Ketamine

as

a

promising

prototype

for

a

new

generation

of

rapid-acting

antidepressants

The

discovery

of

ketamine's

rapid

and

robust

antidepressant

effects

opened

a

window

into

a

new

generation

of

antidepressants.

Multiple

controlled

trials

and

open-label

studies

have

demonstrated

these

effects

across

a

variety

of

patient

populations

known

to

often

achieve

little

to

no

response

from

traditional

antidepressants.

Ketamine

has

been

generally

well

tolerated

across

patient

groups,

with

transient

mild

to

moderate

adverse

effects

during

infusion.

However,

the

optimal

dosing

and

route

of

administration

and

the

safety

of

chronic

treatment

is

not

fully

known.

This

review

summarizes

the

clinical

effects

of

ketamine

and

its

neurobiological

underpinnings

and

mechanisms

of

action

that

may

provide

insight

into

the

neurobiology

of

depression,

relevant

biomarkers,

and

treatment

targets.

Moreover,

we

offer

suggestions

for

future

research

that

can

continue

to

advance

the

field

forward

and

ultimately

improve

the

psychopharmacologic

interventions

available

for

those

individuals

struggling

with

depressive

and

trauma-related

disorders.

Depressive

disorders

are

a

leading

cause

of

disability

affecting

millions

worldwide,

often

causing

chronic

recurrent

symptoms,

increased

morbidity,

heightened

risk

of

suicide,

poor

functional

outcomes,

and

profound

socioeconomic

burden.

However,

the

past

five

decades

of

research

focusing

on

antidepressant

development

has

unfortunately

seen

little

success

in

creating

fundamentally

novel

psychopharmacologic

interventions.

Over

twenty

antidepressant

medications

are

currently

available,

all

targeting

the

monoaminergic

system.

However,

the

efficacy

of

these

medications

is

limited,

with

a

substantial

proportion

of

patients

experiencing

residual

symptoms,

persistent

functional

impairment,

and

failure

to

achieve

sustained

remission

even

when

symptoms

do

improve.

Further,

the

full

clinical

benefit

of

these

traditional

antidepressants

is

only

achieved

following

weeks

to

months

of

treatment.

A

large

study

by

the

National

Institute

of

Mental

Health

found

that

regardless

of

the

primary

or

adjunctive

antidepressant

medication

selected

for

treatment,

less

than

onethird

of

depressed

patients

achieved

remission

within

weeks

and

of

patients

did

not

achieve

remission

at

all

despite

trials

of

four

antidepressant

medications

over

a

period,

leaving

clinicians

with

few

therapeutic

options

for

treatment-refractory

patients.

Thus,

there

is

a

clear

and

urgent

need

for

the

development

of

novel,

rapid-acting

antidepressants

with

robust

efficacy.

Mounting

evidence

suggests

that

low

doses

of

ketamine

may

possess

both

of

these

properties,

acting

rapidly

and

robustly

to

treat

severely

treatment-resistant

depressed

patients..

Ketamine,

a

glutamate

N-methyl-D-aspartate

receptor

(NMDA-R)

antagonist,

is

a

U.S.

Food

and

Drug

Administration

(FDA)-approved

sedative

medication

originally

developed

for

the

induction

and

maintenance

of

anesthesia

in

adults.

Ketamine

has

a

short

plasma

half-life

of

min

and

a

plasma

terminal

half-life.

It

can

be

administered

intravenously

(most

common),

intramuscularly

bioavailability

(BA)),

intranasally

BA),

intrarectally

BA),

and

orally

BA).

In

addition

to

its

role

as

an

anesthetic

and

as

a

pharmacological

model

of

the

core

symptoms

of

schizophrenia,

ketamine

has

received

considerable

attention

in

psychiatric

research

as

a

prototype

for

a

new

generation

of

antidepressants

after

the

discovery

of

its

profound

and

rapid

effects

on

depressive

symptoms.

This

review

provides

a

discussion

of

clinical

trials

investigating

ketamine's

rapid

antidepressant

effects,

safety,

and

tolerability.

In

addition,

we

summarize

some

recent

research

examining

the

effect

of

ketamine

on

symptoms

of

posttraumatic

stress

disorder

(PTSD)

and

neurocognitive

functioning.

We

then

briefly

present

mechanisms

thought

to

underlie

the

rapid

antidepressant

effects

of

ketamine,

including

the

neurobiology

and

potential

clinical

biomarkers

of

depression,

neurocircuitry

critical

to

affective

regulation,

and

molecular

pathways

in

synaptogenesis.

We

conclude

by

discussing

the

prospect

for

next-generation

rapid-acting

antidepressants

and

the

clinical

implications

of

these

findings

on

ketamine.

The

discovery

of

the

rapid

antidepressant

effects

of

ketamine

opened

a

window

into

a

new

generation

of

antidepressants

and

a

better

understanding

of

the

biological

underpinnings

of

depression.

Ketamine

studies

showed

us

that

rapid

improvement

in

complex

mood

states

such

as

depression,

PTSD,

and

suicidality

are

possible

with

therapeutic

interventions.

It

also

highlighted

the

utility

of

targeting

the

glutamatergic

system,

a

truly

novel

antidepressant

mechanism.

However,

it

is

important

to

emphasize

that

ketamine

remains

primarily

an

investigational

drug

at

this

stage,

with

abuse

liability

and

unknown

safety

and

efficacy

following

chronic

treatment..

Excitement

in

the

field

has

led

to

concerted

preclinical

and

clinical

effort

over

the

past

decade

by

many

research

groups

across

the

nation

and

throughout

the

world.

Significant

discoveries

and

major

pathways

have

been

implicated

in

the

pathology

and

treatment

of

depression.

Novel

NMDA-R

modulators

are

being

tested

to

mimic

the

rapid

antidepressant

effects

of

ketamine

while

minimizing

adverse

effects

(for

a

review,

see

Ref.

However,

several

questions

remain

unanswered

and

require

further

investigation:

the

optimal

dose

and

preferable

route

of

administration

of

ketamine,

the

frequency

and

dose

at

which

ketamine

administration

becomes

harmful

instead

of

beneficial,

the

regimen

to

maintain

treatment

response,

the

relationship

between

cognitive

function

and

ketamine

treatment,

the

sustainability

of

anti-suicidal

properties

and

generalizability

to

the

general

population,

and

the

role

of

combined

ketamine

treatment

and

cognitive

behavioral

therapy.

Mechanisms

underlying

the

rapid

andidepressant

effects

of

ketamine.

Changes

in

appear

to

be

region

specific,

with

evidence

for

increased

in

the

medial

prefrontal

cortex

but

not

the

hippocampus.

Abbreviations:

ADE,

antidepressant-like

effects;

NMDA-R,

N-methyl-D-aspartate

glutamate

receptor;

AMPA-R,

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic

acid

receptor;

subunit

of

AMPA-R;

eukaryotic

elongation

factor

kinase;

BDNF,

brain-derived

neurotrophic

factor;

pmTOR,

mammalian

target

of

rapamycin;

glycogen

synthase

kinase

B 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 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 B O O O O O O O O O O O O O O B 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 B 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 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 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 B 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 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 B 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 B O O B O O B 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 B O O O O O B O O B O O O O O O O O O O O O O O O O O O B B 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 B 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 B O O O O O O O O O O B 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 B 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 B 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


A New Model for Graph Matching and Its Algorithm Graph matching is a NP-Hard problem. In this paper, we relax the admissible set of permutation matrices and meantime incorporate a barrier function into the objective function. The resulted model is equivalent to the original model. Alternate iteration algorithm is designed to solve it. It is proven that the algorithm proposed is locally convergent. Our experimental results reveal that the proposed algorithm outperforms the algorithm in [1] . Graphs are commonly used as abstract representations for complex structures, including DNA sequences, documents, text, and images. A graph G is an ordered pair G = (V, W), where V is a set of n vertices in the graph, and W is a weighting function, which gives a real nonnegative value W(v i , v j ) to each pair of vertices (v i , v j ). The adjacency matrix of a graph G = (V, W) is given by A = (a i j ) nn , where a i j = W(v i , v j ). The problem of matching two graphsḠ = (V,W) andG = (Ṽ,W) consists of finding a permutation π from the setV = {v 1 ,v 2 , · · · ,vn} toṼ = {ṽ 1 ,ṽ 2 , · · · ,ṽñ} (generally, n ≤ñ), that makesḠ andG as close as possible with respect to a certain matching cost. In this paper, we consider the following graph matching model:. where Sn ,ñ is the set of permutations from {v 1 ,v 2 , · · · ,vn} to {ṽ 1 ,ṽ 2 , · · · ,ṽñ}. This model has been widely studied during the past thirty years [2] , [3] . However, it has been proved that (1) is NP-hard [3] . Indeed, whenn =ñ, (1) is a quadratic assignment problem. Researchers have showed that the quadratic assignment problem with more 30 nodes are practically intractable [4] . There has been no polynomial time algorithm that can directly solve it with 0-1 integer solutions. A wise method is to find a good approximate solution or a sub-optimality solution in reasonable time. Continuous optimization method is one of the most important methods for graph matching, such as graduated assignment [5] , RKHS methods [6] , alternate iteration method [1] , etc. The common principle of continuous optimization algorithm for graph matching algorithm is to cast graph matching, which is a inherently discrete optimization problem, into a continuous optimization problem. There are many optimization algorithms that can be used to find a solution of this continuous optimization problem. But these algorithms do not ensure the optimality of the solution. Furthermore, the solution of continuous optimization must be converted back from the continuous domain into the initial discrete domain by a heuristic process. The aim of this paper is to present a new equivalent model of (1) and avoid heuristic process which is a common process in most of continuous optimization methods for graph matching with same size. The resulted model is as follows:. where. is Frobenius norm, α is a barrier coefficient, P(n) denotes the set of permutation matrices and Ω ⊂ P(n). Let (X * , Y * ) be an optimal solution of (2), then it is proved that X * is an optimal solution of (1) if α ≥ Ā + Ã . This avoids the heuristic process in most of continuous optimization methods. Meantime, alternate iteration algorithm is designed to solve it in this paper. It is proved that the algorithm proposed is locally convergent. A related work of this paper appears in [1] , but, the model in [1] is not a equivalent model of model (1) and it does not avoid heuristic process. The rest of this paper can be organized as follows. In Sect. 2, A new model for graph matching with same size is proposed. The experimental results given in Sect. 3 show the effectiveness of the proposed algorithm. This paper is concluded in Sect. 4. In this paper, a new equivalent model of (1) for graph matching with same size is proposed. It avoid heuristic process which is a common process in most of continuous optimization methods for graph matching. And alternate iteration algorithm is designed to solve it. It is proved that this algorithm is locally convergent. The experiments done in this paper show that the proposed algorithm outperforms the algorithm in [1] and its matching performance is very good when the graph is similar. But the matching performance is strongly dependent on the choices of initial point and the relaxation set because it is a local algorithm. It is the emphasis of our future work. The performance of alternate iteration algorithm (AIA) is compared with the performance of the algorithm in [1] (Z-AIA) and relaxation method (RGM). The (RGM) consists the following two steps: X * ∈ arg min{ X − Y * 2 |X ∈ P(n)} X * is chosen as the approximate solution of (RGM) and Y * is chosen as the initial point of (AIA) in this paper. In order to evaluate the performance of AIA, the following procedure is used. Weighted graphs set is randomly generated, where each graph has weights ranging from 0 to 1. Matching graph H is generated from each graph G in the set by adding uniformly distributed noise in the range of 0 to 1 to each weight in G, and then shuffling the order of nodes. Then, the above three graph matching algorithms are applied to graph matching for every pair H and G. The estimated probability of a correct vertex-vertex assignment is calculated for a given noise level , after 20 trials for each algorithm. From a point of view of probability, this reflects how well an algorithm performs for a given noise level. All programs are written in Matlab7.0 and run by PC with Pentium (R) Dual-Core CPU E5200 and 2 G RAM.. The results of estimated probability of correct vertexvertex matching versus noise level are displayed in Fig. 1 and Fig. 2 . The result of estimated probability of correct vertex-vertex matching versus size is displayed in Fig. 3 . All results show that the matching of (AIA) is best than (Z-AIA) and (RGM) for the pairs of graph of uniformly distribute.

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 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 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 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 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 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 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 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 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 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 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 B I 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


The coexistence of engineering meanings of function: Four responses and their methodological implications In this position paper, the ambiguity of functional descriptions in engineering is considered from a methodological point of view. Four responses to this ambiguity are discussed, ranging from defining a single meaning of function and rejecting the different meanings that are currently used in engineering to accepting these meanings as coexisting in engineering and taking function as a family resemblance concept. Rejecting the different meanings is described as the straightforward response to resolving the ambiguity of functional descriptions, yet in engineering research and design methodology it rather seems to be accepted that engineers do use the coexisting meanings side by side. In this paper, explanations are given of why this practice is beneficial to engineering. Then it is explored how the particular meaning that engineers attach to function depends on the tasks for which functional descriptions are used. Finally, the methodological implications of the four responses to the ambiguity of functional descriptions are discussed. It is clear that functional descriptions of technical devices are ambiguous in engineering, yet the implications are not. Engineers use the term function with more than one meaning, and this is acknowledged to hamper the use and communication of functional descriptions. However, the obvious solution of disambiguation is typically not embraced in engineering. For more than a decade, engineering researchers and design methodologists have been aware of the coexistence of the different meanings attached to the term 1 but usually avoid disputes about it or other efforts aimed at resolving it. Functional descriptions are ambiguous in engineering and effectively kept so; the maxim that consensus about key terms is beneficial to science and technology is ignored. Researchers and methodologists adopt other means to making functional descriptions useful and interoperable: precision is achieved by giving function relatively well-defined meanings, and communication is made possible by ensuring that engineers who collaborate in teams temporarily align the meanings they use or by attempts at translating functional descriptions that are based on different meanings.. The ambiguity of functional descriptions has methodological implications, and these depend on how one judges the ambiguity and responds to it. Despite the general tolerance in engineering, one may reject having coexisting meanings of function, setting the methodological task of finding ways to remove the ambiguity and to arrive at a single meaning of function. One may also accept the ambiguity of functional descriptions and take it as intrinsic to engineering. This alternative has more novel methodological implications. First, it should then be acknowledged that function is a conceptual anomaly in engineering because it is a key term, yet it is one with different meanings that are not explicitly separated. The different meanings are relatively distinct and well defined; hence, they could easily be set apart. For instance, engineers could have developed the practice to refer to "x functions" when attaching meaning x to function and to "y functions" when attaching meaning y to function. Nevertheless, engineers in general do not separate the different meanings but speak about function simpliciter. Second, methodological questions emerge of why engineers use the coexisting meanings side by side without separating them explicitly. Does this practice have particular benefits to engineering? Third, practical issues present themselves about how to manage the ambiguity. What methodological tasks does this ambiguity set to engineering research and design methodology?. In this position paper, I consider the ambiguity of functional descriptions in engineering. Complementary to the position papers by Claudia Eckert (2013) on the practical consequences of this ambiguity in industry and by Ashok Goel (2013) on how different modeling approaches developed in response to goals of functional modeling, I explore the methodological implications of four responses to the ambiguity. Sections 2 and 3 are on two responses in which the ambiguity is rejected. In the first, a single meaning of function is to be derived on the basis of analyses of the current meanings. In the second response, this single meaning is posited. In Sections 4 and 5, two responses are considered in which one accepts the coexisting meanings. In the first, an overarching concept of function is given that has some or all of the coexisting meanings as instances. In the second response, function is taken as a family resemblance concept. The benefits of the ambiguity of functional descriptions in engineering are considered in Sections 6 and 7, and in Section 8, it is explored how the meaning of function may depend on the tasks for which functional descriptions are used. All four considered responses have their advantages and disadvantages, and in Section 9 I consider the implications of these responses for engineering research and design methodology.

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 O O O O O O O O O O O O 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 O O O O O O O O O O O O O O O O O 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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 O O 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 O O O O O O O O O O O O O O O O O O O O O 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 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 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


Identifying related landmark tags in urban scenes using spatial and semantic clustering AbstractThere is considerable interest in developing landmark saliency models as a basis for describing urban is perceived by the user? This paper presents a web based experiment in which users were asked to tag and label 10 the most salient features from urban images for the purposes of navigation and exploration. In order to rank 11 landmark popularity in each scene it was necessary to determine which tags related to the same object (e.g. tags 12 relating to a particular café). Existing clustering techniques did not perform well for this task, and it was 13 therefore necessary to develop a new spatial-semantic clustering method which considered the proximity of 14 nearby tags and the similarity of their label content. The annotation similarity was initially calculated using 15 trigrams in conjunction with a synonym list, generating a set of networks formed from the links between related 16 tags. These networks were used to build related word lists encapsulating conceptual connections (e.g. church 17 tower related to clock) so that during a secondary pass of the data related network segments could be merged.This approach gives interesting insight into the partonomic relationships between the constituent parts of 19 landmarks and the range and frequency of terms used to describe them. The knowledge gained from this will be 20 used to help calibrate a landmark saliency model, and to gain a deeper understanding of the terms typically 21 associated with different types of landmarks. 22 23

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Linear-Time Algorithm for the Length-Constrained Heaviest Path Problem in a Tree with Uniform Edge Lengths Given a tree T with edge lengths and edge weights, and a value B, the length-constrained heaviest path problem is to find a path in T with maximum path weight whose path length is at most B. We present a linear time algorithm for the problem when the edge lengths are uniform, i.e., all one. This algorithm with slight modification can be used to find the heaviest path of length exactly B in T in linear time. key words: length-constrained paths, heaviest paths, uniform edge lengths * * We follow the definition given in [4] . Let T = (V, E) be an undirected tree with |V| = n. Each edge e ∈ E is associated with two real numbers, l(e) and w(e), called its length and weight, respectively. Let π(u, v) denote the path between two vertices u, v ∈ V. The length of π(u, v) is the sum of the lengths of the edges in it, l(π(u, v)) = e∈π (u,v) l(e), and the weight of π(u, v) is the sum of the weights of the edges in it, w(π(u, v)) = e∈π (u,v) w(e).. The length-constrained heaviest path problem is: Given an undirected tree T with edge lengths l(e) and edge weights w(e), and a real number B, find the heaviest path of length at most B in T , namely, the path π such that w(π) = max u,v∈V {w(π(u, v)) | l(π(u, v)) ≤ B}.. Wu et al. [8] introduced the length-constrained heaviest path problem and solved it in O(n log 2 n) time, and later, Bhattacharyya and Dehne [1] improved the time complexity by showing an O(n log n) time algorithm.. We are interested in the case where the edge lengths are uniform. In the case of uniform edge lengths, l(e) = 1 for all e ∈ E and B is a positive integer. We present an O(n) time algorithm for finding the heaviest path of length at most B in a tree with uniform edge lengths. Both algorithms [1] , [8] for the nonuniform edge length case are divide-and-conquer ones, and they cannot solve the uniform edge length case in linear time. A modified version of our algorithm can find the heaviest path of length exactly B in O(n) time if such a path exists. In this paper, we present a linear-time algorithm for the length-constrained heaviest path problem on a tree with uniform edge lengths. The algorithm can be modified to find the heaviest path of a specific length on a tree with uniform edge lengths. An interesting future work is to find other problems that can be solved in linear time using our method developed in this paper.

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The lifecontingencies Package: Performing Financial and Actuarial Mathematics Calculations in R It is possible to model life contingency insurances with the lifecontingencies R package, which is capable of performing financial and actuarial mathematics calculations. Its functions permit one to determine both the expected value and the stochastic distribution of insured benefits. Therefore, life insurance coverage can be priced and portfolios risk-based capital requirements can be assessed. This paper briefly summarizes the theory regarding life contingencies that is based on financial mathematics and demographic concepts. Then, with the aid of applied examples, it shows how the lifecontingencies package can be a useful tool for executing routine, deterministic, or stochastic calculations for life-contingencies actuarial mathematics. This vignette is based on the package's paper published in JSS, Spedicato (2013) . Apart of keeping track of package's updates, a major difference with respect to JSS publication is that parallel features are turned off to cope with CRAN packages' submission policies. As of March 2014, the lifecontingencies package (Spedicato 2013) appears as the first R package that deals with life contingent actuarial mathematics. The R statistical programming environment (Team 2012) has become the primary reference software for academics. Even in a business context, R is now considered a valid alternative to affirmed proprietary packages for statistics and data analysis, namely SAS (SAS Institute Inc. 2011), MATLAB (The MathWorks, Inc. 2011) and SPSS (IBM Corp 2012). Some packages for actuarial applications have already been developed within R. However, most of them mainly focus on non-life insurance. In fact, non-life insurance modeling involves more data analysis and applied statistical modeling than that of life insurance. Functions allowing one to fit loss distributions and perform credibility analysis are provided within the package actuar (Christophe Dutang, Vincent Goulet, and Mathieu Pigeon 2008) . This package represents the computational side of the classical actuarial textbook on loss distribution (Klugman, Panjer, Willmot, and Venter 2009) . The package ChainLadder (Gesmann and Zhang 2011) provides functions that are capable of estimating loss reserves for non-life insurance. Generalized linear models (GLMs), widely used in nonlife insurance rate-making, can be fit by functions bundled within base R distributions. The generalized additive models for location, shape and scale (GAMLSS) and tweedie regression, which are both more advanced predictive models used by actuaries, are handled by specifically developed packages such as gamlss (Rigby and Stasinopoulos 2005; Stasinopoulos and Rigby 2007) and cplm (Zhang 2011) .. Life insurance actuarial work deals mainly with demographic and financial data. The CRAN task view "Empirical Finance" (Eddelbuettel 2013a ) lists several packages tailored specifically for financial analysis. Packages YieldCurve (Guirreri 2010) and termstrc (Ferstl and Hayden 2010) are capable of financial modeling for interest rates. Among the few packages that handle demographic data, demography (Rob J Hyndman, Heather Booth, Leonie Tickle, and John Maindonald 2011) and LifeTables (Riffe 2011) can be used to manage demographic projections and life tables.. On the other hand, many commercial software packages tailored specifically for the actuarial analysis of life insurance are already available. MoSes (Towers Watson 2011) and Prophet (SunGard 2012) are currently the leading actuarial software packages for life insurance modeling. The lifecontingencies package aims to represent the computational R companion of the theoretical concepts exposed in textbooks like the classical Bowers, Jones, Gerber, Nesbitt, and Hickman (1997) and Dickson, Hardy, and Waters (2009) for actuarial mathematics and Broverman (2008) for financial mathematics. Package lifecontingencies is available from the Comprehensive R Archive Network at http://CRAN.R-project.org/ package=lifecontingencies. The examples used throughout this paper have been taken from Chris Ruckman and Joe Francis (2006) and Finan (2014) , both freely available financial and actuarial mathematics textbooks. The paper is structured as follows: Section 2 outlines the statistical and financial mathematical theory regarding life contingencies, Section 3 overviews the structure of the lifecontingencies package, Section 4 gives a wide choice of applied lifecontingencies examples, and finally, Section 5 discusses the packages current and future development as well as its known limitations.

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Generalized T-splines and VMCR T-meshes The paper deals with the extension of the T-spline approach to the generalized B-splines (GB-splines), a relevant class of non-polynomial splines. This requires both to deepen the study of some basic properties of the GB-splines, in particular of the knot insertion formulae, and the formalization of the concept of T-splines constructed using GB-splines. The study of the linear independence of the soobtained functions leads to the definition of a class of T-meshes which guarantees the linear independence of the associated T-spline functions (both for the polynomial and non-polynomial case) and properly includes the class of analysis-suitable Tmeshes for any order. We refer to this class as VMCR T-meshes. In the last years, the introduction of the so-called T-splines and of the spline spaces defined over T-meshes introduced significant advancements for the use of polynomial spline functions in the CAD and CAGD techniques. The main idea of this approach, in the basic case of surface modelling in IR 3 , is to free the control points of the surface from the constraint to lie, topologically, on a rectangular grid whose edges intersect only at "cross junctions", and allow instead partial lines of control points, which leads to the possibility to have "T-junctions"between the edges of the grid. Such a framework gave some important improvements in CAD and CAGD methods: the possibility to locally refine the surfaces, a considerable reduction of the quantity of control points needed, the ability to easily avoid gaps between surfaces to be joined (see, e.g., [11] and [12] ), just to name a few. All these advantages became even more important in the applications, such as the isogeometric approach for the analysis problems represented by partial differential equations (see, e.g., [6] , [7] and [1] ).. Email addresses: cesare.bracco@unito.it (C. Bracco), durkbin@dongguk.edu (D. Cho).. The T-spline idea has been applied mainly to polynomial splines, while we know that several type of non-polynomial splines are used for certain applications because of their particular properties. For this reason, recently we proposed a generalization of the Tspline approach to the trigonometric GB-splines (see [3] ), a particularly relevant class of non-polynomial splines because of their adaptability and their application to the already mentioned isogeometric analysis (see, e.g., [8] and [10] ). Roughly speaking, the GB-splines are a basis of spaces of piecewise functions, locally spanned both by polynomials and by non-polynomial functions, which in the trigonometric case are sin(ωs) and cos(ωs), with a given frequency ω. Such functions have been successfully used to construct tensor-product surfaces (see, e.g., [10] and references therein) with control points on rectangular grids.. The first goal in this paper is to provide a natural extension of the results obtained in [3] to any type of GB-spline, in order to be able to take full advantage of the features of the GB-splines while, at the same time, using the T-spline approach. In order to achieve this goal, the first step will be to clarify some key issues in the univariate case, in particular about the knot insertion formula and the conditions needed to be able to get it: we will explicitly show that the choice of the non-polynomial functions corresponding to the new intervals obtained after a knot insertion is not free. This allows us to introduce the new concept of Generalized T-splines (GT-splines) and to study their main properties, including the fundamental issue of their linear independence. Similarly to the trigonometric case (see [3] ), we will prove that there exists a strong relation between the GT-splines of bi-order (p, q) and the polynomial T-splines of the same bi-order. During this study we will achieve our second main goal, that is, introducing the class of VMCR T-meshes (Void Matrix after Column Reduction T-meshes): such class, whose basic concept was implicitly contained in [3] , guarantees the linear independence of the associated GT-spline and T-spline blending functions. Such a class and its relationship with the well-known analysis-suitable (equivalently, dual-compatible) T-meshes (see, e.g., [5] and [9] ) will be analyzed, eventually showing that it strictly includes the one of analysis-suitable T-meshes for any bi-order (p, q).. The paper is organized as follows. In Section 2 we recall the definition and the basic properties of the univariate GB-splines, and we deal with the conditions needed to get a knot insertion formula. In Section 3, after having recalled the definition of T-mesh, we introduce the GT-splines and we give some properties following directly from their definition. In Section 4 we study the linear independence of the GT-spline blending functions and, more importantly, the class of VMCR T-meshes. Finally, Section 5 contains some concluding remarks. In this paper we completed the work of generalizing the T-spline approach to the GBsplines (started in [3] for the trigonometric case). The key points to reach this result were the complete study of the knot insertion formulae for GB-splines in the one-dimensional case and the study of the linear independence of the obtained GT-splines. This second issue led to another relevant achievement, that is, the introduction of VMCR T-meshes, a new class of T-meshes guaranteeing the linear independence of both the T-spline and GT-spline associated blending functions with the same bi-order. We showed that this class of T-meshes properly contains the analysis-suitable (dual-compatible) T-meshes.

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Lifting/Descending Processes for Polynomial Zeros The recently proposed Chebyshev-like lifting map for the zeros of a univariate polynomial was motivated by its applications to splitting a univariate polynomial p(x) numerically into factors, which is a major step of some most e ective algorithms for approximating polynomial zeros. We complement the Chebyshev-like lifting process by a descending process, decrease the estimated computational cost of performing the algorithm, demonstrate its correlation to Grae e's lifting/descending process and generalize lifting from Grae e's and Chebyshev-like maps to any xed rational map of the zeros of the input polynomial.

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Introducing Mr. DLib, a Machine-readable Digital Library In this demonstration-paper we present Mr. DLib, a machinereadable digital library. Mr. DLib provides access to several millions of articles in full-text and their metadata in XML and JSON format via a RESTful Web Service. In addition, Mr. DLib provides related documents for given academic articles. The service is intended to serve researchers who need bibliographic data and full-text of scholarly literature for their analyses (e.g. impact and trend analysis); providers of academic services who need additional information to enhance their own services (e.g. literature recommendations); and providers who want to build their own services based on data from Mr. DLib. Researchers who need bulk access to citation data or the full text of academic articles currently have two options. Either they write parsers for digital libraries, such as ACM Digital Library, to collect the required data from the libraries' websites or they use data from some of the few academic services offering their data via an API (for instance, the social bookmarking service Bibsonomy offers an API to access their data in XML [1] and so does Arxiv.org and DBLP). However, existing services have some shortcomings. They either have very little data, offer it only in one format, maintain their API and documentation with low priority (because their focus lies on the web-interface), allow free access only to a limited set of data, or they have no full-text of articles in their database which is important for some analyses.. In this paper, we introduce Mr. DLib, a Machine-readable Digital Library. Mr. DLib's purpose is to provide machinereadable access, in XML and JSON format via an API, to fulltext of academic articles and metadata including impact metrics * Work of this author was supported in part by the National Science Foundation Award 0835773 (Bibliographic Knowledge Network). Copyright is held by the author/owner(s). JCDL'11, June 13-17, 2011, Ottawa, Ontario, Canada. ACM 978-1-4503-0744-4/11/06. and information about relatedness of documents. Mr. DLib is not intended to serve a digital library's "end-user" -a researcher looking for a single academic paper or information about it. Instead, Mr. DLib is intended to serve the following users: 1) Researchers requiring bibliographic data and full-text of scholarly literature for their analyses in bulk. For instance, Mr. DLib provides citation graphs and citation counts for scientific articles to perform impact and trend analysis and with full-text of academic articles, document similarities or plagiarism detection could be performed by the users. 2) Providers of academic services requiring additional bibliographic information for enhancing their services. For instance, the upcoming version of the reference manager JabRef uses Mr. DLib to obtain metadata of PDF files to make manual data entry superfluous. Also, the academic literature suite Docear uses Mr. DLib to provide literature recommendations to its users. 3) Providers who want to build complete services based on data from Mr. DLib. For instance, the Probability Abstract Service (PAS) 1 at the University of California, Berkeley has installed a web site informing users about the latest articles in the field of Probability. Every time a user visits the PAS website, data is delivered in real-time by Mr. DLib.

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


Systems-level evidence of transcriptional co-regulation of yeast protein complexes Protein complexes are functional units in the cell whose formation is regulated by a number of mechanisms. Previous studies have suggested that transcriptional co-regulation of protein components play a minor role in assembly of individual complexes. Recent developments in experimental approaches and bioinformatic analyses offer an opportunity to investigate the cell at a global or systems level with better quality. Here we show that, using genome-/proteome-wide yeast data of protein complexes and protein-DNA interactions in normal growth conditions, a contribution of transcriptional co-regulation to global formation of protein complexes is statistically significant at a systems level. A significant fraction of proteins that form complexes shares common transcription factors on a global scale. We provide evidence for the significant contribution by quantifying transcriptional co-regulation of complexes as a global topological pattern of an integrated network. Our co-regulation measure for a complex takes into account both the absolute fraction of co-regulated protein components and their probabilistic scores from the hypergeometric distribution for all transcription factors. Biological relevance is examined by functional analysis of highly co-regulated complexes. Our finding indicates that there exists linear causality at a systems level between transcriptional co-regulation of genes and formation of multi-protein complexes in the unicellular organism. Full Length PaperReferences

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


A Visual Approach to Efficient Analysis and Quantification of Ductile Iron and Reinforced Sprayed Concrete Abstract-This paper describes advanced volume visualization and quantification for applications in non-destructive testing (NDT), which results in novel and highly effective interactive workflows for NDT practitioners. We employ a visual approach to explore and quantify the features of interest, based on transfer functions in the parameter spaces of specific application scenarios. Examples are the orientations of fibres or the roundness of particles. The applicability and effectiveness of our approach is illustrated using two specific scenarios of high practical relevance. First, we discuss the analysis of Steel Fibre Reinforced Sprayed Concrete (SFRSpC). We investigate the orientations of the enclosed steel fibres and their distribution, depending on the concrete's application direction. This is a crucial step in assessing the material's behavior under mechanical stress, which is still in its infancy and therefore a hot topic in the building industry. The second application scenario is the designation of the microstructure of ductile cast irons with respect to the contained graphite. This corresponds to the requirements of the ISO standard 945-1, which deals with 2D metallographic samples. We illustrate how the necessary analysis steps can be carried out much more efficiently using our system for 3D volumes. Overall, we show that a visual approach with custom transfer functions in specific application domains offers significant benefits and has the potential of greatly improving and optimizing the workflows of domain scientists and engineers. In recent years, the introduction and rapidly increasing use of 3D computed tomography in non-destructive testing (NDT) applications has opened up many powerful possibilities for analyzing and testing industrial parts such as cast metal without destroying them. However, many important tasks in this area such as designating the microstructure of ductile cast irons are still routinely carried out using a (destructive) metallographic approach and subsequent manual visual analysis. The metal under inspection is examined by sequentially removing layers via grinding or etching, and taking microscopic photographs. Due to the complexity of the observed structures, in current practice the clas- sification of important properties such as the form of graphite particles that are crucial for ductility is performed by human visual analysis and manual comparison with reference images. This process could be simplified tremendously by using computed tomography (CT) and powerful visual tools. However, currently there is a clear lack in visualization solutions that provide sufficient flexibility for exploration and inspection, as well as ultimately quantification. Moreover, the use of CT in non-destructive testing is increasingly employed for non-metallic or compound materials. For example, concrete is probably the most widely used non-natural material worldwide, and the use of CT for the inspection of concrete is becoming more widespread. However, the subsequent analyses are very time-consuming and in current practice still involve a considerable amount of manual work due to insufficient tools. In this paper, we describe novel visual workflows that are customized for specific applications with a high relevance for NDT practitioners. The presented approaches have been developed jointly with expert users from this domain, both from a more practical engineering and testing perspective, as well as from a materials research point of view. The first application scenario that we describe (Section 3) is the analysis of SFRSpC, illustrated in Figure 1 , which is of very high importance in the building industry. We are concerned with the examination and analysis of the enclosed steel fibres with respect to their orientations and distribution relative to the application direction in which the concrete has been sprayed. SFRSpC is a relatively new material that is used in various applications in geotechnics. Although the dis- Fig. 2 . Multi-pass region growing in a pre-processing step (left) results in detected features, which can then be explored and quantified interactively (right). The specific requirements of either application scenario are accommodated by pre-computing additional global as well as per-feature statistics for steel fibres or graphite microstructure, respectively. Default TFs for the exploration phase are also generated. The user explores features and feature classes by changing TFs, interactive exploration of statistical parameters, and the 3D volume view. The selected steel fibres are visualized in a Direction Sphere Histogram, whereas the graphite microstructure is classified according to ISO standard requirements.. tribution of fibre directions could strongly influence the mechanical properties of the material, they have not been properly explored yet. Instead, a continuous distribution was assumed. A preferred orientation of the fibres, however, can result from the application process of the concrete, which could significantly alter its mechanical behavior.. Our solution provides an interactive exploration and automatic statistical analysis, based on automatic detection of the enclosed steel fibres, and the specification of transfer functions in the space of fibre directions. The second application scenario (Section 4) is the designation of the graphite microstructure in ductile cast irons, corresponding to the ISO standard 945-1. We illustrate how the analysis steps required by this established standard can be met much more efficiently by our system than the standard workflow of testing practitioners. We compute application-specific information such as histograms of particle diameter or roundness over density, which can then be explored interactively using transfer functions in these domains. This allows for interactive exploration and quantification in line with the requirements of the ISO standard. Transfer function presets enable easy classification according to whether the cast iron is vermicular, intermediate, or nodular, for example. Additionally, we compute properties such as the nodularity according to ISO standard 1611. The basis for the application-specific approaches in this paper is a pipeline for interactive exploration and quantification of industrial CT data [8] . This pipeline employs an interactive, visualization-driven approach for feature detection, exploration, and quantification. This is made possible by pre-computing a family of feature segmentations over parameter domains instead of fixed parameter settings. The precomputation has to be performed only once for a given data set. It is based on region growing that is computed in multiple passes, where the main region growing parameter such as the density variance allowed in a region is successively increased from pass to pass. The resulting features and their changes are tracked and stored in compact form in an additional feature volume and feature size curves [8] . Moreover, in contrast to the usual approach of segmenting only a single type of feature, in our system users can explore different feature classes simultaneously. In this paper, we extend this basic pipeline for the specific requirements of the two application scenarios outlined above through specialized transfer functions in feature space and additional visualization and quantification capabilities. Specifically, the novel application-triggered technical contributions of this paper are:. • The orientations of the steel fibres in SFRSpC are computed automatically in the pre-computation phase. Their distribution is visualized interactively in a Direction Sphere Histogram (DSH) that color-codes the frequency of occurrence of directions.. • Fibres are selected and visualized according to direction transfer functions (DTFs) in the domain of angles α and γ relative to the application direction of the concrete, as well as material density. DTFs interactively determine the 2D and 3D visualization, as well as the set of fibres selected for depiction in the DSH.. • In addition to the size or volume of features, we have integrated the specific properties of feature diameter and feature roundness that are required by the ISO standards for classification of the graphite microstructure of ductile cast iron. These are used in application-specific transfer function domains, which enable the advantages of interactive exploration and quantification to be combined with the requirements of the respective standards.. • The classification of the microstructure of ductile cast irons is accomplished with respect to the contained graphite. This includes the nodularity and is done according to the requirements of the ISO 945-1 and ISO 16112 standards for single 2D slice images, as well as in 3D.. Overall, we illustrate the large potential of customized, visual workflows to improve the daily routine of NDT practitioners, as well as opening up entirely new possibilities for exploration and analysis. We have presented interactive exploration and quantification of features for two real-world applications of high practical relevance in the building industry. We have demonstrated that our system helps to bridge the gap between visualization, feature detection and quantification, and has the potential of significantly improving the current workflow of NDT practitioners. In the future we would like to integrate more possibilities for interactive measurement, as well as performing further evaluations of correctness of the resulting quantifications. This can be accomplished by further comparisons of manual quantifications, as intended for the 3D case of the graphite microstructure in ductile cast iron. The integration of sub-voxel classification to improve quantification accuracy is also an important future goal. Table 6 . The data sets from this paper, with typical pre-computation times and typical volume rendering frame rates (viewport 512x512). We first review related work in the application domains used in this paper. The first international standard on graphite classification by visual analysis was adopted in 1975 as ISO 945:1975. It was left nearly unaltered until 2000, when work started on the first part of a revised version that was published as ISO 945-1:2008. The use of image analysis systems in many production laboratories of foundries that could lead to a more impartial classification of the graphite morphology required appropriate standards for their application. Currently, there is no information published when this part will become available. To evaluate the 3D shape of the graphite particles, metallographic serial sectioning techniques [17] can be used. For the special case of flake graphite, a 3D approach using focused ion beam (FIB) is used to investigate the whole network of spatially interconnected particles [20] . But as the sample is sectioned slice-wise, its integrity is lost. Furthermore, the data acquisition process is quite tedious. The resolution achieved with the FIB tomography is very high due to the imaging with scanning electron microscopy, but the acquired volume is quite small, especially with respect to the size of the graphite particles that are analyzed. The need for impartial classification and evaluation of the graphite microstructure has led to the development of several suggestions to analyze the form of graphite in metallographic sections [11, 16, 19] . These processes are based on different evaluation schemes such as image analytical parameters, shape parameters, or morphological transformations. However, fully automatic methods are very susceptible to the choice of parameters. In contrast to the case of ductile cast iron, the norm-guidelines for SFRSpC were evaluated by the European Committee for Standardization (CEN) in the last few years. This has resulted in general standards for sprayed concrete and steel fibres, and for their control [15] . These standardization efforts are under constant further development, where also national institutions such as concrete or construction societies are involved. We are not aware of any analysis of the influence of the fibre distribution in SFRSpC, except almost completely manual approaches [3] . Table 1 . High-level comparison of the features of our system to two wide-spread existing systems: MAVI [14] , and VGStudio MAX [21] .. In visualization, the previous work most directly related to ours are size-based transfer functions [5] , and specifying transfer functions over volume density, feature size, and region growing parameter [8] .. The former computes a local size of the region surrounding any given voxel using scale space analysis. The latter detects connected regions and enables transfer functions over the size of these regions. We build on the second approach since it directly enables quantification of the features of interest, which is crucial in our application context. In our system, the detection of features such as steel fibres or graphite particles is performed using region growing [22] . The specification of seed points is crucial and can be tackled by evaluating multiple seed points at the same time [1] , iteratively specifying seed points for region of interest selection [4] , or allowing each voxel in the volume to potentially become a seed [8] . Gyulassi et al. [7] have presented two methods for the generation of topologically clean distance fields for the analysis of the filament structure of a porous material in molecular dynamics simulations. Using morse theory or an advancing front method they extract a stable core structure of the porous solid which is used for identifying material properties and comparing simulation results over different time steps. The two most related commercial tools that handle quantification of industrial CT data are MAVI [14] , and VGStudio MAX [21] . Table 1 gives a high-level comparison of available features of these systems to the features of the system presented in this paper.. For volume visualization, we use GPU-based ray-casting [13, 18] with 3D textures and multi-dimensional transfer functions [12] . This allows for real-time rendering combined with considerable flexibility, including efficient memory managment for large volumes [2] . Region growing techniques have been integrated into volume visualization systems [9] , which can also be used to define two-dimensional transfer functions that highlight the regions selected by region growing. This has also been demonstrated to be very useful in the context of industrial CT data [10] . However, the result is only an approximation and in general cannot reproduce the exact set of voxels of any given feature. In our context, it is crucial that all voxels are included in a feature to enable accurate quantification.

O O 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 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 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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


Radial vibration measurements directly from rotors using laser vibrometry: The effects of surface roughness, instrument misalignments and pseudo-vibration Laser Doppler vibrometry (LDV) offers an attractive solution when radial vibration measurement directly from a rotor surface is required. Research to date has demonstrated application on polished-circular rotors and rotors coated with retro-reflective tape. In the latter case, however, a significant cross-sensitivity to the orthogonal radial vibration component occurs and post-processing is required to resolve individual radial vibration components. Until now, the fundamentally different behaviour observed between these cases has stood as an inconsistency in the published literature, symptomatic of the need to understand the effect of surface roughness. This paper offers the first consistent mathematical description of the polished-circular and rough rotor behaviours, combined with an experimental investigation of the relationship between surface roughness and cross-sensitivity. Rotors with surface roughness up to 10 nm satisfy the polished-circular rotor definition if vibration displacement is below 100% beam diameter, for a 90 μm beam, and below 40% beam diameter, for a 520 μm beam. On rotors with roughness between 10 nm and 50 nm, the polished-circular rotor definition is satisfied for vibration displacements up to 25% beam diameter, for a 90 μm beam, and up to 10% beam diameter, for a 520 μm beam. As roughness increases, cross-sensitivity increases but only rotors coated in retro-reflective tape satisfied the rough rotor definition fully. Consequently, when polished-circular surfaces are not available, rotor surfaces must be treated with retro-reflective tape and measurements post-processed to resolve individual vibration components. Through simulations, the value of the resolution and correction algorithms that form the post-processor has been demonstrated quantitatively. Simulations incorporating representative instrument misalignments and measurement noise have enabled quantification of likely error levels in radial vibration measurements. On a polished-circular rotor, errors around 0.2% for amplitude and 2 mrad for phase are likely, rising a little at the integer orders affected by pseudo-vibration. Higher pseudo-vibration levels and the need for resolution increase errors in the rough rotor measurements, especially around the synchronous frequency where errors reach 20% by amplitude and 100 mrad for phase. Outside a range of half an order either side of first order, errors are ten times lower and beyond fifth order errors are similar to those for the polished-circular rotor. Further simulations were performed to estimate sensitivities to axial vibration, speed variation and bending vibrations. Vibration is readily acknowledged as the most effective measure of the condition of rotating machines. Such vibrations are inevitable but their consequences can be dramatic, extending from loss of efficiency through to safety-critical failures. There are also the associated issues of noise generation and user discomfort which can, for example, affect perceptions of product quality and adherence to legislative requirements. Monitoring techniques are mature; the earliest significant attempts to quantify acceptable machinery vibration levels date from the late 1930s [1] and the value of vibration analysis in the diagnosis of machine health is regularly reiterated in the published literature, e.g., [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] .. Transducer selection first involves consideration of whether to measure displacement, velocity or acceleration. Vibration velocity is generally regarded as the optimum measurement parameter but traditional velocity transducers cannot match the dynamic range and frequency range of the ubiquitous piezo-electric accelerometer, even after integration of the measured signal [2] . In addition, choice must be made between measurement of shaft absolute vibration, shaft vibration relative to bearings or housing absolute vibration (usually taken at bearing locations) [3] . Measurement of any two of these options allows derivation of the third and this requirement is typically met via proximity probes (generally eddy current based) for the second option and piezo-electric accelerometers for the third option.. This paper is concerned with the application of laser Doppler vibrometry (LDV) to the monitoring of rotating machinery. Laser vibrometers are now well established as an effective alternative to more traditional vibration transducers. For the application in question, they offer direct measurement of the favoured parameter (i.e., velocity) with dynamic and frequency ranges at least matching and generally exceeding those offered by piezo-electric accelerometers. Measurements from non-rotating parts are straightforward, provided optical access is available, with particular advantages where the context demands high frequency operation or remote transducer operation, or when the structure itself is hot or light. Most importantly, they also offer the opportunity to measure directly from rotating parts. This is not a new realisation; since the appearance of commercial instruments in the 1980s, measurements directly from rotating targets have been regularly highlighted by manufacturers and researchers as a major application area. LDV applications for axial vibration measurement directly from rotating blades date back over 40 years [15] and interest in similar applications continues today using both stationary [16] and scanning [17] laser beams. Radial, torsional and bending vibration measurements have also been successfully demonstrated [18] .. Radial vibration measurements are the specific focus of this paper. Applications of particular interest include automotive powertrain [18] , hard disks and their drive spindles [19, 20] and tool condition monitoring in turning [21] and milling [22, 23] . Similar measurement configurations have revealed details related to shaft rotation [24, 25] . Early attempts to use LDV for radial vibration measurements on rotors, however, identified a cross-sensitivity to the radial vibration component perpendicular to the radial component it is intended to measure. This cross-sensitivity was shown to be a consequence of oscillation in the position of the rotor centre relative to the fixed line of incidence of the beam [26] . The finding prompted development of a model to predict measured velocity for arbitrary beam orientation and arbitrary target motion [27] ultimately resulting in confirmation that this cross-sensitivity could not be resolved by laser beam orientation alone. A resolution procedure based on three simultaneous measurements was subsequently formulated [28] .. These cross-sensitivity studies had concentrated on rotating surfaces treated with retro-reflective tape (Scotchlite highgain sheeting type 7610), a common surface treatment intended to maximise the intensity of light scattered back towards the instrument's collecting optics. In a separate study [29] , vibration measurements on a painted rotor confirmed the presence of this cross-sensitivity but measurements made on a polished rotor (Ra 20 nm) showed no such crosssensitivity. Resolution of this inconsistency is one of the main novelties of this paper. An initial study [30] has highlighted the dependence of the extent of the cross-sensitivity in radial vibration measurements on not just surface roughness but also on incident laser beam diameter, emphasising the urgent need for a thorough study.. Having identified the surface conditions under which radial vibration measurements can be made, this paper then proceeds to use simulation to estimate the errors likely in real measurements as a result of (i) inevitable instrument misalignment (relative to rotor axes), (ii) other motion components and (iii) measurement noise. Incorporation of these aspects into simulations is enabled by two important recent developments. The study of misalignments and sensitivity to other motion components is facilitated by a new, vectorial framework for modelling measured velocity in laser vibrometry [31] while the inclusion of measurement noise is enabled by the recent quantification of pseudo-vibration sensitivities as a function of surface roughness or treatment for a range of commercial laser vibrometers [32, 33] . Further novelty in this paper lies in this application of the modelling framework and its combination with the pseudo-vibration study. This paper has combined an experimental study of the cross-sensitivity encountered in LDV measurements of rotor radial vibration with a quantitative evaluation of measurement errors, including sensitivities to other motions, based on simulation. The evaluation of the effects of misalignments and other motions, for both rough and polished-circular rotors, was made possible by a recently developed framework for a comprehensive mathematical prediction of measured velocity that is without approximation. The ease in modelling adds further weight to the assertion [31] that this modelling framework can be applied universally for laser vibrometry applications.. The study of the effect on cross-sensitivity of surface roughness and treatment resolved a significant inconsistency in the published literature and delivered an important conclusion regarding the rotor surface conditions under which measurements can be made. Of the rotors tested in this study, those with surface roughness up to 50 nm and out-ofroundness below 10 mm satisfied the polished-circular rotor definition, provided vibration displacement does not exceed a specific threshold related to beam diameter. Only rotors coated in retro-reflective tape satisfied the rough rotor definition although the painted surface was close. The extent of the cross sensitivity did not reach 100% for the roughest of the rotors tested here (Ra 1100 nm) and so, when polished-circular surfaces are not available, rotor surfaces must be treated with retro-reflective tape. In such circumstances, measurements can again be made reliably (except at the synchronous frequency) but measurements must be post-processed to resolve the individual radial motion components. The overall conclusion to be drawn from the second part of the paper is that measurement errors and sensitivities to other motions can be readily predicted for any specific measurement scenario. The essential requirement for postprocessing of the rough rotor measurement has been demonstrated quantitatively, as has the effectiveness of the resolution algorithm. In the presence of speed fluctuations, the value of a complementary correction algorithm has also been confirmed and two iterations through the algorithm are now recommended wherever speed fluctuation (including torsional vibration) is present.. For equal amplitude radial vibrations, data have been generated for typical misalignments, measurement noise and speed measurement errors to provide typical error levels for the user to have in mind. Typical sensitivities to axial vibration, speed variation (including torsional vibration and roll) and bending vibrations are also quantified for both rotor surface conditions. This study of the effects of surface roughness, instrument misalignments and measurement noise delivers an essential practical guide for the vibrometer user.. The matrices can be applied singly or in series. Where rotations around more than one axis are by large angles (e.g., for laser beam orientation), their order must be maintained. When rotations are by small angles (e.g., for angular vibrations and misalignments), this is not necessary. 3) has been presented [27] . Note that the measured velocity is the sum of six terms, each the product of a combination of geometric parameters and a so-called 'vibration set'. These sets are an inseparable combination of motion parameters (shown in square brackets) and are referred to by the parameter that is regarded as the intended measurement and shown first in the sets. Section 2.1 makes specific use of the first two of these sets, the x-radial and the y-radial sets. The reader should note the different angle convention used here compared to [27] .

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