20240722_184420

p: (=Effect) 는 표준식으로 log2 fold-change after adjusting for the covariate effects on the outcome”.

Psychosis in PD

pipeline

Target	mechanism	Design	results
Nuplazid (pimavanserin) by Acadia	- approved by the FDA for the treatment of hallucinations and delusions associated with PD psychosis - an inverse agonist and antagonist at serotonin 5-HT2A receptors with high binding affinity (Ki 0.087 nM) and at serotonin 5-HT2C receptors with lower binding affinity (Ki 0.44 nM). Acadia developed (?)/used a new scale called Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D), (Acadia modified the clinical score such as deletion of synptom that pimavanserin didn't work on)

Radiochemical

	radioactivity	specific activity (Ci/mmol)	tSIS,	CPM: Counts per minute.	Efficiency	DPM (AK For binding I use DPM typically)	Concentration - fmol/mg	Concentration - molarity
	Curies per millimole (Ci/mmol) 1 Ci equals 2.22 × 10¹² dpm (disintegrations per minute) AK: 2220000dpm = 1 uci	the amount of radiolabeled mass in a sample, Ci/mmol or Ci/mg. For example, 33P-gamma-ATP has a specific activity of 3000 Ci/mmol (on the calibration date). These units indicate that there are 3000 Curies per millimole of ATP	Transformed spectral index of the sample, (?) Quench correction methods In all liquid scintillation counting, there is some degree of reduction of efficiency of counting due to an interference with energy transfer processes leading to the production of a photon or to absorption of the photon by coloured or other light-absorbing substances present.s	CPM provides for the exact quantity of those atoms that have actually decayed. CPM: Quenched sample count rates	This value will be based on the type of radiation detector being used and the energy of the radioactive isotopes. Efficiency is a parameter measured as part of IPA (Instrument Performance Assessment) -Efficiency is the fraction of the radioactive disintegration that are detected by the counter. -With 3H, counting efficiency is much lower (maximally ca. 60%)	DPM merely measures the number of atoms that decay in one minute given a select amount of radioactive material. DPM: absolute activity 2220000dpm = 1 uci	[Homogenate binding assay] fmol/mg = fmole radioligand bound per mg of protein (One fmol is 10⁻¹⁵ mol.) 분모가 i) homogenate 실험의 경우는 바로 protein의 mg일 것. Convert from cpm to fmol/mg using the amount of protein in each tube (0.01 mg), the efficiency of the counting (90%), and the specific radioactivity of the ligand (2190 Ci/mmol). fmol/mg = cpm / (2.22 × 10¹² dpm Ci × 0.90 cpm/dpm × 2190 Ci mmol × 10⁻¹² mmol/fmol × 0.01 mg) Good resource: 'Analyzing Binding Data'	[Homogenate assay] Assumptions: - the brain density around 1 g wet weight; assumes ~1 mg of protein per mg of wet weight -1 fmol/mg of protein 으로 be approximated 0.1 fmol/mg of wet tissue. [ARG] (2008 Patel) Assumption for ARG study: there is 50 mg of protein per g of brain tissue. So, 100 fmol/mg protein 은 5 nM. (This conversion factor is only valid for brain) 근데 위의 assumption 이해 안 감. saturation binding (only HC)에서 AK가 계산한 Kd를 써서 nM로 바꾼듯 한데.
e g				tSIS value: a parameter to monitor for the color quench level of samples,	22,000	22%	DPM = CPM / Efficiency DPMs = 22,000 / .22 = 100,000. This means that given a measurement of 22,000 CPMs as per a 22% efficiency rating, this measurement is equivalent to 100,000 DPMs.
	I'm assuming they're still using the tSIS error to calculate DPM? If you could ask TNTechnos for their normalization file for tritium and their IPA				I'm assuming they're still using the microβ platereader?).	TNT are still using the tSIS error to calculate DPM? If you could ask TNTechnos for their normalization file for tritium and their IPA
When a radioactive decay event occurs in an LSC cocktail → Scintillator (a type of phosphor) emit fluorescence when exposed to radiation such as X-rays and gamma rays. The molecules of the fluors/scintillator dissolved in the solvent absorb the energy released by the solvent and re-emit this energy (at a higher wavelength) as visible light of wavelength around 420 nm
Definitions Radioactive decay. - the process by which an unstable isotope emits energy to reach a more stable state (Entropy). Radioactive material decays until only stable substance is left and the decay of a substance is fixed and measurable Half life - the time it takes for a product to decay sufficiently to convert half of its mass to a stable form. The half life of an isotope is fixed Curie or Ci - the most common unit of measure for the radioactivity of a substance. 1 Ci = 3.7×10¹⁰ disintegrations per second = 2.22×10¹² disintegrations per minute (dpm). The term is most often used as a microCurie (μCi). 1 μCi = 3.7×10⁴ disintegrations per second = 2.22×10⁶ disintegrations per minute (dpm). Bequerel or Bq - IUPAC unit of measure for radioactivity of a substance. 1 Bq = the quantity of material in which one nucleus decays per second. dpm - disintegrations per minute. measures of the activity of the source of radioactivity. This unit is directly related to the count one detects in a radiometric detection instrument. Specific activity (SA) - the amount of radiolabeled mass in a sample, often expressed as Ci/mmol or Ci/mg. For example, 33P-gamma-ATP in below has a specific activity of 3000 Ci/mmol on the calibration date. These units indicate that there are 3000 Curies per millimole of ATP. Specific activity can be changed by adding more "cold" (unlabeled) compound (in this case, unlabeled ATP). Theoretical maximum specific activity Each radioisotope has a maximum theoretical specific activity if 100% of the molecules contain one isotopic label. For example, the theoretical maximum specific activity is ~5000 Ci/mmol. The closer the specific activity of 33P-gamma-ATP (which has only one possible labeling position) is to the theoretical maximum specific activity for 33P, the greater the proportion of nucleotide molecules that are labeled with the radioisotope. See also Percent radioactive material. radioactive concentration, =radiochemical conc (mCi/mL or μCi/mL) - the total amount of radioactivity per unit volume Molar concentration (μM) - the total concentration (in moles) of both the labeled and unlabeled product per unit volume resource https://www.perkinelmer.com/lab-products-and-services/application-support-knowledgebase/radiometric/radiochemical-calculations.html calculator Radiochemical calculator online tool. This is only for PerkinElmer's counters. • 1 Bq = 2.7×10⁻¹¹ Ci = 1 dps = 60 dpm • 1 Ci = 3.7×10¹⁰ Bq = 3.7×10¹⁰ dps = 2.22×10¹² dpm unit conversion To convert from to: Multiply by: from Ci to Bq 3.7×10¹⁰ from Bq to Ci 2.7×10⁻¹¹ from Ci to dpm 2.22×10¹² from mCi to dpm 2.22×10⁹ from nCi to dpm 2.22×10³ from dpm to Ci 4.50×10⁻¹³ from dpm to mCi 4.50×10⁻¹⁰ from Bq to dpm 60 from TBq to dpm 6.0×10¹³ from dpm to Bq 1.67×10⁻² from dpm to TBq 1.67×10⁻¹⁴ Notes: 1 mCi (milliCurie) = 10⁻³ Ci 1 TBq (TeraBecquerel) = 10¹² Bq

Rare Disease

			Population
sPD		1mil in US	3 억 (US population) 0.3% (NLRP3 EPOP) 즉 3/1,000
		1	300
GBA-PD			US: 1 Mil의 10% → 100,000 (200,000보다 적으니 rare disease이긴 하네)
CMT1		1	2,500
AGS		1-5	10,000 orpha.net/consor/cgi-bin/OC_Exp.php?Expert=51&lng=EN
FTLD-Tau		1	20,000 5-7 per 100,000 {Bahia, 2013 #21}: 위와 유사해야 하는데, Daria: 10-20/100,000 (theoretical genetic prevalence of biallelic ...)

(Page footer table continues onto next photo with Terminology columns “in general population” / “with symptomatic PD” / “mutations with symptomatic PD” — United States and Europe 23,000-70,000 / 1,622-13,000 / 33,000-45,000; United States 10,000-30,000 / 930-7,400 / 19,000-26,000.)

Uncertain Spans

location	transcription	uncertainty
ARG concentration cell	1 fmol/mg of protein 으로 be approximated 0.1 fmol/mg of wet tissue	Mixed Korean/English fragment with non-standard “be approximated” verb form; preserved as written.