Evolution of sirenians

Sirenia is the order of placental mammals which comprises modern "sea cows" (manatees and the Dugong) and their extinct relatives. They are the only extant herbivorous marine mammals and the only group of herbivorous mammals to have become completely aquatic. Sirenians are thought to have a 50-million-year-old fossil record (early Eocene-recent). They attained modest diversity during the Oligocene and Miocene, but have since declined as a result of climatic cooling, oceanographic changes, and human interference. Two genera and four species are extant: "Trichechus", which includes the three species of manatee that live along the Atlantic coasts and in rivers and coastlines of the Americas and western Africa, and "Dugong", which is found in the Indian and Pacific oceans.
Origins.
Sirenians, along with Proboscidea (elephants), group together with the extinct Desmostylia and likely the extinct Embrithopoda to form the Tethytheria. Tethytheria is thought to have evolved from primitive hoofed mammals ("condylarths") along the shores of the ancient Tethys Ocean.
Tethytheria, combined with Hyracoidea (hyraxes), forms a clade called Paenungulata. Paenungulata and Tethytheria (especially the latter) are among the least controversial mammalian clades, with strong support from morphological and molecular interpretations. The ancestry of Sirenia is remote from that of Cetacea and Pinnipedia, although they are thought to have evolved an aquatic lifestyle around the same time.
Fossil history.
The first appearance of sirenians in the fossil record was during the early Eocene, and by the late Eocene, sirenians had significantly diversified. Inhabitants of rivers, estuaries, and nearshore marine waters, they were able to spread rapidly. The most primitive sirenian known to date, "Prorastomus", was found in Jamaica, not the Old World; however more recently the contemporary "Sobrarbesiren" has been recovered from Spain. The first known quadrupedal sirenian was "Pezosiren" from the early Eocene.
The earliest known sea cows, of the families Prorastomidae and Protosirenidae, are both confined to the Eocene, and were about the size of a pig, four-legged amphibious creatures. By the time the Eocene drew to a close, came the appearance of the Dugongidae; sirenians had acquired their familiar fully aquatic streamlined body with flipper-like front legs with no hind limbs, powerful tail with horizontal caudal fin, with up and down movements which move them through the water, like cetaceans.
The last of the sirenian families to appear, Trichechidae, apparently arose from early dugongids in the late Eocene or early Oligocene. The current fossil record documents all major stages in hindlimb and pelvic reduction to the extreme reduction in the modern manatee pelvis, providing an example of dramatic morphological change among fossil vertebrates.
Since sirenians first evolved, they have been herbivores, likely depending on seagrasses and aquatic angiosperms (flowering plants) for food. To the present, almost all have remained tropical (with the notable exception of Steller's Sea Cow), marine and angiosperm consumers. Sea cows are shallow divers with large lungs. They have heavy skeletons to help them stay submerged; the bones are pachyostotic (swollen) and osteosclerotic (dense), especially the ribs which are often found as fossils.
Eocene sirenians, like Mesozoic mammals but in contrast to other Cenozoic ones, have five instead of four premolars, giving them a 3.1.5.3 dental formula. Whether this condition is truly a primitive retention in sirenians is still under debate.
Although cheek teeth are relied on for identifying species in other mammals, they do not vary to a significant degree among sirenians in their morphology, but are almost always low-crowned (brachyodont) with two rows of large, rounded cusps (bunobilophodont). The most easily identifiable parts of sirenian skeletons are the skull and mandible, especially the frontal and other skull bones. With the exception of a pair of tusk-like first upper incisors present in most species, front teeth (incisors and canines) are lacking in all, except the earliest sirenians.


List of bioluminescent organisms

Bioluminescence is the production of light by living organisms. This list of bioluminescent organisms is organized by the environment, covering terrestrial, marine, and microorganisms.


Phenylalanine dehydrogenase

In enzymology, a phenylalanine dehydrogenase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are L-phenylalanine, H2O, and NAD+, whereas its 4 products are phenylpyruvate, NH3, NADH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH2 group of donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is L-phenylalanine:NAD+ oxidoreductase (deaminating). Other names in common use include L-phenylalanine dehydrogenase, and PHD. This enzyme participates in phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis.
Structural studies.
As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes and .


SN-22

SN-22 is a chemical compound which acts as a moderately selective agonist at the 5-HT2 family of serotonin receptors, with a Ki of 19nM at 5HT2 subtypes vs 514 nM at 5-HT1A receptors. Many related derivatives are known, most of which are ligands for 5-HT1A, 5-HT6 or dopamine D2 receptors or show SSRI activity.


Metabotropic glutamate receptor 4

Metabotropic glutamate receptor 4 is a protein that in humans is encoded by the "GRM4" gene.
Together with GRM6, GRM7 and GRM8 it belongs to group III of the metabotropic glutamate receptor family. Group III receptors are linked to the inhibition of the cyclic AMP cascade.
Activation of GRM4 has potential therapeutic benefits in the treatment of parkinson's disease. Splice variant "taste-GRM4" is involved in the perception of umami taste.


EHNA

EHNA (erythro-9-(2-hydroxy-3-nonyl)adenine) is a potent adenosine deaminase inhibitor, which also acts as a phosphodiesterase inhibitor that selectively inhibits phosphodiesterase type 2 (PDE2).


Insulin-like growth factor receptor

The insulin-like growth factor receptors (IGFRs) include the following two receptors:


Pargolol

Pargolol is a beta adrenergic receptor antagonist.


Nuage (cell biology)

Nuage are "Drosophila melanogaster" germline granules. Nuage are the hallmark of "Drosophila melanogaster" germline cells, which have an electron-dense perinuclear structure and can silence the selfish genetic elements in "Drosophila melanogaster". The term 'Nuage' comes from the French word for 'cloud', as they appear as nebulous electron-dense bodies by electron microscopy. They are found in nurse cells of the developing "Drosophila melanogaster" egg chamber and are composed of various types of proteins, including RNA-helicases, Tudor domain proteins, Piwi-clade Argonaute proteins, in addition to a PRMT5 methylosome composed of Capsuléen and its co-factor, Valois (MEP50).
See piRNA for more information.


Max Jaffe


Primidolol

Primidolol is a beta adrenergic receptor antagonist.
Synthesis.
J. Augstein, D. A. Cox and A. L. Ham., (1973). Chem. Abstr. jte, 136325e (1973).


Chandu (opium)

Chandu is a rare concentrated preparation of opium which can be smoked. It is made by straining and boiling raw opium. Chandu was prepared for smoking in opium pipes in Asian regions specifically China and India in opium dens. Chandu form of opium delivers the purest euphoric and strongest rush of opium. The dealers of Chandu used to adulterate it with the left over ash which was morphine adding more numbing effect, although it is the morphine content in the opium which elevates pain relief and numbing properties. Chandu is usually vaporized in pipes where its subjected to heat of flame leaving no residue.
Health Hazards are discovered in users consuming it as it can impact the tolerance level of the extract every time it is subjected. Other health Hazards are minimally researched pulmonary and lung disorders arising due to frequent use. Since the user is subjected to the deadly neurological rush activating the pleasure circuits of brain it can be fatal in severe doses used to achieve the fix after a period of obsessive and compulsive need for the substance leading to several levels of addiction stages. The term chandu is believed to originate from the Malay language.


Quinelorane

Quinelorane is a drug which acts as a dopamine agonist for the D2 and D3 receptor.


Margaret Jope

Margaret Jope (1913–2004) was a Scottish biochemist, born Henrietta Margaret Halliday in Peterhead, Scotland. She carried out research into brachiopods.
Biography.
She took her degree in chemistry at the University of Aberdeen, and her DPhil at Somerville College, Oxford. She met her future husband Martyn Jope while working at the Dyson Perrins Laboratory at University of Oxford. After their marriage she accompanied him to Belfast, where he later became Professor of Archaeology at Queen's University.
Margaret continued her research while at Belfast, in the Geology Department, where she worked primarily on brachiopods, especially on their shell protein. Her other research interests included the crystallisation of haemoglobin, and working with Martyn, made studies of animal bones, especially bird bones, at archaeological sites mainly in Northern Ireland and Oxfordshire.


TRNA(His) guanylyltransferase

tRNA(His) guanylyltransferase (, "histidine tRNA guanylyltransferase", "Thg1p", "Thg1") is an enzyme with systematic name "p-tRNA(His):GTP guanylyltransferase (ATP-hydrolysing)". This enzyme catalyses the following chemical reaction
The enzyme requires a divalent cation for activity.


ReNeuron

ReNeuron is a UK-based stem cell research company whose shares are listed on the Alternative Investment Market. Its focus is on the development of stem-cell therapies targeting areas of poorly-met medical need, including peripheral arterial disease, strokes, and retinal diseases.
ReNeuron is testing the effects of neural stem cells on spinal cords for neuroregeneration. They are also testing the use of fetal stem cells on stroke patients.


EF-24

EF-24 is a compound that is a synthetic analogue of curcumin, a bioactive phytochemical from turmeric. Curcumin has antioxidant, antibiotic, anti-inflammatory and anti-cancer properties "in vitro" but has low potency and very poor bioavailability when taken orally, resulting in limited efficacy. EF-24 was developed to try and improve upon these properties, and has been found to be around 10x more potent than curcumin and with much higher systemic bioavailability. It has never been developed for medical use, though research continues to investigate whether it may be useful as an adjuvant treatment for some cancers alongside conventional chemotherapy drugs.


Lectican

Lecticans, also known as hyalectans, are a family of proteoglycans (a type protein that is attached to chains of negatively charged polysaccharides) that are components of the extracellular matrix. There are four members of the lectican family: aggrecan, brevican, neurocan, and versican. Lecticans interact with hyaluronic acid and tenascin-R to form a ternary complex.
Tissue distribution.
Aggrecan is a major component of extracellular matrix in cartilage whereas versican is widely expressed in a number of connective tissues including those in vascular smooth muscle, skin epithelial cells, and the cells of central and peripheral nervous system. The expression of neurocan and brevican is largely restricted to neural tissues.
Structure.
All four lecticans contain an N-terminal globular domain (G1 domain) that in turn contains an immunoglobulin V-set domain and a Link domain that binds hyaluronic acid; a long extended central domain (CS) that is modified with covalently attached sulfated glycosaminoglycan chains, and a C-terminal globular domain (G3 domain) containing of one or more EGF repeats, a C-type lectin domain and a CRP-like domain. Aggrecan has in addition a globular domain (G2 domain) that is situated between the G1 and CS domains.


Ribose repressor

The Ribose repressor (RbsR) is a bacterial DNA-binding transcription repressor protein and a member of the LacI/GalR protein family. In "Escherichia coli", RbsR is responsible for regulation of genes involved in D-ribose metabolism. In "Bacillus subtilis", RbsR was shown to interact with Histidine-containing protein (HPr), an allosteric effector of the related LacI/GalR protein Catabolite Control Protein A (CcpA).


MMP8

Neutrophil collagenase, also known as matrix metalloproteinase-8 (MMP-8) or PMNL collagenase (MNL-CL), is a collagen cleaving enzyme which is present in the connective tissue of most mammals. In humans, the MMP-8 protein is encoded by the "MMP8" gene.
The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is stored in secondary granules within neutrophils and is activated by autolytic cleavage.
Function.
Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The primary function of MMP-8 is the degradation of type I, II and III collagens.
In cancer, loss of MMP-8 in the murine MMTV-PyMT breast cancer model has been associated with increased tumor growth and metastatic burden, as well as enhanced tumor vascularity and altered immune cell infiltration. Furthermore, analysis of MMP-8 in breast cancer cell lines revealed a causal connection between MMP-8 activity and IL6 and IL8 production, suggesting a role for MMP-8 in the regulation of the innate immune system.


Streptavidin

Streptavidin is a 52.8 (tetramer) kDa protein purified from the bacterium "Streptomyces avidinii". Streptavidin homo-tetramers have an extraordinarily high affinity for biotin (also known as vitamin B7 or vitamin H). With a dissociation constant (Kd) on the order of ≈10−14 mol/L, the binding of biotin to streptavidin is one of the strongest non-covalent interactions known in nature. Streptavidin is used extensively in molecular biology and bionanotechnology due to the streptavidin-biotin complex's resistance to organic solvents, denaturants (e.g. guanidinium chloride), detergents (e.g. SDS, Triton X-100), proteolytic enzymes, and extremes of temperature and pH.
Structure.
The crystal structure of streptavidin with biotin bound was reported by two groups in 1989. The structure was solved using multi wavelength anomalous diffraction by Hendrickson et al. at Columbia University and using multiple isomorphous replacement by Weber et al. at E. I. DuPont Central Research and Development Department. As of September 2017, there are 171 structures deposited in the Protein Data Bank. See this link for a complete list. The N and C termini of the 159 residue full-length protein are processed to give a shorter ‘core’ streptavidin, usually composed of residues 13–139; removal of the N and C termini is necessary for the highest biotin-binding affinity. The secondary structure of a streptavidin monomer is composed of eight antiparallel β-strands, which fold to give an antiparallel β-barrel tertiary structure. A biotin binding-site is located at one end of each β-barrel. Four identical streptavidin monomers (i.e. four identical β-barrels) associate to give streptavidin’s tetrameric quaternary structure. The biotin binding-site in each barrel consists of residues from the interior of the barrel, together with a conserved Trp120 from a neighboring subunit. In this way, each subunit contributes to the binding site on the neighboring subunit, and so the tetramer can also be considered a dimer of functional dimers.
Origins of the high affinity.
The numerous crystal structures of the streptavidin-biotin complex have shed light on the origins of the remarkable affinity. Firstly, there is high shape-complementarity between the binding pocket and biotin. Secondly, there is an extensive network of hydrogen bonds formed to biotin when in the binding site. There are eight hydrogen bonds directly made to residues in the binding site (the so-called 'first shell' of hydrogen bonding), involving residues Asn23, Tyr43, Ser27, Ser45, Asn49, Ser88, Thr90 and Asp128. There is also a 'second shell' of hydrogen bonding involving residues that interact with the first shell residues. However, the streptavidin-biotin affinity exceeds that which would be predicted from the hydrogen bonding interactions alone, suggesting another mechanism contributing to the high affinity. The biotin-binding pocket is hydrophobic, and there are numerous van der Waals force-mediated contacts and hydrophobic interactions made to the biotin when in the pocket, which is also thought to account for the high affinity. In particular, the pocket is lined with conserved tryptophan residues. Lastly, biotin binding is accompanied by the stabilisation of a flexible loop connecting β-strands 3 and 4 (L3/4), which closes over the bound biotin, acting like a 'lid' over the binding pocket and contributing to the extremely slow biotin dissociation rate.
Most attempts at mutating streptavidin result in a lowered biotin-binding affinity, which is to be expected in such a highly optimized system. However, a recently engineered mutant of streptavidin, named traptavidin, was found to have more than ten-fold slower biotin dissociation, in addition to higher thermal and mechanical stability. This decreased dissociation rate was accompanied by a two-fold decrease in the association rate.
Biotin-binding affinity can be impaired by chemical labeling of streptavidin, such as with amine-reactive fluorophores. Flavidin is a streptavidin mutant without lysine side-chains, which retains good biotin binding characteristics after such fluorescent dye labeling.
Uses in biotechnology.
Among the most common uses of streptavidin are the purification or detection of various biomolecules. The strong streptavidin-biotin interaction can be used to attach various biomolecules to one another or onto a solid support. Harsh conditions are needed to break the streptavidin-biotin interaction, which often denatures the protein of interest being purified. However, it has been shown that a short incubation in water above 70 °C will reversibly break the interaction (at least for biotinylated DNA) without denaturing streptavidin, allowing re-use of the streptavidin solid support. A further application of streptavidin is for purification and detection of proteins genetically modified with the Strep-tag peptide. Streptavidin is widely used in Western blotting and immunoassays conjugated to some reporter molecule, such as horseradish peroxidase.
Streptavidin has also been used in the developing field of Nanobiotechnology, the use of biological molecules such as proteins or lipids to create nanoscale devices/structures. In this context streptavidin can be used as a building block to link biotinylated DNA molecules to create single walled carbon nanotube scaffolds or even complex DNA polyhedra.
The tetrameric streptavidin has also been used as a hub around which other proteins may be arranged, either by an affinity tag such as Strep-tag or AviTag or by genetic fusion to SpyTag. Fusion to SpyTag allowed generation of assemblies with 8 or 20 streptavidin subunits. As well as a molecular force probe for atomic force microscopy studies, novel materials such as 3D crystalline lattices have also been created. Streptavidin has a mildly acidic isoelectric point (pI) of ~5, but a recombinant form of streptavidin with a near-neutral pI is also commercially available.
Pretargeted immunotherapy uses streptavidin conjugated to a monoclonal antibody against cancer cell-specific antigens followed by an injection of radiolabelled biotin to deliver the radiation only to the cancerous cell. Initial hurdles involve saturation of the biotin binding sites on streptavidin with endogenous biotin instead of the injected radiolabelled biotin, and a high degree of radioactive exposure in the kidneys due to streptavidin’s strong cell adsorptive properties. It is currently thought that this high level of binding to adherent cell types, such as activated platelets and melanomas, is a result of integrin binding mediated through the RYD sequence in streptavidin.
Variants with a controlled number of binding sites.
Streptavidin is a tetramer and each subunit binds biotin with equal affinity. Multivalency is an advantage in some applications, for example where avidity effects improve the ability of molecules attached to streptavidin to detect specific T cells. In other cases, such as the use of streptavidin for imaging specific proteins on cells, multivalency can perturb the function of the protein of interest. Monovalent streptavidin is an engineered recombinant form of streptavidin which is a tetramer but only one of the four binding sites is functional. This single binding site has 10−14 mol/L affinity and cannot cause cross-linking. Applications of monovalent streptavidin have included fluorescent tracking of cell surface receptors, decorating DNA origami, and acting as a pointer to identify specific regions for cryo-electron microscopy.
Monomeric streptavidin is a recombinant form of streptavidin with mutations to break the tetramer into a monomer and to enhance the solubility of the resultant isolated subunit. Monomeric streptavidin versions have an affinity for biotin of 10−7mol/L 10−8mol/L and so are not ideal for labeling applications but are useful for purification, where reversibility is desirable.
A streptavidin with exactly two biotin binding sites per tetramer can be produced by mixing subunits with and without a functional biotin binding site and purification by ion-exchange chromatography. The functional binding sites here have the same biotin binding stability as wild-type streptavidin. Divalent streptavidin with the two biotin binding sites together (cis-divalent) or apart (trans-divalent) can be separately purified.
A streptavidin with exactly three biotin binding sites per tetramer can also be produced using the same principle as to produce divalent streptavidins.
Streptavidins of higher valency has been obtained by utilizing the chemistry of isopeptide bond conjugation using the SpyTag/SpyCatcher technology. This involves having a streptavidin tetramer with three biotin binding sites and a dead streptavidin fused to either SpyTag or SpyCatcher. When the different tetramers are mixed together, a covalent linkage occurs to enable higher number of biotin binding sites. Six and twelve biotin binding sites per molecule have been made with this method.
Comparison to avidin.
Streptavidin is not the only protein capable of binding to biotin with high affinity. Avidin is the other most notable biotin-binding protein. Originally isolated from egg yolk, avidin only has 30% sequence identity to streptavidin, but almost identical secondary, tertiary and quaternary structure. Avidin has a higher affinity for biotin (Kd ~ 10−15M) but in contrast to streptavidin, avidin is glycosylated, positively charged, has pseudo-catalytic activity (avidin can enhance the alkaline hydrolysis of an ester linkage between biotin and a nitrophenyl group) and has a higher tendency for aggregation. On the other hand, streptavidin is the better biotin-conjugate binder; avidin has a lower binding affinity than streptavidin when biotin is conjugated to another molecule, despite avidin having the higher affinity for free, unconjugated biotin. Because streptavidin lacks any carbohydrate modification and has a near-neutral pI, it has the advantage of much lower nonspecific binding than avidin. Deglycosylated avidin (NeutrAvidin) is more comparable to the size, pI, and nonspecific binding of streptavidin.
External links.
Groups investigating and developing streptavidin or avidin-family proteins (Alphabetical order)


CloudWalk Technology

CloudWalk Technology Co. Ltd. is a Chinese developer of facial recognition software.
The company has been sanctioned by the United States government for allegedly participating in major human rights abuses.
History.
CloudWalk was founded by Zhou Xi, a graduate of the University of Science and Technology of China with an academic background in artificial intelligence and pattern recognition. CloudWalk was founded in April 2015, following Zhou's departure from the Chinese Academy of Sciences.
In 2017, CloudWalk raised $379 million in Series B funding from investors including Shunwei Capital, Oriza Holdings, and Puhua Capital.
Role in mass surveillance of the Uyghurs.
On May 22, 2020, the United States Department of Commerce added CloudWalk Technology to its Entity List for its role in aiding the Chinese government in the mass surveillance of the Uyghur population. CloudWalk Technology partnered with the University of Illinois at Urbana–Champaign to develop the surveillance technology. According to U.S officials, CloudWalk Technology was, "complicit in human rights violations and abuses committed in China’s campaign of repression, mass arbitrary detention, forced labor and high-technology surveillance against Uighurs, ethnic Kazakhs, and other members of Muslim minority groups in the Xinjiang Uighur Autonomous Region (XUAR)".
Customers.
CloudWalk is the primary supplier of facial recognition technology to the Bank of China and Haitong Securities.
In 2018, CloudWalk signed a deal to provide the government of Zimbabwe with a mass facial recognition system, which will monitor all major transportation hubs, as well as create a national facial ID database.


Chromogenic in situ hybridization

Chromogenic "in situ" hybridization (CISH) is a cytogenetic technique that combines the chromogenic signal detection method of immunohistochemistry (IHC) techniques with "in situ" hybridization. It was developed around the year 2000 as an alternative to fluorescence "in situ" hybridization (FISH) for detection of HER-2/neu oncogene amplification. CISH is similar to FISH in that they are both "in situ" hybridization techniques used to detect the presence or absence of specific regions of DNA. However, CISH is much more practical in diagnostic laboratories because it uses bright-field microscopes rather than the more expensive and complicated fluorescence microscopes used in FISH.
Procedure.
Probe design.
Probe design for CISH is very similar to that for FISH with differences only in labelling and detection. FISH probes are generally labelled with a variety of different fluorescent tags and can only be detected under a fluorescence microscope, whereas CISH probes are labelled with biotin or digoxigenin and can be detected using a bright-field microscope after other treatment steps have been applied.
CISH probes are approximately 20 nucleotides in length and are designed for DNA targets. They are complementary to the targeted sequence and bind to it after a denaturation and hybridization step. Only a few CISH probes are available commercially, so for most applications they have to be extracted, amplified, sequenced, labelled and mapped from bacterial artificial chromosomes (BACs). BACs were developed during the Human Genome Project as it was necessary to isolate and amplify short fragments of human DNA for sequencing purposes. Nowadays, BACs can be selected and positioned on the human genome using public databases such as the UCSC Genome Browser. This ensures optimal complementarity and sequence specificity. DNA is extracted from the BAC clones and amplified using a polymerase-based technique, such as degenerate oligonucleotide primed (DOP)-PCR. Next, the clones are sequenced and their position on the genome is verified. Probe labelling can be carried out by using either random priming or nick translation to incorporate biotin or digoxigenin.
Preparation of tissue, hybridization of probes, and detection.
For CISH to work optimally, chromosomes must be in either interphase or metaphase. Tissue samples are securely attached to a surface, which is usually a glass slide, with paraffin. The tissue samples must then be washed and heated several times to remove any paraffin before the hybridization step. After this, the sample has to undergo pepsin digestion to ensure the target is accessible. As a final step, 10–20 μL of probe is added, the sample is covered with a coverslip which is sealed with rubber cement, and the slide is heated to 97 °C for 5–10 minutes to denature the DNA. The slide is then placed in a 37 °C oven overnight so that the probe can hybridize. On the next day, the sample is washed and a blocker for nonspecific protein binding sites is applied. If horseradish peroxidase (HRP) is going to be used, the sample must be incubated in hydrogen peroxide to suppress endogenous peroxidase activity. If digoxigenin was used as a probe label, an anti-digoxigenin fluorescein primary antibody followed by a HRP-conjugated anti-fluorescein secondary antibody are then applied. If biotin was used as a probe label, non-specific binding sites must first be blocked using bovine serum albumin (BSA). Then, HRP-conjugated streptavidin is used for detection. HRP then converts diaminobenzidine (DAB) into an insoluble brown product, which can be detected in a bright-field microscope under 40- to 60-fold magnification. A counterstain such as hematoxylin and eosin can be used to make the product more visible.
Comparison to other techniques.
Compared to FISH.
FISH is considered to be the gold standard for the detection of chromosomal abnormalities because it is very sensitive and has high resolution. Other techniques that are developed to detect chromosomal abnormalities are usually compared to the sensitivity and specificity of FISH to see how they measure up. For example, compared to FISH, CISH has been shown to have a sensitivity of 97.5% and a specificity of 94% for detection of HER-2/neu gene amplification. The concordance rate between FISH and CISH was 94.8%, showing CISH to be a comparable technique to FISH. Most other sources agree and report an almost equal performance on gene amplification assays for FISH and CISH. However, sometimes CISH shows lower sensitivity for low level amplifications.
CISH has some advantages over FISH in the reagents and equipment it uses. As noted above, CISH is much cheaper and is easier to use because it uses bright-field microscopes instead of fluorescence microscopes. In addition, the CISH reagents are more stable than the FISH reagents so it is possible to store the samples and examine the same sample multiple times. FISH reagents fade over time due to photobleaching so a sample can only be examined once. Apart from the expensive fluorescence microscope, FISH also requires a high-resolution digital camera to capture micrographs of the sample before the fluorescence fades. Another advantage of using bright-field microscopy is that the tissue or cell sample as a whole can be visualized through CISH whereas cell morphology is difficult to assess using fluorescence microscopy in FISH.
CISH also differs from FISH in the probes that are used as well as in the overall method. There are many different types of FISH probes available, such as repeat probes, probes that detect specific genes or telomeres, and probes that detect chromosomal abnormalities. In contrast, there is a limited variety of commercially available CISH probes, including probes that bind the centromere of chromosomes 3, 7, 8, 9, 10, 11, 17, 18, X, and Y as well as gene-specific probes for cancer-related genes, such as HER-2, EGFR, MYC, and TOP2A. Despite the limited variety of available CISH probes, they are generally more cost-effective than FISH probes. With regard to the overall method, FISH can be performed using direct labelling—fluorochromes are attached to the probes—or indirect labelling—the probes are labelled with biotin or digoxigenin which are then detected using fluorescently-labelled streptavidin or antibodies, respectively. CISH is performed using indirect labelling in which antibodies or streptavidin are conjugated to enzymes such as HRP or alkaline phosphatase (AP).
Compared to IHC.
CISH and IHC are similar in that both are used for the same purpose (mainly to detect HER-2/neu amplification) and they both use enzyme reactions (HRP/AP) to measure amplification. CISH and IHC are different in that IHC measures protein expression whereas CISH measures DNA amplification. This difference is particularly useful for HER-2/neu because it has been found that gene amplification is of higher prognostic value than protein expression.
A disadvantage of IHC is that it is not possible to identify false-negative and false-positive results. In CISH, if there is no signal for the reference probe, the assay has failed.
For low and high protein overexpression/gene amplification, CISH and IHC show a concordance of over 86% and over 89%, respectively. It has been shown that monoclonal antibodies are better than polyclonal antibodies for detection in both IHC and CISH as they bind more specifically, which leads to a higher concordance rate.
For medium protein overexpression/gene amplification concordance varies, but is higher when monoclonal antibodies are used than when polyclonal antibodies are used. The variable concordance is due to the fact that gene amplification does not strictly correlate with protein expression and that tumor heterogeneity can make it difficult to detect protein overexpression in a tissue.
Medical applications.
CISH is frequently applied to assess gene amplification, such as HER-2/neu status in breast cancer samples. HER-2/neu amplification is associated with higher mortality, higher recurrence rate, and poor prognosis in breast cancer. The monoclonal antibody trastuzumab is a receptor blocker that has been proven to be clinically very effective in HER-2/neu-overexpressing tumors. Therefore, it is crucial to determine receptor status before starting cancer treatment.
CISH is also used for detection of chromosomal rearrangements and fusions, such as the fusion of ALK tyrosine kinase domain with the promoter and 5’ region of EML4 in lung cancer. ALK-positive tumors are a clinically relevant subgroup as they can be very effectively treated with the ALK inhibitor crizotinib.
Apart from cancers, CISH has also been shown to be useful in detecting human papillomavirus infections.
Variations.
Silver-enhanced "in situ" hybridization (SISH).
SISH uses a similar method as CISH, but a silver precipitate is the end product rather than a brown product. In this method, a probe tagged with dinitrophenol (DNP) binds to the target sequence. A primary anti-DNP antibody is then added followed by a secondary antibody conjugated to HRP. Silver acetate, hydroquinone, and hydrogen peroxide are subsequently added to the secondary antibody and HRP catalyzes the polymerization of silver in the presence of hydrogen peroxide. Silver metal is consequently deposited into the nuclei of the cell. Amplification of HER-2/neu is seen as black dots.
DuoCISH.
DuoCISH is a variation of CISH that addresses the need for two different probes on the same slide. It is a well-established technique for HER-2/neu amplification detection even though it is sometimes reported to be less effective than FISH. In this technique, one probe binds the reference which, in the case of HER-2/neu amplification detection, is CEN17 (the centromere of chromosome 17) while the other probe binds the target sequence which is HER-2/neu. DuoCISH combines both FISH and CISH in that it converts signals from FISH probes to chromogenic substrates. It works on the principle that blue cyanine dye is a substrate for HRP and red dye is a substrate for AP. For example, green fluorescein isothiocyanate (FITC) signals are converted to blue chromogenic precipitates through an anti-FITC antibody conjugated to HRP, and Texas Red signals are converted to red chromogenic precipitates through an anti-Texas Red antibody conjugated to AP. An advantage of DuoCISH is that it is possible to distinguish between chromosomal aneuploidy and gene amplification as the reference gene will also be amplified in aneuploidy but not in gene amplification detection.


Neurohypophysial hormone

The neurohypophysial hormones form a family of structurally and functionally related peptide hormones. Their main representatives are oxytocin and vasopressin. They are named after the location of their release into the blood, the neurohypophysis (another name for the posterior pituitary).
Most of the circulating oxytocin and vasopressin hormones are synthesized in magnocellular neurosecretory cells of the supraoptic nucleus and paraventricular nucleus of the hypothalamus. They are then transported in neurosecretory granules along axons within the hypothalamo-neurohypophysial tract by axoplasmic flow to axon terminals forming the pars nervosa of the posterior pituitary. There, they are stored in Herring bodies and can be released into the circulation on the basis of hormonal and synaptic signals with assistance from pituicytes.
Oxytocin mediates contraction of the smooth muscle of the uterus and mammary gland, while vasopressin has antidiuretic action on the kidney, and mediates vasoconstriction of the peripheral vessels. Due to the similarity of the two hormones, there is cross-reaction: oxytocin has a slight antidiuretic function, and high levels of AVP can cause uterine contractions. In common with most active peptides, both hormones are synthesised as larger protein precursors that are enzymatically converted to their mature forms.
Members of this family are found in birds, fish, reptiles and amphibians (mesotocin, isotocin, valitocin, glumitocin, aspargtocin, vasotocin, seritocin, asvatocin, phasvatocin), in worms (annetocin, nematocin), octopuses (cephalotocin), "Locusta migratoria" (Migratory locust) (locupressin or neuropeptide F1/F2) and in molluscs (conopressins G and S).


Reticular cell

A reticular cell is a type of fibroblast that synthesizes collagen alpha-1(III) and uses it to produce reticular fibers. The cell surrounds the fibers with its cytoplasm, isolating it from other tissue components and cells. Reticular cells provide structural support, since they produce and maintain the thin networks of fibres that are a framework for most lymphoid organs.
They are found in many tissues including the spleen, lymph nodes and lymph nodules. They also direct B cells and T cells to specific regions within the tissue.


Star Force

, released in North America by Video Ware in the arcades as Mega Force, is a vertical-scrolling shooter released in 1984 by Tehkan.
Gameplay.
In the game, the player pilots a starship called the Final Star, while shooting various enemies and destroying enemy structures for points.
Unlike later vertical scrolling shooters, like Toaplan's "Twin Cobra", the Final Star had only two levels of weapon power, and no secondary weapons like missiles and/or bombs. Each stage in the game was named after a letter of the Greek alphabet. In certain versions of the game, there is an additional level called "Infinity" (represented by the infinity symbol) which occurs after Omega, after which the game repeats indefinitely.
In the NES version, after defeating the Omega target, the player can see a black screen with Tecmo's logo, announcing the future release of the sequel Super Star Force. After that, the infinity target becomes available and the game repeats the same level and boss without increasing the difficulty.
Reception.
In Japan, "Game Machine" listed "Star Force" on their December 1, 1984 issue as being the fourteenth most-successful table arcade unit at the time.
Legacy.
Ports and related releases.
"Star Force" was ported and published in 1985 by Hudson Soft to both the MSX home computer and the Family Computer (Famicom) in Japan. The North American version for the Nintendo Entertainment System (NES) was published in 1987 by Tecmo. Although the NES version is the same Hudson port that had been released for the Famicom in Japan, Tecmo made alterations to the graphics, music, and control, and increased the difficulty of the game. Also, despite the U.S. arcade version being titled "Mega Force", Tecmo decided to release the NES version under the original name of "Star Force".
"Star Force" was also ported to the SG-1000 by Sega, X68000 by Dempa Shimbunsha and mobile phones by Tecmo.
In 1995, along with two other NES shooters, the Famicom version of "Star Force" was remade by Hudson Soft with minimal upgrades for the Super Famicom as part of the Japan-only release of the "Caravan Shooting Collection". The same version was also included in Hudson's compilation of NES shooters in 2006 in "Hudson Best Collection Vol. 5".
The original arcade version was later added to the compilation titled "Tecmo Classic Arcade", which was released for the Xbox. In 2009, the arcade version was made available for download on the Wii Virtual Console for 500 Wii Points as one of the four initial offerings for the "Virtual Console Arcade" category of the Wii Shop Channel (the other three being "Gaplus", "Mappy", and "The Tower of Druaga" from Namco).
In 1986, Hudson Soft released the shoot 'em up game "Star Soldier", which is considered a spiritual successor to "Star Force". The game spawned numerous sequels.


Slotket

In computer hardware terminology, slotkets, also known as slockets, (both short for "slot to socket adapter") are adapters that allow socket-based microprocessors to be used on slot-based motherboards.
Slotkets were first created to allow the use of Socket 8 Pentium Pro processors on Slot 1 motherboards. Later, they became more popular for inserting Socket 370 Intel Celerons into Slot 1 based motherboards. This lowered costs for computer builders, especially with dual processor machines. High-end motherboards accepting two Slot 1 processors (usually Pentium 2) were widely available, but double-socketed motherboards for the less expensive Socket 370 Celerons were not. The slotkets remained popular in the transition period from Slot to Socket-based Pentium III processors by allowing CPU upgrades in existing Slot 1 motherboards.
Slotkets were never introduced to take advantage of the AMD Athlon processors' transition from the Slot A form factor to the Socket A form factor.
Today, slotkets have largely disappeared, as neither Intel nor AMD currently manufacture CPUs in slot form factors.


Surface Pro X

The Surface Pro X is a 2-in-1 detachable tablet computer developed by Microsoft. It was developed alongside and was announced on 2 October 2019 alongside the Surface Pro 7 and Surface Laptop 3. Updated hardware was announced alongside Surface Laptop Go and Surface accessories on 1 October 2020. The device starts at $999 US/£999.
The Surface Pro X comes with a Microsoft SQ1 or SQ2 ARM processor, which the company claimed that it has three times the performance of a MacBook Air while also having a 13-hour battery life, owing to the power efficiency of ARM processors compared to traditional x86 processors. Microsoft has previously used ARM processors in the discontinued Surface RT and Windows Phone devices.
Configuration.
The Surface Pro X starts at $999/£999 for the cheapest model, with 8 GB RAM and 128 GB storage.
The device can be bought with either 8 GB or 16 GB RAM. Users can also choose between 128 GB, 256 GB and 512 GB of storage.
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Hardware and design.
The Surface Pro X is the 7th addition to Surface Pro lineup alongside the Surface Pro 7. Microsoft markets the tablet as a "go-anywhere, do-anything PC". Microsoft claims the Surface Pro X's battery can last up to 13 hours of use.
Compared to the Surface Pro 6, the Surface Pro X is slimmer and has rounder edges featuring a matte black finish construction in platinum and black finish. The device contains 2 USB C ports, an eSIM and a SIM card slot for LTE, a removable SSD, and the Surface Connect port for charging. There are no microSD card slot and headphone jack on the tablet, requiring its users to use dongles and USB-C or Bluetooth enabled headphones.
The device's screen is a 13 inch touchscreen display, with smaller bezels compared to other Surface Pro devices.
The device uses Microsoft SQ1 or SQ2 ARM processors co-developed by Qualcomm, based on the Snapdragon 8cx Gen 1 and Gen 2 processors respectively. A Qualcomm X24 LTE modem is also featured in the device for both processors.
Software.
The Surface Pro X comes pre-installed with an ARM-based version of Windows 10, which supports ARM32 and ARM64 UWP and desktop apps from the Microsoft Store or from other sources. x86 applications can be run through emulation, addressing a major issue of Windows RT. Emulation of x64 applications is an upcoming feature that is already available to Windows Insiders for testing. In addition, Hyper-V can be installed on ARM64 devices such as the Surface Pro X running the Pro or Enterprise editions of Windows 10.


VTech 3D Gamate

The 3D Gamate, is a handheld video game console developed and manufactured by VTech, released in 1983.
It is the first video game console to incorporate 3D effects in game-play to some capacity, predating the Vectrex 3D Imager.
Games.
Only three games are known to exist for the system, all of which were released for the ProScreen a year later:
The box advertised three other games that seem to never have been released:


Realm of Nauga

Realm of Nauga is an adventure game for the TRS-80 Color Computer released on cassette as part of "Chromasette"s August 1982 issue, then available at RadioShack.
Plot.
The objective of "Realm of Nauga" is for the player to traverse three levels of dense forest to retrieve the Magic Golden Scepter for King Thomas II. In exchange for the Scepter, King Thomas promises one-quarter of his kingdom as reward. The player is warned that retrieving the Scepter will not be easy, as several monsters of increasing difficulty will be encountered along the way. To reach each successive level of forest, the player must find a doorway and the key that unlocks it. Throughout the player's journey several objects will aid in the quest, including a sword, a bow, arrows, magic potions, health potions, a rope to traverse trees, and a boat to cross water. After crossing the first two levels of the forest, the player will encounter the most difficult challenge of all: the Nauga.
The Nauga is an immortal creature, but it may be stunned to buy time for the adventurer. It will relentlessly pursue the player until the player dies or completes the quest. The Nauga possesses powerful magic and can transport itself instantly to whichever section of the forest the player is currently exploring. It also shoots with magic power, severely decreasing the health of the adventurer. Along with this magic power, the Nauga also has a bite that is equally debilitating. As powerful as the Nauga is, it is possible for the adventurer to shelter in the trees or on the water, provided the rope or the boat has been found.
If the adventurer finds the Magic Golden Scepter in the third forest and retrieves the key to the final doorway without being devoured by the Nauga, the player will win the game.
Gameplay.
User interface.
"Nauga" uses the standard Color Computer 32x16 character display with green background. Objects and creatures are represented on screen by single characters, sometimes using inverse video mode. Geographic features, such as trees and rivers, are represented using the CoCo's 8-color graphics support in the standard text mode.
Each level of forest spans several different screens laid out in a 4x3 grid, with each section of forest numbered 1-12 so that the player can determine the present location. The layout of the forest has finite boundaries and does not allow the adventurer to travel across non-adjacent sections of forest. The player can however use magic to randomly jump to other sections of forest. This use of magic is unpredictable; sometimes the adventurer simply transports to a different location within the same section of forest.
The game exploits the CoCo's processor clock rate doubling, activated by the "POKE 65495,0" command, and deactivated it after a normal exit. Players who reflexively hit the Break key when death seems imminent, prematurely terminating the game, are treated to an unusually rapid flashing color cursor at the OK prompt.
Movement.
"Nauga" is not turn-based; creatures move independent of the timing of user input. The player moves his character with the joystick and picks up objects by pressing the joystick button. The player uses the keyboard to perform additional tasks, pressing '1' to use the sword, '2' to use the bow and arrow, '3' to use magic, '4' to show the status report, and '0' to use a healing potion.
Combat.
During combat, the adventurer can employ several attacks dependent on items held in inventory. If the adventurer is equipped with a sword, the player can attack monsters within the one or two cells adjacent to the current position. If the adventurer uses the bow and arrow, the player can fire a shot that seeks out the closest monster. The bow and arrow is limited by line-of-sight targeting and cannot shoot through trees. The player's third offensive option is use of magic that temporarily immobilizes the affected monster. Due to the unpredictability of magic, it is never a guaranteed strategy.
A common strategy during combat is to use the rope or boat if the adventurer has them in inventory. With these two items, the player can hide on the edge of trees or on the water and shoot arrows, or use the sword to attack adjacent monsters.


Steve Capps

Steve Capps is an American computer programmer, who was one of the designers of the original Apple Macintosh computer.
Capps started working at the Xerox Corporation while still a computer science student at the Rochester Institute of Technology. In 1981, Capps started working for Apple on the Lisa project and he continued his work on the Macintosh, principally writing the Finder (along with Bruce Horn) and Macintosh system utilities—such as ResEdit.
During a break in 1986, he wrote three music programs including Jam Session, SoundEdit, and Super Studio Session; SoundEdit was eventually sold to Macromedia. From 1987 to 1996, he was the chief architect and Apple Fellow for the Apple Newton, where he led the specification and development of the user interface of Newton, shepherded the team of software developers, and wrote many portions of the built-in application software. From 1996 until 2001, he was a user interface architect at Microsoft. His early work at Microsoft resulted in the Internet Explorer Search, History, and Favorites panes. He was also a co-founder of the MSN Explorer project.
As of 2010, he was working at Silicon Valley start-up Kwedit, now called PayNearMe, focusing on online payment systems. At that time, he was married to lawyer Marie D'Amico and had one child, Emma T Capps, who was born in 1997.


Canon EOS D60

The Canon EOS D60 is a discontinued 6.3 megapixel digital single lens reflex (DSLR) camera body, announced by Canon on February 22, 2002. It is part of the Canon EOS range, and accepts Canon EF, TS-E and MP-E lenses, but not Canon's later digital-only EF-S lens range.
The EOS D60 sits in the prosumer (professional-consumer) line of digital SLR cameras. It succeeded the three megapixel EOS D30 and was replaced by the improved, six megapixel EOS 10D.
In America, its initial pricing was US$1,999 for the basic body, or US$2,199 including battery, charger, and DC kit.
Features.
The EOS D60 features:


Pixar Image Computer

The Pixar Image Computer is a graphics computer originally developed by the Graphics Group, the computer division of Lucasfilm, which was later renamed Pixar. Aimed at commercial and scientific high-end visualization markets, such as medicine, geophysics and meteorology, the original machine was advanced for its time, but sold poorly.
History.
Creation.
When George Lucas recruited people from NYIT in 1979 to start their Computer Division, the group was set to develop digital optical printing, digital audio, digital non-linear editing and computer graphics. Computer graphics quality was just not good enough due to technological limitations at the time. The team then decided to solve the problem by starting a hardware project, building what they would call the Pixar Image Computer, a machine with more computational power that was able to produce images with higher resolution.
Availability.
About three months after their acquisition by Steve Jobs on February 3, 1986, the computer became commercially available for the first time, and was aimed at commercial and scientific high-end visualization markets, such as medical imaging, geophysics, and meteorology. The machine sold for $135,000, but also required a $35,000 workstation from Sun Microsystems or Silicon Graphics (in total, ). The original machine was well ahead of its time and generated many single sales, for labs and research. However, the system did not sell in quantity.
In 1987, Pixar redesigned the machine to create the P-II second generation machine, which sold for $30,000. In an attempt to gain a foothold in the medical market, Pixar donated ten machines to leading hospitals and sent marketing people to doctors' conventions. However, this had little effect on sales, despite the machine's ability to render CAT scan data in 3D to show perfect images of the human body. Pixar did get a contract with the manufacturer of CAT Scanners, which sold 30 machines. By 1988 Pixar had only sold 120 Pixar Image Computers.
In 1988, Pixar began the development of the PII-9, a nine slot version of the low cost P-II. This machine was coupled with a very early RAID model, a high performance bus, a hardware image decompression card, 4 processors (called Chaps or channel processors), very large memory cards (VME sized card full of memory), high resolutions video cards with 10-bit DACs which were programmable for a variety of frame rates and resolutions, and finally an overlay board which ran NeWS, as well as the 9 slot chassis. A full-up system was quite expensive, as the 3 GiB RAID was $300,000 alone. At this time in history most file systems could only address 2 GiB of disk. This system was aimed at high-end government imaging applications, which were done by dedicated systems produced by the aerospace industry and which cost a million dollars a seat. The PII-9 and the associated software became the prototype of the next generation of commercial "low cost" workstations.
Demise and legacy.
In 1990, the Pixar Image Computer was defining the state-of-the-art in commercial image processing. Despite this, the government decided that the per-seat cost was still too high for mass deployment and to wait for the next generation systems to achieve cost reductions. This decision was the catalyst for Pixar to lay off its hardware engineers and sell the imaging business. There were no high volume buyers in any industry. Fewer than 300 Pixar Image Computers were ever sold.
The Pixar computer business was sold to Vicom Systems in 1990 for $2,000,000. Vicom Systems filed for Chapter 11 within a year afterwards.
Many of the lessons learned from the Pixar Image Computer made it into the Low Cost Workstation (LCWS) and Commercial Analyst Workstation (CAWS) program guidelines in the early and mid 1990s. The government mass deployment that drove the PII-9 development occurred in the late 1990s, in a program called Integrated Exploitation Capability (IEC).
Design.
The P-II could have two Channel Processors, or Chaps. The chassis could hold 4 cards. The PII-9 could hold 9 cards (4 Chaps, 2 video processors, 2 Off Screen Memory (OSM) cards, and an Overlay Board for the NeWS windowing system). NeWS was extended to control the image pipeline for roaming, image comparison, and stereo image viewing.
Each Chap is a 4-way parallel (RGBA) image computer. This was a SIMD architecture, which was good for imagery and video applications. It processed four image channels in parallel, one for red, one for green, one for blue, and one for the alpha channel (whose inventors have connections to Pixar). Images were stored with 12 bits per color channel (or 48 bits per pixel). The 12-bit data represented an unusual (for today) fixed-point format that ranged from -1.5 to 2.5 using 2 bits for the integer portion, meaning the range from 0 to 1 had 10 bit accuracy.
A Unix host machine was generally needed to operate it (to provide a keyboard and mouse for user input). The system could communicate image data externally over an 80M per second "Yapbus" or a 2M per second multibus to other hosts, data sources, or disks, and had a performance measured equivalent to 200 VUPS, or 200 times the speed of a VAX-11/780.
Usage.
Walt Disney Feature Animation, whose parent company later purchased Pixar in 2006, used dozens of the Pixar Image Computers for their Computer Animation Production System (CAPS) and was using them in production up through "Pocahontas" in 1995.


Star Warrior

Star Warrior is a 1980 science fiction role-playing video game written and published by Automated Simulations (later renamed to Epyx) for the Apple II, TRS-80, and Atari 8-bit family. The game is branded as part of the "Starquest" series, consisting of "Star Warrior" and the otherwise unrelated "Rescue at Rigel".
Description.
Players take on the role of one of two members of the Furies, a mercenary group that only accepts assignments that meet their Samurai-like code. In "Star Warrior" the Furies have been hired by the people of Fornax, who were recently annexed by the Interstellar Union of Civilized Peoples but wish a return to autonomous rule. Two agents are sent on separate missions, which are assumed to occur simultaneously. In one, the agent must draw off and destroy enemy forces to guarantee success of the second, where the agent tracks down and kills the Stellar Union's military governor. A "directional indicator" points the way to mission objectives.
Gameplay.
"Star Warrior" is based on a modified version of the BASIC game engine as previous "Apshai"-based games. In previous games the playfield was presented as a top-down view of a series of interconnected rooms. Only one room would be displayed at a time, and a new room would be drawn after the player moved through a door. In "Star Warrior" the action takes place outdoors, the first Epyx game to do so, with the display showing a one-kilometer area from a seven-by-nine kilometer map, redrawn and re-centered when the player reaches the edge of the current displayed area.
Sighting and range considerations were added to the engine, allowing the player to only see objects within the line-of-sight, and at distances based on target size. The computer shares this limitation, allowing the player to hide behind objects to escape detection. In older "Apshai"-based games sighting was much simpler, simply showing everything within the current room. Another change is the use of energy to power most player devices, including weapons, shielding, and sensors. This limits the number of devices that can be turned on at once and requires recharge time after taking damage.
The map includes various buildings, both civilian and military fortresses, as well as mobile and fixed-place enemies, such as turrets. Buildings can only be damaged by the Fury's limited number of missiles, while the blaster and powergun can damage smaller targets. The player selects one of three suits of armor at the start of the game, each with different equipment tradeoffs, including sensor suite, shield strength, weapons, and the ability to fly. Players can also design their own suits at the start of the game, selecting among various equipment within a total budget of 2,500 credits. Equipment damaged in combat can be automatically repaired, although this depletes both energy and time, and most suits include a medical system that does the same for the player character.
The game is turn-based, with the user given a certain number of points to be spent every turn, with various actions assigned different point values. The system in "Star Warrior" is similar to the one used in previous games like "Temple of Apshai". In the decoy mission the player selects their own time limit before being recalled to his or her ship, but in the assault mission the game ends only when the governor or player is killed. This differs somewhat from the other "Starquest" release, "Rescue at Rigel", which has a fixed time limit of sixty turns.
Reception.
Glenn Mai reviewed "Money Madness" in "The Space Gamer" No. 39. Mai commented that "If you have the money buy the game; if you don't have the money, get the money and buy the game. Highly recommended to any wargamer or arcade buff."
"Star Warrior" was granted an award in the category of "Best Science Fiction/Fantasy Computer Game" at the 4th annual Arkie Awards where judges noted that "even the instruction book is a cut above the rest".


Canon EOS 5D

The EOS 5D is a 12.8 megapixel digital single-lens reflex (DSLR) camera body produced by Canon. The EOS 5D was announced by Canon on 22 August 2005, and at the time was priced above the EOS 20D but below the EOS-1D Mark II and EOS-1Ds Mark II in Canon's EOS digital SLR series. The camera accepts EF lens mount lenses.
The EOS 5D is notable for being the first full-frame DSLR camera with a standard body size (as opposed to the taller, double-grip "professional" camera body style). It is also notable for its price, suggested at US$3299 without lens, which set a significant new low price point for full-frame DSLRs; its only full-frame competition at the time was the Canon 1Ds Mark II, which cost more than twice as much.
On 17 September 2008, Canon announced the camera's successor, the Canon EOS 5D Mark II.
Features.
Sensor and image processing.
The 5D has a DIGIC II processor and a 35.8 x 23.9 mm full-frame CMOS sensor with 13.3 million pixels (12.7 megapixel effective) and a pixel density of 1.5 megapixels per square centimetre. ISO speeds from 100 to 1600 are provided, adjustable in 1/3 steps (ISO can be expanded to L: 50 or H: 3200 with a menu function). The ISO 50 setting reduces dynamic range by a stop in the highlights.
Autofocus and metering.
The 5D has nine autofocus points (plus six "invisible assist AF points" available only during continuous-focus tracking) arranged in a horizontal diamond pattern. The AF system was a minor upgrade to the one on the 20D. The camera uses TTL 35-zone SPC metering with four variations (evaluative, center-weighted, partial, spot) and exposure compensation of −2 EV to +2 EV in steps of 1/3 EV.E-TTL II flash metering is provided.
Shutter.
The shutter is rated to 100,000 shots, and is capable of speeds up to 1/8000 sec, with a flash sync speed of 1/200 sec.
Ergonomics.
The 5D is very similar in design to the 20D, and most of the controls are identical or nearly so. Differences include:
Speed.
The 5D can shoot up to 3 frames per second, with a buffer that can store up to 60 frames in large JPEG mode, and up to 17 frames in RAW.
File numbering.
The 5D is the first prosumer Canon DSLR where 9,999 images are stored to one folder (which was exclusive to the EOS-1D series), unlike its predecessors where 100 images are stored.
Software.
The package includes the following software:
The EOS 5D is compatible with Magic Lantern firmware (old versions only).


OctaMED

OctaMED is a popular sound tracker for the Commodore Amiga, written by Teijo Kinnunen. The first version, 1.12, was released in 1989 under the name MED, which stands for Music EDitor. In April 1990, version 2.00 was released with MIDI support as the main improvement. In 1991 the first version with the name OctaMED was released, so-called as it could replay eight independent channels on the Amiga's four-channel sound chip. This was also the first commercial version of the software. The publisher throughout has been RBF Software of Southampton, UK which is run by Ray Burt-Frost.
History.
The distinguishing feature of MED and OctaMED in comparison to other music trackers on the Amiga was that MED and OctaMED had native MIDI support for external instruments via the Amiga's serial port – this allowed many musicians to sequence a combination of outboard studio equipment and internally generated sounds to create studio quality releases such as "I Created Disco" by Calvin Harris.
OctaMED was chiefly used by musicians to create stand-alone works, rather than by game or demo musicians to make tunes that play in the context of a computer game or demo.
Firstly, this is because the MED and OctaMED music replay routine is simply too slow to be used in a game or demo. Most trackers are optimised for speed of replay code, taking less than 3% of CPU time. MED took roughly 20% of CPU time. Secondly, and this is also one of the reasons why MED draws more CPU power, the MED format allowed a greater degree of complexity in music construction, with arbitrary length of pattern sheets, sections and blocks rather than a simple pattern-list, and a greater number of effects for the sound. This additional complexity was welcomed by music composers, who preferred more sophisticated structure to their compositions and did not see it as a simple list of timed note-presses.
The technique of playing more channels of music than the Amiga hardware was capable of was first introduced with Jochen Hippel's "Hippel 7V" routine, which used code initially developed for the Atari ST to perform software mixing of 4 channels to a single output, played back alongside the remaining three Amiga hardware sound channels. The seven-channel routine then appeared in TFMX. Finally, the routine was optimised so it could mix an additional channel, resulting in eight channels of sound. The 8-channel routine first appeared in another tracker called Oktalyzer and Face The Music. Finally, this appeared in OctaMED.
OctaMED was developed on the Amiga until 1996. The last version, called OctaMED Soundstudio, had features like MIDI file support, ARexx support, support for 16-bit and stereo samples, hard disk recording, and support for up to 64 channels.
Teijo Kinnunen handed over the development of OctaMED to other programmers soon after the final Amiga version was released. The new programmers later released a Windows port, but the lack of features and presence of noticeable bugs meant this edition did not achieve the same level of fame as the Amiga release. More versions of the Windows port were later released. It was subsequently renamed to MED Soundstudio, and has had several releases under that name.
A later approach to extend the features of the Amiga version of OctaMED was performed by Kjetil Matheussen starting in 1997. By hacking the binary he managed to make a more low-level plugin system than was already available via the ARexx language. With the help of NSM the users could now get access to the CAMD MIDI library, 48-channel MIDI interfaces, signal processing plugins for the sample editor, interaction with the sequencer Bars&Pipes, and many other esoteric features, far extending the features offered for the commercial Windows version of OctaMED.
Current version is available for Windows and AmigaOS platforms, called MED SoundStudio.


Sigma DP2x

The Sigma DP2x is a large-sensor digital compact camera announced by Sigma Corporation on February 8, 2011. It features a Foveon X3 sensor.
Software.
Sigma Photo Pro provides processing of raw X3F files to JPEG for all digital SIGMA cameras. Version 6.x is a free download for Windows 7+ and Mac OS ab Version 10.7 (6.3.x). As of 2017, versions are 6.5.4 (Win 7+) and 6.5.5 (MacOSX 10.9+).


Panasonic Lumix DMC-FZ62

The Panasonic Lumix DMC-FZ60 or Panasonic Lumix DMC-FZ62 is a DSLR-like ultrazoom bridge camera announced by Panasonic back in 2012. FZ60 is for Americas and Asia-Pacific, while the FZ62 is for Europe and CIS. The highest-resolution pictures it records is 16.1 megapixels, through its 25mm Leica DC VARIO-ELMARIT.
Its successor is the FZ70/72 with a 16 megapixel sensor and 60x optical zoom lens.


Money Madness (video game)

Money Madness is a 1980 video game published by Instant Software for the TRS-80.
Contents.
"Money Madness" is a game package containing two programs, "Millionaire" and "Timber Baron".
Reception.
Bruce Campbell reviewed "Money Madness" in "The Space Gamer" No. 39. Campbell commented that "For those interested in a business simulation, I recommend this package. Many single programs cost more. While "Timber Baron" is of primary interest, you may also enjoy a few games of "Millionaire"."


Mapping the Atari

Mapping the Atari, written by Ian Chadwick and published by COMPUTE! Publications in 1983, is a location-by-location explanation of the memory layout of the Atari 8-bit family of home computers. The introduction is by Optimized Systems Software co-founder Bill Wilkinson.
The book covers the 64K address space of the system's 6502 processor from low to high, including addresses used by the operating system or mapped to hardware registers, as well as how to use them. For example, location 756 (2F4) codice_1 contains the starting memory address that tells ANTIC where to find the character set. The author explains how to use this feature to build custom character sets.
An updated version covering changes to the operating system and newer machines like the 130XE followed in 1985. "Antic" magazine serialized the book in 1989 and 1990.
Reception.
"The Addison-Wesley Book of Atari Software 1984" recommended "Mapping the Atari", calling it "the most valuable reference book for machine language programmers".
"Antic" stated when serializing the book:


Panasonic Lumix DMC-FZ38

The Panasonic Lumix DMC-FZ38 is a superzoom bridge digital camera, replacing the similar Panasonic Lumix DMC-FZ28 and earlier Panasonic Lumix DMC-FZ18. It is also known as the DMC-FZ35 in North America.


Armor Alley

Armor Alley is a computer wargame for MS-DOS and Mac OS. Its gameplay is modelled on the Apple II game "Rescue Raiders". Player can compete against the computer or other humans in a LAN environment. The game supports cooperative multiplayer of up to two players per side. The player controls a helicopter armed with a limited number of munitions, such as missiles, bombs, machine guns, and napalm. As the player requisitions computer-controlled tanks, infantry, engineers. Mobile missile platforms, and vans round out available firepower.
Gameplay.
Objective.
The objective is to destroy an opposing base at the opposite end of the play area. Various units are deployed for this purpose, which can be assisted by the player's helicopter. The enemy has the same arsenal as the player, so tactics and convoy composition are vital. Only the van, which contains electronic warfare equipment, can achieve victory by coming into contact with the enemy base. Its armor is quite weak, so these units must be protected at all times.
The two-dimensional battlefield is a long strip of ground, with the player's base on the left end and the enemy's base on the right. Every map has these two bases, but each map has a different pattern of fixed terrain features. The game ends when one of these two bases is captured.
The player's view is always focused on the central unit, the helicopter. The helicopter carries 2 guided missiles, 10 bombs and has a machine gun with 64 rounds of ammunition (at higher levels the machine gun is replaced by 6 unguided missiles). The helicopter's fuel is limited, so each player has to return to base before there's insufficient fuel left for the trip back. The helicopter is very vulnerable to enemy fire and so relies on its agility and the player's control to survive on the battlefield.
Budget.
War funds slowly trickle into a spending account that allows purchase of units. Each unit has an associated cost. A helicopter costs 20, tanks 4, mobile missile launchers 3, vans 2, infantry and engineers 5. The player must spend carefully to ensure the purchase of equipment as needed. The farther the helicopter is from its landing pad, the higher the rate of funding. The more assets you have on the ground at the end of a battle the more funds you have to start the next battle.
All units must be purchased by the player, but once bought, they blindly advance to the right towards the enemy base. Extra lives may be purchased by buying more helicopters.
Reception.
The game was reviewed in 1991 in "Dragon" #166 by Hartley, Patricia, and Kirk Lesser in "The Role of Computers" column. The reviewers gave the game 5 out of 5 stars. 1992 and 1994 "Computer Gaming World" surveys of wargames with modern settings gave the game one and a half stars out of five, describing it as "a short entertaining diversion, but little of serious import".


ICL DRS 300


Canon EOS 5D Mark III

The Canon EOS 5D Mark III is a professional-grade 22.3 megapixels full-frame digital single-lens reflex (DSLR) camera made by Canon.
Succeeding the EOS 5D Mark II, the Mark III was announced on 2 March 2012. This date coincided with the 25th anniversary of the announcement of the first camera in the EOS line, the EOS 650, and was also Canon's 75th anniversary. The Mark III went on sale later in March with a retail price of $3,499 in the US, £2999 in the UK, and €3569 in the Eurozone.
On 25 August 2016, Canon announced the camera's successor, the Canon EOS 5D Mark IV.
Features.
New features over the EOS 5D Mark II are:
Along with the 5D Mark II, the shutter life is rated at 150,000 cycles.
Known defects.
Canon issued a product advisory indicating that the camera's LCD panel, when illuminated in extremely dark environments, may impact the camera's light metering when shooting. Any camera bodies sold with the issue will be fixed by Canon free of charge, and any body shipped after the first week of May 2012 likely had the defect already rectified.
Firmware updates.
Firmware 1.2.1 was released on 30 April 2013 to allow the camera to output uncompressed video via HDMI and permit autofocus ability up to f/8.
Firmware 1.2.3 was released on 30 October 2013, fixing a number of minor bugs.
Firmware 1.3.3 was released on 29 January 2015, fixing minor menu issues and improved AF control-ability when shooting in Live View mode with a wide-angle lens.
Firmware 1.3.4 was released on 14 November 2016, it corrects a phenomenon in which when using the camera with the EF 70-300mm f/4-5.6 IS II USM lens, even if lens aberration correction is set to "Enable", correction will not be applied.
Firmware 1.3.5 was released on 29 November 2017, it corrects a phenomenon in which standard exposure may not be obtained, or an irregular exposure may result, when Silent LV (Live View) shooting with the following TS-E lenses: TS-E 50mm f/2.8L MACRO, TS-E 90mm f/2.8L MACRO, or TS-E 135mm f/4L MACRO.
Firmware 1.3.6 was released on 12 September 2019, it corrects a PTP communications vulnerability, and corrects a vulnerability related to firmware update.
Cubesat.
In July 2020 an attempt was made to launch a cubesat named CE-SAT 1B equipped with a 5DIII sensor on an Electron rocket. The rocket failed to reach orbit.


Time capture

Time capture is the concept of making sense of time-related data based on timestamps generated by system software. Software that run on PCs and other digital devices rely on internal software clocks to generate timestamps. In turn, these timestamps serve as the basis for representing when an event has occurred (i.e. when an outgoing call was made), and for how long that event lasted (i.e. the duration of a phone call).
Time capture software use data mining techniques to index, cleanse and make sense of this data. Applications include automated time tracking, where software can track the time a user spends on various PC-based tasks, such as time in applications, files/documents, web pages (via browser), and emails.
This is a comparison of notable time capture software packages.


Comparison of netbook-oriented Linux distributions

Netbooks are small laptops, with screen sizes between approximately 7 and 12 inches and low power consumption. They use either an SSD (solid state disk) or a HDD (hard disk drive) for storage, have up to 2 gigabytes of RAM (but often less), lack an optical disk drive, and usually have USB, Ethernet, WiFi and often Bluetooth connectivity. The name emphasizes their use as portable Internet appliances.
Netbook distributions.
There are special Linux distributions, called netbook distributions, for these machines. All such distributions purport to be optimized for use with small, low-resolution displays. They tend to include a broad mix of VOIP and web-focused tools, including proprietary applications rarely seen installed by default by mainstream desktop distributions. For instance, Nokia Maemo and Asus' customized Xandros both ship with Skype and Adobe Flash installed, and Ubuntu's Netbook Edition offers the option to do the same for OEMs.
Comparison.
Google Trends.
While no public numbers measuring the install-base of these operating systems are available, Google Trends data on a handful of them indicate their relative popularity:


Varnish (software)

Varnish is an HTTP accelerator designed for content-heavy dynamic web sites as well as APIs. In contrast to other web accelerators, such as Squid, which began life as a client-side cache, or Apache and nginx, which are primarily origin servers, Varnish was designed as an HTTP accelerator. Varnish is focused exclusively on HTTP, unlike other proxy servers that often support FTP, SMTP and other network protocols.
History.
The project was initiated by the online branch of the Norwegian tabloid newspaper "Verdens Gang". The architect and lead developer is Danish independent consultant Poul-Henning Kamp (a well-known FreeBSD developer), with management, infrastructure and additional development originally provided by the Norwegian Linux consulting company Linpro. The support, management and development of Varnish was later spun off into a separate company, Varnish Software.
Varnish is free and open source software, available under a two-clause BSD license. Commercial support is available from Varnish Software, amongst others.
Version 1.0 of Varnish was released in 2006, Varnish 2.0 in 2008, Varnish 3.0 in 2011, Varnish 4.0 in 2014, Varnish 5.0 in 2016, and Varnish 6.0 in March 2018.
Architecture.
Varnish stores data in virtual memory and leaves the task of deciding what is stored in memory and what gets paged out to disk to the operating system. This helps avoid the situation where the operating system starts caching data while it is moved to disk by the application.
Varnish is heavily threaded, with each client connection being handled by a separate worker thread. When the configured limit on the number of active worker threads is reached, incoming connections are placed in an overflow queue; when this queue reaches its configured limit incoming connections will be rejected.
The principal configuration mechanism is "Varnish Configuration Language" (VCL), a domain-specific language (DSL) used to write hooks that are called at critical points in the handling of each request. Most policy decisions are left to VCL code, making Varnish more configurable and adaptable than most other HTTP accelerators. When a VCL script is loaded, it is translated to C, compiled to a shared object by the system compiler, and loaded directly into the accelerator which can thus be reconfigured without a restart.
A number of run-time parameters control things such as the maximum and the minimum number of worker threads, various timeouts, etc. A command-line management interface allows these parameters to be modified, and new VCL scripts to be compiled, loaded and activated, without restarting the accelerator.
In order to reduce the number of system calls in the fast path to a minimum, log data is stored in shared memory, and the task of monitoring, filtering, formatting and writing log data to disk is delegated to a separate application.
Performance metrics.
Varnish Cache can speed up information delivery by a factor of several hundred. To ensure proper operation and performance, Varnish exposes metrics that can be monitored in the following areas:
Metric collection.
Varnish Cache ships with monitoring and logging tools. One of the most used is varnishstat which gives a detailed snapshot of Varnish’s current performance. It provides access to in-memory statistics such as cache hits and misses, resource consumption, threads created, and more.
varnishstat.
Running varnishstat from the command line returns a continuously updating list of all available Varnish metrics. If the -1 flag is added, varnishstat will exit after printing the list one time. Varnishstat can be used as a standalone tool to spot-check the health of the cache. In order to graph metrics over time, correlate with other statistics from across an infrastructure, and set up alerts about any problems that may arise, monitoring services can integrate with Varnish and collect varnishstat metrics.
varnishlog.
Varnishlog is a tool that can be used to debug or tune Varnish's configuration, as it provides detailed information about each individual request.
Load balancing.
Varnish supports load balancing using both a round robin and a random director, both with a per-backend weighting. Basic health-checking of backends is also available.
Other features.
Varnish Cache also features:


Samsung T559 Comeback

The Samsung Comeback (SGH-T559) is a mobile phone announced by T-Mobile on 22 July 2009 and released in Q3 2009. The phone has a full QWERTY keyboard, and is primarily a messaging phone, though it does have internet capability.
Overview.
The Comeback has a 2.0-megapixel camera, an HTML browser with Flash Lite, 3G support, stereo Bluetooth, and a music player that supports MP3, AAC/AAC+, WMA, MPEG4, WAV, MIDI, and RealAudio formats. It has an SAR of 1.35 watts per kilogram.
The phone comes in White/Cherry Red or Grey/Plum colors.
The Alphanumeric keypad glows orange on both color choices.
References.
Samsung Comeback retrieved 16-2-2010

Samsung Comeback phone details from T-Mobile retrieved 16-2-2010

Samsung Comeback review at CNET retrieved 16-2-2010