The starting unit is then modified by a series of Claisen condensations with malonyl or methylmalonyl substrates, which are attached to an acyl carrier protein (ACP) and extend the polyketide by two carbons each. After each successive condensation, the growing polyketide is further modified according to enzymatic domains that are present to reduce and dehydrate it, thereby introducing the diversity of functionalities observed in rapamycin (figure 1). Once the linear polyketide is complete, L-pipecolic acid, which is synthesized by a lysine cycloamidase from an L-lysine, is added to the terminal end of the polyketide by an NRPS. Then, the NSPS cyclizes the polyketide, giving prerapamycin, the first enzyme-free product. The macrocyclic core is then customized by a series of post-PKS enzymes through methylations by MTases and oxidations by P-450s to yield rapamycin. Research
Cancer
The antiproliferative effects of sirolimus may have a role in treating cancer. When dosed appropriately, sirolimus can enhance the immune response to tumor targeting or otherwise promote tumor regression in clinical trials. Sirolimus seems to lower the cancer risk in some transplant patients.Sirolimus was shown to inhibit the progression of dermal Kaposis sarcoma in patients with renal transplants. Other mTOR inhibitors, such as temsirolimus (CCI-779) or everolimus (RAD001), are being tested for use in cancers such as glioblastoma multiforme and mantle cell lymphoma. However, these drugs have a higher rate of fatal adverse events in cancer patients than control drugs.A combination therapy of doxorubicin and sirolimus has been shown to drive Akt-positive lymphomas into remission in mice.
Hypercementosis is an idiopathic, non-neoplastic condition characterized by the excessive buildup of normal cementum (calcified tissue) on the roots of one or more teeth. A thicker layer of cementum can give the tooth an enlarged appearance, which mainly occurs at the apex or apices of the tooth. Signs and symptoms
It is experienced as an uncomfortable sensation in the tooth, followed by an aching pain.It may be shown on radiographs as a radiopaque (or lighter) mass at each root apex. Cause
Can be caused by many things. A way to remember the causes is "PIG ON TAP"Local factors- 

Occlusal Trauma
Trauma
Non-functional tooth
Unopposed tooth (and impacted teeth, embedded teeth, teeth without antagonists)Systemic factors-

Idiopathic
Pituitary Gigantism
Pagets Disease
Acromegaly
Periapical granuloma
Arthritis
Calcinosis
Rheumatic feverIt may be one of the complications of Pagets disease of bone in the form of generalized hypercementosis. It may also be a compensatory mechanism in response to attrition to increase occlusal tooth height. Complications
Such deposits form bulbous enlargements on the roots and may interfere with extractions, especially if adjacent teeth become fused (concrescence). It may also result in pulpal necrosis by blocking blood supply via the apical foramen. References


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