bluuebunny/crossref_metadata_2025_split huggingface dataset:
DOES VENTURE CAPITAL REQUIRE AN ACTIVE STOCK MARKET?
Authors: Black Bernard S. , Gilson Ronald J. 
Published: April 2005

The United States has both an active venture capital industry and well‐developed stock markets. Japan and Germany have neither. The authors argue that this is no accident— that venture capital flourishes especially, and perhaps only, when venture capitalists can exit from successful portfolio companies through initial public offerings (IPOs), which in turn require an active stock market.Understanding the link between the stock market and the venture capital market requires understanding the contractual arrangements between entrepreneurs and venture capital providers, particularly (1) the importance of exit by venture capitalists and (2) the implicit contract over control between venture capitalists and entrepreneurs created by the possibility of exit through an IPO. This possibility gives entrepreneurs a valuable option that, in the event they are successful, allows them to reacquire control of their enterprises from venture capitalists.
CONTROL: GETTING IT AND KEEPING IT IN BUSINESS PROCESS OUTSOURCING
Authors: Linder Jane C. , Sawyer Joseph P. 
Published: April 2005

Proposals to outsource corporate functions often meet with resistance because of control issues and concerns about proprietary information. But proponents of outsourcing are quick to note that many of these reservations dwell on perceptions and apprehensions, rather than on the track record of outsourced projects. In fact, veterans of successful arrangements observe that outsourcing frees up valuable management time and thus enables an enhanced form of control.The key is to supplement direct, supervisory control mechanisms like service control agreements and performance tracking with indirect, enabling controls—senior team affiliation, performance visibility, interface management, and employee allegiance—and then lay the groundwork for these enabling controls early in the outsourcing relationship. Rather than getting locked into static controls, forward‐looking managers adopt a broad control framework to go beyond achieving the expected improvements and create the potential to add new value. The result is an outsourcing relationship that can accommodate change, move in a new direction, and seize emerging opportunities.
FOREIGN EXCHANGE AND CROSS‐BORDER VALUATION
Authors: O'Brien Thomas J. 
Published: April 2005

Should a corporate financial manager analyze a cross‐border investment proposal from the perspective of the foreign currency or the home currency? The conventional wisdom among economists is that it doesn't matter–the valuation of an asset should be the same in one currency as in another, given the spot FX rate. This assertion implies that it is irrelevant whether we analyze an overseas investment's NPV in the home currency or the foreign currency, as long as we use consistent cross‐border conversions.But what happens if managers' foreign exchange forecasts differ from the efficient markets forecast that is implicit in interest rates? In that case, as this article demonstrates through a series of examples, managers' FX forecasts can affect their investment, hedging, and financing decisions.
A Conformational Change in the Adeno-Associated Virus Type 2 Capsid Leads to the Exposure of Hidden VP1 N Termini
Authors: Kronenberg Stephanie , Böttcher Bettina , von der Lieth Claus W. , Bleker Svenja , Kleinschmidt Jürgen A. 
Published: April 2005

ABSTRACT

The complex infection process of parvoviruses is not well understood so far. An important role has been attributed to a phospholipase A
2
domain which is located within the unique N terminus of the capsid protein VP1. Based on the structural difference between adeno-associated virus type 2 wild-type capsids and capsids lacking VP1 or VP2, we show via electron cryomicroscopy that the N termini of VP1 and VP2 are involved in forming globules inside the capsids of empty and full particles. Upon limited heat shock, VP1 and possibly VP2 become exposed on the outsides of full but not empty capsids, which is correlated with the disappearance of the globules in the inner surfaces of the capsids. Using molecular modeling, we discuss the constraints on the release of the globularly organized VP1-unique N termini through the channels at the fivefold symmetry axes outside of the capsid.
Array Analysis of Simian Varicella Virus Gene Transcription in Productively Infected Cells in Tissue Culture
Authors: Deitch Steven B. , Gilden Donald H. , Wellish Mary , Smith John , Cohrs Randall J. , Mahalingam Ravi 
Published: April 2005

ABSTRACT

Simian varicella virus (SVV) is a neurotropic alphaherpesvirus of monkeys that is a model for varicella pathogenesis and latency. Like human varicella-zoster virus (VZV), SVV causes chicken pox (varicella), becomes latent in ganglia along the entire neuraxis, and reactivates to produce shingles (zoster). We developed macroarrays to determine the extent of viral transcription from all 70 predicted SVV open reading frames (ORFs) in infected cells in tissue culture. Cloned fragments (200 to 400 bp) from the 5′ and 3′ ends of each ORF were PCR amplified, quantitated, spotted onto nylon membranes, and fixed by UV cross-linking. Using a cDNA probe prepared from poly(A)
+
RNA extracted from SVV-infected Vero cells at the height of the cytopathic effect (3 days after infection) and chemiluminescence for detection, transcripts corresponding to all SVV ORFs were identified. The abundance of each SVV transcript was compared with that previously demonstrated for VZV in infected tissue culture cells.
RhoA Signaling Is Required for Respiratory Syncytial Virus-Induced Syncytium Formation and Filamentous Virion Morphology
Authors: Gower Tara L. , Pastey Manoj K. , Peeples Mark E. , Collins Peter L. , McCurdy Lewis H. , Hart Timothy K. , Guth Alex , Johnson Teresa R. , Graham Barney S. 
Published: April 2005

ABSTRACT

Respiratory syncytial virus (RSV) is an important human pathogen that can cause severe and life-threatening respiratory infections in infants, the elderly, and immunocompromised adults. RSV infection of HEp-2 cells induces the activation of RhoA, a small GTPase. We therefore asked whether RhoA signaling is important for RSV replication or syncytium formation. The treatment of HEp-2 cells with
Clostridium botulinum
C3, an enzyme that ADP-ribosylates and specifically inactivates RhoA, inhibited RSV-induced syncytium formation and cell-to-cell fusion, although similar levels of PFU were released into the medium and viral protein expression levels were equivalent. Treatment with another inhibitor of RhoA signaling, the Rho kinase inhibitor Y-27632, yielded similar results. Scanning electron microscopy of C3-treated infected cells showed reduced numbers of single blunted filaments, in contrast to the large clumps of long filaments in untreated infected cells. These data suggest that RhoA signaling is associated with filamentous virus morphology, cell-to-cell fusion, and syncytium formation but is dispensable for the efficient infection and production of infectious virus in vitro. Next, we developed a semiquantitative method to measure spherical and filamentous virus particles by using sucrose gradient velocity sedimentation. Fluorescence and transmission electron microscopy confirmed the separation of spherical and filamentous forms of infectious virus into two identifiable peaks. The C3 treatment of RSV-infected cells resulted in a shift to relatively more spherical virions than those from untreated cells. These data suggest that viral filamentous protuberances characteristic of RSV infection are associated with RhoA signaling, are important for filamentous virion morphology, and may play a role in initiating cell-to-cell fusion.
Amino Acid Changes in Proteins 2B and 3A Mediate Rhinovirus Type 39 Growth in Mouse Cells
Authors: Harris Julie R. , Racaniello Vincent R. 
Published: April 2005

ABSTRACT
Many steps of viral replication are dependent on the interaction of viral proteins with host cell components. To identify rhinovirus proteins involved in such interactions, human rhinovirus 39 (HRV39), a virus unable to replicate in mouse cells, was adapted to efficient growth in mouse cells producing the viral receptor ICAM-1 (ICAM-L cells). Amino acid changes were identified in the 2B and 3A proteins of the adapted virus, RV39/L. Changes in 2B were sufficient to permit viral growth in mouse cells; however, changes in both 2B and 3A were required for maximal viral RNA synthesis in mouse cells. Examination of infected HeLa cells by electron microscopy demonstrated that human rhinoviruses induced the formation of cytoplasmic membranous vesicles, similar to those observed in cells infected with other picornaviruses. Vesicles were also observed in the cytoplasm of HRV39-infected mouse cells despite the absence of viral RNA replication. Synthesis of picornaviral nonstructural proteins 2C, 2BC, and 3A is known to be required for formation of membranous vesicles. We suggest that productive HRV39 infection is blocked in ICAM-L cells at a step posttranslation and prior to the formation of a functional replication complex. The observation that changes in HRV39 2B and 3A proteins lead to viral growth in mouse cells suggests that one or both of these proteins interact with host cell proteins to promote viral replication.
Recombinant, Live-Attenuated Tetravalent Dengue Virus Vaccine Formulations Induce a Balanced, Broad, and Protective Neutralizing Antibody Response against Each of the Four Serotypes in Rhesus Monkeys
Authors: Blaney Joseph E. , Matro Jennifer M. , Murphy Brian R. , Whitehead Stephen S. 
Published: April 2005

ABSTRACT

Three tetravalent vaccine (TV) formulations of previously described monovalent dengue (DEN) virus vaccine candidates were compared to a tetravalent formulation of wild-type DEN viruses (T-
wt
) for replication in SCID mice transplanted with human liver cells (SCID-HuH-7) or for replication and immunogenicity in rhesus monkeys. TV-1 consists of recombinant DEN1, -2, -3, and -4, each with a 30-nucleotide deletion in the 3′ untranslated region (Δ30). TV-2 consists of rDEN1Δ30, rDEN4Δ30, and two antigenic chimeric viruses, rDEN2/4Δ30 and rDEN3/4Δ30, both also bearing the Δ30 mutation. TV-3 consists of rDEN1Δ30, rDEN2Δ30, rDEN4Δ30, and a 10-fold higher dose of rDEN3/4Δ30. TV-1 and TV-2 were attenuated in SCID-HuH-7 mice with minimal interference in replication among the virus components. TV-1, -2, and -3 were attenuated in rhesus monkeys as measured by duration and peak of viremia. Each monkey immunized with TV-1 and TV-3 seroconverted to the four DEN components by day 28 with neutralization titers ranging from 1:52 to 1:273 and 1:59 to 1:144 for TV-1 and TV-3, respectively. TV-2 induced low antibody titers to DEN2 and DEN3, but a booster immunization after 4 months increased the neutralizing antibody titers to greater than 1:100 against each serotype and elicited broad neutralizing activity against 19 of 20 DEN subtypes. A single dose of TV-2 induced protection against wild-type DEN1, DEN3, and DEN4 challenge, but not DEN2. However, two doses of TV-2 or TV-3 induced protection against DEN2 challenge. Two tetravalent formulations, TV-2 and TV-3, possess properties of a successful DEN vaccine and can be considered for evaluation in clinical trials.
Regulation of Translation by Ribosome Shunting through Phosphotyrosine-Dependent Coupling of Adenovirus Protein 100k to Viral mRNAs
Authors: Xi Qiaoran , Cuesta Rafael , Schneider Robert J. 
Published: April 2005

ABSTRACT
Adenovirus simultaneously inhibits cap-dependent host cell mRNA translation while promoting the translation of its late viral mRNAs during infection. Studies previously demonstrated that tyrosine kinase activity plays a central role in the control of late adenovirus protein synthesis. The tyrosine kinase inhibitor genistein decreases late viral mRNA translation and prevents viral inhibition of cellular protein synthesis. Adenovirus protein 100k blocks cellular mRNA translation by disrupting the cap-initiation complex and promotes viral mRNA translation through an alternate mechanism known as ribosome shunting. 100k protein interaction with initiation factor eIF4G and the viral 5′ noncoding region on viral late mRNAs, known as the tripartite leader, are both essential for ribosome shunting. We show that adenovirus protein 100k promotes ribosome shunting in a tyrosine phosphorylation-dependent manner. The primary sites of phosphorylated tyrosine on protein 100k were mapped and mutated, and two key sites are shown to be essential for protein 100k to promote ribosome shunting. Mutation of the two tyrosine phosphorylation sites in 100k protein does not impair interaction with initiation factor 4G, but it severely reduces association of 100k with tripartite leader mRNAs. 100k protein therefore promotes ribosome shunting and selective translation of viral mRNAs by binding specifically to the adenovirus tripartite leader in a phosphotyrosine-dependent manner.
Memory T-Cell Response to Rotavirus Detected with a Gamma Interferon Enzyme-Linked Immunospot Assay
Authors: Kaufhold Robin M. , Field Jodie A. , Caulfield Michael J. , Wang Su , Joseph Heather , Wooters Melissa A. , Green Tina , Clark H. Fred , Krah David , Smith Jeffrey G. 
Published: April 2005

ABSTRACT

Measurements of serum-neutralizing antibody and anti-rotavirus immunoglobulin A (IgA) are the current standard for assessing immune responses following rotavirus vaccination. However, there is ongoing debate as to whether antibody titers correlate with protection against rotavirus gastroenteritis. Children recovering from rotavirus gastroenteritis have increased gamma interferon release from cultured peripheral blood mononuclear cells (PBMCs), suggesting that cell-mediated immunity (CMI) may play a role in viral clearance and protection from subsequent gastroenteritis. We have developed a gamma interferon enzyme-linked immunospot (ELISPOT) assay for evaluation of CMI responses to rotavirus using frozen PBMCs obtained from healthy adults. Responses to three different rotavirus antigen types were analyzed—a peptide pool based on the human VP6 sequence; reassortant human:bovine vaccine strains; and cell culture-adapted (CCA) human G1, G2, G3, G4, and bovine (WC3) G6 strains. The reassortant strains consist of a bovine WC3 genome background expressing the human rotavirus surface proteins VP7 (G1, G2, G3, or G4) or VP4 (P1). Responses to titrations of the peptide pool as well as CCA and reassortant strains were assessed. Gamma interferon ELISPOT responses were similar for CCA and reassortant strains, whether live or UV inactivated, and when tested either individually or pooled. For most subjects, responses to the VP6 peptide pool positively correlated with responses to CCA and reassortant strains. Cell depletion studies indicate the memory responses detected with these frozen adult PBMCs were primarily due to the CD4
+
T-cell population. This gamma interferon ELISPOT assay provides a new tool to apply in clinical studies for the characterization of natural or vaccine-induced CMI to rotavirus.
Binding and Transfer of Human Immunodeficiency Virus by DC-SIGN+Cells in Human Rectal Mucosa
Authors: Gurney Kevin B. , Elliott Julie , Nassanian Hoorig , Song Carol , Soilleux Elizabeth , McGowan Ian , Anton Peter A. , Lee Benhur 
Published: April 2005

ABSTRACTThe role of DC-SIGN on human rectal mucosal dendritic cells is unknown. Using highly purified human rectal mucosal DC-SIGN+cells and an ultrasensitive real-time reverse transcription-PCR assay to quantify virus binding, we found that HLA-DR+/DC-SIGN+cells can bind and transfer more virus than the HLA-DR+/DC-SIGN−cells. Greater than 90% of the virus bound to total mucosal mononuclear cells (MMCs) was accounted for by the DC-SIGN+cells, which comprise only 1 to 5% of total MMCs. Significantly, anti-DC-SIGN antibodies blocked 90% of the virus binding when more-physiologic amounts of virus inoculum were used. DC-SIGN expression in the rectal mucosa was significantly correlated with the interleukin-10 (IL-10)/IL-12 ratio (r= 0.58,P< 0.002;n= 26) among human immunodeficiency virus (HIV)-positive patients. Ex vivo and in vitro data implicate the role of IL-10 in upregulating DC-SIGN expression and downregulating expression of the costimulatory molecules CD80/CD86. Dendritic cells derived from monocytes (MDDCs) in the presence of IL-10 render the MDDCs less responsive to maturation stimuli, such as lipopolysaccharide and tumor necrosis factor alpha, and migration to the CCR7 ligand macrophage inflammatory protein 3β. Thus, an increased IL-10 environment could render DC-SIGN+cells less immunostimulatory and migratory, thereby dampening an effective immune response. DC-SIGN and the IL-10/IL-12 axis may play significant roles in the mucosal transmission and pathogenesis of HIV type 1.
Association of the Influenza A Virus RNA-Dependent RNA Polymerase with Cellular RNA Polymerase II
Authors: Engelhardt Othmar G. , Smith Matt , Fodor Ervin 
Published: April 2005

ABSTRACT
Transcription by the influenza virus RNA-dependent RNA polymerase is dependent on cellular RNA processing activities that are known to be associated with cellular RNA polymerase II (Pol II) transcription, namely, capping and splicing. Therefore, it had been hypothesized that transcription by the viral RNA polymerase and Pol II might be functionally linked. Here, we demonstrate for the first time that the influenza virus RNA polymerase complex interacts with the large subunit of Pol II via its C-terminal domain. The viral polymerase binds hyperphosphorylated forms of Pol II, indicating that it targets actively transcribing Pol II. In addition, immunofluorescence analysis is consistent with a new model showing that influenza virus polymerase accumulates at Pol II transcription sites. The present findings provide a framework for further studies to elucidate the mechanistic principles of transcription by a viral RNA polymerase and have implications for the regulation of Pol II activities in infected cells.
Characterization of Herpes Simplex Virus Type 1 Thymidine Kinase Mutants Selected under a Single Round of High-Dose Brivudin
Authors: Andrei Graciela , Balzarini Jan , Fiten Pierre , De Clercq Erik , Opdenakker Ghislain , Snoeck Robert 
Published: April 2005

ABSTRACT

A broad variety of herpes simplex virus type 1 clones was selected under a single round of high-dose selection with brivudin. Mutations in the thymidine kinase (
TK
) genes consisted of 42% frameshift mutations within homopolymer repeats of G's and C's and single nucleotide substitutions (58%) that produced stop codons (Q261 and R281) or a new codon at the site of the substitution (A168T, R51W, G59W, G206R, R220H, Y239S, and T287 M). The A168T change, associated with an altered TK phenotype, proved to be the most commonly selected substitution. For the different mutants, a correlation between phenotype, genotype, and in vivo neurovirulence was observed.
Characterization of the 11-Year Solar Signal Using a Multiple Regression Analysis of the ERA-40 Dataset
Authors: Crooks Simon A. , Gray Lesley J. 
Published: April 2005

Abstract
A multiple linear regression analysis of the ERA-40 dataset for the period 1979–2001 has been used to study the influence of the 11-yr solar cycle on atmospheric temperature and zonal winds. Volcanic, North Atlantic Oscillation (NAO), ENSO, and quasi-biennial oscillation (QBO) signatures are also presented. The solar signal is shown to be readily distinguishable from the volcanic signal. The main solar signal is a statistically significant positive response (i.e., warmer in solar maximum) of 1.75 K over the equator with peak values at 43 km and a reversed signal of similar magnitude at high latitudes that is seasonally dependent. Consistent with this is a statistically significant zonal wind response of up to 6 m s−1 in the subtropical upper stratosphere/lower mesosphere that is also seasonally dependent. The wind anomalies are westerly/easterly in solar maximum/minimum. In addition, there is a statistically significant temperature response in the subtropical lower stratosphere that shows similarity in spatial structure to the QBO response, suggesting a possible interaction between the solar and QBO signals in this region. The solar response in tropospheric zonal winds is small but significant, confirming previous studies that indicate a possible modulation of the Hadley circulation.
Airway allergen exposure stimulates bone marrow eosinophilia partly via IL-9
Authors: Sitkauskiene Brigita , Rådinger Madeleine , Bossios Apostolos , Johansson Anna-Karin , Sakalauskas Raimundas , Lötvall Jan 
Published: April 2005

Abstract
Background
Interleukin (IL)-9 is a Th2-derived cytokine with pleiotropic biological effects, which recently has been proposed as a candidate gene for asthma and allergy. We aimed to evaluate the therapeutic effect of a neutralizing anti-IL-9 antibody in a mouse model of airway eosinophilic inflammation and compared any such effect with anti-IL-5 treatment.

Methods
OVA-sensitized Balb/c mice were intraperitoneally pretreated with a single dose (100 μg) of an anti-mouse IL-9 monoclonal antibody (clone D9302C12) or its vehicle. A third group was given 50 μg of a monoclonal anti-mouse IL-5 antibody (TRFK-5) or its vehicle. Animals were subsequently exposed to OVA on five days via airways. Newly produced eosinophils were labelled using 5-bromo-2'-deoxyuridine (BrdU). BrdU+ eosinophils and CD34+ cell numbers were examined by immunocytochemistry. After culture and stimulation with OVA or PMA+IC, intracellular staining of IL-9 in bone marrow cells from OVA-exposed animals was measured by Flow Cytometry. The Mann-Whitney U-test was used to determine significant differences between groups.

Results
Anti-IL-9 significantly reduced bone marrow eosinophilia, primarily by decrease of newly produced (BrdU+) and mature eosinophils. Anti-IL-9 treatment also reduced blood neutrophil counts, but did not affect BAL neutrophils. Anti-IL-5 was able to reduce eosinophil numbers in all tissue compartments, as well as BrdU+ eosinophils and CD34+ progenitor cells, and in all instances to a greater extent than anti-IL-9. Also, FACS analysis showed that IL-9 is over-expressed in bone marrow CD4+ cells after allergen exposure.

Conclusions
Our data shows that a single dose of a neutralizing IL-9 antibody is not sufficient to reduce allergen-induced influx of newly produced cells from bone marrow to airways. However, in response to allergen, bone marrow cells over-express IL-9. This data suggest that IL-9 may participate in the regulation of granulocytopoiesis in allergic inflammation.