bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrin β3-mediated Src activation regulates apoptosis in IEC-6 cells via Akt and STAT3
Authors: Bhattacharya Sujoy , Ray Ramesh M. , Johnson Leonard R.
Published: July 2006

Intestinal epithelial (IEC-6) cells are resistant to apoptosis following the inhibition of ODC (ornithine decarboxylase) and subsequent polyamine depletion. The depletion of polyamines rapidly activates NF-κB (nuclear factor κB) and STAT3 (signal transducer and activator of transcription 3), which is responsible for the observed decrease in apoptosis. Since both NF-κB and STAT3 signalling pathways can be activated by Src kinase, we examined its role in the antiapoptotic response. Inhibition of ODC by DFMO (α-difluoromethylornithine) increased the activity of Src and ERK1/2 (extracellular-signal-regulated kinase 1/2) within 30 min, which was prevented by exogenous polyamines added to the DFMO-containing medium. Conversely, epidermal growth factor-mediated Src and ERK1/2 activation was not prevented by the addition of polyamines. Inhibition of Src with PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine} and a DN-Src (dominant-negative Src) construct prevented the activation of Akt, JAK (Janus kinase) and STAT3. Spontaneous apoptosis was increased in DN-Src-expressing cells and the protective effect of polyamine depletion was lost. Polyamine depletion by DFMO increased integrin β3 Tyr785 phosphorylation. Cells plated on fibronectin had significantly higher β3 phosphorylation and Src activation compared with plastic. Exogenous polyamines added to the fibronectin matrix prevented Src activation. Arg-Gly-Asp-Ser inhibited β3, Src and Akt phosphorylation and sensitized polyamine-depleted cells to tumour necrosis factor α/cycloheximide-mediated apoptosis. Fibronectin activated Src and subsequently protected cells from apoptosis. Together, these results suggest that the inhibition of ODC rapidly removes a small pool of available polyamines triggering the activation of β3 integrin, which in turn activates Src. The subsequent Akt and JAK activation is accompanied by translocation of NF-κB and STAT3 to the nucleus and the synthesis of antiapoptotic proteins.
Anomalous scattering analysis of Agrobacterium radiobacter phosphotriesterase: the prominent role of iron in the heterobinuclear active site
Authors: Jackson Colin J. , Carr Paul D. , Kim Hye-Kyung , Liu Jian-Wei , Herrald Paul , Mitić Nataša , Schenk Gerhard , Smith Clyde A. , Ollis David L.
Published: July 2006

Bacterial phosphotriesterases are binuclear metalloproteins for which the catalytic mechanism has been studied with a variety of techniques, principally using active sites reconstituted in vitro from apoenzymes. Here, atomic absorption spectroscopy and anomalous X-ray scattering have been used to determine the identity of the metals incorporated into the active site in vivo. We have recombinantly expressed the phosphotriesterase from Agrobacterium radiobacter (OpdA) in Escherichia coli grown in medium supplemented with 1 mM CoCl2 and in unsupplemented medium. Anomalous scattering data, collected from a single crystal at the Fe–K, Co–K and Zn–K edges, indicate that iron and cobalt are the primary constituents of the two metal-binding sites in the catalytic centre (α and β) in the protein expressed in E. coli grown in supplemented medium. Comparison with OpdA expressed in unsupplemented medium demonstrates that the cobalt present in the supplemented medium replaced zinc at the β-position of the active site, which results in an increase in the catalytic efficiency of the enzyme. These results suggest an essential role for iron in the catalytic mechanism of bacterial phosphotriesterases, and that these phosphotriesterases are natively heterobinuclear iron–zinc enzymes.
Structural features of mouse telomerase RNA are responsible for the lower activity of mouse telomerase versus human telomerase
Authors: Garforth Scott J. , Wu Yan Yun , Prasad Vinayaka R.
Published: July 2006

Human and mouse telomerases show a high degree of similarity in both the protein and RNA components. Human telomerase is more active and more processive than the mouse telomerase. There are two key differences between hTR [human TR (telomerase RNA)] and mTR (mouse TR) structures. First, the mouse telomerase contains only 2 nt upstream of its template region, whereas the human telomerase contains 45 nt. Secondly, the template region of human telomerase contains a 5-nt alignment domain, whereas that of mouse has only 2 nt. We hypothesize that these differences are responsible for the differential telomerase activities. Mutations were made in both the hTR and mTR, changing the template length and the length of the RNA upstream of the template, and telomerase was reconstituted in vitro using mouse telomerase reverse transcriptase generated by in vitro translation. We show that the sequences upstream of the template region, with a potential to form a double-stranded helix (the P1 helix) as in hTR, increase telomerase activity. The longer alignment domain increases telomerase activity only in the context of the P1 helix. Thus the TR contributes to regulating the level of activity of mammalian telomerases.
Cellular mechanisms underlying the cardiovascular actions of oestrogens
Authors: Ling Shanhong , Komesaroff Paul , Sudhir Krishnankutty
Published: July 2006

Although pre-menopausal women enjoy relative cardiovascular protection, hormone (oestrogen±progestin)-replacement therapy has not shown cardiovascular benefits in post-menopausal women, suggesting that the effects of oestrogens on the cardiovascular system are much more complex than previously expected. Endothelial cells, smooth muscle cells, cardiac myocytes and fibroblasts, the cellular components of blood vessels and the heart, play important roles in cardiovascular health and disease. During the development and progression of cardiovascular disease, changes occur both in the structure and function of these cells, resulting in a wide range of abnormalities, which affect growth, death and physiological function. These cells contain functional oestrogen receptors and are targets for oestrogen action. This review focuses on recent studies on the effects of oestrogen on cardiovascular cell function. Oestrogens, particularly 17β-oestradiol, exert multiple effects on cardiovascular cells, and these effects may contribute to the gender-associated protection against cardiovascular diseases.
Liver breath tests non-invasively predict higher stages of non-alcoholic steatohepatitis
Authors: Portincasa Piero , Grattagliano Ignazio , Lauterburg Bernhard H. , Palmieri Vincenzo O. , Palasciano Giuseppe , Stellaard Frans
Published: July 2006

Effectively assessing subtle hepatic metabolic functions by novel non-invasive tests might be of clinical utility in scoring NAFLD (non-alcoholic fatty liver disease) and in identifying altered metabolic pathways. The present study was conducted on 39 (20 lean and 19 obese) hypertransaminasemic patients with histologically proven NAFLD {ranging from simple steatosis to severe steatohepatitis [NASH (non-alcoholic steatohepatitis)] and fibrosis} and 28 (20 lean and eight overweight) healthy controls, who underwent stable isotope breath testing ([13C]methacetin and [13C]ketoisocaproate) for microsomal and mitochondrial liver function in relation to histology, serum hyaluronate, as a marker of liver fibrosis, and body size. Compared with healthy subjects and patients with simple steatosis, NASH patients had enhanced methacetin demethylation (P=0.001), but decreased (P=0.001) and delayed (P=0.006) ketoisocaproate decarboxylation, which was inversely related (P=0.001) to the degree of histological fibrosis (r=−0.701), serum hyaluronate (r=−0.644) and body size (r=−0.485). Ketoisocaproate decarboxylation was impaired further in obese patients with NASH, but not in patients with simple steatosis and in overweight controls. NASH and insulin resistance were independently associated with an abnormal ketoisocaproate breath test (P=0.001). The cut-off value of 9.6% cumulative expired 13CO2 for ketoisocaproate at 60 min was associated with the highest prediction (positive predictive value, 0.90; negative predictive value, 0.73) for NASH, yielding an overall sensitivity of 68% and specificity of 94%. In conclusion, both microsomal and mitochondrial functions are disturbed in NASH. Therefore stable isotope breath tests may usefully contribute to a better and non-invasive characterization of patients with NAFLD.
Effect of fatty acids on endothelium-dependent relaxation in the rabbit aorta
Authors: Edirisinghe Indika , McCormick Hallam Kellie , Kappagoda C. Tissa
Published: July 2006

The metabolic syndrome, Type II (non-insulin-dependent) diabetes and obesity are associated with endothelial dysfunction and increased plasma concentrations of NEFAs (non-esterified fatty acids; free fatty acids). The present study was undertaken to define the inhibitory effects of saturated NEFAs on EDR (endothelium-dependent relaxation). Experiments were performed in rings of rabbit aorta to establish (i) dose–response relationships, (ii) the effect of chain length, (iii) the effect of the presence of double bonds, (iv) reversibility and time course of inhibition, and (v) the effect on nitric oxide production. Aortic rings were incubated (1 h) with NEFA–albumin complexes derived from lauric (C12:0), myristic (C14:0), palmitic (C16:0), stearic (C18:0) and linolenic (C18:3) acids. EDR induced by acetylcholine (0.1–10 μmol/l) was measured after pre-contraction with noradrenaline. Inhibition of EDR was dose-dependent (0.5–2 mmol/l NEFA), and the greatest inhibition (51%) was observed with stearic acid (2 mmol/l). Lauric acid had the smallest inhibitory effect. The inhibitory effects were always reversible and were evident after 15 min of incubation. Linolenic acid caused a significantly lower inhibition of EDR than stearic acid. SOD (superoxide dismutase) restored the inhibitory effect caused by NEFAs, suggesting the involvement of ROS (reactive oxygen species) in removing nitric oxide. The nitric oxide concentration measured after exposure of the rings to acetylcholine was lower after incubation with NEFAs than with Krebs buffer alone. This finding is consistent with removal of nitric oxide by ROS. This claim was supported by the demonstration of increased concentrations of nitrated tyrosine in the rings incubated with NEFAs.
Therapeutic potential of immunostimulatory monoclonal antibodies
Authors: Gray Juliet C. , Johnson Peter W. M. , Glennie Martin J.
Published: July 2006

The aim of cancer immunotherapy is to employ the specificity of the immune system to provide a more effective, less toxic, treatment compared with conventional therapies. Although many strategies have been used to try to generate effective anticancer immune responses, very few have reached mainstream clinical use. A new approach introduced over the last few years is to use immunostimulatory mAbs (monoclonal antibodies) to boost weak endogenous antitumour immune responses to levels which are therapeutic. Such agonistic or antagonistic mAbs bind to key receptors in the immune system acting to enhance antigen presentation, provide co-stimulation or to counteract immunoregulation. In animal models, this approach has been shown to promote powerful tumour-specific T-cell responses capable of clearing established tumour and leaving the animal with long-term immunity. In addition to this impressive therapy seen in tumour models, these same mAbs also have the potential to be therapeutically useful in autoimmune and infectious diseases. This review discusses the use of these mAbs as therapeutic agents, their advantages and disadvantages and the challenges that need to be overcome to use them clinically.
Glycaemic instability is an underestimated problem in Type II diabetes
Authors: Praet Stephan F. E. , Manders Ralph J. F. , Meex Ruth C. R. , Lieverse A. G. , Stehouwer Coen D. A. , Kuipers Harm , Keizer Hans A. , van Loon Luc J. C.
Published: July 2006

The aim of the present study was to assess the level of glycaemic control by the measurement of 24 h blood glucose profiles and standard blood analyses under identical nutritional and physical activity conditions in patients with Type II diabetes and healthy normoglycaemic controls. A total of 11 male patients with Type II diabetes and 11 healthy matched controls participated in a 24 h CGMS (continuous subcutaneous glucose-monitoring system) assessment trial under strictly standardized dietary and physical activity conditions. In addition, fasting plasma glucose, insulin and HbA1c (glycated haemoglobin) concentrations were measured, and an OGTT (oral glucose tolerance test) was performed to calculate indices of whole-body insulin sensitivity, oral glucose tolerance and/or glycaemic control. In the healthy control group, hyperglycaemia (blood glucose concentration >10 mmol/l) was hardly present (2±1% or 0.4±0.2/24 h). However, in the patients with Type II diabetes, hyperglycaemia was experienced for as much as 55±7% of the time (13±2 h over 24 h) while using the same standardized diet. Breakfast-related hyperglycaemia contributed most (46±7%; P<0.01 as determined by ANOVA) to the total amount of hyperglycaemia and postprandial glycaemic instability. In the diabetes patients, blood HbA1c content correlated well with the duration of hyperglycaemia and the postprandial glucose responses (P<0.05). In conclusion, CGMS determinations show that standard measurements of glycaemic control underestimate the amount of hyperglycaemia prevalent during real-life conditions in Type II diabetes. Given the macro- and micro-vascular damage caused by postprandial hyperglycaemia, CGMS provides an excellent tool to evaluate alternative therapeutic strategies to reduce hyperglycaemic blood glucose excursions.
Nuclear Proliferation: The Islamic Republic of Iran
Authors: Bahgat Gawdat
Published: July 2006

Since the mid-1980s, Israel, thGawdat Bahgate United States, and other Western powers have accused Iran of pursuing nuclear weapons capability. Iranian officials have categorically denied these accusations and claimed that their nuclear program is designed for civilian purposes. This essay examines the history of Iran's nuclear program since the late 1950s and analyzes the forces that shape the country's nuclear policy. These forces include perception of security threats from Pakistan, Iraq, Israel, and the United States; domestic economic and political dynamics; and national pride. The following section will discuss the European and Russian stance on Iran's nuclear ambition as well as the International Atomic Energy Agency's efforts to reach a compromise that would satisfy the international community's concerns and Tehran's demands. The essay concludes with some predictions on how Iran's nuclear program is likely to evolve in the next few decades.
Communications, Qajar Irredentism, and the Strategies of British India: The Makran Coast Telegraph and British policy of Containing Persia in the East (Baluchistan)—Part I
Authors: Shahvar Soli
Published: July 2006

Qajar irredentism brought Persia to make some advances in Baluchistan in the 1830s and 1840s, but in early 1860s, the continuation of this advance was threatened by one of Britain's main imperial interests and needs: the Indo-European telegraph line, which was to cross the Makran Coast overland. Persia sought to use this need for getting British recognition for its claims over Baluchistan. This put the British under pressure, for they did not wish to alienate Persia, through whose territories the line was to pass. The British government tried to appease the Persians with a simple declaration that the telegraph would not affect their claims and by taking the telegraph away from disputed territories. One major thing was faulty in this “solution,” for it was the British who decided which territories were “disputed” or “undisputed,” not the Persians.
Memoir as Iranian Exile Cultural Production: A case study of Marjane Satrapi'sPersepolisSeries
Authors: Malek Amy
Published: July 2006

In this essay, Iranian exile cultural production is examined via a cultural studies approach, applying Hamid Naficy's work on the concept of liminality and its productive potential to analyze the Iranian women's memoir phenomenon of the past eleven years. Focus is placed primarily upon Marjane Satrapi's graphic novelPersepolis, which is analyzed as part of this larger memoir phenomenon. I will argue thatPersepolisis a prime example of exile cultural production—as a site for experimentation within various genres (here, that of the memoir and graphic novel), and also for identity negotiation, self-reflection, and cultural translation—thanks to the liminality and hybridity of an artist and author who feels she is “in-between.”
State Repression in the Iranian Bazaar, 1975–1977: The Anti-Profiteering Campaign and an Impending Revolution
Authors: Mazaheri Nimah
Published: July 2006

This article examines state repression in the Iranian bazaar during the anti-profiteering campaign from 1975–1977. While many have argued that the anti-profiteering campaign helped spark the revolutionary mobilization of the bazaar itself, this article posits that scholars should also consider the notion that the campaign helped to foster popular support for the revolutionary movement as a whole. Given the bazaar's ties to middle and lower classes of Iranian society, as well as their status as the country's “economic barometer,” this article presents the theory that the anti-profiteering campaign played a role in generating popular discontent against the former regime in the period just prior to the 1979 Revolution.
An inhibitory role for FAK in regulating proliferation: a link between limited adhesion and RhoA-ROCK signaling
Authors: Pirone Dana M. , Liu Wendy F. , Ruiz Sami Alom , Gao Lin , Raghavan Srivatsan , Lemmon Christopher A. , Romer Lewis H. , Chen Christopher S.
Published: July 2006

Focal adhesion kinase (FAK) transduces cell adhesion to the extracellular matrix into proliferative signals. We show that FAK overexpression induced proliferation in endothelial cells, which are normally growth arrested by limited adhesion. Interestingly, displacement of FAK from adhesions by using a FAK−/− cell line or by expressing the C-terminal fragment FRNK also caused an escape of adhesion-regulated growth arrest, suggesting dual positive and negative roles for FAK in growth regulation. Expressing kinase-dead FAK-Y397F in FAK−/− cells prevented uncontrolled growth, demonstrating the antiproliferative function of inactive FAK. Unlike FAK overexpression–induced growth, loss of growth control in FAK−/− or FRNK-expressing cells increased RhoA activity, cytoskeletal tension, and focal adhesion formation. ROCK inhibition rescued adhesion-dependent growth control in these cells, and expression of constitutively active RhoA or ROCK dysregulated growth. These findings demonstrate the ability of FAK to suppress and promote growth, and underscore the importance of multiple mechanisms, even from one molecule, to control cell proliferation.
Paraxial protocadherin mediates cell sorting and tissue morphogenesis by regulating C-cadherin adhesion activity
Authors: Chen Xuejun , Gumbiner Barry M.
Published: July 2006

Little is known about how protocadherins function in cell adhesion and tissue development. Paraxial protocadherin (PAPC) controls cell sorting and morphogenetic movements in the Xenopus laevis embryo. We find that PAPC mediates these functions by down-regulating the adhesion activity of C-cadherin. Expression of exogenous C-cadherin reverses PAPC-induced cell sorting and gastrulation defects. Moreover, loss of endogenous PAPC results in elevated C-cadherin adhesion activity in the dorsal mesoderm and interferes with the normal blastopore closure, a defect that can be rescued by a dominant-negative C-cadherin mutant. Importantly, activin induces PAPC expression, and PAPC is required for activin-induced regulation of C-cadherin adhesion activity and explant morphogenesis. Signaling through Frizzled-7 is not required for PAPC regulation of C-cadherin, suggesting that C-cadherin regulation and Frizzled-7 signaling are two distinct branches of the PAPC pathway that induce morphogenetic movements. Thus, spatial regulation of classical cadherin adhesive function by local expression of a protocadherin is a novel mechanism for controlling cell sorting and tissue morphogenesis.
Condensin I recruitment and uneven chromatin condensation precede mitotic cell death in response to DNA damage
Authors: Blank Michael , Lerenthal Yaniv , Mittelman Leonid , Shiloh Yosef
Published: July 2006

Mitotic cell death (MCD) is a prominent but poorly defined form of death that stems from aberrant mitosis. One of the early steps in MCD is premature mitosis and uneven chromatin condensation (UCC). The mechanism underlying this phenomenon is currently unknown. In this study, we show that DNA damage in cells with a compromised p53-mediated G2/M checkpoint triggers the unscheduled activation of cyclin-dependent kinase 1 (Cdk1), activation and chromatin loading of the condensin I complex, and UCC followed by the appearance of multimicronucleated cells, which is evidence of MCD. We demonstrate that these processes engage some of the players of normal mitotic chromatin packaging but not those that drive the apoptotic chromatin condensation. Our findings establish a link between the induction of DNA damage and mitotic abnormalities (UCC) through the unscheduled activation of Cdk1 and recruitment of condensin I. These results demonstrate a clear distinction between the mechanisms that drive MCD-associated and apoptosis-related chromatin condensation and provide mechanistic insights and new readouts for a major cell death process in treated tumors.
Entry of muscle satellite cells into the cell cycle requires sphingolipid signaling
Authors: Nagata Yosuke , Partridge Terence A. , Matsuda Ryoichi , Zammit Peter S.
Published: July 2006

Adult skeletal muscle is able to repeatedly regenerate because of the presence of satellite cells, a population of stem cells resident beneath the basal lamina that surrounds each myofiber. Little is known, however, of the signaling pathways involved in the activation of satellite cells from quiescence to proliferation, a crucial step in muscle regeneration. We show that sphingosine-1-phosphate induces satellite cells to enter the cell cycle. Indeed, inhibiting the sphingolipid-signaling cascade that generates sphingosine-1-phosphate significantly reduces the number of satellite cells able to proliferate in response to mitogen stimulation in vitro and perturbs muscle regeneration in vivo. In addition, metabolism of sphingomyelin located in the inner leaflet of the plasma membrane is probably the main source of sphingosine-1-phosphate used to mediate the mitogenic signal. Together, our observations show that sphingolipid signaling is involved in the induction of proliferation in an adult stem cell and a key component of muscle regeneration.
On neoclassical Schottky groups
Authors: Hidalgo Rubén , Maskit Bernard
Published: July 2006

The goal of this paper is to describe a theoretical construction of an infinite collection of non-classical Schottky groups. We first show that there are infinitely many non-classical noded Schottky groups on the boundary of Schottky space, and we show that infinitely many of these are “sufficiently complicated”. We then show that every Schottky group in an appropriately defined relative conical neighborhood of any sufficiently complicated noded Schottky group is necessarily non-classical. Finally, we construct two examples; the first is a noded Riemann surface of genus

3
3

that cannot be uniformized by any neoclassical Schottky group (i.e., classical noded Schottky group); the second is an explicit example of a sufficiently complicated noded Schottky group in genus

3
3

.
Inseparable extensions of algebras over the Steenrod algebra with applications to modular invariant theory of finite groups
Authors: Neusel Mara
Published: July 2006

We consider purely inseparable extensions

H

↪

H

P

∗

\textrm {H}\hookrightarrow \sqrt [\mathscr {P}^*]{\textrm {H}}

of unstable Noetherian integral domains over the Steenrod algebra. It turns out that there exists a finite group

G
≤

GL

(
V
)

G\le \textrm {GL}(V)

and a vector space decomposition

V
=

W
0

⊕

W
1

⊕
⋯
⊕

W
e

V=W_0\oplus W_1\oplus \dotsb \oplus W_e

such that
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper H overbar equals left-parenthesis double-struck upper F left-bracket upper W 0 right-bracket circled-times double-struck upper F left-bracket upper W 1 right-bracket Superscript p Baseline circled-times midline-horizontal-ellipsis circled-times double-struck upper F left-bracket upper W Subscript e Baseline right-bracket Superscript p Super Superscript e Superscript Baseline right-parenthesis Superscript upper G">

H

¯

=
(

F

[

W
0

]
⊗

F

[

W
1

]
p

⊗
⋯
⊗

F

[

W
e

]

p
e

)
G

\overline {\textrm {H}}=(\mathbb {F}[W_0] \otimes \mathbb {F}[W_1]^p\otimes \dotsb \otimes \mathbb {F}[W_e]^{p^e})^G

and

H

P

∗

¯

=

F

[
V

]
G

\overline {\sqrt [\mathscr {P}^*]{\textrm {H}}}=\mathbb {F}[V]^G

, where

(
−
)

¯

\overline {(-)}

denotes the integral closure. Moreover,

H

\textrm {H}

is Cohen-Macaulay if and only if

H

P

∗

\sqrt [\mathscr {P}^*]{\textrm {H}}

is Cohen-Macaulay. Furthermore,

H

¯

\overline {\textrm {H}}

is polynomial if and only if

H

P

∗

\sqrt [\mathscr {P}^*]{\textrm {H}}

is polynomial, and

H

P

∗

=

F

[

h
1

,
…
,

h
n

]

\sqrt [\mathscr {P}^*]{\textrm {H}}=\mathbb {F}[h_1,\dotsc ,h_n]

if and only if
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper H equals double-struck upper F left-bracket h 1 comma ellipsis comma h Subscript n 0 Baseline comma h Subscript n 0 plus 1 Superscript p Baseline comma ellipsis comma h Subscript n 1 Superscript p Baseline comma h Subscript n 1 plus 1 Superscript p squared Baseline comma ellipsis comma h Subscript n Sub Subscript e Subscript Superscript p Super Superscript e Superscript Baseline right-bracket comma">

H

=

F

[

h
1

,
…
,

h

n
0

,

h

n
0

+
1

p

,
…
,

h

n
1

p

,

h

n
1

+
1

p
2

,
…
,

h

n
e

p
e

]
,

\textrm {H}=\mathbb {F}[h_1,\dotsc ,h_{n_0},h_{n_0+1}^p,\dotsc ,h_{n_1}^p, h_{n_1+1}^{p^2},\dotsc ,h_{n_e}^{p^e}],

\]
where

n
e

=
n

n_e=n

and

n
i

=

dim

F

⁡
(

W
0

⊕
⋯
⊕

W
i

)

n_i=\dim _{\mathbb {F}}(W_0\oplus \dotsb \oplus W_i)

.
The invariant factors of the incidence matrices of points and subspaces in 𝑃𝐺(𝑛,𝑞) and 𝐴𝐺(𝑛,𝑞)
Authors: Chandler David , Sin Peter , Xiang Qing
Published: July 2006

We determine the Smith normal forms of the incidence matrices of points and projective

(
r
−
1
)

(r-1)

-dimensional subspaces of

PG
⁡
(
n
,
q
)

\operatorname {PG}(n,q)

and of the incidence matrices of points and

r
r

-dimensional affine subspaces of

AG
⁡
(
n
,
q
)

\operatorname {AG}(n,q)

for all

n
n

,

r
r

, and arbitrary prime power

q
q

.
Open loci of graded modules
Authors: Rotthaus Christel , Şega Liana
Published: July 2006

Let

A
=

⨁

i
∈

N

A
i

A=\bigoplus _{i\in \mathbb {N}}A_i

be an excellent homogeneous Noetherian graded ring and let

M
=

⨁

n
∈

Z

M
n

M=\bigoplus _{n\in \mathbb {Z}}M_n

be a finitely generated graded

A
A

-module. We consider

M
M

as a module over

A
0

A_0

and show that the

(

S
k

)

(S_k)

-loci of

M
M

are open in

Spec
⁡
(

A
0

)

\operatorname {Spec}(A_0)

. In particular, the Cohen-Macaulay locus

U

C
M

0

=
{

p

∈
Spec
⁡
(

A
0

)
∣

M

p

is Cohen-Macaulay

}

U^0_{CM}=\{\mathfrak {p}\in \operatorname {Spec}(A_0) \mid M_\mathfrak {p} \; \mbox {is Cohen-Macaulay}\}

is an open subset of

Spec
⁡
(

A
0

)

\operatorname {Spec}(A_0)

. We also show that the

(

S
k

)

(S_k)

-loci on the homogeneous parts

M
n

M_n

of

M
M

are eventually stable. As an application we obtain that for a finitely generated Cohen-Macaulay module

M
M

over an excellent ring

A
A

and for an ideal

I
⊆
A

I\subseteq A

which is not contained in any minimal prime of

M
M

, the

(

S
k

)

(S_k)

-loci for the modules

M

/

I
n

M

M/I^nM

are eventually stable.
Ratio limit theorem for parabolic horn-shaped domains
Authors: Collet Pierre , Martinez Servet , San Martin Jaime
Published: July 2006

We prove that for horn-shaped domains of parabolic type, the ratio of the heat kernel at different fixed points has a limit when the time tends to infinity. We also give an explicit formula for the limit in terms of the harmonic functions.
Jointly hyponormal pairs of commuting subnormal operators need not be jointly subnormal
Authors: Curto Raúl , Yoon Jasang
Published: July 2006

We construct three different families of commuting pairs of subnormal operators, jointly hyponormal but not admitting commuting normal extensions. Each such family can be used to answer in the negative a 1988 conjecture of R. Curto, P. Muhly and J. Xia. We also obtain a sufficient condition under which joint hyponormality does imply joint subnormality.
On almost one-to-one maps
Authors: Blokh Alexander , Oversteegen Lex , Tymchatyn E.
Published: July 2006

A continuous map

f
:
X
→
Y

f:X\to Y

of topological spaces

X
,
Y

X, Y

is said to be almost

1
1

-to-

1
1

if the set of the points

x
∈
X

x\in X

such that

f

−
1

(
f
(
x
)
)
=
{
x
}

f^{-1}(f(x))=\{x\}

is dense in

X
X

; it is said to be light if pointwise preimages are zero dimensional. We study almost 1-to-1 light maps of some compact and

σ
\sigma

-compact spaces (e.g.,

n
n

-manifolds or dendrites) and prove that in some important cases they must be homeomorphisms or embeddings. In a forthcoming paper we use these results and show that if

f
f

is a minimal self-mapping of a 2-manifold

M
M

, then point preimages under

f
f

are tree-like continua and either

M
M

is a union of 2-tori, or

M
M

is a union of Klein bottles permuted by

f
f

.
Intrinsic ultracontractivity of the Feynman-Kac semigroup for relativistic stable processes
Authors: Kulczycki Tadeusz , Siudeja Bartłomiej
Published: July 2006

Let

X
t

X_t

be the relativistic

α
\alpha

-stable process in

R

d

\mathbf {R}^d

,

α
∈
(
0
,
2
)

\alpha \in (0,2)

,

d
>
α

d > \alpha

, with infinitesimal generator
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper H 0 Superscript left-parenthesis alpha right-parenthesis Baseline equals minus left-parenthesis left-parenthesis negative normal upper Delta plus m Superscript 2 slash alpha Baseline right-parenthesis Superscript alpha slash 2 Baseline minus m right-parenthesis">

H
0

(
α
)

=
−
(
(
−
Δ
+

m

2

/

α

)

α

/

2

−
m
)

H_0^{(\alpha )}= - ((-\Delta +m^{2/\alpha })^{\alpha /2}-m)

. We study intrinsic ultracontractivity (IU) for the Feynman-Kac semigroup

T
t

T_t

for this process with generator

H
0

(
α
)

−
V

H_0^{(\alpha )} - V

,

V
≥
0

V \ge 0

,

V
V

locally bounded. We prove that if

lim

|

x

|

→
∞

V
(
x
)
=
∞

\lim _{|x| \to \infty } V(x) = \infty

, then for every

t
>
0

t >0

the operator

T
t

T_t

is compact. We consider the class

V

\mathcal {V}

of potentials

V
V

such that

V
≥
0

V \ge 0

,

lim

|

x

|

→
∞

V
(
x
)
=
∞

\lim _{|x| \to \infty } V(x) = \infty

and

V
V

is comparable to the function which is radial, radially nondecreasing and comparable on unit balls. For

V
V

in the class

V

\mathcal {V}

we show that the semigroup

T
t

T_t

is IU if and only if

lim

|

x

|

→
∞

V
(
x
)

/

|

x

|

=
∞

\lim _{|x| \to \infty } V(x)/|x| = \infty

. If this condition is satisfied we also obtain sharp estimates of the first eigenfunction

ϕ
1

\phi _1

for

T
t

T_t

. In particular, when

V
(
x
)
=

|

x

|

β

V(x) = |x|^{\beta }

,

β
>
0

\beta > 0

, then the semigroup

T
t

T_t

is IU if and only if

β
>
1

\beta >1

. For

β
>
1

\beta >1

the first eigenfunction

ϕ
1

(
x
)

\phi _1(x)

is comparable to
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="exp left-parenthesis minus m Superscript 1 slash alpha Baseline StartAbsoluteValue x EndAbsoluteValue right-parenthesis left-parenthesis StartAbsoluteValue x EndAbsoluteValue plus 1 right-parenthesis Superscript left-parenthesis negative d minus alpha minus 2 beta minus 1 right-parenthesis slash 2 Baseline period">

exp
⁡
(
−

m

1

/

α

|

x

|

)

(

|

x

|

+
1

)

(
−
d
−
α
−
2
β
−
1
)

/

2

.

\exp (-m^{1/{\alpha }}|x|) \, (|x| + 1)^{(-d - \alpha - 2 \beta -1 )/2}.

\]
Groupoid cohomology and extensions
Authors: Tu Jean-Louis
Published: July 2006

We show that Haefliger’s cohomology for étale groupoids, Moore’s cohomology for locally compact groups and the Brauer group of a locally compact groupoid are all particular cases of sheaf (or Čech) cohomology for topological simplicial spaces.
Semifree symplectic circle actions on 4-orbifolds
Authors: Godinho L.
Published: July 2006

A theorem of Tolman and Weitsman states that all symplectic semifree circle actions with isolated fixed points on compact symplectic manifolds must be Hamiltonian and have the same equivariant cohomology and Chern classes of

(

C

P
1

)
n

(\mathbb {C}P^1)^n

equipped with the standard diagonal circle action. In this paper, we show that the situation is much different when we consider compact symplectic orbifolds. Focusing on

4
4

-orbifolds with isolated cone singularities, we show that such actions, besides being Hamiltonian, can now be obtained from either

S
2

×

S
2

S^2\times S^2

or a weighted projective space, or a quotient of one of these spaces by a finite cyclic group, by a sequence of special weighted blow-ups at fixed points. In particular, they can have any number of fixed points.
Inverse scattering with fixed energy and an inverse eigenvalue problem on the half-line
Authors: Horváth Miklós
Published: July 2006

Recently A. G. Ramm (1999) has shown that a subset of phase shifts

δ
l

\delta _l

,

l
=
0
,
1
,
…

l=0,1,\ldots

, determines the potential if the indices of the known shifts satisfy the Müntz condition

∑

l
≠
0
,
l
∈
L

1
l

=
∞

\sum _{l\neq 0,l\in L}\frac {1}{l}=\infty

. We prove the necessity of this condition in some classes of potentials. The problem is reduced to an inverse eigenvalue problem for the half-line Schrödinger operators.
Frequently hypercyclic operators
Authors: Bayart Frédéric , Grivaux Sophie
Published: July 2006

We investigate the subject of linear dynamics by studying the notion of frequent hypercyclicity for bounded operators

T
T

on separable complex

F

\mathcal {F}

-spaces:

T
T

is frequently hypercyclic if there exists a vector

x
x

such that for every nonempty open subset

U
U

of

X
X

, the set of integers

n
n

such that

T

n

x

T^{n}x

belongs to

U
U

has positive lower density. We give several criteria for frequent hypercyclicity, and this leads us in particular to study linear transformations from the point of view of ergodic theory. Several other topics which are classical in hypercyclicity theory are also investigated in the frequent hypercyclicity setting.
Harnack inequalities and Gaussian estimates for a class of hypoelliptic operators
Authors: Pascucci Andrea , Polidoro Sergio
Published: July 2006

We prove a global Harnack inequality for a class of degenerate evolution operators by repeatedly using an invariant local Harnack inequality. As a consequence we obtain an accurate Gaussian lower bound for the fundamental solution for some meaningful families of degenerate operators.
On the characterization of the kernel of the geodesic X-ray transform
Authors: Chappa Eduardo
Published: July 2006

Let

Ω
¯

\overline {\Omega }

be a compact manifold with boundary. We consider covariant symmetric tensor fields of order two that belong to a Sobolev space

H

k

(

Ω
¯

)
,
k
≥
1

H^{k}(\overline {\Omega }), k \geq 1

. We prove, under the assumption that the metric is simple, that solenoidal tensor fields that belong to the kernel of the geodesic X-ray transform are smooth up to the boundary. As a corollary we obtain that they form a finite-dimensional set in

H

k

H^{k}

.
Stationary isothermic surfaces and uniformly dense domains
Authors: Magnanini R. , Prajapat J. , Sakaguchi S.
Published: July 2006

We establish a relationship between stationary isothermic surfaces and uniformly dense domains. A stationary isothermic surface is a level surface of temperature which does not evolve with time. A domain

Ω
\Omega

in the

N
N

-dimensional Euclidean space

R

N

\mathbb {R}^N

is said to be uniformly dense in a surface

Γ
⊂

R

N

\Gamma \subset \mathbb {R}^N

of codimension

1
1

if, for every small

r
>
0
,

r>0,

the volume of the intersection of

Ω
\Omega

with a ball of radius

r
r

and center

x
x

does not depend on

x
x

for

x
∈
Γ
.

x\in \Gamma .

We prove that the boundary of every uniformly dense domain which is bounded (or whose complement is bounded) must be a sphere. We then examine a uniformly dense domain with unbounded boundary

∂
Ω

\partial \Omega

, and we show that the principal curvatures of

∂
Ω

\partial \Omega

satisfy certain identities.

The case in which the surface

Γ
\Gamma

coincides with

∂
Ω

\partial \Omega

is particularly interesting. In fact, we show that, if the boundary of a uniformly dense domain is connected, then (i) if

N
=
2

N=2

, it must be either a circle or a straight line and (ii) if

N
=
3
,

N=3,

it must be either a sphere, a spherical cylinder or a minimal surface. We conclude with a discussion on uniformly dense domains whose boundary is a minimal surface.
𝑊^{{}2,𝑝}–estimates for the linearized Monge–Ampère equation
Authors: Gutiérrez Cristian , Tournier Federico
Published: July 2006

Let

Ω
⊆

R

n

\Omega \subseteq \mathbb {R}^n

be a strictly convex domain and let

ϕ
∈

C
2

(
Ω
)

\phi \in C^2(\Omega )

be a convex function such that

λ
≤
det

D
2

ϕ
≤
Λ

\lambda \leq \text {det}D^2\phi \leq \Lambda

in

Ω
\Omega

. The linearized Monge–Ampère equation is

L

Φ

u
=

trace

(
Φ

D
2

u
)
=
f
,

\begin{equation*} L_{\Phi }u=\textrm {trace}(\Phi D^2u)=f, \end{equation*}

where

Φ
=
(
det

D
2

ϕ
)
(

D
2

ϕ

)

−
1

\Phi = (\text {det}D^2\phi )(D^2\phi )^{-1}

is the matrix of cofactors of

D
2

ϕ

D^2\phi

. We prove that there exist

p
>
0

p>0

and

C
>
0

C>0

depending only on

n
,
λ
,
Λ

n,\lambda ,\Lambda

, and

dist

(

Ω
′

,
Ω
)

\textrm {dist}(\Omega ^\prime ,\Omega )

such that
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="double-vertical-bar upper D squared u double-vertical-bar Subscript upper L Sub Superscript p Subscript left-parenthesis normal upper Omega prime right-parenthesis Baseline less-than-or-equal-to upper C left-parenthesis double-vertical-bar u double-vertical-bar Subscript upper L Sub Superscript normal infinity Subscript left-parenthesis normal upper Omega right-parenthesis Baseline plus double-vertical-bar f double-vertical-bar Subscript upper L Sub Superscript n Subscript left-parenthesis normal upper Omega right-parenthesis Baseline right-parenthesis">

‖

D
2

u

‖

L
p

(

Ω
′

)

≤
C
(
‖
u

‖

L
∞

(
Ω
)

+
‖
f

‖

L
n

(
Ω
)

)

\begin{equation*} \|D^2u\|_{L^p(\Omega ^\prime )}\leq C(\|u\|_{L^\infty (\Omega )}+\|f\|_{L^n(\Omega )}) \end{equation*}

for all solutions

u
∈

C
2

(
Ω
)

u\in C^2(\Omega )

to the equation

L

Φ

u
=
f

L_{\Phi }u=f

.
Bayesian variable selection for the analysis of microarray data with censored outcomes
Authors: Sha Naijun , Tadesse Mahlet G. , Vannucci Marina
Published: July 2006

Motivation: A common task in microarray data analysis consists of identifying genes associated with a phenotype. When the outcomes of interest are censored time-to-event data, standard approaches assess the effect of genes by fitting univariate survival models. In this paper, we propose a Bayesian variable selection approach, which allows the identification of relevant markers by jointly assessing sets of genes. We consider accelerated failure time (AFT) models with log-normal and log-t distributional assumptions. A data augmentation approach is used to impute the failure times of censored observations and mixture priors are used for the regression coefficients to identify promising subsets of variables. The proposed method provides a unified procedure for the selection of relevant genes and the prediction of survivor functions.

Results: We demonstrate the performance of the method on simulated examples and on several microarray datasets. For the simulation study, we consider scenarios with large number of noisy variables and different degrees of correlation between the relevant and non-relevant (noisy) variables. We are able to identify the correct covariates and obtain good prediction of the survivor functions. For the microarray applications, some of our selected genes are known to be related to the diseases under study and a few are in agreement with findings from other researchers.

Availability: The Matlab code for implementing the Bayesian variable selection method may be obtained from the corresponding author.

Contact:  mvannucci@stat.tamu.edu

Supplementary Information: Supplementary data are available at Bioinformatics online.
No abnormal prion protein detected in the milk of cattle infected with the bovine spongiform encephalopathy agent
Authors: Everest Sally J. , Thorne Leigh T. , Hawthorn Jeremy A. , Jenkins Russell , Hammersley Clare , Ramsay Andrew M. , Hawkins Stephen A. , Venables Lindsay , Flynn Linda , Sayers Robin , Kilpatrick John , Sach Amanda , Hope James , Jackman Roy
Published: July 2006

Milk specimens were collected from lactating cows that had previously been challenged with bovine spongiform encephalopathy (BSE)-infected brain at 4–6 months of age. One group of 10 animals received a single oral dose of 100 g, a second group received 1 g and the third was made up of unexposed controls. The cows were inseminated artificially, and calved at approximately 2 years of age and annually thereafter. Milking was done within the first week following calving and at 10-weekly intervals during the lactation period. Specimens were centrifuged to obtain a fraction enriched for somatic cells and these fractions were analysed for disease-associated, abnormal prion protein (PrPBSE) by using a modified commercial BSE ELISA and a different confirmatory assay. No abnormal prion protein has so far been identified in the cell fraction of milk from cattle incubating BSE by using these methods at their limits of detection.
Codon 129 polymorphism of the human prion protein influences the kinetics of amyloid formation
Authors: Lewis Patrick A. , Tattum M. Howard , Jones Samantha , Bhelt Daljit , Batchelor Mark , Clarke Anthony R. , Collinge John , Jackson Graham S.
Published: July 2006

The human prion protein (PrP) has a common polymorphism at residue 129, which can be valine or methionine. This polymorphism has a strong influence on susceptibility to prion diseases and on prion-strain properties. Previous work has shown that this amino acid variation has no measurable effect on the native structure of cellular PrP (PrPC). Here, it is shown that the polymorphism does not change the efficiency of conversion to the β-PrP conformation or affect the binding of copper(II) ions. However, in a partially denatured conformation, the polymorphic variation has a profound influence on the ability of the protein to form amyloid fibrils spontaneously.
Prolonged survival of Puumala hantavirus outside the host: evidence for indirect transmission via the environment
Authors: Kallio Eva R. , Klingström Jonas , Gustafsson Elisabeth , Manni Tytti , Vaheri Antti , Henttonen Heikki , Vapalahti Olli , Lundkvist Åke
Published: July 2006

The capability of rodent-borne viruses to survive outside the host is critical for the transmission dynamics within rodent populations and to humans. The transmission of Puumala virus (PUUV) in colonized bank voles (Clethrionomys glareolus) was investigated and additional longevity studies in cell culture with PUUV and Tula (TULV) hantaviruses were performed. Wild-type PUUV excreted by experimentally infected donor bank voles was shown to be transmitted indirectly between rodents through contaminated beddings, and maintained its infectivity to recipient voles at room temperature for 12–15 days. In cell culture supernatants, PUUV and TULV remained infectious for 5–11 days at room temperature and up to 18 days at 4 °C, but were inactivated after 24 h at 37 °C. Interestingly, a fraction of dried virus was still infectious after 1 h at 56 °C. These results demonstrated that hantavirus transmission does not require direct contact between rodents, or between rodents and humans, and that the indirect transmission of PUUV through contaminated environment takes place among the rodents for a prolonged period of time. The results also have implications for safety recommendations for work with hantaviruses and for preventive measures.
Identification of Hepatitis B virus putative intergenotype recombinants by using fragment typing
Authors: Yang Jie , Xing Ke , Deng Riqiang , Wang Jinwen , Wang Xunzhang
Published: July 2006

Eight hundred and thirty-seven human Hepatitis B virus (HBV) genomes were categorized into pure genotypes and potential intergenotypes, according to their fragment types which were determined based on similarity and phylogenetic analyses of 13 contrived fragments of 250 bp against the corresponding fragments of the consensus sequences of genotypes A–H. Twenty-five intergenotypes, including 171 genomes, were revealed from the potential intergenotype recombinants by phylogenetic analysis of the precisely derived mosaic fragments. Among these, four new intergenotypes were discovered. Many genomes were revealed as putative intergenotype recombinants for the first time. About 87 % of the putative recombinants were B/C (120) and A/D (29) hybrids. The other recombinants comprised A/B/C, A/C, A/E, A/G, C/D, C/F, C/G, C/U (U for unknown genotype) and B/C/U hybrids. Genotypes A and C showed a higher recombination tendency than did other genotypes. The results also demonstrated region priority and breakpoint hot spots in the intergenotype recombination. Recombination breakpoints were found to be concentrated mainly in the vicinity of the DR1 region (nt 1640–1900), the pre S1/S2 region (nt 3150–100), the 3′-end of the C gene (nt 2330–2450) and the 3′-end of the S gene (nt 650–830). These results support the suggestion that intergenotype recombinants may result from co-infection with different genotypes.
Co-localization of gammaretroviral RNAs at their transcription site favours co-packaging
Authors: Rasmussen Søren Vestergaard , Pedersen Finn Skou
Published: July 2006

A retroviral vector-rescue system in which co-packaging of the two co-expressed vectors is required for transduction of one of the vectors has been established previously. By using this rescue system, two distinct packaging-cell populations have been generated. One cell population expressed retroviral RNA from co-localized transcription sites, resulting in local and overlapping accumulation of both RNA transcripts. In the other cell population, the two transcription cassettes were introduced separately, leading to distinct transcription sites of the two RNAs and no significant co-localization of the RNAs. Titre measurements from the two distinct cell populations showed large differences in rescue titre, which is an indirect measure of co-packaging efficiency. Thus, the cell populations with overlapping RNA accumulation gave rise to 15–80-fold-higher rescue titres than cell populations with non-overlapping RNA accumulation. These data show that the spatial position of proviral transcription sites affects the level of retroviral RNA co-packaging and suggest that there is already a linkage of RNAs for co-packaging at the transcription site. It is hypothesized that this linkage is due to RNA dimerization taking place at the transcription site.