Persius/hicric huggingface dataset:
DNA-DNA reassociation
DNA-DNA hybridization generally refers to a molecular biology technique that measures the degree of genetic similarity between pools of DNA sequences. It is usually used to determine the genetic distance between two species.  When several species are compared that way, the similarity values allow the species to be arranged in a phylogenetic tree; it is therefore one possible approach to carrying out molecular systematics.
Charles Sibley and Jon Ahlquist, pioneers of the technique, used DNA-DNA hybridization to examine the phylogenetic relationships of avians (the Sibley-Ahlquist taxonomy) and primates. Critics argue that the technique is inaccurate for comparison of closely related species, as any attempt to measure differences between orthologous sequences between organisms is overwhelmed by the hybridization of paralogous sequences within an organism's genome. DNA sequencing and computational comparisons of sequences is now generally the method for determining genetic distance, although the technique is still used in microbiology to help identify bacteria.

# Method
The method, as developed by Sibley and Ahlquist, compares the melting of a labeled sample after it is hybridized to itself vs. its melting after hybridized to unlabeled DNA of another organism. DNA from the two species to be compared is extracted, purified and cut into short pieces (e.g., 600-800 base pairs). The DNA of one organism is labeled, then mixed with the unlabelled DNA to be compared against. The mixture is incubated to allow DNA strands to dissociate and reanneal, forming hybrid double-stranded DNA. Hybridized sequences with a high degree of similarity will bind more firmly, and require more energy to separate them: i.e. they separate when heated at a higher temperature than dissimilar strands, a process known as "DNA melting".
To assess the melting profile of the hybridized DNA, the double-stranded DNA is bound to a column and the mixture is heated in small steps. At each step, the column is washed; sequences that melt become single-stranded and wash off the column. The temperatures at which labeled DNA comes off the column reflects the amount of similarity between sequences (and the self-hybridization sample serves as a control). These results are combined to determine the degree of genetic similarity between organisms.
DNA polymerase lambda
DNA polymerase lambda, also known as POLL, is a protein found in eukaryotes. In humans, it is encoded by the POLLA gene.

# Function
Pol  is a member of the X family of DNA polymerases.  It is thought to resynthesize missing nucleotides during non-homologous end joining (NHEJ), a pathway of DNA double-strand break (DSB) repair. NHEJ is the main pathway in higher eukaryotes for repair of DNA DSBs.  Chromosomal DSBs are the most severe type of DNA damage.  During NHEJ, duplexes generated by the alignment of broken DNA ends usually contain small gaps that need to be filled in by a DNA polymerase.  DNA polymerase lambda can perform this function.
The crystal structure of pol  shows that, unlike the DNA polymerases that catalyze DNA replication, pol  makes extensive contacts with the 5' phosphate of the downstream DNA strand.  This allows the polymerase to stabilize the two ends of a double-strand break and explains how pol  is uniquely suited for a role in non-homologous end joining.
In addition to NHEJ, pol  can also participate in base excision repair (BER), where it provides backup activity in the absence of Pol .  BER is the major pathway for repair of small base damages resulting from alkylation, oxidation, depurination/depyrimidination, and deamination of DNA.
Besides its catalytic polymerase domain, pol  has an 8 kDa domain and a BRCT domain.  The 8 kDa domain has lyase activity that can remove a 5' deoxyribosephosphate group from the end of a strand break.  The BRCT domain is a phosphopeptide binding domain that is common among DNA repair proteins and is likely involved in coordinating protein-protein interactions.  Pol  is structurally and functionally related to pol , another member of the X family that also participates in non-homologous end joining.  Like pol , pol  participates in V(D)J recombination, the process by which B-cell and T-cell receptor diversity is generated in the vertebrate immune system.  Whereas pol  is important for heavy-chain rearrangements, pol  seems to be more important for light-chain rearrangements.  The yeast Saccharomyces cerevisiae has a single homolog of both pol  and pol  called Pol4.
Translesion synthesis is a damage tolerance mechanism in which specialized DNA polymerases substitute for replicative poymerases in copying across DNA damages during replication.  DNA polymerase lambda appears to be involved in translesion synthesis of abasic sites and 8-oxodG damages.

# Interactions
Pol  has been shown to interact with PCNA.
Diastrophic dysplasia

# Overview
Diastrophic dysplasia (DTD) is an autosomal recessive congenital disorder which affects cartilage and bone development.
Affected individuals have short stature with very short arms and legs and joint problems that restrict mobility.

# Symptoms
This condition is also characterized by an inward- and downward-turning foot (called clubfoot), progressive curvature of the spine, and unusually positioned thumbs (hitchhiker thumbs). About half of infants with diastrophic dysplasia are born with an opening in the roof of the mouth called a cleft palate. Swelling of the external ears is also common in newborns and can lead to thickened, deformed ears.
The signs and symptoms of diastrophic dysplasia are similar to those of another skeletal disorder called atelosteogenesis, type 2. Diastrophic dysplasia tends to be less severe, however.

# Genetic prevalence
Diastrophic dysplasia affects about 1 in 100,000 births. Mutations in the SLC26A2 gene cause diastrophic dysplasia, and it is one of a spectrum of skeletal disorders caused by mutations in the SLC26A2 gene. The protein made by this gene is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, but in adulthood this tissue continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of diastrophic dysplasia.
This condition is an autosomal recessive disorder, which means the defective gene is located on an autosome, and both parents must carry one copy of the defective gene in order to have a child born with the disorder. The parents of a child with an autosomal recessive disorder are usually not affected by the disorder.

# Diagnosis
Dark field microscopy

# Overview
Dark field microscopy (Dark Ground Microscopy) is an optical microscopy illumination technique used to enhance the contrast in unstained samples. It works on the principle of illuminating the sample with light that will not be collected by the objective lens, so not form part of the image. This produces the classic appearance of a dark, almost black, background with bright objects on it.

# The light's path
- Light enters the microscope for illumination of the sample.
- A specially sized disc, the "patch stop" blocks some light from the light source, leaving an outer ring of illumination.
- The condenser lens focuses the light towards the sample.
- The light enters the sample. Most is directly transmitted, while some is scattered from the sample.
- The scattered light enters the objective lens, while the directly transmitted light simply misses the lens and is not collected.
- Only the scattered light goes on to produce the image, while the directly transmitted light is omitted.

# Advantages and disadvantages
Dark field microscopy is a very simple yet effective technique and well suited for uses involving live and unstained biological samples, such as a smear from a tissue culture or individual water borne single-celled organisms. Considering the simplicity of the setup, the quality of images obtained from this technique are impressive.
The main limitation of dark field microscopy is the low light levels seen in the final image. This means the sample must be very strongly illuminated, and can cause damage to the sample.
Dark field microscopy techniques are almost entirely free of artifacts, due to the nature of the process. However the interpretation of dark field images must be done with great care as common dark features of bright field microscopy images may be invisible, and vice versa.

# Related chapters
- Syphilis Lab Test

# Resources
- Live blood photos under a Darkfield Microscope
Darunavir description

# Description
PREZISTA (darunavir) is an inhibitor of the human immunodeficiency virus (HIV-1) protease. PREZISTA (darunavir), in the form of darunavir ethanolate, has the following chemical name: amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamic acid (3R,3aS,6aR)-hexahydrofurofuran-3-yl ester monoethanolate. Its molecular formula is C27H37N3O7S - C2H5OH and its molecular weight is 593.73. Darunavir ethanolate has the following structural formula:
Darunavir ethanolate is a white to off-white powder with a solubility of approximately 0.15 mg/mL in water at 20C.
PREZISTA 100 mg/mL oral suspension is available as a white to off-white opaque suspension for oral administration.
PREZISTA 75 mg tablets are available as white, caplet-shaped, film-coated tablets for oral administration. PREZISTA 150 mg tablets are available as white, oval-shaped, film-coated tablets for oral administration. PREZISTA 600 mg tablets are available as orange, oval-shaped, film-coated tablets for oral administration. PREZISTA 400 mg tablets are available as light orange, oval-shaped, film-coated tablets for oral administration. PREZISTA 800 mg tablets are available as dark red, oval-shaped, film-coated tablets for oral administration.
Each mL of the oral suspension contains darunavir ethanolate equivalent to 100 mg darunavir. In addition, each mL contains the inactive ingredients hydroxypropyl cellulose, microcrystalline cellulose, sodium carboxymethylcellulose, methylparaben sodium, citric acid monohydrate, sucralose, masking flavor, strawberry cream flavor, hydrochloric acid (for pH adjustment) and purified water.
Each 75 mg tablet contains darunavir ethanolate equivalent to 75 mg of darunavir. Each 150 mg tablet contains darunavir ethanolate equivalent to 150 mg of darunavir. Each 400 mg tablet contains darunavir ethanolate equivalent to 400 mg of darunavir. Each 600 mg tablet contains darunavir ethanolate equivalent to 600 mg of darunavir. Each 800 mg tablet contains darunavir ethanolate equivalent to 800 mg of darunavir. During storage, partial conversion from ethanolate to hydrate may occur; however, this does not affect product quality or performance. Each tablet also contains the inactive ingredients colloidal silicon dioxide, crospovidone, magnesium stearate, and microcrystalline cellulose. The 800 mg tablet also contains hypromellose. The 75 and 150 mg tablet film coating, OPADRY White, contains polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, and titanium dioxide. The 400 and 600 mg tablet film coating, OPADRY Light Orange and OPADRY Orange, respectively, contains FD&C Yellow No. 6, polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, and titanium dioxide. The 800 mg tablet film coating, OPADRY Dark Red, contains iron oxide red, polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, and titanium dioxide.
All dosages for PREZISTA are expressed in terms of the free form of darunavir.
Toe pain and swelling

# Overview
Causes can be as simple as trauma or infection. They can also be rheumatoid arthritis, endocarditis or athlerosclerotic vascular disease. The most common cause/complaint is Gout.
Gout can be so excruciating at times that even the weight of a bed sheet is unbearable.

# Differential Diagnosis
In alphabetical order.  
- Cholesterol emboli
- Infective endocarditis
- Ingrown toenail
- Pseudogout
- Seronegative spondyloarthropathy
- Septic arthritis
- Trauma

# Laboratory Findings
- CBC
- Electrolytes
- BUN / creatinine
- Calcium
- Magnesium
- Phosphorus
- ESR
- Lyme titers
- Iron (psudogout)
- Synovial fluid analysis

## Imaging Findings
- Radiographs
- Fractures
- Osteomyelitis signs
- Psoriatic arthritis

## Other Diagnostic Studies
- Synovial fluid analysis
- Look for an infection, crystals, inflammation
- Gram stain, polarized light microscopy
- Cell counts should result in a WBC count less than 50,000/ml if inflamed
- Cell counts should result in a WBC count greater than 50,000/ml in infectious arthritis

# Treatment

## Acute Pharmacotherapies
Gout
- NSAID's
- Colchicine

## Chronic Pharmacotherapies
Gout
- Urate lowering agents
- Colchicine
Ingrown toenails
- Warm soaks
- Toe nail removal
Pseudogout
- NSAIDs
- Corticosteroids
- Colchicine
Reiter's Syndrome
- Prednisone
- Local steroid injection
- Sulfasalazine
- Methotrexate
- Indomethacin
Septic arthritis
- Ceftriaxone -> gram negative infections
- Cefazolin -> gram positive (add gentamicin for psudomonal infections)
Profunda femoris vein
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Profunda femoris vein (or deep femoral vein) is a large deep vein in the thigh.
Its course runs along side of the profunda femoris artery and it drains into the femoral vein.

# Additional images
- Scheme of the femoral artery.
delta Opioid receptor
The -opioid receptors, also known as delta opioid receptor or simply delta receptor, abbreviated DOR, is an opioid receptor that has enkephalins as their endogenous ligands.

# Function
Until comparatively recently, there were few pharmacological tools for the study of  receptors. As a consequence, our understanding of their function is much more limited than those of the other opioid receptors for which selective ligands have long been available.
However there are now several selective delta opioid agonists available, including peptides such as DPDPE and deltorphin II, and non-peptide drugs such as SNC-80, the more potent (+)-BW373U86, a newer drug DPI-287 which does not produce the problems with convulsions seen with the earlier agents, and the mixed mu/delta agonist DPI-3290 which is a much more potent analgesic than the more highly selective delta agonists. Selective antagonists for the delta receptor are also available, with the best known being the opiate derivative naltrindole.
Activation of delta receptors produces some analgesia, although less than that of mu-opioid agonists. Many delta agonists may also cause seizures at high doses, although not all delta agonists produce this effect.
Evidence for whether delta agonists produce respiratory depression is mixed; high doses of the delta agonist peptide DPDPE produced respiratory depression in sheep, but in tests on mice the non-peptide delta agonist SNC-80 produced respiratory depression only at the very high dose of 40 mg/kg. In contrast both the peptide delta agonist Deltorphin II and the non-peptide delta agonist (+)-BW373U86 actually stimulated respiratory function and blocked the respiratory depressant effect of the potent mu-opioid agonist alfentanil, without affecting pain relief. It thus seems likely that while delta opioid agonists can produce respiratory depression at very high doses, at lower doses they have the opposite effect, a fact which may make mixed mu/delta agonists such as DPI-3290 potentially very useful drugs which might be much safer than the mu agonists currently used for pain relief.
Of most interest however is the potential for delta agonists to be developed for use as a novel class of antidepressant drugs, following robust evidence of both antidepressant effects and also upregulation of BDNF production in the brain in animal models of depression. These antidepressant effects have been linked to endogenous opioid peptides acting at delta and mu opioid receptors, and so can also be produced by enkephalinase inhibitors such as RB-101.
Recent work indicates that exogenous ligands which activate the delta receptors mimic the phenomenon known as ischemic preconditioning. Experimentally, if short periods of  transient ischemia are induced the downstream tissues are robustly protected if longer-duration interruption of the blood supply is then effected.  Opiates and opioids with delta activity mimic this effect.  In the rat model introduction of delta active ligands results in significant cardioprotection.
Delta opioid receptor
-Opioid receptors are a class of opioid receptor which have enkephalins as their endogenous ligands.

# Function
Activation of the receptors produces analgesia. Some research suggests that they may also be related to seizures.
Until quite recently, there were few pharmacological tools for the study of  receptors. As a consequence, our understanding of their function is much more limited than those of the other opioid receptors.
Recent work indicates that exogenous ligands which activate the delta receptors mimic the phenomenon known as ischemic preconditioning. Experimentally, if short periods of  transient ischemia are induced the downstream tissues are robustly protected if longer-duration interruption of the blood supply is then effected.
Opiates and opioids with delta activity mimic this effect. In the rat model introduction of delta active ligands results in significant cardioprotection.
Demyelinating disease
A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged.  This impairs the conduction of signals in the affected nerves, causing impairment in sensation, movement, cognition, or other functions depending on which nerves are involved.
The term describes the effect of the disease, rather than its cause; some demyelinating diseases are caused by genetics, some by infectious agents, some by autoimmune reactions, and some by unknown factors.  Organo-phosphates, a class of chemicals which are the active ingredients in commercial insecticides such as sheep dip, weed-killers, and flea treatment preparations for pets, etc, will also demyelinate nerves.

# Demyelinating diseases of the central nervous system
- multiple sclerosis (together with the similar diseases called idiopathic inflammatory demyelinating diseases)
- transverse myelitis
- Devic's disease
- progressive multifocal leukoencephalopathy

# Demyelinating diseases of the peripheral nervous system
- Guillain-Barre syndrome and its chronic counterpart, chronic inflammatory demyelinating polyneuropathy
- anti-MAG peripheral neuropathy.
Soft laser desorption
Soft laser desorption is laser desorption of large molecules that results in ionization without fragmentation. "Soft" in the context of ion formation means forming ions without breaking chemical bonds. "Hard" ionization is the formation of ions with the breaking of bonds and the formation of fragment ions.

# Background
The term "soft laser desorption" has not been widely used by the mass spectrometry community, which in most cases uses matrix-assisted laser desorption/ionization (MALDI) to indicate soft laser desorption ionization that is aided by a separate matrix compound. The term soft laser desorption was used most notably by the Nobel Foundation in public information released in conjunction with the 2002 Nobel Prize in Chemistry. Koichi Tanaka was awarded 1/4 of the prize for his use of a mixture of cobalt nanoparticles and glycerol in what he called the ultra fine metal plus liquid matrix method of laser desorption ionization. With this approach, he was able to demonstrate the soft ionization of proteins. The MALDI technique was demonstrated (and the name coined) in 1985 by Michael Karas, Doris Bachmann, and Franz Hillenkamp, but ionization of proteins by MALDI was not reported until 1988, immediately after Tanaka's results were reported.
Some have argued that Karas and Hillenkamp were more deserving of the Nobel Prize than Tanaka because their crystalline matrix method is much more widely used than Tanaka's liquid matrix. Countering this argument is the fact that Tanaka was the first to use a 337 nm nitrogen laser while Karas and Hillenkamp were using a 266 nm Nd:YAG laser. The "modern" MALDI approach came into being several years after the first soft laser desorption of proteins was demonstrated.

# Examples in mass spectrometry
The matrix-assisted laser desorption/ionization approach typically uses a small organic acid solid matrix, although liquids have been used. The light source is a pulsed IR or UV laser. The  surface-enhanced laser desorption/ionization (SELDI) variand is similar to  MALDI, but uses a biochemical affinity target. The technique known as surface-enhanced neat desorption (SEND) is a variant of MALDI with the matrix is covalently linked to the target surface.The surface-assisted laser desorption/ionization (SALDI) approach can be described as MALDI using a liquid plus particulate matrix. The desorption ionization on silicon (DIOS) approach is laser desorption/ionization of a sample deposited on a porous silicon surface. The technique known as laser induced acoustic desorption (LIAD ) is transmission geometry LDI with a metal film target.