Areca nut, the major component of betel quid, is considered carcinogenic [11]. Treatment of areca nut extract (ANE) increased reactive oxygen species (ROS) and caused morphological alterations such as retraction and autophagosome-like vacuoles in cultured cells [12] and [13]. In contrast, we recently discovered that ANE caused ballooning and pyknosis under serum starvation [14]. By inducing miR-23a, ANE reduced Fanconi anemia group G protein (FANCG) and impeded double-strand break (DSB) DNA repair [15]. ANE also impaired cytokinesis and induced micronuclei in Chinese

hamster ovary (CHO) cells [16]. Induction of cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) by ANE in peripheral blood mononuclear NLG919 molecular weight cells might partially contribute to the mucosa inflammatory infiltration [17]. Among the identified compounds BMS-754807 chemical structure of areca nut, arecoline had been proven genotoxic and might contribute to oral carcinogenesis by facilitating error-prone DNA replication [18]. Areca nut-derived oligomericprocyanidins had also been demonstrated to induce apoptosis in human lymphocytes [19]. Betel quid chewing is associated with various alterations in oral mucosa. It remains obscure how so many different alterations such as deregulated epithelial growth and the adjacent ulcerative inflammation are induced. Under normal condition (10% FBS), however, these alterations could not be easily simulated in

cultured cells. In this study we aim to build a model for studying the cytopathic effects of ANE in oral cells that may facilitate mechanism research in the future. OC2, an oral squamous

cell carcinoma cell line derived from a Taiwanese man with habits of drinking, smoking, and areca nut chewing, was maintained in RPMI1640 medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin. The other oral cancer cell line SAS were maintained in DMEM with similar supplements. Cells were routinely kept in a 37 °C incubator supplied with 5% CO2 and subcultured every two to three days. Twelve to sixteen hours after seeding, experiments were performed soon after medium refreshing when cell confluence was about 70-90% except for the morphological tests (30-40%). For low serum culture, cells were washed twice with and cultured in medium containing no FBS or 1% FBS immediately before treatment. Areca nut extract (ANE) was prepared find more from fresh nuts. In brief, the nuts were chopped into about 0.5-1 cm3 dices by a blender and the water-soluble ingredients were extracted at 4 °C overnight. The supernatant was harvested and concentrated by -70 °C lyophilisation. The powder derived from water extract was weighed, re-dissolved in ddH2O, and stored at -20 °C before experimental use. Wortmannin, N-acetylcysteine (NAC), acridine orange (AO), propidium iodide (PI), and dimethyl sulfoxide (DMSO) were purchased from Sigma-Aldrich (St. Louis, MO, USA). NF-κB inhibitor quinazoline (QNZ) was from Cayman (Ann Arbor, MC, USA).

Visual assessments of infection were made 116 days after sowing (DAS) in 2006 and 113 DAS in 2007, corresponding approximately to early milk

development (GS 75) in each season. For analysis, the scores were converted to percentages using the midpoint of each category on the scale and arcsin x transformed for analysis of variance (ANOVA). In both years, a 1.5 m segment of each row was randomly cut at ground CDK assay level from each plot just prior to harvest. These samples were used to determine biomass, after drying at 50 °C for 48 h, and grain yield. Final grain yield was also obtained at maturity by harvesting each 10.0 m × 1.8 m plot with a Kew experimental plot header. Grain protein concentration was determined by NIR reflectance. The trial was harvested 145 DAS in 2006 and 154 DAS in 2007.

Data were analysed by ANOVA. The amount of N harvested in the grain protein was calculated from yield and grain GSK2118436 clinical trial protein content, using a conversion factor of protein content of 5.61 times amino acid N content [8]. N in protein was used rather than total grain N (which is about 1.05 times higher) because commercial prices are based on protein content. The Mitscherlich diminishing returns function, Y=α(1–βρN)Y=α1–βρNwhere Y represents grain protein N yield and N represents nitrogen application rate, was fitted to response curves for the susceptible varieties in each year using nonlinear regression in PASW Statistics version 18. This function was shown to give good fits to the response of yield and protein content of wheat in field trials from northern New South Wales [9]. The parameters are interpreted as estimates of maximum yield (α), responsiveness to added N (β) and curvature of the response (ρ) [9]. Stripe rust was the only foliar

disease detected. No rust symptoms developed on the resistant variety Ellison in either year. In 2006 stripe rust severity at GS 75 was high in the susceptible variety HM, and was significantly (P < 0.05) reduced by about half by fungicide treatment ( Fig. 1). Severity was very low in the moderately resistant Niclosamide variety Baxter. Nitrogen had a significant effect on rust severity, with severity increasing in both HM and Baxter as N rate increased ( Fig. 1). Severity of stripe rust was also high in the susceptible variety H45 in 2007 (Fig. 2). The fungicide treatment was more effective (P < 0.0001) in reducing severity than in 2006. Although there was a trend for increased severity with increasing N, this was not significant (P = 0.1). There were no significant effects of fungicide, variety or nitrogen on vegetative biomass in 2006. Mean biomass was 6.22 t ha− 1. The effect on grain yield of the interaction between variety and N application rate was significant (P < 0.05) in 2006. Grain yield was the highest in Ellison, and in HM with fungicide treatment ( Fig. 3). Yield was reduced in HM without fungicide treatment, and was lowest in Baxter.

Finally, the smoke

delivery levels of nickel, chromium and selenium are in most cases below the quantification limits of the protocols commonly used for their determination [29]. Conversely, sizeable amounts of cadmium, lead and arsenic can be found in tobacco smoke [30]. In the light of these observations, the present study focuses on cadmium (Cd), lead (Pb) and arsenic (As). The cigarette delivery of elements to mainstream smoke can be addressed as a combination of two factors, the amount of these elements present in tobacco and their transfer rate, which is specific to element speciation and is impacted by cigarette design. The transfer of elements during smoking NVP-BEZ235 has been the subject of a number of studies over decades. Nevertheless, despite this wealth of information, it is difficult to obtain a clear model of elements transfer to smoke (sidestream or mainstream),

or their retention (in ash or butt). Even for the specific subject of the phase-distribution for each JAK phosphorylation element in the smoke aerosol, there is a lack of agreement. This point is central to a discussion on transfer since a compound must be at least partly present in the gas-phase to be selectively removed from mainstream smoke by adsorbents. The uncertainty that prevails about the elements transfer or speciation is likely due to the complexity of the quantification of elements yields at trace levels, despite dramatic improvements in instrumentation and analytical methods over the years. Sample contamination

is a constant problem. The small size of the data sets taken into account in many studies is an additional cause for discrepancies among authors’ assessments. Based on data from three worldwide market surveys of commercial cigarettes performed between 2008 and 2012, which included the determination of tobacco and mainstream smoke levels of As, Cd and Pb, we investigated the transfer of each of these elements from tobacco to mainstream smoke generated under both International Organization for Standardization Cyclin-dependent kinase 3 (ISO) and Health Canada Intense (HCI) machine-smoking regimes. Of particular interest is the fact that market surveys data can very effectively evidence selective removal of an element by activated carbon through a comparison of its filtration to that of nicotine. Results, including data from specially designed prototypes, are discussed and the conclusions strengthened by a review of the relevant literature on elements specific filtration. In order to best observe the impact of cigarette design and tobacco blend, brands were selected to cover as many cigarette design specificities as possible, rather than sampling based on local market share. 568 samples of commercial brands from 27 different manufacturers were bought in 2008 (205 samples), 2009 (63 samples) and 2012 (300 samples) at the point of sale in 23 countries.

e. without the use of satellites, (e.g. Rozwadowska & Isemer

1998, Rozwadowska 2004, 2007, Krężel et al 2008, Keevallik & Loitjärv 2010, Kowalczuk et al. 2010, see also the review by Dera & Woźniak 2010) and also by the results of the numerous studies we have started, using the remote sensing methodology described here. The next stage in the sunlight-driven existence and functioning of the Earth’s ecosystems (here: marine ecosystems) and climate are the processes taking place in and around the sea-atmosphere Z-VAD-FMK chemical structure interface, and then within the sea itself. Figure 1 shows that most of the solar radiation reaching the sea surface (flux (5)) is transmitted across the surface into the water (see flux (7) – total radiation entering the water), and some is reflected from this surface (flux (6) – radiation reflected by the surface) back into the atmosphere. The flux (7) then diffuses2 down into the water. There it is partially

backscattered, and some of this backscattered radiation may return to the atmosphere (flux (8) – radiation scattered upwards by the sea water), but most is absorbed by the components of sea water (flux (9) – radiation absorbed in the sea). Flux (9) consists of three 4��8C components. Two of these are the radiation absorbed by water molecules (flux (10)) and that absorbed by the organic/inorganic Selleckchem Veliparib substances dissolved/suspended in the water (flux (11) – the radiation absorbed by admixtures other than phytoplankton pigments). We give separate and detailed

treatment to the third component of this absorption, namely, the radiation absorbed by phytoplankton pigments (PUR3) and the partial utilization of this absorbed energy for the photosynthesis (i.e. primary production) of organic matter in the sea (flux (13) – PSR4). In other words, this part of the energy utilized in photosynthesis supplies marine ecosystems with the energy essential for their functioning. Figure 4 shows a diagram of this energy supply in marine ecosystems. As one might guess, the mathematical description of this problem, enabling the quantitative estimation of the magnitudes characterizing this process, is extremely complicated. This is because we are dealing here with two not quite complete energy transformations (the absorption of radiation and photosynthesis), which are governed by various environmental factors in an exceedingly complex manner.

We validated our hits with quantitative realtime RT-PCR assays for Hepcidin expression and characterized them

by their effects on genes regulated by BMP’s or Stat3, as well as Western blots to detect phosphorylation of Smad1,5,8 or Stat3. We confirmed 16 small molecule Hepcidin stimulating agents in a broad range of functional classes. All of the chemicals identified increased expression of bone morphogenic protein-dependent and/or Stat3-dependent genes, however none of them strongly increased phosphorylation of Smad1,5,8 Anti-infection Compound Library in vivo or Stat3. Several of the Hepcidin stimulatory chemicals inhibit growth factor receptor dependent signaling (AG1296, GTP 14564, AS252424, 10058-F, SU6668, and pterostilbene), decrease inflammation (leflunomide, amlexanox), or impair DNA repair and promote apoptosis (daunorubicin, 9-aminocridine, ethacridine), while the small molecules, vorinostat and SB 204741, inhibit histone deacetylase and serotonin receptor 2B, respectively. Two of the molecules, ipriflavone and vorinostat, were active at concentrations that were 10-fold below those required for genistein’s effect and thus appear to be intriguing candidates for further development. The human hepatocarcinoma cell line, HepG2, (American Type Culture Collection, Manassas, VA) was maintained in α-Minimum Essential Medium

(α-MEM)/10% certified endotoxin-free fetal bovine serum (FBS)/1% penicillin–streptomycin (Life Technologies, Grand Island, NY) at 37 °C, 5% CO2. To generate a Hepcidin reporter cell line, HepG2 cells, were transfected using SuperFect Alectinib mouse (Qiagen, Valencia, CA) transfection PAK6 reagent and a reporter construct including a 2.7 kb fragment of the

human Hepcidin promoter upstream of a firefly luciferase promoter (gift of Drs. Ganz and Nemeth). Transfected clones were selected for resistance to G418 (Life Technologies) and subsequently maintained in the conditions described above with the addition of G418 1 mg/ml. Bone morphogenic protein 6 (BMP6) (R&D Systems, Minneapolis, MN), interleukin-6 (R&D Systems), and genistein (Sigma-Aldrich, St. Louis, MO) were used as positive controls for Hepcidin-luciferase activity, while dorsomorphin (#171260, Calbiochem, Billerica, MA) was used as a negative control. WP1066 (#573097, Calbiochem) was used as an inhibitor of Stat3 signaling. Interleukin-6, EGF, FGF, PDGF, and VEGFA were obtained from R&D Systems. The Institute of Chemistry and Cell Biology (ICCB) Screening Facility at Harvard Medical School provided drug libraries. The complete list of chemicals screened and the screening data are provided in Supplementary Table 1. The day before the addition of compounds, HepG2-Hepcidin luciferase cells were plated at 5000 cells in 30 μl per well of a 384-well microtiter plate (Nunc 142762) in α-MEM/1% penicillin/streptomycin using a WellMate MicroPlate Dispenser (Thermo Scientific, Rockford, IL).

Os autores declaram ter recebido consentimento

escrito dos pacientes e/ou sujeitos mencionados no artigo. O autor para correspondência deve estar na posse deste documento. Os autores declaram não haver conflito de interesses. “
“Granular cell tumor (GCT) was first reported by Abrikossoff by the name of granular cell myoblastoma.1 These tumors are found mainly in skin, oral cavity and digestive tract. Most are benign lesions, but there are reports that malignancy may occur in 1–2%.2 The diagnosis is made by histopathology. GCT has eosinophilic cytoplasmatic granules and positivity for S-100 protein and neuron specific enolase. Although AZD5363 in vitro their cellular origin remained controversial for years, currently it is thought that GCT originates from Schwann cells.2 A 54-year-old

man presented with epigastric pain and was submitted to upper endoscopy. The endoscopy revealed a 10 mm subepithelial esophageal lesion above the esophagogastric junction. The lesion had a yellowish-white appearance, covered with normal mucosa, and was firm when prodded with the biopsy forceps. Although these characteristics are typical of CGT, it is not possible to make an accurate differential diagnosis from other subepithelial lesions such as lipomas by endoscopy.3 Biopsies (bite-on-bite) were performed and histopathological evaluation was suggestive of GCT. The lesion was characterized p38 MAPK cancer by ecoendoscopy as hypoechoid, heterogeneous and limited to the submucosa. Ultrasonography evaluation was important in the pre-treatment evaluation to confirm that the tumor was limited to the submucosa and presented minimal risk of perforation

during resection.4 The patient was being evaluated for an aortic aneurysm and a thoracoabdominal computed tomography was performed with no other lesions. 3-mercaptopyruvate sulfurtransferase Due to the most likely benign nature of the lesion, annual follow-up3 or endoscopic resection of the lesion were discussed with the patient, who agreed with the endoscopic approach. The lesion’s borders were marked with Argon-plasma coagulation (Fig. 1), and submucosal injection (10 ml) of sodium chloride 9% solution and adrenaline (1:100 000) elevated the lesion that was completely removed (Fig. 2) with a snare (Endocut® mode 2, ICC200, ERBE Elektromedizin GmbH, Germany). There were no procedure related complications. The histopathological evaluation confirmed the diagnosis (Fig. 3) and the surgical margin was tumor-free. The tumor site was reviewed six months later, with no lesion. There are no current guidelines for the treatment of GCT. Two different approaches are possible: endoscopic follow-up for lesions <10 mm or removal of larger lesions (>20 mm), specially when symptomatic or suspicious of malignancy.

Since 2002, sediment infilling of the Sanmenxia reservoir (Fig. 1) was substantially alleviated by practices that release turbid water through the Water-Sediment Modulation. This regime was specially designed to mitigate pool infilling and to scour the hanging riverbed of the lower reaches that had resulted from progressive sedimentation. The Sanmenxia reservoir has benefited from this kind of sediment output through human-made hyperpycnal

currents, and the pool has transit from infilling http://www.selleckchem.com/products/ldk378.html to output since 2002. By 2012, the Sanmenxia reservoir had trapped ∼64.11 × 108 m3 in sediments since its construction in 1960. Sediment is also trapped behind the Xiaolangdi dam, largely because of its location at the end of the middle reaches, where FK228 order the Huanghe gains a majority of its suspended sediment load. The Xiaolangdi reservoir traps approximately 84% of the sediment passing through (Chen et al., 2012a). Sediment infilling in the reservoir remains high at 2.36 × 108 m3 per year since 2002, despite the flushing of part of the entrapped sediments through the annual WSM. Between 1997 and 2012, up to 21.8% of the Xiaolangdi

reservoir had been filled by sediment. Additional details of the WSM are discussed in Water-Sediment Modulation section. Average annual sediment flux to the sea in the period 2000–2010 was just 1.37 × 108 t, or ∼10% of its 1950s level. As shown in Fig. 8, stepwise decreases in water and sediment discharges correspond to the construction of the C1GALT1 four large reservoirs. This trend is particularly pronounced after 1968, when Liujiaxia reservoir was constructed. Construction of each reservoir is followed by a sharp decrease in water and sediment discharges to the sea, reflecting the effects of water storage and sediment sequestration. 1960–2010, an average of 1.72 × 108 t of sediment was sequestrated annually in the Sanmenxia reservoir, corresponding to a 27.7% reduction in annual sediment discharge to the sea. Sediment infilling seems more severe for the Xiaolangdi reservoir, which annually sequestered up to 3.07 × 108 t sediments between 2002

and 2010, nearly two times the annual sediment flux to the sea. These two large reservoirs therefore serve as important contributors to the loss in Huanghe sediment flux to the sea. Although a total of 17.6 × 108 t sediments had been scoured from the riverbed during 1999–2009, up to ∼44 × 108 t sediments had been trapped by the Xiaolangdi reservoir. In comparison, the increasing water consumption favored by flow regulation seems to play an equally important role in the loss of sediment and water discharges to the sea (Wang et al., 2006). Without human intervention, the inter-annual water discharge to the sea exhibits order of magnitude fluctuations with >62% of the 1950s-level annual discharge occurring in flood season. This pattern, however, is gradually weakened with the construction of the four large reservoirs.

The mice were given free access to control diet or alcohol Lieber–DeCarli liquid Venetoclax nmr diet for 4 weeks with or without RGE (250 mg/kg or 500 mg/kg, per os, n = 8) The mice were randomly assigned to the groups specified. The second was a mouse model of chronic–binge EtOH intake. The mice were fed with the control diet for 5 days, and then divided into four groups. The EtOH groups were fed with the Lieber–DeCarli liquid diet containing 5% EtOH for 10 days with or without RGE (250 mg/kg or 500 mg/kg, per os, n = 8). The control groups were pair-fed the

control diet for 10 days. At Day 11, mice in EtOH groups were gavaged a single dose of EtOH (5 g/kg body weight, 20% EtOH), whereas mice in control groups were gavaged isocaloric dextrin maltose. The mice were sacrificed 9 hours after gavage. AML12 cell lines were purchased from ATCC (Manassas, VA, USA). Cells were plated at a density of 3 × 105/well in 60 mm dishes and grown to 70–80% confluency. Cells were maintained in Dulbecco’s Modified Eagle Medium: Nutrient Mixture F-12 containing 10% fetal bovine serum (Hyclone, Logan, UT, USA), 50 units/mL penicillin, 50 μg/mL streptomycin, INCB024360 in vivo 0.005 mg/mL insulin, 0.005 mg/mL transferrin, 5 ng/mL selenium, and 40 ng/mL dexamethasone at 37°C in a humidified atmosphere with 5% CO2. RGE or ginsenosides were dissolved in phosphate-buffered saline (PBS) and added to the cells. The cells were then incubated at

37°C for the indicated time period, and washed twice with ice-cold PBS prior to sample preparation. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase Baf-A1 molecular weight (AST) were analyzed using Spectrum, an automatic blood chemistry analyzer (Abbott Laboratories, Abbott Park, IL, USA). Samples from the liver

were separated and fixed in 10% neutral buffered formalin. The samples were then embedded in paraffin, sectioned (3–4 μm), and stained with hematoxylin and eosin (H&E) for general histopathological analysis. In addition, the effect of RGE treatment on the 4-HNE and nitrotyrosine immunoreactivity was also observed by immunohistochemical methods. For the analysis of fat accumulation in the liver, 10-μm sections were cut from frozen samples and stained with Oil Red O for 10 min. The slides were rinsed in water and counterstained with Mayer’s hematoxylin, followed by analysis using light microscopy. Lipid droplet formation in hepatocytes was determined by Oil Red O staining. Cells were grown on a six-well plate. After treatment, the cells were fixed 4% formaldehyde in PBS for 1 h and rinsed with 60% isopropanol. Cells were then stained with Oil Red O solution. Hepatic lipid content was measured as described previously [25]. Briefly, lipids from the total liver homogenate were extracted using chloroform/methanol (2:1), evaporated, and dissolved in 5% triton X-100. Triglyceride content was determined using Sigma Diagnostic Triglyceride Reagents (Sigma).

, 2007 and Steffen et al., 2011) suggested that AD 1800, roughly the start of the Industrial Revolution in Europe, be considered as the beginning of the Anthropocene. Others have taken a longer view, especially Ruddiman, 2003, Selleck Crenolanib Ruddiman, 2005 and Ruddiman, 2013, who argued that greenhouse gas concentrations, deforestation, soil erosion, plant and animal extinctions, and associated climate changes all accelerated at least 8000 years ago with wide-scale global farming (see also Smith and Zeder, 2014). Doughtry et al. (2010) suggested that the Anthropocene should be pushed back to 14,000 or 15,000

years ago, eliminating the Holocene, and correlating with the extinction of Pleistocene megafauna and the associated climate changes brought on by these events. At the other end of the spectrum, some scholars argue for a starting date of AD 1950, based on changes in riverine fluxes (Maybeck and Vörösmarty, 2005) or the appearance of artificial radionucliotides resulting from atomic detonations (Crutzen and Steffen, 2003). In 2008, a proposal

for the formal designation of the Anthropocene was presented to the Stratigraphy Commission of the Geological Society of London (Zalasiewicz et al., 2008). An Anthropocene Working Group, part of the Subcommission on Quaternary Stratigraphy, has been formed to ZD1839 purchase help determine if the Anthropocene will be formally accepted into the Geological Time Scale and when it began (Zalasiewicz et al., 2010,

p. 2228). In line with Crutzen’s arguments, the proposal suggests a genesis at the dawn of the Industrial Revolution or the nuclear era of the 1950s. Ultimately, any date chosen for the beginning of the Anthropocene is likely to be relatively arbitrary and controversial, a point at which scientists can logically argue that we have moved from a planet dominated by natural processes into one dominated by anthropogenic forces. No single date can do justice, moreover, to the long process of human geographic expansion, technological VAV2 development, and economic change that led up to the Industrial Revolution, the nuclear age, or any other singular hallmark in planetary history. As demonstrated by the papers in this issue, archeology—the study of material remains left behind by past human cultures—has much to contribute to understanding the deep history of human impacts on earth’s landscapes and ecosystems. From the controversial and often polarized debates about the history of anthropogenically driven extinctions, to the origins and spread of agricultural and pastoral societies, the effects of humans on marine fisheries and coastal ecosystems, to the acceleration of colonialism and globalization, archeological records can be utilized by scholars to understand not just when humans dominated earth’s ecosystems, but the processes that led to such domination.

, 2010), and the issue of utilization of UGT-cleared integrase inhibitors for HIV/AIDS during fetal development and early infancy, given the low UGT activity during this phase (Strassburg et al., 2002). Glucuronidation studies of compound 1 and, for comparison, raltegravir, were determined in pooled human liver microsomes verified to contain UGT 1A1, 1A4, 1A6, 1A9 and 2B7. Compound 1 was not a substrate for these key UGTs in human liver microsomes or for specific cDNA-expressed UGT isozymes, UGT1A1 Panobinostat datasheet and UGT1A3 (Table 4). Furthermore, in the kinetic studies in human liver microsomes, there was no indication of the

activation of UGT isozymes. In contrast, raltegravir was a substrate for UGT (Fig. 4), which is consistent with previously reported data (Kassahun et al., 2007). We also examined the possible competitive inhibition of UGTs by compound 1 using 4-methylumbelliferone (4-MU), a substrate for multiple isoforms of UGT. However, no evidence for significant competitive inhibition of the key UGT isozymes

1A1, 1A6, 1A9 and 2B7 was found (IC50 > 300 μM). In addition, compound 1 was not an inhibitor of another key UGT isozyme, namely UGT1A4. In summary, we have discovered a new HIV integrase Selleck PS341 inhibitor (1), that exhibits significant antiviral activity against a diverse set of HIV-1 isolates, as well as against HIV-2 and SIV and that displays low in vitro cytotoxicity. It has a favorable resistance and related drug susceptibility profile. Compound 1 is not a substrate for key human UGT isoforms, which is of particular relevance, both in HIV co-infection therapeutics and in HIV treatments during fetal development and early infancy. Finally, Cyclin-dependent kinase 3 the CYP isozyme profile of compound 1 suggests that it is not expected to interfere with normal human CYP-mediated metabolism. Support of this research by the National

Institutes of Health (R01 AI 43181 and NCRR S10-RR025444) is gratefully acknowledged. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. One of us (VN) also acknowledges support from the Terry Endowment (RR10211184) and from the Georgia Research Alliance Eminent Scholar Award (GN012726). The in vitro anti-HIV data were determined by Southern Research Institute, Frederick, MD, using federal funds from the Division of AIDS, NIAID, NIH, under contract HHSN272200700041C entitled “Confirmatory In Vitro Evaluations of HIV Therapeutics.” We acknowledge the help of Dr. Byung Seo and Dr. Pankaj Singh in the early structure-activity studies. We thank Dr. John Bacsa of Emory University for the X-ray crystal structure data. “
“Viral hemorrhagic fever (VHF) designates a group of diseases caused by enveloped, single-stranded RNA viruses belonging to four different families of viruses that include the Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae.