bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real Asset Valuation: A Back‐to‐basics Approach
Authors: Laughton David , Guerrero Raul , Lessard Donald 
Published: July 2008

Different valuation methods can lead to different corporate investment decisions, and the conventional “static, single discount rate” DCF approach in particular is biased against many of the kinds of decisions that corporate managers tend to view as “strategic.” Reducing the bias from valuations involves two main tasks: treating risk in a way that is consistent with observed market pricing, and accounting for the ability of companies to make decisions “dynamically” over time. The authors propose two separate tools, market‐based valuation and complete decision tree analysis, for accomplishing these two improvements in valuation.The authors also suggest working with the full distribution of future cash flows, one possible realization at a time, rather than working with the aggregate measure of expected cash flow. From a technical perspective, it is necessary to work with the full distribution to value real options properly. Valuing the cash flows one realization at a time also leads to a much better understanding of the interaction between economy‐level, systematic risks and local asset‐level, technical risks. Just as important, the proposed approaches support an effective division of labor between local asset managers, who are better positioned to model technical considerations and other asset specifics, and the central finance staff, who can ensure the consistent treatment of economy‐wide risk and to create the rules of engagement for evaluating opportunities.After presenting an overview of both the valuation and the organizational issues, the authors present a case involving a corporate investment in carbon capture and storage that illustrates both the application of the proposed methods and the various sources of bias in the typical DCF analysis.
Expected Inflation and the Constant‐Growth Valuation Model*
Authors: Bradley Michael , Jarrell Gregg A. 
Published: July 2008

In the presence of inflation, the standard Constant‐Growth valuation model found throughout the finance literature is not valid in cases where a company either (1) makes no net new investments or (2) invests only in zero Net Present Value projects. If expected inflation is positive, the generally accepted and widely used expression for the value of the firm under either of these two conditions seriously understates the true value of the firm, even with modest levels of inflation.The authors also show that the Weighted Average Cost of Capital (WACC), as developed by Modigliani and Miller (M&M), will be misleading if inflation is positive. They provide an adjustment factor that corrects this deficiency of the M&M model. Finally, the authors show that the WACC formula developed by Miles and Ezzell is correct when the parameters are stated in nominal terms, and therefore no adjustment is necessary.
The Era of Cross‐Border M&A: How Current Market Dynamics are Changing the M&A Landscape
Authors: Zenner Marc , Matthews Matt , Marks Jeff , Mago Nishant 
Published: July 2008

Rising equity volatility, surging energy prices, a weakening dollar, and widening credit spreads are influencing both tactical financing decisions and long‐term financial strategy. Amid this turbulence is a quickly changing global M&A landscape that portends long‐term opportunities to deliver value to shareholders.In this environment, the authors offer the following suggestions for U.S. multinationals: (1) continue looking overseas for well‐positioned targets, especially in emerging markets, even in the context of a weak U.S. dollar; (2) consider using their financial flexibility for opportunistic deals today now that asset values are contracting; and (3) critically evaluate non‐core assets at home or abroad that might be valuable to cross‐border acquirers.For multinationals in Europe and developing economies, the time may be right to consider transformational cross‐border “megadeals.” Emerging‐market companies have the opportunity to buy low and sell high by using high‐valued equity as an acquisition currency, particularly to gain access to developed markets. Companies in need of new capital should consider the financial and strategic benefits of selling minority stakes to a sovereign wealth fund or other foreign partner.
The Equity Market Risk Premium and the Valuation of Overseas Investments
Authors: Soenen Luc , Johnson Robert 
Published: July 2008

There is little agreement among academics or practitioners about how to measure the size of the equity market risk premium, particularly when it relates to investments in emerging markets. Using monthly equity returns for 22 developed and 24 emerging markets covering the period 1976–2006, the authors find that developed capital markets have experienced significant increases in their degree of integration with the U.S. and world market indexes, while emerging markets remain at least partly segmented from those of the U.S. and the world.For countries that are reasonably well integrated into global capital markets, the authors suggest using the U.S.—based equity market risk premium. But when valuing investments in emerging markets, they recommend use of the Capital Asset Pricing Model adjusted for political risk and a measure of co‐movement between the foreign and U.S. stock markets. The authors also remind readers that the equity market risk premium is supposed to be a forward‐looking measure, and that the common practice of inferring the future from the past can be misleading, particularly in the case of rapidly developing emerging markets.
Stock Option Expensing: The Role of Corporate Governance
Authors: Deshmukh Sanjay , Howe Keith M. , Luft Carl 
Published: July 2008

Analysis of the corporate stock option expensing decision (before the practice became mandatory in 2006) continues to be of interest because it provides insight into the underlying factors affecting not only expense recognition, but the overall corporate decision‐making process. Using a sample of 207 companies that volunteered to expense options and more than 1,000 non‐expensing firms, the authors found that companies that provide more disclosure and appeared to have a stronger alignment of managerial and shareholder interests were also more likely to expense stock options—a finding that the authors view as indirect evidence that voluntary expensing was more likely to occur in companies that practiced effective corporate governance. And consistent with the prediction of efficient market theorists, the study also found no significant market reaction to announcements of these decisions to expense options.The study also found that companies that were the heaviest users of options—notably, smaller, high—growth, and less‐profitable firms—were least likely to expense them. And while this finding adds to the weight of evidence suggesting that companies often make accounting decisions designed to boost reported earnings, the authors also recognize that the possibility that the decision by other companies not to expense may have been a strategy designed primarily to preserve access to capital markets.
Real Options Valuation: A Case Study of an E‐commerce Company
Authors: Sáenz‐Diez Rocío , Gimeno Ricardo , De Abajo Carlos 
Published: July 2008

This paper presents a real options valuation model with original solutions to some issues that arise frequently when trying to apply these models to real‐life situations. The authors build on existing models by introducing an innovative and intuitive risk neutral adjustment that allows us to work with all the simulated paths. The problem of incorporating real options into each path is solved with a “nearest neighbors” technique, and uncertainty is simulated using a beta distribution that adapts better to company‐specific information.The model is then applied to a real life e‐commerce company to produce the following insights: the expanded present value is higher than the traditional present value; the presence of several real options make them interact so that their values are nonadditive; and part of the expanded present value is explained by the presence of “Jensen's inequality” that stems from the “convexity” between the value of each year's cash flow and the uncertain variables.
Native wildlife on rangelands to minimize methane and produce lower‐emission meat: kangaroos versus livestock
Authors: Wilson George R. , Edwards Melanie J. 
Published: July 2008

AbstractRuminant livestock produce the greenhouse gas methane and so contribute to global warming and biodiversity reduction. Methane from the foregut of cattle and sheep constitutes 11% of Australia's total greenhouse gas emissions (GHG). Kangaroos, on the other hand, are nonruminant forestomach fermenters that produce negligible amounts of methane. We quantified the GHG savings Australia could make if livestock were reduced on the rangelands where kangaroo harvesting occurs and kangaroo numbers increased to 175 million to produce same amount of meat. Removing 7 million cattle and 36 million sheep by 2020 would lower Australia's GHG emissions by 16 megatonnes, or 3% of Australia's annual emissions. However, the change will require large cultural and social adjustments and reinvestment. Trials are underway based on international experiences of managing free‐ranging species. They are enabling collaboration between farmers, and if they also show benefits to sustainability, rural productivity, and conservation of biodiversity, they could be expanded to incorporate change on the scale of this article. Farmers have few options to reduce the contribution that livestock make to GHG production. Using kangaroos to produce low‐emission meat is an option for the Australian rangelands which would avoid permit fees under Australia's Emissions Trading Scheme, and could even have global application.
In Vitro and In Vivo Studies of the Trypanocidal Activity of a Diarylthiophene Diamidine against
Trypanosoma cruzi
Authors: da Silva Cristiane França , Batista Marcos Meuser , Batista Denise da Gama Jaen , de Souza Elen Mello , da Silva Patrícia Bernardino , de Oliveira Gabriel Melo , Meuser Andrea Souza , Shareef Abdur-Rafay , Boykin David W. , Soeiro Maria de Nazaré C. 
Published: July 2008

ABSTRACT

Aromatic diamidines are DNA minor groove-binding ligands that display excellent antimicrobial activity against fungi, bacteria, and protozoa. Due to the currently unsatisfactory chemotherapy for Chagas’ disease and in view of our previous reports regarding the effect of diamidines and analogues against both in vitro and in vivo
Trypanosoma cruzi
infection, this study evaluated the effects of a diarylthiophene diamidine (DB1362) against both amastigotes and bloodstream trypomastigotes of
T. cruzi
, the etiological agent of Chagas’ disease. The data show the potent in vitro activity of DB1362 against both parasite forms that are relevant for mammalian infection at doses which do not exhibit cytotoxicity. Ultrastructural analysis and flow cytometry studies show striking alterations in the nuclei and mitochondria of the bloodstream parasites. In vivo studies were performed at two different drug concentrations (25 and 50 mg/kg/day) using a 2-day or a 10-day regimen. The best results were obtained when acutely infected mice were treated with two doses at the lower concentration, resulting in 100% survival, compared to the infected and untreated mice. Although it did not display higher efficacy than benznidazole, DB1362 reduced both cardiac parasitism and inflammation, and in addition, it protected against the cardiac alterations (determined by measurements) common in
T. cruzi
infection. These results support further investigation of diamidines and related compounds as potential agents against Chagas’ disease.
Tipranavir-Ritonavir Genotypic Resistance Score in Protease Inhibitor-Experienced Patients
Authors: Marcelin Anne-Genevieve , Masquelier Bernard , Descamps Diane , Izopet Jacques , Charpentier Charlotte , Alloui Chakib , Bouvier-Alias Magali , Signori-Schmuck Anne , Montes Brigitte , Chaix Marie-Laure , Amiel Corinne , Santos Georges Dos , Ruffault Annick , Barin Francis , Peytavin Gilles , Lavignon Marc , Flandre Philippe , Calvez Vincent 
Published: July 2008

ABSTRACTTo identify mutations associated with the virological response (VR) to a tipranavir-ritonavir (TPV/r)-based regimen, 143 patients previously treated with protease inhibitor (PI) were studied. VR was defined by a decrease of at least 1 log10in, or undetectable, human immunodeficiency virus (HIV) RNA at month 3. The effect of each mutation in the protease, considering all variants at a residue as a single variable, on the VR to TPV/r was investigated. Mutations at six residues were associated with a lower VR (E35D/G/K/N, M36I/L/V, Q58E, Q61D/E/G/H/N/R, H69I/K/N/Q/R/Y, and L89I/M/R/T/V), and one mutation was associated with a higher VR (F53L/W/Y). The genotypic score M36I/L/V − F53L/W/Y + Q58E + H69I/K/N/Q/R/Y + L89I/M/R/T/V was selected as providing a strong association with VR. For the seven patients with a genotypic score of −1 (viruses with only mutation at codon 53), the percentage of responders was 100% and the percentages were 79%, 56%, 33%, 21%, and 0% for those with scores of 0, 1, 2, 3, and 4, respectively. The percentage of patients showing a response to TPV/r was lower for patients infected with non-clade B viruses (n= 16, all non-B subtypes considered together) than for those infected with clade B viruses (n= 127) (25% and 59%, respectively;P= 0.015). Most mutations associated with VR to TPV/r had not previously been associated with PI resistance. This is consistent with phenotypic analysis showing that TPV has a unique resistance profile. Mutations at five positions (35, 36, 61, 69, and 89) were observed significantly more frequently in patients infected with a non-B subtype than in those infected with the B subtype, probably explaining the lower VR observed in these patients.
Heterocyclic Compounds That Inhibit Rev-RRE Function and Human Immunodeficiency Virus Type 1 Replication
Authors: Shuck-Lee Deidra , Chen Fei Fei , Willard Ryan , Raman Sharmila , Ptak Roger , Hammarskjold Marie-Louise , Rekosh David 
Published: July 2008

ABSTRACTA cell-based screening assay was performed to identify compounds that inhibited the postintegration stage of the human immunodeficiency virus (HIV) life cycle. This assay utilized a cell line that contains the HIVgagandpolgenes expressed in a Rev-dependent fashion. The cell line produces about 10 to 15 ng of p24 per milliliter of medium over a 24-h period in the form of viruslike particles. Any compound that inhibits a postintegration step in the HIV life cycle scores in this assay by decreasing particle production. Forty thousand compounds were screened, and 192 compounds were selected from the original screen because they showed more than 50% inhibition at a 10 μM concentration. The cumulative evidence presented in this study strongly suggests that 2 of the 192 compounds work as inhibitors of HIV Rev function. This was determined by a variety of cell-based assays, although the compounds do not interfere with Rev-RRE (Rev response element) binding in vitro. Both compounds inhibit replication of the lab isolate NL4-3 as well as an HIV primary isolate from Brazil (93BR021) and thus are promising leads as therapeutic candidates that target HIV replication through inhibition of Rev function.
In Vivo Pharmacodynamic Target Investigation for Micafungin against
Candida albicans
and
C. glabrata
in a Neutropenic Murine Candidiasis Model
Authors: Andes D. R. , Diekema D. J. , Pfaller M. A. , Marchillo K. , Bohrmueller J. 
Published: July 2008

ABSTRACT

Previous studies using in vivo candidiasis models have demonstrated that the concentration-associated pharmacodynamic indices, the maximum concentration of a drug in serum/MIC and 24-h area under the curve (AUC)/MIC, are associated with echinocandin treatment efficacy. The current investigations used a neutropenic murine model of disseminated
Candida albicans
and
C. glabrata
infection to identify the 24-h AUC/MIC index target associated with a stasis and killing endpoint for the echinocandin, micafungin. The kinetics after intraperitoneal micafungin dosing were determined in neutropenic infected mice. Peak levels and AUC values were linear over the 16-fold dose range studied. The serum drug elimination half-life ranged from 7.5 to 16 h. Treatment studies were conducted with 4
C. albicans
and 10
C. glabrata
isolates with micafungin MICs varying from 0.008 to 0.25 μg/ml to determine whether similar 24-h AUC/MIC ratios were associated with efficacy. The free drug AUC/MICs associated with stasis and killing (1-log) endpoints were near 10 and 20, respectively. The micafungin exposures associated with efficacy were similar for the two
Candida
species. Furthermore, the free drug micafungin exposures required to produce stasis and killing endpoints were similar to those recently reported for another echinocandin, anidulafungin, against the identical
Candida
isolates in this model.
In Vitro and In Vivo Treatments of
Echinococcus
Protoscoleces and Metacestodes with Artemisinin and Artemisinin Derivatives
Authors: Spicher Martin , Roethlisberger Carole , Lany Catharina , Stadelmann Britta , Keiser Jennifer , Ortega-Mora Luis M. , Gottstein Bruno , Hemphill Andrew 
Published: July 2008

ABSTRACT

In vitro treatment of
Echinococcus multilocularis
and
Echinococcus granulosus
larval stages with the antimalarials dihydroartemisinin and artesunate (10 to 40 μM) exhibited promising results, while 6 weeks of in vivo treatment of mice infected with
E. multilocularis
metacestodes (200 mg/kg of body weight/day) had no effect. However, combination treatments of both drugs with albendazole led to a substantial but statistically not significant reduction in parasite weight compared to results with albendazole alone.
Immunomodulatory Effects of Voriconazole on Monocytes Challenged withAspergillus fumigatus: Differential Role of Toll-Like Receptors
Authors: Simitsopoulou Maria , Roilides Emmanuel , Paliogianni Fotini , Likartsis Christodoulos , Ioannidis John , Kanellou Kalliopi , Walsh Thomas J. 
Published: July 2008

ABSTRACTVoriconazole (VRC) has activity againstAspergillus fumigatus, the most frequent cause of invasive aspergillosis in immunocompromised patients. The combination of VRC andA. fumigatushyphae induced a more pronounced profile of expression of genes encoding inflammatory molecules in human monocytes thanAspergillusalone did. Herein, we provide further evidence of the potential mechanism underlying this immunomodulatory effect of VRC on human monocytes in response toA. fumigatushyphae. A significant additive antifungal effect was shown when VRC was combined with monocytes againstA. fumigatushyphae. BothA. fumigatushyphae and VRC induced pronounced profiles of mRNA and protein expression of Toll-like receptor 2 (TLR2) as well as tumor necrosis factor alpha (TNF-α) in THP-1 monocytic cells compared to untreated cells. The VRC-induced increase was greater than that induced by hyphae. The combination of VRC and hyphae increased mRNA and protein expression of TLR2 and TNF-α to even higher levels than did either VRC or hyphae alone. In contrast, TLR4 expression, both at the mRNA and protein levels, was not increased by either VRC or hyphae or their combination. In addition, significantly more NF-κB was translocated to the nuclei of THP-1 cells treated with VRC than untreated cells. While VRC induced more NF-κB than hyphae did, treatment with the combination of the two factors induced the greatest NF-κB expression. The pronounced profile of TLR2 signaling, TNF-α expression, and NF-κB activation in the presence of VRC suggests an immunomodulatory effect leading to a more efficient response toA. fumigatus.
Delay of Active Antimicrobial Therapy and Mortality among Patients with Bacteremia: Impact of Severe Neutropenia
Authors: Lin Michael Y. , Weinstein Robert A. , Hota Bala 
Published: July 2008

ABSTRACT

Increasing bacterial antimicrobial resistance has prompted physicians to choose broad-spectrum antimicrobials in order to reduce the likelihood of inactive empirical therapy. However, for bacteremic patients already receiving supportive care, it is unclear whether delay of active antimicrobial therapy significantly impacts patient outcomes. We performed a retrospective cohort study of patients with monomicrobial bloodstream infections at a large urban hospital in the United States from 2001 to 2006. We assessed the impact of delay of active antimicrobial therapy on mortality by using multivariable logistic regression modeling with and without propensity score methodology. We evaluated 1,523 episodes of monomicrobial bacterial bloodstream infections at our institution. Nine hundred eighty-three bacteremic episodes (64.5%) were treated with an active antimicrobial agent within 24 h of the index blood culture; the remaining 540 episodes (35.5%) were considered to have delay of active antimicrobial therapy. In adjusted analysis, among patients in the non-intensive-care-unit setting with an absolute neutrophil count (ANC) of <100 cells/μl, delay was associated with increased mortality (odds ratio [OR], 18.0; 95% confidence interval [CI], 2.84 to 114.5;
P
< 0.01); among intensive-care-unit patients with an ANC of <100 cells/μl, the effect of delay on mortality was nearly significant (OR, 5.56; 95% CI, 0.85 to 36.3;
P
= 0.07). However, for patients who were nonneutropenic (ANC, >500 cells/μl) or had ANCs of 100 to 500 cells/μl, delay was not associated with increased mortality. While the delay of active antimicrobial therapy was not significantly associated with higher mortality for most patients in this cohort, patients with severe neutropenia appeared to be vulnerable.
Analysis ofPRA1and Its Relationship toCandida albicans- Macrophage Interactions
Authors: Marcil A. , Gadoury C. , Ash J. , Zhang J. , Nantel A. , Whiteway M. 
Published: July 2008

ABSTRACTPhagocytosis ofCandida albicansby either primary bone marrow-derived mouse macrophages or RAW 264.7 cells upregulated transcription ofPRA1, which encodes a cell wall/membrane-associated antigen previously described as a fibrinogen binding protein. However, apra1null mutant was still able to bind fibrinogen, showing that Pra1p is not uniquely required for fibrinogen binding. As well, Pra1 tagged with green fluorescent protein did not colocalize with AlexaFluor 546-labeled human fibrinogen, and whilePRA1expression was inhibited whenCandidawas grown in fetal bovine serum-containing medium,Candidabinding to fibrinogen was activated by these conditions. Therefore, it appears that Pra1p can play at most a minor role in fibrinogen binding toC. albicans. PRA1gene expression is induced in vitro by alkaline pH, and therefore its activation in phagosomes suggested that phagosome maturation was suppressed by the presence ofCandidacells. LysoTracker red-labeled organelles failed to fuse with phagosomes containing liveCandida, while phagosomes containing deadCandidaunderwent a normal phagosome-to-phagolysosome maturation. Immunofluorescence staining with the early/recycling endosomal marker transferrin receptor (CD71) suggested that liveCandidamay escape macrophage destruction through the inhibition of phagolysosomal maturation.