bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Multiple-Channel Polycrystalline Silicon Thin-Film Transistors Employing Asymmetric Spacing
Authors: Choi Sung-Hwan , Han Min-Koo
Published: March 2011

A novel multiple-channel structure that improves the reliability of polycrystalline silicon thin-film transistors (poly-Si TFTs) employing the sequential lateral solidification (SLS) process under high gate and drain bias stress was proposed and fabricated without any additional processes. It was successfully verified that the proposed asymmetric-spacing (AS) multiple-channel TFT effectively suppressed the threshold voltage shift by about 47% and reduced the mobility variation of the poly-Si TFT by about 3% compared with those of a conventional device by using a larger spacing in the central region of the channel area. This is possibly due to the emission of induced heat inside the device during operation. Our experimental results show that the proposed AS multiple-channel TFT has more stable electrical characteristics than the conventional-structure TFT under a high gate and drain bias condition.
Flexibility of Low Temperature Polycrystalline Silicon Thin-Film Transistor on Tungsten Foil
Authors: Lee Won Gyu , Lim Tae Hoon , Jang Jin
Published: March 2011

We have studied the mechanical bending effect of low-temperature polycrystalline silicon (LTPS) thin-film transistors (TFTs) on flexible tungsten foil. The p-channel TFTs on tungsten foil, using the poly-Si obtained by metal induced crystallization, exhibited a field-effect mobility of 88.8 cm2 V-1 s-1, threshold voltage of -4.8 V, subthreshold swing of 0.64 V/decade, and a minimum off current of <10-12 A/µm. The tungsten foil was chosen because its thermal expansion coefficient is similar to that of the Si thin film. The TFTs on flexible tungsten foil is extremely stable until the bending radius of 5 mm, which corresponds to the strain of 0.58%. Additionally, the devices can be repetitively flexed with a strain of 0.58% for 5,000 times of bending.
Water-Related Instability in Low-Temperature Polycrystalline Silicon Thin-Film Transistors Caused by Self-Heating
Authors: Tsuchiya Toshiaki , Tsuboi Shinzo , Kawachi Genshiro , Matsumura Masakiyo
Published: March 2011

It was observed that the bias stressing of low-temperature polycrystalline silicon thin-film transistors (LTPS-TFTs) gave rise to anomalous instabilities in device characteristics, such as negative threshold voltage shifts in both n- and p-channel TFTs, and the recovery of the shift even under stress. From detailed investigations of these phenomena, it was found that the instability is caused by self-heating due to the drain current, and is related to hydrogen and/or water diffusing into the gate oxide from the interlayer dielectric. It is considered that these phenomena will become more significant in future scaled TFTs; therefore, it is important that low-temperature processes taking account of water-related components are carefully introduced.
Positive Bias Instability of Bottom-Gate Zinc Oxide Thin-Film Transistors with a SiOx/SiNx-Stacked Gate Insulator
Authors: Furuta Mamoru , Kamada Yudai , Hiramatsu Takahiro , Li Chaoyang , Kimura Mutsumi , Fujita Shizuo , Hirao Takashi
Published: March 2011

The positive bias instabilities of the zinc oxide thin-film transistors (ZnO TFTs) with a SiO
x
/SiN
x
-stacked gate insulator have been investigated. The film quality of a gate insulator of SiO
x
, which forms an interface with the ZnO channel, was varied by changing the gas mixture ratio of SiH4/N2O/N2 during plasma-enhanced chemical vapor deposition. The positive bias stress endurance of ZnO TFT strongly depended on the deposition condition of the SiO
x
gate insulator. From the relaxations of the transfer curve shift after imposition of positive bias stress, transfer curves could not be recovered completely without any thermal annealing. A charge trapping in a gate insulator rather than that in bulk ZnO and its interface with a gate insulator is a dominant instability mechanism of ZnO TFTs under positive bias stress.
Application of Thermal Plasma Jet Irradiation to Crystallization and Gate Insulator Improvement for High-Performance Thin-Film Transistor Fabrication
Authors: Higashi Seiichiro , Hayashi Shohei , Hiroshige Yasuo , Nishida Yusuke , Murakami Hideki , Miyazaki Seiichi
Published: March 2011

Large grains with a maximum length of ∼60 µm were grown by high speed scanning (∼4000 mm/s) of a molten region in amorphous silicon (a-Si) films formed by micro-thermal-plasma-jet (µ-TPJ) irradiation. By reducing the TPJ nozzle diameter and increasing the spacing between anode and cathode, the power density transferred to a-Si film surface increased to as high as 53 kW/cm2, which enabled melting and lateral solidification in the microsecond time domain. The a-Si transformed to crystalline through solid-phase crystallization, followed by melting and recrystallization induced by the movement of the molten region with the maximum size of ∼483 µm in width and ∼990 µm in length. The laterally crystallized Si films show anisotropic large grains and a high crystalline volume fraction of ∼100% and preferential surface orientation of (111) plane. Thin-film transistors (TFTs) fabricated by solid-phase-crystallized microcrystalline Si (µc-Si) show a small field effect mobility (µFE) of ∼2 cm2 V-1 s-1 with small variation less than 1%, while the high-speed lateral-crystallization (HSLC) Si film shows a very high µFE of 350 cm2 V-1 s-1. We improved the bulk bond network of the low-temperature-deposited gate SiO2 films by TPJ-induced millisecond annealing. By combining TPJ annealing and postmetallization annealing (PMA), a high-quality SiO2/Si interface with a density of interface states (D
it) of 3.0 ×1010 cm-2 eV-1 is obtained. In addition, we found that the improvement in the bulk bond network of SiO2 is quite effective to improve the stress immunity of µc-Si TFTs. TFTs fabricated with TPJ-annealed gate SiO2 films show much smaller on-current degradation and threshold voltage shift after DC bias stress compared with untreated TFTs. Not only the threshold voltage (V
th) shift under high-gate-field stress condition, but also on-current degradation under drain avalanche hot carrier (DAHC) generation condition are markedly suppressed. This improvement is attributed to the reduction of Si–OH bonds and relaxation of the bulk chemical bond network of SiO2 induced by TPJ annealing.
Voltage Drop Compensation Method for Active Matrix Organic Light Emitting Diode Displays
Authors: Choi Sang-moo , Ryu Do-hyung , Kim Keum-nam , Choi Jae-beom , Kim Byung-hee , Berkeley Brian
Published: March 2011

In this paper, the conventional voltage drop compensation methods are reviewed and the novel design and driving scheme, the advanced power de-coupled (aPDC) driving method, is proposed to effectively compensate the voltage IR drop of active matrix light emitting diode (AMOLED) displays. The advanced PDC driving scheme can be applied to general AMOLED pixel circuits that have been developed with only minor modification or without requiring modification in pixel circuit. A 14-in. AMOLED panel with the aPDC driving scheme was fabricated. Long range uniformity (LRU) of the 14-in. AMOLED panel was improved from 43% without the aPDC driving scheme, to over 87% at the same brightness by using the scheme and the layout complexity of the panel with new design scheme is less than that of the panel with the conventional design scheme.
Organic Light-Emitting Diode-on-Silicon Pixel Circuit Using the Source Follower Structure with Active Load for Microdisplays
Authors: Kwak Bong-Choon , Lim Han-Sin , Kwon Oh-Kyong
Published: March 2011

In this paper, we propose a pixel circuit immune to the electrical characteristic variation of organic light-emitting diodes (OLEDs) for organic light-emitting diode-on-silicon (OLEDoS) microdisplays with a 0.4 inch video graphics array (VGA) resolution and a 6-bit gray scale. The proposed pixel circuit is implemented using five p-channel metal oxide semiconductor field-effect transistors (MOSFETs) and one storage capacitor. The proposed pixel circuit has a source follower with a diode-connected transistor as an active load for improving the immunity against the electrical characteristic variation of OLEDs. The deviation in the measured emission current ranges from -0.165 to 0.212 least significant bit (LSB) among 11 samples while the anode voltage of OLED is 0 V. Also, the deviation in the measured emission current ranges from -0.262 to 0.272 LSB in pixel samples, while the anode voltage of OLED varies from 0 to 2.5 V owing to the electrical characteristic variation of OLEDs.
3.4-Inch Quarter High Definition Flexible Active Matrix Organic Light Emitting Display with Oxide Thin Film Transistor
Authors: Hatano Kaoru , Chida Akihiro , Okano Tatsuya , Sugisawa Nozomu , Inoue Tatsunori , Seo Satoshi , Suzuki Kunihiko , Oikawa Yoshiaki , Miyake Hiroyuki , Koyama Jun , Yamazaki Shunpei , Eguchi Shingo , Katayama Masahiro , Sakakura Masayuki
Published: March 2011

In this paper, we report a 3.4-in. flexible active matrix organic light emitting display (AMOLED) display with remarkably high definition (quarter high definition: QHD) in which oxide thin film transistors (TFTs) are used. We have developed a transfer technology in which a TFT array formed on a glass substrate is separated from the substrate by physical force and then attached to a flexible plastic substrate. Unlike a normal process in which a TFT array is directly fabricated on a thin plastic substrate, our transfer technology permits a high integration of high performance TFTs, such as low-temperature polycrystalline silicon TFTs (LTPS TFTs) and oxide TFTs, on a plastic substrate, because a flat, rigid, and thermally-stable glass substrate can be used in the TFT fabrication process in our transfer technology. As a result, this technology realized an oxide TFT array for an AMOLED on a plastic substrate. Furthermore, in order to achieve a high-definition AMOLED, color filters were incorporated in the TFT array and a white organic light-emitting diode (OLED) was combined. One of the features of this device is that the whole body of the device can be bent freely because a source driver and a gate driver can be integrated on the substrate due to the high mobility of an oxide TFT. This feature means “true” flexibility.
Embedded Touch Sensing Circuit Using Mutual Capacitance for Active-Matrix Organic Light-Emitting Diode Display
Authors: Park Young-Ju , Seok Su-Jeong , Park Sang-Ho , Kim Ohyun
Published: March 2011

We propose and simulate an embedded touch sensing circuit for active-matrix organic light-emitting diode (AMOLED) displays. The circuit consists of three thin-film transistors (TFTs), one fixed capacitor, and one variable capacitor. AMOLED displays do not have a variable capacitance characteristic, so we realized a variable capacitor to detect touches in the sensing pixel by exploiting the change in the mutual capacitance between two electrodes that is caused by touch. When a dielectric substance approaches two electrodes, the electric field is shunted so that the mutual capacitance decreases. We use the existing TFT process to form the variable capacitor, so no additional process is needed. We use advanced solid-phase-crystallization TFTs because of their stability and uniformity. The proposed circuit detects multi-touch points by a scanning process.
Data structures for mergeable trees
Authors: Georgiadis Loukas , Kaplan Haim , Shafrir Nira , Tarjan Robert E. , Werneck Renato F.
Published: March 2011

Motivated by an application in computational geometry, we consider a novel variant of the problem of efficiently maintaining a forest of dynamic rooted trees. This variant includes an operation that merges two tree paths. In contrast to the standard problem, in which a single operation can only add or delete one arc, one merge can add and delete up to a linear number of arcs. In spite of this, we develop three different methods that need only polylogarithmic time per operation. The first method extends a solution of Farach and Thorup [1998] for the special case of paths. Each merge takes
O
(log
2
n
) amortized time on an
n
-node forest and each standard dynamic tree operation takes
O
(log
n
) time; the latter bound is amortized, worst case, or randomized depending on the underlying data structure. For the special case that occurs in the motivating application, in which arbitrary arc deletions (cuts) do not occur, we give a method that takes
O
(log
n
) time per operation, including merging. This is best possible in a model of computation with an Ω(
n
log
n
) lower bound for sorting
n
numbers, since such sorting can be done in
O
(
n
) tree operations. For the even-more-special case in which there are no cuts and no
parent
queries, we give a method that uses standard dynamic trees as a black box: each mergeable tree operation becomes a constant number of standard dynamic tree operations. This third method can also be used in the motivating application, but only by changing the algorithm in the application. Each of our three methods needs different analytical tools and reveals different properties of dynamic trees.
Decision trees for entity identification
Authors: Chakaravarthy Venkatesan T. , Pandit Vinayaka , Roy Sambuddha , Awasthi Pranjal , Mohania Mukesh K.
Published: March 2011

We consider the problem of constructing decision trees for entity identification from a given relational table. The input is a table containing information about a set of entities over a fixed set of attributes and a probability distribution over the set of entities that specifies the likelihood of the occurrence of each entity. The goal is to construct a decision tree that identifies each entity unambiguously by testing the attribute values such that the average number of tests is minimized. This classical problem finds such diverse applications as efficient fault detection, species identification in biology, and efficient diagnosis in the field of medicine. Prior work mainly deals with the special case where the input table is binary and the probability distribution over the set of entities is uniform. We study the general problem involving arbitrary input tables and arbitrary probability distributions over the set of entities. We consider a natural greedy algorithm and prove an approximation guarantee of
O
(
r

K

⋅ log
N
), where
N
is the number of entities and
K
is the maximum number of distinct values of an attribute. The value
r

K

is a suitably defined Ramsey number, which is at most log
K
. We show that it is NP-hard to approximate the problem within a factor of Ω(log
N
), even for binary tables (i.e.,
K
=2). Thus, for the case of binary tables, our approximation algorithm is optimal up to constant factors (since
r
2
=2). In addition, our analysis indicates a possible way of resolving a Ramsey-theoretic conjecture by Erdös.
Tree exploration with logarithmic memory
Authors: Ambühl Christoph , Gąsieniec Leszek , Pelc Andrzej , Radzik Tomasz , Zhang Xiaohui
Published: March 2011

We consider the task of network exploration by a mobile agent (robot) with small memory. The agent has to traverse all nodes and edges of a network (represented as an undirected connected graph), and return to the starting node. Nodes of the network are unlabeled and edge ports are locally labeled at each node. The agent has no a priori knowledge of the topology of the network or of its size, and cannot mark nodes in any way. Under such weak assumptions, cycles in the network may prevent feasibility of exploration, hence we restrict attention to trees. We present an algorithm to accomplish tree exploration (with return) using
O
(log
n
)-bit memory for all
n
-node trees. This strengthens the result from Diks et al. [2004], where
O
(log
2
n
)-bit memory was used for tree exploration, and matches the lower bound on memory size proved there. We also extend our
O
(log
n
)-bit memory traversal mechanism to a weaker model in which ports at each node are ordered in circular manner, however, the explicit values of port numbers are not available.
Shortest vertex-disjoint two-face paths in planar graphs
Authors: Verdière Éric Colin De , Schrijver Alexander
Published: March 2011

Let
G
be a directed planar graph of complexity
n
, each arc having a nonnegative length. Let
s
and
t
be two distinct faces of
G
let
s
1
,…,
s

k

be vertices incident with
s
let
t
1
,…,
t

k

be vertices incident with
t
. We give an algorithm to compute
k
pairwise vertex-disjoint paths connecting the pairs (
s

i

,
t

i

) in
G
, with minimal total length, in
O
(
kn
log
n
) time.
Streaming and fully dynamic centralized algorithms for constructing and maintaining sparse spanners
Authors: Elkin Michael
Published: March 2011

We present a streaming algorithm for constructing sparse spanners and show that our algorithm significantly outperforms the state-of-the-art algorithm for this task (due to Feigenbaum et al.). Specifically, the processing time per edge of our algorithm is
O
(1), and it is drastically smaller than that of the algorithm of Feigenbaum et al., and all other efficiency parameters of our algorithm are no greater (and some of them are strictly smaller) than the respective parameters of the state-of-the-art algorithm.

We also devise a fully dynamic centralized algorithm maintaining sparse spanners. This algorithm has incremental update time of
O
(1), and a nontrivial decremental update time. To our knowledge, this is the first fully dynamic centralized algorithm for maintaining sparse spanners that provides nontrivial bounds on both incremental and decremental update time for a wide range of stretch parameter
t
.
Constrained pattern matching
Authors: Choi Yongwook , Szpankowski Wojciech
Published: March 2011

Constrained sequences are strings satisfying certain additional structural restrictions (e.g., some patterns are forbidden). They find applications in communication, digital recording, and biology. In this article, we restrict our attention to the so-called (
d
,
k
) constrained binary sequences in which any run of zeros must be of length at least
d
and at most
k
, where 0≤
d
<
k
. In many applications, one needs to know the number of occurrences of a given pattern
w
in such sequences, for which we coin the term
constrained pattern matching
. For a given word
w
, we first estimate the mean and the variance of the number of occurrences of
w
in a (
d
,
k
) sequence generated by a memoryless source. Then we present the central limit theorem and large deviations results. As a by-product, we enumerate asymptotically the number of (
d
,
k
) sequences with exactly
r
occurrences of
w
, and compute Shannon entropy of (
d
,
k
) sequences with a given number of occurrences of
w
. We also apply our results to detect under- and overrepresented patterns in neuronal data (spike trains), which satisfy structural constraints that match the framework of (
d
,
k
) binary sequences. Throughout this article we use techniques of analytic combinatorics such as combinatorial calculus, generating functions, and complex asymptotics.
Discovering almost any hidden motif from multiple sequences
Authors: Fu Bin , Kao Ming-Yang , Wang Lusheng
Published: March 2011

We study a natural probabilistic model for motif discovery. In this model, there are
k
background sequences, and each character in a background sequence is a random character from an alphabet Σ. A motif
G
=
g
1
g
2
…
g

m

is a string of
m
characters. Each background sequence is implanted with a probabilistically generated approximate copy of
G
. For a probabilistically generated approximate copy
b
1
b
2
…
b

m

of
G
, every character is probabilistically generated such that the probability for
b

i

≠
g

i

is at most α.

In this article, we develop an efficient algorithm that can discover a hidden motif from a set of sequences for any alphabet Σ with |Σ|≥ 2 and is applicable to DNA motif discovery. We prove that for α < 1/8(1- 1/|Σ|), there exist positive constants
c
0
, ϵ, and δ
2
such that if there are at least
c
0
log
n
input sequences, then in
O
(
n
2
/
h
(log
n
)

O

(1)) time this algorithm finds the motif with probability at least 3/4 for every
G
∈ Σ
ρ
-Ψ

ρ,
h
,ϵ

(Σ), where
n
the length of longest sequences, ρ is the length of the motif,
h
is a parameter with ρ≥ 4
h
≥ δ
2
log
n
, and Ψ

ρ,
h
,ϵ

(Σ) is a small subset of at most 2

−Θ(ϵ
2
h
)

fraction of the sequences in Σ
ρ
.
Lower Bounds for Coin-Weighing Problems
Authors: Purdy Eric
Published: March 2011

Among a set of
n
coins of two weights (good and bad), and using a balance, we wish to determine the number of bad coins using as few measurements as possible. There is a known adaptive decision tree that answers this question in
O
((log(
n
))
2
) measurements, and a slight modification of this decision tree determines the parity of the number of bad coins in
O
(log
n
). In this article, we prove an Ω(\sqrt{
n
}) lower bound on the depth of any oblivious decision tree which solves either the counting or the parity problem. Our lower bound can also be applied to any function of high average sensitivity, which includes most random functions and most random symmetric functions. With a slight generalization of this result, we derive lower bounds for the size of threshold circuits for a wide class of Boolean functions.

We demonstrate an exponential gap between the nonadaptive and adaptive coin-weighing complexities of the counting and parity problems. We prove a tight
Θ
(log
n
) bound on the adaptive coin-weighing complexity of the parity problem.
Solvable Group Isomorphism Is (Almost) in NP ∩ coNP
Authors: Arvind Vikraman , Torán Jacobo
Published: March 2011

The Group Isomorphism problem consists in deciding whether two input groups
G
1
and
G
2
given by their multiplication tables are isomorphic. We first give a 2-round Arthur-Merlin protocol for the Group Nonisomorphism problem such that on input groups (
G
1
,
G
2
) of size
n
, Arthur uses
O
(log
6
n
) random bits and Merlin uses
O
(log
2
n
) nondeterministic bits. We derandomize this protocol for the case of solvable groups showing the following two results:

(a) We give a uniform NP machine for solvable Group Nonisomorphism, that works correctly on all but 2log
O
(1)(
n
) inputs of any length
n
. Furthermore, this NP machine is always correct when the input groups are nonisomorphic. The NP machine is obtained by an unconditional derandomization of the aforesaid AM protocol.

(b) Under the assumption that EXP \not\subseteq i.o--PSPACE we get a complete derandomization of the aforesaid AM protocol. Thus, EXP \not\subseteq i.o--PSPACE implies that Group Isomorphism for solvable groups is in NP ∩ coNP.
A Complexity Dichotomy for Finding Disjoint Solutions of Vertex Deletion Problems
Authors: Fellows Michael R. , Guo Jiong , Moser Hannes , Niedermeier Rolf
Published: March 2011

We investigate the computational complexity of a general “compression task” centrally occurring in the recently developed technique of iterative compression for exactly solving NP-hard minimization problems. The core issue (particularly but not only motivated by iterative compression) is to determine the computational complexity of the following task: given an already inclusion-minimal solution for an underlying (typically NP-hard) vertex deletion problem in graphs, find a smaller
disjoint
solution. The complexity of this task is so far lacking a systematic study. We consider a large class of vertex deletion problems on undirected graphs and show that a few cases are polynomial-time solvable, and the others are NP-hard. The considered class of vertex deletion problems includes Vertex Cover (where the compression task is polynomial time) and Undirected Feedback Vertex Set (where the compression task is NP-complete).
Generalized Second‐Order Mixed Symmetric Duality in Nondifferentiable Mathematical Programming
Authors: Agarwal Ravi P. , Ahmad Izhar , Gupta S. K. , Kailey N.
Published: March 2011

This paper is concerned with a pair of second‐order mixed symmetric dual programs
involving nondifferentiable functions. Weak, strong, and converse duality theorems are proved for
aforementioned pair using the notion of second‐order F‐convexity/pseudoconvexity assumptions.
Life-Threatening Laryngeal Edema and Hyponatremia during Hysteroscopy
Authors: Wegmüller Barbara , Hug Kerstin , Meier Buenzli Charlotte , Yuen Bernd , Maggiorini Marco , Rudiger Alain
Published: March 2011

We report on a 43-year-old patient undergoing a hysteroscopic myomectomy. After 80 minutes of operation, the patient developed laryngeal edema, requiring emergency tracheostomy. Hyponatremia (serum sodium 78 mmoL/L) indicated an irrigation fluid absorption. The patient developed shock, acute respiratory distress syndrome, acute renal failure, and diffuse intravascular coagulopathy. Resuscitation including continuous venovenous hemodiafiltration was required. Finally, the patient made a full clinical recovery. Hysteroscopy usually has low risks. However, absorption of the irrigation fluid can result in life-threatening fluid overload and electrolyte disturbances. Accurate fluid balancing and limiting the operation time may prevent these complications.
Quasimultipliers on F‐Algebras
Authors: Adib Marjan , Riazi Abdolhamid , Khan Liaqat Ali
Published: March 2011

We investigate the extent to which the study of quasimultipliers
can be made beyond Banach algebras. We will focus mainly on the class of F‐algebras, in particular on complete k‐normed algebras, 0 < k ≤ 1, not necessarily
locally convex. We include a few counterexamples to demonstrate that some of
our results do not carry over to general F‐algebras. The bilinearity and joint continuity of quasimultipliers on an F‐algebra A are obtained under the assumption of strong factorability. Further, we establish several properties of the strict and
quasistrict topologies on the algebra QM(A) of quasimultipliers of a complete
k‐normed algebra A having a minimal ultra‐approximate identity.
Interleukin-15, IL-15 Receptor-Alpha, and Obesity: Concordance of Laboratory Animal and Human Genetic Studies
Authors: Quinn LeBris S. , Anderson Barbara G.
Published: March 2011

Interleukin-15 (IL-15) is a cytokine which inhibits lipid deposition in cultured adipocytes and decreases adipose tissue deposition in laboratory rodents. In human subjects, negative correlations between circulating IL-15 levels and both total and abdominal fat have been demonstrated. Deletions ofIL15in humans and mice are associated with obesity, while gain-of-function IL-15 overexpressing mice are resistant to diet-induced obesity. IL-15 is highly (but not exclusively) expressed at the mRNA level in skeletal muscle tissue, and the regulation of IL-15 translation and secretion is complex. Conflicting evidence exists concerning whether circulating IL-15 is released from skeletal muscle tissue in response to exercise or other physiological stimuli. The IL-15 receptor-alpha (IL-15Rα) subunit has a complex biochemistry, encoding both membrane-bound and soluble forms which can modulate IL-15 secretion and bioactivity. The gene encoding this receptor,IL15RA,resides on human chromosome 10p, a location linked to obesity and type-2 diabetes. Several single-nucleotide polymorphisms (SNPs) in humanIL15RAandIL15correlate with adiposity and markers of the metabolic syndrome. Genetic variation inIL15RAmay modulate IL-15 bioavailability, which in turn regulates adiposity. Thus, IL-15 and the IL-15Rαmay be novel targets for pharmacologic control of obesity in the human population.
A Dynamic Dual Fixed-Point Arithmetic Architecture for FPGAs
Authors: Vera G. Alonzo , Pattichis Marios , Lyke James
Published: March 2011

In FPGA embedded systems, designers usually have to make a compromise between numerical precision and logical resources. Scientific computations in particular, usually require highly accurate calculations and are computing intensive. In this context, a designer is left with the task of implementing several arithmetic cores for parallel processing while supporting high numerical precision with finite logical resources. This paper introduces an arithmetic architecture that uses runtime partial reconfiguration to dynamically adapt its numerical precision, without requiring significant additional logical resources. The paper also quantifies the relationship between reduced logical resources and savings in power consumption, which is particularly important for FPGA implementations. Finally, our results show performance benefits when this approach is compared to alternative static solutions within bounds on the reconfiguration rate.
CCL5/RANTES Gene Polymorphisms in Slavonic Patients with Myocardial Infarction
Authors: Tereshchenko Irina P. , Petrkova Jana , Voevoda Mikhail I. , Taborsky Milos , Navratilova Zdenka , Romaschenko Aida G. , Maksimov Vladimir N. , Mrazek Frantisek , Petrek Martin
Published: March 2011

Coronary artery inflammation is a critical process in the pathogenesis of myocardial infarction (MI). The chemokine CCL5/RANTES (regulated upon activation, normal T cells expressed and secreted) is expressed in advanced atherosclerotic lesions. Functional polymorphisms of the RANTES gene can, therefore, be involved in the pathogenesis of coronary artery disease. We examined the association of polymorphisms in the RANTES gene with myocardial infarction in Slavonic populations of Czech and Russian origin. A total of 467 post-MI patients and 337 control subjects were genotyped for RANTES promoter G-403A (rs2107538) and intron 1.1 T/C (rs2280789) variants by PCR-SSP. Both RANTES genotypes and allele frequencies did not differ between case and control groups. Haplotype-based analysis also failed to reveal an association between MI and investigated markers. Strong linkage disequilibrium was detected between particular RANTES alleles. The data do not support an association between RANTES G-403A polymorphism and MI, as reported previously.
ModEnzA: Accurate Identification of Metabolic Enzymes Using Function Specific Profile HMMs with Optimised Discrimination Threshold and Modified Emission Probabilities
Authors: Desai Dhwani K. , Nandi Soumyadeep , Srivastava Prashant K. , Lynn Andrew M.
Published: March 2011

Various enzyme identification protocols involving homology transfer by sequence-sequence or profile-sequence comparisons have been devised which utilise Swiss-Prot sequences associated with EC numbers as the training set. A profile HMM constructed for a particular EC number might select sequences which perform a different enzymatic function due to the presence of certain fold-specific residues which are conserved in enzymes sharing a common fold. We describe a protocol, ModEnzA (HMM-ModE Enzyme Annotation), which generates profile HMMs highly specific at a functional level as defined by the EC numbers by incorporating information from negative training sequences. We enrich the training dataset by mining sequences from the NCBI Non-Redundant database for increased sensitivity. We compare our method with other enzyme identification methods, both for assigning EC numbers to a genome as well as identifying protein sequences associated with an enzymatic activity. We report a sensitivity of 88% and specificity of 95% in identifying EC numbers and annotating enzymatic sequences from the E. coli genome which is higher than any other method. With the next-generation sequencing methods producing a huge amount of sequence data, the development and use of fully automated yet accurate protocols such as ModEnzA is warranted for rapid annotation of newly sequenced genomes and metagenomic sequences.
Evaluation of the Component Chemical Potentials in Analytical Models for Ordered Alloy Phases
Authors: Oates W. A. , Wang H. , Xu D. S. , Yang R.
Published: March 2011

The component chemical potentials in models of solution phases with a fixed number of sites can be evaluated easily when the Helmholtz energy is known as an analytical function of composition. In the case of ordered phases, however, the situation is less straightforward, because the Helmholtz energy is a functional involving internal order parameters. Because of this, the chemical potentials are usually obtained numerically from the calculated integral Helmholtz energy. In this paper, we show how the component chemical potentials can be obtained analytically in ordered phases via the use of virtual cluster chemical potentials. Some examples are given which illustrate the simplicity of the method.
miR-125b Is Methylated and Functions as a Tumor Suppressor by Regulating the ETS1 Proto-oncogene in Human Invasive Breast Cancer
Authors: Zhang Yan , Yan Li-Xu , Wu Qi-Nian , Du Zi-Ming , Chen Jing , Liao Ding-Zhun , Huang Ma-Yan , Hou Jing-Hui , Wu Qiu-Liang , Zeng Mu-Sheng , Huang Wen-Lin , Zeng Yi-Xin , Shao Jian-Yong
Published: March 2011

The microRNA miR-125b is dysregulated in various human cancers but its underlying mechanisms of action are poorly understood. Here, we report that miR-125b is downregulated in invasive breast cancers where it predicts poor patient survival. Hypermethylation of the miR-125b promoter partially accounted for reduction of miR-125b expression in human breast cancer. Ectopic restoration of miR-125b expression in breast cancer cells suppressed proliferation, induced G1 cell-cycle arrest in vitro, and inhibited tumorigenesis in vivo. We identified the ETS1 gene as a novel direct target of miR-125b. siRNA-mediated ETS1 knockdown phenocopied the effect of miR-125b in breast cell lines and ETS1 overexpression in invasive breast cancer tissues also correlated with poor patient prognosis. Taken together, our findings point to an important role for miR-125b in the molecular etiology of invasive breast cancer, and they suggest miR-125b as a potential theranostic tool in this disease. Cancer Res; 71(10); 3552–62. ©2011 AACR.
Endoglin Regulates Cancer–Stromal Cell Interactions in Prostate Tumors
Authors: Romero Diana , O'Neill Christine , Terzic Aleksandra , Contois Liangru , Young Kira , Conley Barbara A. , Bergan Raymond C. , Brooks Peter C. , Vary Calvin P.H.
Published: March 2011

Endoglin is an accessory receptor for TGF-β that has been implicated in prostate cancer cell detachment, migration, and invasiveness. However, the pathophysiologic significance of endoglin with respect to prostate tumorigenesis has yet to be fully established. In this study, we addressed this question by investigation of endoglin-dependent prostate cancer progression in a TRAMP (transgenic adenocarcinoma mouse prostate) mouse model where endoglin was genetically deleted. In this model, endoglin was haploinsufficient such that its allelic deletion slightly increased the frequency of tumorigenesis, yet produced smaller, less vascularized, and less metastatic tumors than TRAMP control tumors. Most strikingly, TRAMP:eng+/−-derived tumors lacked the pronounced infiltration of carcinoma-associated fibroblasts (CAF) that characterize TRAMP prostate tumors. Studies in human primary prostate-derived stromal cells (PrSC) confirmed that suppressing endoglin expression decreased cell proliferation, the ability to recruit endothelial cells, and the ability to migrate in response to tumor cell–conditioned medium. We found increased levels of secreted insulin-like growth factor–binding proteins (IGFBP) in the conditioned medium from endoglin-deficient PrSCs and that endoglin-dependent regulation of IGFBP-4 secretion was crucial for stromal cell–conditioned media to stimulate prostate tumor cell growth. Together, our results firmly establish the pathophysiologic involvement of endoglin in prostate cancer progression; furthermore, they show how endoglin acts to support the viability of tumor-infiltrating CAFs in the tumor microenvironment to promote neovascularization and growth. Cancer Res; 71(10); 3482–93. ©2011 AACR.
Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene and Protein Expression Profiling of Responses to Cyclophosphamide
Authors: Moschella Federica , Valentini Mara , Aricò Eleonora , Macchia Iole , Sestili Paola , D'Urso Maria Teresa , Alessandri Cristiano , Belardelli Filippo , Proietti Enrico
Published: March 2011

Certain chemotherapeutic drugs, such as cyclophosphamide (CTX), can enhance the antitumor efficacy of immunotherapy because of their capacity to modulate innate and adaptive immunity. Indeed, it has been argued that this capacity may be more significant to chemotherapeutic efficacy in general than is currently appreciated. To gain insights into the core mechanisms of chemoimmunotherapy, we methodically profiled the effects of CTX on gene expression in bone marrow, spleen, and peripheral blood, and on cytokine expression in plasma and bone marrow of tumor-bearing mice. Gene and protein expression were modulated early and transiently by CTX, leading to upregulation of a variety of immunomodulatory factors, including danger signals, pattern recognition receptors, inflammatory mediators, growth factors, cytokines, chemokines, and chemokine receptors. These factors are involved in sensing CTX myelotoxicity and activating repair mechanisms, which, in turn, stimulate immunoactivation events that promote efficacy. In particular, CTX induced a T-helper 17 (Th17)-related gene signature associated with an increase in Th17, Th1, and activated CD25+CD4+Foxp3− T lymphocytes and a slight recovery of regulatory T cells. By analyzing gene and protein expression kinetics and their relationship to the antitumor efficacy of different therapeutic schedules of combination, we determined that optimal timing for performing adoptive immunotherapy is approximately 1 day after CTX treatment. Together, our findings highlight factors that may propel the efficacy of chemoimmunotherapy, offering a mechanistic glimpse of the important immune modulatory effects of CTX. Cancer Res; 71(10); 3528–39. ©2011 AACR.
Therapeutic Implications of the Emerging Molecular Biology of Uveal Melanoma
Authors: Patel Mrinali , Smyth Elizabeth , Chapman Paul B. , Wolchok Jedd D. , Schwartz Gary K. , Abramson David H. , Carvajal Richard D.
Published: March 2011

Uveal melanoma represents the most common primary intraocular malignancy in adults. Although uveal and cutaneous melanomas both arise from melanocytes, uveal melanoma is clinically and biologically distinct from its more common cutaneous counterpart. Metastasis occurs frequently in this disease, and once distant spread occurs, outcomes are poor. No effective systemic therapies are currently available; however, recent advances in our understanding of the biology of this rare and devastating disease, combined with the growing availability of targeted agents, which can be used to rationally exploit these findings, hold the promise for novel and effective therapies in the foreseeable future. Herein, we review our rapidly growing understanding of the molecular biology of uveal melanoma, including the pathogenic roles of GNAQ (guanine nucleotide binding protein q polypeptide)/11, PTEN (phosphatase and tensin homolog), IGF (insulin-like growth factor)/IGF-1 receptor, MET (hepatocyte growth factor), BAP1 [breast cancer 1, early onset (BRCA1)-associated protein-1], and other key molecules, potential therapeutic strategies derived from this emerging biology, and the next generation of recently initiated clinical trials for the treatment of advanced uveal melanoma. Clin Cancer Res; 17(8); 2087–100. ©2011 AACR.
Association between Serum IL-16 Levels and the Degree of Sensitization in Patients with Atopic Dermatitis
Authors: Nagy Georgina , Gáspár Krisztián , Irinyi Beatrix , Gál Mónika , Tumpek Judit , Gyimesi Edit , Sipka Sándor , Remenyik Éva , Szodoray Péter , Szegedi Andrea
Published: March 2011

Background: Interleukin (IL)-16 has been characterized as an immunomodulatory cytokine. Besides its chemotactic properties, IL-16 amplifies inflammatory processes and possesses immunoregulatory functions. Our aim was to investigate the association between serum IL-16 levels and the degree of allergic sensitization in patients with atopic dermatitis (AD). Methods: The serum level of IL-16 was measured by immunoenzymatic assays. Eosinophil cell count, serum total and specific IgE levels were assessed; prick tests were also carried out. Based on specific IgE levels and prick tests, AD patients were divided into sensitized and nonsensitized subgroups, and correlations among serum IL-16, total IgE levels and eosinophil cell counts were measured in the total patient group and in subgroups. Results: In the total patient group, significantly higher levels of IL-16 were found in the sera of patients with AD, compared to healthy individuals and patients with psoriasis. A significant correlation was detected between serum levels of IL-16 and total IgE, total IgE and eosinophil counts, but not between IL-16 and eosinophils. When sensitized and nonsensitized subgroups were compared, IL-16 levels showed a significant difference in subgroups that were divided based on specific IgE measurements, but not in those subgroups which were divided based on prick tests. On the other hand, serum total IgE levels showed a significant difference between sensitized and nonsensitized subgroups, assessed by the specific IgE method and also by prick test. Conclusion: Serum IL-16 levels of AD patients correlate to some extent with sensitization. This correlation is not as strong as the correlation between total IgE levels and allergic sensitization.
Effects of Traffic Air Pollution and Hornbeam Pollen on Adult Asthma Hospitalizations in Zagreb
Authors: Krmpotic Diana , Luzar-Stiffler Vesna , Rakusic Neven , Stipic Markovic Asja , Hrga Ivana , Pavlovic Mladen
Published: March 2011

Background: Environmental factors play an important role in asthma morbidity, although the contribution of individual pollutants or pollens in exacerbating asthma is not completely elucidated. Despite the evidence of importance of the hornbeam pollen in inducing allergic sensitization, its role in provoking asthma exacerbation has not been evaluated. The aim of the present study was to investigate effects of traffic pollutants on adult asthma hospitalization adjusting for pollens including hornbeam. Methods: During a 3-year period, health and environmental data were collected and analyzed. Daily asthma hospitalizations were regressed on pollutants and potential confounding variables using an autoregressive Poisson model. Results: The risk of asthma hospitalization was associated significantly with the 95th to 99th percentile increase in levels of nitrogen dioxide (RR = 1.22; 95% CI: 1.05–1.40), carbon monoxide (RR = 1.25; 95% CI: 1.01–1.55) and hornbeam pollen (RR = 1.21; 95% CI: 1.11–1.30). The effect of nitrogen dioxide was delayed by 5 days. No statistically significant increase in the risk of asthma hospitalization was found for PM10 particles. A comparison among the standardized regression coefficients and their respective p values indicates that the most important risk factor for asthma hospitalization is associated with hornbeam pollen levels. No statistically significant interactions between pollutants and pollens were detected. Conclusions: The current results suggest that traffic-related air pollution is associated with increased risk of adult asthma hospitalization. Nonetheless, the most significant risk for asthma hospitalization is associated with hornbeam pollen levels in the city of Zagreb.
IL-17A Induces CCL28, Supporting the Chemotaxis of IgE-Secreting B Cells
Authors: Scanlon Karen M. , Hawksworth Richard J. , Lane Stephen J. , Mahon Bernard P.
Published: March 2011

Background: Atopic asthma is an allergic disease typically associated with TH2 cytokines. IL-17A is also associated with asthma, through the induction of chemokines. Mucosal CCL28 concentrations correlate with cellular recruitment to inflamed airways and support migration of IgA+ B cells. Here, a link between IL-17A, CCL28 and IgE-secreting B cell chemotaxis is examined. Methods: Primary human airway cells and the airway epithelial line A549 were used to characterize IL-17A receptor expression and the effect of IL-17A on CCL28 transcription and translation. B cells, differentiated to IgE+ cells ex vivo, were assessed for CCR10 surface expression and chemotaxis to CCL28 by flow cytometry, transwell migration and ELISpot. Results: Human airway epithelium expressed both IL-17RA and IL-17RC, and was responsive to IL-17A stimulation. Cultured human IgE+ B cells expressed surface CCR10 and displayed CCR10-dependent chemotaxis towards recombinant CCL28. Enhanced levels of CCL28 were observed upon A549 cell incubation with IL-17A, and this up-regulation significantly increased the migration of IgE+ antibody-secreting B cells. The specificity of chemotaxis was confirmed by migration blockade in the presence of anti-CCL28 or anti-CCR10. Conclusions: This work identifies a novel chemokine for the migration of IgE+ B cells, in addition to characterizing induction of CCL28 by IL-17A. Taken together the results presented here propose a new role for IL-17A in the allergic airways, linking this cytokine with the recruitment of IgE+ antibody-secreting B cells, via the induction of CCL28. These observations justify further in vivo studies of larger cohorts.
Cbl Family Proteins: Balancing FcεRI-Mediated Mast Cell and Basophil Activation
Authors: Gasparrini Francesca , Molfetta Rosa , Santoni Angela , Paolini Rossella
Published: March 2011

The binding of IgE to high-affinity IgE receptors (FcΕRI) expressed on the surface of mast cells and basophils initiates a cascade of signaling events that results in the release of a wide array of proinflammatory mediators. In order to limit the intensity and duration of cell activation, FcΕRI aggregation has been understood to additionally generate negative signals through the coordinated action of adapters, phosphatases, and ubiquitin ligases. Among them, Cbl family proteins negatively regulate FcΕRI-mediated signals mainly by promoting ubiquitination of the activated receptor subunits and associated protein tyrosine kinases. Notably, FcΕRI ubiquitination has become recognized as an important signal for the internalization and delivery of engaged receptor complexes to lysosomes for degradation. The surface expression of activated FcΕRI complexes is further downregulated through a pathway that is functionally separable from Cbl ligase activity and is dependent on the interaction of Cbl proteins with adapters involved in clathrin-dependent endocytosis. In this article, we review recent advances in our understanding of the molecular mechanisms through which Cbl proteins negatively regulate FcΕRI-mediated mast cell and basophil functions.
Suitability of Different Glycoproteins and Test Systems for Detecting Cross-Reactive Carbohydrate Determinant-Specific IgE in Hymenoptera Venom-Allergic Patients
Authors: Mertens Melanie , Brehler Randolf
Published: March 2011

Background: In hymenoptera venom allergy, about 75% of detected in vitro double positivity to yellow jacket and honeybee venom is ascribed to specific IgE (sIgE) directed against cross-reactive carbohydrate determinants (CCDs). To date, for the detection of CCD-sIgE, different carbohydrate antigens and methods are used. The most suitable one still has to be identified. Methods: Eighty-seven patients with confirmed hymenoptera venom allergy and venom sIgE values of ≧0.7 kU/l were investigated. Sixty-five patients showed sIgE reactivity to both yellow jacket and honeybee venom, 22 were venom mono positive and served as controls. Occurrence of CCD-sIgE was determined using bromelain, horseradish peroxidase (HRP) and MUXF3 on system A, and ascorbic acid oxidase (AAO), bromelain and HRP on system B. Further, a reference standard for CCD-sIgE evaluation was created: CCD positivity was assumed when at least 4 of the 6 test results were positive. Results: According to the defined reference standard, 45/65 venom double positive patients exhibited CCD-sIgE. Using system A, comparison with the reference standard revealed sensitivity and specificity values of 96 and 97%, respectively, for MUXF3, 100 and 100%, respectively, for bromelain, and 96 and 97%, respectively, for HRP. Using system B, sensitivity and specificity was 98 and 97%, respectively, for AAO, 62 and 95%, respectively, for bromelain, and 96 and 69%, respectively, for HRP. Results of the 3 test allergens obtained with system A showed strong correlations (r = 0.932–0.976), whereas results with system B showed lower correlations (r = 0.714–0.898). Conclusions: All 3 test allergens used with system A are suitable for CCD-sIgE detection in hymenoptera venom allergy. With system B, only AAO seems to be a reliable tool.