However, early on in evolution, oxygen sensing has emerged, as a central control mechanism LY2835219 of energy metabolism and vasculogenesis. At the heart of this regulatory system is the Hypoxia-Inducible Factor, HIF, which controls, among other gene products, the expression of

VEGF-A and Angiopoïetin-2, two key angiogenic factors in vertebrates. This finding has placed the hypoxia-signaling pathway at the forefront of nutritional control. HIF controls glycolysis, intracellular pH (pHi), angiogenesis, cell migration and invasion, and so has become recognized as a strong promoter of tumor growth. We will highlight some of the HIF-induced gene products that participate in tumor adaptation, resistance and progression in a nutrient-depleted and acidic microenvironment. First we will demonstrate that the two HIF-induced ‘BH3-only’-proteins (BNIP3, BNIP3L/NIX), in contrast to current belief, do not trigger cell death but, by inducing macro-autophagy, stimulate Stem Cells inhibitor tumor cell survival. BMN673 Second, we will show how tumor cells by expressing two HIF-dependent membrane-bound carbonic anhydrases, CAIX and CAXII, acidify the extracellular milieu, and ensure a more alkaline intracellular pH favoring migration, survival and growth in a hostile acidic microenvironment.

Third, HIF-induced glycolysis in most hypoxic tumor cells is essential to ensure maintenance of ATP levels for growth and cell survival. Two MonoCarboxylate Transporters MCT-1 and MCT-4, stabilized in the plasma membrane by the common chaperon basigin/CD147, play a key role in cancer metabolism. We propose that appropriate exploitation of these HIF-regulated proteins and new validated cancer targets, which control exacerbated tumor metabolism and intracellular pH, will be at the forefront of anti-cancer therapy. O8 Identifying New Anti-Cancer Therapeutics Using Synthetic Lethality Amato Giaccia 1 , Sandra Turcotte1, Patrick Sutphin1, William Denny2, Michael Hay2, Denise Chan1 1 Radiation Oncology, Stanford University, Stanford, CA, USA, 2 Experimental Therapeutics, University of Auckland, Auckland, New Zealand

Synthetic lethality results when two nonallelic mutations that by themselves are not lethal, answer in cell death when combined. To screen for small molecules that acted in a synthetic lethal manner to the loss of VHL, we needed Cediranib (AZD2171) a means of tracking cell growth in microwell plates when exposed to a library of small molecules. Renal carcinoma cell lines with naturally occurring VHL mutations and their genetically matched wild-type VHL counterparts were stably labeled with enhanced yellow fluorescent protein (EYFP). Cells were then seeded onto 384-well plates and allowed to attach overnight. Baseline fluorescence readings were obtained and a compound library was added at a concentration of 5 μM. Fluorescence intensity was read once a day for four days. An increase in fluorescence intensity was used as a surrogate marker for cell growth.

Nat Nanotechnol 2008, 3:563.CrossRef 12. Myung S, Solanki A, Kim C, Park J, Kim KS, Lee KB: Graphene‐encapsulated nanoparticle‐based biosensor for the PSI-7977 selective detection of cancer biomarkers. Adv Mater 2011, 23:2221.CrossRef 13. Zou RJ, Zhang ZY, Xu KB, Jiang L, Tian QW, Sun YG, Chen ZG, Hu JQ: A method for joining individual graphene sheets. Carbon 2012, 50:4965.CrossRef 14. Kim KS, Zhao Y, Jang H, Lee SY, Kim JM, Kim KS, Ahn JH, Kim P, Choi JY, Hong BH: Large-scale pattern growth of graphene films for stretchable transparent electrodes. Nature 2009, 457:706.CrossRef 15. Kim K, Choi JY, Kim T, Cho SH, Chung HJ: A role for graphene in silicon-based

find more semiconductor devices. Nature 2011, 479:338.CrossRef 16. Zunger A, Katzir A, Halperin A: Optical

properties of hexagonal boron nitride. Phys Rev B 1976, 13:5560.CrossRef 17. Han WQ, Wu LJ, Zhu YM, Watanabe K, Taniguchi T: Structure of chemically derived mono-and few-atomic-layer boron nitride sheets. Appl Phys Lett 2008, 93:223103.CrossRef 18. Shi YM, Hamsen C, Jia XT, Kim KK, Reina A, Hofmann M, Hsu AL, Zhang K, Li HN, Juang ZY, Dresselhaus MS, Li LJ, Kong J: Synthesis of few-layer hexagonal boron nitride thin film by chemical vapor deposition. Nano Lett 2010, 10:4134.CrossRef 19. Golberg D: Exfoliating the inorganics. Nat Nanotechnol 2011, 6:200.CrossRef 20. Coleman JN, Lotya M, O’Neill A, Bergin SD, King PJ, Khan GDC 0032 supplier U, Young K, Gaucher A, De S, Smith RJ, Shvets IV, Arora SK, Stanton G, Kim HY, Lee K, Kim GT, Duesberg GS, Hallam T, Boland JJ, Wang JJ, Donegan JF, Grunlan JC, Moriarty G, Shmeliov A, Nicholls RJ, Perkins JM, Grieveson EM, Theuwissen K, McComb DW, Nellist PD, Nicolosi V: Two-dimensional nanosheets

produced by liquid exfoliation of layered materials. Science 2011, 331:568.CrossRef 21. Wei XL, Wang MS, Bando Y, Golberg D: Electron-beam-induced substitutional carbon doping of boron nitride nanosheets, nanoribbons, and nanotubes. ACS Nano 2011, 5:2916.CrossRef 22. Wang WL, Bando Y, Zhi CY, Fu WY, Wang E, Golberg D: Aqueous noncovalent functionalization and controlled near-surface carbon doping of multiwalled Bumetanide boron nitride nanotubes. J Am Chem Soc 2008, 130:8144.CrossRef 23. Tang CC, Bando Y, Huang Y, Yue SL, Gu CZ, Xu FF, Golberg D: Fluorination and electrical conductivity of BN nanotubes. J Am Chem Soc 2005, 127:6552.CrossRef 24. Xiang HJ, Yang JL, Hou JG, Zhu QS: Are fluorinated boron nitride nanotubes n-type semiconductors? Appl Phys Lett 2005, 87:243113.CrossRef 25. Zhou J, Wang Q, Sun Q, Jena P: Electronic and magnetic properties of a BN sheet decorated with hydrogen and fluorine. Phys Rev B 2010, 81:085442.CrossRef 26. Ma YD, Dai Y, Guo M, Niu CW, Yu L, Huang BB: Strain-induced magnetic transitions in half-fluorinated single layers of BN. GaN and graphene. Nanoscale 2011, 3:2301.CrossRef 27.

Int J Antimicrob Agents. 2013;41:337–42.PubMedCrossRef 43. Zhang H, Xiao M, Yang QW, et al. High ceftaroline non-susceptibility in Staphylococcus aureus isolated from acute skin infections in 15 tertiary hospitals in China. J Med Microbiol. 2012;62:496–7.PubMedCrossRef 44. File TM Jr, Low DE, Eckburg PB, et al. Integrated analysis of FOCUS 1 and FOCUS 2: randomized, SN-38 nmr doubled-blinded, multicenter

phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with community-acquired pneumonia. Clin Infect Dis. 2010;51:1395–405.PubMedCrossRef 45. File TM Jr, Wilcox MH, Stein GE. Summary of ceftaroline fosamil clinical trial studies and clinical safety. Clin Infect Dis. 2012;55:S173–80.PubMedCrossRef 46. Mandell LA, Wunderink RG, Anzueto A, et al.

Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44:S27–72.PubMedCrossRef 47. Corey GR, Wilcox M, Talbot GH, et al. Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure Y-27632 mw infection. Clin Infect Dis. 2010;51:641–50.PubMedCrossRef 48. Forest Research Institute I. Briefing book—ceftaroline fosamil for injection; 2010. http://​www.​fda.​gov/​downloads/​advisorycommitte​es/​committeesmeetin​gmaterials/​drugs/​anti-infectivedrugsad​visorycommittee/​ucm224657.​pdf (Accessed 9 July 2013). 49. Friedland HD, O’Neal T, Biek D, et al. CANVAS 1 and 2: analysis of clinical response at day 3 in two phase 3 trials of ceftaroline fosamil versus vancomycin plus aztreonam in treatment

of acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2012;56:2231–6.PubMedCentralPubMedCrossRef 50. Rank DR, Friedland HD, Laudano JB. Integrated safety summary of FOCUS 1 and FOCUS 2 trials: phase III randomized, double-blind studies evaluating ceftaroline fosamil for the treatment of patients with Aspartate community-acquired pneumonia. J Antimicrob Chemother. 2011;66:iii53–9. 51. Corrado ML. Integrated safety summary of CANVAS 1 and 2 trials: Phase III, randomized, double-blind studies evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J Antimicrob Chemother. 2010;65:iv67–71. 52. Panagiotidis G, Backstrom T, Asker-Hagelberg C, Jandourek A, Weintraub A, Nord CE. Effect of ceftaroline on normal human intestinal Dasatinib microflora. Antimicrob Agents Chemother. 2010;54:1811–4.PubMedCentralPubMedCrossRef 53. Riccobene TA, Rekeda L, Rank D, Llorens L. Evaluation of the effect of a supratherapeutic dose of intravenous ceftaroline fosamil on the corrected QT interval. Antimicrob Agents Chemother. 2013;57:1777–83.PubMedCentralPubMedCrossRef 54.

Sequences most closely related to iron-reducing (Geobacter) and sulfate-reducing (Desulfobulbaceae and Desulfobacteraceae) bacteria are relatively more abundant in LS and NS wells where sulfate concentrations were low (< 0.2 mM) compared to wells with higher sulfate

concentrations (Figure 6). Geobacter sequences comprised 34% of all bacterial sequences in NS wells and 22% of LS wells, but only 15% of HS wells. Conversely, ∆-Proteobacteria clones related to families associated with sulfate reduction, Desulfobulbaceae and Desulfobacteraceae, click here were of lower relative abundance in bacterial communities in wells with low sulfate concentrations. In HS wells, members of these families represented 20% of all Dasatinib attached bacterial sequences, but comprised 8% of the total in LS wells and 3% in NS wells. Figure 6 The taxonomy and relative distribution of bacterial populations attached to the sediment of in situ samplers. Sequences were classified to the genus level using Mothur [33] with the “Hugenholtz” taxonomic nomenclature in Greengenes [34]. The area of each circle is proportional to the percentage of sequences represented by that class within those wells, which are grouped together according to the concentration of

sulfate in groundwater. SIMPER analysis also shows that sequences classified as belonging to families of methanogens (Methanosarcinaceae and Methanosaetaceae) dominated the archaeal communities Selleckchem AZD0156 in both the suspended and attached fractions of NS wells, were considerably less abundant in LS wells, and were nearly absent in HS wells (Figure 7). In HS and LS wells, where few sequences in this group were detected, methane concentrations were low or undetectable (Figure 2). Clones from the Methanosarcinales

comprise on average < 0.5% of the archaeal sequences in HS wells and 1 - 4% of the community in LS wells. In NS wells, which contain abundant methane, methanogen sequences Rapamycin mw represent 73 – 80% of the entire archaeal community. Euryarchaeal sequences from the Mahomet Arc 1, identified mostly in suspended communities, are more prevalent in LS wells (56%) relative to both HS and NS (~4% in each) wells (Figure 7). Figure 7 The taxonomy and relative distribution of archaeal populations attached to the sediment of in situ samplers. Sequences were classified to the genus level in Mothur [33] with the “Hugenholtz” taxonomic nomenclature in Greengenes [34]. The area of each circle is proportional to the percentage of sequences represented by that class within those wells, which are grouped together according to the concentration of sulfate in groundwater. Discussion The distinct physical and geochemical niches within the Mahomet aquifer harbour characteristic populations of bacteria and archaea.

Nat Genet 1996,13(4):399–408.PubMedCrossRef 7. Shi WJ, Chen H, Zhou B, Cheng J: [Association of mutations of HFE gene Selleck Z IETD FMK and hepatocellular carcinoma following chronic hepatitis B]. Zhonghua Gan Zang Bing Za Zhi 2005,13(9):682–684.PubMed 8. Lauret E, Rodriguez M, Gonzalez S, Linares A, Lopez-Vazquez A, Martinez-Borra

J, Rodrigo L, Lopez-Larrea C: HFE gene mutations in alcoholic and virus-related cirrhotic patients with hepatocellular carcinoma. Am J Gastroenterol 2002,97(4):1016–1021.PubMedCrossRef 9. Fargion S, Stazi MA, Fracanzani AL, Mattioli M, Sampietro M, Tavazzi D, Bertelli C, Patriarca V, Mariani C, Fiorelli G: Mutations in the HFE gene and their interaction with exogenous risk factors in hepatocellular carcinoma. Blood Cells Mol Dis 2001,27(2):505–511.PubMedCrossRef 10. Willis G, Bardsley V, Fellows IW, Lonsdale R, Wimperis JZ, Jennings BA: Hepatocellular carcinoma and the penetrance of HFE C282Y mutations: a cross sectional study. BMC Gastroenterol 2005, 5:17.PubMedCrossRef 11. Hellerbrand C, Poppl A, Hartmann A, Scholmerich J, Lock G: HFE C282Y heterozygosity in hepatocellular

carcinoma: evidence for an increased prevalence. Clin Gastroenterol Hepatol 2003,1(4):279–284.PubMedCrossRef 12. Cauza selleck screening library E, Peck-Radosavljevic M, Ulrich-Pur H, Datz C, Gschwantler

M, Schoniger-Hekele M, Hackl F, Polli C, Rasoul-Rockenschaub S, Muller C, Wrba F, Gangl A, Ferenci P: Mutations of the HFE gene in patients with hepatocellular carcinoma. tuclazepam Am J Gastroenterol 2003,98(2):442–447.PubMedCrossRef 13. Willis G, Wimperis JZ, Lonsdale R, Fellows IW, Watson MA, Skipper LM, Jennings BA: Incidence of liver disease in people with HFE mutations. Gut 2000,46(3):401–404.PubMedCrossRef 14. Ezzikouri S, El Feydi AE, El Kihal L, Afifi R, Benazzouz M, Hassar M, Chafik A, Pineau P, Benjelloun S: Prevalence of common HFE and SERPINA1 mutations in patients with hepatocellular carcinoma in a Moroccan STAT inhibitor population. Arch Med Res 2008,39(2):236–241.PubMedCrossRef 15. Nahon P, Sutton A, Rufat P, Ziol M, Thabut G, Schischmanoff PO, Vidaud D, Charnaux N, Couvert P, Ganne-Carrie N, Trinchet JC, Gattegno L, Beaugrand M: Liver iron, HFE gene mutations, and hepatocellular carcinoma occurrence in patients with cirrhosis. Gastroenterology 2008,134(1):102–110.PubMedCrossRef 16. Ropero P, Briceno O, Lopez-Alonso G, Agundez JA, Gonzalez Fernandez FA, Garcia-Hoz F, Villegas Martinez A, Diaz-Rubio M, Ladero JM: [The H63D mutation in the HFE gene is related to the risk of hepatocellular carcinoma]. Rev Esp Enferm Dig 2007,99(7):376–381.PubMedCrossRef 17.

We believe that the photogenerated charges are extracted from these devices to not simply produce the photocurrent but instead cause some new changes in these devices SB203580 which impel

further free carriers to be generated and transported through the devices. In this work, the photocurrent enhancement mechanisms of these bilayer nanofilm-based UV PDs are explained. Especially, we prove a concept for light trapping in the hollow-sphere nanofilm-based UV PDs through the use of wavelength-scale resonant hollow spheres that support WGMs to enhance absorption and photocurrent. We numerically demonstrate this enhancement using full-field finite element method (FEM) simulations of hollow-sphere nanofilm-based UV PDs. It is proved that the WGM is an important concept for the manufacturing of the hollow-sphere nanofilm-based UV PDs, which facilitates the coupling of light into the resonant

modes and substantial enhancement of the light path in the active materials, thus dramatically enhancing absorption and photocurrent. Methods The preparation of hollow spheres is quite simple and scalable without the need for lithography. Figure 1a depicts a ZnO hollow-sphere nanofilm-based UV PD. Well-defined polystyrene (PS)/ZnO core/shell nanospheres were prepared and then self-assembled at a hexane-water interface to form a precursor film. The precursor core/shell film was then transferred onto a Si substrate covered with a 200-nm-thick layer of Selleckchem SN-38 SiO2. Annealing this precursor film under optimal conditions, a ZnO hollow-sphere nanofilm with a densely packed network structure was obtained. The front view is depicted in Figure 1b. Finally, after a pair of Cr/Au electrodes was deposited on the as-transformed ZnO hollow-sphere nanofilm on a SiO2/Si substrate using an Au microwire as the mask, a UV PD was successfully constructed

[8, 10]. Figure 1c,d shows the typical transmission electron microscopy (TEM) images of the ZnO hollow spheres. One can see that the thickness of the ZnO shell is about 20 nm selleck chemicals (average outer radius R out = 120 nm and inner radius R in = 100 nm). On the other hand, well-ordered ZnO/ZnS bilayer films were also fabricated by oil-water interfacial self-assembly. First, a large number of PS/ZnO Cl-amidine research buy core-shell microspheres were self-assembled at a hexane-water interface. Second, another monolayer film, using PS/ZnS core-shell microspheres, was fabricated at the hexane-water interface in another vessel. This monolayer was then transferred onto the substrate covered with the first PS/ZnO monolayer. The stacking sequence of these bilayer nanofilms can be easily tailored through the layer-by-layer deposition order. Then, we prepared two bilayer nanofilms composed of hollow microspheres with different stacking sequences. These two bilayer nanofilms are here referred to as ‘ZnO/ZnS/SiO2/Si (ZnO/ZnS)’ and ‘ZnS/ZnO/SiO2/Si (ZnS/ZnO).’ For the optoelectronic property measurements, a drastic increase of current up to 2.

In addition, the data (DNA or AA) used to create the trees is listed. This relates to the degree of conservation in the data; more conserved sequences require DNA trees #PD-0332991 mw randurls[1|1|,|CHEM1|]# to provide signal, less conserved sequences require AA trees

to avoid excessive noise. Figure 4 Aberrant tree. Tree inferred from the gene Asub on Chromosome I that is inconsistent with the trees inferred by other methods as described in this paper, including the trees for the individual gene phylogenies at other nearby genes. In this tree, the V. splendidus clade is found next to the V. fisheri clade, making it basal to its expected position. This tree is also referred to as “”I”" in Table 1, column 1. As click here shown, the tree is not fully resolved and branches with low support have been collapsed. Conclusions Rampant horizontal

gene transfer and plasmid exchange might create doubt as to the fidelity of paired chromosomes to one another. Further, this genetic mobility can create serious difficulties for anyone reconstructing a phylogeny for something as large as a chromosome, just as they do for someone inferring organismal and species phylogenies. Here, these difficulties have been overcome by using a range of methods that operate at different temporal

and genetic scales. At the smallest scale, a number of individual gene phylogenies were reconstructed. At an intermediate scale, the gene content of a conserved region was used to infer a phylogeny. At the largest scale, concatenation of predominantly chromosome specific genes (though they may, in other genomes, be transferred among the chromosomes) provided an estimate of the history of the whole chromosome. In each case, the observed patterns were consistent – though, while many individual genes do not present a conflicting individual history, they may not support the hypothesis for lack of signal. This congruence between the whole of the chromosome Fossariinae and the origin of replication suggests that the region around the origin of replication is either too large to relocate or is difficult to transfer because of its specific function. Individual genes in this region may experience horizontal gene transfer – witness the inclusion of a mobile genetic region in V. cholerae B33. Individual genes also appear amenable to transfer, deletion and insertion. More than being able to create a relative history for each chromosome, it appears that since the origin of the two chromosomes in the ancestral Vibrio, they have continued as a pair.

This is somewhat surprising as tree diameter has previously been shown to be positively correlated with the number of species

(Grove 2002; Ranius and Jansson 2000; Sverdrup-Thygeson et al. 2010). However, in the present study, the trap catches and the circumferences are estimates check details relevant on stand scale rather than on the scale of individual trees. Therefore, other variables might have confounded the results. Furthermore, all sites were characterised by trees that had reached a size and age defining them as ancient, and the degree of ancientness may be more important than diameter itself. Pollarding slows down growth and because of that, thin trunks may be ancient trees. In oaks, 50% of trees form hollows by about 250 years of age (Ranius

et al. 2009). For lime trees, this age is probably lower, as lime rots faster than oak and especially so in pollarded trees as the formation of hollows is enhanced where NCT-501 manufacturer branches are shed. However, hollowness need not imply a rich fauna if the trees are too young, as seen in the case TSA HDAC clinical trial of 80-year old hollow limes in the park at Drottningholm, which had fewer species, especially red-listed species, than the old limes in the same park (Jonsell 2008). The amount of habitat, measured as number of hollow lime trees on each site (No. of trees), had significant relationship to species number for all wood and bark living species, and it was negative. This lack of relation, or relation opposite to what should be expected, could be due to that the variables no. of trees and type were confounded with somewhat more trees in parks than in the other type of sites (2.6 compared to 1.9 for the two others). Also problems with quantifying this variable may contribute. First the data collected for each

locality had several uncertainties in itself (see “Materials and methods”). The numbers obtained also give just the present situation, totally disregarding the history of the site. In addition to that, the definition of where the borders for a locality should be drawn is also problematic. Most of these sites are found in regions where old hollow trees may occur here and there. Data on suitable trees for the whole landscape with estimates Rucaparib mw of connectivity related to distance to each of these occurrences should probably be more explanatory (Ranius et al. 2010). Such an analysis would probably suggest that the rich saproxylic beetle fauna on several sites in the Mälaren area is due to a dense patchwork of sites. The number of sites is high, there is a high connectivity between them, several sites are large and the individual trees in them are often a high quality habitat, all factors that contribute to a sustainable metapopulation system (Hanski 1994; Ranius 2007).

SBO can be classified according to completeness: Partial vs. Complete (or high grade vs. low grade), according to etiology: Adhesional vs. Non-adhesional, according to timing: Early vs. Late (>30 days after surgery). The most important risk factor for adhesive SBO is the type of surgery and extent of peritoneal damage. Surgeries of the colon and rectum are associated with a higher risk of adhesion-related

DZNeP solubility dmso problems [14]. Total colectomy PU-H71 nmr with ileal pouch-anal anastomosis is the procedure with the highest incidence for adhesion-related problems with an overall incidence of SBO of 19.3%. Other high-risk procedures include gynecologic surgeries (11.1%) and open colectomy (9.5%). Other possible risk factors include age younger than 60 years, previous laparotomy within 5 years, peritonitis, multiple laparotomies,

emergency surgery, omental resection, and penetrating abdominal trauma, especially gunshot wounds [15–18]. The number of prior episodes is the strongest predictor of recurrence; in fact ASBO recurred after 53% of initial episodes and 85% or more of second, third, or later episodes in the experience of Barkan et al. Recurrence occurred check details sooner and more frequently in patients managed nonoperatively than in patients managed operatively [19]. With growing numbers of previous episodes of SBO requiring adhesiolysis, the risk for future re-admission for SBO

increases, thus nonsurgical management of the initial episode has been Etomidate advocated as a risk factor for recurrence [20]. Age younger than 40 years, the presence of matted adhesions, and surgical complications during the surgical management of the first episode as independent risks for recurrence [21]. Williams et al. [22] in a retrospective review of 329 patients (487 admissions) demonstrated that operatively treated patients had a lower frequency of recurrence (26.8% vs 40.5% P < 0.009) and a longer time interval to recurrence (411 vs 153 days P < 0.004); however, they also had a longer hospital stay than that of patients treated nonoperatively (12.0 vs 4.9 days; P < 0.0001). There was no significant difference in treatment type or in incidence or type of prior surgery among patients with early and late small bowel obstruction. The authors have also reported [23] early postoperative mortality of 3% and long-term mortality of 7% with the following independent risk factors: age >75 years old, medical complications, and a mixed mechanism of obstruction. Prevalence of medical and surgical morbidity was 8% and 6%, respectively.

It is likely that adjacent states with similar deer populations, large parks with no easy access for hunters, and lands that do not allow hunting have seen or will see impacts to vegetation similar to these. Without long-term data sets

as a point of reference, even catastrophic declines such as the ones published here, may go unnoticed. Acknowledgments We thank the Maryland Department of Natural Resources, Wildlife and Heritage Service for allowing us time toward this project. We thank the multitude of landowners who allowed access to study sites. We thank the public land managers where these surveys occurred including staff of Catoctin Mountain Park, Cunningham Falls State Park, Frederick Municipal Forest, and Gambrill State Park. A valuable and critical review of this manuscript was provided by D. Whigham. Numerous individuals assisted in this project in various ways or made Microtubule Associated inhibitor comments selleck chemicals to better this paper

including, D. Brinker, G. Brewer, B. Eyler, J. Harrison, R. Loncosky, W. McAvoy, J. McKnight, R. Naczi, D. Rohrback, S. Smith, T. Larney, and G. Therres. Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. References Alexandersson R, Agren J (1996) Population size, Selleck MK5108 pollinator visitation and fruit production in the deceptive orchid Calypso bulbosa. Oecologia 107:533–540CrossRef Alverson WS, Waller DM, Solheim SL (1998) Forests too deer: edge effects in northern Wisconsin. Conserv Biol 2:348–358CrossRef Anderson DJ (1994) Height of white-flowered trillium (Trillium grandiflorum) as an only index of deer browsing intensity. Ecol Appl 4:104–109CrossRef Augustine DJ, Frelich LE (1998) Effects of white-tailed deer on populations of an understory forb in fragmented deciduous forests. Conserv Biol 12:995–1004CrossRef

Behrend DF, Mattfeld GF, Tierson WD, Wiley JE III (1970) Deer density control for comprehensive forest management. J For 68:695–700 Brown RG, Brown ML (1984) Herbaceous plants of Maryland. Port City Press, Baltimore, p 1127 Côté SD, Rooney TP, Tremblay JP, Dussault C, Waller DM (2004) Ecological impacts of deer overabundance. Annu Rev Ecol 35:113–147CrossRef de Calesta DS (1994) Effects of white-tailed deer on songbirds within managed forests in Pennsylvania. J Wildl Manag 58:711–718CrossRef Fieberg J, Ellner SP (2001) Stochastic matrix models for conservation and management: a comparative review of methods. Ecol Lett 4:244–266CrossRef Fletcher JD, Shipley LA, McShea WJ, Shumway DL (2001) Wildlife herbivory and rare plants: the effects of white-tailed deer, rodents, and insects on growth and survival of Turk’s cap lily. Biol Conserv 101:229–238CrossRef Freker K, Sonnier G, Waller DM (2013) Browsing rates and ratios provide reliable indices of ungulate impacts on forest plant communities.