here are eight of the most popular designs to choose from this year:
The Royal & Captivating Anarkali Design
Anarkali suits are stylish and elegant and make you look gorgeous with their flowing and flared styles. Modern-day Anarkali suits are available in styles ranging from dramatic to chic, demure to bold. The range of colors and materials used to make them gives you an even broader spectrum of styles and combinations.
This trendy yet traditional outfit profile is utterly feminine and flatters all body shapes. It is usually a frock-style kurta with a form-fitting or loose-fitting bodice and a pleated or flared skirt. The churidar (a slim-fit legging-style salwar) balances out the Anarkalis flaring form in this outfit. Even the Anarkali Suit comes in a variety of styles:
A-Line Anarkali- In this style, the "kurta" has a narrower bodice and an impressive flared skirt. It's an excellent style for women with a well-defined waistline and broader hips.
Frock-Style Anarkali- This style is more structured, with a shorter flared kurta that stops at the knees and works well for women with a straighter body form.
Floor-Length Anarkali- The most preferred Anarkali style, this outfit looks superbly feminine and helps give women a fuller form a more sculpted look.
Simple Yet Elegant: The Classic Punjabi Suit
Punjabi suits or the traditional salwar kameez are simple, graceful, and flatter all body types, and Punjabi women swear by this quintessential comfort wear. Typically, these suits have shorter kurtas in a variety of fabrics, and the pleated salwar adds surprising grace to the attire. From chic to edgy, bold to muted, you can find stylish Punjabi suits for every occasion, formal, festive, unique, or traditional, while there is a variety of styles in salwars, the latest ones include:
Patiala Salwar- Derived from its namesake city in Punjab, this outfit was worn by royalty here in days gone by. In Patiala suits, the pleats of the salwars start at the waistline folding gentry towards the back of the legs.
Dhoti Salwar- Drawing inspiration from the dhoti, this salwar style has multitudes of pleats that form a 'U' shape as they lead from the front around the sides and towards the backs of the legs. This design was inspired by the ancient dhoti and looks great on short kurtis.
The Modern Palazzo Pant Suits
This ultimate fusion wear offers the best of both worlds, where traditional Indian styling meets bold western fashion. The smart, straight-cut kameez paired with wide, flared women's trousers creates a breezy and modern style. This style appears to be a good fit for petite women and those with tall stature appear to be even taller and smarter. Everyone, including celebrities, veer toward Palazzo suits- a perfect casual and formal attire.
Long & Straight Cut Suits
This style is the epitome of minimalism and simplicity, making straight-cut suits the ultimate day and formal wear. These suits have pant or churidar style bottoms paired with straight-cut, body-fitting kameez, and the design oozes elegance sprinkled with the right amount of chic.
Pant Style Salwar Suit
Ankle-length pant-style salwar suits are also called trouser suits inspired by traditional trouser bottoms. The pants pair well with achkan neck patterns on straight-cut kameez, and the outfit looks graceful, chic, and stylish. It's the perfect look for formal occasions and works well for casual events.
The Elegant Sharara Suits
Sharara suits are often mistaken for Palazzo suits, but the former has a distinguishing characteristic that differentiates it from Palazzo. Its wider leg span makes it look more like a skirt that's pulled in at the waist with a drawstring. The sharara suit is paired with a knee-length or short kameez, and the entire outfit screams comfort. Sharara suits are perfect for all occasions and seasons, and their voluminous profile looks particularly flattering on women with a slim build.
Churidar & Kameez Style
The churidar kameez needs no introduction, and it has been the go-to attire for many Indian women for decades. It continues to be a widely preferred salwar suit style and is second in line only to Anarkalis suits and salwar kameez. This attire comprises a churidar( a close-fitting, legging-like bottom) that gives the wearer a slimmer and taller look while accentuating their natural curves. The kurta worm with the churidar is generally short and does not fall below knee length.
Pakistani Embroidered Salwar Suits
An embodiment of Pakistan's tradition and culture, these suits are popularly known as lawn suits. The embellishments and designs reflect the essential charm and elegance of the country's artistry, and the suits are perfect for formal and casual occasions. With their distinctive style- the kameez is usually loose and flowing while the pants are baggy and comfortable. Pakistani suits have lately gained popularity and demand, owing to the vibrancy and vividness of the colors, detailed threadwork, and beadwork. These are simply perfect for anyone who needs a perfect mix of comfort and oomph.
As you can see, each of these salwar suit designs has gone through many changes in style throughout history. Whether you prefer conventional patterns or something more modernistic, contemporary, and sleek, there's a salwar kurta for you that you may personalize to your taste.
Traditional Salwar suits come in a massive range of colors, materials, and combination fabrics, with and without threadwork, zari work, beadwork, and other embellishments. At Lashkaraa, we keep a constant check on these fashion updates and stock an impressive range of salwar suit styles for women, so you will definitely be able to find something that catches your fancy.
Whether you are thinking of buying a new one or simply want to keep track of the latest trends in salwar suits, the internet is a fabulous resource. Bazaars and fashion shows help you witness all the latest fashion catwalk trends that will improve your overall style statement. Lashkaraa keeps a constant check on these fashion updates and


The Ariegeois is a breed of dog, specifically a French pack-hunting scenthound developed late in the last century. It is distinguished by its friendly nature with other hounds and affection for human companions.
Overall, the Ariegeois are talented scenthounds, and affectionate and serene in the home. Dogs of this breed are even-tempered and friendly. Some of them can be outgoing, while there are others that are reserved. These dogs, however, are never vicious or shy. As a working or hunting scenthound, the Ariegeois needs to work with other hounds and their handlers. Due to this, aggression towards people and other hounds is considered a fault. These dogs have a deep, powerful voice and a large amount of endurance.
This breed originated in France in 1912, making it a fairly new breed. It is not yet well known outside of its own region. The Ariegeois was developed through a series of matings between the Grand Gascon-Saintongeois, Grand Bleu de Gascogne, and local Briquet hounds.
The Ariegeois is now being bred in Italy and used to hunt wild boar, performing well in this endeavour under italian conditions.
Ariegeois normally weigh 63-70 lbs and are 24 to 27 inches tall. Their coat is smooth and short. They are tricolor, black and white with tan points mainly at the head. The head of the dog is lean and elonganted. There are no wrinkles. The eyes are dark and gentle. The ears are very soft and medium-length. Muzzle is medium length as well, while the nose is black. The neck is slender and arched slightly, to the chest which is narrow and deep. The ribs are well-sprung with a strong, sloping back. They have straight legs in the front and strong, powerful hindlegs. Feet are hard and foxlike. Tail is slightly curved.
When used in the show ring, the Ariegeois is not supposed to be penalized for its scars. Cuts, notches, or nicks on the ears, or ears frayed at the edges due to working in tall grass should not be considered as faults because Ariegeois primarily work as hunting hounds. Scars of these dogs are considered results of honorable wounds.
There are no known genetic health issues associated with the Ariegeois.
DATE OF PUBLICATION OF THE ORIGINAL VALID STANDARD : 24.01.1996.
Scenthound used for driving game to waiting guns and for coursing. His medium size and lightness make him a precious auxiliary, whether he hunts on his own or in a pack, capable of evolving easily on difficult terrains. Hare hunting is his favorite type of hunting; but he is also used in tracking roe deer or wild boar..
Group 6	Scenthounds, and related breeds.
Section	1.2	Medium sized Hounds.
Originates from the Ariège, product of a crossing of a Briquet with a "chien d'ordre" (scenthound hunting in a pack) which could have been the Bleu de Gascogne or the Gascon Saintongeois. Physically he has kept the typical characteristics of the "chien d'ordre", with, however, less distinction, less size and more lightness.
Light dog, medium size, elegant and distinguished.
Behavior : From his origins he is hardworking dog being at the same time very good at driving game to the waiting guns and showing proof of much initiative and enterprise. He has a resounding voice and is quick in his plotting.
Character : Happy and sociable; easy to train.
Skull : Seen from the front, slightly domed, not too broad; the occipital protuberance only slightly marked. Seen from above, the back of the skull is of lightly pronounced ogival shape. The forehead is full. Superciliary arches only slightly marked.
Stop : Only slightly accentuated.
Nose : Black, developed; nostrils well opened.
Muzzle : Nasal bridge straight or slightly arched; muzzle of equal length with that of the skull.
Lips : Tight, rather thin. The upper lip must just cover the lower jaw but without giving the muzzle a pointed profile.
Jaws/Teeth : Scissor bite. Incisors set square to the jaws.
Eyes : Well open, brown; eyelids without looseness. Alert, bright expression.
Leathers : Fine, supple, curled in, must be able to reach the onset of the nose without going beyond its extremity. The leather is narrow at its base and is set just below the eye level.
Light, rather thin, long, slightly arched.
Back : Well muscled and sustained (firm).
Loin : Well fused, slightly arched.
Ribs : Long, moderately rounded.
Chest : Long, medium width, let down to elbow level.
Flank : Flat and slightly drawn up.
Well set, fine at its extremity, reaching the point of the hock. Carried gaily, sabre blade style.
View of the ensemble : solidly constructed.
Shoulder : Moderately oblique, muscular without heaviness.
Elbow : Close to body.
View of ensemble : well proportioned.
Upper thigh : Quite long and muscled without excess.
Hock : Well set in the axis of the body, well let down. No dewclaw.
FEET: Elongated oval, i.e. "harefeet"; toes lean and tight. Pads and nails black.
Fine, supple, not closely adherent to the body but not allowing the presence of dewlap, folds or wrinkles. Mucous membranes (hairless zones) black.
White with jet black markings with well defined outlines; sometimes mottled. Presence of quite pale tan on the cheeks and above the eyes.
Height at the withers : males :	52 to 58 cm.
females :	50 to 56 cm.
Skull flat or too pronounced dome.
Profile of the extremity of the muzzle too square.
Presence of wrinkles or dewlap.
Leathers too flat; thick, badly set, too long or too short.
Cow hocks seen from behind.
Any coat other than scheduled in the standard.


LED-KEYBOARD - Cool keyboard led \ Download LED-KEYBOARD Winamp visualization for free on litwinscy.com Visualization Keyled - small plugin use change keyboard led into visualization winamp! Download Visualization Keyled Winamp visualization for free on. Keyboard Lights 2 - Make keyboard's lock lights dance to music. Download Keyboard Lights 2 Winamp plugin for free on litwinscy.com I was kind of disappointed that you can't watch AVS visualizations at the same time, though.
12 Mar - 40 sec - Uploaded by kasthan1 Winamp Visualization Keyboard Led. Logitech K Wireless Illuminated Keyboard in Action. I was flying through the random directories on winamps ftp and foound this jem LED Vis for winamp it lets winamp take control of your LEDS. 31 Jan I have seen several keyboard LED visualization plugins so I assume its possible, but I haven't found something like this. sgusev is offline.
Keyboard LED Sound Meter/Visualization - posted in Scripts and Soon after I found a winamp plugin that did a similar thing with music. Keyboard LED Visualization Winamp Plug-in. Friday, May 23, Keyboard LED Visualization plug-in takes control of LED'S on the keyboard. Download. I've started messing around with Advanced Visualization Studio and think that it's I vote for the Keyboard Lights Visualizer big grin roll eyes. I suggest using Winamp as your player since the lights continue flashing the LightFX file, then just go Option > Visualization > Select Plug-in. 31 Dec Visualization key led plugin do winamp v full Pipe for control dmx visualization litwinscy.com g force nowfree litwinscy.comdpixel is a.
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You always hear things about freshman year of college, like how it goes by so fast and how it will be the best year of your life. But it is also a huge transition year, and sometimes it is okay to feel like you have no idea what you are doing and like reality slapped you in the face.
Textbooks are super expensive and sometimes you will not even need them for a class, even if the professor recommends it. Instead, try out the class for a couple of weeks without it, and if you are struggling and think a textbook would help, then get it. Plus, if you do not think you will use it after the class, rent it so that you can get some money back at the end of the year.
You always hear jokes about being a broke college student, but soon it will not be funny when the joke turns into reality. Make sure that you use codes and coupons whenever possible, because you never realize how much things add up until you are living on your own. Wherever you go, ask if they have student discounts -- you may be surprised.
In case you did not know, the Cinemark Movie Theatre has a reduced ticket price if you bring your student ID!
If you come into college wanting to make new friends or knowing nobody, it is up to you to take the first steps. Say hi to everyone you pass in your dorm hallway or at the library. Invite someone to go get a cup of coffee or explore downtown. Suggest group study sessions with classmates. Join a club or sports team. There are so many ways to make new friends, and sometimes you are the one that has to put in the first bit of effort.
Sometimes it is hard to stay on top of work during the week, so you just think you will catch up on everything when the weekend rolls around. Sorry to say this, but you probably will not. Your friends will be going out and you will want to join, or you will just be too lazy on a rainy Sunday. So, try to get as much done during the week as possible, even if you have to stay at the library until 2 a.m.
Simple, but very important. Yes, I just said to stay on top of your work, but that does not mean college should be all work and no play. It is okay if you do not do something here and there to go out with your friends. Go to sports games, concerts, formals and parties. Do not sit in your room watching Netflix all weekend and do not sit at the library studying all weekend. Do not miss a fun opportunity to discover your favorite things about college, meet new people and make lifelong memories.
This may seem like a weird tip, but trust me, you will thank me later. Set an alarm when you nap, because that 20-minute power nap can turn into a three-hour sleep coma. When doing your laundry, set a timer. If you go to get your clean clothes a minute after the machine stops, you will find them on the floor and another student's load in its place. When you randomly think of something you need to do, like sending out a birthday card, set a reminder. Your mom is not here to remind you constantly, and if you do not write it down, you will forget to do it.
You may be relieved now that May 1 has passed, you know where you are going to college and there are no more applications to fill out, for now. Soon, you will have to start thinking about other ones. Apply for scholarships. Applications are tedious, but worth it if they reduce your tuition, even for a semester. Apply for jobs. If you think you will have time balancing schoolwork, find a job near or on campus. There are plenty of student job opportunities at colleges, and they can be flexible with your class schedule. Apply for internships. Paid or not, these will look the most impressive on your resume when looking for a real job after college is over. Plus, it is great to get hands on experience in your field of study.
Obviously, there are so many things in college that are very different from high school. But, this tip is not going to tell you what you already know. You are not in high school anymore means do not act like you are still in high school. Do not sweat the petty things, get involved in drama and act like everything is a popularity contest. To be honest, no one gives a sh*t in college who you were in high school, and no one wants to deal with unnecessary drama. D not ruin your freshman year stuck in a place you could not wait to get out of.
There will be plenty of time to make memories freshman year, but spend these next few months making memories with the people you have known your whole life. Take long drives with your friends, talking about how high school flew by. But, do not skip out on family dinners to hang out with friends. Let your family know how much you will miss them, and thank them for being there for you up to this point. Get in as many late-night ice cream runs, bonfires, road trips,and hugs as you can before you will have to leave and start making new memories.
College is tough. Freshman year is tough. Leaving a place you have lived your whole life is tougher.
Hopefully these small pieces of advice will make that transition a little easier, but it is ultimately up to you to make your experience a good one.
Think positively and go into freshman year confident that you made the right decision of where to start living in the real world.


text:
Biografia
Era il figlio del barone, e poi conte, Aleksandr Sergeevič Stroganov, e della sua seconda moglie, Ekaterina Petrovna Trubeckaja, figlia del principe Pëtr Nikitič Trubeckoj.

Figlioccio dell'imperatore Paolo I, fu un amico d'infanzia del futuro Alessandro I. Ricevette un'educazione eccellente a casa ed i primi anni della sua giovinezza li trascorse a Parigi, durante la rivoluzione, con il suo tutore Romme. Sotto lo pseudonimo di Paul Očër, fu un giacobino, membro del club "Amici della Legge". A Parigi, era accompagnato da Andrej Nikiforovič Voronichin. Nel 1790 ritorna in Russia, alla morte del padre.

Carriera
Iniziò la sua carriera militare con il grado di cornetta nel reggimento di cavalleria dal 1779 al 1791, dopodiché divenne un tenente del Reggimento Preobraženskij. Nel 1792 venne nominato Lord of the Bedchamber e nel 1798 divenne ciambellano. Nel 1802 ottenne il rango di consigliere segreto, il titolo di senatore e la posizione di Vice Ministro degli Affari Interni. Nel 1805 partecipò con l'imperatore Alessandro I alla battaglia di Austerlitz.

Nel 1807 si unì nell'esercito volontario e comandò un reggimento cosacco. Il 21 dicembre 1807 venne nominato maggior generale. Poi, il 27 gennaio 1808, entrò nel reggimento Izmajlovskij, combattendo contro gli svedesi nel 1808-1809, sotto il comando del generale Pëtr Ivanovič Bagration, partecipando alla transizione verso le isole Åland.

Dal 1809 al 1811 era nell'esercito sul Danubio e si distinse in diverse battaglie contro i turchi. Il 28 maggio 1809 divenne comandante del reggimento dei granatieri e direttore generale di brigata della 1ª Divisione dei Granatieri. Il 15 settembre 1811 divenne aiutante generale.

Nel 1812 comandò la 1ª Divisione dei Granatieri nella battaglia di Borodino, sostituì il generale Nikolaj Alekseevič Tučkov come comandante del 3º battaglione di fanteria e il 31 ottobre 1812 è stato insignito del grado di tenente generale.

Nel 1813 partecipò alla battaglia di Lipsia. Nel 1814 ha combattuto in Francia. Il 3 settembre 1814 venne nominato comandante della 2º battaglione di fanteria.

Matrimonio
Nel 1794 sposò la principessa Sof'ja Vladimirovna Golicyna (1775-1845), figlia del principe Vladimir Borisovič Golicyn. Ebbero cinque figli:

 Aleksandr Pavlovič (1794-23 febbraio 1814);
 Natal'ja Pavlovna (1796-1872), sposò il conte Sergej Grigor'evič Stroganov, ebbero sette figli;
 Adelaida Pavlovna (1799-1882), sposò il principe Vladimir Golicyn;
 Elizaveta Pavlovna (1802-1863), sposò il principe Ivan Dmitrievič Saltykov;
 Ol'ga Pavlovna (1808-1837), sposò il conte Pavel Karlovič Fersen.

Morte
Morì il 22 giugno 1817 nei pressi di Copenaghen. Fu sepolto al Cimitero di San Lazzaro nel Monastero di Aleksandr Nevskij a San Pietroburgo.

Onorificenze

Altri progetti

Collegamenti esterni

Pavel Aleksandrovic
Cavalieri dell'Ordine di San Giorgio
Cavalieri dell'Ordine di San Vladimiro
Cavalieri dell'Ordine Imperiale di Aleksandr Nevskij
Cavalieri dell'Ordine di Sant'Anna
Cavalieri dell'Ordine di San Giovanni di Gerusalemme (Russia)

redpajama_set_name: RedPajamaWikipedia


Résumé : Carbon Nanotubes (CNTs) can be used as key elements in nanoelectromechanical systems (NEMS) such as nanorelays, nanoswitches, nanotweezers and feedback device which are designed for memory, sensing or actuation uses. Their electric field induced deformation is a key character for these promising applications, as well as for their fabrication, separation and electromanipulation.
We have computed the deformations of semiconducting and metallic CNTs induced by uniform electrostatic fields, by minimizing total potential energy calculated using a monopole-dipole-interaction model combined with an empirical many-body potential (AIREBO). The effects of field strength, field direction tube geometries and defects on the electrostatic deformation are investigated for both single- and double-walled CNTs. For metallic CNTs, they are much easier to be deflected than semiconducting ones. The deflection is not changed by reversing the field direction. The curve of alignment ratio versus field strength is found to change with field directions. The deflection is found to decrease with the increase of the tube radius ; conversely, it increases when the tube is longer. The multi-walled metallic CNTs are found to be much harder to be bent in electric fields than SWCNTs. Furthermore, we find that the electrostrictive deformation of SWCNTs is proportional to the square of field strength.
Currently, we are investigating the distribution of the charge and the induced dipole in CNTs submitted to electrostatic fields. The results of our calculation show that the charge density at the edge of the open-ended tube is higher than that of the closed tube with net charges. The same effects can be found for the distribution of induced dipoles.
These studies could apply to recently designed devices based on cantilevered carbon nanotubes. Moreover, we wish that they could help to design some new nanoelectromechanical devices.


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        specify(^{
            [[theValue(thingToWatch) should] equal:theValue(1)];
        });

    });

    #pragma mark UIControl+AJWValidator

});

SPEC_END

redpajama_set_name: RedPajamaGithub


GLR Offices is a family owned business that specialises in providing tailored office solutions to small and medium sized businesses. With over 20 years' experience, we know that the right location and facilities will influence the way you work, and how your business performs. As no two businesses are the same we offer flexibility of terms, and work closely with you to ensure your requirements are met from day one.


"In view of the wide variety of nationalities and customs involved, the arbitrator should ensure that the procedures are understood by the parties and that evidence can be given both in writing and orally by the parties' representatives and by their expert witnesses. If necessary, evidence can be taken by video conference and through authorised interpreters." Hearings can take place outside the United Kingdon if agreed by the parties and if consistent with the arbitration rules.
Edward believes that due process is important in order to ensure that the parties are dealt with on a fair and equal basis.


When Hermès comes to Los Angeles, you know the iconic brand will draw a stylish crowd. But among the celebrities and editors at the opening of the Hermès Carré Club, there was one standout attendee: Maye Musk. The model looked impossibly chic wearing Hermès head-to-toe, of course. She mixed stripes and polka dots likes a pro and completed the look with an It bag and wedged ankle boots. Could she look any more stylish?
"Hermès Carré Club showcases the creative energy and artistic expression at the core of the Hermès silk universe, highlighting the House's contemporary vision," the press release reads. The interactive space is complete with artist stations, a karaoke booth, a café, and more. The traveling exhibit has already stopped in New York City, Toronto, and Singapore, and will head over to Milan after Los Angeles. If you're in L.A., be sure to stop by the free admission club, which is open until Sunday, November 11 from 12 p.m. to 8 p.m. Scroll down to see Maye Musk's perfect party outfit.
March 13, 2019 Comments Off on Organic Snacks Aren't Necessarily Healthier Than Junk Food. Here's Why.


text:
via Damian Barr's Literary Salon
Melissa Scholes Young Reads a Passage from The Hive
From Damian Barr's Literary Salon Podcast
By Damian Barr's Literary Salon
Damian Barr's Literary Salon tempts the world's best writers to read exclusively from their latest greatest works and share their own personal stories. Star guests include Jojo Moyes, John Waters, Yaa Gyasi, Mary Beard, Diana Athill and Louis de Bernières—all in front of a live audience at leading glamorous locations world-wide. Our London home is the Savoy. Suave Salonnière Damian Barr is your host.
In this episode, Melissa Scholes Young reads from The Hive. After Robbie Fehler's sudden death, his wife and daughters unite in their struggle to save their pest control company's finances and the family's future. To survive, they must overcome a political chasm that threatens a new civil war as the values that once united them now divide the very foundation they've built. Through alternating point-of-views, grief and regret gracefully give way to the enduring strength of the hive.
This podcast is produced and edited by Megan Bay Dorman. To listen to the rest of the episode, as well as the whole archive of Damian Barr's Literary Salon, subscribe and listen on iTunes or wherever else you find your favorite podcasts.
Damian BarrLit Hub RadioMelissa Scholes YoungpodcastsThe HiveThe Literary Salon
Damian Barr's Literary Salon
Damian Barr's Literary Salon tempts the world's best writers to read exclusively from their latest greatest works and share their own personal stories. Star guests have included Bret Easton Ellis, Jojo Moyes, John Waters, Helen Fielding, Diana Athill and Louis de Bernières - all in front of a live audience at leading glamourous locations. Suave salonnière Damian Barr is your host. Don't worry it's not a book club - there's no homework. Salon Selective!
How Gaslighting in Fiction Can Reflect the Realities of Psychological Abuse
Healthcare Has a Race—and Gender—Problem
For years I didn't have a name for gaslighting. The feeling though and the anger that accompanied it were always palpable,...


Introducing multi-tenancy : What is a tenant?
A tenant is a separate and distinct set of users within a multi-tenant database. For example, a tenant can equate to one company, or a division within one company.
Access to a tenant's data is restricted to users that are authenticated to the tenant via a security domain. For information on security domains, see Security domains for a brief discussion, or see OpenEdge Getting Started: Identity Management for complete details.
For tables that are defined to be multi-tenant, each tenant has its own instance of the multi-tenant table (unless a partition for that table has explicitly not been allocated for that tenant). Tenants have access to the data in the instances designated for that specific tenant as well as to tables that are shared.
Super-tenant users — Super-tenants users (or simply super tenants) can access all of the data in the database, typically for maintenance purposes.


Children of all ages are welcome here. When you arrive, ushers will greet you and your little ones and provide busy bags for their enjoyment during the service. We start here knowing that many children prefer to be in the sanctuary with their families. Plus, we love having little ones attend our services! Often, however, during the service they become bored, and the "toy room (nursery)" or Sunday school room may become more appealing. You are welcome to try either option, to see what you and your children are most comfortable with. Sunday School is an option, on request, during the regular school year from 10:00 AM to approximately 10:40. After class, the children join their parents in the service, at the Peace, before communion. Nursery care is available year-round when requested. Our volunteers are Safe Church certified.
Are you looking for our Family Centered Services on the Second and Fourth Saturdays?


text:
Q: Show that $(g \circ f)^{-1} = f^{-1} \circ g^{-1}$
Let $f: A \to B$ and $g: B \to C$ be invertible mappings; that is, mappings such that $f^{-1}$ and $g^{-1}$ exist. Show that $(g \circ f)^{-1} = f^{-1} \circ g^{-1}$.

I tried using the facts that $f^{-1}(f(x)) = x$ and $g^{-1}(g(x)) = x$ but that didn't seem to help and got me trivial statements.

A: You have to show that $f^{-1}\circ g^{-1}$ is the inverse of $g\circ f$. Hence you have to show that $$f^{-1}\circ g^{-1} \circ g\circ f = id$$ and $$g\circ f \circ f^{-1}\circ g^{-1} = id.$$ Can you finish ?

redpajama_set_name: RedPajamaStackExchange


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December 29, 2018 Feminism / Revolutionary Review / Theory
Feminism and Identity Politics Today
Posted by theforgenews
By Linda, Asha – Lesbians for Liberation
There is no doubt that women face oppression in society today. The perpetuation and normalization of women's oppression, however, could not have been accomplished without the universal framework. The "universal" is a framework which centers men as the standard and anyone who deviates from it as "different", or inferior. It is a framework that is ubiquitous in nature, and very effectively naturalizes women's oppression. From the universal framework stems justifications for women's place under patriarchal capitalism: women are biologically inferior to men; women are innately more "feminine" and "inclined" to be domestic housewives; women are naturally subhumans in need of paternalism—the woman must serve and center men until her death. These are the obvious examples of misogyny that have been and continue to be permeate and drive society today.
The universal is a framework that shapes the consciousness of society—compelling the mind to center men as the norm and women as the supplemental. This framework for understanding society has great impact on how women are treated in organizing spaces and liberatory movements. When there have been movements to liberate workers, the male worker was the subject to be liberated. When there have been movements to end racism, it was the man of color who took center stage—the women of color, in this case, were not "marginalized" but entirely erased. Adhering to the universal framework, women are an afterthought at best—their struggles either reduced to the bourgeois/proletariat antagonism or wholesale invisibilized. In each of these cases, there is a failure to clearly and ruthlessly critique how the universal framework has tainted the consciousness and as a consequence, revolutionary movements.
Bioessentialism:
Monique Wittig said, "One is not born a woman." (1) Through this quote, Wittig drives home the point that nobody is innately a "woman"—this quote proves especially salient in the face of the "universal". The "universal" centers men as the natural superior to women, and women's place in society as a natural consequence of their biological difference from men. Liberal feminists claim to care for women's liberation yet adhere to the very framework that propagates women's inferiority as a natural result of women's biological difference from men.
But if one is not born a woman, how is one made into a woman? "Woman" is engendered upon women as a class via the violent enforcement of all the roles and expected behaviors of womanhood. Womanhood is defined by the forced subordination to and centering of men in women's lives. All the labor roles, norms, and standards which accompany womanhood serve the material interests of patriarchal capitalism and benefit men as a class. The woman must cook, clean, and rear because it is the labor that maintains and reproduces society. Furthermore, the woman must always be for male consumption—every action she takes must be carried out with the man's interests at heart. She can be hypersexualized and objectified by men, but she can never possess true autonomy over her personhood. A woman's body is for the consumption and gaze of men—and never should she believe that she owns it or has autonomy over it. Rape, understood through a materialist lens, is an institution. Marital rape, for example, remains legalized and normalized in most countries in the world. Outside of marital rape, rape victims rarely (if ever) find justice and rapists are glorified; their violence justified. Through rape, women are controlled, dominated, forced into obedience—through rape, womanhood is enforced upon women as a class. Womanhood necessitates the fear and submission of women, always. Through fear of poverty, women are forced to stay in abusive relationships. Through fear of worthlessness, women are compelled to be on the constant lookout for a man to center in their lives. Through fear of rejection, women are made to dehumanize and hyper or desexualize themselves for male consumption and validation. The fear that permeates womanhood perpetuates the subordination of women to men. Never does a woman have autonomy or power over her own circumstances within this vicious structure. These are the tenets of womanhood.
The "universal" portrays womanhood as "innate" to women as a class via the propagation of women's supposed biological difference (read: inferiority) from men. The "universal" not only erases trans women, but naturalizes the subjugation of womanhood and violence of patriarchy. If women are "innately" inclined to be "passive" or "fearful", then the logical conclusion is that women's oppression is natural and the rape of women justifiable. This is the violence of the universal framework.
There are many supposed "revolutionaries" who implicitly and explicitly, through their actions, support the universal framework and all its violence. These "revolutionaries" care about women only insofar as women can be tools used to further their own cause. These "revolutionaries" view women's liberation as supplemental and secondary; as reducible to the bourgeois/proletariat antagonism and therefore depolitical. These "revolutionaries" patronize women and treat women as children who need to be "empowered", rather than comrades they should actively be listening to and working in solidarity with. These revolutionaries don't explicitly state their hatred for women or their support for the rape of women, but in practice participate in the perpetuation of this violently misogynistic framework.
Manhood:
"This thought which impregnates all discourses, including common-sense ones (Adam's rib or Adam is, Eve is Adam's rib), is the thought of domination." (2)- Monique Wittig
Womanhood's complement within the "universal" is manhood. Womanhood would not exist without manhood, which requires the domination and control of women. These two interlinked modalities within patriarchy are cemented by the universal framework. Together, womanhood and manhood create the structural gender binary, which is violently enforced upon every subject of patriarchy—women and LGBT people in particular. Manhood, commonly referred to as "toxic masculinity" by radical liberals, is inherently violent. There is no man who does not benefit materially from manhood, similar to how there is no white person who does not benefit materially from whiteness. Manhood entails the abuse and control of women, lack of emotional empathy, the construance of the man's most irrational and illogical emotions as "rational", and the general entitlement to women's labor and time. Manhood stunts men and prevents them from ever becoming worthy comrades or reciprocatory human beings. Manhood is detrimental to men's psyche but beneficial to all men materially—at the expense of women as a class. Manhood is unequivocally incompatible with liberatory revolution.
The "universal" centers manhood as the norm and naturalizes manhood and womanhood as essential to men and women as classes. The "universal" violently reinforces the dominance and abuse of women via the stigmatization of empathy and kindness as unnatural traits in men. All men who cling to manhood are misogynists and actively perpetuate the oppression of women. It is only through ruthlessly interrogating and betraying the "universal", manhood, and all that they entail, that men can become traitors to the class of men and join women in fighting for liberation from patriarchal capitalism.
LGBT:
Women who transgress the requirements of womanhood face unique forms of marginalization, stigmatization, and dehumanization. Monique Wittig said, "Lesbians are not women." While lesbians are surely classed as women and face violent misogyny and homophobia under patriarchal capitalism, lesbians are not considered "women"—they are considered "spoiled goods" in need of "disciplining". This is because lesbians subvert the central core of what it means to be a "woman": centering men in their lives. As a result of this transgression, lesbians face forced conversion—often manifested in corrective rape; sexual and domestic violence driven by misogyny and homophobia (lesbophobia); and disproportionately high rates of poverty and homelessness. Since lesbians are considered "spoiled goods", they are not considered objects worthy of the social contractual "protection" given to heterosexual men's objects, heterosexual women. In this sense, lesbians are not only fugitives of womanhood—lesbians are not women.
Here again, liberal feminism fails to interrogate the root causes of women's oppression. In fact, through adhering to the universal framework's conception of women as "biologically different than men", liberal feminism effectively perpetuates women's oppression. It is unstated, but the meaning of difference within the "universal" is one which necessarily renders women to be naturally inferior. There is no such thing as "equality" or "agency" within a framework that entails the violent subjugation of women—a reality which liberal feminism actively obscures. In addition, via the propagation of bioessentialist rhetoric, liberal feminists actively participate in the transmisogynistic erasure of trans women.
Take for example trans women's overrepresentation in sex work. Sex work is a gendered form of exploited labor based on the violent commodification of women's bodies for male consumption. As a result of the systematic exclusion in the labor market and disproportionately high rates of evictions, homelessness, and poverty trans women face, they are often driven to the only work available to them for survival: sex work. The overrepresentation of trans women in sex work speaks to the violent material oppression and feminization of labor that trans women face under patriarchal capitalism, which is naturalized by the "universal". Similar to how any form of paid work outside the home was criminalized and violently suppressed (whilst the destitute conditions which drove women to seek such work in the first place were maintained) during the era of primitive accumulation (3), trans women forced into sex work face "…high levels of interaction with the police. (4) In addition, the intense pressure foisted upon trans women to adhere to heterosexuality and dehumanize themselves for male consumption parallels their overrepresentation in sex work. It is clear that any "feminism" which adheres to the universal framework is violently transphobic and unequivocally counterrevolutionary to women's liberation.
The failure to properly critique how the universal framework continues to be adhered to and perpetuated within supposedly "revolutionary" political movements have had dire material consequences. Spaces that claim to advocate for "liberation of oppressed peoples" in practice reproduce the very axes of oppression—patriarchy, racism, ableism—they claim to fight against. The general lack of effort to engage with understanding how axes of oppression target specific identities via capitalism has resulted in supposedly "revolutionary" spaces being dominated by overwhelmingly white, heterosexual, and male voices. This chauvinism has resulted in the rampant rape, abuse, and violence against the very women, BIPOC, and disabled people whose liberation these movements claim to fight for.
Self proclaimed "revolutionaries" who eschew identity politics—in the process completely failing to understand what they are even denouncing—hold an idealist and anti-Marxist understanding of how the numerous axes of oppression work via capitalism. Ultimately, these "revolutionaries" in practice adhere to the violent universal framework, and fail to understand that identity is not an "aesthetic", but materially constructed.
There is no hope for liberation using the oppressor's framework. Just as revolution can not be achieved via the bourgeois electoral system, adhering to the violently oppressive universal framework will never bring true liberation. One needs only to look at the history of liberatory struggles to understand that oppression will not simply cease because marginalized peoples learn to speak in the oppressor's language.
This is why Materialist-Feminism is not just important, but necessarily central to any movement that claims to be "liberatory". Materialist-Feminism subverts the violent naturalization of the "universal", instead presenting a different framework—a liberatory framework. Through Materialist-Feminism, the root of women's oppression can be understood as not "biological", but rooted in the material structures of patriarchal capitalism. Through a dialectical materialist lens, the gendered division of labor and construction of the antagonistic classes of men and women can be understood as the material roots of women's oppression under patriarchy. Materialist-Feminism is ideology and praxis; it is the active effort to center women and dismantle bioessentialist notions of gender which naturalize women's oppression. Materialist-Feminism refuses to speak on the oppressor's terms, instead offering a framework which understands "women" as a socially constructed class antagonistic to the class of men—and the destruction of patriarchal capitalism as integral to the liberation of all subaltern women.
1. Wittig, Monique. "One is not born a woman." The lesbian and gay studies reader (1993): 103-109.
2. Wittig, Monique. "The category of sex." Sex in question: French materialist feminism (1996): 24-29.
3. Federici, Silvia. Caliban and the Witch. Autonomedia, 2004.
4. Fitzgerald, Erin, et al. Meaningful work: Transgender experiences in the sex trade. National Center for Transgender Equality, 2015.
The Origins of Class Society
The Rez and the Reds: How Communists Fail Indigenous Nations


There is neither an academic nor an accurate legal consensus regarding the definition of terrorism. Various legal systems and government agencies use different definitions. Moreover, governments have been reluctant to formulate an agreed upon, legally binding definition. These difficulties arise from the fact that the term is politically and emotionally charged.
Angus Martyn in a briefing paper for the Australian Parliament has stated that "The international community has never succeeded in developing an accepted comprehensive definition of terrorism. During the 1970s and 1980s, the United Nations attempts to define the term foundered mainly due to differences of opinion between various members about the use of violence in the context of conflicts over national liberation and self-determination." These divergences have made it impossible to conclude a Comprehensive Convention on International Terrorism that incorporates a single, all-encompassing, legally binding, criminal law definition of terrorism.


Wellington-based design agency Chrometoaster have won the won the Good Design of the Year Award at the Good Design Awards Australia in Sydney with Game of Awesome.
"What an honour! We're humbled that the judging panel selected Game of Awesome to represent the very best of design from across Australia, and the globe," said Aaron McKirdy, Design Director at Chrometoaster.
Massey University won the Best Overall in Social Innovation for the Design + Democracy Project – VoteLocal: Helping Kiwis Take Part in the Future of Their Cities. Warren & Mahoney Architects won the Best in Category for Interior Design in Architectural Design for TVNZ Television Network Centre Refurbishment and Milk Studio took out Best in Category for Packaging in Communication Design for Only Good.


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Die Abenteuer von Brigsby Bear (Originaltitel: Brigsby Bear) ist eine US-amerikanische Tragikomödie von Dave McCary, die am 23. Januar 2017 im Rahmen des Sundance Film Festivals ihre Weltpremiere feierte, wo sie im U.S. Dramatic Competition gezeigt wurde.

Handlung
Die Abenteuer von Brigsby Bär ist eine Fernsehshow für Kinder mit genau einem Zuschauer: James. Als die Sendung plötzlich eingestellt wird, erkennt James, dass alles, was er über das Leben zu wissen glaubte, eine Lüge ist. Er muss lernen, mit den Realitäten einer neuen Welt klarzukommen, und er macht sich auf, die Geschichte selbst zu beenden.

Produktion

Stab und Besetzung
Regie führte Dave McCary. Es handelt sich bei Brigsby Bear um den ersten Kinofilm, bei dem McCary Regie führte. Das Drehbuch schrieben Kevin Costello und Kyle Mooney.

Mooney übernahm im Film auch die Hauptrolle von James Pope. Mark Hamill spielt Ted Hope, Claire Danes spielt Clare, und Andy Samberg ist in der Rolle von Eric zu sehen. Matt Walsh übernahm die Rolle von Greg Pope, und Greg Kinnear spielt Detective Vogel.

Dreharbeiten und Filmmusik

Die Dreharbeiten hatten im Sommer 2016 in Salt Lake City im US-amerikanischen Bundesstaat Utah stattgefunden, die für die Zeit von 19. Juli bis 23. August 2016 angesetzt waren. Für die Dreharbeiten waren eine Wüstengegend und Vorstädte benötigt worden, so Mooney, die in Utah vorhanden gewesen seien. Zudem habe der Bundesstaat der Filmproduktion einen Steueranreiz geboten. Weitere Drehorte waren die Bonneville Salt Flats, die Gegend um das Smith and Morehouse Reservoir am Oberlauf des Weber Rivers im Westen der Uinta Mountains und ein dort gelegener Campingplatz.

Die Filmmusik wurde von David Wingo komponiert. Der Soundtrack zum Film wurde am 28. Juli 2017 von Lakeshore Records als Download veröffentlicht.

Veröffentlichung
Der Film feierte am 23. Januar 2017 im Rahmen des U.S. Dramatic Competition des Sundance Film Festivals seine Premiere, wo sich Sony Pictures Classics die weltweiten Verwertungsrechte für Brigsby Bear sicherte. Im Mai 2017 wurde der Film im Rahmen der Internationalen Filmfestspiele von Cannes als Abschlussfilm der Semaine internationale de la critique vorgestellt. Ebenfalls im Mai 2017 wurde Brigsby Bear im Rahmen des Seattle International Film Festivals in der Sektion New American Cinema gezeigt. Ab 8. Juni 2017 wurde der Film beim Sydney Film Festival gezeigt. Ebenfalls im Juni 2017 wurde der Film beim Shanghai International Film Festival vorgestellt, wo er sich im Wettbewerb um den Golden Goblet Award befand, und beim Filmfest München vorgestellt. Am 28. Juli 2017 kam der Film in ausgewählte US-amerikanische Kinos. Ende September und Anfang Oktober 2017 wurde der Film im Rahmen des Zurich Film Festivals gezeigt. Im Oktober 2017 wurde der Film beim London Film Festival gezeigt und kam am 8. Dezember 2017 in die Kinos im Vereinigten Königreich. Der Film erschien am 8. März 2018 im deutschen Handel auf DVD und Blu-ray.

Rezeption

Kritiken
Der Film konnte bislang 82 Prozent der Kritiker bei Rotten Tomatoes überzeugen.

John DeFore von The Hollywood Reporter beschreibt den Film als eine bezaubernde, überraschend unaufgeregte Lobeshymne auf die Popkultur-Besessenheit.

Einspielergebnis
In den USA, wo der Film am 28. Juli 2017 in drei ausgewählten Kinos gestartet war, konnte Brigsby Bear bislang rund 40.000 US-Dollar einspielen.

Auszeichnungen
Am 18. Dezember 2017 gab die Academy of Motion Picture Arts and Sciences bekannt, dass sich David Wingos Arbeit auf einer Shortlist befindet, aus der die Nominierungen in der Kategorie Beste Filmmusik im Rahmen der Oscarverleihung 2018 erfolgen werden. Im Folgenden eine Auswahl von Nominierungen und Auszeichnungen im Rahmen weiterer Filmpreise.

Internationale Filmfestspiele von Cannes 2017
 Nominierung für die Caméra d'Or (Dave McCary)

National Board of Review Awards 2017
 Aufnahme in die Top 10 Independent Movies

Sundance Film Festival 2017
 Nominierung für den großen Preis der Jury im U.S. Dramatic Competition (Dave McCary)

Synchronisation

Weblinks

 Brigsby Bear – Drehbuch zum Film von Sony Pictures Classics (PDF, englisch)
 Sundance 2017 – Brigsby Bear. Interview mit Cast und Crew bei der Sundance-Premiere von Park City Television bei Youtube (Video, englisch)
 Mark Hamill & Kyle Mooney on Poignant, Offbeat Comedy 'Brigsby Bear' im Gespräch mit Variety bei Youtube (Video, englisch)

Einzelnachweise

Filmtitel 2017
US-amerikanischer Film
Filmdrama
Filmkomödie
Independentfilm


Lab is an award-winning independent Digital Agency and has been partnered with HardSoft for IT hardware and support since 2014. Lab had recently subscribed to HardSoft's Devices for Teams Solution that's finally provided them with the flexibility they needed to scale after a period of exponential growth since their first HardSoft Lease.
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HardSoft's Devices for Teams solution is our unique AppleDaaS solution. An Apple Mac subscription that allows high-growth companies, like Lab, the freedom & flexibility to add, change and return deviceswhenever & however they need.
HardSoft's unique IT & Subscription Solutions enable Lab's team to provide their always outstanding service to clients. From 2014 to Present-day our relationship ensured lasting 360° support to foster Lab' s exponential growth & ensure their cultural focus on flexibility & freedom carried through to their aqusition of IT hardware & Software.
Lab offers its clients a full suite of digital services, uniquely mixed with a blend of neuro-marketing, psychology and behavioural economics. Matt Lintott, Operations Director and Pilot @ Lab found HardSoft in 2014 whilst looking for an affordable IT solution which would enable his team to have the right equipment at the right time for projects and the opportunity to grow – it's now 2019 & he hasn't looked back!