bluuebunny/crossref_metadata_2025_split huggingface dataset:
Irreducibility of equisingular families of curves
Authors: Keilen Thomas 
Published: July 2005

In 1985 Joe Harris proved the long-standing claim of Severi that equisingular families of plane nodal curves are irreducible whenever they are nonempty. For families with more complicated singularities this is no longer true. Given a divisor

D
D

on a smooth projective surface

Σ
\Sigma

it thus makes sense to look for conditions which ensure that the family

V

|

D

|

i
r
r

(

S

1

,
…
,

S

r

)

V_{|D|}^{irr}\big (\mathcal {S}_1,\ldots ,\mathcal {S}_r\big )

of irreducible curves in the linear system

|

D

|

l

|D|_l

with precisely

r
r

singular points of types

S

1

,
…
,

S

r

\mathcal {S}_1,\ldots ,\mathcal {S}_r

is irreducible. Considering different surfaces, including general surfaces in

P

C

3

\mathbb P_{\mathbb C}^3

and products of curves, we produce a sufficient condition of the type

∑

i
=
1

r

deg
⁡

(

X
(

S

i

)

)

2

>
γ
⋅
(
D
−

K
Σ

)
2

,

\begin{equation*} \sum \limits _{i=1}^r\deg \big (X(\mathcal {S}_i)\big )^2 > \gamma \cdot (D- K_\Sigma )^2, \end{equation*}

where

γ
\gamma

is some constant and

X
(

S

i

)

X(\mathcal {S}_i)

some zero-dimensional scheme associated to the singularity type. Our results carry the same asymptotics as the best known results in this direction in the plane case, even though the coefficient is worse. For most of the surfaces considered these are the only known results in that direction.
Harnack inequalities for non-local operators of variable order
Authors: Bass Richard , Kassmann Moritz 
Published: July 2005

We consider harmonic functions with respect to the operator
\[

L

u
(
x
)
=
∫
[
u
(
x
+
h
)
−
u
(
x
)
−

1

(

|

h

|

≤
1
)

h
⋅
∇
u
(
x
)
]
n
(
x
,
h
)

d
h
.

\mathcal {L} u(x)=\int [u(x+h)-u(x)-1_{(|h|\leq 1)} h\cdot \nabla u(x)] n(x,h) \, dh.

\]
Under suitable conditions on

n
(
x
,
h
)

n(x,h)

we establish a Harnack inequality for functions that are nonnegative and harmonic in a domain. The operator

L

\mathcal {L}

is allowed to be anisotropic and of variable order.
The Aronsson-Euler equation for absolutely minimizing Lipschitz extensions with respect to Carnot-Carathéodory metrics
Authors: Bieske Thomas , Capogna Luca 
Published: July 2005

We derive the Euler-Lagrange equation (also known in this setting as the Aronsson-Euler equation) for absolute minimizers of the

L

∞

L^{\infty }

variational problem
\[

{

inf

|

|

∇
0

u

|

|

L

∞

(
Ω
)

,
u
=
g
∈
L
i
p
(
∂
Ω
)
on
∂
Ω
,

\begin {cases} \inf ||\nabla _0 u||_{L^{\infty }(\Omega )}, u=g\in Lip(\partial \Omega ) \text { on }\partial \Omega , \end {cases}

\]
where

Ω
⊂

G

\Omega \subset \mathbf {G}

is an open subset of a Carnot group,

∇
0

u

\nabla _0 u

denotes the horizontal gradient of

u
:
Ω
→

R

u:\Omega \to \mathbb {R}

, and the Lipschitz class is defined in relation to the Carnot-Carathéodory metric. In particular, we show that absolute minimizers are infinite harmonic in the viscosity sense. As a corollary we obtain the uniqueness of absolute minimizers in a large class of groups. This result extends previous work of Jensen and of Crandall, Evans and Gariepy. We also derive the Aronsson-Euler equation for more “regular" absolutely minimizing Lipschitz extensions corresponding to those Carnot-Carathéodory metrics which are associated to “free" systems of vector fields.
On the behavior of the algebraic transfer
Authors: Bruner Robert , Hà Lê , Hưng Nguyễn 
Published: July 2005

Let

T

r
k

:

F

2

⊗

G

L
k

P

H
i

(
B

V

k

)
→
E
x

t

A

k
,
k
+
i

(

F

2

,

F

2

)

Tr_k:\mathbb {F}_2\underset {GL_k}{\otimes } PH_i(B\mathbb {V}_k)\to Ext_{\mathcal {A}}^{k,k+i}(\mathbb {F}_2, \mathbb {F}_2)

be the algebraic transfer, which is defined by W. Singer as an algebraic version of the geometrical transfer

t

r
k

:

π
∗
S

(
(
B

V

k

)
+

)
→

π
∗
S

(

S
0

)

tr_k: \pi _*^S((B\mathbb {V} _k)_+) \to \pi _*^S(S^0)

. It has been shown that the algebraic transfer is highly nontrivial and, more precisely, that

T

r
k

Tr_k

is an isomorphism for

k
=
1
,
2
,
3

k=1, 2, 3

. However, Singer showed that

T

r
5

Tr_5

is not an epimorphism. In this paper, we prove that

T

r
4

Tr_4

does not detect the nonzero element

g
s

∈
E
x

t

A

4
,
12
⋅

2
s

(

F

2

,

F

2

)

g_s\in Ext_{\mathcal {A}}^{4,12\cdot 2^s}(\mathbb {F}_2, \mathbb {F}_2)

for every

s
≥
1

s\geq 1

. As a consequence, the localized

(
S

q
0

)

−
1

T

r
4

(Sq^0)^{-1}Tr_4

given by inverting the squaring operation

S

q
0

Sq^0

is not an epimorphism. This gives a negative answer to a prediction by Minami.
Nontoxic membrane translocation peptide from protamine, low molecular weight protamine (LMWP), for enhanced intracellular protein delivery: in vitro and in vivo study
Authors: Park Yoon Jeong , Chang Li‐Chien , Liang Jun Feng , Moon Cheol , Chung Chong‐Pyoung , Yang Victor C. 
Published: July 2005

ABSTRACTNaturally derived, nontoxic peptides from protamine by the authors, termed low molecular weight protamines (LMWPs), possess high arginine content and carry significant sequence similarity to that of TAT, by far the most potent protein transduction domain peptide. Therefore, it was hypothesized that these LMWPs would also inherit the similar translocation activity across the cell membrane, which enables any impermeable species to be transduced into the cells. LMWPs were prepared by enzymatic digestion of protamine, examined their capability of transducing an impermeable protein toxin into the tumor cells by chemical conjugation, and determined cytotoxicity of transduced protein toxin (e.g., gelonin) against cancer cell lines and a tumor‐bearing mouse. In vitro results showed that LMWPs could indeed translocate themselves into several mammalian cell lines as efficiently as TAT, thereby transducing impermeable gelonin into the cells by chemical conjugation. In vivo studies further confirmed that LMWP could carry an impermeable gelonin across the tumor mass and subsequently inhibit the tumor growth. In conclusion, the presence of equivalent cell translocation potency, absence of toxicity of peptide itself, and the suitability for low‐cost production by simple enzymatic digestion could expand the range of clinical applications of LMWPs, including medical imaging and gene/protein therapies.
Prospective identification of cardiac progenitors by a novel single cell‐based cardiomyocyte induction
Authors: Yamashita Jun K. , Takano Makoto , Hiraoka‐Kanie Mina , Shimazu Chikashi , Peishi Yan , Yanagi Kentoku , Nakano Akiko , Inoue Emi , Kita Fumiyo , Nishikawa Shin‐Ichi 
Published: July 2005

ABSTRACTDissection of cardiomyocyte differentiation process at the cellular level is indispensable in the research for cardiac development and regeneration. Previously, we have established an embryonic stem cell differentiation system that reproduces early vascular development from progenitor cells that express Flk1, a vascular endothelial growth factor receptor, by the combinatory application of 2‐dimensional culture and flowcytometry. Here we show that cardiomyocytes can be successfully induced from a single Flk1+ cell on 2‐dimensional culture, enabling the direct observation of differentiating cardiomyocytes and the prospective identification of cardiac progenitor potentials. Flk1+ cells could give rise to cardiomyocytes, as well as endothelial cells, from a single cell by the co‐culture on OP9 stroma cells in a fusion‐independent manner. Among the cell populations in intermediate stages from Flk1+ cells to cardiomyocytes, Flk1+/CXCR4+/vascular endothelial cadherin− cells were cardiac‐specific progenitors at the single cell level. Noggin, a bone morphogenetic protein inhibitor, abolished cardiomyocyte differentiation by inhibiting the cardiac progenitor induction. However, wnt inhibitors Dkk‐1 or Frizzled‐8/Fc chimeric protein augmented, but wnt3a inhibited, cardiomyocyte differentiation. In vitro reproduction of cardiomyocyte differentiation process should be a potent tool for the cellular and molecular elucidation of cardiac development, which would provide various targets for cardiac regeneration.
Immunotherapy in multiple myeloma – possibility or probability?
Authors: Harrison S. J. , Cook G. 
Published: July 2005

SummaryIn a small number of patients with multiple myeloma (MM), long‐term disease‐free survival has been achieved by harnessing the immune phenomenon, ‘graft‐versus‐tumour’ effect, induced by allogeneic haemopoietic stem cell transplantation. This has prompted many investigators to examine ways in which a patient's own immune system can be more effectively directed against their disease, with the ultimate aim of tumour eradication. In this review we assess the current understanding of immunobiology in MM, and how the different components of the immune system, such as dendritic cells, T cells and natural killer cells, may be harnessed using in‐vitro and in‐vivo priming techniques. We look at the clinical immunotherapy trials reported to date and whether, in light of the current information, immunotherapy for MM is an achievable goal.
Perinatal stroke – risk factors and management
Authors: Chalmers Elizabeth A. 
Published: July 2005

SummaryStroke is an uncommon but increasingly recognised cause of mortality and long‐term neurological morbidity in children. A significant number of these events appear to be caused by thromboembolic disease and, as with other childhood thrombotic problems, the incidence of central nervous system events appears highest during the neonatal period. In contrast to peripheral arterial and venous thrombotic problems, it is likely that a proportion of cerebral thromboembolic events occur either in utero or perinatally and reflect different risk factors from those occurring in older infants and children. The pathophysiology of perinatal stroke is complex and in many cases is likely to be multifactorial. It is now recognised that risk factors may relate to both maternal and placental problems as well as fetal and neonatal disorders. Large prospective studies of perinatal stroke are currently lacking and efforts to define the relative contribution from each of these areas are at an early stage. The complex nature of these disorders requires collaboration between a number of different disciplines including obstetrics, fetal medicine, pathology, neonatology and neurology. Of particular interest to haematologists is the possible impact of prothrombotic abnormalities in the pathophysiology of these events and also the potential for the use of antithrombotic agents in both management and prevention.
Conventional second‐line salvage chemotherapy regimens are not warranted in patients with malignant lymphomas who have progressive disease after first‐line salvage therapy regimens
Authors: Ardeshna Kirit M. , Kakouros Nicholaos , Qian Wendi , Powell Michael G. , Saini Nishaat , D'Sa Shirley , Mackinnon Stephen , Hoskin Peter J. , Goldstone Anthony H. , Linch David C. 
Published: July 2005

SummaryThis study aimed to determine the outcome of patients with relapsed or refractory lymphoma who have an inadequate response to first‐line salvage therapy (1°ST) and who subsequently receive a second‐line salvage regimen (2°ST) with the intention of ultimately proceeding to high‐dose therapy. The outcome of 57 patients [Hodgkin's Lymphoma 17, histologically‐aggressive non‐Hodgkin's Lymphoma (NHL) 26, histologically‐indolent NHL 14] who received more than one modality of conventional‐dose salvage therapy was analysed. Sixteen patients had a partial response (PR) to 1°ST, but subsequently received 2°ST because the PR was judged to be inadequate (iPR) because of persisting disease bulk or marrow infiltration. Of these 16 patients, 10 (63%) continued to respond to 2°ST. Of the 15 patients who had stable disease following 1°ST, 5 (33%) responded to 2°ST. Only one of the 24 (4%) with progressive disease (PD) following 1°ST, responded to 2°ST. 25 of the 57 patients ultimately underwent stem cell transplantation. The 2‐year progression‐free survival (PFS) and the 3‐year overall survival (OS) for all patients was 24% and 31%, respectively. Long‐term survival was highly dependent on response to 1°ST (P = 0·0001); in patients with PD following 1°ST, the PFS and OS at 3 years was only 4%. This analysis indicates that patients with malignant lymphomas, who have PD on 1°ST, are not rescued by subsequent salvage regimens. They should either be treated palliatively or novel approaches should be explored.
Identification of APOBEC3B as a potential target for the graft‐versus‐lymphoma effect by SEREX in a patient with mantle cell lymphoma
Authors: Hishizawa Masakatsu , Imada Kazunori , Sakai Tomomi , Ueda Maki , Uchiyama Takashi 
Published: July 2005

SummaryRecently, a graft‐versus‐lymphoma (GVL) effect has been shown in patients allografted for mantle cell lymphoma (MCL), but the antigenic targets of this response remain unclear. We screened an MCL cDNA expression library with sera at GVL response after allogeneic haematopoietic stem cell transplantation and isolated five genes including APOBEC3B. Antibody responses to APOBEC3B were correlated with clinical response. Furthermore, APOBEC3B‐specific T‐cell response was induced with one of the HLA‐A*0201 binding peptides. In addition, APOBEC3B mRNA appeared to be upregulated in some MCL. These findings warrant further investigation of APOBEC3B as a candidate gene eliciting an effective immune response against MCL.
Environmental risk factors for inhibitor development in children with haemophilia A: a case–control study
Authors: Santagostino Elena , Mancuso Maria Elisa , Rocino Angiola , Mancuso Giacomo , Mazzucconi Maria Gabriella , Tagliaferri Annarita , Messina Maria , Mannucci Pier Mannuccio 
Published: July 2005

SummaryThis case–control study investigated the interactions between genetic and environmental factors and inhibitor development in 108 children with haemophilia A exclusively treated with recombinant factor VIII (FVIII). Sixty patients with inhibitors were compared with 48 inhibitor‐free controls. Family history of inhibitors and null mutations in theFVIIIgene were more prevalent in cases than in controls (20% vs. 2%,P = 0·001 and 83% vs. 64%,P = 0·04, respectively). On the other hand, there was no difference between cases and controls for such putative risk factors of inhibitor development as amniocentesis/villocentesis, premature/caesarean birth, breast‐feeding, treatment during infections/vaccinations, surgical procedures and central nervous system bleeding. A trend was found for an increased risk of inhibitor development in children first treated at a young age (<11 months); however, this was not confirmed after adjusting for genetic factors. The implementation of prophylaxis was evaluated as a putative risk factor in a subgroup of 25 cases: seven who started prophylaxis prior to inhibitor development and 18 potentially eligible for prophylaxis because they were inhibitor‐free up to the age of 35 months (i.e. the upper limit of the age range at prophylaxis onset in cases and the median age at prophylaxis onset in controls). Patients who started prophylaxis had a lower inhibitor risk than those treated on demand (adjusted odds ratio 0·2, 95% confidence interval 0·06–0·9). The protective effect on inhibitor development shown by prophylaxis may represent an additional advantage prompting its use in haemophilic children.
Effects of imatinib and interferon on primitive chronic myeloid leukaemia progenitors
Authors: Angstreich Greg R. , Matsui William , Huff Carol Ann , Vala Milada S. , Barber James , Hawkins Anita L. , Griffin Constance A. , Douglas Smith B. , Jones Richard J. 
Published: July 2005

SummaryImatinib has impressive activity against chronic myeloid leukaemia (CML), but does not appear to completely eradicate the disease. Although responses to interferon‐alpha (IFN) are slower and less dramatic than those to imatinib, they can be durable even after discontinuation of the drug. Unlike imatinib, the specific mechanisms responsible for IFN's clinical activity in CML are unknown. We found that IFN induced a G1 cell cycle arrest, as well as terminal differentiation, of the CML cell line KT‐1 and CML CD34+ cells from clinical specimens. Myeloid growth factors augmented the antileukaemic activity of IFN, and neutralising antibodies directed against myeloid growth factors inhibited IFN's antileukaemic activity. We next directly compared the effects of imatinib and IFN against differentiated and primitive CML progenitors from newly‐diagnosed patients. Although less active against CML granulocyte‐macrophage colony forming units than imatinib, IFN was significantly more toxic to primitive CML progenitors responsible for the maintenance of long‐term cultures. Imatinib and IFN appear to have divergent effects on CML progenitors at different stages of maturation, with imatinib more active against differentiated CML progenitors and IFN more active against primitive CML progenitors. The different target cells for these agents may explain the disparities in the kinetics and durability of their clinical responses. At least part of the clinical effect of IFN in CML appears to result from its ability to differentiate primitive CML progenitors.
Influence of the intensity of the conditioning regimen on the characteristics of acute and chronic graft‐versus‐host disease after allogeneic transplantation
Authors: Pérez‐Simón José A. , Díez‐Campelo María , Martino Rodrigo , Brunet Salut , Urbano Álvaro , Caballero María D. , de León Ángel , Valcárcel David , Carreras Enric , Del Cañizo María C. , López‐Fidalgo Jesús , Sierra Jordi , San Miguel Jesús F. 
Published: July 2005

SummaryThe graft‐versus‐host disease (GVHD) characteristics of 150 consecutive patients undergoing reduced intensity conditioning allogeneic (allo‐RIC) transplants and 88 patients undergoing myeloablative conditioning regimen were analysed. All patients received the same GVHD prophylaxis and peripheral blood stem cells from a human leucocyte antigen identical sibling. The cumulative incidence of acute GVHD (aGVHD) was 67% and 44% in the myeloablative and allo‐RIC regimen groups, respectively (P < 0·001), and was 39% vs. 29%, respectively (P = 0·043), for grades 2–4 aGVHD. Only conditioning type (myeloablative versus allo‐RIC) significantly influenced the incidence of aGVHD in multivariate analysis: Hazard ratio (HR) = 2·16 [95% confidence interval (CI): 1·52–3·07], P < 0·0001. The cumulative incidence of chronic GVHD (cGVHD) was 63% and 71% among myeloablative and allo‐RIC patients respectively (P = 0·084). This trend was because of the higher incidence of limited cGVHD, but not extensive cGVHD among allo‐RIC recipients [HR = 3·3 (95% CI: 1·42–8·08), P = 0·0017]. Moreover, among patients who developed cGVHD, the cumulative incidence of limited cGVHD was significantly lower in the myeloablative group than in the allo‐RIC group (7% vs. 25%, P = 0·007). Duration of immunosuppression was shorter among allo‐RIC patients (35·5% vs. 68·8% required systemic immunosuppression 36 months after transplant, P = 0·028). Although prospective controlled trials are required to further evaluate the effect of the conditioning regimen on GVHD, our results suggest that RIC modifies the incidence and characteristics of both acute and cGVHD after allogeneic transplantation, and decreases the immunosuppression requirements in long‐term follow up when compared with myeloablative conditioning.
Sirolimus in combination with tacrolimus and corticosteroids for the treatment of resistant chronic graft‐versus‐host disease
Authors: Couriel D. R. , Saliba R. , Escalón M. P. , Hsu Y. , Ghosh S. , Ippoliti C. , Hicks K. , Donato M. , Giralt S. , Khouri I. F. , Hosing C. , de Lima M. J. , Andersson B. , Neumann J. , Champlin R. 
Published: July 2005

SummaryChronic graft‐versus‐host disease (cGVHD) remains a major cause of morbidity and mortality in haematopoietic transplant recipients. Sirolimus is a macrocyclic triene antibiotic with immunosuppressive, antifungal and antitumour properties, that has activity in the prevention and treatment of acute GVHD. We conducted a phase II trial of sirolimus combined with tacrolimus and methylprednisolone in patients with steroid‐resistant cGVHD. Thirty‐five patients who developed GVHD after day 100 post‐transplant were studied. Six patients had a complete response and 16 a partial response with an overall response rate of 63%. Major adverse events related to the combination of tacrolimus and sirolimus were hyperlipidaemia, renal dysfunction and cytopenias. Four patients had thrombotic microangiopathy (TMA) and 27 (77%) had infectious complications. The median survival for the whole group was 15 months. A significantly better outcome was observed in patients with a platelet count ≥100 × 109/l, as well as in those with true chronic manifestations of GVHD compared to those with acute GVHD beyond day 100. Controlled trials comparing this approach with alternative strategies to determine which can best achieve the goal of GVHD‐free survival are warranted.
Clonal granulocytes in polycythaemia vera and essential thrombocythaemia have shortened telomeres
Authors: Ferraris Anna Maria , Pujic Natalija , Mangerini Rosa , Rapezzi Davide , Gallamini Andrea , Racchi Omar , Casciaro Salvatore , Gaetani Gian Franco 
Published: July 2005

SummaryThe purpose of this study was to evaluate telomere length in peripheral blood granulocytes and mononuclear cells collected from 22 women with polycythaemia vera (PV) and essential thrombocythaemia (ET). PV and ET are chronic myeloproliferative diseases whose heterogeneity of stem cell origin and clonal development has been established through analysis of X‐chromosome inactivation patterns. The results from clonality assay and determination of telomere length show that only clonal granulocytes have shortened telomeres.
Serological identification of adult T‐cell leukaemia‐associated antigens
Authors: Hishizawa Masakatsu , Imada Kazunori , Sakai Tomomi , Ueda Maki , Hori Toshiyuki , Uchiyama Takashi 
Published: July 2005

SummaryAdult T‐cell leukaemia (ATL) is a peripheral T‐cell neoplasm caused by human T‐cell leukaemia virus type I (HTLV‐I). Several clinical observations suggest that some tumour‐associated antigens in ATL may be recognised by the immune system. In this study, we performed the serological screening of an expression library to identify ATL‐associated antigens by using materials from a unique ATL patient with long‐term stable disease. Among five distinct genes isolated, serine/arginine protein kinase 1 (SRPK1), which has been reported to have a restricted normal tissue distribution, was found to be overexpressed in most acute type ATL samples, but not in chronic type ATL or in normal peripheral blood mononuclear cells by real‐time reverse transcription polymerase chain reaction. Interestingly, the overexpression of SRPK1 in aggressive types of ATL was more exclusively observed at the protein level than at the mRNA level. Autologous antibody to SRPK1 was confirmed in the ATL patient using Western blot analysis with plasma, but not detected in asymptomatic HTLV‐I carriers or in healthy volunteers. These results indicate that SRPK1 may be useful for the development of therapeutic and diagnostic methods for patients with ATL.