text:
In vitro

In vitro (meaning in glass, or in the glass) studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and its subdisciplines are traditionally done in labware such as test tubes, flasks, Petri dishes, and microtiter plates. Studies conducted using components of an organism that have been isolated from their usual biological surroundings permit a more detailed or more convenient analysis than can be done with whole organisms; however, results obtained from in vitro experiments may not fully or accurately predict the effects on a whole organism. In contrast to in vitro experiments, in vivo studies are those conducted in living organisms, including humans, known as clinical trials, and whole plants.

Definition
In vitro (Latin for "in glass"; often not italicized in English usage ) studies are conducted using components of an organism that have been isolated from their usual biological surroundings, such as microorganisms, cells, or biological molecules. For example, microorganisms or cells can be studied in artificial culture media, and proteins can be examined in solutions. Colloquially called "test-tube experiments", these studies in biology, medicine, and their subdisciplines are traditionally done in test tubes, flasks, Petri dishes, etc. They now involve the full range of techniques used in molecular biology, such as the omics. In contrast, studies conducted in living beings (microorganisms, animals, humans, or whole plants) are called in vivo.

Examples
Examples of in vitro studies include: the isolation, growth and identification of cells derived from multicellular organisms (in cell or tissue culture); subcellular components (e.g. mitochondria or ribosomes); cellular or subcellular extracts (e.g. wheat germ or reticulocyte extracts); purified molecules (such as proteins, DNA, or RNA); and the commercial production of antibiotics and other pharmaceutical products. Viruses, which only replicate in living cells, are studied in the laboratory in cell or tissue culture, and many animal virologists refer to such work as being in vitro to distinguish it from in vivo work in whole animals.

 * Polymerase chain reaction is a method for selective replication of specific DNA and RNA sequences in the test tube.
 * Protein purification involves the isolation of a specific protein of interest from a complex mixture of proteins, often obtained from homogenized cells or tissues.
 * In vitro fertilization is used to allow spermatozoa to fertilize eggs in a culture dish before implanting the resulting embryo or embryos into the uterus of the prospective mother.
 * In vitro diagnostics refers to a wide range of medical and veterinary laboratory tests that are used to diagnose diseases and monitor the clinical status of patients using samples of blood, cells, or other tissues obtained from a patient.
 * In vitro testing has been used to characterize specific adsorption, distribution, metabolism, and excretion processes of drugs or general chemicals inside a living organism; for example, Caco-2 cell experiments can be performed to estimate the absorption of compounds through the lining of the gastrointestinal tract; The partitioning of the compounds between organs can be determined to study distribution mechanisms; Suspension or plated cultures of primary hepatocytes or hepatocyte-like cell lines (HepG2, HepaRG) can be used to study and quantify metabolism of chemicals. These ADME process parameters can then be integrated into so called "physiologically based pharmacokinetic models" or PBPK.

Advantages
In vitro studies permit a species-specific, simpler, more convenient, and more detailed analysis than can be done with the whole organism. Just as studies in whole animals more and more replace human trials, so are in vitro studies replacing studies in whole animals.

Simplicity
Living organisms are extremely complex functional systems that are made up of, at a minimum, many tens of thousands of genes, protein molecules, RNA molecules, small organic compounds, inorganic ions, and complexes in an environment that is spatially organized by membranes, and in the case of multicellular organisms, organ systems. These myriad components interact with each other and with their environment in a way that processes food, removes waste, moves components to the correct location, and is responsive to signalling molecules, other organisms, light, sound, heat, taste, touch, and balance. This complexity makes it difficult to identify the interactions between individual components and to explore their basic biological functions. In vitro work simplifies the system under study, so the investigator can focus on a small number of components.

For example, the identity of proteins of the immune system (e.g. antibodies), and the mechanism by which they recognize and bind to foreign antigens would remain very obscure if not for the extensive use of in vitro work to isolate the proteins, identify the cells and genes that produce them, study the physical properties of their interaction with antigens, and identify how those interactions lead to cellular signals that activate other components of the immune system.

Species specificity
Another advantage of in vitro methods is that human cells can be studied without "extrapolation" from an experimental animal's cellular response.

Convenience, automation
In vitro methods can be miniaturized and automated, yielding high-throughput screening methods for testing molecules in pharmacology or toxicology.

Disadvantages
The primary disadvantage of in vitro experimental studies is that it may be challenging to extrapolate from the results of in vitro work back to the biology of the intact organism. Investigators doing in vitro work must be careful to avoid over-interpretation of their results, which can lead to erroneous conclusions about organismal and systems biology.

For example, scientists developing a new viral drug to treat an infection with a pathogenic virus (e.g., HIV-1) may find that a candidate drug functions to prevent viral replication in an in vitro setting (typically cell culture). However, before this drug is used in the clinic, it must progress through a series of in vivo trials to determine if it is safe and effective in intact organisms (typically small animals, primates, and humans in succession). Typically, most candidate drugs that are effective in vitro prove to be ineffective in vivo because of issues associated with delivery of the drug to the affected tissues, toxicity towards essential parts of the organism that were not represented in the initial in vitro studies, or other issues.

In vitro test batteries
A method which could help decrease animal testing is the use of in vitro batteries, where several in vitro assays are compiled to cover multiple endpoints. Within developmental neurotoxicity and reproductive toxicity there are hopes for test batteries to become easy screening methods for prioritization for which chemicals to be risk assessed and in which order. Within ecotoxicology in vitro test batteries are already in use for regulatory purpose and for toxicological evaluation of chemicals. In vitro tests can also be combined with in vivo testing to make a in vitro in vivo test battery, for example for pharmaceutical testing.

In vitro to in vivo extrapolation
Results obtained from in vitro experiments cannot usually be transposed, as is, to predict the reaction of an entire organism in vivo. Building a consistent and reliable extrapolation procedure from in vitro results to in vivo is therefore extremely important. Solutions include:

 * Increasing the complexity of in vitro systems to reproduce tissues and interactions between them (as in "human on chip" systems)
 * Using mathematical modeling to numerically simulate the behavior of the complex system, where the in vitro data provide model parameter values

These two approaches are not incompatible; better in vitro systems provide better data to mathematical models. However, increasingly sophisticated in vitro experiments collect increasingly numerous, complex, and challenging data to integrate. Mathematical models, such as systems biology models, are much needed here.

Extrapolating in pharmacology
In pharmacology, IVIVE can be used to approximate pharmacokinetics (PK) or pharmacodynamics (PD). Since the timing and intensity of effects on a given target depend on the concentration time course of candidate drug (parent molecule or metabolites) at that target site, in vivo tissue and organ sensitivities can be completely different or even inverse of those observed on cells cultured and exposed in vitro. That indicates that extrapolating effects observed in vitro needs a quantitative model of in vivo PK. Physiologically based PK (PBPK) models are generally accepted to be central to the extrapolations.

In the case of early effects or those without intercellular communications, the same cellular exposure concentration is assumed to cause the same effects, both qualitatively and quantitatively, in vitro and in vivo. In these conditions, developing a simple PD model of the dose–response relationship observed in vitro, and transposing it without changes to predict in vivo effects is not enough.

title: In vitro


text:
IEEE 754-1985

IEEE 754-1985 is a historic industry standard for representing floating-point numbers in computers, officially adopted in 1985 and superseded in 2008 by IEEE 754-2008, and then again in 2019 by minor revision IEEE 754-2019. During its 23 years, it was the most widely used format for floating-point computation. It was implemented in software, in the form of floating-point libraries, and in hardware, in the instructions of many CPUs and FPUs. The first integrated circuit to implement the draft of what was to become IEEE 754-1985 was the Intel 8087.

IEEE 754-1985 represents numbers in binary, providing definitions for four levels of precision, of which the two most commonly used are:

The standard also defines representations for positive and negative infinity, a "negative zero", five exceptions to handle invalid results like division by zero, special values called NaNs for representing those exceptions, denormal numbers to represent numbers smaller than shown above, and four rounding modes.

Representation of numbers

Floating-point numbers in IEEE 754 format consist of three fields: a sign bit, a biased exponent, and a fraction. The following example illustrates the meaning of each.

The decimal number 0.1562510 represented in binary is 0.001012 (that is, 1/8 + 1/32). (Subscripts indicate the number base.) Analogous to scientific notation, where numbers are written to have a single non-zero digit to the left of the decimal point, we rewrite this number so it has a single 1 bit to the left of the "binary point". We simply multiply by the appropriate power of 2 to compensate for shifting the bits left by three positions:

 * $$0.00101_2 = 1.01_2 \times 2^{-3}$$

Now we can read off the fraction and the exponent: the fraction is .012 and the exponent is −3.

As illustrated in the pictures, the three fields in the IEEE 754 representation of this number are:

 * sign = 0, because the number is positive. (1 indicates negative.)
 * biased exponent = −3 + the "bias". In single precision, the bias is 127, so in this example the biased exponent is 124; in double precision, the bias is 1023, so the biased exponent in this example is 1020.
 * fraction = .01000…2.

IEEE 754 adds a bias to the exponent so that numbers can in many cases be compared conveniently by the same hardware that compares signed 2's-complement integers. Using a biased exponent, the lesser of two positive floating-point numbers will come out "less than" the greater following the same ordering as for sign and magnitude integers. If two floating-point numbers have different signs, the sign-and-magnitude comparison also works with biased exponents. However, if both biased-exponent floating-point numbers are negative, then the ordering must be reversed. If the exponent were represented as, say, a 2's-complement number, comparison to see which of two numbers is greater would not be as convenient.

The leading 1 bit is omitted since all numbers except zero start with a leading 1; the leading 1 is implicit and doesn't actually need to be stored which gives an extra bit of precision for "free."

Zero
The number zero is represented specially:

 * sign = 0 for positive zero, 1 for negative zero.
 * biased exponent = 0.
 * fraction = 0.

Denormalized numbers
The number representations described above are called normalized, meaning that the implicit leading binary digit is a 1. To reduce the loss of precision when an underflow occurs, IEEE 754 includes the ability to represent fractions smaller than are possible in the normalized representation, by making the implicit leading digit a 0. Such numbers are called denormal. They don't include as many significant digits as a normalized number, but they enable a gradual loss of precision when the result of an operation is not exactly zero but is too close to zero to be represented by a normalized number.

A denormal number is represented with a biased exponent of all 0 bits, which represents an exponent of −126 in single precision (not −127), or −1022 in double precision (not −1023). In contrast, the smallest biased exponent representing a normal number is 1 (see examples below).

Representation of non-numbers
The biased-exponent field is filled with all 1 bits to indicate either infinity or an invalid result of a computation.

Positive and negative infinity
Positive and negative infinity are represented thus:

 * sign = 0 for positive infinity, 1 for negative infinity.
 * biased exponent = all 1 bits.
 * fraction = all 0 bits.

NaN
Some operations of floating-point arithmetic are invalid, such as taking the square root of a negative number. The act of reaching an invalid result is called a floating-point exception. An exceptional result is represented by a special code called a NaN, for "Not a Number". All NaNs in IEEE 754-1985 have this format:

 * sign = either 0 or 1.
 * biased exponent = all 1 bits.
 * fraction = anything except all 0 bits (since all 0 bits represents infinity).

Range and precision
Precision is defined as the minimum difference between two successive mantissa representations; thus it is a function only in the mantissa; while the gap is defined as the difference between two successive numbers.

Single precision
Single-precision numbers occupy 32 bits. In single precision:
 * The positive and negative numbers closest to zero (represented by the denormalized value with all 0s in the exponent field and the binary value 1 in the fraction field) are
 * ±2−23 × 2−126 ≈ ±1.40130
 * The positive and negative normalized numbers closest to zero (represented with the binary value 1 in the exponent field and 0 in the fraction field) are
 * ±1 × 2−126 ≈ ±1.17549
 * The finite positive and finite negative numbers furthest from zero (represented by the value with 254 in the exponent field and all 1s in the fraction field) are
 * ±(2−2−23) × 2127 ≈ ±3.40282

Some example range and gap values for given exponents in single precision:

As an example, 16,777,217 cannot be encoded as a 32-bit float as it will be rounded to 16,777,216. However, all integers within the representable range that are a power of 2 can be stored in a 32-bit float without rounding.

Double precision
Double-precision numbers occupy 64 bits. In double precision:
 * The positive and negative numbers closest to zero (represented by the denormalized value with all 0s in the Exp field and the binary value 1 in the Fraction field) are
 * ±2−52 × 2−1022 ≈ ±4.94066
 * The positive and negative normalized numbers closest to zero (represented with the binary value 1 in the Exp field and 0 in the fraction field) are
 * ±1 × 2−1022 ≈ ±2.22507
 * The finite positive and finite negative numbers furthest from zero (represented by the value with 2046 in the Exp field and all 1s in the fraction field) are
 * ±(2−2−52) × 21023 ≈ ±1.79769

Some example range and gap values for given exponents in double precision:

Extended formats
The standard also recommends extended format(s) to be used to perform internal computations at a higher precision than that required for the final result, to minimise round-off errors: the standard only specifies minimum precision and exponent requirements for such formats. The x87 80-bit extended format is the most commonly implemented extended format that meets these requirements.

Examples
Here are some examples of single-precision IEEE 754 representations:

Comparing floating-point numbers
Every possible bit combination is either a NaN or a number with a unique value in the affinely extended real number system with its associated order, except for the two combinations of bits for negative zero and positive zero, which sometimes require special attention (see below). The binary representation has the special property that, excluding NaNs, any two numbers can be compared as sign and magnitude integers (endianness issues apply). When comparing as 2's-complement integers: If the sign bits differ, the negative number precedes the positive number, so 2's complement gives the correct result (except that negative zero and positive zero should be considered equal). If both values are positive, the 2's complement comparison again gives the correct result. Otherwise (two negative numbers), the correct FP ordering is the opposite of the 2's complement ordering.

Rounding errors inherent to floating point calculations may limit the use of comparisons for checking the exact equality of results. Choosing an acceptable range is a complex topic. A common technique is to use a comparison epsilon value to perform approximate comparisons. Depending on how lenient the comparisons are, common values include  or   for single-precision, and   for double-precision. Another common technique is ULP, which checks what the difference is in the last place digits, effectively checking how many steps away the two values are.

Although negative zero and positive zero are generally considered equal for comparison purposes, some programming language relational operators and similar constructs treat them as distinct. According to the Java Language Specification, comparison and equality operators treat them as equal, but  and   distinguish them (officially starting with Java version 1.1 but actually with 1.1.1), as do the comparison methods ,   and even   of classes   and.

Rounding floating-point numbers
The IEEE standard has four different rounding modes; the first is the default; the others are called directed roundings.

 * Round to Nearest – rounds to the nearest value; if the number falls midway it is rounded to the nearest value with an even (zero) least significant bit, which means it is rounded up 50% of the time (in IEEE 754-2008 this mode is called roundTiesToEven to distinguish it from another round-to-nearest mode)
 * Round toward 0 – directed rounding towards zero
 * Round toward +∞ – directed rounding towards positive infinity
 * Round toward −∞ – directed rounding towards negative infinity.

Extending the real numbers
The IEEE standard employs (and extends) the affinely extended real number system, with separate positive and negative infinities. During drafting, there was a proposal for the standard to incorporate the projectively extended real number system, with a single unsigned infinity, by providing programmers with a mode selection option. In the interest of reducing the complexity of the final standard, the projective mode was dropped, however. The Intel 8087 and Intel 80287 floating point co-processors both support this projective mode.

Standard operations
The following functions must be provided:
 * Add, subtract, multiply, divide
 * Square root
 * Floating point remainder. This is not like a normal modulo operation, it can be negative for two positive numbers. It returns the exact value of $x–(round(x/y)·y)$.
 * Round to nearest integer. For undirected rounding when halfway between two integers the even integer is chosen.
 * Comparison operations. Besides the more obvious results, IEEE 754 defines that −∞ = −∞, +∞ = +∞ and x ≠  for any x (including  ).

Recommended functions and predicates

 * returns x with the sign of y, so  equals  . This is one of the few operations which operates on a NaN in a way resembling arithmetic. The function   is new in the C99 standard.
 * −x returns x with the sign reversed. This is different from 0−x in some cases, notably when x is 0. So −(0) is −0, but the sign of 0−0 depends on the rounding mode.
 * a predicate for "x is a finite value", equivalent to −Inf < x < Inf
 * a predicate for "x is a NaN", equivalent to "x ≠ x"
 * , which turns out to have different behavior than NOT(x = y) due to NaN.
 * is true when "x is unordered with y", i.e., either x or y is a NaN.
 * returns the next representable value from x in the direction towards y
 * is true when "x is unordered with y", i.e., either x or y is a NaN.
 * returns the next representable value from x in the direction towards y
 * returns the next representable value from x in the direction towards y

History
In 1976, Intel was starting the development of a floating-point coprocessor. Intel hoped to be able to sell a chip containing good implementations of all the operations found in the widely varying maths software libraries.

John Palmer, who managed the project, believed the effort should be backed by a standard unifying floating point operations across disparate processors. He contacted William Kahan of the University of California, who had helped improve the accuracy of Hewlett-Packard's calculators. Kahan suggested that Intel use the floating point of Digital Equipment Corporation's (DEC) VAX. The first VAX, the VAX-11/780 had just come out in late 1977, and its floating point was highly regarded. However, seeking to market their chip to the broadest possible market, Intel wanted the best floating point possible, and Kahan went on to draw up specifications. Kahan initially recommended that the floating point base be decimal but the hardware design of the coprocessor was too far along to make that change.

The work within Intel worried other vendors, who set up a standardization effort to ensure a "level playing field". Kahan attended the second IEEE 754 standards working group meeting, held in November 1977. He subsequently received permission from Intel to put forward a draft proposal based on his work for their coprocessor; he was allowed to explain details of the format and its rationale, but not anything related to Intel's implementation architecture. The draft was co-written with Jerome Coonen and Harold Stone, and was initially known as the "Kahan-Coonen-Stone proposal" or "K-C-S format".

As an 8-bit exponent was not wide enough for some operations desired for double-precision numbers, e.g. to store the product of two 32-bit numbers, both Kahan's proposal and a counter-proposal by DEC therefore used 11 bits, like the time-tested 60-bit floating-point format of the CDC 6600 from 1965. Kahan's proposal also provided for infinities, which are useful when dealing with division-by-zero conditions; not-a-number values, which are useful when dealing with invalid operations; denormal numbers, which help mitigate problems caused by underflow;  and a better balanced exponent bias, which can help avoid overflow and underflow when taking the reciprocal of a number.

Even before it was approved, the draft standard had been implemented by a number of manufacturers. The Intel 8087, which was announced in 1980, was the first chip to implement the draft standard.

In 1980, the Intel 8087 chip was already released, but DEC remained opposed, to denormal numbers in particular, because of performance concerns and since it would give DEC a competitive advantage to standardise on DEC's format.

The arguments over gradual underflow lasted until 1981 when an expert hired by DEC to assess it sided against the dissenters. DEC had the study done in order to demonstrate that gradual underflow was a bad idea, but the study concluded the opposite, and DEC gave in. In 1985, the standard was ratified, but it had already become the de facto standard a year earlier, implemented by many manufacturers.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: IEEE 754-1985


text:
Intel 80186

The Intel 80186, also known as the iAPX 186, or just 186, is a microprocessor and microcontroller introduced in 1982. It was based on the Intel 8086 and, like it, had a 16-bit external data bus multiplexed with a 20-bit address bus.

Description

The 80186 series was designed to reduce the number of integrated circuits required. It included features such as clock generator, interrupt controller, timers, wait state generator, DMA channels, and external chip select lines. It was used in numerous embedded systems, as microcontrollers with external memory.

The initial clock rate of the 80186 was 6 MHz, but due to more hardware available for the microcode to use, especially for address calculation, many individual instructions completed in fewer clock cycles than on an 8086 at the same clock frequency. For instance, the common register+immediate addressing mode was significantly faster than on the 8086, especially when a memory location was both (one of) the operand(s) and the destination. Multiply and divide also showed great improvement, being several times as fast as on the original 8086, and multi-bit shifts were done almost four times as quickly as in the 8086.

A few new instructions were introduced with the 80186 (referred to as the 8086-2 instruction set in some datasheets): enter/leave (replacing several instructions when handling stack frames), pusha/popa (push/pop all general registers), bound (check array index against bounds), and ins/outs (input/output of string). A useful immediate mode was added for the push, imul, and multi-bit shift instructions. These instructions were also included in the contemporary 80286 and in successor chips.

The (redesigned) CMOS version, 80C186, introduced DRAM refresh, a power-save mode, and a direct interface to the 80C187 floating-point numeric coprocessor. Intel second-sourced this microprocessor to Fujitsu Limited around 1985. Both packages for Intel 80186 version were available in 68-pin PLCC and PGA in sampling at third quarter of 1985. The available 12.5 MHz Intel 80186-12 version using the 1.5 μm HMOS-III process for US$36 in quantities of 100. The available 12.5 MHz Intel 80C186 version using the CHMOS III-E technology using approximately 90 mA under normal load and only 32 mA under power-save mode. It was available in 68-pin PLCC, CPGA, or CLCC package. The military version of Intel M80C186 embedded controller was available in 10 and 12 MHz version. They met MIL-STD-883 Rev. C and MIL-STD-1553 bus application standards. The 12 MHz CHMOS version consumes approximately 100 mA. The available packages were 68-pin CPGA and CQFP. The 10 MHz M80C186 PGA version was available for US$378 in 100-unit quantities. The available 80C186EB in fully static design for the application-specific standard product using the 1 μm CHMOS IV technology. They were available in 3- and 5-volt versions with 84-lead PLCC and 80-lead EIAJ QFP packaging. It was also available for US$16.95 in 1,000-unit quantities. The Intel 80C186EC contains 4 DMA channels, 2 interrupt controllers, 22 I/O which control two serial channels, and 4 timers. This version was available for US$17.70 in quantites of 1,000 units. This microcontroller only available in 5-volt version. Both Intel 80C186EC and 80C186EA contains three different power-management modes, which has idle, powerdown and powersave. The 80C186EA has both 5- and 3-volt versions. The 80C186XL version was available up to 20 MHz, which is compatible with existing CMOS version of 80C186 that has 25% higher performance and 50% lower power consumption. This version used 1 μm CHMOS process technology. Both 80C186EA and 80C186XL were available for US$11.80 in quantities of 1,000 units.

80188 series
The 80188 variant, with an 8-bit external data bus was also available; this made it less expensive to connect to peripherals. The 16-bit registers and the one megabyte address range were unchanged, however. It had a throughput of 1 million instructions per second. Intel second sourced this microprocessor to Fujitsu Limited around 1985. Both packages of Intel 80188 version were available in 68-pin PLCC and PGA in sampling at third quarter of 1985. The available 80C188EB in fully static design for the application-specific standard product using the 1-micron CHMOS IV technology. They were available in 3- and 5-Volts version with 84-lead PLCC and 80-lead EIAJ QFP version. It was also available for US$15.15 in 1,000 unit quantities.

The 80188 series was generally intended for embedded systems, as microcontrollers with external memory. Therefore, to reduce the number of chips required, it included features such as clock generator, interrupt controller, timers, wait state generator, DMA channels, and external chip select lines. While the N80188 was compatible with the 8087 numeric co-processor, the 80C188 was not. It did not have the ESC control codes integrated.

In personal computers
Because the integrated hardware included in the 80186 was incompatible with the support chips chosen by IBM for the 8088-based IBM PC released a few months earlier, the chip did not see wide success in the PC market. IBM chose the 80286 for its successor, the IBM PC/AT, released in autumn 1984. Most other PC-compatible manufactures followed.

Regardless, several notable personal computers used the 80186:
 * Danish Regnecentralen: RC750 Partner running CCP/M
 * Danish Regnecentralen: RC759 Piccoline running CCP/M
 * Australian Dulmont Magnum laptop, one of the first laptops
 * Wang Office Assistant, marketed as a PC-like stand-alone word processor
 * MAD-1, a semi–IBM PC-compatible desktop computer with a modular design
 * Pronto System 16, another PC compatible
 * Mindset, a very early graphics workstation
 * Siemens (not 100% IBM PC compatible but using MS-DOS 2.11)
 * Compis, a Swedish school computer
 * French SMT-Goupil G4
 * RM Nimbus PC-186, the first version of a series of British school computers
 * Unisys ICON, a Canadian school computer
 * ORB Computer by ABS
 * HP 100LX, HP 200LX, HP 1000CX, and HP OmniGo 700LX
 * Tandy 2000 desktop, a somewhat PC-compatible workstation with sharp graphics for its day
 * Telex 1260, a desktop PC-XT compatible
 * Philips :YES
 * Nokia MikroMikko 2
 * IBM PCradio

In addition to the above examples of stand-alone implementations of the 80186 for personal computers, there were at least two examples of "add-in" accelerator card implementations: the BBC Master 512, Acorn's plug-in for the BBC Master range of computers containing an 80186–10 with 512 KB of RAM, and the Orchid Technology PC Turbo 186, released in 1985. It was intended for use with the original Intel 8088-based IBM PC (Model 5150).

Other devices
The Intel 80186 and 80188 are often embedded in electronic devices that are not primarily computers. For example:
 * The 80186 was used to control the Microtek 8086 in-circuit emulator.
 * The 80188 was embedded inside the Intel 14.4EX modem released in 1991. The 16 MHz processor was used to perform complex algorithms needed for forward error correction, trellis modulation, and echo cancellation in the modem.
 * The second-generation SatisFAXtion board, which is a FAX/modem ISA card, uses this processor.
 * The IBM 7171 protocol converter, which made ASCII character-oriented terminals appear as an IBM 3270 terminal to an IBM mainframe, used the Intel 80186 as its CPU.
 * It was also used on the controller card for Digital Equipment Corporation's DECtalk speech synthesizer system.

End of life
On March 30, 2006, Intel announced that production of the 80186 and 80188, along with the production of other processor models such as the 80386 and 80486, would cease at the end of September 2007. Pin- and instruction-compatible replacements might still be manufactured by various third-party sources, and FPGA versions are publicly available.

title: Intel 80186


text:
Inquisition

The Inquisition was a judicial procedure and a group of institutions within the Catholic Church whose aim was to combat heresy, apostasy, blasphemy, witchcraft, and customs considered deviant. Violence, torture, or the simple threat of its application, were used by the Inquisition to extract confessions and denunciations from heretics. Studies of the records have found that the overwhelming majority of sentences consisted of penances, but convictions of unrepentant heresy were handed over to the secular courts, which generally resulted in execution or life imprisonment. The Inquisition had its start in the 12th-century Kingdom of France, with the aim of combating religious deviation (e.g. apostasy or heresy), particularly among the Cathars and the Waldensians. The inquisitorial courts from this time until the mid-15th century are together known as the Medieval Inquisition. Other groups investigated during the Medieval Inquisition, which primarily took place in France and Italy, include the Spiritual Franciscans, the Hussites, and the Beguines. Beginning in the 1250s, inquisitors were generally chosen from members of the Dominican Order, replacing the earlier practice of using local clergy as judges.

During the Late Middle Ages and the early Renaissance, the scope of the Inquisition grew significantly in response to the Protestant Reformation and the Catholic Counter-Reformation. During this period, the Inquisition conducted by the Holy See was known as the Roman Inquisition. The Inquisition also expanded to other European countries, resulting in the Spanish Inquisition and the Portuguese Inquisition. The Spanish and Portuguese Inquisitions were instead focused particularly on the New Christians or Conversos, as the former Jews who converted to Christianity to avoid antisemitic regulations and persecution were called, the anusim (people who were forced to abandon Judaism against their will by violence and threats of expulsion) and on Muslim converts to Catholicism. The scale of the persecution of converted Muslims and converted Jews in Spain and Portugal was the result of suspicions that they had secretly reverted to their previous religions, although both religious minority groups were also more numerous on the Iberian Peninsula than in other parts of Europe, as well as the fear of possible rebellions and armed uprisings, as had occurred in previous times. During this time, Spain and Portugal operated inquisitorial courts not only in Europe, but also throughout their empires in Africa, Asia, and the Americas. This resulted in the Goa Inquisition, the Peruvian Inquisition, and the Mexican Inquisition, among others.

With the exception of the Papal States, the institution of the Inquisition was abolished in the early 19th century, after the Napoleonic Wars in Europe and the Spanish American wars of independence in the Americas. The institution survived as part of the Roman Curia, although it underwent a series of name changes. In 1908, it was renamed the Supreme Sacred Congregation of the Holy Office. In 1965, it became the Congregation for the Doctrine of the Faith. In 2022, this office was renamed the Dicastery for the Doctrine of the Faith.

Definition and goals

The term "Inquisition" comes from the Medieval Latin word inquisitio, which described any court process based on Roman law, which had gradually come back into use during the Late Middle Ages. Today, the English term "Inquisition" can apply to any one of several institutions that worked against heretics or other offenders against the canon law of the Catholic Church. Although the term "Inquisition" is usually applied to ecclesiastical courts of the Catholic Church, it refers to a judicial process, not an organization. Inquisitors '...were called such because they applied a judicial technique known as inquisitio, which could be translated as "inquiry" or "inquest".' In this process, which was already widely used by secular rulers (Henry II used it extensively in England in the 12th century), an official inquirer called for information on a specific subject from anyone who felt he or she had something to offer."

Theoretically, the Inquisition, as a church court, had no jurisdiction over Muslims and Jews as such. Despite several exceptions, like the infamous example of the Santo Niño de La Guardia, the Inquisition was concerned mainly with the heretical behaviour of Catholic adherents or converts (including forced converts).

The overwhelming majority of sentences seem to have consisted of penances like wearing a cross sewn on one's clothes or going on pilgrimage. When a suspect was convicted of major, willful, unrepentant heresy, canon law required the inquisitorial tribunal to hand the person over to secular authorities for final sentencing. A secular magistrate, the "secular arm", would then determine the penalty based on local law. Those local laws included proscriptions against certain religious crimes, and the punishments included death by burning, although the penalty was more usually banishment or imprisonment for life, which was generally commuted after a few years. Thus the inquisitors generally knew the expected fate of anyone so remanded. The "secular arm" didn't  have access to the  trial record of the defendants, only executed the sentences and was obliged to do so on pain of heresy and excommunication.

The 1578 edition of the Directorium Inquisitorum (a standard Inquisitorial manual) spelled out (by Francisco Peña) the purpose of inquisitorial penalties: ... quoniam punitio non refertur primo & per se in correctionem & bonum eius qui punitur, sed in bonum publicum ut alij terreantur, & a malis committendis avocentur (translation: "... for punishment does not take place primarily and per se for the correction and good of the person punished, but for the public good in order that others may become terrified and weaned away from the evils they would commit").

Origin
Before the 12th century, the Catholic Church suppressed what they believed to be heresy, usually through a system of ecclesiastical proscription or imprisonment, but without using torture, and seldom resorting to executions. Such punishments were opposed by a number of clergymen and theologians, although some countries punished heresy with the death penalty. Pope Siricius, Ambrose of Milan, and Martin of Tours protested against the execution of Priscillian, largely as an undue interference in ecclesiastical discipline by a civil tribunal. Though widely viewed as a heretic, Priscillian was executed as a sorcerer. Ambrose refused to give any recognition to Ithacius of Ossonuba, "not wishing to have anything to do with bishops who had sent heretics to their death".

In the 12th century, to counter the spread of Catharism, and other heresies, prosecution of heretics became more frequent. The Church charged councils composed of bishops and archbishops with establishing inquisitions (the Episcopal Inquisition). Pope Lucius III issued the bull Ad Abolendam (1184), which condemned heresy as contumacy toward ecclesiastical authority. The bull Vergentis in Senium in 1199 stipulated that heresy would be considered, in terms of punishment, equal to treason (Lèse-majesté), and the punishment would be imposed also on the descendants of the condemned. The first Inquisition was temporarily established in Languedoc (south of France) in 1184. The murder of Pope Innocent III's papal legate Pierre de Castelnau in 1208 sparked the Albigensian Crusade (1209–1229). The Inquisition was permanently established in 1229 (Council of Toulouse), run largely by the Dominicans in Rome and later at Carcassonne in Languedoc.

Medieval Inquisition
Historians use the term "Medieval Inquisition" to describe the various inquisitions that started around 1184, including the Episcopal Inquisition (1184–1230s) and later the Papal Inquisition (1230s). These inquisitions responded to large popular movements throughout Europe considered apostate or heretical to Christianity, in particular the Cathars in southern France and the Waldensians in both southern France and northern Italy. Other Inquisitions followed after these first inquisition movements. The legal basis for some inquisitorial activity came from Pope Innocent IV's papal bull Ad extirpanda of 1252, which authorized the use of tortures in certain circumstances by the Inquisition for eliciting confessions and denunciations from heretics. By 1256 Alexander IV's Ut negotium allowed the inquisitors to absolve each other if they used instruments of torture.

In the 13th century, Pope Gregory IX (reigned 1227–1241) assigned the duty of carrying out inquisitions to the Dominican Order and Franciscan Order. By the end of the Middle Ages, England and Castile were the only large western nations without a papal inquisition. Most inquisitors were friars who taught theology and/or law in the universities. They used inquisitorial procedures, a common legal practice adapted from the earlier Ancient Roman court procedures. They judged heresy along with bishops and groups of "assessors" (clergy serving in a role that was roughly analogous to a jury or legal advisers), using the local authorities to establish a tribunal and to prosecute heretics. After 1200, a Grand Inquisitor headed each Inquisition. Grand Inquisitions persisted until the mid 19th century.

Inquisition in Italy
Only fragmentary data is available for the period before the Roman Inquisition of 1542. In 1276, some 170 Cathars were captured in Sirmione, who were then imprisoned in Verona, and there, after a two-year trial, on February 13 from 1278, more than a hundred of them were burned. In Orvieto, at the end of 1268/1269, 85 heretics were sentenced, none of whom were executed, but in 18 cases the sentence concerned people who had already died. In Tuscany, the inquisitor Ruggiero burned at least 11 people in about a year (1244/1245). Excluding the executions of the heretics at Sirmione in 1278, 36 Inquisition executions are documented in the March of Treviso between 1260 and 1308. Ten people were executed in Bologna between 1291 and 1310. In Piedmont, 22 heretics (mainly Waldensians) were burned in the years 1312-1395 out of 213 convicted. 22 Waldensians were burned in Cuneo around 1440 and another five in the Marquisate of Saluzzo in 1510. There are also fragmentary records of a good number of executions of people suspected of witchcraft in northern Italy in the 15th and early 16th centuries. Wolfgang Behringer estimates that there could have been as many as two thousand executions. This large number of witches executed was probably because some inquisitors took the view that the crime of witchcraft was exceptional, which meant that the usual rules for heresy trials did not apply to its perpetrators. Many alleged witches were executed even though they were first tried and pleaded guilty, which under normal rules would have meant only canonical sanctions, not death sentences. The episcopal inquisition was also active in suppressing alleged witches: in 1518, judges delegated by the Bishop of Brescia, Paolo Zane, sent some 70 witches from Val Camonica to the stake.

Inquisition in France
The Albigensian Crusade (1209-1229) a crusade proclaimed by the Catholic Church against heresy, mainly Catharism, with his many thousands victims, men, women and children, some of them catholics, had already made the way to the posterior Inquisition.

France has the best preserved archives of the medieval inquisition (13th-14th centuries), although they are still very incomplete. The activity of the inquisition in this country was very diverse, both in terms of time and territory. In the first period (1233 to c. 1330), the courts of Languedoc (Toulouse, Carcassonne) are the most active. After 1330 the center of the persecution of heretics shifted to the Alpine regions, while in Languedoc they ceased almost entirely. In northern France, the activity of the Inquisition was irregular throughout this period and, except for the first few years, it was not very intense.

France's first Dominican inquisitor, Robert le Bougre, working in the years 1233-1244, earned a particularly grim reputation. In 1236, Robert burned about 50 people in the area of Champagne and Flanders, and on May 13, 1239, in Montwimer, he burned 183 Cathars. Following Robert's removal from office, Inquisition activity in northern France remained very low. One of the largest trials in the area took place in 1459-1460 at Arras; 34 people were then accused of witchcraft and satanism, 12 of them were burned at the stake.

The main center of the medieval inquisition was undoubtedly the Languedoc. The first inquisitors were appointed there in 1233, but due to strong resistance from local communities in the early years, most sentences concerned dead heretics, whose bodies were exhumed and burned. Actual executions occurred sporadically and, until the fall of the fortress of Montsegur (1244), probably accounted for no more than 1% of all sentences. In addition to the cremation of the remains of the dead, a large percentage were also sentences in absentia and penances imposed on heretics who voluntarily confessed their faults (for example, in the years 1241-1242 the inquisitor Pierre Ceila reconciled 724 heretics with the Church). Inquisitor Ferrier of Catalonia, investigating Montauban between 1242 and 1244, questioned about 800 people, of whom he sentenced 6 to death and 20 to prison. Between 1243 and 1245, Bernard de Caux handed down 25 sentences of imprisonment and confiscation of property in Agen and Cahors. After the fall of Montsegur and the seizure of power in Toulouse by Count Alfonso de Poitiers, the percentage of death sentences increased to around 7% and remained at this level until the end of the Languedoc Inquisition around from 1330.

Between 1245 and 1246, the inquisitor Bernard de Caux carried out a large-scale investigation in the area of Lauragais and Lavaur. He covered 39 villages, and probably all the adult inhabitants (5,471 people) were questioned, of whom 207 were found guilty of heresy. Of these 207, no one was sentenced to death, 23 were sentenced to prison and 184 to penance. Between 1246 and 1248, the inquisitors Bernard de Caux and Jean de Saint-Pierre handed down 192 sentences in Toulouse, of which 43 were sentences in absentia and 149 were prison sentences.

In Pamiers in 1246/1247 there were 7 prison sentences [201] and in Limoux in the county of Foix 156 people were sentenced to carry crosses. Between 1249 and 1257, in Toulouse, the Inquisition handed down 306 sentences, without counting the penitential sentences imposed during "times of grace". 21 people were sentenced to death, 239 to prison, in addition, 30 people were sentenced in absentia and 11 posthumously; In another five cases the type of sanction is unknown, but since they all involve repeat offenders, only prison or burning is at stake. Between 1237 and 1279, at least 507 convictions were passed in Toulouse (most in absentia or posthumously) resulting in the confiscation of property; in Albi between 1240 and 1252 there were 60 sentences of this type.

The activities of Bernard Gui, inquisitor of Toulouse from 1307 to 1323, are better documented, as a complete record of his trials has been preserved. During the entire period of his inquisitorial activity, he handed down 633 sentences against 602 people (31 repeat offenders), including:

 * 41 death sentences,
 * 40 convictions of fugitive heretics (in absentia),
 * 20 sentences against people who died before the end of the trial (3 of them Bernardo considered unrepentant, and his remains were burned at the stake),
 * 69 exhumation orders for the remains of dead heretics (66 of whom were subsequently burned),
 * 308 prison sentences, with confiscation of property,
 * 136 orders to carry crosses,
 * 18 mandates to make a pilgrimage (17) or participate in a crusade (1),
 * in one case, sentencing was postponed.

In addition, Bernard Gui issued 274 more sentences involving the mitigation of sentences already served to convicted heretics; in 139 cases he exchanged prison for carrying crosses, and in 135 cases, carrying crosses for pilgrimage. To the full statistics, there are 22 orders to demolish houses used by heretics as meeting places and one condemnation and burning of Jewish writings (including commentaries on the Torah).

The episcopal inquisition was also active in Languedoc. In the years 1232–1234, the Bishop of Toulouse, Raymond, sentenced several dozen Cathars to death. In turn, Bishop Jacques Fournier of Pamiers (he was later Pope Benedict XII) in the years 1318-1325 conducted an investigation against 89 people, of whom 64 were found guilty and 5 were sentenced to death.

After 1330, the center of activity of the French Inquisition moved east, to the Alpine regions, where there were numerous Waldensian communities. The repression against them was not continuous and was very ineffective. Data on sentences issued by inquisitors are fragmentary. In 1348, 12 Waldensians were burned in Embrun, and in 1353/1354 as many as 168 received penances. In general, however, few Waldensians fell into the hands of the Inquisition, for they took refuge in hard-to-reach mountainous regions, where they formed close-knit communities. Inquisitors operating in this region, in order to be able to conduct trials, often had to resort to the armed assistance of local secular authorities (e.g. military expeditions in 1338–1339 and 1366). In the years 1375–1393 (with some breaks), the Dauphiné was the scene of the activities of the inquisitor Francois Borel, who gained an extremely gloomy reputation among the locals. It is known that on July 1, 1380, he pronounced death sentences in absentia against 169 people, including 108 from the Valpute valley, 32 from Argentiere and 29 from Freyssiniere. It is not known how many of them were actually carried out, only six people captured in 1382 are confirmed to be executed.

In the 15th and 16th centuries, major trials took place only sporadically, e.g. against the Waldensians in Delphinate in 1430–1432 (no numerical data) and 1532–1533 (7 executed out of about 150 tried) or the aforementioned trial in Arras 1459–1460. In the 16th century, the jurisdiction of the Inquisition in the kingdom of France was effectively limited to clergymen, while local parliaments took over the jurisdiction of the laity. Between 1500 and 1560, 62 people were burned for heresy in the Languedoc, all of whom were convicted by the Parliament of Toulouse.

Between 1657 and 1659, twenty-two alleged witches were burned on the orders of the inquisitor Pierre Symard in the province of Franche-Comte, then part of the Empire.

The inquisitorial tribunal in papal Avignon, established in 1541, passed 855 death sentences, almost all of them (818) in the years 1566–1574, but the vast majority of them were pronounced in absentia.

Inquisition in Germany
The Rhineland and Thuringia in the years 1231-1233 were the field of activity of the notorious inquisitor Konrad of Marburg. Unfortunately, the documentation of his trials has not been preserved, making it impossible to determine the number of his victims. The chronicles only mention "many" heretics that he burned. The only concrete information is about the burning of four people in Erfurt in May 1232.

After the murder of Konrad of Marburg, burning at the stake in Germany was virtually unknown for the next 80 years. It was not until the early fourteenth century that stronger measures were taken against heretics, largely at the initiative of bishops. In the years 1311-1315, numerous trials were held against the Waldensians in Austria, resulting in the burning of at least 39 people, according to incomplete records. In 1336, in Angermünde, in the diocese of Brandenburg, another 14 heretics were burned.

The number of those convicted by the papal inquisitors was smaller. Walter Kerlinger burned 10 begards in Erfurt and Nordhausen in 1368-1369. In turn, Eylard Schöneveld burned a total of four people in various Baltic cities in 1402-1403.

In the last decade of the 14th century, episcopal inquisitors carried out large-scale operations against heretics in eastern Germany, Pomerania, Austria, and Hungary. In Pomerania, of 443 sentenced in the years 1392-1394 by the inquisitor Peter Zwicker, the provincial of the Celestinians, none went to the stake, because they all submitted to the Church. Bloodier were the trials of the Waldensians in Austria in 1397, where more than a hundred Waldensians were burned at the stake. However, it seems that in these trials the death sentences represented only a small percentage of all the sentences, because according to the account of one of the inquisitors involved in these repressions, the number of heretics reconciled with the Church from Thuringia to Hungary amounted to about 2,000.

In 1414, the inquisitor Heinrich von Schöneveld arrested 84 flagellants in Sangerhausen, of whom he burned 3 leaders, and imposed penitential sentences on the rest. However, since this sect was associated with the peasant revolts in Thuringia from 1412, after the departure of the inquisitor, the local authorities organized a mass hunt for flagellants and, regardless of their previous verdicts, sent at least 168 to the stake (possibly up to 300) people. Inquisitor Friedrich Müller (d. 1460) sentenced to death 12 of the 13 heretics he had tried in 1446 at Nordhausen. In 1453 the same inquisitor burned 2 heretics in Göttingen.

Inquisitor Heinrich Kramer, author of the Malleus Maleficarum, in his own words, sentenced 48 people to the stake in five years (1481-1486). Jacob Hoogstraten, inquisitor of Cologne from 1508 to 1527, sentenced four people to be burned at the stake.

A duke of Brunswick in German was so shocked by the methods used by Inquisitors in his realm that he asked two famous Jesuit scholars to supervise. After careful study, the two 'told the Duke, "The Inquisitors are doing their duty. They are arresting only people who have been implicated by the confession of other witches."' The Duke then led the Jesuits to a woman being stretched on the rack and asked her, "You are a confessed witch. I suspect these two men of being warlocks. What do you say? Another turn of the rack, executioners." “No, no!” screamed the woman. “You are quite right. I have often seen .. . They can turn themselves into goats, wolves, and other animals. ... Several witches have had children by them. ... The children had heads like toads and legs like spiders." The Duke then asked the Jesuits. "Shall I put you to the torture until you confess, my friends?" One of the Jesuits was Friedrich Spee, who thanked God he had been led to this insight by a friend, not an enemy.

Inquisition in Hungary and the Balkans
Very little is known about the activities of the inquisition in Hungary and the countries under its influence (Bosnia, Croatia), as there are few sources about this activity. Numerous conversions and executions of Bosnian Cathars are known to have taken place around 1239/40, and in 1268 the Dominican inquisitor Andrew reconciled many heretics with the Church in the town of Skradin, but precise figures are unknown. The border areas with Bohemia and Austria were under major inquisitorial action against the Waldensians in the early 15th century. In addition, in the years 1436-1440 in the Kingdom of Hungary, the Franciscan Jacobo de la Marcha acted as an inquisitor... his mission was mixed, preaching and inquisitorial. The correspondence preserved between James, his collaborators, the Hungarian bishops and Pope Eugene IV shows that he reconciled up to 25,000 people with the Church. This correspondence also shows that he punished recalcitrant heretics with death, and in 1437 numerous executions were carried out in the diocese of Sirmium, although the number of those executed is also unknown.

Inquisition in the Czech Republic and Poland
In Bohemia and Poland, the inquisition was established permanently in 1318, although anti-heretical repressions were carried out as early as 1315 in the episcopal inquisition, when more than 50 Waldensians were burned in various Silesian cities. The fragmentary surviving protocols of the investigations carried out by the Prague inquisitor Gallus de Neuhaus in the years 1335 to around 1353 mention 14 heretics burned out of almost 300 interrogated, but it is estimated that the actual number executed could have been even more than 200, and the entire process was covered to varying degrees by some 4,400 people.

In the lands belonging to the Kingdom of Poland little is known of the activities of the Inquisition until the appearance of the Hussite heresy in the 15th century. Polish courts of the inquisition in the fight against this heresy issued at least 8 death sentences for some 200 trials carried out.

There are 558 court cases finished with conviction researched in Poland from XV to XVIII centuries.

Manuals for inquisitors
Over the centuries that it lasted, the Inquisition produced several procedure manuals, true "instruction books" for dealing with different types of heresy. The primordial text was Pope Innocent IV's bull, Ad Extirpanda, from 1252, which in its thirty-eight laws details in detail what must be done and authorizes the use of torture. Of the various manuals produced later, some stand out: by Nicholas Eymerich, Directorium Inquisitorum, written in 1376; by Bernardo Gui, Practica inquisitionis heretice pravitatis, written between 1319 and 1323. Witches were not forgotten: the book Malleus Maleficarum ("the witches' hammer"), written in 1486, by Heinrich Kramer, deals with the subject.

In Portugal, several "Regimentos" (four) were written for the use of the inquisitors, the first in 1552 at the behest of the inquisitor Cardinal D. Henrique and the last in 1774, this sponsored by the Marquis of Pombal. The Portuguese 1640 Regiment determined that each court of the Holy Office should have a Bible, a compendium of canon and civil law, Eymerich's Directorium Inquisitorum, and Diego de Simancas' Catholicis institutionibus.

In 1484, Spanish inquisitor Torquemada, based in Nicholas Eymerich's  Directorium Inquisitorum, wrote his twenty eight articles code, Compilación de las instrucciones del oficio de la Santa Inquisición (i.e. Compilation of the instructions of the office of the Holy Inquisition). Later additions would be made, based on experience, many by the canonist Francisco Peña.

Early modern European history
With the sharpening of debate and of conflict between the Protestant Reformation and the Catholic Counter-Reformation, Protestant societies came to see/use the Inquisition as a terrifying "other", while staunch Catholics regarded the Holy Office as a necessary bulwark against the spread of reprehensible heresies. Since the beginning of the most serious heretic groups, like the Cathars or the Waldensians, they were soon accused of the most fantastic behavior, like having wild sexual orgies, eating babies, copulating with demons, worshipping the Devil...

Witch-trials
While belief in witchcraft, and persecutions directed at or excused by it, were widespread in pre-Christian Europe, and reflected in Germanic law, the influence of the Church in the early medieval era resulted in the revocation of these laws in many places, bringing an end to traditional pagan witch hunts. Throughout the medieval era, mainstream Christian teaching had denied the existence of witches and witchcraft, condemning it as pagan superstition. However, Christian influence on popular beliefs in witches and maleficium (harm committed by magic) failed to entirely eradicate folk belief in witches.

The fierce denunciation and persecution of supposed sorceresses that characterized the cruel witchhunts of a later age were not generally found in the first thirteen hundred years of the Christian era. The medieval Church distinguished between "white" and "black" magic. Local folk practice often mixed chants, incantations, and prayers to the appropriate patron saint to ward off storms, to protect cattle, or ensure a good harvest. Bonfires on Midsummer's Eve were intended to deflect natural catastrophes or the influence of fairies, ghosts, and witches. Plants, often harvested under particular conditions, were deemed effective in healing.

Black magic was that which was used for a malevolent purpose. This was generally dealt with through confession, repentance, and charitable work assigned as penance. Early Irish canons treated sorcery as a crime to be visited with excommunication until adequate penance had been performed. In 1258, Pope Alexander IV ruled that inquisitors should limit their involvement to those cases in which there was some clear presumption of heretical belief but slowly this vision changed.

The prosecution of witchcraft generally became more prominent in the late medieval and Renaissance era, perhaps driven partly by the upheavals of the era – the Black Death, the Hundred Years War, and a gradual cooling of the climate that modern scientists call the Little Ice Age (between about the 15th and 19th centuries). Witches were sometimes blamed. Since the years of most intense witch-hunting largely coincide with the age of the Protestant Reformation and Counter-Reformation, some historians point to the influence of the Reformation on the European witch-hunt. However, witch-hunting began almost one hundred years before Luther's ninety-five theses.

Dominican priest Heinrich Kramer was assistant to the Archbishop of Salzburg. In 1484 Kramer requested that Pope Innocent VIII clarify his authority to prosecute witchcraft in Germany, where he had been refused assistance by the local ecclesiastical authorities. They maintained that Kramer could not legally function in their areas.

The papal bull Summis desiderantes affectibus ("the witch bull") sought to remedy this jurisdictional dispute by specifically identifying the dioceses of Mainz, Köln, Trier, Salzburg, and Bremen. The bull stated that "many persons of both sexes, unmindful of their own salvation and straying from the Catholic Faith, have abandoned themselves to devils, incubi and succubi (...)". Some scholars view the bull as "clearly political". The bull failed to ensure that Kramer obtained the support he had hoped for. In fact he was subsequently expelled from the city of Innsbruck by the local bishop, George Golzer, who ordered Kramer to stop making false accusations. Golzer described Kramer as senile in letters written shortly after the incident. This rebuke led Kramer to write a justification of his views on witchcraft in his 1486 book Malleus Maleficarum ("Hammer against witches"). The book is noted for its hatred against women.

In the Malleus, Kramer stated that witchcraft was feminine: women were prone to it due to their weakness, their alleged insatiable sexual lust, being "intellectually like children". His work distinguishes itself from other demonologies by its obsessive hate of women and sex, seemingly reflecting the twisted psyche of the author. Levack calls this "scholastic pornography" and Malcolm Gaskill finds Kramer a "superstitious psychopath".

Despite Kramer's claim that the book gained acceptance from the clergy at the University of Cologne, it was in fact condemned by the clergy at Cologne for advocating views that violated Catholic doctrine and standard inquisitorial procedure. In 1538 the Spanish Inquisition cautioned its members not to believe everything the Malleus said. Despite this, Heinrich Kramer was never excommunicated and even enjoyed considerable prestige till his death.

Spanish Inquisition

Portugal and Spain in the late Middle Ages consisted largely of multicultural territories of Muslim and Jewish influence, reconquered from Islamic control, and the new Christian authorities could not assume that all their subjects would suddenly become and remain orthodox Catholics. So the Inquisition in Iberia, in the lands of the Reconquista counties and kingdoms like León, Castile, and Aragon, had a special socio-political basis as well as more fundamental religious motives.

In some parts of Spain towards the end of the 14th century, there was a wave of violent anti-Judaism, encouraged by the preaching of Ferrand Martínez, Archdeacon of Écija. In the pogroms of June 1391 in Seville, hundreds of Jews were killed, and the synagogue was completely destroyed. The number of people killed was also high in other cities, such as Córdoba, Valencia, and Barcelona.

One of the consequences of these pogroms was the mass conversion of thousands of surviving Jews. Forced baptism was contrary to the law of the Catholic Church, and theoretically anybody who had been forcibly baptized could legally return to Judaism. However, this was very narrowly interpreted. Legal definitions of the time theoretically acknowledged that a forced baptism was not a valid sacrament, but confined this to cases where it was literally administered by physical force. A person who had consented to baptism under threat of death or serious injury was still regarded as a voluntary convert, and accordingly forbidden to revert to Judaism. After the public violence, many of the converted "felt it safer to remain in their new religion". Thus, after 1391, a new social group appeared and were referred to as conversos or New Christians. King Ferdinand II of Aragon and Queen Isabella I of Castile established the Spanish Inquisition in 1478. In contrast to the previous inquisitions, it operated completely under royal Christian authority, though staffed by clergy and orders, and independently of the Holy See. It operated in Spain and in most Spanish colonies and territories, which included the Canary Islands, the Kingdom of Sicily, and all Spanish possessions in North, Central, and South America. It primarily focused upon forced converts from Islam (Moriscos, Conversos, and "secret Moors") and from Judaism (Conversos, Crypto-Jews, and Marranos)—both groups still resided in Spain after the end of the Islamic control of Spain—who came under suspicion of either continuing to adhere to their old religion or of having fallen back into it.

All Jews who had not converted were expelled from Spain in 1492, and all Muslims ordered to convert in different stages starting in 1501. Those who converted or simply remained after the relevant edict became nominally and legally Catholics, and thus subject to the Inquisition.

Inquisition in the Spanish overseas empire
In 1569, King Philip II of Spain set up three tribunals in the Americas (each formally titled Tribunal del Santo Oficio de la Inquisición): one in Mexico, one in Cartagena de Indias (in modern-day Colombia), and one in Peru. The Mexican office administered Mexico (central and southeastern Mexico), Nueva Galicia (northern and western Mexico), the Audiencias of Guatemala (Guatemala, Chiapas, El Salvador, Honduras, Nicaragua, Costa Rica), and the Spanish East Indies. The Peruvian Inquisition, based in Lima, administered all the Spanish territories in South America and Panama.

Portuguese Inquisition

The Portuguese Inquisition formally started in Portugal in 1536 at the request of King João III. Manuel I had asked Pope Leo X for the installation of the Inquisition in 1515, but only after his death in 1521 did Pope Paul III acquiesce. At its head stood a Grande Inquisidor, or General Inquisitor, named by the Pope but selected by the Crown, and always from within the royal family. The Portuguese Inquisition principally focused upon the Sephardi Jews, whom the state forced to convert to Christianity. Spain had expelled its Sephardi population in 1492; many of these Spanish Jews left Spain for Portugal but eventually were subject to inquisition there as well.

The Portuguese Inquisition held its first auto-da-fé in 1540. The Portuguese inquisitors mostly focused upon the Jewish New Christians (i.e. conversos or marranos). The Portuguese Inquisition expanded its scope of operations from Portugal to its colonial possessions, including Brazil, Cape Verde, and Goa. In the colonies, it continued as a religious court, investigating and trying cases of breaches of the tenets of orthodox Catholicism until 1821. King João III (reigned 1521–57) extended the activity of the courts to cover censorship, divination, witchcraft, and bigamy. Originally oriented for a religious action, the Inquisition exerted an influence over almost every aspect of Portuguese society: political, cultural, and social.

According to Henry Charles Lea, between 1540 and 1794, tribunals in Lisbon, Porto, Coimbra, and Évora resulted in the burning of 1,175 persons, the burning of another 633 in effigy, and the penancing of 29,590. But documentation of 15 out of 689 autos-da-fé has disappeared, so these numbers may slightly understate the activity.

Goa Inquisition
The Goa Inquisition began in 1560 at the order of John III of Portugal. It had originally been requested in a letter in the 1540s by Jesuit priest Francis Xavier, because of the New Christians who had arrived in Goa and then reverted to Judaism. The Goa Inquisition also focused upon Catholic converts from Hinduism or Islam who were thought to have returned to their original ways. In addition, this inquisition prosecuted non-converts who broke prohibitions against the public observance of Hindu or Muslim rites or interfered with Portuguese attempts to convert non-Christians to Catholicism. Aleixo Dias Falcão and Francisco Marques set it up in the palace of the Sabaio Adil Khan.

Brazilian Inquisition
The inquisition was active in colonial Brazil. The religious mystic and formerly enslaved prostitute, Rosa Egipcíaca was arrested, interrogated and imprisoned, both in the colony and in Lisbon. Egipcíaca was the first black woman in Brazil to write a book - this work detailed her visions and was entitled ''Sagrada Teologia do Amor Divino das Almas Peregrinas. ''

Roman Inquisition
With the Protestant Reformation, Catholic authorities became much more ready to suspect heresy in any new ideas, including those of Renaissance humanism, previously strongly supported by many at the top of the Church hierarchy. The extirpation of heretics became a much broader and more complex enterprise, complicated by the politics of territorial Protestant powers, especially in northern Europe. The Catholic Church could no longer exercise direct influence in the politics and justice-systems of lands that officially adopted Protestantism. Thus war (the French Wars of Religion, the Thirty Years' War), massacre (the St. Bartholomew's Day massacre) and the missional and propaganda work (by the Sacra congregatio de propaganda fide) of the catholic Counter-Reformation came to play larger roles in these circumstances, and the Roman law type of a "judicial" approach to heresy represented by the Inquisition became less important overall. In 1542 Pope Paul III established the Congregation of the Holy Office of the Inquisition as a permanent congregation staffed with cardinals and other officials. It had the tasks of maintaining and defending the integrity of the faith and of examining and proscribing errors and false doctrines; it thus became the supervisory body of local Inquisitions. A famous case tried by the Roman Inquisition was that of Galileo Galilei in 1633.

The penances and sentences for those who confessed or were found guilty were pronounced together in a public ceremony at the end of all the processes. This was the sermo generalis or auto-da-fé. Penances (not matters for the civil authorities) might consist of pilgrimages, a public scourging, a fine, or the wearing of a cross. The wearing of two tongues of red or other brightly colored cloth, sewn onto an outer garment in an "X" pattern, marked those who were under investigation. The penalties in serious cases were confiscation of property by the Inquisition or imprisonment. This led to the possibility of false charges to enable confiscation being made against those over a certain income, particularly rich marranos. Following the French invasion of 1798, the new authorities sent 3,000 chests containing over 100,000 Inquisition documents to France from Rome.

Denunciations
The usual procedure began with the visitation by the inquisitors in a chosen location. The so-called heretics were then asked to be present and denounce themselves and others; it was not enough to denounce himself as a heretic.

Many confessed alleged heresies for fear that a friend or neighbor might do so later. The terror of the Inquisition provoked chain reactions and denunciations even of spouses, children and friends.

If they confessed within a "grace period" — usually 30 days — they could be accepted back into the church without punishment. In general, the benefits proposed by the "edicts of grace" to those who presented themselves spontaneously were the forgiveness of the death penalty or life imprisonment and the forgiveness of the penalty of confiscation of property.

Anyone suspected of knowing about another's heresy and who did not make the obligatory denunciation would be excommunicated and then subject to prosecution as a "promoter of heresy." If the denouncer named other potential heretics, they would also be summoned. All types of complaints were accepted by the Inquisition, regardless of the reputation or position of the complainant. Rumors, mere suppositions, and even anonymous letters were accepted, "if the case were of such a nature that such action seemed appropriate to the service of God and the good of the Faith". It was foreseen that prison guards themselves could report and be witnesses against the accused.

This strategy transformed everyone into an Inquisition agent, reminding them that a simple word or deed could bring them before the tribunal. Denunciation was elevated to the status of a superior religious duty, filling the nation with spies and making every individual suspicious of his neighbor, family members, and any strangers he might met.

Methods of torture used
Defendants were commonly interrogated under torture and finally punished if found guilty, with their property being confiscated in the process to defray legal and prison costs, and to maintain the heavy  machinery of persecution. The victims could also repent of their accusation and receive reconciliation with the Church. The execution of the tortures was attended by the inquisitor, the doctor, the secretary and the executioner, applying them on the nearly naked prisoner. In the year 1252, the bull Ad extirpanda allowed torture, but always with a doctor involved to avoid endangering life, and limited its use to non-bloody methods:

 * Strappado: the victim was lifted to the ceiling with his arms tied behind his back, and then dropped violently, but without touching the ground. This usually meant the dislocation of the victim's arms.
 * Rack or potro: the prisoner was tied to a frame and the executioner pressed until the meat was pierced and blood flowed. In another version, the victim was streched on a sort of table, usually with serious consequences for life.
 * Water cure, now known as water boarding: the prisoner was tied, a cloth was inserted through his mouth down to his throat, and one liter jugs of water were poured in to his mouth. The victim had the sensation of drowning, and the stomach swelled until near bursting.

According to Catholic apologists, the method of torture (which was socially accepted in the context of the time) was adopted only in exceptional cases, and the inquisitorial procedure was meticulously regulated in interrogation practices.

 * Torture could not endanger the subject's life. Torture was allowed when guilt was "half proven" or even not proven, or there existed a "presumption of guilt", or confession was considered incomplete, as stated in Article XV of Torquemada's instruciones and in Eymerich's directions or Portuguese Regimentos.
 * Torture could not cause the subject to lose a limb. The defendant was informed that if he died, broke any limbs or lose consciousness during torment, it would be his fault, and not theirs, the inquisitors, because with "such impudence" he put himself in danger of life and health.
 * Torture could only be applied once, and only if the subject appeared to be lying. In practice, torture was repeated or "continued". The Portuguese instructions (Regimentos) stipulate that defendants may not appear at autos de fé showing marks of torture, so did not recommend using torture other than potro in the previous fortnight.

The summary of the Directorium Inquisitorum, by Nicolás Aymerich, made by Marchena, notes a comment by the Aragonese inquisitor: Quaestiones sunt fallaces et inefficaces ("The interrogations are misleading and useless"). This did not stop the use of torture, strongly advised in the volume by Aymerich himself.

Despite the loss of thousands of documents over the years, many of the meticulous records of torture sessions have survived. They are extraordinary documents, dry bureaucratic expositions, which record even the screams of the tortured, and which go on for pages and pages.

Fake instruments of torture
Despite what is popularly believed, the cases in which torture was used during the inquisitorial processes were rare, since it was considered (according to some authors) to be ineffective in obtaining evidence. Before torture, inquisitors displayed  the  instruments mainly on the purpose of intimidation of the accused, so  he may  understood what to expect. If he wished to avoid punishment, he should only confess his faults.

In the words of historian Helen Mary Carrel: "the common view of the medieval justice system as cruel and based on torture and execution is often unfair and inaccurate." As the historian Nigel Townson wrote: "The sinister torture chambers equipped with cogwheels, bone crushing contraptions, shackles, and other terrifying mechanisms only existed in the imagination of their detractors."

In fact, it seems likely that the Inquisition favoured simpler and "cleaner" methods, which left few apparent marks. Aymerich points out that canon law does not prescribe either this or that particular torture, so judges can use whatever they see fit, as long as it's not an unusual torture. Many types of torments have been chosen, but Eymerich think they seem more like the inventions of executioners than the works of theologians. "It is true that it is a very praiseworthy practice to subject the accused to torture, but no less reprehensible are those bloodthirsty judges who base their vain glory on the invention of crude and exquisite torments" - he adds. Many torture instruments were designed by late 18th and early 19th century pranksters, entertainers, and con artists who wanted to profit from people's morbid interest in the Dark Age myth by charging them to witness such instruments in Victorian-era circuses.

However, several torture instruments are accurately described in Foxe's Book of Martyrs, including but not limited to the dry pan.

Some of the instruments that the Inquisition never used, but that are erroneously registered in various inquisition museums:

 * The troublemaker's flute: Created in the 17th century. Its first mention comes from the years 1680-90 of the Republic of Venice used against deserters from the war between the Ottoman Empire and the Republic of Venice.
 * Head crusher: Created in the 14th century. Its first mention comes from 1340 in Germany. It was not used by the Inquisition but by the German courts against the enemies of some prince-electors.
 * Judas's cradle: Created in the fifteenth century. Its first mention comes from 1450-80 in France. Used by the parlement and not by the Inquisition, it was abolished in 1430.
 * The Spanish donkey: Created in the 16th century. The name connects the instrument to the Spanish Inquisition, although it was only used in certain regions, which were not primarily Spain nor as part of the Inquisition, but by Central European civil authorities (most notably Reformed Germany and the Bohemian Crown), New France, the Netherlands Antilles, the British Empire, and the United States. It is unclear exactly who invented this device, and it is likely that it was ascribed to Spain as "Black Legend" propaganda.
 * The Spanish tickle: Created in 2005 as a false rumor on Wikipedia.
 * The Thumbscrew: Created in the 16th century. It was used for the persecution of Catholics by William Cecil in England during the reign of Elizabeth I. It was not used by the Inquisition, but by the English courts against dissidents to the Protestant Reformation, later also for the torture of slaves.
 * The saw: Created in the fifteenth century. Its first mention comes from 1450-70. Used by the Hungarian court against Muslims in the context of the war between the Ottoman Empire, the Byzantine Empire and the Kingdom of Hungary.
 * Pear of anguish: Created in the fifteenth century. Its first mention comes from 1450. Used by the French parlement and not by the Inquisition, it was abolished in 1430. The historian Chris Bishop came to postulate that it could have actually been a sock stretcher, since it has been proven that it was too weak to open into a body orifice.
 * The Spanish Boot: Created in the 14th century. Its first mentions come from Scotland with the buskin. Used by the authorities in England to persecute Catholics in Ireland. Later the civil authorities of France and Venice would use it, but not by the Spanish Inquisition.
 * The "Cloak of Infamy". Created in the 17th century. It was first mentioned by Johann Philipp Siebenkees in 1790, and was used by the Nuremberg parliament (Protestant) against thieves and prostitutes.
 * The Iron Maiden. The use of iron maidens in judicial proceedings or executions is doubted. Several replicas of the Iron Maiden existed, and the one of Nuremberg Castle was destroyed in 1944 as a result of bombing during  World War II. It was probably based on the 17th century Cloak of Infamy.
 * The Breast ripper. Created at the end of the 16th century. The first reference dates back to Bavaria (Germany) in 1599 and presumably it would have been used in France and Holy Roman Empire by civil authorities and not by the Inquisition. However, there are no reliable first-hand historical sources on the use of the devices, so, like the Iron Maiden, there is a possibility that the devices shown in the images are fakes of a later manufacture (such as from the 17th century) or assembled from small fragments that may have been parts of another device. Most likely, it was often mentioned to frighten and force the accused to confess, rather than such dubiously existent torture being inflicted on them.
 * The Stocks. Created in the Middle Ages and used by the civil authorities of London, not the Inquisition, in order to publicly shame criminals, but not physically harm them or take life.
 * The bronze bull. Created in the Ancient Age and never used in medieval Europe, much less in the Inquisition. In fact, there is a chance that it never existed at all and was just a popular legend of Greco-Latin culture.
 * The Scold's bridle. Created in the 16th century. It was never legalized and was only used unofficially by some civilians in Scotland and England, not by the Inquisition.
 * The dungeon of rats. Created in the 16th century, its main reference is from John Lothrop Motley about some anecdotes of torture against the "papists" during the Dutch war of independence. It is also said that Catholics who resisted the Church of England under Elizabeth I were tortured in the Tower of London. Used by some Protestant governments and not by the Inquisition.
 * Heretic's Fork, Boots, Cat's Paw, and Iron Cage. Created in the 15th-16th century. Used by the French parlement and not by the Inquisition.

Trials
The Inquisition's trials were secret and there was no possibility of appealing the decisions. The defendant was constantly pressured to confess to the "crimes" assigned to him. The Inquisitors kept the accusations made and the evidence they possessed hidden, in order to achieve a confession without announcing the accusation. The main goal was to make the defendant confess.

Each court had its own staff (lawyers, prosecutors, notaries, etc.) and its own prison. The guards who served the inquisition spied the accused in their cells; if they refused to eat, for example, this action could be considered a fast, a Jewish custom.

In many cases, it was common for false accusations to be made against New Christians and it was difficult to prove their innocence. It was therefore more convenient for many to make a false confession to the inquisitors, including a list of imaginary accomplices, in the hope that they would not receive extreme penalties, such as the death penalty, but only the confiscation of property or lesser penalties.

In fact, there wasn't a trial in the modern sense of the term, but an extensive interrogation; the prisoner was kept in the dark about the reasons for his arrest — often for months or even years. There was no precise accusation and therefore little chance of a plausible defence. The prisoner was simply advised "to search his conscience, confess the truth, and trust to the mercy of the tribunal’".

Eventually, the prisoner was informed of the charges against him — omitting the names of the witnesses. Thus, the charade continued. After the interminable interrogations, hearings and waiting periods came to an end, the sentence could be pronounced.

The Inquisition trials had little to do with justice. Walter Ullmann, a historian, summarises his evaluation: "There is hardly one item in the whole Inquisitorial procedure that could be squared with the demands of justice; on the contrary, every one of its items is the denial of justice or a hideous caricature of it [...] its principles are the very denial of the demands made by the most primitive concepts of natural justice [...] This kind of proceeding has no longer any semblance to a judicial trial but is rather its systematic and methodical perversion."

In one of his books, Portuguese author A. José Saraiva points out the analogy of the trials with the absurdity of the Kafka's novel The Trial or the show trials of Stalin's era in Moscow.

Punishments
The Inquisition's sentences could be simple penances, for example private devotions, or heavy punishments. One of the Inquisition's punishments was the forced wearing of distinctive clothing or signs such as the sambenito, sometimes for an entire life.

Other punishments were exile, compulsory pilgrimages, fines, the galleys, life imprisonment (in fact prison for some years) and in addition the confiscation of goods and property. The bull Ad Extirpanda determined that the houses of heretics should be completely razed to the ground. Furthermore, the impact of the Inquisition's activity on the fabric of society was not limited to these penances or punishments. As under the terror of the Inquisition entire families denounced each other, they were soon reduced to misery,  completed  by the confiscation of property, public humiliation and ostracism.

Even dead people could be accused, and sentenced up to forty years after the death. When inquisitors considered proven that the deceased were heretics in their lifetime, their corpses were exhumed and burned, their property confiscated and the heirs disinherited.

Legitimation by the texts
The Inquisition always referred to biblical passages, as well as to church fathers, like Augustine of Hippo, to legitimise his actuation.

The New Testament contains some sentences that the church could interpret for dealing with heretics. The excommunication of a deviant from the faith was equivalent to handing him over to the Devil: "When you have gathered together, and my spirit with you, in the power of our Lord Jesus, hand this man over to Satan for destruction of the flesh, so that his spirit may be saved on the day of the Lord." (The Pauline letters: 1 Corinthians, B. Incest in Corinth, 5:4 and 5:5 )

The sentence of Paul could also be understood in this way: he handed over to the Devil those "who have suffered shipwreck in the faith [...] so that they may be taught not to be blasphemous." (The Pastoral epistles: 1 Timothy - The first letter from Paul to Timothy—Timothy’s responsibility: 1:19 and 1:20)

Paul's view reflects less the idea of punishment than the idea of isolation when he says: " After a first and second warning have nothing to do with a disputatious person, since you may be sure that such a person is warped and is self-condemned as a sinner." (The Pastoral epistles : Titus - The letter from Paul to Titus—3:10 and 3:11)

In the Gospel of John, Jesus tells the apostates in a parable: " I am the vine,you are the branches. Whoever remains in me, and I in that person, bears fruit in plenty; for apart from me you can do nothing.Anyone who does not remain in me is thrown away like a branch and withers.These branches are collected, thrown on the fire and burnt." This parable can be interpreted as the burning of stubborn heretics at the stake. (The Gospel according to John: The true vine—15:5 and 15:6)

Saint Augustine (354-430) led a debate in Africa with the Donatist community, which had split from the Roman Church. In his works, he called for moderate severity or measures by secular power, including the death penalty,  against heretics, however he did not consider it desirable: “Corrigi eos volumus, non necari, nec disciplinam circa eos negligi volumus, nec suppliciis quibus digni sunt exerci", meaning “We would like them to be improved, not killed; we desire the triumph of church discipline, not the death they deserve.”

The celebrated theologian Thomas Aquinas (1225-1274) supplied the theoretical foundation for the medieval Inquisition. In his Summa theologica  he called for excommunication and the death penalty for heretics: “Accipere fidem est voluntatis, sed tenere fidem iam acceptam est  necessitatis"  (i.e. "The acceptance of faith is voluntary, maintaining the accepted faith is necessary"),  a vision that we also find today in islamic extremism.

Luis de Páramo, theologian and Inquisitor of then Spanish-ruled Sicily from 1584 to 1605, asserted that Jesus Christ was "the first Inquisitor under the Evangelical law" and  that John the Baptist and the apostles were also inquisitors.

Opposition and resistance
In many regions and times, there was opposition to the Inquisition. Heretics and other targets did not hesitate to attempt to murder the inquisitors, or destroy its voluminous archives, because they had much to lose in the face of an inquisitorial investigation: their freedom, their property, their lives. Opposition sometimes came from more tolerant and open minded individuals within the clergy itself. The much hated Inquisitor Konrad von Marburg, who also initiated inquisition trials against nobles, was murdered in 1233 by six mounted men on an open country road on the way to Marburg.

In 1242, a Cathar group armed with axes entered the castle of the town of Avignonet (southern France) and murdered the inquisitors Guillaume Arnaud and Étienne de Saint-Thibéry.

In 1252, the inquisitor Peter of Verona was killed by Cathars. Eleven months after his assassination, he was made a Catholic saint, the quickest canonization in history. As Christine Ames writes, “Inquisition changed what it meant to be a martyr, to be holy, and to be an imitator of Christ.”

In 1395 near Steyr, where the inquisitor Petrus Zwicker was quartered with associates, an assassination attempt on him failed: someone had tried to set fire to the place and burn him alive.

During French Inquisition, a Franciscan friar, Bernard Délicieux, opposed the actions of the Inquisition in Languedoc. The infamous Bernard Gui presented him as the commander-in-chief of the "iniquitous army" against the Dominicans and the Inquisition. Délicieux alleged the Inquisitiors were pursuing innocent Catholics for heresy, trying to destroy their towns. He stated that the methods of the inquisition would have condemned even Peter and Paul as heretics if they appeared before the inquisitors. Délicieux later became one more victim of the Inquisition for his criticism. In 1317, Pope John XXII called him and other Franciscan Spirituals to Avignon, and he was arrested, questioned, and tortured by the Inquisition. In 1319, he was found guilty and sentenced to life in prison. Fragile and old, he died shortly thereafter.

In Portugal, Father António Vieira (1608-1697), himself a Jesuit, philosopher, writer and orator, was one of the most important opponents of the Inquisition. Arrested by the Inquisition for "heretical, reckless, ill-sounding and scandalous propositions" in October 1665,was imprisoned until December 1667. Under the Inquisitorial sentence, he was forbidden to teach, write or preach. Only perhaps Vieira's prestige, his intelligence and his support among members of the royal family saved him from greater consequences.

He is believed to have been the author of the famous anonymous writing Notícias Recônditas do Modo de Proceder a Inquisição de Portugal com os seus Presos, which reveals a great deal about the inner workings of the Inquisitorial mechanism and which he delivered to Pope Clement X in favour of the cause of the persecuted of the Inquisition. It is true that the Inquisition was suspended by papal order between 1674 and 1681.

Father Vieira led an anti-inquisition movement in Rome, where he spent six years. In addition to his humanitarian objections, he also had others: he realised that a mercantile middle class was being attacked that would be sorely missed in the country's economic development.

Statistics
Beginning in the 19th century, historians have gradually compiled statistics drawn from the surviving court records, from which estimates have been calculated by adjusting the recorded number of convictions by the average rate of document loss for each time period. Gustav Henningsen and Jaime Contreras studied the records of the Spanish Inquisition, which list 44,674 cases of which 826 resulted in executions in person and 778 in effigy (i.e. a straw dummy was burned in place of the person). William Monter estimated there were 1000 executions in Spain between 1530–1630 and 250 between 1630 and 1730. Jean-Pierre Dedieu studied the records of Toledo's tribunal, which put 12,000 people on trial. For the period prior to 1530, Henry Kamen estimated there were about 2,000 executions in all of Spain's tribunals.

Italian Renaissance history professor and Inquisition expert Carlo Ginzburg had his doubts about using statistics to reach a judgment about the period. "In many cases, we don't have the evidence, the evidence has been lost," said Ginzburg.

Ending of the Inquisition in the 19th and 20th centuries
By decree of Napoleon's government in 1797, the Inquisition in Venice was abolished in 1806.

In Portugal, in the wake of the Liberal Revolution of 1820, the "General Extraordinary and Constituent Courts of the Portuguese Nation" abolished the Portuguese Inquisition in 1821.

The wars of independence of the former Spanish colonies in the Americas concluded with the abolition of the Inquisition in every quarter of Hispanic America between 1813 and 1825.

The last execution of the Inquisition was in Spain in 1826. This was the execution by garroting of the Catalan school teacher Gaietà Ripoll for purportedly teaching Deism in his school. In Spain the practices of the Inquisition were finally outlawed in 1834.

In Italy, the restoration of the Pope as the ruler of the Papal States in 1814 brought back the Inquisition to the Papal States. It remained active there until the late-19th century, notably in the well-publicised Mortara affair (1858–1870). In 1908 the name of the Congregation became "The Sacred Congregation of the Holy Office", which in 1965 further changed to "Congregation for the Doctrine of the Faith", as retained to.

Documents and works

 * Directorium Inquisitorum
 * Histoire de l'Inquisition en France
 * Malleus Maleficarum

Notable inquisitors

 * Grand Inquisitor
 * Konrad von Marburg
 * Tomás de Torquemada
 * Bernard Gui

Notable cases

 * Galileo affair
 * Execution of Giordano Bruno
 * Trial of Joan of Arc
 * Edgardo Mortara
 * Basque witch trials
 * Caterina Tarongí
 * Rosa Egipcíaca

Repentance

 * List of apologies made by Pope John Paul II

title: Inquisition