2,178 research outputs found
Angiogenic and Metastatic Determinants of Malignant Melanoma
Cutaneous melanoma or malignant melanoma of the skin is a highly metastatic disease, with an increasing rate of incidence, poor prognosis and high resistance to therapeutic intervention. Although early diagnosis and surgical resection of the primary lesion could significantly improve survival, the high propensity of melanomas to disseminate through intradermal, haematogenous and lymphatic routes to regional and visceral sites leads to poor prognosis and high mortality rates. While the clinical staging and progression of melanoma is well defined, the molecular etiology of the disease is less well characterized. The principal goal of this thesis was to obtain novel mechanistic insights into melanoma biology and identify molecular determinants of this disease.
We identified the capacity of melanoma-derived small molecules to promote long-term survival of endothelial cells under severe hypoxic conditions. This observation excludes known proangiogenic molecules which have been the focus of anti-angiogenic therapies and sets the stage for the identification of novel regulators with therapeutic potential. Moreover, TIMP3 was identified as a dominant negative regulator of melanoma development. The inhibitory role of TIMP3 in melanoma angiogenesis was validated and further extended to clinical samples from melanoma patients. We showed that promoter methylation mediated TIMP3 silencing impacts clinical outcome in melanoma and also evaluated the implications of the tumor suppressor role of TIMP3 in melanoma metastasis, using matched samples from melanoma patients. A decrease in TIMP3 expression with observed with disease progression and further TIMP3 inhibited melanoma cell migration and invasion. To characterize core mediators of the metastatic cascade of melanomas, we determined the migratory profile of melanoma cell lines and performed correlation analysis to identify potential genetic modulators. WNT5A was identified as a dominant regulator of the metastatic cascade in melanoma and further we show that WNT5A inhibition decreases the migratory and metastatic potential of melanoma cells.
Additionally, this thesis describes novel tools to quantitatively characterize several biological processes. The ring barrier-based migration assay enables the quantitative assessment of several parameters of cell migration. The eNOS-Tag-GFP mouse model provides a platform for the in vivo and ex vivo study of early angiogenic events in physiological and pathological conditions. Collectively, the results presented in this thesis identify crucial pathophysiological determinants of melanoma. These insights and tools may further guide the discovery of novel regulators of melanoma biology and result in the implementation of new treatment rationales for therapeutic benefit
Promoting the first generation women entrepreneurs in Sri Lanka: a lesson from India
The women entrepreneurs of Sri Lanka were victims of war. They did
not become entrepreneurs out of choice; they became entrepreneurs as a result of war, in
their pursuit of supporting themselves and their families. Majority of them were in
business for the first time as they lost their husbands and/or children to the war and saw
business as a means to end and their success in the venture is making a balance between
family and work. These women were educated with a minimum level education and
were involved in businesses such as livestock farming, services and craft/textile which
did not require a high capital outlay and expert skills and knowledge of the business.
While the international attention has somewhat shifted elsewhere, the
international community are still trying to play a constructive role in building up a postwar
Sri Lanka. What is more difficult to know- is what strategies (long and short term)
exists for development in Sri Lanka? How will the civilians more particularly women
start a new life after the camps and how will they become self-sufficient? In this context
the present paper entitled "Promoting the First Generation Women Entrepreneurs in Sri
Lanka: A lesson from India" is a modest attempt to unearth the problems and prospects
of women entrepreneurs in retail trade. By taking a sample of 281 women and 161 men
retail-traders from India, the results confirm the fact that, though women retail-traders
face a lot of problems in transacting their business, still there exists a better scope for
growth.
The findings of this research are important for several reasons. The women
entrepreneurs of the Sri Lanka, like anywhere in the world are powerful driving force
for the economic development of the country. The findings of the study will certainly
pave the way for the up liftmen of socio-economic status of first generation women
entrepreneurs in war-torn areas of Sri Lanka
Pseudo-Schwarzschild Spherical Accretion as a Classical Black Hole Analogue
We demonstrate that a spherical accretion onto astrophysical black holes,
under the influence of Newtonian or various post-Newtonian pseudo-Schwarzschild
gravitational potentials, may constitute a concrete example of classical
analogue gravity naturally found in the Universe. We analytically calculate the
corresponding analogue Hawking temperature as a function of the minimum number
of physical parameters governing the accretion flow. We study both the
polytropic and the isothermal accretion. We show that unlike in a general
relativistic spherical accretion, analogue white hole solutions can never be
obtained in such post-Newtonian systems. We also show that an isothermal
spherical accretion is a remarkably simple example in which the only one
information--the temperature of the fluid, is sufficient to completely describe
an analogue gravity system. For both types of accretion, the analogue Hawking
temperature may become higher than the usual Hawking temperature. However, the
analogue Hawking temperature for accreting astrophysical black holes is
considerably lower compared with the temperature of the accreting fluid.Comment: Final Version to appear in the journal General Relativity &
Gravitation, Volume 27, Issue 11, 2005. 17 pages, Two colour and one black
and white figures. Typos corrected. Recent reference on analogue effect in
relativistic accretion disc adde
Gauge Theory Correlators from Non-Critical String Theory
We suggest a means of obtaining certain Green's functions in 3+1-dimensional
supersymmetric Yang-Mills theory with a large number of colors
via non-critical string theory. The non-critical string theory is related to
critical string theory in anti-deSitter background. We introduce a boundary of
the anti-deSitter space analogous to a cut-off on the Liouville coordinate of
the two-dimensional string theory. Correlation functions of operators in the
gauge theory are related to the dependence of the supergravity action on the
boundary conditions. From the quadratic terms in supergravity we read off the
anomalous dimensions. For operators that couple to massless string states it
has been established through absorption calculations that the anomalous
dimensions vanish, and we rederive this result. The operators that couple to
massive string states at level acquire anomalous dimensions that grow as
2\left (n g_{YM} \sqrt {2 N} )^{1/2} for large `t Hooft coupling. This is a
new prediction about the strong coupling behavior of large SYM theory.Comment: 15 pages, harvmac with btxmac; minor revisions, 1 reference added,
the version to appear in Physics Letters
Corporate behaviours towards foreign exchange risk management Practices: an investigative study in Indian scenario
Indian economy in the post-liberalisation era has witnessed increasing awareness of the need
for introduction of various risk management products to enable hedging against market risk
in a cost effective way. This industry-wide, cross-sectional study concentrates on recent
foreign exchange risk management practices and derivatives product usage by large nonbanking
Indian-based firms. The study is exploratory in nature and aims at an understanding
the risk appetite and FERM (Foreign Exchange Risk Management) practices of Indian
corporate enterprises. This study focuses on the activity of end-users of financial derivatives
and is confined to 501 non-banking corporate enterprises. A combination of simple random
and judgement sampling was used for selecting the corporate enterprises and the major
statistical tools used were Correlation and Factor analysis. The factor analysis finds that there
are three derived factors of non-usage of derivative products namely, Perceptual Issues,
Technical & policy factor and Pricing & Cost considerations. Further, the correlation
analysis reveals positive relation between the nine variables representing the reasons as nonusage
of derivatives by Indian corporates. The study finds wide usage of derivative products
for risk management and the prime reason of hedging is reduction in volatility of cash flows.
VAR (Value-at-Risk) technique was found to be the preferred method of risk evaluation by
maximum number of Indian corporate. Further, in terms of the external techniques for risk
hedging, the preference is mostly in favour of forward contracts, followed by swaps and
cross-currency options This article throws light on various concerns of Indian firms
regarding derivative usage and reasons for non-usage, apart form techniques of risk hedging,
risk evaluation methods adopted, risk management policy and types of derivatives used
Particle Production in Matrix Cosmology
We consider cosmological particle production in 1+1 dimensional string
theory. The process is described most efficiently in terms of anomalies, but we
also discuss the explicit mode expansions. In matrix cosmology the usual vacuum
ambiguity of quantum fields in time-dependent backgrounds is resolved by the
underlying matrix model. This leads to a finite energy density for the "in"
state which cancels the effect of anomalous particle production.Comment: 24 pages, 1 figure; v2: references added, minor change
HIV infection significantly reduces lipoprotein lipase which remains low after 6 months of antiretroviral therapy
Purpose of the study
Fractional clearance rate of apolipoprotein B100-containing
lipoproteins is reduced in HIV infection before and
after antiretroviral (ARV) treatment [1]. We compared
lipoprotein lipase (LPL) activity and gene expression in
HIV-positive subjects before and 6 months after ARV with
HIV-negative controls.
Methods
Fasting blood post heparin total and hepatic lipase activity,adiponectin, leptin, insulin, glucose, and lipid measurementswere made in 32 HIV-infected and 15 HIVnegative
controls. LPL was estimated by subtractinghepatic lipase from total lipase. Adiponectin, LPL andhormone sensitive lipase (HSL) gene expression weremeasured from iliac crest subcutaneous fat biopsies.Patients were tested before, and 6 months after randomisation to AZT/3TC (n = 15) or TDF/FTC (n = 17) with EFV.Between-group comparison was by Mann-Whitney andpaired samples by the Wilcoxon signed rank tests.
Summary of results
There were no differences in gender, ethnicity, baseline
BMI, regional fat distribution (whole body DEXA) and
visceral (VAT) and subcutaneous fat (SAT) measured by
abdominal CT scans between controls and patients. Trunk
fat/BMI ratio, VAT and VAT:SAT ratio significantly
increased after 6-month ARV therapy (p = 0.01). There
were no differences between groups in serum NEFA,HOMA and leptin levels. Selected other results are shown
in Table 1.
Conclusion
Post heparin lipoprotein lipase activity is reduced in HIV
and does not return to control levels after 6 months of
ARV therapy. AZT-containing regimens are associated
with a greater increase in LPL, LPL gene expression and
plasma adiponectin than TDF
Validity of the zero-thermodynamic law in off-equilibrium coupled harmonic oscillators
In order to describe the thermodynamics of the glassy systems it has been
recently introduced an extra parameter also called effective temperature which
generalizes the fluctuation-dissipation theorem (FDT) to systems
off-equilibrium and supposedly describes thermal fluctuations around the aging
state. Here we investigate the applicability of a zero-th law for
non-equilibrium glassy systems based on these effective temperatures by
studying two coupled subsystems of harmonic oscillators with Monte Carlo
dynamics. We analyze in detail two types of dynamics: 1) sequential dynamics
where the coupling between the subsystems comes only from the Hamiltonian and
2) parallel dynamics where there is a further coupling between the subsystems
arising from the dynamics. We show that the coupling described in the first
case is not enough to make asymptotically the effective temperatures of two
interacting subsystems coincide, the reason being the too small thermal
conductivity between them in the aging state. This explains why different
interacting degrees of freedom in structural glasses may stay at different
effective temperatures without never mutually thermalizing.Comment: 23 pages, REVTeX, 4 eps figure
On The Problem of Particle Production in c=1 Matrix Model
We reconsider and analyze in detail the problem of particle production in the
time dependent background of matrix model where the Fermi sea drains away
at late time. In addition to the moving mirror method, which has already been
discussed in hep-th/0403169 and hep-th/0403275, we describe yet another method
of computing the Bogolubov coefficients which gives the same result. We
emphasize that these Bogolubov coefficients are approximately correct for small
value of the deformation parameter.
We also study the time evolution of the collective field theory stress-tensor
with a special point-splitting regularization. Our computations go beyond the
approximation of the previous treatments and are valid at large coordinate
distances from the boundary at a finite time and up-to a finite coordinate
distance from the boundary at late time. In this region of validity our
regularization produces a certain singular term that is precisely canceled by
the collective field theory counter term in the present background. The energy
and momentum densities fall off exponentially at large distance from the
boundary to the values corresponding to the static background. This clearly
shows that the radiated energy reaches the asymptotic region signaling the
space-time decay.Comment: 37 pages, 5 figures. Section 6 is modified to clarify main
accomplishments of the paper including a discussion comparing stress-tensor
analysis with those preexisted in literature. Other modifications include
minor changes in the text and addition of one reference. Version accepted for
publication in JHE
On the Nonperturbative Consistency of String Theory
An infinite number of distinct matrix models reproduce the perturbation
theory of string theory. Due to constraints of causality, however, we
argue that none of the existing constructions gives a consistent
nonperturbative definition of the string.Comment: 10 pages, 2 figures, LaTeX (author's name added
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