bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditional disruption of ubiquitous calpains in the mouse
Authors: Tan Yinfei , Dourdin Nathalie , Wu Chao , De Veyra Teresa , Elce John S. , Greer Peter A. 
Published: June 2006

AbstractUbiquitous μ‐ and m‐calpain proteases are implicated in development and apoptosis. They are heterodimers consisting of 80‐kDa catalytic subunits encoded by capn1 and capn2, respectively, and a common 28‐kDa regulatory subunit encoded by capn4. The regulatory subunit is required to maintain stability and activity of μ‐ and m‐calpains; thus, genetic disruption of capn4 was predicted to eliminate both calpain activities. Germline disruption of capn4 caused embryonic lethality, hampering the use of those mouse models to explore physiological calpain functions. Here we describe a loxP/cre conditional capn4 targeted mouse model that enables tissue‐specific and temporal deletion of calpain activity. Disruption of the floxed capn4 gene using a ubiquitous cytomegalovirus promoter driven Cre recombinase transgene led to midgestation embryonic lethality. Fibroblasts from these embryos lacked detectable regulatory subunit expression, had reduced levels of the μ‐ and m‐calpain catalytic subunits, and had no detectable μ‐ and m‐calpain activities. These defects were corrected with a capn4‐encoding lentivirus. genesis 44:297–303, 2006. © 2006 Wiley‐Liss, Inc.
A bubble‐stabilized finite element method for Dirichlet constraints on embedded interfaces
Authors: Mourad Hashem M. , Dolbow John , Harari Isaac 
Published: June 2006

AbstractWe examine a bubble‐stabilized finite element method for enforcing Dirichlet constraints on embedded interfaces. By ‘embedded’ we refer to problems of general interest wherein the geometry of the interface is assumed independent of some underlying bulk mesh. As such, the robust imposition of Dirichlet constraints using a Lagrange multiplier field is not trivial. To focus issues, we consider a simple one‐sided problem that is representative of a wide class of evolving‐interface problems. The bulk field is decomposed into coarse and fine scales, giving rise to coarse‐scale and fine‐scale one‐sided sub‐problems. The fine‐scale solution is approximated with bubble functions, permitting static condensation and giving rise to a stabilized form bearing strong analogy with a classical method. Importantly, the method is simple to implement, readily extends to multiple dimensions, obviates the need to specify any free stabilization parameters, and can lead to a symmetric, positive‐definite system of equations. The performance of the method is then examined through several numerical examples. The accuracy of the Lagrange multiplier is compared to results obtained using a local version of the domain integral method. The variational multiscale approach proposed herein is shown to both stabilize the Lagrange multiplier and improve the accuracy of the post‐processed fluxes. Copyright © 2006 John Wiley & Sons, Ltd.
Localized excitons and defects in PbWO4 single crystals: a luminescence and photo‐thermally stimulated disintegration study
Authors: Krasnikov A. , Nikl M. , Zazubovich S. 
Published: June 2006

AbstractThe cover picture refers to the article by Aleksei Krasnikov et al., that was selected as Editor's Choice [1]. It depicts a fragment of a lead tungstate (PbWO4) crystal lattice structure and illustrates the complex anion (WO4)2– tetrahedra bonded to the Pb2+ cation. Perturbation of the (WO4)2– tetrahedra by defects nearby results in exciton localization near the defects and a slightly different emission spectrum, which is shown in the diagram. Localized excitons are evidenced for the first time in the PbWO4 structure. Under selective irradiation of PbWO4 crystals in the ultraviolet spectral region, the decay of various localized excitons into stable defects takes place, which can be detected by a sensitive thermally stimulated luminescence method. Aleksei Krasnikov is a PhD student at the University of Tartu, Estonia. Martin Nikl holds a position as a senior scientist and head of the Laboratory of Luminescence and Scintillation Materials at the Institute of Physics of the Czech Academy of Sciences. Svetlana Zazubovich is a senior scientist at the Institute of Physics, University of Tartu. The research groups of Martin Nikl and Svetlana Zazubovich have been collaborating closely for the last 15 years mainly in the field of optical spectroscopy of wide band‐gap scintillation materials.
Blockage of oncostatin M-induced LDL receptor gene transcription by a dominant-negative mutant of C/EBPβ
Authors: Zhou Yue , Zhang Fang , Abidi Parveen , Lin Meihong , Thiel Gerald , Liu Jingwen 
Published: June 2006

OM (oncostatin M) activates the human LDLR [LDL (low-density lipoprotein) receptor] gene transcription in HepG2 cells through the SIRE (sterol-independent regulatory element) of LDLR promoter. The SIRE sequence consists of a C/EBP (CCAAT/enhancer-binding protein)-binding site and a CRE (cAMP-response element). Our previous studies [Zhang, Ahlborn, Li, Kraemer and Liu (2002) J. Lipid Res. 43, 1477–1485; Zhang, Lin, Abidi, Thiel and Liu (2003) J. Biol. Chem. 278, 44246–44254] have demonstrated that OM transiently induces EGR-1 (early growth response gene product 1) expression and EGR-1 activates LDLR transcription primarily through a protein–protein interaction with C/EBPβ, which serves as a co-activator of EGR-1. In the present study, we examined the direct role of C/EBPβ as a transactivator in OM-regulated LDLR gene transcription independent of EGR-1. We show that OM induces C/EBPβ expression with kinetics slower than EGR-1 induction. A significant increase in C/EBPβ protein level is detected by 2 h of OM treatment and remains elevated for 24 h. Chromatin immunoprecipitation assays demonstrate that the amount of C/EBPβ bound to the LDLR SIRE sequence is increased 2.8-fold of control by 2 h of OM treatment, reached the highest level of 8-fold by 4 h, and slowly declined thereafter. To further examine the requirement of C/EBPβ in OM-stimulated LDLR expression, we developed a His-tagged dominant-negative mutant of C/EBPβ (His–C/EBPβ-P4; where P4 is plasmid 4 in our mutation series), consisting of the DNA-binding and leucine zipper domains of C/EBPβ (amino acids 246–345). Expression of His–C/EBPβ-P4 in HepG2 cells significantly diminishes the OM-induced increase in LDLR promoter activity and the elevation of endogenous LDLR mRNA expression. Taken together, these new findings identify C/EBPβ as an OM-induced transactivator in LDLR gene transcription and provide a better understanding of the molecular mechanism underlying the sterol-independent regulation of LDLR expression.
Gaps in parental understandings and experiences of vaccine‐preventable diseases: a qualitative study
Authors: Hilton S. , Hunt K. , Petticrew M. 
Published: June 2006

AbstractObjective  To explore parents’ understandings of the diseases included in the current UK Childhood Immunization Programme (CIP), and the role of first‐ and second‐hand experiences of these diseases in assessments of their severity.Methods  A qualitative study in which 66 parents (58 mothers and 8 fathers) of children aged 6 years and below, and six mothers of immuno‐compromised children, took part in 18 focus group discussions between November 2002 and March 2003.Results  There were many gaps in parents’ knowledge about some vaccine‐preventable diseases, most notably diphtheria, tetanus and haemophilus influenzae type b, three of the diseases covered by the pentavalent vaccine (introduced into the UK CIP in 2004). These gaps led some parents to question the need for vaccination. First‐hand experiences of the diseases reinforced the need for vaccination in some cases (e.g. Men C), but undermined it in others (e.g. pertussis, measles, rubella, mumps). Poliomyelitis and diphtheria were no longer seen as a threat to children’s health in Britain. Some parents saw mumps as only a threat to boys’ health and rubella as only having relevance to girls’.Conclusions  As fewer parents have direct experiences of vaccine‐preventable diseases, there is an increasing need to provide parents with accessible information about these diseases. It is also important to recognize that direct or indirect experiences of any of the diseases may either heighten or diminish parents’ assessments of the severity of these diseases.
Perforin-independent rejection of transplanted human stem cells
Authors: Kaiser S , Kägi D , Ihorst G , Kapp U 
Published: June 2006

SummaryThe NOD/SCID mouse model is one of the most established model systems for the analysis of human stem cells in vivo. The lack of mature B and T cells renders NOD/SCID mice susceptible to transplantable human stem and progenitor cells. One remaining functional component of the immune system in NOD/SCID mice is natural killer (NK) cells. We rationalized that by eliminating NK cell-mediated cytotoxicity in this model system engraftment of human haematopoietic stem cells could be improved. Thus perforin-deficient NOD/SCID mice (PNOD/SCID) were generated, which display a complete lack of NK cell-mediated cytotoxicity. To test the engraftment potential of human stem cells in PNOD/SCID mice, we compared the repopulating potential of human haematopoietic stem cells in these mice with the repopulating potential in NOD/SCID mice. Upon injection with varying numbers of mononuclear cells from human cord blood, the number of engrafted PNOD/SCID mice was lower (34·8%) than the number of engrafted NOD/SCID mice (64·7%). Similarly, injection of purified CD34+ human cord blood cells led to engraftment in 32·3% PNOD/SCID versus 60% in NOD/SCID mice. Surprisingly, these results show that the inactivation of cytotoxic activity of NK cells in PNOD/SCID mice did not result in better engraftment with human haematopoietic stem cells. A potential reason for this observation could be that compensatory activation of NK cells in PNOD/SCID mice induces high levels of soluble factors resulting in an environment unfavourable for human stem cell engraftment.
Assessment ofin vitroimmunity toM ycobacterium tuberculosisin a human peripheral blood infection model using a luciferase reporter construct ofM. tuberculosisH37Rv
Authors: Al-Attiyah R , El-Shazly A , Mustafa A S 
Published: June 2006

SummaryProtective immune responses to tuberculosis in man are primarily cell-mediated and require the interaction of specific T cells, cytokines and activated macrophages. In the present study, Mycobacterium tuberculosis H37Rv labelled with luciferase reporter enzyme was used to analyse the anti-mycobacterial immunity in man using an in vitro whole blood infection model. Peripheral blood samples obtained from M. bovis bacille Calmette–Guérin (BCG)-vaccinated tuberculin-positive healthy volunteers (n = 23) were cultured with M. tuberculosis H37Rv reporter strain. The growth of bacteria in the whole blood cultures was monitored after 48 and 96 h of infection. The results showed that the growth of M. tuberculosis was significantly inhibited after 96 h (P &lt; 0·029) of culture. Among the cytokines studied, interleukin (IL)-10 and IL-12 were not detected at all, whereas low levels of interferon (IFN)-γ after 96 h (0·4 IU/ml) and tumour necrosis factor (TNF)-α after 48 (135 pg/ml) and 96 h (47 pg/ml) of culture were detected in the supernatants of whole blood infected with M. tuberculosis. The magnitude of bacterial growth correlated directly with the concentration of TNF-α detected after 48 h (r = 0·722) and 96 h (r = 0·747) of culture (P ≤ 0·0001 and P ≤ 0·0001, respectively). However, the addition of monoclonal antibodies specific to TNF-α and IFN-γ to the blood cultures did not alter mycobacterial growth indicating the role of other mechanisms/factors in restricting the growth of M. tuberculosis in whole blood cultures.
Abscess of the orbit arising 48 h after root canal treatment of a maxillary first molar
Authors: Koch F. , Breil P. , Marroquín B. B. , Gawehn J. , Kunkel M. 
Published: June 2006

AbstractAim  To discuss a rare, but severe complication arising following routine root canal treatment.Summary  An orbital abscess is reported that occurred following routine root canal treatment. A young, healthy female patient, with no history of chronic paranasal infection had undergone root canal treatment of the right maxillary first molar. On hospital admission, she presented with extensive periorbital swelling and discreet diplopia. Computed tomography imaging identified massive purulent sinusitis and subsequent involvement of the orbit via the inferior and medial orbital wall within 48 h after completion of root canal treatment. Immediate surgical drainage of the maxillary sinus and the orbit was established and a high dose of perioperative antibiotics (Amoxicillin/Clavulanic acid, Gentamycin, Metronidazole) were administered. Vision remained undisturbed and mobility of the globe recovered within 10 days.Key learning points • Rapid exacerbation of a periapical inflammation may occur following root canal treatment and may even involve the orbit.• A typical speed of disease progression or ophthalmic symptoms should alert the clinician to at least consider unusual early orbital spread of odontogenic infection.• When extra‐alveolar spread and especially orbital spread is suspected, immediate referral to a maxillofacial or other specialized unit is mandatory.
Candida peritonitis in a patient with necrotising cholecystitis and pancreatitis
Authors: Scheele Jan , Kujath Peter 
Published: June 2006

SummaryAn 80‐year‐old patient in previously excellent state of health presented with septic syndrome for gangrenous cholecystitis and concomitant pancreatitis. Diagnostic paracentesis revealed microbiological evidence of Candida albicans in the abdominal cavity. Laparoscopic cholecystectomy was performed and examination of histological specimens confirmed peritonitis by fungal perforation of the gall bladder. In a complicated postoperative course the patient was finally cured choosing voriconazole (Vfend) for antimycotic therapy.
Comparison of different protocols for DNA preparation and PCR for the detection of fungal pathogens in vitro
Authors: Lugert R. , Schettler C. , Gross U. 
Published: June 2006

SummaryAlthough a large number of different PCR protocols for the detection of fungal DNA from clinical samples have been described, a generally recognised standardisation has not yet been developed. In a first step, we compared six different methods to isolate DNA under in vitro conditions from Aspergillus fumigatus, Candida albicans and Saccharomyces cerevisiae with respect to efficiency and expenditure of time. To this end, methods were tested that are based on both mechanical and enzymatic/thermic lysis. Thereby, enzymatic/thermic lysis were shown to be superior to mechanical lysis, although these methods of DNA isolation were more time consuming. The subsequent comparison of three different PCR protocols showed real‐time PCR to be the most sensitive method.
Intervention in a Higher Education Market: a Case Study
Authors: Temple Paul 
Published: June 2006

AbstractIn many countries today, public higher education operates within some form of market framework, typically a government‐regulated quasi‐market. However, having created a market environment, how should the government agencies involved act when they wish to use higher education to achieve a particular policy goal? This paper considers the impact on the English higher education market of an initiative by the national funding agency to expand Chinese studies. It is argued that, in an already competitive market, this intervention led to the misallocation of resources because it encouraged universities to expand provision in ways that they would not otherwise have done. As a result, although some effective new provision resulted, excess capacity was created overall. It can be argued that the collective understanding of the universities about this specific market was more accurate than that of an expert committee advising on national provision. The paper suggests how intervention might have been more effectively arranged.
A Communitarian Approach: A Viewpoint on the Study of the Legal, Ethical and Policy Considerations Raised by DNA Tests and Databases
Authors: Etzioni Amitai 
Published: June 2006

This article seeks to outline a viewpoint on the study of the legal, ethical and policy considerations raised by DNA tests and databases (from here on, DNA usages). It does not delve into the specifics involved. It outlines a way of thinking that has proven productive elsewhere1 and seems promising in dealing with DNA usages in the United States, but little more. Given that this essay is about a communitarian approach that draws on specific communitarian values, I turn next to briefly present the approach here followed.Communitarianism is a social philosophy that maintains that society should articulate what is good, and asserts that such articulations are both necessary and legitimate. Communitarianism is often contrasted with classical liberalism, a philosophical position that holds that individuals should formulate their idea of good on their own. Communitarians examine the ways shared conceptions of the good (values) are formed, transmitted, justified, and enforced.
The Role of an Advanced Land Model in Seasonal Dynamical Downscaling for Crop Model Application
Authors: Shin D. W. , Bellow J. G. , LaRow T. E. , Cocke S. , O'Brien James J. 
Published: June 2006

Abstract
An advanced land model [the National Center for Atmospheric Research (NCAR) Community Land Model, version 2 (CLM2)] is coupled to the Florida State University (FSU) regional spectral model to improve seasonal surface climate outlooks at very high spatial and temporal resolution and to examine its potential for crop yield estimation. The regional model domain is over the southeast United States and is run at 20-km resolution, roughly resolving the county level. Warm-season (March–September) simulations from the regional model coupled to the CLM2 are compared with those from the model with a simple land surface scheme (i.e., the original FSU model). In this comparison, two convective schemes are also used to evaluate their roles in simulating seasonal climate, primarily for rainfall. It is shown that the inclusion of the CLM2 produces consistently better seasonal climate scenarios of surface maximum and minimum temperatures, precipitation, and shortwave radiation, and hence provides superior inputs to a site-based crop model to simulate crop yields. The FSU regional model with the CLM2 exhibits some capability in the simulation of peanut (Arachis hypogaea L.) yields, depending upon the convective scheme employed and the site selected.
Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein
Authors: Nielsen Marianne Jensby , Petersen Steen Vang , Jacobsen Christian , Oxvig Claus , Rees David , Møller Holger Jon , Moestrup Søren Kragh 
Published: June 2006

AbstractHaptoglobin-related protein (Hpr) is a primate-specific plasma protein associated with apolipoprotein L-I (apoL-I)-containing high-density lipoprotein (HDL) particles shown to be a part of the innate immune defense. Despite the assumption hitherto that Hpr does not bind to hemoglobin, the present study revealed that recombinant Hpr binds hemoglobin as efficiently as haptoglobin (Hp). However, in contrast to Hp, Hpr did not promote any high-affinity binding to the scavenger receptor CD163. Binding of hemoglobin to circulating native Hpr incorporated into the HDL fraction was indicated by hemoglobin-affinity precipitation of plasma Hpr together with apoL-I. In conclusion, plasma has 2 high-affinity hemoglobin-binding haptoglobins instead of one, but only Hp-hemoglobin complexes are efficiently recognized by CD163. Circulating Hpr-bound hemoglobin should therefore be taken into consideration when measuring “free” plasma hemoglobin. Furthermore, Hpr-bound hemoglobin might contribute to the biologic activity of the circulating apoL-I/Hpr-containing HDL particles.
Insulated piggyBac vectors for insect transgenesis
Authors: Sarkar Abhimanyu , Atapattu Asela , Belikoff Esther J , Heinrich Jörg C , Li Xuelei , Horn Carsten , Wimmer Ernst A , Scott Maxwell J 
Published: June 2006

Abstract

Background
Germ-line transformation of insects is now a widely used method for analyzing gene function and for the development of genetically modified strains suitable for pest control programs. The most widely used transposable element for the germ-line transformation of insects is piggyBac. The site of integration of the transgene can influence gene expression due to the effects of nearby transcription enhancers or silent heterochromatic regions. Position effects can be minimized by flanking a transgene with insulator elements. The scs/scs' and gypsy insulators from Drosophila melanogaster as well as the chicken β-globin HS4 insulator function in both Drosophila and mammalian cells.

Results
To minimize position effects we have created a set of piggyBac transformation vectors that contain either the scs/scs', gypsy or chicken β-globin HS4 insulators. The vectors contain either fluorescent protein or eye color marker genes and have been successfully used for germ-line transformation of Drosophila melanogaster. A set of the scs/scs' vectors contains the coral reef fluorescent protein marker genes AmCyan, ZsGreen and DsRed that have not been optimized for translation in human cells. These marker genes are controlled by a combined GMR-3xP3 enhancer/promoter that gives particularly strong expression in the eyes. This is also the first report of the use of the ZsGreen and AmCyan reef fluorescent proteins as transformation markers in insects.

Conclusion
The insulated piggyBac vectors should protect transgenes against position effects and thus facilitate fine control of gene expression in a wide spectrum of insect species. These vectors may also be used for transgenesis in other invertebrate species.
Utility of Computed Tomography and Magnetic Resonance Imaging Staging Before Completion Lymphadenectomy in Patients With Sentinel Lymph Node–Positive Melanoma
Authors: Aloia Thomas A. , Gershenwald Jeffrey E. , Andtbacka Robert H. , Johnson Marcella M. , Schacherer Christopher W. , Ng Chaan S. , Cormier Janice N. , Lee Jeffrey E. , Ross Merrick I. , Mansfield Paul F. 
Published: June 2006

Purpose Although melanoma patients with regional nodal metastases are frequently imaged with computed tomography (CT) and magnetic resonance imaging (MRI) scans, the efficacy of routine radiologic staging in asymptomatic patients with microscopic nodal involvement has not been established. To determine the utility of this approach, we analyzed the incidence of synchronous distant metastases (SDM) detected by CT or MRI of the head, chest, and abdomen in a large group of patients with sentinel lymph node (SLN) –positive melanoma. Patients and Methods Positive SLNs were identified in 314 (16.2%) of the 1,934 melanoma patients who underwent sentinel lymphadenectomy at our institution from 1996 to 2003. Within 3 months of sentinel lymphadenectomy, 270 (86.0%) of the 314 SLN-positive patients were radiologically staged. To determine which prognostic factors were associated with SDM, associations between final staging outcomes and clinicopathologic variables, including SLN tumor burden, were analyzed. Results CT and/or MRI scans identified lesions that were suspicious for SDM in 23 (8.6%) of the 270 patients who underwent staging. In eight of these patients, further diagnostic studies determined that these abnormalities were benign. The remaining 15 suspicious lesions were percutaneously biopsied (10 negative and five positive), yielding a radiologically detectable SDM rate of 1.9%. Detection of SDM was associated with primary tumor thickness (P = .011), ulceration (P = .018), and SLN tumor burden (P = .018). Conclusion These data suggest that the vast majority of asymptomatic patients with a new diagnosis of microscopic SLN-positive melanoma do not harbor radiologically detectable SDM and can proceed to completion lymph node dissection without immediate CT or MRI staging.