bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Human Cytomegalovirus Virion Possesses an Activated Casein Kinase II That Allows for the Rapid Phosphorylation of the Inhibitor of NF-κB, IκBα
Authors: Nogalski Maciej T. , Podduturi Jagat P. , DeMeritt Ian B. , Milford Liesl E. , Yurochko Andrew D. 
Published: March 2007

ABSTRACTWe documented that the NF-κB signaling pathway was rapidly induced following human cytomegalovirus (HCMV) infection of human fibroblasts and that this induced NF-κB activity promoted efficient transactivation of the major immediate-early promoter (MIEP). Previously, we showed that the major HCMV envelope glycoproteins, gB and gH, initiated this NF-κB signaling event. However, we also hypothesized that there were additional mechanisms utilized by the virus to rapidly upregulate NF-κB. In this light, we specifically hypothesized that the HCMV virion contained IκBα kinase activity, allowing for direct phosphorylation of IκBα following virion entry into infected cells. In vitro kinase assays performed on purified HCMV virion extract identified bona fide IκBα kinase activity in the virion. The enzyme responsible for this kinase activity was identified as casein kinase II (CKII), a cellular serine-threonine protein kinase. CKII activity was necessary for efficient transactivation of the MIEP and IE gene expression. CKII is generally considered to be a constitutively active kinase. We suggest that this molecular characteristic of CKII represents the biologic rationale for the viral capture and utilization of this kinase early after infection. The packaging of CKII into the HCMV virion identifies that diverse molecular mechanisms are utilized by HCMV for rapid NF-κB activation. We propose that HCMV possesses multiple pathways to increase NF-κB activity to ensure that the correct temporal regulation of NF-κB occurs following infection and that sufficient threshold levels of NF-κB are reached in the diverse array of cells, including monocytes and endothelial cells, infected in vivo.
Mitogen-Activated Protein Kinases Activate the Nuclear Localization Sequence of Human Papillomavirus Type 11 E1 DNA Helicase To Promote Efficient Nuclear Import
Authors: Yu Jei-Hwa , Lin Biing Yuan , Deng Wentao , Broker Thomas R. , Chow Louise T. 
Published: March 2007

ABSTRACT
Human and animal papillomavirus DNA replicates as multicopy nuclear plasmids. Replication requires two viral proteins, the origin-recognition protein E2 and the replicative DNA helicase E1. Using genetic, biochemical, and immunofluorescence assays, we demonstrated that efficient nuclear import of the human papillomavirus (HPV) type 11 E1 protein depends on a codominant bipartite nuclear localization sequence (NLS) and on phosphorylation of the serine residues S89 and S93 by the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase, and c-Jun N-terminal protein kinase. The NLS and the MAPK substrates are located within a 50-amino-acid-long peptide near the amino terminus, previously designated the localization regulatory region (LRR). The downstream NLS overlaps the cyclin-binding motif RRL, which is necessary for phosphorylation by the cyclin-dependent kinases to inactivate a dominant nuclear export sequence, also in the LRR. Alanine mutations of the MAPK substrates significantly impaired nuclear import, whereas phospho-mimetic mutations partially restored nuclear import. We further identified two MAPK docking motifs near the C terminus of E1 that are conserved among E1 proteins of many HPVs and bovine papillomavirus type 1. Mutations of these MAPK docking motifs or addition of specific MAPK inhibitors significantly reduced nuclear import. Interestingly, a fraction of the NLS-minus E1 protein was cotransported with the E2 protein into the nucleus and supported transient viral DNA replication. In contrast, E1 proteins mutated in the MAPK docking motifs were completely inactive in transient replication, an indication that additional properties were adversely affected by those changes.
Sphingomyelinase Restricts the Lateral Diffusion of CD4 and Inhibits Human Immunodeficiency Virus Fusion
Authors: Finnegan Catherine M. , Rawat Satinder S. , Cho Edward H. , Guiffre Danielle L. , Lockett Stephen , Merrill Alfred H. , Blumenthal Robert 
Published: March 2007

ABSTRACT
Previously, we reported that treatment of cells with sphingomyelinase inhibits human immunodeficiency virus type 1 (HIV-1) entry. Here, we determined by measuring fluorescence recovery after photobleaching that the lateral diffusion of CD4 decreased 4-fold following sphingomyelinase treatment, while the effective diffusion rate of CCR5 remained unchanged. Notably, sphingomyelinase treatment of cells did not influence gp120 binding, HIV-1 attachment, or fluid-phase and receptor-mediated endocytosis. Furthermore, sphingomyelinase treatment did not affect the membrane disposition of the HIV receptor proteins CD4, CXCR4, and CCR5, as determined by Triton X-100 extraction. Restriction of CD4 diffusion by antibody cross-linking also inhibited HIV infection. We therefore interpret the decrease in CD4 lateral mobility following sphingomyelinase treatment in terms of clustering of CD4 molecules. Examination of fusion intermediates indicated that sphingomyelinase treatment inhibited HIV at a step in the fusion process after CD4 engagement. Maximal inhibition of fusion was observed following short coculture times and with target cells that express low levels of CD4. As HIV entry into cells requires the sequential engagement of viral envelope protein with CD4 and coreceptor, we propose that sphingomyelinase inhibits HIV infection by inducing CD4 clustering that prevents coreceptor engagement and HIV fusion.
Epigenetic Status of an Adenovirus Type 12 Transgenome upon Long-Term Cultivation in Hamster Cells
Authors: Hochstein Norbert , Muiznieks Indrikis , Mangel Laurence , Brondke Holger , Doerfler Walter 
Published: March 2007

ABSTRACT
The epigenetic status of integrated adenovirus type 12 (Ad12) DNA in hamster cells cultivated for about 4 decades has been investigated. Cell line TR12, a fibroblastic revertant of the Ad12-transformed epitheloid hamster cell line T637 with 15 copies of integrated Ad12 DNA, carries one Ad12 DNA copy plus a 3.9-kbp fragment from a second copy. The cellular insertion site for the Ad12 integrate, identical in both cell lines, is a >5.2-kbp inverted DNA repeat. The Ad12 transgenome is packaged around nucleosomes. The cellular junction is more sensitive to micrococcal nuclease at Ad12-occupied sites than at unoccupied sites. Bisulfite sequencing reveals complete de novo methylation in most of the 1,634 CpGs of the integrated viral DNA, except for its termini. Isolated unmethylated CpGs extend over the entire Ad12 integrate. The fully methylated transgenome segments are characterized by promoter silencing and histone H3 and H4 hypoacetylation. Nevertheless, there is minimal transcriptional activity of the late viral genes controlled by the fully methylated major late promoter of Ad12 DNA.
Amino Acid 226 in the Hemagglutinin of H9N2 Influenza Viruses Determines Cell Tropism and Replication in Human Airway Epithelial Cells
Authors: Wan Hongquan , Perez Daniel R. 
Published: March 2007

ABSTRACT
Influenza A viruses of the H9N2 subtype are endemic in poultry in many Eurasian countries and have occasionally caused clinical respiratory diseases in humans. While some avian H9N2 viruses have glutamine (Q) at amino acid position 226 of the hemagglutinin (HA) receptor-binding site, an increasing number of isolates have leucine (L) at this position, which has been associated with the establishment of stable lineages of the H2 and H3 subtypes of viruses in humans. Little is known about the importance of this molecular trait in the infection of H9N2 viruses in humans. We show here that during the course of a single cycle of infection in human airway epithelial (HAE) cells cultured in vitro, the L-226-containing H9N2 viruses displayed human virus-like cell tropisms (preferentially infecting nonciliated cells) different from the tropisms showed by Q-226-containing H9N2 isolates (which infect both ciliated and nonciliated cells at ratios of 1:1 to 3:2) or other waterfowl viruses (which preferentially infect ciliated cells). During multiple cycles of replication in HAE cultures, L-226-containing H9N2 isolates grew consistently more efficiently and reached approximately 100-fold-higher peak titers than those containing Q-226, although peak titers were significantly lower than those induced by human H3N2 viruses. Our results suggest that the variation in residue 226 in the HA affects both cell tropism and replication of H9N2 viruses in HAE cells and may have implications for the abilities of these viruses to infect humans.
Long-Term Control of Simian Immunodeficiency Virus Replication with Central Memory CD4
+
T-Cell Preservation after Nonsterile Protection by a Cytotoxic T-Lymphocyte-Based Vaccine
Authors: Kawada Miki , Tsukamoto Tetsuo , Yamamoto Hiroyuki , Takeda Akiko , Igarashi Hiroko , Watkins David I. , Matano Tetsuro 
Published: March 2007

ABSTRACT

Induction of virus-specific CD8
+
cytotoxic T-lymphocyte (CTL) responses is a promising strategy for AIDS vaccine development. However, it has remained unclear if or how long-term viral containment and disease control are attainable by CTL-based nonsterile protection. Here, we present three rhesus macaques that successfully maintained Env-independent vaccine-based control of simian immunodeficiency virus (SIV) mac239 replication without disease progression for more than 3 years. SIV-specific neutralizing antibody induction was inefficient in these controllers. Vaccine-induced Gag-specific CTLs were crucial for the chronic as well as the primary viral control in one of them, whereas those Gag-specific CTL responses became undetectable and CTLs specific for SIV antigens other than Gag, instead, became predominant in the chronic phase in the other two controllers. A transient CD8
+
cell depletion experiment 3 years postinfection resulted in transient reappearance of plasma viremia in these two animals, suggesting involvement of the SIV non-Gag-specific CTLs in the chronic SIV control. This sustained, neutralizing antibody-independent viral control was accompanied with preservation of central memory CD4
+
T cells in the chronic phase. Our results suggest that prophylactic CTL vaccine-based nonsterile protection can result in long-term viral containment by adapted CTL responses for AIDS prevention.
Early percutaneous transhepatic gallbladder drainage compared with endoscopic retrograde cholangiopancreatography and papillotomy treatment for severe gallstone associated acute pancreatitis
Authors: Yu Wenkui , Li Weiqin , Wang Zhiming , Ye Xianghong , Li Ning , Li Jieshou 
Published: March 2007

Abstract

Objective
Percutaneous transhepatic gallbladder drainage (PTGD) was compared with endoscopic treatment (within 72 hours after the onset of symptoms) in patients with severe biliary pancreatitis to evaluate the curative effect of PTGD in preventing bile track complications in these patients.

Methods
Eligible patients were randomised to receive early treatment with PTGD or endoscopic treatment. If the initial emergency endoscopic or PTGD treatment failed, patients received another drainage treatment within 24 hours. From November 2001 to August 2005, 101 patients were randomly assigned to early PTGD (n = 51) or endoscopic retrograde cholangiopancreatography (ERCP) (n = 50). Overall mortality, mortality due to pancreatitis and complications were compared in these two groups.

Results
48 of 52 patients were successfully treated with ERCP and 53 of 55 with PTGD. Seven patients (6.9%; three in the endoscopic treatment group and four in the PTGD group) died within four months after the onset of pancreatitis (p = 0.798); three patients in the endoscopic group and three in the PTGD group died from acute biliary pancreatitis. The overall rate of complications was similar in the two groups and there were no major differences in the incidence of local or systemic complications.

Conclusions
PTGD treatment is a simple, convenient and effective treatment of severe gallstone associated acute pancreatitis when endoscopic treatment fails.
Raised cardiac troponin T levels in patients without acute coronary syndrome
Authors: Wong P , Murray S , Ramsewak A , Robinson A , van Heyningen C , Rodrigues E 
Published: March 2007

Abstract

Objective
To investigate the frequency, diagnosis and outcome of patients admitted to hospital with acute coronary syndrome (ACS) or other conditions associated with raised levels of cardiac troponin T.

Design
Observational study.

Setting
A large university hospital.

Patients
Consecutive patients admitted over an 8-week period who had a serum troponin T test as part of their clinical assessment were included. Patients were separated into those with raised (⩾0.01 μg/l) or normal (&lt;0.01 μg/l) troponin T levels, and further categorised into those with or without a diagnosis of ACS.

Main outcome measures
In-hospital mortality in all patients; and 6-month hospital re-admissions and all-cause mortality in patients without or with ACS and raised levels of troponin T.

Results
Of 1021 patients, 118 patients had no ACS but raised troponin T levels, 195 had ACS with raised troponin T, 80 had ACS with normal troponin T and 628 had no ACS with normal troponin T. Their in-hospital all-cause mortalities were 36%, 18%, 0% and 3%, respectively (p&lt;0.001, highest mortality v other groups). 6-month all-cause mortality remained higher in patients without ACS and with raised levels of troponin T than in those with ACS and raised troponin T (42% v 29%; p = 0.020).

Conclusions
Patients without ACS but with raised levels of troponin T comprised 38% of all hospitalised patients found to have raised troponin T. These patients had worse in-hospital and 6-month outcome than those having ACS with raised levels of troponin T.
Heights and haematology: the story of haemoglobin at altitude
Authors: Windsor Jeremy S , Rodway George W 
Published: March 2007

Abstract
In order to compensate for the low partial pressure of oxygen at altitude, the human body undergoes a number of physiological changes. A vital component in this process is the increase in the concentration of circulating haemoglobin. The role of HIF-1α, erythropoietin and red blood cells in this acclimatisation process is described, together with the fall in plasma volume that increases the concentration of haemoglobin in the early stages of hypoxic exposure.
How do you treat bleeding disorders with desmopressin?
Authors: Özgönenel Bülent , Rajpurkar Madhvi , Lusher Jeanne M 
Published: March 2007

Abstract
Desmopressin is an analog of vasopressin that exerts a substantial haemostatic effect by inducing the release of von Willebrand factor from its storage sites in endothelial cells. It has proved useful in treating or preventing bleeding episodes in patients with von Willebrand disease, haemophilia A and platelet function defects. Its efficacy in achieving a satisfactory level of haemostasis has reduced the use of blood products to treat bleeding episodes. Clinicians need to become familiar with the use of this drug that has become a home medication for many patients with inherited bleeding disorders.
Prevalence and risk factors of fatty liver disease in the Shuiguohu district of Wuhan city, central China
Authors: Wang Zhongli , Xia Bing , Ma Chunwei , Hu Zhengguo , Chen Xiangqun , Cao Ping 
Published: March 2007

Abstract

Background
Fatty liver disease (FLD) is highly prevalent in Western countries, but recent data have shown that FLD is also emerging in China.

Aim
To investigate the prevalence and risk factors of FLD in the Shuiguohu district of Wuhan city, central China, during 1995–2004.

Methods
12247 individuals (7179 men and 5068 women) over 18 years of age who were living in the area were investigated for FLD in the Zhongnan Hospital of Wuhan University from 1995 to 2004. FLD was determined by the ultrasonographic method. Height, weight, blood pressure, fasting blood sugar, alanine aminotransferase, total cholesterol and triglyceride were determined by routine laboratory methods.

Results
The prevalence of FLD was 12.5% in 1995, and rose gradually to 24.5% by 2003–4. The prevalence was twice as high in men (28.1%) as in women (13.8%), and increased with age in females, and males &lt;60 years of age. Multivariate analysis showed that several risk factors were profoundly associated with the prevalence of FLD, including male sex, old age, obesity, hyperlipidaemia (cholesterol or triglyceride), fasting hyperglycemia and hypertension.

Conclusion
The prevalence of FLD in the Shuiguohu district of Wuhan city, central China, was shown to have increased during the 10-year period, 1995 to 2004. The FLD was found to be closely associated with sex, age, obesity and other metabolic syndrome features.
NT-proBNP and the diagnosis of left ventricular systolic dysfunction within two acute NHS trust catchment areas: the initial Teesside experience
Authors: Turley A J , Roberts A P , Davies A , Rowell N , Drury J , Smith R H , Shyam-Sundar A , Stewart M J 
Published: March 2007

Abstract

Purpose
To evaluate the predictive value of N-terminal pro B-type natiuretic peptide (NT-proBNP) reference cut-off values as diagnostic markers for left ventricular systolic dysfunction (LVSD).

Study design
A retrospective study assessing the use of NT-proBNP in the diagnostic algorithm for the investigation of patients with suspected signs and symptoms of LVSD presenting to primary care.

Results
A generic NT-proBNP cut-off (150 ng/l) value has similar negative and positive predictive valves, specificity and sensitivity compared to age and sex specific cut-off values.

Conclusion
When using NT-proBNP as a triage tool for screening patients with signs and symptoms suggestive of LVSD, a simple generic cut-off level is as effective as more complex age sex specific cut-off values.
Inhaled insulins
Authors: Ghosh Sujoy , Collier Andrew 
Published: March 2007

Abstract
As a result of knowledge gained from the management of asthma with inhalers and nebulisers, pulmonary delivery devices for insulin have been developed. Particle size of the aerosol particularly influences drug delivery. Although several pharmaceutical companies are developing different systems, Pfizer have launched the first inhaled insulin (Exubera). Clinical trials have taken place in patients with both type 1 and type 2 diabetes, but have shown similar glucose control as subcutaneous insulin delivery. However, patient satisfaction does seem to be increased in patients taking inhaled insulins. Further studies are needed to investigate compliance, side-effect profiles, quality of life, long-term glycaemia control and cost effectiveness.
ON GRAPH-THEORETIC IDENTIFICATIONS OF ADINKRAS, SUPERSYMMETRY REPRESENTATIONS AND SUPERFIELDS
Authors: DORAN C. F. , FAUX M. G. , GATES S. J. , HÜBSCH T. , IGA K. M. , LANDWEBER G. D. 
Published: March 2007

In this paper, we discuss off-shell representations of N-extended supersymmetry in one dimension, i.e. N-extended supersymmetric quantum mechanics, and following earlier work on the subject, we codify them in terms of graphs called Adinkras. This framework provides a method of generating all Adinkras with the same topology, and so also all the corresponding irreducible supersymmetric multiplets. We develop some graph theoretic techniques to understand these diagrams in terms of a relatively small amount of information, namely, at what heights various vertices of the graph should be "hung." We then show how Adinkras that are the graphs of N-dimensional cubes can be obtained for superfields satisfying constraints that involve superderivatives. This dramatically widens the range of supermultiplets that can be described using the superspace formalism and also organizes them. Other topologies for Adinkras are possible, and we show that it is reasonable that these are also the result of constraining superfields using superderivatives. We arrange the family of Adinkras with an N-cubical topology, and so also the sequence of corresponding irreducible supersymmetric multiplets, in a cyclic sequence, which we call the main sequence. We produce the N = 1 and N = 2 main sequences in detail, and indicate some aspects of the situation for higher N.
Simulation of Flow in Turbopump Vaneless and VanedDiffusers with Fluid Injection
Authors: Ogut Ali , Pastor Diego Garcia 
Published: March 2007

In future space missions by NASA there will be a need for “Space Transfer Vehicles” to perform varying orbital transfers and descents. This requires engines capable of producing different levels of thrust. To accomplish this, the turbopumps employed in these engines should efficiently provide a wide range of flow outputs. However, current fuel and oxidizer turbopumps with vaned diffusers do not perform efficiently at off‐design (low) flow rates mainly due to flow separation in the vaned diffuser.This paper evaluates the effectiveness of boundary layer control by fluid injection
(blowing) for suppressing or eliminating the flow separation in a vaned diffuser. A 3‐D flow
model including vaneless and vaned diffusers of a liquid hydrogen (LH2) turbopump is studied using the CFD code FIDAP. The paper presents the results of the model at design and offdesign flow conditions.The model results showed that flow separation occurs at the top or suction surface of the vaneless diffuser and at the bottom or pressure surface of the vaned diffuser at off‐design flow rates. When fluid injection was applied through the bottom surface of the vaned diffuser, the separated flow region was reduced almost entirely, resulting in an increase in pressure recovery of up to 21% with varying fluid injection rates. Results also showed that there is an optimum injection rate which is most effective in reducing or eliminating the region of flow separation.
Vibration Criteria Considered from Case Studies of ActiveMagnetic Bearing Equipped Rotating Machines
Authors: Matsushita Osami , Kanemitsu Youichi , Azuma Takao , Fukushima Yasuo 
Published: March 2007

The main part of turbo machinery is conventionally supported by oil film lubricated bearings.
The rotor vibrations can be suppressed within low levels as to satisfy vibration criteria, e.g.,
ISO standards for general rotors and API 617 for process compressors. Recently, the
sophisticated advantages of the active magnetic bearing (AMB) have been increasing the
number of applications to industrial rotors. The AMB vibration control design requires
the weak support which induces inevitably large vibration amplitude, though it is normal for
AMB itself. Vibration criteria indicated by present standards are thus too strict for AMB
equipped rotors. The difference of the bearing dynamic characteristics between the oil film
lubricated bearing and the AMB compels us to prepare a new ISO standard which
recommends the acceptance of higher vibration levels for AMB operation.In this paper, a case study was executed concerning AMB equipped LP and HP
compressors experiencing long‐term operation with no major trouble since December, 1992.
The rotating rated speed, 10900 rpm, is beyond the first bending critical speed with 5300 kW
of power. The average value of the rotor vibration was about 50 μmpp in the site operation. By reviewing the rotor design concept and field data of these AMB equipped machines, new vibration criteria are considered for a proposal of ISO standardization.