bluuebunny/crossref_metadata_2025 huggingface dataset:
The Knowledge‐Based Organization: An International Survey
Authors: Chase Rory L.
Published: September 2004

An international survey, sponsored by the Journal of Knowledge Management in association with the Best Practice Club™ and The Benchmarking Exchange, sought to explore the drivers and approaches to creating knowledge‐based organizations from the viewpoint of those practitioners who are actually responsible for implementing Knowledge Management as a business strategy. Three major conclusions have emerged from the study. Whilst organizations recognize the importance of creating, managing and transferring knowledge, so far they have been unable to translate this competitive need into organizational strategies. Secondly, successful Knowledge Management implementation is mainly linked to “soft” issues, such as organizational culture and people. Finally, most organizations are struggling to effectively use Knowledge Management tools and techniques. The study reveals that although most of the survey group understood the commercial or institutional imperative to implement Knowledge Management as an organizational strategy, few benchmarks of best practice have yet to emerge.
Rethinking Knowledge Work: Creating Value through Idiosyncratic Knowledge
Authors: Guns William D. , Välikangas Liisa
Published: September 2004

This paper adopts a way of looking at knowledge work that is inherently personal and more intimate: How we know depends on who we are. SRI’s Values and Lifestyles™ research offers empirical findings that help shape the knowledge profiles of different people. The knowledge profiles can be used to create, communicate and package knowledge more effectively. Such an approach to knowledge also helps us understand how the subjectivity of knowledge may greatly contribute to value creation in knowledge work.
Are You Creative?
Authors: Godfrey Sue
Published: September 2004

As part of Glaxo Wellcome’s executive development programme, leaders are finding new ways to release their own potential and generate creative climates for staff. A “storyboard” exercise to encourage creativity and an exercise to create supportive work climates, both used in the company’s programme, are discussed.
Mapping out the future progress of eB2B
Authors: Collins Russell
Published: September 2004

Highlights eBusiness‐to‐business (eB2B), which comprises 84 per cent of online revenue – strongest of all in the financial sector. Profiles the various companies involved – such as Westpac and Citicommerce, Chase, American Express, Cybercapital and Epoch Partners. Espouses that there is more than one way to succeed in this e‐area. Concludes that eB2B will be at the foundations of the new economy and that the new market leaders will, industry‐wide, take up the challenge.
Bringing risk management up to date in an e‐commerce world
Authors: Yee Chong Yen
Published: September 2004

Investigates risk and the difference e‐commerce has had on global markets and, in particular, how Western experts managed to get wrong the prospects for the future with regard to banks in Russia and Indonesia. Posits that analysing risk can be done in four different ways: identifying risk factors; evaluating likelihood and effect; prioritizing and budgeting; and planning. Uses two case studies for extra emphasis – BT‐UK versus Vodafone; and Eurasia Mining plc (UK), operating in Russia and gives good advice in the aftermath of these. Closes in stating that risk‐seeking is a factor of modern operational risk and it is a recipe for disaster.
A non‐classical type of alveolar macrophage response to Trichinella spiralis infection
Authors: Dzik J. M. , Gołos B. , Jagielska E. , Zieliṅski Z. , Wałajtys‐Rode E.
Published: September 2004

Studies of arginase expression and activity in guinea pig alveolar macrophages during Trichinella spiralis infection, prompted by earlier observation of innate lung response to the parasite, showed the macrophages to express both activity and protein of arginase type I. In cultured macrophages part of the enzyme was found to be always released to the extracellular medium. Whereas BCG in vivo treatment, alone or preceded by T. spiralis infection, stimulated arginase activity, T. spiralis infection alone affected the enzyme distribution between intracellular and extracellular fractions, and properties (Km and Vmax), rather than total (intracellular + extracellular) activity, with TGF‐β apparently responsible for a part of the effect. Anti‐TGF‐β antibody treatment of the animals influenced both arginase activation by Mn2+ and dependence of the enzyme‐catalysed reaction on pH. Whereas T. spiralis infection activated guinea pig alveolar macrophages by the type II macrophage activation, as indicated by constant arginase expression, associated with previously demonstrated lack of stimulation of nitric oxide production, BCG treatment invoked an alternative type of activation mechanism, reflected by stimulation of macrophage arginase, but not iNOS, activity.
High level of chromosome 15 aneuploidy in head and neck squamous cell carcinoma lesions identified by FISH analysis: limited value of β2‐microglobulin LOH analysis
Authors: Koene G.J.P.A. , Arts‐Hilkes Y.H.A. , Van Der Ven K.J.W. , Rozemuller E.H. , Slootweg P.J. , De Weger R.A. , Tilanus M.G.J.
Published: September 2004

Abstract:  In cancer research, loss of heterozygosity (LOH), defined by microsatellite markers, is frequently used in the identification of gene loss. Especially, genomic alterations in the human leukocyte antigen (HLA) genes and the β2‐microglobulin (β2m) gene on chromosome 15 are of interest regarding their function in the immune system. Because LOH analysis detects any allelic imbalance and not just allelic loss, we evaluated the LOH analysis in 11 head and neck squamous cell carcinoma (HNSCC) lesions using fluorescence in situ hybridization (FISH). The 11 tumors were selected out of 53 HNSCC lesions based upon β2m LOH analysis and β2m expression. Centromere 1 and 15 FISH were developed to determine the chromosome 15 copy number. Sequence‐based mutation analysis of β2m was conducted on tumors without β2m expression; no mutations in the coding sequences were found. For five HNSCC lesions with LOH and β2m expression, centromere 15 FISH indicated gain rather than loss. In the majority of the 11 HNSCC lesions, FISH showed centromere 1 and 15 heterogeneity throughout the tumor. Moreover, FISH indicated a more complex chromosome 1 and 15 distribution than could be concluded from microsatellite LOH analysis. Our results show that microsatellite LOH analysis does not represent the β2m gene copy number and support the results obtained from comparative genomic hybridization (CGH) studies. Conclusions on genomic alterations in tumors cannot be based on LOH data only but depend on the results of immunohistochemical staining, FISH, and CGH.
A new G‐stretch‐DNA‐binding protein, Unichrom, displays cell‐cycle‐dependent expression in sea urchin embryos
Authors: Moritani Kosho , Tagashira Hideki , Shimotori Taishin , Sakamoto Naoaki , Tanaka Shin , Takata Kazuko , Mitsunaga‐Nakatsubo Keiko , Bojiiwa Yuto , Yamamoto Takashi , Shimada Hiraku , Akasaka Koji
Published: September 2004

We report the identification and characterization of Unichrom, a gene encoding a new G‐stretch‐DNA‐binding protein in the sea urchin embryo. The derived amino acid sequence of Unichrom contains plant homeodomain (PHD) finger and high mobility group (HMG) motifs as well as motifs required for cell‐cycle‐dependent degradation. The expression of a Unichrom‐green fluorescent protein (GFP) fusion protein in sea urchin embryonic cells indicates that Unichrom protein accumulates in nuclei during interphase and disperses into the cytoplasm at mitosis. Overexpression of dominant negative Unichrom, which contains the DNA binding domain lacking the motif for cell‐cycle‐dependent degradation, causes impairment of chromosome segregation. These results suggest that Unichrom binds to genome DNA at G‐stretch and that degradation of Unichrom is required for segregation of chromosomes.
A demonstration of pattern formation without positional information in Dictyostelium
Authors: Thompson Christopher R. L. , Reichelt Stefanie , Kay Robert R.
Published: September 2004

Although positional information, conveyed by morphogen gradients, is a widely accepted way of forming patterns during development, an alternative method is conceivable, based on the intermingled differentiation of cells with different fates, followed by their sorting into discrete pattern elements. It has been proposed that Dictyostelium prestalk and prespore cells behave in this way at the mound stage of development. However, it has been difficult to conclusively demonstrate that they initially differentiate intermingled, because rapid cell movement within the mound makes it impossible to be sure where prestalk and prespore cells originate. We have taken a novel approach to address this problem by blocking cell movement at different stages in development, using the actin‐depolymerizing drug, latrunculin‐A. Prestalk and prespore cells differentiate with essentially normal efficiency and timing in such paralyzed structures. When movement is blocked sufficiently early, the major cell types all subsequently differentiate at scattered positions throughout the aggregate, and even in the streams leading into it. Our work strongly supports the idea that the prestalk/prespore pattern in Dictyostelium forms without positional information and demonstrate that latrunculin‐A may provide a useful tool for the investigation of patterning in other organisms.
Home oxygen therapy after preterm birth in Western Australia
Authors: Saletti A , Stick S , Doherty D , Simmer K
Published: September 2004

Objectives:  To review our management of infants discharged home receiving supplemental oxygen. Stable preterm infants receive low flow O2 by nasal cannulae aiming for SaO2 of ≥ 95%. Oxygen‐dependent infants must pass an air test (ability to maintain SaO2 > 80% during 4 h disconnection from oxygen) before discharge home with supplemental oxygen. A sleep study is performed before nocturnal O2 is ceased.

Methods:  Infants less than 33 weeks gestational age (GA) who were admitted January 1999−June 2001 and discharged home with supplemental oxygen were identified through the databases and medical records of the King Edward Memorial/Princess Margaret Hospitals. The data collected were compared with an audit performed a decade earlier.

Results:  Ninety‐three infants were discharged home with supplemental oxygen between 1999 and 2001 (10% neonatal intensive care unit admissions less than 33 weeks GA; median GA 26 weeks (interquartile range 25−28). All infants had an air test before discharge: 63% failed the first air test and 30% at least two air tests. The median delay between the first air test and discharge was 2 weeks. The median postmenstrual age at discharge was 40 weeks gestation (interquartile range 38−41). Ninety infants had a sleep study before nocturnal oxygen was ceased and nine failed the first sleep study. Hospital readmission rate was 60%. More preterm infants (less than 33 weeks) were discharged with supplemental oxygen in 1999−2001 (10%, n = 96 in 1999−2001) than in 1987−1992 (2.5%, n = 53) and this was associated with an earlier discharge (40 vs 44 weeks postmenstrual age), lower oxygen requirements at discharge (60 vs 125 mL/min), earlier discontinuation of daytime and nocturnal oxygen (1 vs 4 months postmenstrual age and 2.5 vs 6 months postmenstrual age) and no increase in readmission rate (64% vs 60%). The incidence of bronchopulmonary dysplasia for these infants has remained stable at 20%.

Conclusion:  Our home oxygen programme, based on an air test predischarge and a sleep study prediscontinuation of nocturnal oxygen, facilitates early discharge home. Our data suggest that over the last decade, bronchopulmonary dysplasia is associated with less impairment in lung function. Further evidence from randomized clinical trials is required to determine optimal target range for oxygen saturation in preterm infants.
Octreotide in the treatment of congenital chylothorax
Authors: Rasiah SV , Oei J , Lui K
Published: September 2004

Abstract:  Congenital chylothorax is the accumulation of lymphatic fluid within the pleural space. Cases unresponsive to conservative management usually require surgery. Octreotide has been used successfully to treat post‐traumatic chylothoraces in the paediatric and adult population. Its exact mode of action is uncertain but it is believed to reduce lymphatic drainage by a direct action on splanchnic lymph flow. We report a case of congenital chylothorax where surgery was avoided with the compassionate trial of the somatostatin analogue, octreotide. Treatment was associated with prompt respiratory improvement prior to cessation of pleural drainage. Further studies are required to ascertain its true value in congenital chylothorax.
How Should the Allocation of Resources Adjust to the Baby Bust?
Authors: De La Croix David , Mahieu Géraldine , Rillaers Alexandra
Published: September 2004

We analyze the impact of a drop in fertility on the optimal allocation of resources in an overlapping generations economy where old workers care about leisure. We also characterize optimal dynamics and study the decentralization of the optimum by means of inter‐generational transfers and/or public debt. We conclude that the policy recommendations of postponing retirement is fragile and depend on preferences and technologies. Also, even when the optimal adjustment of public debt goes into the expected direction in the long run—i.e., public debt should decrease—this may not be the case during the transition.
Rural population and social security in Brazil: An analysis with emphasis on constitutional changes
Authors: Beltrão Kaizô Iwakami , Pinheiro Sonoe Sugahara , De Oliveira Francisco Eduardo Barreto
Published: September 2004

This paper analyses the situation of the Brazilian rural population with respect to social insurance and social assistance at two points in time: 1988 and 1998. The 1988 Constitution defined new rules with regard to eligibility conditions and benefit values for the rural population. But it was only in July 1991, with Law 8213, that these changes were implemented. We compare — by gender and individual age — activity rates and probability of receiving benefits, before and after the changes in legislation. We also compare, at these two points in time, family structure and the importance of the income of older people in the family budget. The analysis makes clear the positive impact brought by the legislation on the coverage and per capita family income of those families with older members in rural Brazil, bringing about some degree of poverty alleviation, as well as bridging the gender gap with respect to access to benefits. In contrast to what occurs in other Latin American countries, nowadays the Brazilian rural population has almost universal access to social security benefits, not only at family level but also in individual terms.
A stronger role for the private sector in France's health insurance?
Authors: Turquet Pascale
Published: September 2004

Social security in France funds the regular costs of medical goods and services up to a maximum of 75.7 per cent only, so there is a significant level of out‐of‐pocket expenses to the individual. Complementary cover can be obtained from a private insurer, but this cover gives rise to numerous inequalities in terms of both access and content. The health insurance reforms scheduled for 2004 may, however, allow private insurers to play a greater role in funding health costs, albeit at the cost of weakening national solidarity.
Skin lifting in aesthetic cervicofacial rhytidectomy: personal experience in more than 1500 patients
Authors: Hodgkinson D , Tiong J
Published: September 2004

Background  Skin lifting alone in face‐lifting surgery is limited to minor lifts in younger patients. The extent of skin undermining depends on the operative plan.

Aims  An optimal aim is to minimize the amount of undermining to achieve a pleasing, natural rejuvenated result.

Results  By respecting the extensive network of the dermal vascular plexus and by good surgical technique, ischaemia of the elevated skin may be minimized.

Conclusion  Moderate to maximal lifting, however, has proven to be anatomically sound in over 1500 cases operated on over the last 20 years using classical face‐lift techniques to correct the pathoanatomy of the ageing face.
Sensitive skin: a complex and multifactorial syndrome
Authors: Pons‐Guiraud A
Published: September 2004

Many people complain of discomfort after application of commonly used skin care products, particularly to the face. This hyperreactivity of the skin is a non‐immunologically mediated skin inflammation. It seems to be the result of an intolerance of the skin to various stimuli that are normally well tolerated. It is difficult to assess the prevalence of ‘sensitive skin’ and sensitive skin‐related cosmetic intolerance because of the many possible exogenous and endogenous factors that trigger or aggravate this multifactorial syndrome.

 A thorough history is essential. Sometimes patch testing is needed both to standard allergens and also to all the patients’ cosmetics and skin care products. All cosmetics should be stopped and then reintroduced one by one, at intervals of one to two weeks. The number, type and frequency of the application of skin care products used in the final programme should remain limited. Some patients benefit from psychological or even psychiatric help. Management is usually difficult and all therapeutic measures should be undertaken with patience and tenacity.
Human Cytomegalovirus Inhibits Cytokine-Induced Macrophage Differentiation
Authors: Gredmark Sara , Tilburgs Tamara , Söderberg-Nauclér Cecilia
Published: September 2004

Human cytomegalovirus (HCMV) infection in immunocompromised patients is associated with impaired immunological function. Blood monocytes, which differentiate into macrophage effector cells, are of central importance for immune reactivity. Here, we demonstrate that HCMV transiently blocks cytokine-induced differentiation of monocytes into functionally active phagocytic macrophages. In HCMV-treated cultures, the cells had classical macrophage markers but lacked the classical morphological appearance of macrophages and had impairments in migration and phagocytosis. Even at very low multiplicities of infection, macrophage differentiation was almost completely inhibited. The inhibition appeared to be mediated by a soluble factor released upon viral treatment of monocytes. Human immunodeficiency virus or measles virus had no such effects. These findings suggest that HCMV impairs immune function by blocking certain aspects of cytokine-induced differentiation of monocytes and demonstrate an efficient pathway for this virus to evade immune recognition that may have clinical implications for the generalized immunosuppression often observed in HCMV-infected patients.
RNAs Are Packaged into Human Cytomegalovirus Virions in Proportion to Their Intracellular Concentration
Authors: Terhune Scott S. , Schröer Jörg , Shenk Thomas
Published: September 2004

The assembly of human cytomegalovirus (HCMV) virions is a complex process and involves the incorporation of viral transcripts. These RNAs are delivered to the newly infected cells and have the potential to be translated in the absence of HCMV gene expression. We have quantified the relative amount of RNAs in HCMV virions and infected cells with real-time reverse transcription-PCR and observed that viral and cellular RNAs are packaged in proportion to the amount of RNA within the cell at the time of assembly. To determine whether
cis
elements influenced RNA packaging, we constructed a recombinant HCMV mutant virus that expressed the yellow fluorescence protein (YFP) gene fused to the virion RNA UL21.5. We also constructed a mutant virus in which the UL21.5 transcription unit was replaced with the YFP gene. YFP RNA was incorporated into both viruses, indicating that RNA is incorporated in the absence of a virus-specific signal motif. Furthermore, with in situ hybridization, packaged transcripts were observed throughout the cytoplasm of the infected cells, including the site of virus assembly. Several proteins that nonspecifically interact with RNA, including the tegument protein pp28, were found within HCMV virions. These studies demonstrate that both viral and cellular RNAs are nonspecifically incorporated into HCMV, potentially through interactions with several virion proteins.
Murine Coronavirus Nonstructural Protein p28 Arrests Cell Cycle in G0/G1Phase
Authors: Chen Chun-Jen , Sugiyama Kazuo , Kubo Hideyuki , Huang Cheng , Makino Shinji
Published: September 2004

Murine coronavirus mouse hepatitis virus (MHV) gene 1 encodes several nonstructural proteins. The functions are unknown for most of these nonstructural proteins, including p28, which is encoded at the 5′ end of the MHV genome. Transient expression of cloned p28 in several different cultured cells inhibited cell growth, indicating that p28 expression suppressed cell proliferation. Expressed p28 was exclusively localized in the cytoplasm. Cell cycle analysis by flow cytometry demonstrated that p28 expression induced G0/G1cell cycle arrest. Characterization of various cellular proteins that are involved in regulating cell cycle progression demonstrated that p28 expression resulted in an accumulation of hypophosphorylated retinoblastoma protein (pRb), tumor suppressor p53, and cyclin-dependent kinase (Cdk) inhibitor p21Cip1. Expression of p28 did not alter the amount of p53 transcripts yet increased the amount of p21Cip1transcripts, suggesting that p28 expression increased p53 stability and that p21Cip1was transcriptionally activated in a p53-dependent manner. Our present data suggest the following model of p28-induced G0/G1cell cycle arrest. Expressed cytoplasmic p28 induces the stabilization of p53, and accumulated p53 causes transcriptional upregulation of p21Cip1. The increased amount of p21Cip1suppresses cyclin E/Cdk2 activity, resulting in the inhibition of pRb hyperphosphorylation. Accumulation of hypophosphorylated pRb thus prevents cell cycle progression from G0/G1to S phase.
Induction of Antiviral Immunity by Double-Stranded RNA in a Marine Invertebrate
Authors: Robalino Javier , Browdy Craig L. , Prior Sarah , Metz Adrienne , Parnell Pamela , Gross Paul , Warr Gregory
Published: September 2004

Vertebrates mount a strong innate immune response against viruses, largely by activating the interferon system. Double-stranded RNA (dsRNA), a common intermediate formed during the life cycle of many viruses, is a potent trigger of this response. In contrast, no general inducible antiviral defense mechanism has been reported in any invertebrate. Here we show that dsRNA induces antiviral protection in the marine crustaceanLitopenaeus vannamei. When treated with dsRNA, shrimp showed increased resistance to infection by two unrelated viruses, white spot syndrome virus and Taura syndrome virus. Induction of this antiviral state is independent of the sequence of the dsRNA used and therefore distinct from the sequence-specific dsRNA-mediated genetic interference phenomenon. This demonstrates for the first time that an invertebrate immune system, like its vertebrate counterparts, can recognize dsRNA as a virus-associated molecular pattern, resulting in the activation of an innate antiviral response.
Human Immunodeficiency Virus Type 1 (HIV-1) Antigen Secretion by Latently Infected Resting CD4
+
T Lymphocytes from HIV-1-Infected Individuals
Authors: Fondere Jean-Michel , Petitjean Gael , Huguet Marie-France , Salhi Sharon Lynn , Baillat Vincent , Macura-Biegum Anna , Becquart Pierre , Reynes Jacques , Vendrell Jean-Pierre
Published: September 2004

In resting CD4
+
T lymphocytes harboring human immunodeficiency virus type 1 (HIV-1), replication-competent virus persists in patients responding to highly active antiretroviral therapy (HAART). This small latent reservoir represents between 10
3
and 10
7
cells per patient. However, the efficiency of HIV-1 DNA-positive resting CD4
+
T cells in converting to HIV-1-antigen-secreting cells (HIV-1-Ag-SCs) after in vitro CD4
+
-T-cell polyclonal stimulation has not been satisfactorily evaluated. By using an HIV-1-antigen enzyme-linked immunospot assay, 8 HIV-1-Ag-SCs per 10
6
CD4
+
resting T cells were quantified in 25 patients with a plasma viral load of <20 copies/ml, whereas 379 were enumerated in 10 viremic patients. In parallel, 369 and 1,238 copies of HIV-1 DNA per 10
6
CD4
+
T cells were enumerated in the two groups of patients, respectively. Only a minority of latently HIV-1 DNA-infected CD4
+
T cells could be stimulated in vitro to become HIV-1-Ag-SCs, particularly in aviremic patients. The difference between the number of HIV-1 immunospots in viremic versus aviremic patients could be explained by HIV-1 unintegrated viral DNA that gave additional HIV-1-Ag-SCs after in vitro CD4
+
-T-cell polyclonal stimulation. The ELISPOT approach to targeting the HIV-1-Ag-SCs could be a useful method for identifying latently HIV-1-infected CD4
+
T cells carrying replication-competent HIV-1 in patients responding to HAART.
Infectious Entry of West Nile Virus Occurs through a Clathrin-Mediated Endocytic Pathway
Authors: Chu J. J. H. , Ng M. L.
Published: September 2004

The pathway of West Nile flavivirus early internalization events was mapped in detail in this study. Overexpression of dominant-negative mutants of Eps15 strongly inhibits West Nile virus (WNV) internalization, and pharmacological drugs that blocks clathrin also caused a marked reduction in virus entry but not caveola-dependent endocytosis inhibitory agent, filipin. Using immunocryoelectron microscopy, WNV particles were seen within clathrin-coated pits after 2 min postinfection. Double-labeling immunofluorescence assays and immunoelectron microscopy performed with anti-WNV envelope or capsid proteins and cellular markers (EEA1 and LAMP1) revealed the trafficking pathway of internalized virus particles from early endosomes to lysosomes and finally the uncoating of the virus particles. Disruption of host cell cytoskeleton (actin filaments and microtubules) with cytochalasin D and nocodazole showed significant reduction in virus infectivity. Actin filaments are shown to be essential during the initial penetration of the virus across the plasma membrane, whereas microtubules are involved in the trafficking of internalized virus from early endosomes to lysosomes for uncoating. Cells treated with lysosomotropic agents were largely resistant to infection, indicating that a low-pH-dependent step is required for WNV infection. In situ hybridization of DNA probes specific for viral RNA demonstrated the trafficking of uncoated viral RNA genomes to the endoplasmic reticulum.
Ring Finger Protein ZIN Interacts with Human Immunodeficiency Virus Type 1 Vif
Authors: Feng Feng , Davis Adam , Lake Julie-Anne , Carr Jill , Xia Wei , Burrell Christopher , Li Peng
Published: September 2004

Virion infectivity factor (Vif) protein of human immunodeficiency virus type 1 (HIV-1) is essential for the productive infection of primary human CD4 T lymphocytes and macrophages. Vif overcomes the HIV-inhibitory effects of cellular factor APOBEC3G, which has cytidine deaminase activity. We previously reported the isolation of a Vif-interacting ring finger protein, Triad 3, from a human leukocyte cDNA library, using the yeast two-hybrid system. The full-length cellular protein homologue of Triad 3 has been recently identified as the zinc finger protein inhibiting NF-κB (ZIN). Sequence analysis indicates that Triad 3 protein contains all four major ring-like motifs of ZIN. We report here that ZIN binds to purified Vif in vitro and that Triad 3/ZIN interacts with HIV-1 Vif in transfected human 293T cells, as demonstrated by coimmunoprecipitation. To test the biological relevance of this interaction, we produced infectious HIV-1 NL4.3 in the presence or absence of cotransfected ZIN. HIV-1 NL4.3 virus stocks produced in the presence of exogenously expressed ZIN were twofold less infectious in a single-cycle infectivity assay than virus produced in the absence of exogenous ZIN. It was further shown that cells infected with HIV NL4.3 virus stocks produced in the presence of exogenously expressed ZIN were impaired in viral DNA synthesis by twofold. The impairment in viral reverse transcription and the reduction in single-cycle viral infectivity were both shown to be dependent on the presence of Vif in the virus producer cells. The possible mechanisms by which ZIN interferes with the early events of HIV-1 replication are discussed.
Lysines Close to the Rous Sarcoma Virus Late Domain Critical for Budding
Authors: Spidel Jared L. , Craven Rebecca C. , Wilson Carol B. , Patnaik Akash , Wang Huating , Mansky Louis M. , Wills John W.
Published: September 2004

The release of retroviruses from the plasma membrane requires host factors that are believed to be recruited to the site of budding by the late (L) domain of the virus-encoded Gag protein. The L domain of Rous sarcoma virus (RSV) has been shown to interact with a ubiquitin (Ub) ligase, and budding of this virus is dependent on Ub. RSV is similar to other retroviruses in that it contains ∼100 molecules of Ub, but it is unique in that none of these molecules has been found to be conjugated to Gag. If transient ubiquitination of RSV Gag is required for budding, then replacement of the target lysine(s) with arginine should prevent the addition of Ub and reduce budding. Based on known sites of ubiquitination in other viruses, the important lysines would likely reside near the L domain. In RSV, there are five lysines located just upstream of the L domain in a region of the matrix (MA) protein that is dispensable for membrane binding, and replacement of these with arginine (mutant 1-5KR) reduced budding 80 to 90%. The block to budding was found to be on the plasma membrane; however, the few virions that were released had normal size, morphology, and infectivity. Budding was restored when any one of the residues was changed back to lysine or when lysines were inserted in novel positions, either within this region of MA or within the downstream p10 sequence. Moreover, the 1-5KR mutant could be rescued into particles by coexpression of budding-competent Gag molecules. These data argue that the phenotype of mutant 1-5KR is not due to a conformational defect. Consistent with the idea that efficient budding requires a specific role for lysines, human T-cell leukemia virus type 1, which does not bud well compared to RSV and lacks lysines close to its L domain, was found to be released at a higher level upon introduction of lysines near its L domain. This report strongly supports the hypothesis that ubiquitination of the RSV Gag protein (and perhaps those of other retroviruses) is needed for efficient budding.
Retroviruses Pseudotyped with the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Efficiently Infect Cells Expressing Angiotensin-Converting Enzyme 2
Authors: Moore Michael J. , Dorfman Tatyana , Li Wenhui , Wong Swee Kee , Li Yanhan , Kuhn Jens H. , Coderre James , Vasilieva Natalya , Han Zhongchao , Greenough Thomas C. , Farzan Michael , Choe Hyeryun
Published: September 2004

Infection of receptor-bearing cells by coronaviruses is mediated by their spike (S) proteins. The coronavirus (SARS-CoV) that causes severe acute respiratory syndrome (SARS) infects cells expressing the receptor angiotensin-converting enzyme 2 (ACE2). Here we show that codon optimization of the SARS-CoV S-protein gene substantially enhanced S-protein expression. We also found that two retroviruses, simian immunodeficiency virus (SIV) and murine leukemia virus, both expressing green fluorescent protein and pseudotyped with SARS-CoV S protein or S-protein variants, efficiently infected HEK293T cells stably expressing ACE2. Infection mediated by an S-protein variant whose cytoplasmic domain had been truncated and altered to include a fragment of the cytoplasmic tail of the human immunodeficiency virus type 1 envelope glycoprotein was, in both cases, substantially more efficient than that mediated by wild-type S protein. Using S-protein-pseudotyped SIV, we found that the enzymatic activity of ACE2 made no contribution to S-protein-mediated infection. Finally, we show that a soluble and catalytically inactive form of ACE2 potently blocked infection by S-protein-pseudotyped retrovirus and by SARS-CoV. These results permit studies of SARS-CoV entry inhibitors without the use of live virus and suggest a candidate therapy for SARS.
Cell Fusion Activities of Hantaan Virus Envelope Glycoproteins
Authors: Ogino Michiko , Yoshimatsu Kumiko , Ebihara Hideki , Araki Koichi , Lee Byoung-Hee , Okumura Megumi , Arikawa Jiro
Published: September 2004

Hantaan virus (HTNV)-infected Vero E6 cells undergo cell fusion with both infected and uninfected cells under low-pH conditions. Flow cytometry and fluorescence microscopy of HTNV-infected Vero E6 cells showed that envelope glycoproteins (GPs) were located both on the cell surface and in the cytoplasm. Neutralizing monoclonal antibodies (MAbs) against the G1 and G2 envelope GPs inhibited cell fusion, whereas nonneutralizing MAbs against G1 or G2 and MAbs against the nucleocapsid protein (NP) did not. Transfected Vero E6 cells that expressed GPs but not those that expressed NP fused and formed syncytia. These results indicate that HTNV GPs act as fusogens at the cell surface. No fusion activity was observed either in infected Vero cells that were passaged more than 150 times or in BHK-21 cells, although GPs appeared to localize to the cell surface. This variability in fusion induction suggests the involvement of host cell factors in the process of cell membrane fusion.
Newly Diagnosed and Previously Known Diabetes Mellitus and 1-Year Outcomes of Acute Myocardial Infarction
Authors: Aguilar David , Solomon Scott D. , Køber Lars , Rouleau Jean-Lucien , Skali Hicham , McMurray John J.V. , Francis Gary S. , Henis Marc , O’Connor Christopher M. , Diaz Rafael , Belenkov Yuri N. , Varshavsky Sergei , Leimberger Jeffrey D. , Velazquez Eric J. , Califf Robert M. , Pfeffer Marc A.
Published: September 2004

Background—

A prior diagnosis of diabetes mellitus is associated with adverse outcomes after acute myocardial infarction (MI), but the risk associated with a new diagnosis of diabetes in this setting has not been well defined.

Methods and Results—

We assessed the risk of death and major cardiovascular events associated with previously known and newly diagnosed diabetes by studying 14 703 patients with acute MI enrolled in the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. Patients were grouped by diabetic status: previously known diabetes (insulin use or diagnosis of diabetes before MI, n=3400, 23%); newly diagnosed diabetes (use of diabetic therapy or diabetes diagnosed at randomization [median 4.9 d after infarction], but no known diabetes at presentation, n=580, 4%); or no diabetes (n=10 719). Patients with newly diagnosed diabetes were younger and had fewer comorbid conditions than did patients with previously known diabetes. At 1 year after enrollment, patients with previously known and newly diagnosed diabetes had similarly increased adjusted risks of mortality (hazard ratio [HR] 1.43; 95% confidence interval [CI], 1.29 to 1.59 and HR, 1.50; 95% CI, 1.21 to 1.85, respectively) and cardiovascular events (HR, 1.37; 95% CI, 1.27 to 1.48 and HR, 1.34; 95% CI, 1.14 to 1.56).

Conclusions—

Diabetes mellitus, whether newly diagnosed or previously known, is associated with poorer long-term outcomes after MI in high-risk patients. The poor prognosis of patients with newly diagnosed diabetes, despite having baseline characteristics similar to those of patients without diabetes, supports the idea that metabolic abnormalities contribute to their adverse outcomes.
Single-Arm Study of Bridging Therapy With Low-Molecular-Weight Heparin for Patients at Risk of Arterial Embolism Who Require Temporary Interruption of Warfarin
Authors: Kovacs M.J. , Kearon C. , Rodger M. , Anderson D.R. , Turpie A.G.G. , Bates S.M. , Desjardins L. , Douketis J. , Kahn S.R. , Solymoss S. , Wells P.S.
Published: September 2004

Background—

When warfarin is interrupted for surgery, low-molecular-weight heparin is often used as bridging therapy. However, this practice has never been evaluated in a large prospective study. This study was designed to assess the efficacy and safety of bridging therapy with low-molecular-weight heparin initiated out of hospital.

Methods and Results—

This was a prospective, multicenter, single-arm cohort study of patients at high risk of arterial embolism (prosthetic valves and atrial fibrillation with a major risk factor). Warfarin was held for 5 days preoperatively. Low-molecular-weight heparin was given 3 days preoperatively and at least 4 days postoperatively. Patients were followed up for 3 months for thromboembolism and bleeding. Eleven Canadian tertiary care academic centers participated; 224 patients were enrolled. Eight patients (3.6%; 95% CI, 1.8 to 6.9) had an episode of thromboembolism, of which 2 (0.9%; 95% CI, 0.2 to 3.2) were judged to be due to cardioembolism. Of these 8 episodes of thromboembolism, 6 occurred in patients who had warfarin deferred or withdrawn because of bleeding. There were 15 episodes of major bleeding (6.7%; 95% CI, 4.1 to 10.8): 8 occurred intraoperatively or early postoperatively before low-molecular-weight heparin was restarted, 5 occurred in the first postoperative week after low-molecular-weight heparin was restarted, and 2 occurred well after low-molecular-weight heparin was stopped. There were no deaths.

Conclusions—

Bridging therapy with subcutaneous low-molecular-weight heparin is feasible; however, the optimal approach for the management of patients who require temporary interruption of warfarin to have invasive procedures is uncertain.
Does the Functional Efficacy of Skeletal Myoblast Transplantation Extend to Nonischemic Cardiomyopathy?
Authors: Pouly Julia , Hagège Albert A. , Vilquin Jean-Thomas , Bissery Alvine , Rouche Andrée , Bruneval Patrick , Duboc Denis , Desnos Michel , Fiszman Marc , Fromes Yves , Menasché Philippe
Published: September 2004

Background—

The benefits of skeletal myoblast (SM) transplantation on infarcted myocardium have been investigated extensively; however, little is known about its effects in nonischemic cardiomyopathy models. To address this issue, we tested SM transplantation in CHF147 Syrian hamsters, a strain characterized by a δ-sarcoglycan deficiency that phenotypically features the human setting of primary dilated cardiomyopathy.

Methods and Results—

Cell culture techniques were used to prepare ≈5×10
6
muscle cells from autologous tibialis anterior muscle, of which 50% were SMs (desmin staining). The cells were injected in 6 sites across the left ventricular wall (n=14). Control animals (n=12) received equivalent volumes of culture medium. Left ventricular systolic function was assessed in a blinded fashion from 2D echocardiographic left ventricular fractional area change, before transplantation, and 4 weeks later. Explanted hearts were processed for the detection of myotubes and quantification of fibrosis. Baseline functional data did not differ between the 2 groups. Four weeks after transplantation, 6 of the 10 surviving grafted hamsters were improved compared with 0 of the 8 survivors of the control group. This translated into a 6% decrease in fractional area change in controls compared with a 24% increase in cell-transplanted hamsters (
P
=0.001). Engrafted myotubes were consistently detected in all SM transplanted hearts by immunohistochemistry, whereas fibrosis was not worsened by cell injections.

Conclusions—

These data suggest that the functional benefits of SM transplantation might extend to nonischemic cardiomyopathy.
Anti-Poverty Policies in Brazil: Reviewing the Past Ten Years
Authors: Andrews Christina W.
Published: September 2004

This article reviews the main anti-poverty policies implemented in Brazil from the early 1990s to the early 2000s. These include focused and universal policies — such as education and health care — as well as the rural development, a ‘middle ground’ policy. Though the inter-municipal consortium, a new institutional arrangement gathering municipalities together, has emerged as a promising policy implementation tool, anti-poverty policies have faced implementation difficulties. Lack of coordination between different programs, even within the same policy area, has impaired their effectiveness. As a consequence, compensatory programs, based on monetary transfers to poor families, which face fewer implementation problems, have become the dominant type of anti-poverty policies in Brazil. Despite these shortcomings, a small Brazilian state, Santa Catarina, was able to reduce by 46 percent the number of individuals living in poverty in just ten years. This is a sign that fighting poverty can, after all, be a feasible endeavor.
The Effects of Initial Differences in Firms’ Espoused Values on Their Postmerger Performance
Authors: Daly Joseph P. , Pouder Richard W. , Kabanoff Boris
Published: September 2004

Recent studies have concluded that most mergers and acquisitions (M&As) reduce rather than increase shareholder value for the acquiring firm, but understanding of why this occurs is limited. To date, most research has focused on issues of strategic fit, whereas this study examines the effects of organizational fit—specifically the effects of differences in firms’ pre-M&A configurations of espoused values in regards to relationships with employees versus production. The dependent variable of interest is the resulting entities’ subsequent financial performance (return on assets, adjusted for industry). The study analyzed 59 M&As between 1989 and 1996. The authors measured the espoused values of both firms in the transaction by content analyzing presidents’letters to shareholders in corporate annual reports. Using a longitudinal design, results show an inverse relationship between differences in espoused values and postmerger performance. Results and methodology are discussed in terms of their application beyond the M&A context.
Brothers and Sisters of Lesbians, Gay Men, and Bisexuals as a Demographic Comparison Group
Authors: Rothblum Esther D. , Balsam Kimberly F. , Mickey Ruth M.
Published: September 2004

This study provides an innovative methodology to study social issues across sexual orientations. Lesbians, gay men, and bisexualwomen and men (LGB) were recruited via LGB periodicals and organizations, and they in turn recruited their siblings. Results of female participants indicate that lesbians are more highly educated, have occupations with greater status, are less religious, and are more geographically mobile than are heterosexual women. Heterosexual women are more similar to census data in terms of marriage, children, religion, and homemaker status. Gay men have moved to large cities and are more highly educated than are heterosexual men. In general, bisexual women are more comparable demographically to lesbians, whereas bisexual men are more similar to heterosexual men. Limiting the sample to paired comparisons between lesbian-heterosexual sisters and gay-heterosexual brothers generally yielded similar means on demographic variables.
Contextual Complexity and Violent Delinquency among Black and White Males
Authors: Bruce Marino A.
Published: September 2004

Most social scientists agree that Whites and African Americans exist in different economic, political, and social environments and assert that these “contextual” differences contribute substantially to group differencesin violence and other antisocial outcomes. This article extends these ideas into the empirical realm by using data from the National Longitudinal Study of Adolescent Health and structural equation modeling to compare a model of violent delinquency among Black adolescents to one among White adolescents. The results from this comparative analysis illustrate how context leads to racial differences in violent delinquency.
The Roof is on Fire
Authors: Collins P. Kamara Sekou
Published: September 2004

The city of Cincinnati has been the location of much racial unrest that has recently garnered U.S. national attention. Rated as one of Ohio’s most livable cities, “The Queen City” of Ohio erupted in racial protest and anger following the killing of unarmed Timothy Thomas, an African American man, by a European American city police officer. This police killing represented the 15th reported death of African American men by Cincinnati’s police officers in the past 5 years. Bearing in mind the contemporary racial situation of Cincinnati, Ohio, this article uses a conceptual/theoretical construct of historical archeology to focus on the political and power-laden historically situated aspects of the city’s race relations, particularly in the field of education.
The Black Church as a Social Welfare Institution
Authors: Este David C.
Published: September 2004

This article examines the role that Union United Church, the oldest Black church in Montreal, Quebec, played as a social welfare institution from 1907 to 1940 during the establishment of the city’s Black community. The Union Church and its affiliated church groups played a significant role in the Black community. As a social welfare institution, it provided the community members with basic necessities, particularly during a downturn in the economy. Social, recreational, and educational activities were organized through the church to promote a sense of community. Through its ministers, community members battled against the “Colour Line” that excluded members of the community from equitable employment and educational opportunities.
Tensile Strength of Carbon–Carbon Composites: I – Effect of C–C Density
Authors: Hatta Hiroshi , Aoi Tatsuji , Kawahara Itaru , Kogo Yasuo , Shiota Ichiro
Published: September 2004

The tensile fracture stress and strain of carbon fiber-reinforced carbon matrix composites (C–Cs) were examined as functions of the bulk density. When the density increased, the interfacial strength of the C–Cs monotonically increased, and the tensile fracture strain decreased. In contrast, the tensile fracture stress was improved and degraded in the regions of density lower and higher than 1.6 g/cm3, respectively. Two tensile fracture mechanisms of the examined C–Cs were identified with the transition at the density of 1.6 g/cm3. In the low-density region, load transfer capability across fiber–matrix interfaces was shown to have an important role, and in the high-density region, stress concentrations at matrix-crack tips were presumed to be a major factor for the tensile fracture of C–Cs. This suggests that the most important interfacial property for tensile fracture is not interfacial sliding but debonding stress.
Re-membered and Re-mobilized: the ‘Sleeping Dead’ in Interwar Germany and Britain
Authors: Goebel Stefan
Published: September 2004

The rituals and rhetoric of war commemoration in the interwar period have traditionally been interpreted as expressions of personal mourning or as tools of political mobilization. To claim that war commemorations were exclusively about the management of bereavement is incomplete; but to reduce their meaning to political manipulation is cynical. Arising out of the shock of bereavement felt by the individual, war commemoration was a social act of public recollection that could not be politically neutral. This article aims to go beyond conventional historiographical polarizations; it explores a commemorative figure that colonized precisely the grey area between the personal and the political realms: the representation of death as a deep and joyous sleep. Embedded in medieval funerary tradition, national mythologies (Barbarossa and King Arthur) and folk tale (Sleeping Beauty), the idea of enchanted sleep fused notions of individual rebirth and national regeneration. Some day, the ‘sleeping dead’ would rise again. Thus families would be reunited and nations salvaged. Enchanted sleep marked an intermediate stage between the untimely departure and the eventual return of the war dead. The widespread popular appeal of this concept, especially in Germany and to a lesser extent also in Britain, is a remarkable indication of the public denial of death and, sometimes, of the refusal to perceive the Great War as totally over.