Listening for infection project7x

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14 Δεκ 2013 (πριν από 3 χρόνια και 6 μήνες)

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Tim Elliott, Benjamin Mawson

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Listening for infection


How mi ght
the
human i mmune system
sound?

A cross
-
disciplinary research project between

Medicine
, Music, & Social Science
:

Exploring and representing complex biomedical phenomena to
wide

audience
s

through
virtual
interactive
soun
d
.


Investigating emerging forms of understanding that
spring
from interaction with the intangible complexity
of molecular biology through the intangi
ble medium of sound.


What happens when the body finds it has an intruder?

How can an immunologist and a composer
collaboratively
express the complex
beauty and wonder of the human immune system?

What can virtual audio do that no other medium can achieve i
n expressing these
biological phenomena to a wide public?

In the human immune system
,

a continual ‘white noise’ of communication
between ‘self’ or native cells signals the health or sickness of the body.

On becoming infected, a cell signals this and selfl
essly invites its own destruction
by
CTL
cells
,

which exist specifically
for this purpose.

If
the CTL are
successful, t
he infection is eradicated and
the body returns to health.

If not, the battle continues between replicating intruders and vigilant guardians.

How could these complex communications and conflicts
be explored through
sound
and what are
the implications for our understanding of these phenomena
in
such a medium
?

How are cultural and scientific spaces (re
-
)defined by exploration of natural
phenomena in a simulated environment, where
participant
experience is
collective yet individuated?




Tim Elliott, Benjamin Mawson

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“Listening for infection”

How mi ght the human i mm
une system sound?




The perpetual motion of the human immune system

................................
................................
...

3

Step 1: Steady
-
state of the normal human genome

................................
................................
.........................

4

Step 2: The peptidome

................................
................................
................................
................................
......

5

Step 3: Add a viral genome after infection

................................
................................
................................
........

7

Step 4: T cells hear the call

................................
................................
................................
................................

8

Telling the story through sound

................................
................................
................................
............

9

The listener experience: live sound

................................
................................
................................
.................

10

The listener experience: virtual sound

................................
................................
................................
............

11

Technology

................................
................................
................................
................................
......................

12

(1)

3DBARE (
”Threadbare”
)


Three Dimensional Binaural Audio Rendering Engine

.............................

13

(2) noTours


software for Android using GPS for listener tracking

................................
............................

15

Why Sound?

................................
................................
................................
................................
.....................

17

Delivery:

................................
................................
................................
................................
...........................

18


Figure 1: a virus cell



Tim Elliott, Benjamin Mawson

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The perpetual motion of the human immune system

In viral infection, a virus
enters one of our cells and hides there
, hijacking the cell
and turn
ing

it into a
factory for producing more virus. Luckily, our immune system can detect the presence of a sequestered
vir
us and will destroy the
infected cell
,

ne
utralising the factory before it has
a chance

to

produce more virus
particles.
Thus in an act of altruistic self
-
sacrifice, the infected cell signals to our immune system that it is
infected
,

thereby bringing on its destruction.

In order for the immune system to detect the presence of a parasitical
pathogen, it

must identify
the invader’s
difference from the surrounding cells.

A perpetual
search
is
conducted,
for cells communicating a ‘correct’

identity and those reveal
ing

their
alien
-
ness

by displaying slight differences.

The agents of this

defensive search
-
and
-
destroy mission
,
specialised
white blood cells
called
cytotoxic T
lymphocytes
,

or
CTL
,

recognise
fragments of viral protein presented
to it

by specialised molecules

(MHC molecules)

on
an
infected
cell’s surface.

These fragments, called peptides,
are strings of
nine amino acids
.
E
ach
one of
these amino acids or building blocks making up the peptide
can be one of 20
different
types
.

An inconceivable
number of permutations thus arise
:

there are
1.21577E+19

possible combinations
that can be

presented


by
the
MHC.


Many of these will

exist in the normal human genome but some will
exist only
in
the viral genome


and this is the chink in the
virus’
armour
,

because CTL will
be able to hunt out these tell
-
tale signs of infection
, by the way the MHC
molecule identifies itself
.

Graphical r
epresentations
(still images or video)
might use variations in colour
and intensity, capable of depicting an overall range. They can either provide fixed snapshots in time of a
wider field of activity or very high magnifications of
changing
micro
-
elemental

activity. In the first instance,
a sweeping and generalised capture of a single moment is
possible whereas, in the latter
,

change over time
is evoked
, but only on a
fractional scale.

This paper proposes a solution to these limitations in depicting the
complexity and flux of the immune
system to a non
-
specialist audience, deploying sound for representations capable of comprehending both
Figure 2: a swarm of
CTL

killing a virus
-

infected cell.


Figure 3:
HLADR1, the CTL’s
-
eye
-
view of a peptide (green)
being presented to it by an
MHC molecule (red)



Tim Elliott, Benjamin Mawson

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the passage of time and multiple simultaneous events or interstices.



Tim Elliott, Benjamin Mawson

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Step 1: Steady
-
state of the normal human genome

Wi
th
20 to the power of 9 different peptides possible in nature

(512 billion)
,
many of these are generated
by the human genome.

So
with

say a thousand million (10 to the power of 9)
peptides
that can be
expressed
by the human genome
,
a
literal representation

of this
is inconceivably
complex.

The sound of
our genome in the form of short peptides would be equivalent to listening for individual drops of water in
the rain.

Exploring effective means of expressing this
biological
activity and conveying its comple
xity while
translating
it
into
a
comprehensible, engaging form accessible to a wide audience is the principal objective
of this stage of the collaboration.

Each cell expresses thousands of MHC molecules on its surface. Each MHC molecule holds up a single
p
eptide.





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Step 2: The peptidome

MHC molecules ar
e actually selective and prefer

anchors
at position
2

and
9

in the
string
,

which never vary.

So
from
the enormous
collective tumult of communication, it is possible to
select only the
molecules

or
‘players’ creating
a specified
sonic tag, expressing peptides
with a common
element
at
positions
2

and
9
.

As
sound
,

this would be impenetrable if literally expressed,
like white noise punctuated with a
sudden, huge
pure tone
every
2
nd

and
9
th

“beat” in the bar

of 9 notes.


If,
instead of
conventional relay via
physically
spaced loudspeakers,
wireless headsets are used, with a
unique set of behaviours in the treatment of the processed audio, responding to listener movement, then
clarification a
nd discovery of the minute activity within the tumult is made possible.


[
The technology for this setting, a software called 3dBARE (“
Threadbare
”), is under
development

and
practice
-
based
comparative

evaluation against
both
loudspeaker

systems and
tra
cking
-
predicated platforms for delivery of virtual audio.

This will be explained in full detail later
in this paper. Before a description of how it is achieved, imagine the following scenario:

Listeners in wireless headsets enter an empty white room. The s
ounds conveyed to them depend
upon where they stand and how they move. They hear sounds apparently coming from a point in
the space and approach to inspect it more closely. If the MHC molecules were orchestral
performers, listener would to hear the perform
ance as if from amongst the woodwind for a while
then move to the back of the violins, then diagonally through the empty space to the brass
section, the instruments’ amplitude growing or diminishing according to their distance, always
apparently rooted in
the same physical spot, despite which way they turned their heads.

]


The cells of the body do not sit in a neat planar configuration; they move in all directions around the
vascular system, on a
similar

scale to humans in a sea. Their
self
-
identifying
messages

must therefore be
‘audible’ from all directi
ons to the human participant as they explore.

Overlapping, related r
hythm
s
and tonal colours
emerge
.

The common factor between all peptides is their
2
nd

and
9
th

elements. Others may concur or differ but
the common elements are constant. (Concurrence is
statistically almost impossible).

Translated into blocks of musical notes, a string might take the form:



Tim Elliott, Benjamin Mawson

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C
E

F# E D C# E D
B

Because sound occurs over time rather than in spatial dimensions, it must be
repeated to remain present.
The MHC molecule repeats itself:

C
E

F# E D C# E D
B


C
E

F# E D C# E D
B


C
E

F# E D C# E D
B


etc

It is joined in chorus by a neighbouring MHC molecule, similar in that its 2
nd

and 9
th

elements are identical
to those of the fi
rst:

A
E

D# B G G# A F
B


A
E

D# B G G# A F
B


A
E

D# B G G# A F
B


etc

A pattern emerges as the listener hears cycles with unison emerging at two periodic points:

C
E

F# E D C# E D
B


C
E

F# E D C# E D
B


C
E

F# E D C# E D
B


etc

A
E

D# B G G# A F
B


A
E

D# B G G# A F
B


A
E

D# B G G# A F
B


etc

As cells evince themselves and declare their identity and condition, the chorus grows:

C
E

F# E D C# E D
B


C
E

F# E D C# E D
B


C
E

F# E D C# E D
B


etc

A
E

D# B G G# A F
B


A
E

D# B G G# A F
B


A
E

D# B G G# A F
B


etc

E
E

A# C C E# B C
B


E
E

A# C C E# B C
B


E
E

A# C C E# B C
B


etc

Each peptide has the same general sound, x
E

x x x x x x
B
; many unique lines with common factors sound
synchronously.

A single cell among billions, each expressing thousands of MHC
molecules, becomes infected by a virus.
Some of the cell’s MHC switch to the viral peptide, differing slightly from the established concord expressed
by the healthy cells.

At first, the variation in the auditory mass is only perceptible to those closest to

it, and then only with focus.
Before long, the virus, which may reproduce at a rate of 100
-
fold per half hour, is not only in evidence in
small corners but threathening to overturn the equilibrium of the whole.

An inescapable widespread battle ensues. A
single cell is engulfed by attacking CTLs, to kill and expel it and
the destructive element it harbours. Any oversight will lead to prolongation or return to battle at an
unspecified future moment: the CTL is forever watchful.

During both
defensive watch and the
battle

itself
, the listener witnesses conflict between self and invader
cells at first hand, as though actually present at a scene of complex molecular conflict.



Tim Elliott, Benjamin Mawson

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Step 3: Add a viral genome after infection

As infection is detected, c
ertain
voices switch to singing the viral genome.

This involve
s

both identical and
differing
parts
,

fraction
s now gen
erating the same sound material
,
the
character
of which
is dictated by the
viral genome
.
With growing heterophonic combination, the viral
evidence becomes more pronounced.

In Figure 5, continual combinatory change emerges from a single repeated cell. After introducing slight
variation to a single line then permitting this, too, to replicate, the listener activates gradual shifts in the
combi
nations forming the whole:
from a single version of the cell, many identical phase
-
shifted copies
create a heter
o
phonic combination where repetition and newly emerging patterns express a growing
concentration of cell activity with common intent.

Each indiv
idual cell’s line is colour
-
coded. Even with only
three cells, continually differing simultaneous combinations emerge.

As the number of CTL cells with the
same or similar identifiers grows, an apparently chaotic but unified whole emerges. While in continua
l flux,
the fluid motion of multiple similarly
-
motivated agents is identifiable:

The original pattern can still be discerned amid irregular combinations of itself as the fundamental element.
Where timbre, spatialisation and processing identify unique emitt
ers the differentiation is made clearer.

S
witch
ing

to the new
peptidome
, including

sounds
unique to the virus
, as
these
become prominent
amongst the complex, apparently chaotic whole, they now
add to and complicate
the background
sounds
that have been esta
blished.




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Step 4: T cells hear the call

Cytotoxic T cells recognise only one peptide

song


derived from a virus

but
,

when they do
,

they destroy the
cell
producing the ‘song’
.

They achieve this recognition via complementary cell
-
surface receptor
s
.

This too

can
be represented
through distinct sonic patterns,

matching
its complimentary sets.

[[Figures 10
-
12: 3 snapshots of sound changing over time as CTLs negotiate ]]



Tim Elliott, Benjamin Mawson

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Telling the story through sound



Tim Elliott, Benjamin Mawson

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The listener experience
: live sound

T
o represent
these
phenomena to audiences
,

we
are
designing
an immersive, interactive sound
environment. This will take two forms, described below,
first
introduced through
live music
-
making.

Visitors will
be led to
start
making
simple sounds either with their voice or an in
strument. They will be
asked to repeat a short phrase metrically. A ‘conductor’ will signal each successive entry of visitors’ CTL
phrase: initially everyone singing or playing is making a very similar sound, albeit in their own rhythm and
cycle
.

As more v
isitors/CTLs are added to the total sound, we listen for change occurring through the fluctuating
whole. At first, it will seem to some participants that they can perceive change due to these fluctuations.

As we become accustomed to the shifting yet essen
tially static nature of the whole, our hearing acquires a
new contextual auditory acuity based in similar forms of pattern recognition occurring in the CTLs
themselves.

The other, sound
-
producing listeners are not what we are listening out for, as they re
present safety in
similarity.

T
he aberrations evinced by the surreptitious incursion of the virus are gradually noticed by neighbouring
‘cells’ (participants)
;

their song
starts
to mimic the newly heard, differing patterns, making these now more
prominent
.

During sessions with school and adult visitor groups to geo
-
located music compositions
,

we have found
experimental choral singing an
effective means of demonstrating some
of the sonic phenomena which they
are about to encounter.

Through experimental enga
gement of the kind outlined here
,

a conceptual framework is introduced by
which to read the more complex sonic exploration that will follow. These singing exercises help both to
illustrate the primary materials and some ways in which geo
-
location can affec
t their combination.



Tim Elliott, Benjamin Mawson

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The listener experience: virtual sound

In its simplest form, the abundance of healthy, protective CTL cells can be illustrated by
heterophonic
multiplication of a single melodic line,
varied through
simultaneous differing tempi and ph
asing

of unequal
length

cells who are in other respects near
-
identical
.

Translating the scales of permutations into sonic fragments which are more or less similar within a limited
range, the complex fluctuating stasis of the healthy state is clearly disce
rnible in sound.

The
recognition by
the CTL of the uniqueness of the viral codes will create subtle

variations in patterns

which at first will be
barely perceptible
.

The listener ceases to represent the cells as they had during singing, now instead shadowing them. Moving
around the space

in
a wireless tracking system and headphones
, they
hear a fluctuating combination of

closely
-
related cells with common, defensive pur
pose.
While the whole is both complex and endlessly
changing in its detail, the overall effect of a literal representation would be similar to white noise.

For this reason


that
the data would be overwhelming and incomprehensible if represented in its en
tirety


sonic cells are introduced sequentially, with reduced individual and collective complexity to their
biological analogues.
1

As the listener moves between virtual zones, each containing unique sonic cells they start to recognise the
different ‘tags’ or MHC molecules worn on the surface of the viral intruders, drawing
CTLs along with it to
investigate.
By engaging in complex mimi
cry they both announce and ultimately overcome the intrusive,
aberrant element.

The
cumulative heard
effect is that across a wide physical area, listeners will act
in concert with the sound
-
producing
CTLs, rooting out the viral components in the sound fiel
d.

Through their interaction they will
incrementally add to the prominence of the viral infection

as activity
in the area
intensifies
, before
overcoming the intruders
.

As listeners become biological agents
,

exploring and partaking in a microscopic field o
f conflict, they are
confronted with the astonishing complexity and order of micro
-
biological systems,
of
the human body and
the continual fight against disease and infection that continues there unseen.




1

A
string of
9
elements comprised of any combination of
20
sources

has
6.4 billion

possible
permutations
.



Tim Elliott, Benjamin Mawson

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Technology

T
wo
proposed means of exploring
these phe
nomena through sound
.

As the listener moves
in the
designated situational
space, they encounter the four stages of interaction between the CTLs and the viral
peptides. They
shadow
the cytotoxic T cell, surveying the landscape for signs of infection.

The vi
ral “song” is
more or less in evidence according to the way in which they explore the soundscape.



Tim Elliott, Benjamin Mawson

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(1)

3DBARE

(
”T
hreadbare

)


Three Dimensional Binaural Audio Rendering Engine

Currently under collaborative development
between Music and
ISVR, 3DBARE is a
new
means for virtual
spatialization of multi
-
channel audio to a tracked, wireless headset. It consists of an audio rendering engine,
a user interface and tracking controller.

As the listener moves and turns to face different directions, they hear sounds fixe
d to various virtual
locations in their surroundings. They are able both to move between sounds as though they were actually
being produced in the space and to trigger them by their action.

I
ndividual
audio
stems
are virtually spaced around the
listener. A
t a given position in the space, the listener
perceives one or more sounds seeming to come from fixed points. As they turn, the sound remains in its
original position by means of our audio rendering engine, giving the listener the illusion of moving betwee
n
real sound
-
producing objects.




Transition through differing sonic areas is seamless


those sounds entering or

leaving audible range are
faded in/out
. One appears to move between real, fixed position sounds. Each audio may be either a
recorded or a generated sound: endless permutations are possible.

Other elements to the simulation
will eventually also include
vi
rtual occlusion

(walls, doorways and other
barriers/openings)
and
room impulse responses
, evoking room size and shape as well as more detailed
Listener in position A at
centre of audible sources
(in red)





Listener at position B
now hears different
sources, closest to them



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information about the position and orientation of the virtual sound source
. The
distance
over which a
source
is
a
udible
may also be controlled
according to context
.

A

demonstration
model of 3DBARE
is now ready with a limited range of functionality and number of
sources. We are able to demonstrate the user experience in two interactive forms: a computer
-
based user
int
erface, controlled by mouse/keyboard action and an
iPhone

app with two sources and listener
-
orientation controlled audio rendering.



Tim Elliott, Benjamin Mawson

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(2)
noTours


software for Android using GPS for listener tracking

During
develop
ment of
3DBARE,
we have conducted parallel experiments in geo
-
located audio, working
with
the developers of noTours

since mid
-
2011

to construct
immersive virtual soundscapes at London’s
South Bank (Impossible Brilliance Festival), St Paul’s Churchyard (for Cap Gemini and
Google Maps) and the
University of Southampton (London 2012 Musical Alphabet & ‘Audio Portrait of a City’ with Southampton
Music Hub).

noTours is software for
Android
, using
GPS
for
listener
tracking
to
facilitate “editing a place with sounds”,
allowing listeners to walk inside a soundscape, encountering sound objects of differen
t character, duration
and behaviours arranged in a complex pattern of circles across a wide area.

The
listener triggers a sound

by
entering a virtual circle (whose
radius and centre
-
point’s longitude
and latitude are registered by the
handset and exchange
d with GPS for
real
-
time triangulation)
. They may
hear one or many sounds at once,
their combinations varying
continually according to position,
movement and relative time
between onsets
.


There is no practical limit to the
number of circles and therefore
differing audio fragments that may
be integrated to a single project (hard
-
coded limit is one million: thousands of times more than could
perceived by a listener).

Two types of circle are possible:

Soundpoint


a single sound, emanating from wherever in l
istener
-
relational field sound has been placed
when processed in studio. (E.g. binaural simulation of car crossing rear auditory field, left to right. File will
be heard in same rendering regardless of listener orientation)
.

Figure 14: Three
noTours
projects during 2012

(1) Jubilee Gdns, London SE1,

(2) St Paul’s Churchyard, London EC2,



(3) Highfield Campus, University of Southampton



Tim Elliott, Benjamin Mawson

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Sound
scape


circle containing

four audio files, audible according to listener orientation. By default these
are set to four equal quadrants, enabling
the cross
-
fading of four audio recordings
identical except for the binaural
rendering (movement and direction of
sound).

The behaviours

of a given circle may be
specified as follows:



Speaker


louder towards the centre of a circle



Vibrate


handset vibrates to notify user of entering new circle



Fade in


default 4 second fade
-
in as listener enters circle



Fade out


as above, fades out



Pla
y once


play once on entering then stop. Re
-
entry to circle re
-
triggers audio



Loop, continue


entering zone causes audio to play in continuous loop, even after leaving circle



Loop, pause


loops until listener leaves, resumes at point paused on re
-
entry
to circle



Loop, stop


loops until listener leaves circle

then stops

Circles may be of any size or position. Efficacy of sound
-
map depends on r
esponse of GPS, which has a
gene
ral accuracy of
around 10
metres. Each circle needs therefore to be at least 25 m
etres in diameter

for
sufficient

overlap to work dependably on listener movement
.

Twenty circles of this size can be
accommoda
ted within a one hectare space. Previous projects have used between 22 and 53 circles. Where
smaller numbers of circles are used (
due to perimeter restrictions of a site, such as Valley Gardens,
University of Southampton) whose diameters must be great enough for reliable GPS location, audios may
be placed consecutively within a single circle (by splicing them into a single sequence).


It is
thus
possible to programme

complex fixed
set
s

whose permutations are
infinite
ly variable,
delivering a
real
-
time illustration of the cumulative activity at points of infection where CTLs encounter and combat the
viral intruder.

The complexity of the phenomena represented are such that an infinitesimal fraction of the
whole is auditorily perceptible to the human ear.



Tim Elliott, Benjamin Mawson

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Why Sound?

M
otivic repetitions within and between CTL peptides behave differently in visual and aural representati
ons
in that while the eye may perceive differentiation
,
boundaries and fluctuations within
a
cycle, the ear
attaches significance to fluctuations or prominences

occurring in time rather than space
, ascribing

notional

boundaries to these details.

A princip
le focus from a
sonic
perspective will be upon how the complexity of the biological phenomena
outlined can
,

through sound alone
,

be expressed accurately and engagingly, remaining as close as possible
to their source.

By spreading sound across s
pace and per
mitting its detail

to be revealed both in physical and temporal
dimensions we open
possibilities

for perception not only of the
phenomena explored but of the situational
space, our interaction with other participants and our altered perception of the space

in which the
encoun
t
er occurs.

It has been found during recent demonstrations of geo
-
located sound projects that listeners were alerted
to physical, topographic and other sensory aspects of the situational space as a result of focussing on the
more
unusual primary sense of hearing.

We would seek to investigate the means by which for complex scientific data to be conveyed at a purely
sensory level to public audiences through combined expertise in medical
, social science

and music
compositional researc
h of the team

and to create a study of modes of spectating and the experiential
results for participants in the programme.

How usefully can
specific factual
phenomena be mapped onto other forms of expression than those
conventionally understood to convey c
lear and specific information?

What new insights are to be gained
particularly
into intercellular activity and current perception of it
through examining and presenting the concepts in this new form?

R
epresenting
data
in sound
requires
quasi
-
linguistic
tra
nslation akin to the
representation
of time

in two
dimensions
.

What are the most effective means of doing this in specific social and research
contexts?



Tim Elliott, Benjamin Mawson

Mar
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Delivery:

For the
sonic elements to the project, a
combination of programming (MAX), composition and au
dio
delivery to audiences is required.

(1)
Programming

algorithmic generation of primary
sound
material
using
MAX/msp.

(2)
Composing

the stems
: selecting, developing,
combining this material into sonic
CTLs and MHC peptides.

(3)
Constructing the soundwalk
: testing wide area interactive sound map deploying the sound material.

(4) E
vents at which listeners navigate the soundfield as though at the site of the battle with infection.

An additional online resource
is intended
to serve both as longer term outreac
h for the project and an
archive both of the research and the listener experience.
The constructional logic and technical frameworks
for these two forms are largely different though bui
lt around the same key elements
.