bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor Vascular Disrupting Agents
Authors: Tozer Gillan , Kanthou Chyso
Published: August 2009

Tumor vascular disrupting agents (VDAs) are characterized by their ability to
produce a very rapid and selective shut-down of tumor blood flow sufficient to induce
extensive secondary tumor cell death. This effect is brought about by efficacy against
established tumor blood vessels, making their mode of action conceptually distinct from that of
the anti-angiogenic agents. Three main groups of VDAs are currently in clinical trial, consisting
of DMXAA (5, 6-dimethylxanthenone-4-acetic acid), tubulin binding agents including the
combretastatins and junctional protein inhibitors. These agents have different primary targets
but produce similar morphological and functional effects on the tumor vasculature. The
signaling pathways that mediate these effects are only partially understood but, in the case of
disodium combretastatin A-4 3-0-phosphate (CA-4-P), undoubtedly involve activation of the
small GTP-ase Rho and Rho kinase. Innate and induced resistance mechanisms need to be
investigated in order to provide new targets for improving the efficacy of VDAs, especially in
combination with conventional cancer treatments. Here, we review the developmental status of,
and mechanisms of action and resistance to, currently available VDAs.
Inhibitors of Angiogenesis Based on Thrombospondin-1
Authors: Taraboletti Giulia , Bonezzi Katiuscia
Published: August 2009

Angiogenesis-driven pathologies, including cancer, are sustained by a preponderance
of angiogenic factors over endogenous inhibitors of new-vessel formation. Restoring this
balance represents a logical therapeutic strategy to treat these pathologies. Therefore,
endogenous inhibitors of angiogenesis, and in particular thrombospondin-1 (TSP-1), are a
powerful source of potential antiangiogenic tools. Different therapeutic approaches have been
proposed to exploit the antiangiogenic properties of TSP-1, including TSP-1 fragments,
synthetic peptides and peptidomimetics, gene therapy strategies and agents that up-regulate
TSP-1 expression. This review focuses on the possibility of exploiting TSP-1 for the design of
antiangiogenic agents, with particular reference on their use in antineoplastic therapies.
Novel Antiangiogenic Molecules in Multiple Myeloma
Authors: M. Roccaro Aldo , M. Ghobrial Irene
Published: August 2009

The paradigm for the treatment of multiple myeloma (MM) has significantly
changed: therapeutic options have evolved from the introduction of melphalan and prednisone
in the 1960s, high-dose chemotherapy and stem cell transplantation in the late 1980s and 1990s,
to the rapid introduction of small novel molecules within the last seven years. Based on the
understanding of the complex interaction of MM cells with bone marrow microenvironment;
and of the role of neoangiogenesis in MM pathogensis, a number of novel therapeutic agents
with anti-angiogenic properties are now available, playing a key role in the treatment of MM
both in the preclinical settings and as part of clinical trials.
Successful of Control Program for Enterobiasis Among Hilltribers in a Rural Community, Northern Thailand
Authors: Wiwanitkit Viroj
Published: August 2009

Enterobius vermicularis is an important helminthic infection among children in rural areas of developing
countries. In our previous reports, a high prevalence of enterobiasis among the children in the far rural community,
Mae Suk, Northern Thailand was noted. An active control program for enterobiasis in our community is set and
distribution of antihelminthic drugs and a longitudinal follow-up to assess the effectiveness of our control program
was performed. Here, the author reports a dramatic decrease of the prevalence of enterobiasis in this rural area.
Overview of Conjunctivitis in Thailand
Authors: Atchaneeyasakul Kunakorn , Wiwanitkit Viroj
Published: August 2009

Conjunctivitis is an infectious disease of the eye which is very common in Thailand. The disease can
spread widely and especially during the rainy season in Thailand. The authors performed a literature review on the
reports of Conjunctivitis outbreak in Thailand in order to summarize the outbreak information. A literature review of
the papers concerning Conjunctivitis outbreak in Thailand was performed using the database of published works
cited in the Index Medicus and Science Citation index. The literature review focused mainly on all conjunctivitis
outbreaks that have been published. The reported location of the outbreak in the literature usually occurred in central
Thailand mostly in the capital city, Bangkok. Some outbreaks can be found in other parts of Thailand such as the
Northeastern Thailand. The time of outbreak is usually around August which is around the rainy season in Thailand.
There is no significant difference of the infection between male and female. The calculated overall mean age of
patients is 16 years which is the school age. Conjunctivitis is a common eye infection caused by many kinds of
organisms which is highly contagious and is able to spread just by contact. The disease is not severe and can be
treated by topical antibiotics. However it is much wise to keep the infection from spreading by keeping the patients
away from social for about a week.
Hemagglutin Gene of Bird Flu Virus in Thailand: A Variation of Their Encoding Proteins
Authors: Wiwanitkit Viroj
Published: August 2009

Background: Bird flu or avian flu, caused by H5N1 virus, is a new emerging infectious disease. It is noted
that this H5N1 virus jumped the species barrier and caused severe disease with high mortality in humans in Vietnam
and Thailand. Many were reported noted on nucleotide for HA of H5N1 in Thailand. However, there is no
comparison on the structure of the protein encoded by the isolated HA in Thailand.

Method: Here, the author performed this study to compare the secondary and tertiary structures of the isolated HA
from different sources in Thailand. The author used a bioinformatic technique to predict the secondary and tertiary
structures of HA of H5N1 isolated in Thailand.

Result: Using NNPREDICT and CPHmodels 2.0 servers, the calculation for secondary and tertiary structures of
H5N1 of HA isolated in Thailand was performed. The predicted structures of all 20 HA are same.

Conclusion: The structures of H5N1 derived from natural and non-natural hosts of virus are same. This implies that
the mutation might not be the important factor leading to the cross species infection in Thailand but the individual
defect of non-avian host might be the possible factor.
Legionella and Free Living Amoeba Contamination in Natural Hot Spring Pools in Thailand: Overview
Authors: Wiwanitkit Viroj
Published: August 2009

Legionella is important human pathogen.The surveillance for legionella in water reservoir is suggested.
Contamination by legionella in natural hot springs may pose a significant health risk to people who use such water
for recreation activities.The aim of this work is to summarize the pattern on legionella contamination in hot spring
pools in Thailand. According to the search, there are 13 on radon in 83 hot spring pools in Thailand (December
2007). The number of hot springs with legionella contamination is equal to 48 (57.8 %). In addition to legionella,
situation on free living amoeba in hot spring pools in Thailand is also presented in this article.
Encephalopathy in Dengue with Hepatic Failure, Summary of Thai Cases
Authors: Wiwanitkit Viroj
Published: August 2009

Dengue infection is a major vector-borne disease. The classical sings and symptoms of this infection
include high fever, violent headache, chill and rash. However, there are a number of atypical forms of dengue
infection including those presented with severe liver dysfunction. Sporadic case reports of dengue hepatic
encephalopathy are documented in Thailand. Here, the author presents a summative study on the clinical
presentation and outcome among Thai patients with dengue encephalopathy in the previous studies. A literature
review on the prospective studies concerning dengue hepatic encephalopathy in Thailand was performed. According
to this study, 4 reports covering 19 cases (12 females and 7 males) of dengue encephalopathy among the Thai can be
detected. The summative on clinical presentation of all patients are presented in Table 1. The average age (mean ±
SD) of all subjects is 8.0 ± 3.0 (range = 2-13 years old). Classified by grade on dengue infection, there are 14 grade
IV, 4 grade III and 1 grade II. Most of the hepatic encephalopathy occur in convalescent stage (14 cases, 73.7 %).
Concerning the depth of hepatic encephalopathy, there are 8 level IV, 6 level III, 4 level II and 1 level I. Of 16
known cases, the duration of encephalopathy ranges from 0.8 to 26 days (average 8.2 ± 6.6 days). Of 15 known
cases, the liver span ranges from 2 to 6 cm (average 3.7 ± 1.2 cm). Concerning the laboratory investigation, severe
hepatitis (SGOT and SGPT > 200 U/L) can be seen in all cases. Hypoglycemia and hyponatremia can be detected in
6 and 5 cases, respectively. Most of the cases (15 cases, 78.9 %) received conventional treatment and most (12
cases, 63.2 %) recovered completely.
Prevalence of Cryptosporidiosis Among Thai HIV-Infected Patients with Diarrhea at Present and in the Past Decade: İs There any Effect of HAART Therapy
Authors: Wiwanitkit Viroj
Published: August 2009

An important parasitic infection among HIV infected patients is the cryptosporidiosis. Cryptosporidium
parvum is an intestinal parasitic protozoon that causes severe diarrhea and may lead to death in
immunocompromised hosts. In HIV infected cases with cryptosporidiasis, four main clinical syndromes were
identified: chronic diarrhea, choleralike disease, transient diarrhea, and relapsing illness. In this paper, the authors
presented the prevalence of cryptosporidiosis among Thai HIV-infected patients with diarrhea in comparison to the
previous noted prevalence in the past decade. The prevalence of among Thai HIV infected patients with diarrhea in
the previous decade is equal to 7.14 %. The present prevalence of among Thai HIV infected patients with diarrhea is
investigated with the same protocol. Overall 25 HIV infected cases could be detected giving the prevalence equal to
18.95 % (25/193). Of interest, although the HAART therapy is easily available in Thailand, at present the
prevalence of cryptosporidiosis is still very high in the HIV seropositive patients with diarrhea. Therefore, the
authors hereby propose that the wide distribution of HAART therapy did not affect the prevalence of
cyrptosporidiosis among HIV seropositive patients with diarrhea.
Capillaria phillipinensis Infection, Summary from 12 Previously Noted Thai Cases
Authors: Kue-A-Pai Pongsatorn , Wiwanitkit Viroj
Published: August 2009

CONTEXT: Capillaria phillipinensis infection is a round worm infection. Capillaria phillipinensis is
considered a zoonotic disease of migratory fish-eating birds.

OBJECTIVE: Here, the author performed a literature review on the reports of C. philippinensis in Thailand in order
to summarize the characteristics of this infection among the Thai patients.

DESIGN: This study was designed as a descriptive retrospective study. A literature review of the papers concerning
C. philippinensis infections in Thailand was performed.

RESULTS: Due to this study, there have been at least 8 reports of C. philippinensis infection, of which 1 case was
lethal (Table 1). There are at least 12 Thai cases with C. philippinensis infections. The age ranges from 13 to 58
years. Of seven well-documented cases, 5 were males and 2 were females. Most (10/12) cases were detected from
stool examination: One was detected by Gastroduodenoscopy: The other case (1/12) was detected after the patient
died.

CONCLUSION: In conclusion, C. philippinensis infection is sporadically noted in Thailand. The diagnosis is
usually by stool examination. The survival rate of these infections is high if the diagnosis is correct and is quite low
if the diagnosis is too late. The treatment of this infection is an antiparasitic drug such as mebendazole and
albendazole.
New Researches on Molecular Biology Aspect of Hepatitis Virus: Some New Examples
Authors: Wiwanitkit Viroj
Published: August 2009

Hepatitis virus infection is an important infection in medicine. There are many hepatitis viruses. There
are many new researches on molecular biology aspect of hepatitis viruses. The author hereby presents some new
example on epitope preference in wild and mutated precore of hepatitis B virus, weak linkage in HGV 5' non-coding
region and transmembrane topology of hepatitis B envelope proteins.
The Unfolded Protein Response in Mammalian Cells
Authors: Hoon Back Sung , R. Hassler Justin , J. Kaufman Randal
Published: August 2009

The endoplasmic reticulum (ER) is a well-orchestrated factory where secretory and
membrane proteins are manufactured, modified and correctly folded prior to trafficking to their final
destinations. Conditions that interfere with ER function lead to an evolutionarily conserved cellular
stress response termed the unfolded protein response (UPR). The UPR initially transduces signals to reestablish
ER homeostasis but with prolonged or acute ER stress these signals undergo a transition that
initiate cell death. In this review, we summarize our current understanding of the mammalian UPR and
discuss the cell-type and tissue-specific functions of UPR components revealed by studies from genetic
mouse models.
The ER Chaperone GRP78 and Cancer
Authors: Ye Risheng , Zhang Yi , S. Lee Amy
Published: August 2009

The unfolded protein response (UPR) is emerging as a major contributor to cancer cell
adaptation to the pathophysiological stress of tumorigenesis. As a major endoplasmic reticulum (ER)
chaperone, GRP78/BiP is induced by the UPR, and functions as a master regulator of the UPR signaling
pathways. In this review, recent global analysis of Grp78 mRNA level in specific human tissues and its
role in ER stress signaling and cell survival are discussed. Very recently the dynamic molecular events
during the transcriptional induction of Grp78 were elucidated, providing kinetics of factor occupancy
along the Grp78 promoter in cells subjected to ER stress. In addition to its established function of an
apoptotic protein, a regulatory role of GRP78 in stress-induced autophagy in mammalian cells is also
recently defined. In multiple cancer models, both in vitro and in vivo, GRP78 confers growth advantage
and drug resistance to solid tumors. Finally, the newly discovered cell surface GRP78 provides potential
cancer specific therapy.
Endoplasmic Reticulum Stress and Protein Misfolding in Amyotrophic Lateral Sclerosis
Authors: K. Walker A. , J. Turner B. , D. Atkin J.
Published: August 2009

The accumulation of ubiquitinated protein inclusions is a hallmark of amyotrophic laterals
sclerosis (ALS), a rapidly progressing fatal neurodegenerative disease primarily affecting motor
neurons. However, the exact cause of motor neuron death in ALS remains unclear. The unfolded
protein response (UPR) is a homeostatic mechanism, which is activated in response to endoplasmic
reticulum (ER) stress caused by unfolded or misfolded proteins within the ER lumen. The UPR
activates three signalling pathways that lead to an up-regulation of protein chaperones and a block in
general protein synthesis. However, chronic UPR activation promotes cell death via apoptosis. Here
we review evidence from human patients and experimental models implicating ER-stress induced cell
death in ALS. Recently, activation of all three UPR transduction pathways was shown in spinal cords
of patients affected by ALS, including up-regulation of protein disulfide isomerase (PDI), an
important ER chaperone, and activation of the ER stress-specific apoptotic factor caspase-4. Similarly,
expression of mutant superoxide dismutase 1 (SOD1) proteins, which cause 20% of familial ALS
cases, leads to activation of the UPR in neuronal cell culture and transgenic mutant SOD1 mice,
which are the most widely accepted animal model of disease. Microsomal localisation and SNARE
complex-regulated secretion of SOD1 implies entry into the ER-Golgi secretory pathway, and we
discuss the disruptive effects of mutant SOD1 on the Golgi apparatus and general protein export.
Importantly, the links between ER stress and other pathways implicated in ALS, including autophagy,
oxidative stress and the ubiquitin-proteasome system, are becoming increasingly recognised,
suggesting that ER stress is a central mechanism in disease. These observations suggest novel
potential therapeutic targets for ALS.
ER Stress Signaling Network in Pancreatic β-Cells
Authors: G. Fonseca Sonya , Urano Fumihiko
Published: August 2009

Pancreatic β-cells are specialized to control blood glucose levels by producing and
secreting the hormone insulin. Increasing evidence indicates that the endoplasmic reticulum (ER)
stress signaling network has an important function in maintaining β-cell homeostasis. Thus,
dysfunction of ER stress signaling has harmful effects on β-cell function, leading to β-cell
dysfunction and death in type 1 and type 2 diabetes. In this article, we will summarize the role of ER
stress signaling in pancreatic β-cells.
Heritable Neurodevelopmental Disorders and Endoplasmic Reticulum Stress
Authors: Momoi Takashi , Fujita Eriko
Published: August 2009

The molecular pathogenesis of heritable neurodevelopmental disorders, including autism
spectrum disorder (ASD) and speech-language disorder, is not well understood; although, several
mutations in genes encoding neuroligin and FOXP2 have been identified. Here, we evaluate the
relationship between the protein quality control system of the endoplasmic reticulum (ER) and the
molecular pathogenesis of these disorders.
ER Quality Control, ER Stress-Induced Apoptosis, and Neurodegenerative Diseases
Authors: Nishitoh Hideki , Kadowaki Hisae , Takeda Kohsuke , Ichijo Hidenori
Published: August 2009

The endoplasmic reticulum (ER) is the intracellular organelle in which newly synthesized
secretory and transmembrane proteins achieve proper structure as a result of post-translational
modification, folding, and oligomerization. However, many of these proteins are malfolded (unfolded
or misfolded) as a result of various intracellular or extracellular stimuli. ER stress is caused by
disturbances of ER function with the accumulation of malfolded proteins and alterations in calcium
homeostasis. To restore ER function, cells possess a highly specific ER quality control system to
increase the capacity of protein folding and to reduce the amount of malfolded proteins in the ER. In
case of prolonged ER stress or malfunction of the ER quality control system, apoptosis signaling is
activated. ER stress-induced apoptosis has recently been implicated in human neurodegenerative
diseases such as Alzheimer disease, Parkinson disease, polyglutamine diseases, and amyotrophic
lateral sclerosis. This review summarizes the molecular mechanisms of the ER quality control system
and ER stress-induced apoptosis and the possible roles of ER stress in neurodegenerative diseases.
Contributors
Authors: Hetz Claudio
Published: August 2009

Full text available
Role of Alzheimer’s β-Amyloid on Wnt Signaling
Authors: C. Inestrosa Nibaldo , Grabowski Catalina , Arrazola Macarena , Varela-Nallar Lorena , M. Toledo Enrique
Published: August 2009

Recent evidence supports a neuroprotective role for Wnt signaling in neurodegenerative
disorders such as Alzheimer´s Disease. In fact, a relationship between amyloid-β-peptide induced
neurotoxicity and a decrease in the cytoplasmic levels of β-catenin has been observed. Apparently,
Aβ binds to the extracellular cysteine-rich domain of the Frizzled receptor inhibiting Wnt/β-catenin
signaling. These studies indicate that a sustained loss of Wnt signaling function may be involved in
the Aβ-dependent neurodegeneration observed in Alzheimer’s brain. So far, we have demonstrated
that activation of Wnt signaling protects neurons against neurotoxic injuries, including both amyloid-β
fibrils and Aβ oligomers by using either lithium, an inhibitor of the glycogen synthase kinase 3β, or
different Wnt ligands. In particular, the activation of non-canonical Wnt signaling was able to protect
postsynaptic regions and dendritic spines against Aβ oligomers. In conclusion, the activation of the
Wnt signaling pathway could be proposed as a therapeutic target for the treatment of AD.
β-Amyloid Peptide, Endoplasmic Reticulum Stress, and Alzheimer’s Disease
Authors: Ghribi Othman
Published: August 2009

Accumulation of β-amyloid (Aβ) peptide in the brain is suggested to play a key role in the
pathogenesis of Alzheimer’s disease (AD). Both the inherited familial and the sporadic forms of AD
are characterized by increased levels of Aβ42. Incubation of cells with synthetic Aβ or administration
of this peptide to animals is also associated with cellular degeneration. Currently, the mechanisms by
which Aβ accumulates as well as the mechanisms that underlie Aβ-induced neurodegeneration in AD
are not fully understood. Aβ is generated in part in the endoplasmic reticulum of neurons, degraded
chiefely by the insulin degrading enzyme, and cleared out of the brain primarily by the low-density
lipoprotein receptor-related protein. Stress in the endoplasmic reticulum can affect the processes
involved in Aβ generation, degradation, and clearance, thus resulting in increased levels of this
peptide in the brain. In this chapter, first, supportive data of role of disturbances in the endoplasmic
reticulum homeostasis as an underlying mechanism of Aβ accumulation will be provided. Second,
evidence from in vitro and in vivo studies showing that the endoplasmic reticulum is a target organelle
for exogenous Aβ will be demonstrated. When applied to cells or administered to animals Aβ triggers
endoplasmic reticulum stress that is ultimately deleterious to cells. Collectively, data from AD brains,
animal models for AD, and in vitro studies converge to present compelling evidence that the
endoplasmic reticulum stress is relevant to the pathogenesis of AD.
Endoplasmic Reticulum Stress Response in Prion Diseases
Authors: Mukherjee Abhisek , Soto Claudio
Published: August 2009

Prion diseases are infectious neurodegenerative diseases associated with the brain
accumulation of the misfolded prion protein. Despite substantial knowledge of the mechanism of
infection and disease transmission, little is known about the molecular pathways involved in
neurodegeneration. Recent findings implicate endoplasmic reticulum (ER) stress as a key event in
brain dysfunction. The available evidence indicates that accumulation of misfolded prion protein
induces ER stress, followed by the activation of the unfolded protein response. Chronic stress
produced by the sustained formation of misfolded proteins lead to neuronal apoptosis and synaptic
alterations. In this article we discuss the role of ER stress in prion neurodegeneration and the
signaling pathways implicated.
Autophagy and the Ubiquitin-Proteasome System - Protein Catabolism Comes Full Circle
Authors: B. Nedelsky Natalia , Paul Taylor J.
Published: August 2009

All cells are endowed with two catabolic pathways for degrading protein: the ubiquitinproteasome
system (UPS) and autophagy. While these routes of protein degradation were long
considered to be parallel and complementary systems, new evidence has revealed interaction between
the UPS and autophagy, suggesting a coordinated relationship that becomes critical in times of
cellular stress. Here we introduce the basics and parallels of the UPS and autophagy, review the
evidence for cross-regulation of the two systems, and highlight their emerging coordinated
relationship. Throughout, we review the evidence suggesting that impairment of autophagy could
contribute to the initiation or progression of age-related neurodegeneration.
Connected Dominating Sets
Authors: Wu Yiwei , Li Yingshu
Published: August 2009

Wireless sensor networks (WSNs) are now widely used in many applications. However, routing in
WSNs is very challenging due to the inherent characteristics that distinguish these networks from other
wireless networks. The concept of hierarchical routing is widely used to perform energy-efficient routing in
WSNs. Thus, a Connected Dominating Set (CDS) has been recommended to serve as a virtual backbone for
a WSN to reduce routing overhead. Fault tolerance and routing flexibility are necessary for routing since
nodes in WSNs are prone to failures. Hence, it is important to maintain a certain degree of redundancy in a
CDS. Therefore, the concept of k-connected m-dominating sets (kmCDS) is used to provide these
redundancies. In this chapter, we present CDS based routing protocols and focus on how to construct CDS
and kmCDS, including both centralized and distributed algorithms.
Distributed Localization in Wireless Sensor Networks
Authors: K.G. Seah Winston , B.S. Tan Eddie , Wong Sau-Yee , Tay Jeffrey
Published: August 2009

Wireless sensor networks (WSNs) continue to be an active research area as the deployment of
low cost wireless sensors is a promising technique for various applications such as early warning and alert
systems, ecosystem monitoring, warehousing, logistics and surveillance. Sensor data is typically
interpreted with reference to a sensor’s location, e.g. reporting the occurrence of an event, tracking of a
moving object or monitoring the physical conditions of a region. The process of determining the location
of a sensor node in a wireless sensor network, commonly known as localization, is a challenging problem
as reliance on infrastructure-based technology like GPS is infeasible due to constraints arising from limited
on-board computation power and energy supply, as well as, physical deployment conditions (e.g. indoors
or underwater). In this chapter, we focus on range-free distributed localization schemes, in particular,
schemes based on hop count that can function under realistic conditions.
Area Coverage in Wireless Sensor Networks
Authors: Gallais Antoine
Published: August 2009

Wireless sensor networks are deployed to observe remote or sensitive environments.
To avoid difficult or dangerous manipulations after the deployment, power-saving
strategies are used to prolong the network lifetime. Selecting active sensors, that perform
the monitoring task while passive ones save energy, is one of them. The ensuing sensor area
coverage issue is thus formulated as follows: every part of the deployment area, initially
sensed by n deployed sensors, must be sensed by at least k active ones (k varying between 1
and n). This chapter investigates proposed techniques to designate those sensors along with
existing assumptions and tools that they use.
Heterostructure Growth
Authors: Khlyap Halyna
Published: August 2009

Principal technologies used for heterostructures growth are described: molecular beam epitaxy (MBE), metalorganic
chemical vapor deposition (MOCVD), atomic layer deposition (ALD). The main tools for characterization of the
structures obtained are presented along with recent experimental data on the most important structural and electrical
properties of the heterostructures based on III-V and II-VI semiconductor materials.
Investigation of Electrical Properties of Active Elements Based on Silicon and A2B6-A4B6 Group Materials
Authors: Khlyap Halyna
Published: August 2009

Charge transport mechanisms and photosensitivity of amorhous silicon thin films prepared by magnetron sputtering
are investigated at room temperature. The power law and the power-exponential laws governing the currents observed
experimentally are revealed. The near-IR photosensitivity of the films can be sufficiently improved by means of high-temperature
hydrogenation. Important properties of heterostructures based on PbS, ZnSe, ZnTe and CdTe semiconductors are also discussed
along with the results of numerical analysis of experimental data.
Engineering of Semiconductor-Based Active Elements by Mechanical Deformation and Ion Implantation Technology
Authors: Khlyap Halyna
Published: August 2009

Effect of external electric field on formation of stressed interfaces in heterostructures
grown by molecular beam epitaxy is considered. Ion implantation technology and mechanically
induced deformations are appeared to be effective tools applied to manufacture semiconductor-based
active elements. Indentation seems to be an important instrument for preparing barrier structures with
unique charge carriers transport properties. Ion implantation technique makes it possible to form
additional junctions in the implanted crystal matrix which are very important for the increase of
efficiency of conventional solar cells.
New Narrow-gap Semiconductor ZnCdHgTe: Growth Technology and Principal Features of ZnCdHgTe-Based Structures
Authors: Khlyap Halyna
Published: August 2009

Preparation and main electrophysical characteristics of narrow-gap semiconductor ZnCdHgTe thin films are described.
Experimental room-temperature current-voltage and capacitance-voltage dependences are presented. Energy band diagram
construction procedure and results of the numerical simulation of experimental data are also discussed.
Electric Field-Induced Characteristics of ZnCdHgTe Films Surface
Authors: Khlyap Halyna
Published: August 2009

Charge transport mechanisms and photosensitivity of ZnCdHgTe thin films manufactured by liquid-phase epitaxy and
laser technology are investigated at room temperature. Laser beam-induced formation of barrier structures is also considered.
Effect of hydrogenation as a tool for enhancing device properties of the films is described.
Chalcogenide Semiconductors for Sensor Applications
Authors: Khlyap Halyna
Published: August 2009

Chalcogenide semiconductors A1B5C6 are perspective materials for various sensor applications. The chapter
summarizes unique experimental results on electrical properties of Ag3SbS3 monocrystals and provides necessary data for
manufacture of γ-radiation sensors based on these materials.
Design of Active Elements Based on Nanostructural A1B5C6 Materials
Authors: Khlyap Halyna
Published: August 2009

Preparation and main electrophysical characteristics of A1B5C6 nanostructural semiconductor materials are discussed.
Sensor devices designed for external electric field detection and operation in aggressive environments are described. Numerical
simulation of the main electrical characteristics of these structures is also reported.
Magnetic Field and Delta Connections
Authors: Memari A.R.
Published: August 2009

In order to demonstrate the capability of the developed approach on any types
of transmission line, delta configuration power line has been investigated and numerical
illustration is established. The results are tabulated and the related figures are depicted.
In this chapter, characteristics of the magnetic fields and effect of the altitude of the
auxiliary mitigating loop with respect to the power line are studied. Finally, relationship
between the three types of the magnetic fields for delta - connected configuration has
been scrutinized and the depicted figure illuminates the discussions
Triatomine-Vector of Trypanosoma cruzi Infection
Authors: Diotaiuti Liléia
Published: August 2009

The lifecycles of the organisms involved in the circulation and transmission of the
Trypanosoma cruzi agent of Chagas disease are intimately related. It appears that these cycles
begun after an adaptive process in the quaternary, Mezozoic, Cretaceus, over 90 million years
ago. Gradually, the triatomines became intermediate hosts and vectors of the protozoan infection
to mammals when the enzootic infections contaminated omnivorous mammals, particularly
skunks, armadillos and ant-eaters. Hematophagy resulting from a biochemical requirement for the
insect growth has contributed to approximate triatomines and mammalians. Triatomines adapted
to human dwells generated the endemic Chagas disease. This chapter describes and characterizes
the habits of triatomines, which are important to understanding T. cruzi transmission by the
insect-vector, its control and disease prevention. The success obtained with the spray of
pyrethroids insecticides to control the triatomines intradomicile recommends a lot more actions to
prevent repopulation of the human dwells with the repulsive insect-transmitters of the T. cruzi
infections.
A Review on the Ultrastructure of Trypanosoma cruzi
Authors: de Souza Wanderley , Miranda Kildare , Leal Cunha e Silva Narcisa , Souto-Padrón Thaïs
Published: August 2009

This review analyzes the fine structure of Trypanosoma cruzi as visualized by various
morphological techniques, including scanning electron microscopy, transmission electron
microscopy of thin sections and freeze-fracture replicas, and atomic force microscopy. Data
obtained using cytochemistry and immunocytochemistry are also discussed. Various structures,
such as the glycocalyx, plasma membrane, flagellar pocket, cytoskeleton, flagellum, kinetoplastmitochondrion
complex, glycosome, acidocalcisome, lipid bodies, contractile vacuole, secretory
pathway, endocytic pathway and nucleus, are covered.
Trypanosoma cruzi Mitochondrial DNA and the Parasite Lifecycle
Authors: R. Sturm Nancy
Published: August 2009

As a parasite with a potentially decades-long intracellular stage, Trypanosoma cruzi could
represent a case study for extreme mechanisms for the maintenance of mitochondrial sequence
integrity. While an intact mitochondrial repertoire of membrane-associated cytochromes and NADH
dehydrogenases are required for passage through the insect forms, within the vertebrate host many of
these products may be dispensable, as in vertebrate-exclusive relatives. The degeneration seen in
maxicircle genomes from clinical isolates and from culture indicates that the maintenance of intact
maxicircles and a complete library of minicircles is an uphill battle that the parasite manages actively.
Both the maxicircle and minicircle have been implicated in the clinical manifestation of Chagas
disease. The implications of both these scenarios on the biology of the parasite relative to the host are
discussed.
Trypanosoma cruzi Nuclear DNA and its Correlation with the Parasite Lifecycle
Authors: A. Campbell David
Published: August 2009

T. cruzi undergoes distinct developmental programs during its replication cycle and
during its lifecycle where it shuttles between mammal and triatomine hosts. The information
required to achieve these complex morphological and biochemical changes is encoded in the
genome at several different levels. A preliminary understanding of the biochemical,
physiological, and morphological changes that occur in the different lifestages of T. cruzi requires
a detailed knowledge of the parasites genome composition and function. Here, we review the role
of the nucleus in parasite identity. We begin with an analysis of how gene organization is
resolved by mechanisms of mRNA formation, and the inherent signals in mRNAs that enable
stage-specific protein expression. We continue with a description of the genome of the CL Brener
strain as determined by the T. cruzi genome-sequencing project, including analysis of repetitive
elements, structural genes, and some protein-coding genes. We end with a discussion of T. cruzi
population structure and the discovery of rare nuclear hybridization events.
Host-Parasite Biology of Trypanosoma cruzi Infection
Authors: L. Epting Conrad , M. Bonney Kevin , L. Olson Cheryl , M. Engman David
Published: August 2009

The protozoan parasite Trypanosoma cruzi, the etiologic agent of Chagas disease, is an
intracellular pathogen in its vertebrate host. Here we review the process of cell invasion by T.
cruzi from the perspectives of surface-surface interactions, intracellular signaling, contributions
of donor membranes and the cytoskeleton, and discuss cytoplasmic entry and differentiation after
escape from the parasitophorous vacuole. The chronic host-pathogen relationship depends upon
immune evasion by the parasite and prevention of host apoptosis. Finally, we briefly discuss the
development of cardiac autoimmunity in the pathogenesis of Chagas disease.
Acquired Immunity against Trypanosoma cruzi Infection and Vaccine Development
Authors: Martins Rodrigues Maurício , Cunha de Alencar Bruna , Ronnie Vasconcelos José
Published: August 2009

The obligatory intracellular protozoan Trypanosoma cruzi is an extremely successful parasite
infecting a vast number of distinct mammalian hosts across the Americas. T. cruzi relies heavily on the
innate and adaptive immunological mechanisms to maintain the host alive during the acute phase and to
establish a chronic infection, when the transmission to the invertebrate host occurs. This long term
persistence is considered a major force behind the chronic symptoms of the disease observed in humans.
Mechanisms that keep host alive during the acute phase have been dissected using genetically deficient
mice and they include Toll-like receptors, cytokines (Interferon-gamma, TNF-α, MIF and IL-12),
lymphocytes (B, CD4, CD8 and NKT) and NK cells. Target antigens for specific lymphocytes are
members of the trans-sialidase, mucin-like, cysteine protease families, etc. Vaccination studies are being
performed using different delivery systems such as recombinant proteins, plasmid DNA and
microorganisms. Non-antibody mediated cellular immune responses (CD4+ Th1 and CD8+ Tc1) to
specific parasite antigens/genes can indeed be used for the purpose of vaccination against acute phase
mortality and, in some cases, chronic phase pathology. These results obtained in the mouse model indicate
a possible path for a veterinary or human vaccine development
Clinic Presentation of Chagas Disease
Authors: R.L. Teixeira Antonio
Published: August 2009

What happens to a person infected with the parasite Trypanosoma cruzi? The answer
to this question is essential to the formulation of new ideas throughout the reading of this
chapter, as over two thirds of individuals who acquired the infection will never present any
clinic manifestation related to Chagas disease. Only 5% or less of acute infected individuals will
present symptoms such as fever, generalized joint and muscle pain, indisposition, headache and
other unspecific symptoms of a common cold. The other 95% patients are asymptomatic or do
not report symptoms that allow the healthcare professional to suspect and/or confirm the acute
phase diagnosis of Chagas disease. After three to six months, the patients get to the
intermediary phase of the chronic infection in the absence of signs or symptoms. However,
three or more decades later, circa of one third of the infected individuals may present chronic
Chagas disease symptoms. It is known that 94.5% of chronic chagasic patients will present
manifestations of heart disease and the remaining 5.5% will present esophagus disease
(megaesophagus) or large intestine manifestations (megacolon).
The Pathology of Chagas Disease
Authors: Teixeira Antonio , Pimentel Fernando , Cordeiro Ciro
Published: August 2009

In the acute phase of Chagas disease the nests of Trypanosoma cruzi amastigote
forms are found in tissues, especially in cardiac, skeletal and smooth muscle cells from human
body. However the most important element of severe injuries formation in the heart and
digestive tube tissues is the lymphocyte and macrophage cells infiltration triggering the
destruction of normal, non-parasitized heart muscles, and ganglia from the intestine and
peripheral nervous system. The non-parasitized target cells destruction caused by lymphocytes
and macrophages from the immune system is particularly evident during the chronic phase of
the chagasic infection. The severe inflammation weakens the organs, leading to dilatation and to
insufficiency. The cellular death implies in replacement by fibrous scars which are only a
sequelae from the rejection of the “self” tissue.
Lateral Transfer of Minicircle Sequences of kDNA from Trypanosoma cruzi to the Genome of the Vertebrate Host
Authors: Nitz Nadjar , Teixeira Antonio
Published: August 2009

The treatment of the Trypanosoma cruzi infection with anti-trypanosome drugs did not
interrupt the progression of the cardiac lesion in rabbits and in humans. Then, the question arose:
what would sustain the active lesion in the chagasic heart? A hypothesis of horizontal transference of
DNA from T. cruzi to the genome of the host was proposed because it could answer this question. The
investigation showed that minicircle sequences from the parasite are transferred into specific sites of
the rabbit genome and, also, of the primate genome and a main hotspot of integration was the
retrotransposon LINE-1. Using a model of in vitro infection it was possible to demonstrate that the
kDNA integrated to the LINE-1 could be mobilized to other genome site within the host cell. This
demonstration suggested that the mutation-induced modification in the genotype and in the phenotype
of the target cell, which may accumulate along the cryptic chronic infection, might explain the
variability of clinic manifestations of the human disease as well as the origin and progression of the
rejection of the non-parasitized cell over time. This explanation justifies the long period between the
initial infection and the triggering of the disease. According to this theory, the parasite acts as a
mutation vector and the altered cells are recognized as not-self and are rejected by the immune
defense system.
The Pathogenesis of Chagas Disease in Mammals and Birds
Authors: RL Teixeira Antonio , Nitz Nadjar , F Araujo Perla , M Hecht Mariana
Published: August 2009

After the horizontal transference of kDNA minicircle sequences into the
genome of chagasic mammals it was possible to show the heritage of the kDNA mutation
into those rabbits breed. However, mammals are permissive to infection by T. cruzi,
which may persist through the animal life. To ensure that the kDNA mutation was not
only a noise produced by the cryptic infection it was necessary to dismiss this possibility.
This was possible through experiments using birds that are refractory to T. cruzi infection
but are permissive to infection only in the first 10 days of embryonic life. When the fertile
eggs were inoculated with T. cruzi the breed was born without infection but presenting the
kDNA mutation. In this regard, rabbits and birds with kDNA mutation presented typical
Chagas disease lesions: minimal rejection unit which is characteristic of the pathology of
this disease where the non-parasitized target cell was destroyed by the cells from the
vertebrate host´s immune system. These experiments showed that the minimal rejection
unit is the common denominator of the pathogenesis of Chagas disease in vertebrate
animals. In the chicken model refractory to T. cruzi the cardiomegaly was linked to the
minimal rejection unit’s inflammatory infiltration. Therefore the parasite-free chicken
heart pathology seen in kDNA-mutated chickens could be linked to the genotype and
phenotype alterations. The mechanism whereby these alterations induce the immune
rejection of the chicken’s heart requires further investigation.
The Treatment of Chagas Disease
Authors: Lauria-Pires Liana , de Cassia Rosa Ana , Magalhães Rozeneide , Nery de Castro Cleudson
Published: August 2009

Presently, the treatment of the infection by Trypanosoma cruzi has been
considered unsatisfactory. The eradication of the infection and the interruption of
the chronic disease evolution have not been reached by treatment in several clinic
and experimental trials. To be unanimous, the indication of determined treatment it
should be deposed of undesirable side effects and, even if it did not produce the cure
(elimination) of the infection, it should at least stop its evolution. However, the
treatment with anti-trypanosome nitro derivatives did not show a clear advantage,
when cost and effectiveness were analyzed. Although millions of people with the
acute T. cruzi infection do not present a clinic disease, the treatment is clearly
indicated in several situations in which the patient’s life is in danger. The
controversy on the efficacy of the treatment of T. cruzi infection with the available
drugs shows that this is one of the aspects of the investigation on Chagas disease
that deserve research incentives. The suggestion that the pathogenesis of the disease
is associated to the introduction of kDNA mutations from the parasite’s genome to
the host’s defines the need of one or more drugs that are truly effective against the
infection. The persistence of the infection, throughout the life of the patient may
represent a source of kDNA which introduces cumulative mutations. The effect of
these mutations on the evolution of the disease could be avoided with the infection
elimination. Maybe, this is an aspect of scientific research with possibilities of
generating real benefits to the 18 million people infected by T. cruzi, reminding that
one third of them will present clinic manifestations of Chagas disease.
Perspectives in Drug Development for Chagas Disease Therapy
Authors: M. Dourado Bastos Izabela , Neves David , M. Lima Meire , M. Santana Jaime
Published: August 2009

Research has advanced towards the identification of potential drug targets in
Trypanosoma cruzi as well as the development of new effective drugs for the chemotherapy of
Chagas disease. The first crucial step in this protozoan life cycle within the vertebrate host is the
process of entry into a mammalian cell. Enzymes actively participating in this process are
naturally good drug-target candidates. Right after cell invasion, trypomastigote forms of T. cruzi
must differentiate into amastigotes so as to proceed in their life cycle. The inhibition of key
enzymes from the sugar metabolism, the lipids synthesis, the digestion of host-internalized
proteins and also from the purines salvage pathway could hinder parasite growth, thus placing
these enzymes as potential drug targets. When the cell is populated, amastigotes must differentiate
into trypomastigotes, which will then leave the cell to infect others and hence restart the cycle.
Once well adapted to the intracellular environment, T. cruzi can use several different pathways for
infection and differentiation. Therefore, the best strategy to develop drugs for Chagas disease
therapy is the plural conception of drugs, that is, to consider as targets several enzymes involved
in different physiological processes. So, a drug cocktail would be efficient to treat T.cruzi
infections. Another important step in drug development is the determination of the target’s
tridimensional structure. The knowledge of its architecture facilitates the rational design of
molecules from the enzyme active site. These strategies are believed to provide drugs not only
efficient but also with low side effects for the treatment of Chagas’ disease.
Environment, Interactions Between Trypanosoma cruzi and its Host, and Health
Authors: Teixeira Antonio , Gomes Clever , Lozzi Silene , Hecht Mariana , Rosa Ana , Monteiro, Pedro , Bussacos Ana , Nitz Nadjar , McManus Concepta
Published: August 2009

An intricate epidemiological chain involving the flagellate protozoan Trypanosoma
cruzi is discussed at the environmental level, and in terms of fine molecular interactions in
invertebrate and vertebrate hosts dwelling in different ecosystems. This protozoan has a complex,
genetically controlled plasticity, which confers adaptation to approximately 40 blood-suckling
triatomine species and to over 1,000 mammalian species, fulfilling diverse metabolic
requirements in its complex life-cycle. The T. cruzi infections are deeply embedded in countless
ecotypes, where they are difficult to defeat using the control methods that are currently available.
Many more field and laboratory studies are required to obtain data and information that may be
used for the control and prevention of T. cruzi infections and their various disease manifestations.
Emphasis should be placed on those sensitive interactions at the cellular and environmental levels
that could become selected targets for disease prevention. In the short term, new technologies for
social mobilization should be used by people and organizations working for justice and equality
through health information and promotion. A mass media directed program could deliver
education, information and communication needed to protect the inhabitants at risk of contracting
T. cruzi infections.