A modifier is essentially a variable used in internal calculations. However, unlike Defines, modifiers are dynamically changeable within any modifier block. In general, modifiers are typically used to create a consistent and long-lasting effect that can be easily reversed.Each modifier has the exact same layout: modifier_name = 0.1. This adds the specified value to the modifier's total value for the scope where it is applied. For example, assuming that there are no other modifiers changing that to the country, having political_power_gain = 0.2 and political_power_gain = -0.05 applied to the country (potentially in different modifier blocks) will result in a total of +0.15 political power gain above the base gain. Due to how modifiers work, a modifier with the value of 0 will always do nothing.A modifier's current total value can be received as a variable by reading modifier@modifier_name, such as set_variable = my_var = modifier@political_power_gain . This works for countries and states, but for unit leaders, unit_modifier@modifier_name and leader_modifier@modifier_name is used instead.
No modifiers can have a non-numeric value, including boolean ones that must be 1 to have any effect.Note that modifiers do not support if statements. The closest replica possible of one are dynamic modifiers, which allow using variables.
Victoria 2 Static Modifiers
Modifier blocks support, within them, the hidden_modifier = ... block, which can be used to provent the modifiers within from showing up in the tooltip. Additionally, custom_modifier_tooltip = localisation_key_tt can be used to add a custom localisation string to appear within the localisation as one of the modifiers. In combination, this will look like the following:
Dynamic modifiers, defined in /Hearts of Iron IV/common/dynamic_modifiers/*.txt files, are a type to apply modifiers that accept variables. The modifiers are updated daily, unless the force_update_dynamic_modifier effect is used to forcefully refresh the impact of modifiers. They can be applied to both countries and states, in case of the latter, the variable must be defined for the state, not for the country-owner or controller. They can also be applied to unit leaders.
Modifiers that use variables will not show up in the tooltip of add_dynamic_modifier, while those that are set to a static value will. While this may make the dynamic modifier appear broken when only reading the tooltip, this will not be actually the case once it gets added. In this case, the tooltip of the effect can be changed, with the effect adding the dynamic modifier hidden.
Static modifiers are stored in /Hearts of Iron IV/common/modifiers/*.txt files, where each code block within is a modifier block with the name being the ID of the static modifier. There are 4 main categories of static modifiers:
Global modifiers are applied by the hard-coded game features. Their names mustn't be changed, as the code uses them internally, but their effects can be edited. Examples of global modifiers are the penalty for non-core states or the effects of stability and war support.
Not to be confused with opinion modifiers. The relation modifiers apply a targeted modifier from one country towards an another one, automatically removed when the trigger is met. ROOT is the country that the modifier is applied to and FROM is the target. An example would be:
Province modifiers apply a modifier to a specific province rather than a state. They can be applied via the add_province_modifier effect, and removed with remove_province_modifier. More info on how to use these can be seen in the effects page.An example definition looks like
Many state-scope modifiers will work in province scope as well. In order to make the GFX in GUI, you first need to edit /Hearts of Iron IV/interface/countrystateview.gui. The icon must be defined inside custom_icon_container, similarly to other examples. An example definition looks like
The list of modifiers may be outdated. A complete, but unsorted, list of modifiers can be found in /Hearts of Iron IV/documentation/modifiers_documentation.html or /Hearts of Iron IV/documentation/modifiers_documentation.md.
These modifiers are targeted, meaning that they must be used in a block for targeted modifiers rather than regular modifiers. These include targeted_modifier = ... in ideas, traits, advisors, and decisions; relation modifiers.A targeted_modifier block is structured as such:
Each carcinoma was assigned to a morphologic subgroup (ductal, lobular, medullary, other), which was confirmed using the World Health Organisation International Classification of Diseases 0 code for the classification of tumour type when present. Lymph node status, along with the number of nodes showing metastatic carcinoma, was provided when available. Staging data were based on the AJCC Cancer Staging Manual, Sixth Edition [19], with data provided on overall stage and its major attributes (primary tumour size, regional lymph node involvement and presence of distant metastasis). Histologic grade was determined by local pathologists using modifications of the Scarff-Bloom-Richardson histological grading system as grade 1, 2 or 3. Pathology data for FBCs included in the study are described in detail elsewhere [13].
Breast cancer risk for BRCA1 and BRCA2 pathogenic mutation carriers is modified by risk factors that cluster in families, including genetic modifiers of risk. We considered genetic modifiers of risk for carriers of high-risk mutations in other breast cancer susceptibility genes.
There is marked variability in individual cancer risk between and within BRCA1 and BRCA2 mutation carrier families [1, 2]. Accumulating evidence reviewed in [3] indicates that breast cancer risk in mutation carriers is modified by several risk factors that cluster in families, including genetic modifiers of risk that influence mutation penetrance. Segregation analyses studies have demonstrated that risk prediction models that allow for genes to modify effect on breast cancer risk in BRCA1 and BRCA2 mutation carriers fit significantly better to familial data than models without a modifying component.
Genetic modifiers of risk for carriers of high-risk mutations in other breast cancer susceptibility genes, such as PALB2, are yet to be described. In this study, we examined the exomes of key members of a multiple-case family segregating the pathogenic PALB2:c.3113G>A (p.Trp1038*) mutation (Family A, Fig. 1) to explore the possibility that additional genetic factors could be responsible for modifying the breast cancer risk in this family.
Further work is required to test the hypothesis raised in this report. Studies of genetic modifiers utilising very large sample sizes can be achieved through the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) [3] who have collected DNA and epidemiological and clinical data for over 15,000 BRCA1 carriers and 8,000 BRCA2 carriers. Similar future studies related to PALB2 mutation carriers could possibly be achieve within the PALB2 Interest Group www.palb2.org.
Modifier genes/variants could partly explain inter-individual variation in risk between pathogenic mutation carriers. The identification of modifiers of breast cancer risk will help to refine individual risk estimates and optimise risk management.
Some years ago we established an N-ethyl-N-nitrosourea screen for modifiers of transgene variegation in the mouse and a preliminary description of the first six mutant lines, named MommeD1-D6, has been published. We have reported the underlying genes in three cases: MommeD1 is a mutation in SMC hinge domain containing 1 (Smchd1), a novel modifier of epigenetic gene silencing; MommeD2 is a mutation in DNA methyltransferase 1 (Dnmt1); and MommeD4 is a mutation in Smarca 5 (Snf2h), a known chromatin remodeler. The identification of Dnmt1 and Smarca5 attest to the effectiveness of the screen design.
We have now extended the screen and have identified four new modifiers, MommeD7-D10. Here we show that all ten MommeDs link to unique sites in the genome, that homozygosity for the mutations is associated with severe developmental abnormalities and that heterozygosity results in phenotypic abnormalities and reduced reproductive fitness in some cases. In addition, we have now identified the underlying genes for MommeD5 and MommeD10. MommeD5 is a mutation in Hdac1, which encodes histone deacetylase 1, and MommeD10 is a mutation in Baz1b (also known as Williams syndrome transcription factor), which encodes a transcription factor containing a PHD-type zinc finger and a bromodomain. We show that reduction in the level of Baz1b in the mouse results in craniofacial features reminiscent of Williams syndrome.
Random mutagenesis screens for modifiers of position effect variegation were initiated in Drosophila in the 1960s [1, 2]. The screens used a fly strain, called wv, that displays variegated expression of the white (w) locus resulting in red and white patches in the eye. Variegation refers to the 'salt and pepper' expression of some genes due to the stochastic establishment of an epigenetic state at their promoters. The best characterized example of variegation in mammals is the coat color of mice carrying the Avyallele [3, 4]. In this case there is a correlation between DNA methylation at the promoter and silencing of the gene [5, 6]. Alleles of this type provide us with an opportunity to study epigenetic gene silencing at a molecular level in a whole organism.
The extent of the variegation at the wvlocus, that is, the ratio of red to white patches in the eye, was known to be sensitive to strain background, suggesting the existence of genetic modifiers. Offspring of mutagenized flies were screened for changes in the degree of variegation. These screens have been continued to saturation and the results suggest that there are between 100 and 150 such genes [7, 8]. Approximately one-third of these have been identified and, as expected, most turn out to play critical roles in epigenetic gene silencing [1, 9]. These include genes encoding proteins involved in heterochromatin formation, for example, HP1 and histone methyltransferases [8]. 2ff7e9595c
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