Hit threshold

A sample that produces confirmed activity above the hit threshold in an assay and whose structural identity has been confirmed. A substance becomes a HIT when the properties of an ACTIVE are confirmed by elimination of FALSE POSITIVE... 

The portion of hits that displays confirmed activity in a screen beyond a minimum defined level, the hit threshold. Expressed as a percentage. 

The minimum activity that defines ACTIVES in a PRIMARY SCREEN. It is usually expressed as percentage of inhibition or stimulation. For example, a widely used hit threshold is 50%. 

A substance that does not produce a response above the hit threshold in an assay at the tested concentration. Note a substance may also be designated as inactive when attempts to confirm an ACTIVE fail. 

Hits were defined using a hit threshold of 24 % inhibition, corresponding to the average plus three standard deviations. 

In general, the attempt to retest every compound that passes a statistically defined threshold of activity for each assay and to implement a concomitant assay interference test has been rewarded by recovery of a full spectrum of biological activities and diverse chemotypes in the confirmed hit set. In many cases, the compounds that the medicinal chemists ultimately judge to be the best starting points for lead development exhibited only modest activity (e.g., IC50 values of 0.5-5 pM) in HTS. 

One important point of controversy in risk extrapolation is the existence of the threshold level for carcinogenic and mutagenic response to a pollutant. Some argue that an organism is able to cope with low doses of a substance through metabolic processes or repair mechanisms, so that harmful effects do not appear until a certain minimum threshold, or "safe dose", is surpassed. Others contend that a carcinogenic substance must be considered potentially harmful at any dose, and that even a single molecule may initiate a tumor at the cellular level. This is the so-called "one-hit" hypothesis. 

The most widely-accepted dose response model at the present time is the multi-stage model, which has great flexibility in curve-fitting, and also has a strong physiological justification. Although it is difficult to implement, there are already computer codes in existence that estimate the model parameters (13). The two most widely-used models, until recently, were the one-hit model and the log-probit model. They are both easy to implement, and represent opposite extremes in terms of shape - the former represents the linear non-threshold assumption, whereas the latter has a steep threshold-like curvature. In numerous applications with different substances it has been found that these three... 

Similarly if you toggle the enable pin at a certain rate in many ICs you can get to see current overshoots too. This often depends on allowing the input capacitor to discharge below the UVLO threshold, but not to the point where it hits the internal POR (power on reset) threshold. Because in that case, if you suddenly enable the IC, it has no soft-start anymore, and you will hit max duty cycle, and possibly staircase if the current limit circuitry is not well designed. 

The software tools accompanying the QTRAP MS/MS allow set-up of multiple selected reaction monitoring (SRM) transitions for all likely metabolites after the major product ion transitions for the dosed compound are known. Because QTRAP MS/MS can monitor up to 100 SRM transitions during a single assay, the SRM transitions required for quantitation of the dosed compound and internal standard are obtained along with the possible metabolite transitions. During sample analysis, when a possible metabolite transition exceeds a preset threshold value, the QTRAP MS/MS performs an enhanced product ion (EPI) scan. When the assay is complete, the EPI scans can be used to determine whether the hits are metabolites, and if they are metabolites, what part of the molecule has changed. Thus, one analytical run provides both quantitative and metabolite information. 

Synthesis of Subsection 3.2.4 - Only a minor fraction of sprayed pesticides hits the intended target, while most of them pollute the environment however, pesticides cannot be abandoned. IPM helps to enormously reduce their use and is presently progressing towards the proactive approach . It is impossible to totally ban chemical pesticides, also because botanicals and the other pesticides permitted by organic agriculture are less effective and/or more polluting. One major problem is the determination of threshold values for the treatments. 

One-third of these appeared in the actives for the assay, which was defined using a 30% inhibition threshold. The overall hit rate for the assay was 2.0% in other words, 20% of the actives were false positives due to extreme optical interference with the assay readout. This number rises depending on the level of initial fluorescence used as a cutoff in the selection scheme used by the project team at the time, almost half of the actives were rejected as false positives on the basis of the initial fluorescence readings. The corporate screening collection has been reformatted since then, and many of these problem compounds have been removed. 

A compound is flagged as either active or inactive on the basis of the activity threshold determined as in Section 6.2.2. The probability that the observed number of actives x occurs in a cluster of size n given a background hit rate p (expressed as a fraction) is determined by the binomial probability mass function [38], shown as follows ... 

Next, custom software is used to interrogate the deconvoluted data set to identify the protein s mass and the intensity of the peak, determine any potential modification above a user-defined intensity threshold and, if there is a hit, calculate the mass and the relative conjugation of the fragment. In fact, the percent conjugation is used as a measure of relative affinities of the fragment hits. Since the library is mass encoded (all compounds in a well have a unique mass), the calculated mass of any hits are queried into a database to identify their structures. 

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