Chains (feat. AB)
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In humans and most mammals, an antibody unit consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds.[8]Each chain is a series of domains: somewhat similar sequences of about 110 amino acids each.These domains are usually represented in simplified schematics as rectangles.Light chains consist of one variable domain VL and one constant domain CL, while heavy chains contain one variable domain VH and three to four constant domains CH1, CH2, ...[9]
Structurally an antibody is also partitioned into two antigen-binding fragments (Fab), containing one VL, VH, CL, and CH1 domain each, as well as the crystallisable fragment (Fc), forming the trunk of the Y shape.[10]In between them is a hinge region of the heavy chains, whose flexibility allows antibodies to bind to pairs of epitopes at various distances, to form complexes (dimers, trimers, etc.), and to bind effector molecules more easily.[11]
In an electrophoresis test of blood proteins, antibodies mostly migrate to the last, gamma globulin fraction.Conversely, most gamma-globulins are antibodies, which is why the two terms were historically used as synonyms, as were the symbols Ig and γ.This variant terminology fell out of use due to the correspondence being inexact and due to confusion with γ (gamma) heavy chains which characterize the IgG class of antibodies.[12][13]
The Fc region (the trunk of the Y shape) is composed of constant domains from the heavy chains. Its role is in modulating immune cell activity: it is where effector molecules bind to, triggering various effects after the antibody Fab region binds to an antigen.[2][11]Effector cells (such as macrophages or natural killer cells) bind via their Fc receptors (FcR) to the Fc region of an antibody, while the complement system is activated by binding the C1q protein complex. IgG or IgM can bind to C1q, but IgA cannot, therefore IgA does not activate the classical complement pathway.[18]
The classes differ in their biological properties, functional locations and ability to deal with different antigens, as depicted in the table.[8]For example, IgE antibodies are responsible for an allergic response consisting of histamine release from mast cells, often a sole contributor to asthma (though other pathways exist as do exist symptoms very similar to yet not technically asthma). The antibody's variable region binds to allergic antigen, for example house dust mite particles, while its Fc region (in the ε heavy chains) binds to Fc receptor ε on a mast cell, triggering its degranulation: the release of molecules stored in its granules.[26]
In mammals there are two types of immunoglobulin light chain, which are called lambda (λ) and kappa (κ). However, there is no known functional difference between them, and both can occur with any of the five major types of heavy chains.[2] Each antibody contains two identical light chains: both κ or both λ. Proportions of κ and λ types vary by species and can be used to detect abnormal proliferation of B cell clones. Other types of light chains, such as the iota (ι) chain, are found in other vertebrates like sharks (Chondrichthyes) and bony fishes (Teleostei).
Cartilaginous fish (such as sharks) produce heavy-chain-only antibodies (i.e., lacking light chains) which moreover feature longer chain pentamers (with five constant units per molecule). Camelids (such as camels, llamas, alpacas) are also notable for producing heavy-chain-only antibodies.[2][32]
Following activation with antigen, B cells begin to proliferate rapidly. In these rapidly dividing cells, the genes encoding the variable domains of the heavy and light chains undergo a high rate of point mutation, by a process called somatic hypermutation (SHM). SHM results in approximately one nucleotide change per variable gene, per cell division.[46] As a consequence, any daughter B cells will acquire slight amino acid differences in the variable domains of their antibody chains.
Further work concentrated on characterizing the structures of the antibody proteins. A major advance in these structural studies was the discovery in the early 1960s by Gerald Edelman and Joseph Gally of the antibody light chain,[72] and their realization that this protein is the same as the Bence-Jones protein described in 1845 by Henry Bence Jones.[73] Edelman went on to discover that antibodies are composed of disulfide bond-linked heavy and light chains. Around the same time, antibody-binding (Fab) and antibody tail (Fc) regions of IgG were characterized by Rodney Porter.[74] Together, these scientists deduced the structure and complete amino acid sequence of IgG, a feat for which they were jointly awarded the 1972 Nobel Prize in Physiology or Medicine.[74] The Fv fragment was prepared and characterized by David Givol.[75] While most of these early studies focused on IgM and IgG, other immunoglobulin isotypes were identified in the 1960s: Thomas Tomasi discovered secretory antibody (IgA);[76] David S. Rowe and John L. Fahey discovered IgD;[77] and Kimishige Ishizaka and Teruko Ishizaka discovered IgE and showed it was a class of antibodies involved in allergic reactions.[78] In a landmark series of experiments beginning in 1976, Susumu Tonegawa showed that genetic material can rearrange itself to form the vast array of available antibodies.[79]
The importance of antibodies in health care and the biotechnology industry demands knowledge of their structures at high resolution. This information is used for protein engineering, modifying the antigen binding affinity, and identifying an epitope, of a given antibody. X-ray crystallography is one commonly used method for determining antibody structures. However, crystallizing an antibody is often laborious and time-consuming. Computational approaches provide a cheaper and faster alternative to crystallography, but their results are more equivocal, since they do not produce empirical structures. Online web servers such as Web Antibody Modeling (WAM)[110] and Prediction of Immunoglobulin Structure (PIGS)[111] enables computational modeling of antibody variable regions. Rosetta Antibody is a novel antibody FV region structure prediction server, which incorporates sophisticated techniques to minimize CDR loops and optimize the relative orientation of the light and heavy chains, as well as homology models that predict successful docking of antibodies with their unique antigen.[112] However, describing an antibody's binding site using only one single static structure limits the understanding and characterization of the antibody's function and properties. To improve antibody structure prediction and to take the strongly correlated CDR loop and interface movements into account, antibody paratopes should be described as interconverting states in solution with varying probabilities.[17]
Even the lighter chains are often too heavy to carry comfortably in a bag on your back. It's true: they can easily be attached to your luggage rack, carried in your basket or wrapped around your seat post.
Make sure you've thought about this before you buy one. Is there room on your seat post If not, is there room in your bag or your panniers There are other places to put your lock when you're riding, but chains are more challenging than other bike locks.
Again, with 8 mm chains, I recommend that you secure your bike by wrapping the lock tightly around your top tube, so it can't be maneuvered close to the floor where it's susceptible to bolt cropper attacks.
That's not say they can't be cropped though. They can. 14 mm chains can conceivably be cut by the very biggest bolt cutters. But it takes a experienced thief, of considerable weight who is also able to get the chain in the right position.
With Kryptonite's New York Fahgettaboudit chains you get a 15 mm double locking shackle, the maximum 10/10 in house security rating, and both Motorcycle and Bicycle Gold ratings from Sold Secure. Plus optional anti-theft protection which covers bikes worth up to $3,750 / 2000.
How are chains any better than U-locks if they are secured by a mini u-lock Could a thief not simply turn an angle grinder to the small u-lock shackle and get through it just as easy as any other 14mm U-lock
The escalation of coronavirus cases in China has reminded technology markets around the world that the supply chain challenges of recent years may last longer than expected. The pandemic is not the only disruption and many in the smart buildings and physical security industries are being forced to reconsider their approach to supply chain resilience and how they can future-proof their organizations against unknown disruptions. While supply chain challenges have always existed, the impact of the pandemic left supply chains off-balance while playing catch up on increasing demand.
Other major disruptions have also created new challenges for supply chains. Labor shortages have proved a major issue around the world, partly due to knock-on impacts of COVID. The pandemic also changed demand patterns, such as increased technology demand for work-from-home applications and smart home products, straining the wider technology market. Severe weather also played its part, especially floods and droughts in China that caused power outages and restricted energy supplies to key manufacturing regions. While the War in Ukraine, Brexit, and the US-China relations have had more geographically defined effects.
Many firms, in physical security and beyond, have stated their intention to move a portion of production away from China, including tech giants; Intel, Apple, Google, and Microsoft. This is part of a bigger trend of companies moving away from a single-source supplier strategy to a multiple-source strategy, providing more flexibility to adapt to future disruptions. Governments in Europe and North America are also recognising the issue and investing significant amounts to support the re-structure of supply chains through diversification policies and reshoring funds. Meanwhile, competitive regions like South and Southeast Asia try to seize the greater share of the manufacturing pie with incentives and infrastructural development. 59ce067264
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