Service

Independent

Access

Control

Architecture

for

User

Generated

Content

(UGC)

and

Its

Implementation

Using

Web-based

content

management

systems

such

as

Blog,

an

end

user

can

easily

publish

User

Generated

Content

(UGC).

Although

publishing

of

UGCs

is

easy,

controlling

access

to

them

is

a

difficult

problem

for

end

users.

Currently,

most

of

Blog

sites

offer

no

access

control

mechanism,

and

even

when

it

is

available

to

users,

it

is

not

sufficient

to

control

users

who

do

not

have

an

account

at

the

site,

not

to

mention

that

it

cannot

control

accesses

to

content

hosted

by

other

UGC

sites.

In

this

paper,

we

propose

new

access

control

architecture

for

UGC,

in

which

third

party

entities

can

offer

access

control

mechanism

to

users

independently

of

UGC

hosting

sites.

With

this

architecture,

a

user

can

control

accesses

to

his

content

that

might

be

spread

over

many

different

UGC

sites,

regardless

of

whether

those

sites

have

access

control

mechanism

or

not.

The

key

idea

to

separate

access

control

mechanism

from

UGC

sites

is

to

apply

cryptographic

access

control

and

we

implemented

the

idea

in

such

a

way

that

it

requires

no

modification

to

UGC

sites

and

Web

browsers.

Our

prototype

implementation

shows

that

the

proposed

access

control

architecture

can

be

easily

deployed

in

the

current

Web-based

communication

environment

and

it

works

quite

well

with

popular

Blog

sites.

In

the

era

of

Web

many

users

generate

Web

content

as

well

as

just

browse

through

them.

Web-based

content

management

systems

such

as

various

Blog

sites

make

it

easier

for

users

to

generate

content,

which

are

called

User

Generated

Content

(UGC)

or

Consumer

Generated

Media

(CGM).

UGC

opens

to

access

to

the

public

and

the

openness

encourages

many

users

to

read

them,

which

results

in

active

and

personal

communications

between

generator

and

consumer

users.

We

call

a

user

who

creates

a

content

generator

user,

and

a

user

who

reads

the

content

consumer

user.

However,

the

openness

is

not

always

a

desirable

feature

for

generator

users.

For

example,

a

generator

user

would

want

to

restrict

accesses

to

a

private

portion

of

his

content

except

from

certain

members,

such

as

his

family

or

friends..

Although

some

Blog

sites

offer

access

control

mechanism,

their

functionality

is

limited

within

content

hosted

by

the

site

and

users

registered

on

the

site.

For

example,

Vox

a

popular

Blog

site,

allows

generator

users

to

classify

their

content

into

friends,

family,

neighborhood

and

public,

each

of

which

classes

specifies

who

can

access

the

content.

Although

they

provide

the

fine

granularity

of

accessing

content,

the

content

must

be

hosted

by

VOX.

In

addition,

both

generator

and

consumer

users

must

have

their

accounts

on

VOX.

It

means

that

consumer

users

cannot

read

the

content

unless

they

have

an

identifier

at

the

same

UGC

site

as

generator

users

do..

To

identify

users

who

do

not

have

an

account

at

the

site

but

at

other

sites,

independent

identifiers

such

as

TypeKey

and

OpenID

are

proposed.

If

a

user

possesses

one

of

those

identifiers,

UGC

sites

can

identify

the

user

even

if

the

user

does

not

register

to

the

site.

However,

the

access

control

is

limited

within

content

hosted

by

the

UGC

site,

and

is

not

available

for

content

hosted

by

other

sites

even

if

those

content

are

generated

by

the

same

user..

In

this

paper,

we

propose

new

access

control

architecture

for

UGC,

which

enables

users

to

employ

a

particular

access

control

mechanism

separately

from

the

UGC

site.

The

key

idea

to

separate

access

control

mechanism

from

UGC

hosting

sites

is

to

use

cryptographic

access

control

which

is

originally

proposed

for

access

control

of

distributed

storages.

In

the

cryptographic

access

control,

all

content

are

protected

by

encryption

algorithm

so

that

the

only

user

who

has

a

decryption

key

can

access

to

the

content.

Therefore,

the

system

can

enforce

the

access

policy

of

content

by

controlling

delivery

of

the

decryption

key

instead

of

controlling

accesses

to

the

content..

Our

contributions

are

not

only

the

new

architecture

but

also

its

implementation.

Though

the

previous

works

require

renovation

of

access

control

or

modification

of

UGC

sites

our

architecture

is

implemented

in

such

a

way

that

it

requires

no

modification

to

UGC

sites

or

Web

browsers.

We

evaluate

that

it

can

work

well

with

existing

UGC

sites

such

as

Blogger

and

LiveJournal

This

shows

that

the

proposed

architecture

can

be

easily

deployed

in

the

current

Web

based

communication

environment..

The

rest

of

this

paper

is

organized

as

follows.

We

summarize

background

and

problem

statements

in

Section

In

Section

we

explain

the

proposed

architecture,

and

we

describe

the

implementation

in

Section

Section

discusses

the

security

and

related

work.

Finally,

we

conclude

in

Section

In

this

paper,

we

propose

a

new

access

control

architecture

for

UGC,

which

separates

not

only

authentication

but

also

authorization

from

Content

Hosting

Site.

This

architecture

enables

users

to

employ

desirable

access

control

mechanism,

regardless

of

whether

the

UGC

site

has

an

access

control

mechanism

or

not.

The

key

idea

to

separate

access

control

mechanism

from

UGC

sites

is

to

apply

cryptographic

access

control,

which

encrypts

all

content

and

controls

accesses

to

decryption

keys

instead

of

the

content

themselves.

Using

our

architecture,

the

users

can

publish

their

content,

which

can

be

accessed

by

certain

members,

even

if

the

users

have

an

account

at

the

various

UGC

sites

and

the

content

are

spread

over

various

sites..

Our

contributions

are

not

only

architecture

but

also

its

implementation.

Our

architecture

can

be

applied

to

current

Web

browser

and

UGC

site

without

any

modifications

on

both

sides.

We

believe

that

this

architecture

stimulates

a

Web-based

communication

environment.

According

to

a

survey

istry

of

Internal

Affairs

and

Communication,

million

articles

on

Blog

sites

occupy

T

byte

on

a

storage.

It

means

that

an

article

contains

K

byte

of

text

in

average.

Another

survey

indicates

that

the

number

of

characters

in

an

article

depends

on

Blog

sites,

and

are

about

to

In

our

implementation,

a

User

Agent

can

encrypt

articles

within

from

sec

to

sec

in

average.

In

a

sequence

of

a

content

publication

process,

the

proposed

architecture

increase

additional

sec

to

sec

in

average..

We

believe

that

this

additional

processing

time

is

acceptable

for

users

who

require

more

security

on

current

Content

Hosting

Sites.

It

is

true

that

evaluation

of

users'

patience

is

difficult

without

launching

a

service

of

the

proposal.

However,

considering

a

number

of

related

works

and

implementations,

such

as

OAuth,

we

think

that

the

proposed

functionalities

are

potentially

desired

by

users,

even

if

it

increases

processing

time..

The

key

manager

plays

a

strong

role

in

the

proposed

system,

the

server

handle

the

every

encryption

key.

However,

the

server

cannot

access

the

plain

content

directly,

because

the

content

is

encrypted

and

decrypted

at

the

Browser

of

the

client.

Though

the

server

pdf

could

also

access

the

encrypted

content

published

on

the

user's

Blog

site,

the

server

needs

to

discover

the

location

of

the

encrypted

content

corresponds

to

the

key..

The

architecture,

which

controls

all

accesses

at

a

single

point,

has

both

advantages

and

disadvantages.

As

the

advantage,

the

key

manager

can

easily

enforce

the

all

access

policies

at

a

single

point.

On

the

other

hand,

if

the

key

manager

is

compromised

by

an

attacker,

then

all

controlled

content

become

vulnerable.

However,

there

is

another

barrier;

the

attackers

have

to

find

out

the

location

of

the

encrypted

content,

similar

as

the

above

Key

Managers'

case..

Some

users

may

be

anxious,

even

if

the

above

mechanisms

guarantee

the

security.

For

higher

security

demands,

it

is

possible

to

introduce

more

than

one

Key

Manager.

Applying

cryptographic

secret

sharing

algorithm,

the

system

can

divides

the

encryption

key

into

several

shares.

The

multiple

Key

Managers

store

one

of

these

shares

independently.

It

is

cryptographically

impossible

for

any

attacker

to

retrieve

the

key

from

shares

less

than

threshold..

Furthermore,

a

personal

Key

Manager

is

another

solution

to

enhance

security.

Because

the

format

of

protected

content

contains

Key

ID,

which

works

as

a

bootstrap

to

discover

the

corresponding

Key

Manager,

the

user

can

easily

introduce

a

personal

Key

Manager.

This

concept

is

similar

to

OpenID

protocol,

any

entity,

which

includes

a

user,

can

establish

an

ID

provider.

Because

management

of

a

personal

key

manager

is

costly,

the

users

have

to

balance

between

the

gain

of

security

and

its

cost.

Bauer

et

al.

proposed

an

access

control

system

for

the

Web

content

which

can

be

operated

among

multiple

Web

sites.

However,

the

prototype

system

is

implemented

with

a

local

Web

proxy

and

server

module,

so

that

the

scheme

requires

modification

to

UGC

sites.

As

a

more

feasible

solution,

some

Web

browsers'

extensions

have

mechanisms

to

encrypt

messages

of

Gmail.

However,

those

extensions

also

require

modification

of

Web

browser,

and

have

no

function

to

manage

content..

As

the

protection

of

XML

document,

there

are

some

architectures

which

control

access

to

a

portion

of

the

document

hosted

by

distributed

sites..

Though

the

architectures

have

a

potential,

they

require

conventional

UGC

sites

to

support

the

architecture.

Alternatively,

a

URL

based

Identifier

such

as

OpenID

and

XRI

also

have

messaging

protocols

which

enables

communication

between

users

who

have

an

identifier

at

different

UGC

sites.

However,

those

protocols

have

not

been

implemented

yet

for

popular

Web

browsers

or

UGC

sites..

OAuth

is

an

authorization

protocol,

which

has

a

similar

concept

to

our

proposal

in

terms

of

content's

access

control

on

Web

sites.

However,

there

are

differences

in

the

assumptions,

access

control

methodologies,

and

use

cases.

The

proposed

architecture

assumes

that

a

user

cannot

trust

the

Content

Hosting

Site

completely.

On

the

other

hand,

OAuth

protocol

assumes

that

a

Content

Hosting

Site

is

trustworthy

to

authorize

accesses

to

its

content.

In

this

context,

a

Content

Hosting

Site

corresponds

to

a

Service

Provider

in

OAuth's

specification..

The

assumption

that

our

proposal

employ

is

reasonable,

because

most

Content

Hosting

Sites

are

started

by

venture

companies,

which

forces

on

developing

the

site's

new

functions

rather

than

security

functions.

Furthermore,

it

is

possible

that

the

site's

owner

sells

the

site

and

its

hosted

content

to

other

company.

Concerning

such

situations,

we

introduce

a

Key

Manger

and

User

Agents

as

the

trusted

third

party,

which

enables

to

separate

authorization

from

a

Content

Hosting

Site..

Although,

our

proposal

is

more

secure

than

OAuth,

it

has

disadvantage

in

the

implementation.

We

implement

User

Agent

using

JavaScript

invoked

from

Bookmark

so

that

a

user

does

not

have

to

modify

her

Web

browser.

However,

the

architecture

is

troublesome

for

developers

that

implement

in

a

limited

environment

of

a

programming

language

JavaScript.

As

the

result,

we

only

target

on

text-based

content

in

this

paper.

OAuth

does

not

have

such

limitation

so

that

a

Content

Hosting

Site

can

easily

control

rich

content,

such

as

images

and

videos..

In

addition,

the

proposal

and

OAuth

are

different

in

their

use

cases.

The

proposed

architecture

is

convenient

to

control

accesses

from

individual

users,

rather

than

Web

applications.

On

the

other

hand,

OAuth

has

an

advantage

in

controlling

accesses

from

other

Web

applications

rather

than

individual

users.

OAuth

protocol

requires

initialization,

which

is

acceptable

for

Web

applications

but

bothers

individual

users.

Twitter

announces

that

it

provides

an

interface

of

OAuth

protocol

to

other

Web

applications,

but

not

to

individual

users

who

possess

OpenID.

It

is

an

example

that

OAuth

protocol

is

not

good

for

handling

individual

users

In

this

section,

we

compare

conventional

access

controls

for

UGC

and

the

proposed

architecture.

As

we

explain

in

Section

conventional

UGC

sites

own

their

access

control

mechanism

consists

of

an

authentication,

authorization,

content

hosting

function

individually.

Obviously,

the

UGC

site

cannot

distinguish

users

who

do

not

have

an

identifier

on

the

site.

In

addition,

the

UGC

site

cannot

control

content

hosted

by

other

sites,

even

if

those

content

are

generated

by

a

same

user

Fig.

Using

authentication

APIs

or

OpenID,

the

UGC

site

can

distinguish

users

who

do

not

have

an

identifier

on

the

site

but

have

one

on

an

API's

site

or

an

OpenID's

IDprovider.

Though

the

authentication

function

is

separated

from

access

control,

the

authorization

function

is

still

tied

with

the

content

hosting

site.

It

means

that

the

policies

related

to

content

are

managed

on

a

UGC

site,

and

accesses

to

the

content

are

controlled

by

the

UGC

site.

Therefore,

the

users

cannot

control

access

to

their

own

content

that

spread

over

many

different

UGC

sites

(Fig.

The

proposed

architecture

enables

to

operate

an

authentication,

authorization,

and

content

hosting

function

independently.

Not

only

users

but

also

policy

can

be

managed

by

third

party

entities,

which

is

different

from

the

content

hosting

site.

With

this

architecture,

a

user

can

employ

a

desirable

access

control

mechanism

against

the

content

that

might

be

spread

over

various

UGC

sites,

regardless

of

whether

the

hosting

sites

have

an

access

control

mechanism

or

not

Fig.

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Reconstruction of 3D genome architecture via a two-stage algorithm AbstractThe three-dimensional (3D) configuration of chromosomes within the eukaryote nucleus is an important factor for several cellular functions, including gene expression regulation, and has also been linked with cancer-causing translocation events. While visualization of such architecture remains limited to low resolutions, the ability to infer structures at increasing resolutions has been enabled by recently-devised chromosome conformation capture techniques. In particular, when coupled with next generation sequencing, such methods yield an inventory of genome-wide chromatin contacts or interactions. Various algorithms have been advanced to operate on such contact data to produce reconstructed 3D configurations. Studies have shown that these reconstructions can provide added value over raw interaction data with respect to downstream biological insights. However, only limited, low-resolution reconstructions have been realized for mammals due to computational bottlenecks. Results: Here we propose a two-stage algorithm to partially overcome these computational barriers. The central idea is to initially utilize existing reconstruction techniques on an individual chromosome basis, using intra-chromosomal contacts, and then to relatively position these chromosome-level reconstructions using inter-chromosomal contacts. This two-stage strategy represents a natural approach in view of the within-versus between-chromosome distribution of contacts. It can increase resolution ≈20 fold for mouse and human. After describing the algorithm we present 3D architectures for mouse embryonic stem cells and human lymphoblastoid cells. We evaluate the impact of several factors on reconstruction reproducibility and explore a variety of sampling schemes. We further analyze replicate data at differing resolutions obtained from recently devised in situ Hi-C assays. In all instances we demonstrate insensitivity of the whole-genome 3D reconstruction obtained by the two-stage algorithm to the sampling strategy used. Conclusions: Our two-stage algorithm has the potential to significantly increase the resolution of 3D genome reconstructions. The improvements are such that we can progress from 1 Mb resolution to 100 kb resolution, notable since this latter value has been identified as critical to inferring topological domains in analyses performed on the contact (rather than 3D) level. The proposed two-stage algorithm offers a promising technique for obtaining whole genome 3D reconstructions from Hi-C assays. By sampling 3D coordinates from individual chromosome solutions (obtained using any existing method), and deploying inter-chromosomal contacts to relatively position these solutions, it efficiently leverages contact data enabling substantial improvements in resolution. The purpose of this article was to demonstrate proofof-principle for a two-stage approach to obtaining whole genome 3D reconstructions from Hi-C assays. The advantages of such a strategy include (i) effective use of both within chromosome (majority of interaction counts) and between chromosome (majority of interaction pairs) contacts; (ii) the ability to use existent reconstruction tools, especially for the first stage generation of individual chromosome solutions; and (iii) the potential to obtain higher resolution whole genome reconstructions. As noted, this latter point is consequential with respect to eliciting topological and contact domains in mammalian genomes [11, 12] . The two-stage reconstruction method could potentially be improved by employing more sophisticated sampling schemes. These could make recourse to targeting loci with large inter-chromosomal counts or be based on curvature summary measures for the individual chromosome solutions. Moreover, a variety of sampling schemes could be deployed and a consensus (averaged) structure reported after performing Procrustes alignment. The regression-based testing of between versus within sample variation, as utilized for the comparisons presented in the 'Results' , could be used as a precursor determinant as to whether such averaging was justified, analogous to the consensus index [7] . For demonstration purposes we have, in part, used ChromSDE for stage one reconstructions of individual chromosomes because of its desirable characteristics. Two recent papers purportedly show relatively poor performance of ChromSDE; accordingly we make some brief comments on these assessments. Varoquaux et al. [8] use MDS to provide an initial 3D reconstruction then refine this configuration using Poisson regression. In making comparisons between differing reconstruction approaches, they comment that "ChromSDE does not infer the relative position of chromosomes. " Our twostage algorithm provides such relative positioning thereby expanding the scope and utility of ChromSDE. Moreover, based on simulation studies, [8] contend that ChromSDE performs relatively poorly in low signal-to-noise settings. However, the simulations were based on data generated according to their Poisson model and employed a fixed α value conforming to this model. Such a framework deprives ChromSDE from demonstrating putative advantages associated with estimating α. A more complete comparison would result from applying the Poisson model to data generated with a misspecified α value.. In evaluating ShRec3D, Lesne et al. [24] also make comparisons with ChromSDE, again based on simulation. While the methods are comparable with respect to accuracy, ChromSDE is deemed worse with respect to both problem size capability and computational time. Again, these are aspects wherein our proposed two-stage algorithm can extend applicability of ChromSDE. Further, contrary to [7] , Lesne et al. contend that the choice of α is not critical. As they note, weak or vanishing contact frequencies do not contribute to inferred distances, since shortest path constructions will avoid corresponding links (of large or infinite lengths). Accordingly, ShRec3D involves an implicit filtering. Since 3D solutions are also obtained via MDS it is presumably the degree of this filtering that is responsible for its improved problem size and compute time characteristics.. Recent work by Diament and Tuller [26] also employs sampling as a precursor to 3D genome reconstruction. For S. cerevisiae they demonstrate that even under sparse samplings, down to the 5 % level, the resultant reconstructions are concordant with the original reconstruction in terms of co-localization of various genomic landmarks and functional groups. This concordance is used to suggest the possibility of reducing the scale of Hi-C experimentation, if 3D reconstruction is used to analyze the data. As such, their findings are consistent with our results that show that sampling, also down to the 5 % level, does not impact the 3D reconstruction itself. Accordingly, our two-stage approach is able to realize 20-fold improvements in resolution.. The mouse and human data analyzed herein are diploid. To date, 3D whole-genome reconstructions based on Hi-C data from diploid organisms implicitly treat homologous chromosome pairs as coincident (i.e. as occupying roughly the same position, relative to inter-chromosomal positioning) [7, 8, 24] . The reasonableness of such an assumption is unclear. The emergence of high resolution in situ Hi-C assays [12] has enabled phasing of Hi-C maps. This derives from having sufficient reads overlap SNPs so that contacts can be assigned to specific chromosomal homologs. At present, the resolutions needed for such phasing are such that computational bottlenecks, even with our twostage algorithm, preclude 3D genome reconstruction on a diploid level. Even though the disambiguation provided by phasing shows that, for autosomes, maternal and paternal homologs exhibit very similar inter-and intra-chromosomal contact profiles (Pearson's R > 0.998) and, accordingly, very similar between loci distances, this does not in itself imply that are homologous pairs are roughly coincident in view of results from computational geometry [39] . We note that for a near-haploid chronic leukemia cell line (KBM7) Ay et al., [27] provide a diploid reconstruction.. Contact data at 1 kb resolution from in situ Hi-C assays will challenge existing 3D reconstruction algorithms on both memory and computational complexity grounds. For example, 10 % downsampling of whole genome human 1 kb resolution data will still yield a distance matrix requiring ∼670 GB of RAM. Accordingly, even obtaining individual chromosome solutions will require downsampling and/or algorithmic refinements (cf. [40, 41] ). However, once these are generated, the two-stage approach developed here will again be valuable in eliciting whole genome 3D architecture. The result of a Hi-C experiment, following important preprocessing and normalization steps [13, [16] [17] [18] [19] , is the contact map, a symmetric n × n matrix F = [ F ij ] of contact counts between n (generally binned) genomic loci i, j on a genome-wide basis. This matrix can be exceedingly sparse with many zero entries even after binning. The 3D genome reconstruction problem is then to obtain a 3D point configuration, with a one-to-one correspondence between points and genomic loci, such that the resulting pairwise inter-point distances best recapitulate the corresponding frequencies. We operationalize "best recapitulate" below. Many approaches have been proposed to tackle this problem, with broad distinction [8, 20] between optimization/consensus and probabilistic/ensemble methods, although these can overlap. Our focus here is on the former. A common first step in these reconstruction algorithms (e.g. [6, 8, 9, 14, [24] [25] [26] [27] ) is conversion of the frequency matrix into a distance matrix D = [ D ij ]. This is often followed by a second step which solves the graph realization [28] or multi-dimensional scaling (MDS, [29] ) problem: position points (corresponding to genomic loci) in 3D so that the resultant interpoint distances best conform to the distance matrix. We briefly describe aspects of each of these components in order to position our two-stage algorithm.

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


Tag SNP selection via a genetic algorithm Single Nucleotide Polymorphisms (SNPs) provide valuable information on human evolutionary history and may lead us to identify genetic variants responsible for human complex diseases. Unfortunately, molecular haplotyping methods are costly, laborious, and time consuming; therefore, algorithms for constructing full haplotype patterns from small available data through computational methods, Tag SNP selection problem, are convenient and attractive. This problem is proved to be an NP-hard problem, so heuristic methods may be useful. In this paper we present a heuristic method based on genetic algorithm to find reasonable solution within acceptable time. The algorithm was tested on a variety of simulated and experimental data. In comparison with the exact algorithm, based on brute force approach, results show that our method can obtain optimal solutions in almost all cases and runs much faster than exact algorithm when the number of SNP sites is large. Our software is available upon request to the corresponding author. A new genetic algorithm for htSNP selection problem is presented. The input of our algorithm is m full haplotype each with n SNPs, and the output is a set of htSNPs. We use binary vector of length n to represent an individual of the population in the genetic algorithm. The fitness function is based on the least number of htSNPs and combined with Shannon entropy function. Two new cross over and mutation are designed. The algorithm is implemented on a variety of simulated and biological data sets. The obtained results show the efficiency and accuracy of our algorithm that is comparable with the other considered algorithms. Applying our method to whole human genome and using htSNPs in association studies is our planning for future works. Our algorithm is implemented using Microsoft Visual C++ compiler 6 and run on a 2.4 GHz Pentium 4 processor PC with 512 MB of RAM. First, we present the results of applying our algorithm on multiple simulated and real data sets and compare with exact algorithms. Simulated data sets are generated by using MS of Hudson [10] , a well-known haplotype generator based on the coalescent model of SNP sequence evolution, and Hapmap data [11] is source of our real data sets. One of the most capable ways to find out the genetic basis of complex diseases such as cancer, drug response, or other human phenotypes is genetic association studies. Objective of these studies is to discover relations between genetic variations and such traits, by comparing genetic sequence and phenotypes of individuals sampled from a population [1] .. Single Nucleotide Polymorphisms (SNPs) are very useful in genetic association studies because they make a high-resolution map of the genome available and allow researchers to associate variations in a particular genetic sequence to phenotypes [2] . A SNP refers to the instance of two specific nucleotides of a single locus in a population. Haplotype can be defined as asset of SNPs on a single chromosome that is associated and inherited as a unit. In the context of population genetics, SNPs can be used to determine relationship between alleles at different nearby positions, called linkage disequilibrium (LD) [3] . Very large number of SNPs in the human genome, which makes SNPs so useful, also makes genome wide association studies computationally intensive and thus difficult to apply when large numbers of SNPs and large numbers of individuals are being considered. However, studies in linkage disequilibrium have revealed that for the individuals in the specific regions, the SNPs are grouped into blocks of limited diversity [4] .. SNPs are biallelic, i.e. the number of distinct values of SNPs is just two, that is, only two nucleotides out of four possible nucleotides may be selected as the values of SNPs [4] . Therefore, each SNP can be represented by a binary variable and each haplotype by a binary vector where each element shows a SNP. Consequently a set of haplotypes can be presented by a matrix whose each row presents a haplotype.. Since the number of distinct combinations of SNP alleles within a block is relatively small [5] , thus, selecting a small subset of SNPs that efficiently represent other SNPs in a given block is an important problem for reducing genotyping costs without losing the ability to detect disease associations. This process known as Tag SNP selection, and selected SNPs called Haplotype Tagging SNPs (htSNPs) [2] . More precisely, the input to the problem is haplotypes of a small sample, and the output is smallest subset of htSNPs that can reconstruct any haplotype with desired accuracy.. Note that the complete 100% reconstruction is impossible, because the occurrence a single mutation occurred in new haplotypes (controls), may cause a reconstruction error. Thus we wish to reconstruct haplotypes with highest achievable accuracy. The assumption is that the genotyped htSNPs carry sufficient statistical power for identifying disease associations.. The problem of finding minimum set of htSNPs is shown to be NP-hard [6] . This means that currently there is no way to find an optimal solution in practical time and space. Previous works on htSNPs selection have investigated both exact and approximate methods. Exact methods select a set of htSNPs that accounting for the variations in the sample population [4, 7] , while approximate methods typically select fewer tags than exact methods, but by losing some information [8] .. Many efforts are done to find the minimum set of htSNPs in haplotype blocks. In a large-scale study of human Chromosome 21, Patil et al. [4] partitioned the haplotypes into 4135 blocks with 4563 htSNPs using greedy algorithm. Zhang et al. [9] developed a dynamic programming algorithm and reduced the numbers of blocks and htSNPs to 2575 and 3562, respectively. Sebastiani et al. [7] developed an exact method called BEST, based on the set theory and recursively search the minimal set of htSNPs from which the maximum number of the other SNPs in the data set can be derived with a given function. Nevertheless, its usefulness on genome-wide association is not verified. Bafna et al. [6] proved that the problem of minimizing htSNPs is NP-hard. They studied special cases of this problem and described an efficient algorithm for each case.. In this paper, we design a genetic algorithm for the htSNP selection problem, called GTagger (Genetic Tagger). It is planned to find smallest htSNPs set in blocks with relatively large number of SNP sites. With growing number of individuals genotyped and SNPs in databases, htSNPs selection takes too long to compute, so speeding up the tag SNPs selection is an important issue. Our algorithm helps to reduce number of SNPs without losing information they contain. It removes cost of genotyping unnecessary SNPs and eases association studies by reducing problem size and dimension. Results based on both biological and simulated data sets show that our algorithm can find optimal solutions returned by the exact algorithm in the most cases and in other cases results are very close to the optimal solution. Obviously, these results also show that our algorithm runs much faster than exact algorithm in all cases.. The rest of the paper is organized as follows. Some notions and a detailed problem formulation are given in Section 2. In Section 3 we describe our genetic algorithm in detail. Results are shown in Sections 4 and 5 concludes the paper. In this section, the designed genetic algorithm for solving the htSNP selection problem is presented. The input of the algorithm is m full haplotype patterns each with n SNPs, which are presented as a matrix H. The output will be a set of htSNPs.. Genetic algorithm begins with an initial population of many individuals or solutions. The algorithm then adds some, hopefully, better individuals by letting the best individuals do crossover and mutating the results. Then, all individuals in population compete with each other to survive for the next generation. Genetic algorithm uses two evolutionary operators, mutation and crossover, and a mechanism for selecting candidate individuals to do these operations. The performance of genetic algorithm is influenced mainly by these two operators, thus, a genetic algorithm is efficient if the evolutionary operators provide a well exploration of the problem solution space.

O O O O O B I B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O B I O O O O O O O O O O O O O O O


Segmentation of Vessel-Like Patterns Using Mathematical Morphology and Curvature Evaluation Abstract-This paper presents an algorithm based on mathematical morphology and curvature evaluation for the detection of vessel-like patterns in a noisy environment. Such patterns are very common in medical images. Vessel detection is interesting for the computation of parameters related to blood flow. Its tree-like geometry makes it a usable feature for registration between images that can be of a different nature. In order to define vessel-like patterns, segmentation will be performed with respect to a precise model. We define a vessel as a bright pattern, piece-wise connected, and locally linear. Mathematical Morphology is very well adapted to this description, however other patterns fit such a morphological description. In order to differentiate vessels from analogous background patterns, a cross-curvature evaluation is performed. They are separated out as they have a specific Gaussian-like profile whose curvature varies smoothly along the vessel. The detection algorithm that derives directly from this modeling is based on four steps: 1) noise reduction; 2) linear pattern with Gaussian-like profile improvement; 3) cross-curvature evaluation; 4) linear filtering. We present its theoretical background and illustrate it on real images of various natures, then evaluate its robustness and its accuracy with respect to noise. An efficient algorithm for vessel-like pattern detection has been presented. Robustness and accuracy have been evaluated on different images, demonstrating that it may be useful in a wide range of retinal images. Based on a brief comparison with some other edge detection algorithms, we can conclude that the complementarity of mathematical morphology and linear transforms allows a more complete treatment. It was possible to select vessels using shape properties, connectivity, as well as differential properties like curvature. The robustness and weaknesses of the algorithm have been evaluated and explained in order to facilitate its use for the analysis of retinal images. This segmentation has been used for image registration of images of the retina [13] , and it is the first step toward an automatic diagnosis software.. Even though the scope of this article is limited to eye fundus images, The reader should note that the proposed algorithm has been tested successfully on other images. In Fig. 26 , the road can be described as being a tree-like edge with a Gaussian-like profile. Since this description fits our model, it is not surprising to see that the road is segmented with our algorithm. Some developments in other areas cannot be excluded.

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CONTINUOUS TIME QUANTUM WALKS AND QUOTIENT GRAPHS Continuous-time quantum walks (CTQW) over¯nite group schemes is investigated, where it is shown that some properties of a CTQW over a group scheme de¯ned on a¯nite group G induces a CTQW over group scheme de¯ned on G=H, where H is a normal subgroup of G with prime index. This reduction can be helpful in analyzing CTQW on underlying graphs of group schemes. Even though this claim is proved for normal subgroups with prime index (using the Cli®ord's theorem from representation theory), it is checked in some examples that for other normal subgroups or even non-normal subgroups, the result is also true! It means that CTQW over the graph on G, starting from any arbitrary vertex, is isomorphic to the CTQW over the quotient graph on G=H if we take the sum of the amplitudes corresponding to the vertices belonging to the same cosets. Quantum walks have recently been introduced and investigated with the hope that they may be useful in constructing new e±cient quantum algorithms (for reviews of quantum walks, see Refs. 1À3). A study of random walks on simple graph is wellknown in physics (see Ref. 4) . Recent studies of quantum walks on more general graphs were described in Refs. 1, 5À17. Some of these works study the problem in the important context of algorithmic problems on graphs and suggest that quantum walks is a promising algorithmic technique for designing future quantum algorithms. In particular, the study of continuous-time quantum walks (CTQW) on graphs has shown promising applications in the algorithmic and implementation aspects. Quantum walks have applications other than in the design of new algorithms. In Refs. 18À22, CTQWs on graphs have been used to e±ciently transfer quantum states with perfect or optimal¯delity.. In this paper, we consider CTQW over more general graphs that are underlying graphs of group association schemes. In fact, the theory of association schemes 23 has its origin in the design of statistical experiments. The algebraic formulation of association schemes was done by Bose and Mesner who introduced an algebra generated by the adjacency matrices of the association scheme, known as Bose-Mesner (BM) algebra. We will employ the algebraic structures of these graphs in order to calculate the corresponding probability amplitudes, in terms of the parameters of the corresponding association scheme such as the diameter of the scheme and the so-called¯rst eigenvalue matrix P (which is related to the character table of the corresponding group in the case of group association schemes). As we will see, the preference of this employment is that we are able to give analytical formulas for probability amplitudes of CTQW over these graphs in terms of the irreducible characters of the corresponding group. Then, we use the representation theory to explain aspects of CTQW on certain classes of graphs called underlying graphs of association schemes. We employ the theorem of Cli®ord 24 from representation theory to show that a CTQW over a group association scheme de¯ned on a¯nite group G induces a CTQW over group association scheme de¯ned on G=H, where H is a normal subgroup of G with prime index. In fact, it is shown that if we sum the probability amplitudes corresponding to the vertices belonging to the same cosets of H in G, then the resulted amplitudes are the same as the amplitudes of CTQW over the underlying graph of the quotient group association scheme de¯ned on G=H, up to a computable time scale. This reduction can be helpful in analyzing CTQW on underlying graphs of group association schemes. The structure of the paper is as follows: In Sec. 2, some preliminary facts about association schemes, especially group association schemes and their algebraic formulation are reviewed. In Sec. 3, CTQW over underlying graphs of group association schemes is investigated where it is shown that CTQW on¯nite group G induces a CTQW on G=H where H is a normal subgroup of G with prime index p, if we sum the probability amplitudes corresponding to the vertices belonging to the same cosets of H in G. Section 4 is devoted to CTQW over some examples of underlying graphs of group association schemes and the corresponding coset G=H graphs. The paper ends with a brief conclusion and an Appendix.

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Throughput Scaling of Wireless Networks With Random Connections Abstract-This work studies the throughput scaling laws of ad hoc wireless networks in the limit of a large number of nodes. A random connections model is assumed in which the channel connections between the nodes are drawn independently from a common distribution. Transmitting nodes are subject to an onoff strategy, and receiving nodes employ conventional single-user decoding. The following results are proven:1) For a class of connection models with finite means and variances, the throughput scaling is upper-bounded by O(n 1/3 ) for single-hop schemes, and O(n 1/2 ) for twohop (and multihop) schemes.2) The Θ(n 1/2 ) throughput scaling is achievable for a specific connection model by a two-hop opportunistic relaying scheme, which employs full, but only local channel state information (CSI) at the receivers, and partial CSI at the transmitters.3) By relaxing the constraints of finite mean and variance of the connection model, linear throughput scaling Θ(n) is achievable with Pareto-type fading models.Index Terms-Ad hoc networks, channel state information (CSI), multiuser diversity, opportunistic communication, random connections, scaling law, throughput. Throughout this work, we adopt the broad perspective of the impact of the channel connection models on the network throughput scaling. Specifically, the discussion is based on a general assumption about the connection models (cf. Theorem 1) instead of particularizing to any specific model. Such specific analysis for Rayleigh fading model, for example, can be found in [19] and [17] for single-hop setups, and in [18] for a two-hop setup. Recently, other specific channel models have been studied. See, for example, [23] for a single-hop scheme in lognormal fading.. The random connection model of this work is set in a dense network in that, as n → ∞, the channel connection between any two nodes does not diminish. In the context of the geometric model, a dense network is interpreted as the total geographical area is fixed and the density of nodes increases as n grows. Under the geometric model, the throughput scaling for single-hop schemes had been identified by [3, , with the main result being that the system throughput is limited by interference, and the network throughout is upper-bounded by O(n 1/(1+2/α) ), where α is the path-loss exponent.

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On the concentration of the number of solutions of random satisfiability formulas Let Z(F ) be the number of solutions of a random k-satisfiability formula F with n variables and clause density α. Assume that the probability that F is unsatisfiable is O(1/ log(n) 1+ε ) for ε > 0. We show that (possibly excluding a countable set of 'exceptional' α's) there exists a nonrandom function φ(α) such that, for any δ > 0, (1/n) log Z(F ) ∈ [φ−δ, φ+δ] with high probability. In particular, the assumption holds for all α < 1, which proves the above concentration claim in the whole satisfiability regime of random 2-SAT. We also extend these results to a broad class of constraint satisfaction problems.The proof is based on an interpolation technique from spin-glass theory, and on an application of Friedgut's theorem on sharp thresholds for graph properties.

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Type 2 diabetes in East Asians: similarities and differences with populations in Europe and the United States There is an epidemic of diabetes in Asia. Type 2 diabetes develops in East Asian patients at a lower mean body mass index (BMI) compared with those of European descent. At any given BMI, East Asians have a greater amount of body fat and a tendency to visceral adiposity. In Asian patients, diabetes develops at a younger age and is characterized by early ␤ cell dysfunction in the setting of insulin resistance, with many requiring early insulin treatment. The increasing proportion of young-onset and childhood type 2 diabetes is posing a particular threat, with these patients being at increased risk of developing diabetic complications. East Asian patients with type 2 diabetes have a higher risk of developing renal complications than Europeans and, with regard to cardiovascular complications, a predisposition for developing strokes. In addition to cardiovascular-renal disease, cancer is emerging as the other main cause of mortality. While more research is needed to explain these interethnic differences, urgent and concerted actions are needed to raise awareness, facilitate early diagnosis, and encourage preventive strategies to combat these growing disease burdens. The prevalence of diabetes is increasing globally, but the situation is particularly alarming in Asia. In the latest edition of Diabetes Atlas, an estimated 366 million individuals are affected globally, of whom 36% live in the Western Pacific region, with a significant proportion from East Asia. 1 While it is evident that, for the same BMI, Asian populations have a higher prevalence of diabetes than their European counterparts, 2 there is a need to better understand the factors underlying these interethnic differences.. This review summarizes and discusses the epidemiology, pathophysiology, genetics, and socioeconomic factors that may contribute to these interethnic differences. In addition to drawing on epidemiological and clinical studies performed in Asian populations, we also made reference to lessons learned from Asian subjects living in the United States, Europe, or Australia, notably the Japanese Americans in Seattle who have provided invaluable insight into the pathogenesis of type 2 diabetes (T2D) in people of East Asian origin.

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More discussions for granger causality and new causality measures Abstract Granger causality (GC) has been widely applied in economics and neuroscience to reveal causality influence of time series. In our previous paper (Hu et al., in IEEE Trans on Neural Netw, 22(6), pp. 829-844, 2011), we proposed new causalities in time and frequency domains and particularly focused on new causality in frequency domain by pointing out the shortcomings/limitations of GC or Granger-alike causality metrics and the advantages of new causality. In this paper we continue our previous discussions and focus on new causality and GC or Granger-alike causality metrics in time domain. Although one strong motivation was introduced in our previous paper (Hu et al., in IEEE Trans on Neural Netw, 22(6), pp. 829-844, 2011) we here present additional motivation for the proposed new causality metric and restate the previous motivation for completeness. We point out one property of conditional GC in time domain and the shortcomings/limitations of conditional GC which cannot reveal the real strength of the directional causality among three time series. We also show the shortcomings/limitations of directed causality (DC) or normalize DC for multivariate time series and demonstrate it cannot reveal real causality at all. By calculating GC and new causality values for an example we demonstrate the influence of one of the time series on the other is linearly increased as the coupling strength is linearly increased. This fact further supports reasonability of new causality metric. We point out that larger instantaneous correlation does not necessarily mean larger true causality (e.g., GC and new causality), or vice versa. Finally we conduct analysis of statistical test for significance and asymptotic distribution property of new causality metric by illustrative examples. Given a set of time series, the topic of how to define causality influence among them has kept philosophers busy for over two thousand years and has yet to be completely resolved. In the literature one of the most popular definitions for causality is Granger causality (GC). Due to its simplicity and easy implementation, GC has been widely used in economics and recently in neuroscience. The basic idea of GC was originally conceived (Wiener 1956 ) and later formalized by Granger in the form of linear regression model (Granger 1969; Geweke 1982) . It can be simply stated as follows: if the variance ðr Þ is defined to describe the strength of the causality which the second time series has on the first one (Freiwald et al. 1999; Hesse et al. 2003; Ding et al. 2006; Oya et al. 2007; Bressler and Anil 2010) . From GC value, it is clear that (i) lnðr Þ [ 0 when there is. This GC definition was extended to frequency domain to show causal influence from one time series on the other one in different frequencies (Geweke 1982; Ding et al. 2006) . Several GC or Granger-alike causality metrics in frequency domain have been developed such as spectral GC (Geweke 1982; Ding et al. 2006) , PDC (Baccal and Sameshima 2001) , RPC (Yamashita et al. 2005) , and DTF (Kaminski et al. 2001) . To show whether the influence is a direct component or mediated by the third time series, conditional GC is defined (Geweke 1984; Freiwald et al. 1999; Hesse et al. 2003; Ding et al. 2006; Oya et al. 2007; Bressler and Anil 2010) . In recent years there has been significant interest to discuss causal interactions between brain areas which are highly complex neural networks in both time and frequency domains (Freiwald et al. 1999; Hesse et al. 2003; Roebroeck et al. 2005; Oya et al. 2007; Wang et al. 2007 Wang et al. , 2008 ; Atmanspacher and Rotter 2008; Gow et al. 2008 Gow et al. , 2009 Rajagovindan and Ding 2008; Seth 2008; Cadotte et al. 2009; Zhang et al. 2010) .. Although there are wide applications of GC and Granger-alike causality metrics in both time and frequency domains, some shortcomings/limitations of these metrics were pointed out in our recent paper (Hu et al. 2011) . To overcome these shortcomings/limitations, we proposed new causality metrics in time and frequency domains. In particular, we emphasized that GC or Granger-alike causality metrics in frequency domain cannot reveal real strength of causality at all and new causality metric in frequency domain has advantages over spectral GC or Granger-alike causality metrics.. In this paper we will focus on time domain and show inherent shortcomings of conditional GC and DC or normalized DC. We will demonstrate that the proposed new causality metric better reveal directed real causality from one time series on the other one than conditional GC and DC or normalized DC. Thus, we must be caution in drawing any conclusion based on GC, conditional GC and DC or normalized DC by noting the shortcomings/limitations of GC (Hu et al. 2011 ). We will show the influence of one of the time series on the other is linearly increased as the coupling strength is linearly increased by computing GC and new causality values via an example. We will also discuss statistical test for significance and asymptotic distribution property of new causality metric. In this paper, we further make more discussions for GC or Granger-alike causality and new causality metrics by following our previous paper (Hu et al. 2011 ) and focus on time domain. In addition to the previous motivation for introducing new causality metric in time domain, we provide additional strong motivation (or theoretical basis) to the proposed metric for multivariate time series. After introducing one property for conditional GC, we point out the inherent shortcomings/limitations of conditional GC and demonstrate that it cannot reveal directed causal influence from one time series to the other one among three time series. We also point out the shortcomings/limitations of Granger-alike causality, i.e., DC or normalized DC metric and show that it cannot disclose directed causality influence at all for multivariate time series. Furthermore, all these shortcomings/limitations demonstrate reasonability and advantages of new causality metric. Therefore, researchers must be caution in drawing any conclusion based on DC (or normalized DC) value and conditional GC value. By calculating GC and new causality values for an example we show the influence of one of the time series on the other is linearly increased as the coupling strength is linearly increased. Finally for new causality metric in time domain we analyze statistical test for significance and show significance level for a simulated data, meanwhile we conduct analysis for asymptotic distribution property by an examples in which both GC and new causality metrics follow v 2 (1)-distribution. However, in general, as for whether or not new causality metric follows a v 2 -distribution under the null hypothesis of zero causality keeps unknown and is left for further study in near future. Thus our proposed new causality metrics in time and frequency domains may have wide applications in economics and neuroscience.

O O O B I O B I O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O


On a quasi-ordering on Boolean functions Abstract. It was proved few years ago that classes of Boolean functions definable by means of functional equations [9] , or equivalently, by means of relational constraints [15] , coincide with initial segments of the quasi-ordered set (Ω, ≤) made of the set Ω of Boolean functions, suitably quasi-ordered. The resulting ordered set (Ω/ ≡, ⊑) embeds into ([ω] <ω , ⊆), the set -ordered by inclusion-of finite subsets of the set ω of integers. We prove that (Ω/ ≡, ⊑) also embeds ([ω] <ω , ⊆). We prove that initial segments of (Ω, ≤) which are definable by finitely many obstructions coincide with classes defined by finitely many equations. This gives, in particular, that the classes of Boolean functions with a bounded number of essential variables are finitely definable. As an example, we provide a concrete characterization of the subclasses made of linear functions. Two approaches of Boolean definability have been considered recently. One in terms of functional equations [9] , an other in terms of relational constraints [15] . It turns out that these two approaches define the same classes of Boolean functions. These classes have been completely described by means of a quasi-order on the set Ω of all Boolean functions. The quasi-order is the following: for two functions f, g ∈ Ω set g ≤ f if g can be obtained from f by identifying, permuting or adding variables. These classes coincide with initial segments for this quasiordering called identification minor in [9] , minor in [15] , subfunction in [18] , and simple variable substitution in [4] . Since then, greater emphasis on this quasiordering has emerged. For an example, it was observed that Ω is the union of four blocks with no comparabilities in between, each block made of the elements above a minimal element. In [15] , Pippenger showed that Ω contains infinite antichains. A complete classification of pairs C 1 , C 2 of particular initial segments ("clones") for which C 2 \ C 1 contains no infinite antichains was given in [3] . Our paper is a contribution to the understanding of this quasi-ordering.. Some properties are easier to express in terms of the poset (Ω/ ≡, ⊑) associated with the quasi-ordered set (Ω, ≤) and made of the equivalence classes associated with the equivalence ≡ defined by f ≡ g if f ≤ g and g ≤ f . As we will see (Corollary 1), for each x ∈ Ω/ ≡, the initial segment ↓ x := {y ∈ Ω/ ≡: y ≤ x} is finite, hence (Ω/ ≡, ⊑) decomposes into the levels Ω/ ≡ 0 , . . . Ω/ ≡ n , . . . , where Ω/ ≡ n is the set of minimal elements of Ω/ ≡ \ ∪ {Ω/ ≡ m : m < n}. Moreover, each level is finite; for an example Ω/ ≡ 0 is made of four elements (the equivalence classes of the two constants functions, of the identity and of the negation of the identity). This fact leads to the following: Problem 1. How does the map ϕ Ω/≡ , which counts for every n the number ϕ Ω/≡ (n) of elements of Ω/ ≡ n , behave?. From the fact that for each x ∈ Ω/ ≡, the initial segment ↓ x is finite it follows that initial segments of (Ω/ ≡, ⊑) correspond bijectively to antichains of (Ω/ ≡, ⊑). Indeed, for each antichain A ⊆ (Ω/ ≡, ⊑), the set F orbid(A) := {y ∈ Ω/ ≡ : x ∈ A ⇒ x ⊑ y} is an initial segment of (Ω/ ≡, ⊑). Conversely, each initial segment I of (Ω/ ≡, ⊑) is of this form (if A is the set of minimal elements of Ω/ ≡ \I, then since for each x ∈ Ω/ ≡ the set ↓ x is finite, I = F orbid(A)). Viewing the elements of A as obstructions, this amounts to say that every initial segment can be defined by a minimal set of obstructions.. Another feature of this poset, similar in importance, is the fact that it is upclosed, that is for every pair x, y ∈ (Ω/ ≡), the final segment ↑ x∩ ↑ y is a finite union (possibly empty) of final segments of the form ↑ z. This means that the collection of initial segments of the form F orbid(A) where A runs throught the finite antichains of Ω/ ≡ which is closed under finite intersections is also closed under finite unions.. Such initial segments have a natural interpretation in terms of Boolean functions. Indeed, as we have said, initial segments of (Ω, ≤) coincide with equational classes. Each of these initial segments identifies to an initial segment of (Ω/ ≡, ⊑) and, as in this case, can be written as F orbid(A) for some antichain A of (Ω, ≤) (the difference with an initial segment of (Ω/ ≡, ⊑) is that the antichain A is not unique). Let us consider the set F of classes which can be defined by finitely many equations. They are characterized by the following theorem. Theorem 1. For an initial segment I of (Ω, ≤), the following properties are equivalent:. (i) I ∈ F; (ii) I is definable by a single equation; (iii) I = F orbid(A) for some finite antichain.. The following lemma reassembles the main properties of F .

O O O O B I O O O O O O O O O O B I O O O O B I O O O O O O O B I O O O O B I O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O B I O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O B I O O O O O O O B I O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B I O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O B O O O O O O O O O O O O O O O O B I O O O O O O O B I O O O O O B I O O O O O B I O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


E-learning continuance: The impact of interactivity and the mediating role of imagery, presence and flow A comprehensive model of the direct and indirect effects of interactivity is proposed and validated.Interactivity influences the e-learners' responses through the intervening effects of imagery, spatial and copresence, and flow.Imagery processes influence spatial and copresence feelings, and flow.Behavioural intention is determined by both attitude and copresence, and prompts actual e-learning continuance. This paper empirically examines the impact of the interactivity elicited by e-learning environments for higher education. By considering the underlying processes of imagery, spatial presence, copresence and flow, we analyse how interactivity affects users' responses towards the learning environment, including their actual continuance behaviour. We validate our conceptual model by using survey and registrar data obtained from 2530 students of an open, distance university in the European Higher Education Area. The results suggest that the interactivity elicited by an e-learning environment unleashes imagery that in turn facilitates spatial presence and copresence as well as flow. Significant paths are also found from interactivity to flow and from flow to e-learner response variables (attitude, intention to continue and actual continuance behaviour). The paper provides a novel account of the presence and flow-enabling mechanisms in e-learning and offers novel knowledge on how higher education institutions can facilitate e-learners' continuance behaviour. Since 1960, when the University of Illinois launched the first computer-based teaching initiative, significant advancements have been made in e-learning. At present, most higher education institutions have devised ways of providing e-learning services. Moreover, e-learning is no longer a novelty for tech-savvy students; it has become a mainstream essential for all kinds of individuals with higher education needs [18] .. E-learning lets individuals fulfil their educational needs via a large range of digital technology-supported services. As these systems offer interaction opportunities [151, 11, 137] , e-learners customise their learning-teaching processes according to their specific wishes, building on their knowledge. Examples of these interactive features include multi-blog learning applications, wikispaces for collaborative project learning, software programmes, hypermedia didactic materials, simulators, real-time communication and project video presentations.. As the demand for e-learning grows, higher education institutions face increasing pressure to understand the mechanisms underlying the interactivity features of e-learning. This is because they need to be able to take advantage of the interactivity possibilities of novel education systems to provide students with compelling learning experiences and to promote e-learner continuance [62] . As a consequence, interactivity has emerged as a key player to be considered carefully under the empirical lenses.. Over the years, studies examining e-learning interactivity have increased, although several important subjects are yet to be covered. Firstly, the effects of interactivity that have been studied to date largely relate to attitude or learning performance, but they do not connect with e-learner retention. A number of papers have examined the links between interactivity and positive attitudes and satisfaction (e.g., Refs. [52, 86, 94] ), while many others have assessed the impact of interactivity on e-learning quality and effectiveness (e.g., Refs. [11, 90, 182, 170, 93, 65, 115] ). By contrast, at the time this paper was being prepared, these researchers located only one study paying attention to the behavioural effects of interactivity on e-learning continuance [25] , and no investigation has considered its possible impact on actual continued usage. Secondly, very little notice has been taken of the underlying processes that intervene when individuals are exposed to interactive e-learning initiatives. Instead, previous research has mainly analysed the direct impact of interactivity on e-learning outcomes [39, 172, 98, 122] . While some studies have assumed the existence of internal processes (e.g., Refs. [11, 86, 94, 25] ), such presumptions have not been always validated (e.g., Refs. [115, 73, 127] ). Therefore, this paper aims to fully elucidate and provide further insights into the effects of interactivity on e-learning. For this purpose, we acknowledge the role of imagery, spatial presence, copresence and flow as central underlying mechanisms, and we study their impact on individuals' responses. Despite the scarcity of studies on imagery processes in e-learning, imagery preferences have been noted as crucially important in laying the groundwork for understanding e-learners' experiences [34, 61, 79] . It has been alleged that, when interacting with a virtual environment, imagery processes come into play [77] and, through imagery, individuals feel immersed in the environment [132] and experience intrinsic enjoyment [63] . Furthermore, spatial presence and copresence have been identified as important psychological processes in elearning (e.g., Refs. [94, 15, 66] ). Through these experiences, users feel that the imagined (virtual) terrain depicted by technology is now their actual reality [9, 140] and that they are with the other individuals [10] . Similarly, the mediating role of flow within interactive virtual environments has been suggested [161] , and this translates into states of deep focus on the tasks being carried out and an intrinsic interest in the activities for their own sake [56, 29] . With this approach, we seek to perform the following:. Examine the influence of interactivity on affective and behavioural e-learners' responses. Analyse the interaction between underlying processes (imagery, spatial presence, copresence and flow) unleashed by interactivity. Build a comprehensive conceptual model of the direct and indirect effects of interactivity, including actual continuance behaviour. Find empirical support for the causal paths in the model. We used structural equation modelling (SEM) methodology to test the model. Firstly, we tested the reliability and the validity of the measures obtained from the data in the survey with the objective of consistently building the latent variables in the model. Secondly, we estimated the model through the maximum likelihood approach to check the causal relationships stated in the hypotheses.

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