bluuebunny/crossref_metadata_2025_split huggingface dataset:
Degenerations and limit Frobenius structures in rigid cohomology
Authors: Lauder Alan G. B. 
Published: February 2011

AbstractWe introduce a ‘limiting Frobenius structure’ attached to any degeneration of projective varieties over a finite field of characteristicpwhich satisfies ap-adic lifting assumption. Our limiting Frobenius structure is shown to be effectively computable in an appropriate sense for a degeneration of projective hypersurfaces. We conjecture that the limiting Frobenius structure relates to the rigid cohomology of a semistable limit of the degeneration through an analogue of the Clemens–Schmidt exact sequence. Our construction is illustrated, and conjecture supported, by a selection of explicit examples.
Absence of Class II–Associated Invariant Chain Peptide on Leukemic Blasts of Patients Promotes Activation of Autologous Leukemia-Reactive CD4+ T Cells
Authors: van Luijn Marvin M. , van den Ancker Willemijn , Chamuleau Martine E.D. , Zevenbergen Adri , Westers Theresia M. , Ossenkoppele Gert J. , van Ham S. Marieke , van de Loosdrecht Arjan A. 
Published: February 2011

AbstractImmune escape in cancer poses a substantial obstacle to successful cancer immunotherapy. Multiple defects in HLA class I antigen presentation exist in cancer that may contribute to immune escape, but less is known about roles for HLA class II antigen presentation. On class II+ leukemic blasts, the presence of class II–associated invariant chain peptide (CLIP) is known to be correlated with poor survival in acute myeloid leukemia (AML). In this study, we evaluated the functional significance of CLIP expression on leukemic blasts of AML patients. CD4+ T cells from patients were cocultured with autologous CLIP− and CLIP+ primary leukemic blasts and analyzed for several functional parameters by flow cytometry. Increased HLA-DR and IFN-γ expression was observed for CD4+ T cells stimulated with CLIP− leukemic blasts, in contrast to CLIP+ leukemic blasts, which indicated an activation and polarization of the CD4+ T cells toward T-helper 1 cells. In addition, CLIP− leukemic blasts induced greater outgrowth of effector memory CD4+ T cells (with HLA-DR–restricted T-cell receptor Vβ repertoires) that were associated with better leukemia-specific reactivity than with CLIP+ leukemic blasts. Our findings offer a clinical rationale to downmodulate CLIP on leukemic blasts as a strategy to degrade immune escape and improve leukemia-specific T-cell immunity in AML patients. Cancer Res; 71(7); 2507–17. ©2011 AACR.
Light at Night Activates IGF-1R/PDK1 Signaling and Accelerates Tumor Growth in Human Breast Cancer Xenografts
Authors: Wu Jinghai , Dauchy Robert T. , Tirrell Paul C. , Wu Steven S. , Lynch Darin T. , Jitawatanarat Potjana , Burrington Christine M. , Dauchy Erin M. , Blask David E. , Greene Michael W. 
Published: February 2011

Abstract
Regulation of diurnal and circadian rhythms and cell proliferation are coupled in all mammals, including humans. However, the molecular mechanisms by which diurnal and circadian rhythms regulate cell proliferation are relatively poorly understood. In this study, we report that tumor growth in nude rats bearing human steroid receptor-negative MCF-7 breast tumors can be significantly accelerated by exposing the rats to light at night (LAN). Under normal conditions of an alternating light/dark cycle, proliferating cell nuclear antigen (PCNA) levels in tumors were maximal in the early light phase but remained at very low levels throughout the daily 24-hour cycle period monitored. Surprisingly, PCNA was expressed in tumors continually at a high level throughout the entire 24-hour period in LAN-exposed nude rats. Daily fluctuations of Akt and mitogen activated protein kinase activation in tumors were also disrupted by LAN. These fluctuations did not track with PCNA changes, but we found that activation of the Akt stimulatory kinase phosphoinositide-dependent protein kinase 1 (PDK1) directly correlated with PCNA levels. Expression of insulin-like growth factor 1 receptor (IGF-1R), an upstream signaling molecule for PDK1, also correlated with fluctuations of PDK1/PCNA in the LAN group. In addition, circulating IGF-1 concentrations were elevated in LAN-exposed tumor-bearing nude rats. Finally, RNAi-mediated knockdown of PDK1 led to a reduction in PCNA expression and cell proliferation in vitro and tumor growth in vivo, indicating that PDK1 regulates breast cancer growth in a manner correlated with PCNA expression. Taken together, our findings demonstrate that LAN exposure can accelerate tumor growth in vivo, in part through continuous activation of IGF-1R/PDK1 signaling. Cancer Res; 71(7); 2622–31. ©2011 AACR.
Pivotal Role of Protein Kinase C
δ
in Angiotensin II–Induced Endothelial Cyclooxygenase-2 Expression
Authors: Wong Siu Ling , Lau Chi Wai , Wong Wing Tak , Xu Aimin , Au Chak Leung , Ng Chi Fai , Ng Simon Siu Man , Gollasch Maik , Yao Xiaoqiang , Huang Yu 
Published: February 2011

Objective—
The purpose of this study was to examine the hypothesis that angiotensin II (Ang II) induced endothelial cyclooxygenase-2 (COX-2) expression, which in turn mediated the generation of proinflammatory cytokines.

Methods and Results—

Western blot analysis on primary rat endothelial cells showed Ang II induced COX-2 expression, which was abolished by cotreatment of p38 mitogen-activated protein kinase (SB 202190) and extracellular signal–regulated kinase 1/2 (PD 98059) inhibitors. Protein kinase C
δ
(PKC
δ
) inhibitor (rottlerin) prevented extracellular signal–regulated kinase 1/2 phosphorylation and COX-2 expression. The pivotal role of PKC
δ
was further supported by a similar stimulatory effect of the PKC activator on COX-2 expression, signified by Ang II–stimulated translocation of PKC
δ
to the plasma membrane, and confirmed by PKC
δ
phosphorylation at Tyr311. Small interfering RNA targeting PKC
δ
diminished COX-2 expression, which was further abrogated by SB 202190. Human mesenteric arteries incubated with Ang II showed increased levels of endothelial COX-2 and monocyte chemoattractant protein-1; the former was inhibited by SB 202190 plus rottlerin, whereas the latter was prevented by COX-2 inhibitor.

Conclusion—

The present study pinpoints a novel role of PKC
δ
in Ang II–induced endothelial COX-2 upregulation and identifies a COX-2-dependent proatherosclerotic cytokine monocyte chemoattractant protein-1. The findings raise the possibility of curtailing endothelial COX-2 expression as a means of limiting or preventing vascular inflammation.
Insulin Resistance and the Relationship of a Dyslipidemia to Coronary Heart Disease
Authors: Robins Sander J. , Lyass Asya , Zachariah Justin P. , Massaro Joseph M. , Vasan Ramachandran S. 
Published: February 2011

Objective—
The goal of this study was to examine the effect of insulin resistance (IR) in subjects without diabetes on the relationship of a dyslipidemia with high triglycerides and low high-density lipoprotein cholesterol (HDL-C) to the development of coronary heart disease (CHD).

Methods and Results—

Lower and higher fasting plasma HDL-C and triglyceride concentrations (defined at the study population median) and presence or absence of IR (defined by upper quartile Homeostatic Model Assessment values) were related to the development of myocardial infarction or CHD death in Framingham Heart Study participants without diabetes or a history of CHD (n=2910) attending the 1991 to 1995 examination. During follow-up (mean, 14 years), 128 participants experienced an incident CHD event. With Kaplan-Meier plots, the incidence of CHD was significantly greater with than without IR at either the lowest HDL-C or the highest triglycerides (
P
<0.001). In multivariable Cox models adjusted for major CHD risk factors, including waist circumference, only subgroups with IR had a significantly higher incidence of CHD. Compared with a reference group without IR and with higher-than-median HDL-C or lower-than-median triglycerides, the hazard ratio (HR) for incident events was significant with only IR and a lower HDL-C (HR 2.83,
P
<0.001) or higher triglycerides (HR 2.50,
P
<0.001). These findings were similar in men and women.

Conclusion—
In this community-based sample exclusive of diabetes, incident CHD risk associated with plasma HDL-C or triglycerides was significantly increased only in the presence of IR.
Timeliness of Tissue-Type Plasminogen Activator Therapy in Acute Ischemic Stroke
Authors: Fonarow Gregg C. , Smith Eric E. , Saver Jeffrey L. , Reeves Mathew J. , Bhatt Deepak L. , Grau-Sepulveda Maria V. , Olson DaiWai M. , Hernandez Adrian F. , Peterson Eric D. , Schwamm Lee H. 
Published: February 2011

Background—
The benefits of intravenous tissue-type plasminogen activator (tPA) in acute ischemic stroke are time dependent, and guidelines recommend an arrival to treatment initiation (door-to-needle) time of ≤60 minutes.

Methods and Results—

Data from acute ischemic stroke patients treated with tPA within 3 hours of symptom onset in 1082 hospitals participating in the Get With the Guidelines–Stroke Program from April 1, 2003, to September 30, 2009 were studied to determine frequency, patient and hospital characteristics, and temporal trends in patients treated with door-to-needle times ≤60 minutes. Among 25 504 ischemic stroke patients treated with tPA, door-to-needle time was ≤60 minutes in only 6790 (26.6%). Patient factors most strongly associated with door-to-needle time ≤60 minutes were younger age, male gender, white race, or no prior stroke. Hospital factors associated with ≤60 minute door-to-needle time included greater annual volumes of tPA-treated stroke patients. The proportion of patients with door-to-needle times ≤60 minutes varied widely by hospital (0% to 79.2%) and increased from 19.5% in 2003 to 29.1% in 2009 (
P
<0.0001). Despite similar stroke severity, in-hospital mortality was lower (adjusted odds ratio, 0.78; 95% confidence interval, 0.69 to 0.90;
P
<0.0003) and symptomatic intracranial hemorrhage was less frequent (4.7% versus 5.6%;
P
<0.0017) for patients with door-to-needle times ≤60 minutes compared with patients with door-to-needle times >60 minutes.

Conclusions—
Fewer than one-third of patients treated with intravenous tPA had door-to-needle times ≤60 minutes, with only modest improvement over the past 6.5 years. These findings support the need for a targeted initiative to improve the timeliness of reperfusion in acute ischemic stroke.
Sex Differences in the Response to Poly(ADP-ribose) Polymerase-1 Deletion and Caspase Inhibition After Stroke
Authors: Liu Fudong , Lang Jesse , Li Jun , Benashski Sharon E. , Siegel Matthew , Xu Yan , McCullough Louise D. 
Published: February 2011

Background and Purpose—
Emerging data suggest that the molecular cell death pathways triggered by ischemic insults differ in the male and female brain. Cell death in males is initiated by poly(ADP-ribose) polymerase-1 (PARP-1) activation; however, manipulation of this pathway paradoxically increases ischemic damage in females. In contrast, females are exquisitely sensitive to caspase-mediated cell death. The effect of caspase inhibition in PARP-1 knockout mice was evaluated to determine if the detrimental effects of PARP deletion in females were secondary to increased caspase activation.

Methods—

-Focal stroke was induced by transient or permanent middle cerebral artery occlusion (MCAO) in wild-type (WT) and PARP-1
−/−
mice of both sexes. The pan-caspase inhibitor, quinoline-Val-Asp(Ome)-CH2-O-phenoxy (Q-VD-OPh), was administered 90 minutes after middle cerebral artery occlusion. Infarct size and neurological sores were assessed. Separate cohorts were used for protein analysis for PAR, Apoptosis inducing factor (AIF), caspase-9, and caspase-3.

Results—

WT mice of both sexes had increased nuclear AIF after stroke compared to PARP-1
−/−
mice. PARP-1
−/−
females had higher mitochondrial cytochrome C and activated caspase-9 and -3 levels than WT female mice. PARP-1
−/−
females also had an increase in stroke-induced cytosolic cytochrome C release compared with WT females, which was not seen in males. Q-VD-OPh decreased caspase-9 in both males and females but only led to reduction of infarct in females. PARP-1
−/−
males had smaller infarcts, whereas PARP-1
−/−
females had larger strokes compared with WT. Q-VD-OPh significantly decreased infarct in both WT and PARP-1
−/−
females in both transient and permanent MCAO models, but had no effect in males.

Conclusions—

Deletion of PARP-1 reduces infarct in males but exacerbates injury in females. PARP-1
−/−
females have enhanced caspase activation. The detrimental effects of PARP loss in females can be reversed with caspase inhibition.
Cerebral Infarction After Subarachnoid Hemorrhage Contributes to Poor Outcome by Vasospasm-Dependent and -Independent Effects
Authors: Vergouwen Mervyn D.I. , Ilodigwe Don , Macdonald R. Loch 
Published: February 2011

Background and Purpose—
The pathogenesis of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage remains incompletely understood. It is generally assumed that it is caused by angiographic vasospasm. Our aim was to clarify the relationship among angiographic vasospasm, neurological worsening, cerebral infarction, and poor outcome and to investigate whether cerebral infarction also contributes to poor outcome by vasospasm-independent effects.

Methods—
This exploratory analysis used data from 413 patients included in the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial. We studied the incidence of neurological worsening, cerebral infarction, and poor outcome in patients with and without angiographic vasospasm. Path analysis implemented by structural equation modeling was performed to determine direct and indirect path coefficients.

Results—
Of the 194 patients with moderate to severe vasospasm, 43% had neurological worsening of any cause, 20% had cerebral infarction, and 46% poor outcome. Path coefficients for direct effects on poor outcome were 0.20 for World Federation of Neurological Surgeons Grade 4 to 5, 0.13 for history of hypertension, 0.19 for angiographic vasospasm, 0.16 for neurological worsening, and 0.11 for new cerebral infarction. Cerebral infarction contributed to poor outcome by vasospasm-dependent and -independent effects.

Conclusions—
Our data show that the majority of patients with moderate to severe angiographic vasospasm did not have neurological worsening of any cause or cerebral infarction. Besides, cerebral infarction also has a direct effect on outcome independent of angiographic vasospasm. This suggests that other coexisting factors might be involved in the pathogenesis of delayed cerebral ischemia, which should also be an important research target to improve outcome after subarachnoid hemorrhage.
Age-Dependent Susceptibility to Infarct Growth in Women
Authors: Gokcay Figen , Arsava Ethem Murat , Baykaner Tuna , Vangel Mark , Garg Priya , Wu Ona , Singhal Aneesh B. , Furie Karen L. , Sorensen A. Gregory , Ay Hakan 
Published: February 2011

Background and Purpose—
It is not known if there is a relationship between gender and tissue outcome in human ischemic stroke. We sought to identify whether the proportion of initially ischemic to eventually infarcted tissue was different between men and women with ischemic stroke.

Methods—
We studied 141 consecutive patients with acute ischemic stroke who had a baseline MRI obtained within 12 hours of symptom onset, a follow-up imaging on Day 4 or later, and diffusion-weighted imaging/mean transmit time mismatch on initial MRI. Lesion growth was calculated as percentage of mismatch tissue that underwent infarction on follow-up (percentage mismatch lost). Multivariable analyses explored the effect of gender and other predictors of tissue outcome on percentage mismatch lost.

Results—

There was no difference in median percentage mismatch lost between men (19%) and women (11%;
P
=0.720). There was, however, an interaction between gender and age; median percentage mismatch lost was 7% (0% to 12%) in women and 18% (1% to 35%) in men younger than the population median (71 years,
P
=0.061). The percentage mismatch lost was not different between men and women ≥71 years old (25% in both groups). The linear regression model revealed gender (
P
=0.027) and the interaction between age and gender (
P
=0.023) as independent predictors of percentage mismatch lost.

Conclusions—
There is an age-by-gender interaction in tissue outcome after ischemic stroke; brain infarcts in women <70 years grow approximately 50% less than infarcts in their male counterparts. These findings extend the well-known concept that there is a differential age-by-gender effect on stroke incidence, mortality, and functional outcome to the tissue level.
Ethnicity and Functional Outcome After Stroke
Authors: McNaughton Harry , Feigin Valery , Kerse Ngaire , Barber P. Alan , Weatherall Mark , Bennett Derrick , Carter Kristie , Hackett Maree , Anderson Craig 
Published: February 2011

Background and Purpose—
There is limited information on the influence of ethnicity on functional outcome after stroke. We examined functional outcomes among European New Zealanders, Māori, Pacific, and Asian people 6 months after stroke in a population-based context.

Methods—
This was a prospective incidence and 6-month outcomes study of all new stroke patients (excluding subarachnoid hemorrhage) that occurred over 1 year in a defined geographical area in Auckland, New Zealand, during 2002 to 2003. Ethnicity was self-defined. Outcome measures included the Frenchay Activities Index, 36-item Short Form questionnaire, independence, death, composite of death and dependence, and living situation.

Results—
Functional measures were available in 1127 patients 6 months after stroke. Frenchay Activities Index scores were associated with ethnicity on both univariable and multivariable analysis, with Asian and Pacific people having worse scores. Physical Component Summary score of the 36-item Short Form was associated with ethnicity on univariable (scores for Pacific, Māori, and Asian people were higher than those for Europeans) but not multivariable analysis. Asian people were less likely to be dead compared to Europeans, and Pacific people were more likely to be dependent on others for help than Europeans. Pacific people were more likely to be dead or dependent than Europeans. Asian and Pacific people were more likely to be living at home than Europeans.

Conclusions—
Ethnicity was associated independently with functional outcomes. The association was attenuated when adjusted for stroke severity and other covariates. The direction of the relationship was not consistent between measures for individual ethnic groups.
The Functional Benefits of Tilt Adaptation
Authors: Kristjánsson Árni 
Published: February 2011

AbstractMany have argued that effects of adaptation, such as aftereffects from motion or tilt, reflect that the visual system hones its responses in on the characteristics of the adapting stimulus. This view entails that on average, the discrimination of the characteristics of an adapting stimulus should become easier as viewing time increases since the variation in the response gradually adapts to the range and variation in the stimulus. Here this was tested for adaptation to tilt. Observers viewed a Gabor patch which varied in contrast from 0 to 74% at a rate of 0.6 Hz, for 4, 8, 16 or 32 s, after which the Gabor patch changed orientation (at the point when contrast was 0). The results show that the longer the observers adapt to the dynamic Gabor, the better they become at discriminating between clockwise (CW) or counterclockwise (CCW) changes in tilt (orientation) of the same patch. Experiment 2 confirms that both the direct and indirect tilt aftereffects are seen with this contrast varying Gabor patch and Experiment 3 shows that the aftereffects are only slightly smaller than in other studies with stimuli such as lines and sinusoidal gratings. These results show that adaptation to tilt leads to better discrimination around the orientation of the adapting stimulus itself, and that discrimination performance improves steadily with increased adaptation time. The results support proposals that the visual system adjusts its response characteristics to the properties of the visual input at a given time.
Sound Location Can Influence Audiovisual Speech Perception When Spatial Attention Is Manipulated
Authors: Möttönen Riikka , Tiippana Kaisa , Sams Mikko , Puharinen Hanna 
Published: February 2011

AbstractAudiovisual speech perception has been considered to operate independent of sound location, since the McGurk effect (altered auditory speech perception caused by conflicting visual speech) has been shown to be unaffected by whether speech sounds are presented in the same or different location as a talking face. Here we show that sound location effects arise with manipulation of spatial attention. Sounds were presented from loudspeakers in five locations: the centre (location of the talking face) and 45°/90° to the left/right. Auditory spatial attention was focused on a location by presenting the majority (90%) of sounds from this location. In Experiment 1, the majority of sounds emanated from the centre, and the McGurk effect was enhanced there. In Experiment 2, the major location was 90° to the left, causing the McGurk effect to be stronger on the left and centre than on the right. Under control conditions, when sounds were presented with equal probability from all locations, the McGurk effect tended to be stronger for sounds emanating from the centre, but this tendency was not reliable. Additionally, reaction times were the shortest for a congruent audiovisual stimulus, and this was the case independent of location. Our main finding is that sound location can modulate audiovisual speech perception, and that spatial attention plays a role in this modulation.
An Analytical Model of Wave Bottom Boundary Layers Incorporating Turbulent Relaxation and Diffusion Effects
Authors: Zou Qingping 
Published: February 2011

AbstractTo calculate the effects of turbulent relaxation on oscillatory turbulent boundary layers, a viscoelastic term is added to an eddy viscosity model. The viscoelastic term parameterizes the lag of turbulent properties in response to imposed oscillatory shear and is proportional to the ratio between the timescales of eddy dissipation and of the oscillating flow. It is found that the turbulent relaxation plays an important role in the phase variations of velocity and shear stress with elevation, and that it decreases the friction factor and the phase lead of bed shear stress over free stream velocity.To assess the effects of turbulent diffusion in this problem, the viscoelastic model is extended by further introducing a turbulent diffusion term in the model. The comparisons between these two models indicate that turbulent diffusion significantly reduces the magnitudes of shear stress and velocity perturbation in the outer region of the boundary layer. It is also found that the effects of turbulent relaxation and diffusion increase with increasing relative roughness. As a result, the analytical solutions demonstrate an overall improvement over the eddy viscosity model in predicting the observed temporal evolution of velocity and shear stress profiles; this improvement is more distinct for rough beds than smooth beds.