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NitroMed, Inc. (NTMD) Reports on BiDil XR(TM) Progress Following FDA Meeting, Announces Restructuring and Suspension of BiDil(R) Sales Force, and Retains Investment Bank to Advise on Strategic Options

1/15/2008 2:42:49 PM

LEXINGTON, Mass.--(BUSINESS WIRE)--NitroMed (NASDAQ: NTMD) said today that the Company received minutes of its December 10, 2007 meeting with the U.S. Food and Drug Administration during which the development plan of an extended release formulation of BiDil® (the fixed-dose combination isosorbide dinitrate/hydralazine hydrochloride), known as BiDil XR™, was discussed. The agency agreed that NitroMed's clinical development plan to conduct bioequivalence and pharmacodynamic studies comparing an extended release formulation of BiDil to the current commercial immediate release formulation of BiDil is acceptable. Such a plan could support FDA approval to commercialize BiDil XR, if bioequivalence is demonstrated. The bioequivalence study design compares the pharmacokinetics of the XR formulation to the pharmacokinetics of the immediate release formulation. The adequacy of the results will ultimately be determined during the regulatory review period. BiDil is an orally-administered medicine approved in the United States for the treatment of heart failure in self-identified black patients. BiDil is presently dosed three times daily and the Company is seeking to develop a once-a-day formulation.

NitroMed also announced today that it has implemented a restructuring plan that will eliminate approximately 70 positions over the next month, reducing headcount from approximately 90 to 20. The Company anticipates that headcount may be further reduced over the next several months. The Company is discontinuing its sales and promotional activities for BiDil, although the Company intends to keep BiDil available and on the market for patients. The Company estimates that it will record restructuring charges in a range of approximately $2.5 million to $3.0 million in the first quarter of 2008. The Company has engaged an investment banking firm, Cowen and Company, to advise on strategic alternatives for the Company.

NitroMed’s Chief Executive Officer Kenneth M. Bate said, “We are very pleased with both the FDA’s reaction to our proposed program for BiDil XR and with the results we achieved in our pharmacokinetic studies. We believe that our ability to successfully advance the goal of commercializing BiDil XR is now within reach, especially because our successes with formulation prototypes developed to date suggest bioequivalence may be demonstrated.

Mr. Bate continued, “We find ourselves at an important strategic juncture. We believe that BiDil is promotionally sensitive, and we have seen new prescriptions for BiDil increase by approximately 8-9% from the third quarter to the fourth quarter in 2007 as we heightened our marketing efforts and increased our field force. However, we believe that in order for BiDil to achieve its full potential, a larger marketing and sales effort than we can presently generate is required. In addition, NitroMed also faces a challenging capital market environment.

“Discussions with the FDA were productive and we remain optimistic about our ability to continue on schedule with our clinical work on BiDil XR,” said Mr. Bate. “We anticipate that a formulation could be finalized in 2008, with a goal of initiating pivotal bioequivalence trials in 2009, and a planned filing of the New Drug Application in 2010. In light of the operational considerations we currently face with regard to both BiDil and BiDil XR, we retained Cowen and Company to advise us on exploring strategic options to maximize shareholder value. Furthermore, in order to conserve cash, NitroMed is today suspending sales and marketing activities for BiDil and is implementing a plan to significantly reduce headcount over the next several months. NitroMed intends to continue to sell BiDil, but we are maintaining only essential functions. As part of our ongoing commitment to patients currently taking BiDil, NitroMed will be working with distributors and health care providers to ensure the availability of BiDil.”

Webcast and Conference Call

NitroMed will host a webcast and conference call today at 5:30 p.m. EST.

Date: Tuesday, January 15, 2008

Time: 5:30 p.m. Eastern Time

Access by Conference Call:

Domestic callers: 866/362-4666

International callers: 617/597-5313

Participant passcode: 48258929 #

Access by Webcast: Go to www.nitromed.com for live webcast link.

An audio replay of the earnings conference call will be available two hours after the call and through January 28, 2008. The replay can be accessed by dialing 888-286-8010

International callers should dial 617-801-6888. The replay passcode for all callers is 98642962 #

The webcast will be archived on the Company’s website for an indefinite period of time following the earnings call.

About NitroMed, Inc.

NitroMed of Lexington, Massachusetts is an emerging pharmaceutical company and the maker of BiDil® (isosorbide dinitrate/hydralazine hydrochloride), an orally administered medicine available in the United States for the treatment of heart failure in self-identified black patients. In this population, BiDil is indicated for the treatment of heart failure as an adjunct to current standard therapy, to improve survival, prolong time to hospitalization for heart failure and improve patient-reported functional status. There is little experience in patients with New York Heart Association (NYHA) class IV heart failure. Most patients in the clinical trial supporting effectiveness, referred to as A-HeFT, received, in addition to BiDil or placebo, a loop diuretic, an angiotensin converting enzyme inhibitor or an angiotensin II receptor blocker, and a beta blocker, and many also received a cardiac glycoside or an aldosterone antagonist.

Forward Looking Statements

Statements in this press release about future expectations, plans and prospects for the Company, including the Company’s expectations and timelines for the planned clinical development and commercialization of BiDil XR, its plans to conserve cash through its restructuring plan, its estimates regarding charges related to its first quarter 2008 restructuring plan and its plans to enter into strategic transactions to increase shareholder value, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks related to: difficulties in successfully developing, obtaining regulatory approval for, manufacturing and commercializing BiDil XR; the Company's ability to successfully execute on its first quarter 2008 restructuring plan, including, without limitation, the Company's ability to retain key employees and ability to achieve anticipated cost reductions; the Company's ability to identify and enter into strategic transactions that may potentially create shareholder value; the Company's ability to obtain or maintain intellectual property protection and required licenses; unanticipated expenses related to the Company’s restructuring plan; unanticipated operating expenses; general economic and market conditions; and other important factors discussed in the Section titled “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2007, which has been filed with the SEC, and in the other filings that the Company makes with the SEC from time to time. The forward-looking statements included in this press release represent the Company’s views as of the date of this release. The Company anticipates that subsequent events and developments will cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this release. Contacts

NitroMed, Inc. Jane A. Kramer, 781.266.4220 C: 781.640.8499

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Theravance, Inc. (THRX) Announces Closing of Public Offering of $287.5 Million of Convertible Subordinated Notes

1/25/2013 8:31:18 AM

SOUTH SAN FRANCISCO, CA--(Marketwire - January 24, 2013) - Theravance, Inc. (NASDAQ: THRX) (the "Company"), a biopharmaceutical company with a pipeline of internally discovered product candidates and strategic collaborations with pharmaceutical companies, announced that it closed the sale of its previously announced underwritten public offering of $287.5 million aggregate principal amount of its 2.125% convertible subordinated notes due 2023 (the "notes"), which includes the underwriters' full exercise of their option to purchase an additional $37.5 million aggregate principal amount of the notes. BofA Merrill Lynch acted as the sole book-running manager for the offering.

In connection with the offering of the notes, the Company entered into privately-negotiated capped call option transactions. The aggregate cost of the capped call options was $36.8 million.

The capped call options are expected generally to reduce the potential dilution upon conversion of the notes in the event that the market price of the Company's common stock, as measured under the terms of the capped call transactions, is greater than the strike price of the capped call transactions, which initially corresponds to the conversion price of the notes, and is expected to be subject to customary anti-dilution adjustments. However, if the market price of the Company's common stock, as measured under the terms of the capped call transactions, exceeds $38.00 per share, which is the initial cap price of the capped call transactions, the anti-dilutive effect of the capped call transactions will be limited.

In addition to paying for the cost of entering into the capped call option transactions, the Company intends to use the net proceeds of the offering for potential milestone payments to GlaxoSmithKline plc if there is any approval or launch of products under the parties' long-acting beta2 agonist (LABA) collaboration, including RELVAR™ or BREO™ (fluticasone furoate/vilanterol), ANORO™ (umeclidinium bromide/vilanterol), or vilanterol, for the potential repayment of debt, and for other general corporate purposes.

This press release is neither an offer to sell nor a solicitation of an offer to buy any securities and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale is unlawful.

The offering was made pursuant to a registration statement filed with the U.S. Securities and Exchange Commission (the "SEC") on January 16, 2013 and including a final prospectus dated January 17, 2013 filed with the SEC on January 18, 2013. Before you invest in the notes, you should read the prospectus in that registration statement and the other documents the issuer has filed with the SEC for more complete information about the issuer and the notes. You may get these documents for free by visiting EDGAR on the SEC's website at www.sec.gov. Alternatively, copies of the prospectus may be obtained by contacting the issuer or by calling BofA Merrill Lynch at 866-500-5408. In addition, copies of the final prospectus may be obtained from BofA Merrill Lynch, 222 Broadway, New York, NY 10038, Attn: Prospectus Department, or email dg.prospectus_requests@baml.com.

THERAVANCE®, the Theravance logo, and MEDICINES THAT MAKE A DIFFERENCE® are registered trademarks of Theravance, Inc.

RELVAR™ or BREO™ (FF/VI) and ANORO™ (UMEC/VI) are investigational medicines and are not currently approved anywhere in the world. RELVAR™, BREO™ and ANORO™ are trademarks of the GlaxoSmithKline group of companies. The use of these brand names has not yet been approved by any regulatory authority.

This press release contains certain "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives and future events. Theravance intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These statements are based on the current estimates and assumptions of the management of Theravance as of the date of this press release and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Theravance to be materially different from those reflected in its forward-looking statements. Factors that could cause such differences are described under the heading "Risk Factors" contained in Theravance's final prospectus filed with the SEC on January 18, 2013 related to the offering and the risks discussed in the Company's periodic filings with SEC. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Theravance assumes no obligation to update its forward-looking statements.

Contact Information:
Theravance, Inc.
Michael W. Aguiar
Senior Vice President and Chief Financial Officer

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Elan Corporation PLC (ELN) Announces Commencement of Tender Offer and Consent Solicitation
9/24/2012 9:58:48 AM

DUBLIN--(BUSINESS WIRE)--Elan Corporation, plc (“Elan”) (NYSE: ELN) today announced that its wholly-owned subsidiaries, Elan Finance public limited company (“Elan Finance”) and Elan Finance Corp. (“Elan Corp.” and together with Elan Finance, the “Issuers”), are commencing a cash tender offer (the “Tender Offer”) to purchase any and all of their outstanding:


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Fosun Pharma to Float up to $470 Million in Bonds
11/28/2011 6:48:29 AM

November 25, 2011 -- Shanghai Fosun Pharma received permission from the China Securities Regulatory Commission (CSRC) to offer up to 3 billion RMB ($470 million) of corporate bonds. The bonds will be issued in installments. Half of the total must be offered in the first six months, and the remaining amount can be issued during the next 18 months. Fosun Pharma did not disclose how it intends to use the capital. More details....

Stock Symbol: (SHA: 600196)


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Massachusetts Institute of Technology (MIT) Researchers Devise a Way to Manipulate a Rat's Dreams
9/6/2012 7:50:44 AM

Cognitive scientists working at MIT have devised a means for not only altering the dreams of rats, but of demonstrating a way of testing what they've achieved, offering evidence that it can be done, and in so doing have offered a glimpse into what may lie ahead for people who wish to manipulate their own dreams. Daniel Bendor and Matthew Wilson, working out of MIT's Picower Institute for Learning and Memory have, as they describe in their paper published in Nature Neuroscience, used audio sounds to influence the dreams of rats they were studying.


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Keep up to date with the latest news and content from Biotechnology for Biofuels and BioMed Central.

Open Access Research

Thermoascus aurantiacus is a promising source of enzymes for biomass deconstruction under thermophilic conditions

Shara D McClendon12, Tanveer Batth12, Christopher J Petzold12, Paul D Adams12, Blake A Simmons13 and Steven W Singer145*

Author Affiliations

1 Joint BioEnergy Institute, Emeryville, CA, USA

2 Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

3 Biomass Science and Conversion Technology Department, Sandia National Laboratories, Livermore, CA, USA

4 Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

5 Deconstruction Division, Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA, 94608, USA

For all author emails, please log on.

Biotechnology for Biofuels 2012, 5:54  doi:10.1186/1754-6834-5-54

The electronic version of this article is the complete one and can be found online at:

Received:6 June 2012
Accepted:13 July 2012
Published:28 July 2012

© 2012 McClendon et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Thermophilic fungi have attracted increased interest for their ability to secrete enzymes that deconstruct biomass at high temperatures. However, development of thermophilic fungi as enzyme producers for biomass deconstruction has not been thoroughly investigated. Comparing the enzymatic activities of thermophilic fungal strains that grow on targeted biomass feedstocks has the potential to identify promising candidates for strain development. Thielavia terrestris and Thermoascus aurantiacus were chosen for characterization based on literature precedents.

Thermoascus aurantiacus and Thielavia terrestris were cultivated on various biomass substrates and culture supernatants assayed for glycoside hydrolase activities. Supernatants from both cultures possessed comparable glycoside hydrolase activities when incubated with artificial biomass substrates. In contrast, saccharifications of ionic liquid pretreated switchgrass (Panicum virgatum) revealed that T. aurantiacus enzymes released more glucose than T. terrestris enzymes over a range of protein mass loadings and temperatures. Temperature-dependent saccharifications demonstrated that the T. aurantiacus proteins retained higher levels of activity compared to a commercial enzyme mixture sold by Novozymes, Cellic CTec2, at elevated temperatures. Enzymes secreted by T. aurantiacus released glucose at similar protein loadings to CTec2 on dilute acid, ammonia fiber expansion, or ionic liquid pretreated switchgrass. Proteomic analysis of the T. aurantiacus culture supernatant revealed dominant glycoside hydrolases from families 5, 7, 10, and 61, proteins that are key enzymes in commercial cocktails.

T. aurantiacus produces a complement of secreted proteins capable of higher levels of saccharification of pretreated switchgrass than T. terrestris enzymes. The T. aurantiacus enzymatic cocktail performs at the same level as commercially available enzymatic cocktail for biomass deconstruction, without strain development or genetic modifications. Therefore, T. aurantiacus provides an excellent platform to develop a thermophilic fungal system for enzyme production for the conversion of biomass to biofuels.

Thermoascus aurantiacus; Thielavia terrestris; GH 61; Polysaccharide monooxygenases; Fungal secretome; Ammonia fiber expansion; Ionic liquid; 1-ethyl-3-methylimidazolium acetate; Switchgrass (Panicum virgatum)

The secretomes of thermophilic fungi have been recently identified as promising sources of enzymes for improving the biochemical conversion of lignocellulosic biomass to biofuels [1]. Readily culturable thermophilic fungi are saprophytic and found in a range of environments, such as compost, where decomposition of organic matter occurs at elevated temperatures [2]. Glycoside hydrolase (GH) enzymes from thermophilic fungi function from 60–80°C [1,3-5], whereas commercial fungal cocktails produced by mesophilic fungi perform optimally at 50°C. Performing saccharifications of pretreated biomass at elevated temperatures contributes to increased conversion rates [6] resulting in shorter incubation times and lower enzyme loadings, as well as reducing the risk of downstream contamination by competing microorganisms for fermentable sugars. Therefore, thermophilic fungi may provide new enzymatic cocktails that are optimized for the industrial biochemical conversion of biomass to sugars for fermentation to biofuels.

Prior to fermentation, lignocellulosic biomass (e.g., corn stover, switchgrass) is typically pretreated chemically to reduce its recalcitrant properties. Pretreatment increases the efficiency of subsequent enzymatic hydrolysis of plant polysaccharides. Certain ionic liquids (ILs) have shown excellent promise in generating cellulose from biomass that readily hydrolyzed by enzymatic cocktails [7]. The majority of ILs that are effective biomass solvents are also toxic to microbes, however fungi have been shown to grow in the presence of high concentrations of some ILs [8]. Recently, a strain of the thermotolerant fungus Aspergillus fumigatus was grown on switchgrass in the presence of 5% 1-butyl-3-methylimidazolium chloride, abbreviated as [C4mim]Cl, secreting high amounts of cellulase and hemicellulase enzymes. These GHs were shown to retain residual activity in up to 20% [C4mim]Cl [9]. In addition, increased IL tolerance has been demonstrated for thermophilic glycoside hydrolases from bacteria [10,11] and archaea [12], suggesting a correlation between thermotolerance and IL tolerance. Therefore, thermophilic fungal enzymes may express enzymes that are tolerant to residual IL present in pretreated biomass, enabling a more cost-effective IL conversion process with minimal washing required after pretreatment.

In addition, culture supernatants of thermophilic fungi have been instrumental in identifying new accessory proteins that improve cellulose hydrolysis. Increased glucose release from pretreated barley straw was observed with mixtures of Cellulclast and Novozymes 188 cocktails supplemented with thermophilic fungal crude extracts, indicating that thermophilic fungi produce enhancers for cellulose hydrolysis [13]. Biochemical and proteomic studies identified these enhancement factors as proteins that are members of GH family 61. Addition of purified GH61 proteins from thermophilic fungi Thielavia terrestris or Thermoascus aurantiacus to a commercial Trichoderma reesei enzyme cocktail gave improved cellulose hydrolysis, resulting in 2-fold lower protein loading requirements [14]. Detailed characterization of GH61 from Thermoascus aurantiacus demonstrated that these proteins are Cu-containing monoxygenases that oxidize cellulose chains, facilitating glycoside hydrolase depolymerization [15]. These discoveries demonstrate the potential for studying thermophilic fungi as sources of proteins to improve hydrolysis of lignocellulosic biomass.

Our aim is to gain an understanding of the mechanisms that thermophilic fungi use to deconstruct biomass and develop industrially relevant enzyme cocktails for saccharification of pretreated biomass. Previous studies of thermophilic fungi have indicated that Thielavia terrestris and Thermoascus aurantiacus are promising species for the production of a thermophilic enzymatic cocktail for a lignocellulose deconstruction [13]. In this work, enzymatic hydrolytic activities of supernatants from T. aurantiacus and T. terrestris grown on untreated and chemically pretreated biomass were compared. This comparison, performed on artificial biomass substrates and pretreated biomass, established T. aurantiacus as a promising system to develop thermophilic enzymatic cocktails.

Growth of thermophilic fungi on biomass substrates

Thielavia terrestis NRRL 8126 and Thermoascus aurantiacusATCC 26904 were cultured on ethanol-extracted switchgrass (SG), ammonia fiber expansion treated switchgrass (AFEX-SG), 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]) treated switchgrass (IL-SG), and microcrystalline cellulose (MCC, Sigma #435244) for 3 days at 50°C. Culture supernatants were separated from fungal mycelia and remaining solids by filtration. The protein concentrations of the supernatants were estimated using both Bradford and BCA methods (Table 1). Since the BCA method is sensitive to the reducing sugars present in the supernatant, the proteins were precipitated using acetone to remove components that may interfere with the protein assay [16]. Values using either assay were comparable, except those generated with AFEX-SG; the higher levels of protein observed by SDS-PAGE in the supernatants from the AFEX-SG grown cultures were more consistent with the estimates obtained for the Bradford assay (see below).

Table 1. Estimated protein concentrations of culture supernatants using two protein assay methods1

Supernatant activities on artificial substrates

Cellulase (endoglucanase, cellobiohydrolyase, beta-glucosidase) and hemicelluase (xylanase, beta-xylosidase, arabinofuranosidase) activities were measured for these supernatants using artificial substrates (Table 2). Comparison of the cellulase profiles indicated that higher levels of endoglucanase was present in the T. terrestris supernatant but the T. aurantiacus supernatant possesses higher levels of cellobiohydrolase and β-glucosidase activity. For hemicellulosic substates, xylanase activity was higher for T. aurantiacus but lower for β-xylosidase activity. In general, the highest activities for the artificial biomass substrates were observed on supernatants generated from growth with SG and MCC.

Table 2. Secreted cellulase and hemicellulase activities (U/mg or mU/mg) from thermophilic fungi grown on complex biomass substrates1,2,3

The eight culture supernatants were screened for glucose release on lignocellulosic biomass substrate; these tests were performed to determine the most active samples from each fungal strain. The enzymatic activities were compared to a commercially available enzyme cocktail, Cellic CTec2 (Novozymes), in the saccharification of [C2mim][OAc]-treated switchgrass. Time course data on [C2mim][OAc]-treated switchgrass demonstrated that T. aurantiacus enzymes performed comparably to CTec2 at 50°C, while T. terrestris enzymes released between considerably less glucose compared to the T. aurantiacus supernatant (Figure1). For each strain, supernatants prepared from cultures on AFEX-SG were the most active of all the samples in cellulose hydrolysis, followed by supernatants from untreated switchgrass (SG), [C2mim][OAc]-treated switchgrass (IL-SG), and microcrystalline cellulose (MCC), respectively.

thumbnailFigure 1. Release of glucose from 2% [C2mim][OAc]-pretreated switchgrass. In the reactions, T. aurantiacus and T. terrestris culture supernatants were normalized to 1U CMCase activity. Glucan conversion (based on glucose only): 7 – 68%. Three replicates were performed and the error bars represent standard deviation from the mean.

Saccharification with culture supernatants from thermophilic fungi

The saccharification experiment described above established AFEX-grown cultures of T. aurantiacus and T. terrestris as promising sources of enzymes from thermophilic fungi. [C2mim][OAc] treated switchgrass (IL-SG) was used as a substrate, which has been shown to be an excellent substrate for commercial enzymatic cocktails [7]. Comparable amounts of glucose were released from IL-SG from T. aurantiacus enzymes and CTec2 at a range of protein loadings (Figure 2). Activities from T. terrestris were consistently lower at all protein loading levels. These trends were also observed when saccharifications were performed at different temperatures (Figure 3). The CTec2 cocktail and the AFEX-SG grown T. aurantiacus supernatant had the highest relative activity at 50°C; however the T. aurantiacus supernatant released almost 3-fold more glucose from IL-SG at 70°C than CTec2 and the T. terrestris supernatant. In contrast, the AFEX-SG T. terrestris supernatant had an activity maximum at 60°C, but the T. aurantiacus enzymes were 2-fold more active at the same temperature.

thumbnailFigure 2. Glucose released from [C2mim][OAc]-treated switchgrass at different enzyme loadings for culture supernatants from AFEX-SG grown T. aurantiacus and T. terrestris compared to equivalent enzyme loading from Cellic CTec2. The reactions were performed at 60°C with 2% (w/v) [C2mim][OAc]-pretreated switchgrass. Three replicates were performed and the error bars represent standard deviation from the mean.

thumbnailFigure 3. Temperature profile of the saccharification of [C2mim][OAc]-pretreated switchgrass with T. aurantiacus/T. terrestris culture supernatants and Cellic CTec2. Enzyme loading was set at 0.06 g enzyme/g glucan and biomass loading was 2% [C2mim][OAc]-pretreated switchgrass. Three replicates were performed and the error bars represent standard deviation from the mean.

Saccharifications of this supernatant were the tested against dilute acid and AFEX-SG, which are more recalcitrant substrates compared to IL-SG [7,17]. Comparison of saccharification of dilute acid and AFEX-SG switchgrass by the T. aurantiacus and CTec2 indicated that at high enzyme loadings, more glucose was released by the T. aurantiacus supernatant compared to the CTec2 cocktail for all three substrates (Figure 4). High and low enzyme loadings were applied as suggested by CTec2 recommendations, with 1 – 6% (w/w) enzyme to cellulose representing the range of low to high enzyme concentrations.

thumbnailFigure 4. Conversion of glucan to glucose and cellobiose using culture supernatants from AFEX-SG grown T. aurantiacus and Cellic CTec2 on various pretreated biomass substrates. Reaction conditions were: (2% w/v) biomass, 60°C, pH 5 for 72 hours with mixing. Switchgrass substrates were pretreated in three different ways: IL – ionic liquid, [C2mim][OAc]; DA – dilute acid, H2SO4; AFEX-, NH4. The saccharification reactions were performed at two different enzyme loadings, corresponding to recommended high and low enzyme loadings for Cellic Ctec2 ( Equal amounts of protein from both T. aurantiacus supernatants and Cellic CTec2 were added to each reaction (g enzyme/g glucan): AFEX-high/low ∼ 0.065/0.016; IL-high/low ∼ 0.046/0.011; DA-high/low ∼ 0.043/0.010. Three replicates were performed and the error bars represent standard deviation from the mean.

Proteomic analysis of the T. aurantiacus secretome

Proteomic analysis of the T. aurantaicus supernatants was performed to determine abundant proteins that may be responsible for the observed saccharification activity. Analysis of the T. aurantiacus supernatants showed distinct protein band patterns for each cultivation condition on untreated and pretreated switchgrass (Figure 5). The AFEX-SG supernatant had three prominent protein bands (∼50 kDa, ∼35 kDa, and ∼25 kDa), which were present at lower relative abundances in the other cultivations. Mass spectrometry analysis of the peptides from these three bands revealed that they predominantly consisted of four glycoside hydrolases: GH 7 (cellobiohydrolase), GH 5 (endoglucanase), GH10 (xylanase), and GH61 (copper-dependent polysaccharide monooxygenase) (Table 3). Visual comparison to T. terrestris demonstrated that there were no comparable prominent bands observed for the three cultivation conditions, which was consistent with the lower activity, therefore theT. terrestrisbands were not excised for analysis.

thumbnailFigure 5. SDS-PAGE analysis of supernatants fromT. aurantiacus and T. terrestris on 8-16% Tricine polyacrylamide gels. Lane 1, SG-grown T. aurantiacus; lane 2, AFEX-SG grown T. aurantiacus; lane 3, IL-SG grown T. aurantiacus; lane 4, MW markers; lane 5, SG-grown T. terrestris; lane 6, AFEX-SG grown T. terrestris; lane 7, IL-SG T. terrestris.

Table 3. Mass spectrometry analysis of major protein bands isolated fromT. aurantiacusAFEX-SG secretome.

In this work, we have shown that culture supernatant recovered from growth of T. aurantiacus on AFEX-SG exhibited high levels of saccharification activity on IL-SG. The higher levels of protein in the supernatants from the AFEX-SG grown supernatants may be due to additional nitrogenous compounds formed during the AFEX process [18]. The T. aurantiacus activity was 2–4 fold higher than the culture supernatant from T. terrestris at comparable protein amounts. CMCase activity was not predictive of saccharification activity, as supernatants from T. aurantiacus showed up to 11.5-fold lower activity on CMC compared to supernatants from T. terrestris. Cellobiohydrolase (pNPC) and β-glucosidase (pNPG) activities correlated with overall saccharification activities, demonstrating that exo-acting cellulases are critical for efficient saccharification of cellulose to glucose [19].

T. aurantiacus supernatant saccharification activities were comparable to the commercial enzymatic mixture Cellic CTec2 at 50°C at similar protein mass loadings and retained higher levels of activity up to 70°C. The temperature stability of the T. aurantiacus enzyme mixture is consistent with assays performed on purified endoglucanase and cellobiohydrolase enzymes from T. aurantiacus strains [4]. Cellic CTec2 has been shown to produce oxidized sugar products gluconic acid and cellobionic acid, suggesting the presence of GH61, a recently discovered Cu-containing cellulose monoxygenase expressed by many fungi, in the enzyme mixtures [20]. GH 61 from T. aurantiacus has been shown to reduce enzyme loadings 2-fold with Celluclast/N188 enzymatic cocktails from Novozymes and to be part of a cellulose oxidoreductase enzymatic system with cellobiose dehydrogenase that is synergistic with the well-studied hydrolytic system [13,15]. The presence of a prominent band in the corresponding to a GH61 protein at ∼25 kDA in SDS-PAGE analysis of the T. aurantiacus supernatants suggests that it may contribute to the high observed saccharification activity of T aurantiacus supernatants. The observed dominance of GH7, GH5, GH61 and GH10 in the AFEX-SG grown T. aurantiacus supernatants is similar to the GH profile of an optimal mixture of enzymes for glucose release from pretreated corn stover that was designed through computational modeling and high-throughput assays, a method referred to as GENPLANT [21]. The similarity between the GENPLANT-designed cocktail and the T. aurantiacus supernatants suggests that T. aurantiacus possesses very favorable properties for efficient cellulose hydrolysis.

Using chemical/UV mutagenesis and plate-based screeing, strains of Trichoderma reesei have been developed that secrete large amounts of cellulases and these strains are the basis for industrial production of cellulases for biomass deconstruction [22]. T. aurantiacus is an attractive candidate for a similar program of mutagenesis and screening, because it already secretes large amounts of cellulase enzymes, as demonstrated in the work described here, and it has a readily observed sexual state that could be used to select for specific mutations to enhance secretion of cellulases and remove deleterious mutations that accumulate during random mutagenesis and screening [23]. Therefore, T. aurantiacus has the potential to be a useful fungal species to understand cellulase secretion and biomass deconstruction under thermophilic conditions.

In conclusion, cultivation of T. aurantiacus and T. terrestris on biomass substrates revealed that T. aurantiacus grown on AFEX-pretreated switchgrass afforded high levels of cellulase enzymes in culture supernatants that were used to saccharify pretreated switchgrass at higher temperature and lower protein loadings than Cellic CTec2. Proteomic analysis of the supernatant demonstrated that the high activity could be attributed to the presence of high levels of proteins from the GH5, GH7, GH10 and GH61 families, which have been shown to be key enzymes in efficient cellulose hydrolysis. This work demonstrates that T. aurantiacus is a promising platform for the production of thermophilic enzymes for biomass deconstruction [1].

Fungal strains Thermoascus aurantiacus ATCC 26904 and Thielavia terrestris NRRL 8126 were obtained from American Type Cell Culture Collection. The fungal strains were maintained on potato dextorse agar (PDA) slants at 4°C. Ethanol-washed and [C2mim][OAc]-treated switchgrass (Panicum virgatum L.) were prepared as previously described [11]. Ammonia fiber expansion (AFEX)-treated and dilute acid-treated switchgrass were obtained as generous gifts and prepared using previously reported techniques [24,25]. Composition (cellulose:xylan:lignin content as percentage) of each biomass substrate is as follows: untreated switchgrass (35.1:20:21.2), IL-SG (51:21.4:18.5), AFEX-SG (36:20.8:20), and dilute acid-treated switchgrass (54:7.8:31.5). All chemicals, media, and other substrates were purchased from Sigma-Aldrich (St. Louis, MO) unless otherwise noted.

Thermophilic fungal cultivation

For each fungal strain, spores from a PDA slant were used to inoculate 50 mL of potato dextrose broth (PDB) and cultured at 50°C, 150 rpm. The seed culture was used to inoculate 50 mL culture flasks with biomass substrate (10 g/L), corn steep liquor (50% solids, concentrate of corn solubles) (10 g/L), sodium chloride (2 g/L), potassium phosphate (5 g/L), calcium chloride dihydrate (0.1 g/L), magnesium chloride heptahydrate (0.5 g/L), zinc (II) sulfate heptahydrate (0.002 g/L), manganese (II) chloride tetrahydrate (0.008 g/L), iron (II) sulfate heptahydrate (0.001 g/L), copper (II) sulfate heptahydrate (0.006 g/L), cobalt (II) chloride hexahydrate (0.0002 g/L) and adjusted to pH 5 prior to autoclaving. Fungi were cultured at 50°C, 150 rpm for 3 days. After cultivation, cultures were filtered with Miracloth (EMD Millipore, Billerica, MA) to remove mycelia, followed by a 0.45-μm filter with a cellulose acetate membrane (Thermo Scientific, Waltham, MA) for spore removal. The clarified supernatant was stored at 4°C. Crude enzymes were produced in duplicate cultures and used for all subsequent experiments.

Protein and glycoside hydrolase assays

Protein concentrations were determined using both Bradford assay (Bio-Rad, Hercules, CA) and bicinchoninic (BCA) assay (Pierce® BCA Protein Assay Kit, Thermo Scientific, Rockford, IL) methods using a 96-well plate (200 μL reaction volume) with bovine serum albumin as the standard. For BCA samples and standards, proteins were first precipitated with acetone and resuspended in 50 mM sodium acetate before measuring final concentration to remove interfering sugar residues [26]. All specific activities reported in this work were calculated using Bradford protein values. Endoglucanase and xylanase activities were assessed using the DNS (3,5-dinitrosalicylic acid) method using carboxymethylcellulose and birchwood xylan as substrates, respectively, with either glucose or xylose as the standard [27]. The enzyme reaction volume was 80 μL followed by 80 μL of DNS solution to measure released reducing sugars. One unit (U) of cellulase or xylanase activity was defined as the amount of crude protein releasing μmol of reducing sugar per min per mL of supernatant volume. Cellobiohydrolase (pNPC), β-D-glucosidase (pNPG), and β-D-xylosidase (pNPX) activities were determined using their respective p-nitrophenyl sugar substrates. 90 μL of sugar substrate was incubated with 10 μL of diluted enzyme, incubated for 30 min and quenched with 50 μL of 2% cold sodium bicarbonate. The absorbance of released p-nitrophenol was measured at 410 nm. Activities using p-nitrophenyl substrates were calculated as μmol p-nitrophenol released min-1 mg-1 crude protein. Due to possibility of color interference of the crude enzymes, samples were heat killed at 95°C overnight and used to remove background.

Biomass saccharification

Saccharifications were performed in the presence of 2% (w/v) of AFEX-SG, IL-SG, or dilute-acid pretreated switchgrass. Each mixture was prepared in 50 mM sodium acetate, pH 5.0 with the designated amount of enzymes (g protein per g glucan in biomass), which were added after the reaction mixture was prewarmed to the reaction temperature to a final volume of 1 mL in a 1.5 mL Eppendorf tube. Saccharifications were carried out at specified temperatures in a shaker for 72 hours. In time-course studies on IL-SG (5 mL, performed in 15 mL Falcon tubes), 500 μL samples were removed at designated time points. All hydrolysates were collected via centrifugation at 21,000xg for 5 min and 0.45-μm filtered to remove large biomass particles prior to sugar analysis. After filtration, samples were kept frozen at −20°C and thawed prior to analysis. Glucose and cellobiose concentrations were measured on an Agilent 1200 Series HPLC system equipped with an Aminex HPX-87H column (Bio-Rad) and Refractive Index Detector. Samples were run with an isocratic 4 mM sulfuric acid mobile phase. Sugar concentrations were determined using standards containing both glucose and cellobiose. Glucan conversion (mass of glucose plus cellobiose) was calculated using estimated glucan contents of pretreated switchgrass.

Proteomic analysis of thermophilic fungal secretomes

For SDS-PAGE analysis, supernatants were concentrated 50-fold with 10,000 MWCO PES ultrafiltration column (Vivaspin 500, Sartorius, Germany), loaded onto an 8 – 16% Tris-glycine Mini gel (Invitrogen, Carlsbad, CA) and run at 130 V for 90 minutes. Gels were stained with GelCode Blue Safe Protein Stain (Thermo Scientific). After staining and extensive rinsing, target protein bands were excised and digested using trypsin [28].

Samples were analyzed on an ABSciex TripleTOF 5600 (ABSciex, Foster City, CA) coupled to Eskigent nano-lc systems (Applied Biosystems, Foster City, CA). Peptide samples were injected onto a Pepmap100 μ-guard column (Dionex, Sunnyvale, CA) via a Famos Autosampler (Dionex) and washed for 10 minutes with Buffer A (2% Acetonitrile, 0.1% Formic Acid) at 15 μL/min. Peptides were eluted onto an Acclaim Pepmap100 C18 column (75 μm x 150 mm, 300 nL/min flow rate; Dionex) via a gradient consisting of initial starting condition of 5% buffer B (98% Acetonitrile, 0.1% Formic Acid), increasing B to 10% in 2 minutes followed by a 58 minute ramp to 35% B. Subsequently, B was increased to 90% over 3 minutes and held for 7 minutes followed by a ramp back down to 5% B for 15 minutes to re-equilibrate the column to the original condition. Peptides were introduced to the mass spectrometer by using a Nanospray III source (ABSciex) operating in positive-ion mode (2400 V) and data acquired with Analyst TF 1.5.1. The TripleTOF 5600 was operated in information dependent acquisition (IDA) mode whereby the ten most intense ions within 400 m/z to 1250 m/z mass range exceeding 150 counts (charge states 2–5) were selected for MS/MS analysis (high sensitivity mode, UNIT resolution with rolling collision energy). MS/MS spectra were scanned from 100 m/z to 1600 m/z and were collected for a total accumulation time of 200 ms. Former parent ions were excluded for 16 seconds following MS/MS acquisition. The acquired spectra were exported as.mgf files from Peakview version 1.1.1 (ABSciex) and processed with Mascot version 2.3.02 with a peptide tolerance of ±50 ppm and MS/MS tolerance of ±0.1 Da; variable modification was Oxidation (M) with up to one missed cleavage for trypsin. As a limited number of protein sequences from Thermoascus aurantiacus are available, searches were performed against sequenced T. aurantaicus proteins available in GenBank combined with a full ORF database from Thielavia terrestris obtained through the Genome Portal of the Joint Genome Institute [29], a list of common contaminants (e.g., trypsin, human keratin) and consisted of 10,007 sequences. Mascot DAT files were uploaded into Scaffold version 3.5 and searched via X!Tandem with the same sequences and parameters.

AFEX: Ammonia Fiber Expansion pretreatment; BCA: Bicinchronic Acid; bG: beta-Glucosidase; [C2mim][OAc]: 1-ethyl, 3-methyl imidazolium acetate; CBH: Cellobiohydrolase; CMC: Carboxymethyl Cellulose; IL: Iionic Liquid pretreatment (in this work, 1-ethyl-3-methylimidazolium acetate); MCC: Microcrystalline Cellulose; SG: Switchgrass.

Competing interests

The authors declare that they have no competing interests.

Author’s contribution

SDM and SWS designed the experiments. SDM performed all experiments, analyzed data, and wrote the manuscript. TB and CP setup and performed proteomic sample analysis. SWS, BAS and PAD reviewed and edited the manuscript. All authors read and approved the final manuscript.

Novozymes (Davis, CA) is acknowledged for the generous gift of enzyme cocktails (Cellic CTec2). Bruce Dale (Michigan State University; Great Lakes Bioenergy Center) is acknowledged for providing AFEX-treated switchgrass and Mike Himmel (National Renewable Energy Laboratory; BioEnergy Science Center) is acknowledged for providing dilute acid-treated switchgrass. We thank Dr. Ken Vogel at the United States Department of Agriculture, Lincoln, NE, for supplying switchgrass. This work was performed as part of the DOE Joint BioEnergy Institute ( supported by the U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research, through contract DE-AC02-05CH11231 between Lawrence Berkeley National Laboratory and the U.S. Department of Energy.

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Location Madagascar, Antsiranana
Central coordinates 49o 6.00' East  12o 55.00' South
IBA criteria A1, A2, A3
Area 18,225 ha
Altitude 50 - 409m
Year of IBA assessment 2001

Asity Madagascar (Affiliate)

Site description This reserve is located 70 km south of Antsiranana and 20 km north of Ambilobe. It is delimited by a cliff in the west, by the Mananjeba river in the south and, in the east, by the Route Nationale 6 between Antsiranana and Ambilobe. Ankarana is a massif of Jurassic limestone overlying a basaltic plain. The massif is highly eroded and karstic (‘tsingy’), and is divided by deep, northward-running canyons, penetrated by caves. Several underground rivers, the most important of which are the Ankarana, Mananjeba and Besaboba, flow through these caves in an east–west direction (into Ambavanankarana Bay), creating a very complex drainage system. During the dry season, the massif is an important hydrological reservoir for neighbouring people and their domestic animals. There is a large variety of microhabitats. Flat limestone areas are covered by dense, dry deciduous forest, dominated by Leguminosae and Burseraceae. The basalt floor of the canyons, where little water can infiltrate, allows the presence of dense, humid evergreen forest, similar in structure to such forest in eastern Madagascar, and dominated by Dalbergia, Canarium, Ficus, Zanthoxylum, palms and Pandanaceae. Degraded areas contain bamboo Olyra. Xerophytes such as Adenia, Aloe, Pachypodium and Noronhia cover the tsingy. The surroundings of the massif are covered by typical western savanna with Bismarckia palms.

Key Biodiversity See Box and Tables 2 and 3 for key species. Ninety-four species are known from the site, of which 34 are endemic to Madagascar. The site is important for both forest birds and waterbirds. Forest birds occur in the ‘Foresters Canyon’ and the ‘Grand Canyon’ in the western part of the reserve, as well as in Analamay in the eastern part. Such birds are usually absent from the Tsingy May forest, an area of low vegetation on the most exposed rocks. The site is one of the six known for Mesitornis variegata, and holds (with nearby Andavakoera) the only populations of Caprimulgus enarratus known in the West Malagasy biome.

Non-bird biodiversity: Lemurs: Phaner furcifer ?electromontis (VU), Eulemur coronatus (VU), E. fulvus sanfordi (VU), Hapalemur griseus ?occidentalis (VU), Lepilemur septentrionalis (VU), Propithecus diadema perrieri (CR), Daubentonia madagascariensis (EN). Carnivore: Cryptoprocta ferox (VU).

Populations of IBA trigger species

Species Season Period Population estimate Quality of estimate IBA Criteria IUCN Category
Madagascar Crested Ibis Lophotibis cristata resident  1986  present  A1  Near Threatened
Madagascar Pond-heron Ardeola idae breeding  1986  present  A1  Endangered
Madagascar Heron Ardea humbloti resident  1986  present  A1, A3  Endangered
Madagascar Fish-eagle Haliaeetus vociferoides resident  1986  present  A1, A3  Critically Endangered
Madagascar Sparrowhawk Accipiter madagascariensis resident  1986  present  A1  Near Threatened
White-breasted Mesite Mesitornis variegatus resident  1986  present  A1, A2, A3  Vulnerable
Coquerel's Coua Coua coquereli resident  1986  present  A2, A3  Least Concern
Van Dam's Vanga Xenopirostris damii resident  1986  present  A1, A2  Endangered
Sickle-billed Vanga Falculea palliata resident  1986  present  A3  Least Concern
Sakalava Weaver Ploceus sakalava resident  1986  present  A3  Least Concern

Protected areas

Protected area Designation Area (ha) Relationship with IBA Overlap with IBA (ha)
Ankarana Special Reserve 25,308 protected area contains site 18,225

IUCN habitat Habitat detail Extent (% of site)
Artificial - terrestrial   3%
Unknown   6%
Shrubland   42%
Forest   47%

Land use

Land-use Extent (% of site)
agriculture -
forestry -
nature conservation and research -
water management -
other -
Notes: Firewood collection.
not utilised -

References Decary and Kiener (1970), Fowler et al. (1989), Green et al. (1991), Hawkins et al. (1990), Jenkins (1987), Meyers and Ratsirarson (1988), Nicoll and Langrand (1989), Paulian (1961), Rand (1936), Remillet (1973), Simons et al. (1990), Walters et al. (1986), Wilson (1985), Wilson et al. (1987).

Contribute  Please click here to help BirdLife conserve the world's birds - your data for this IBA and others are vital for helping protect the environment.

Recommended citation  BirdLife International (2015) Important Bird Areas factsheet: Ankarana Special Reserve. Downloaded from on 28/05/2015

To provide new information to update this factsheet or to correct any errors, please email BirdLife


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Innovative projects for conservation funding

By BirdLife Europe, Thu, 27/06/2013 - 09:12

Delivering creative proposals for funding projects aiming at building relationships and aligning interests were some of the main conclusions of the workshop “Impact at the Core: The perfect core-project funding mix for successful nature conservation”, held on June 20 at the BirdLife World Congress. Participants discussed on how to develop strategic and effective ways of obtaining funding and shared examples and best practices of working with donors.

“We don’t need core funding as a way to subsidise our organisation, but we would like core funding increased to boost the actual delivery and the impact of our activities”, said Marco Lambertini, CEO at BirdLife International.

BirdLife Partners provided several examples of how and core funding has been received and what it has been used for, such as the BirdLife Partnership with Arcadia, which has provided $5 million in funding during five years to increase Partners’ capacity, as well as funding that has been provided to BirdLife Kazakhstan for the designation of 9000 hectares of protected land.

Innovation is becoming more and more pertinent to obtain funding and in particular crowdfunding was one method of fundraising that was discussed at the event. Crowdfunding refers to the collective effort of individuals who network and pool their money, usually via the Internet, to support efforts initiated by other people or organizations. Luis Costa, from SPEA (BirdLife in Portugal), talked about a crowdfunding campaign to support the conservation of the Azores Bullfinch. “We raised $13000 through crowdfunding, and also achieved visibility through the media coverage that the campaign attracted”.

Alberto Yanosky, from Guyra (BirdLife in Paraguay) revealed a carbon funding project in his country: “We are aiming to protect 10,000 hectares of forest to compensate up to 800,000 tonnes of CO2 emissions. With $400,000 invested, the companies are helping us to reduce carbon emissions for years”, Yanosky stated.

Creative approaches for raising funds for projects linking conservation work and economy, such as ecotourism and marketing projects were also pointed out.

The European Commission was represented by Karl Falkenberg, Director-General for the environment, who said “We appreciate NGOs and BirdLife’s expertise in many issues related to the environment. We rely on your expertise, feedback and management capacity to implement nature projects to ensure EU biodiversity is defended and put back in a healthy state. Your role is important and deserves budgetary support”.

Lynda Mansson, General Director of the MAVA Foundation, also provided some tips for how to better take advantage of funding opportunities: “Be creative with the range of possibilities, state clearly and truly the reason of asking for funds, have a clear idea of measuring success, build confidence, be careful about eroding trust, plan ahead before emergency arrives, and involve the donor in the conversation about what is happening”.

For more information: please contact Stefania Macchioni, Grant Writing & Donor Management Officer at BirdLife Europe.

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Africa begins Journey to Combat Illegal Trade in Wild Fauna and Flora

Mon, 11/05/2015 - 11:42

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Climate Change

  • Climate change poses new challenges to BirdLife’s approaches to conserving species and Important Bird Areas.

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The Big or Civil Society?

The election of a new Coalition government in the UK has led to a change of direction in third sector policy within England, referred to by the new government as ‘building the Big Society’. Outlining the key commitments of the Big Society agenda and the ideology behind them, Pete Alcock identifies some of the implications for third sector policy and practice.

Pointing to research evidence, the article explores some of the contradictions which seem to lie behind the Big Society philosophy. There is evidence to refute, for example, the idea that reduced public welfare provision leaves more space for voluntary action. The article goes on to question whether the big society agenda may threaten third sector unity.

Research contact:
Pete Alcock


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Guitar Pinata (Each)

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Our Price: $12.99 MSRP: $19.49

Rock out your birthday party with this fun yellow guitar pinata. Your birthday boy and friends will make music when they try to crack open this large yellow and pink paper mache guitar shaped pinata. It can hold up to three pounds of candy and will make a great addition to your upcoming birthday party.

  • Size:  31” x 2 ½” x 12 ½”
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by PowerReviews Express
  • Product Number: BB14880
  • Air Shippable: No
  • Return Eligible: Yes
  • Oversized: No


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Public recapitalisations and bank risk: evidence from loan spreads and leverage

Working Papers No 383
July 2012

A number of countries' authorities put in place bank rescue packages using public funds in response to the global financial crisis. Were these public recapitalisations followed by a reduction of risk in banks' loan books? To answer this question, in this paper the balance sheets and syndicated loan portfolios of 87 large internationally active banks, approximately half of which were rescued during the crisis, are analysed for the period 2000-10. Evidence is presented that banks that were later rescued took on higher risk in their loan books before the crisis than banks that were not, especially in their home markets. Although the riskiness of loan signings started diminishing across the board in 2009, we do not find consistent evidence that rescued banks reduced their risk relatively more than non rescued banks during the crisis.

JEL classification: G15, G21, G32, E51

Keywords: external support, portfolio choices, home bias, risk, banks, syndicated loans


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Intel Sandy Bridge E Review

Intel Sandy Bridge E Review

Manufacturer: Intel
UK price (as reviewed): From £479 to £839 inc VAT
US price (as reviewed): From $555 to $990 ex tax

Sandy Bridge E is a monster in every regard

Sandy Bridge E is a monster in every regard

There’s been plenty of rumour and speculation surrounding Sandy Bridge E since we first heard about the new CPU series back in April 2010. Initially we were under the impression that the 'E' stood for 'Enthusiast' or 'Extreme', even though Intel denied the later at IDF earlier this year. Regardless, having tested several Sandy Bridge E CPUs over the last few months we're not convinced that either moniker is correct, as we'll explain.

If you only glanced at the specs of Sandy Bridge E you could be easily forgiven for dismissing it as merely an existing LGA1155 Sandy Bridge CPU that has had two extra cores bolted on plus a more sophisticated memory controller.

However, that wouldn't really be a fair assessment. This is because, like AMD recently did with its woeful FX-8150, Intel has taken a workstation/server CPU, and repurposed it as a high-end desktop CPU. That 8-core (16-thread) workstation/server CPU, codenamed Romley was first announced at IDF last year.

However, it's yet to be released, as its development has hit a number of snags over the last few months. That hasn't stopped Intel from stripping down Romley and releasing it as Sandy Bridge E.

So what differentiates a Sandy Bridge E processor from a Sandy Bridge CPU? The most obvious difference is the addition of two extra physical cores, bringing the total up to six. As each physical core also sports a secondary logical core thanks to Hyper-Threading, this means that a Sandy Bridge E CPU can process up to 12 twelve threads simultaneously.

While each physical core in a Sandy Bridge E CPU has the same amount of Level 1 and Level 2 cache as a Sandy Bridge processor, there's up to 15MB of Level 3 cache in a Sandy Bridge E processor rather than the 8MB in the Sandy Bridge design. This means that Sandy Bridge E processors have up to 2.5MB of Level 3 cache per core versus 2MB per core of Sandy Bridge. However, as we'll see, not all Sandy Bridge E CPUs have the same amount of Level 3 cache, so check carefully when speccing up a new system.

Intel Sandy Bridge E Review
You can trace the Romley ancestry of Sandy Bridge E in
this die shot, which clearly shows the two 'missing' cores.

To feed all those extra cores, Intel has developed a new memory controller, which is capable of addressing four channels at once. This means you're supposed to install DIMMs in multiples of four for best performance. However, while this in theory provides double the memory bandwidth to the system over Sandy Bridge's dual-channel memory controller, it has grave consequences for motherboard design (more on this later).

The other significant difference between Sandy Bridge E and its Sandy Bridge forebear is that the new 6-core variant lacks the on-die Processor Graphics. This is emminently sensible as the power users that Sandy Bridge E is targetted at are extremely unlikely to use an underpowered on-board GPU. Even so, Sandy Bridge E retains a variant of the ring bus technology of Sandy Bridge, the central bus that links the various units within the CPU togther (i.e. cores, cache, I/O and memory controllers). As such, contrary to the hope of many enthusiasts, Sandy Bridge E doesn't see the return of a massively overclockable bus (more on this later).

Thanks to the extra cores and more complex memory controller, Sandy Bridge E CPUs require many more connections to the motherboard than the 1,155 connections of Sandy Bridge's LGA1155 CPU socket. Instead, Sandy Bridge E CPUs are built into a new far-larger LGA2011 package. This means you'll need to buy a new motherboard if you want to upgrade to Sandy Bridge E.

Intel has announced three Sandy Bridge E processors, although only two will be available to buy at launch. The odd one out, the Core i7-3820, isn't due until early next year. The table below summarises the principle differences between the three Sandy Bridge E chips.

Intel Sandy Bridge E processors
NameNominal FrequencyMax Turbo Boost FrequencyTDPPhysical CoresLevel 2 cacheLevel 3 cacheSRP
*Core i7-3960X Extreme Edition3.33GHz3.9GHz130W66 x 256KB15MB$990
*Core i7-3930K3.2GHz3.8GHz130W66 x 256KB12MB$555
Core i7-38203.6GHz3.9GHz130W44 x 256KB10MBUnknown
* = Launch models

As you can see, the two Sandy Bridge E CPUs that are launching today are clocked at a modest 3.3GHz (the Core i7-3960X Extreme Edition) and 3.2GHz (the Core i7-3930K). However, both support Turbo Boost, so can dynamically overclock themselves up to 3.9GHz and 3.8GHz respectively, depending on the CPU load, power draw and the CPU and VRM temperature.

Finally, before we dive into the CPU reviews themselves its worth pointing out unlike other retail boxed CPUs, Sandy Bridge E chips don't include a cooler as standard. Instead, you'll need to go out and buy your own LGA2011-compatible cooler. Due to the significantly higher TDP of Sandy Bridge E (130W versus 95W) and larger socket, many coolers cannot cope with Sandy Bridge E processors.

Equally, while some LGA1366 coolers physically fit onto LGA2011 motherboards, they may not provide enough clip pressure to ensure sufficient contact between the pins in the processor socket and the pads on the bottom of the CPU, potentially killing the CPU and motherboard.


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Cooling start-up Cryorig announces first product

Cooling start-up Cryorig announces first product

Cryorig, a newcomer to the market, has announced plans to launch its début R1 heatsink in January followed by a more powerful R1 Ultimate in February.

The cooling market just got a little larger with the announcement of the Cryorig R1 dual-tower cooler from the eponymous Taiwanese start-up, founded just five months ago.

While the company itself is brand-spanking new, the team behind it claims years of research - having started work on developing new heatsink designs back in the early 2000s. The company boasts employees who have previously worked for or with well-known brands including Phanteks, Prolimatech and Thermalright, as well as experience of the overclocking and modding communities - so you'd expect plenty from its début product.

At first glance, the Cryorig R1 certainly ticks some buzzword boxes. Based around a dual-tower design, the heatsink features seven 6mm heatpipes soldered into the centre of a pair of two-tone aluminium fin stacks. The company claims to use what it calls DirectCompress Soldering, a method of connecting the heatpipes which results in a claimed 10 per cent increase in surface area contact for improved heat transfer.

The trademarked techniques continue with the heatpipes themselves, which are arranged in a staggered layout dubbed Heatpipe Convex-Align. Another trademarked design can be found in the dual-section tower stacks, which include a 2.4mm gap between the front fins reducing to 1.8mm at the rear fins - an airflow-boosting technique the company has chosen to call the Jet Fin Acceleration System.

Cryorig isn't done with the trademarks there, though. The act of spreading the heatpipes out from the nickel-plated copper base - hardly unique to the Cryorig R1 - gets a trademark of its own as the company's Heatsink Displacement Optimisation technique, while the own-brand fans include High Precision Low Noise (HPLN) sleeve bearings and detachable Acoustic Vibration Absorbers - or rubber pads to you and me.

Finally, the company has a last trademark up its sleeve - and a patent in pending, too - in the form of the MultiSeg Quick Mount System which claims compatibility with all current Intel LGA and AMD socket types.

The Cryorig R1 is designed to be used with a pair of fans - a 140mm, 13mm-thick 65CFM unit dubbed the XT140 at the front and a thicker 25.4mm XF140 offering 76CFM in the centre - and weighs a total of 1,181g when both are fitted. Overall, the heatsink measures 140mm wide by 130mm deep and is 168.3mm high with a 41.5mm motherboard-to-fin gap. The company has also announced plans to launch an R1 Ultimate which replaces the thinner XT140 with a full-size XF140 and adds an extra mounting bracket for optional third fan at the rear of the tower.

Sadly, there's one thing Cryorig isn't yet sharing: the price. The company has confirmed plans to launch the standard Cryorig R1 in January and the Cryorig R1 Ultimate in February 2014, both with the global markets in their sights. More details are available on the official website.

Discuss in the forums Reply
Pookie 2nd December 2013, 11:39 Quote
They even pinched the Crytek color scheme!
enciem 2nd December 2013, 12:40 Quote
Originally Posted by Pookie
They even pinched the Crytek color scheme!

...or they got it from a basic colour wheel, or the yRGB format. Cryorig R1 Ulitmate is damn silly name mind. Sounds like release 1 of the ultimate, that's not very ultimate.
[USRF]Obiwan 2nd December 2013, 13:08 Quote
Lets throw some noncense TM statements: DirectCompress, Heatpipe convex-align, Jet Fin Acceleration System, Heatsink Displacement Optimization, High Precision Low Noise HPLN, MultiSeg...

they must have hired an ex Monster Cable creative advertising guy too.
Corky42 2nd December 2013, 13:25 Quote
Or maybe they plan on making more money from patent infringements than selling products.
fluxtatic 3rd December 2013, 07:21 Quote
High Precision Low Noise (HPLN) sleeve bearings

Unless they're aiming for low-mid market, sleeve bearings aren't anything I'd be mentioning. Maybe they should have skipped some of the brainstorming sessions to come up with names for their Fancy Trademarked Technology and gotten about sourcing some ball bearing fans?

The more marketing speak I see from a company, the lower my expectations get. Given this versus a company that gives the equivalent of "they're heatpipes, what do you want from me?", I'll go with the latter every single time. Or at least show what you can do before your marketing guys leave a trail of slimy sales-grease all down my monitor.
Corky42 3rd December 2013, 09:37 Quote
If your looking for low noise sleeve bearings are preferable as ball bearing fans tend to exhibit a little more noise.
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August 23rd, 2011

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Can I be in please?

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so saaaad

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thanks...i am still deciding on what should happen next...

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Quite a decent series!

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INSPIRATION: Fashion and Architecture Meet at MOCA

This fall, head to the Museum of Contemporary Art to check out the connections between architecture and fashion at the museum’s “Skin & Bones: Parallel Practices in Fashion and Architecture” exhibit. The show will highlight the looks and concepts that the industries have in common—ideas of space, volume, and movement that are also critical to events. The exhibition focuses on the period from 1980 to the present and includes works from 40 architects and fashion designers from the United States, Europe, and Japan. Featured designers include Alexander McQueen, Narciso Rodriguez, Vivienne Westwood, and Yohji Yamamoto, and architecture firms include Diller Scofidio & Renfro, Gehry Partners, Zaha Hadid Architects, and Herzog & de Meuron. The exhibition will run from November 19 through March 5, 2007. Alesandra Dubin
Photo: Satoru Mishima
Posted 05.12.06


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Creative types

Wyatt Brand reps Israel for SXSW — blog

Wyatt Brand is charged with bringing exposure to Israel’s cultural scene during the South by Southwest Interactive, Music and Film Festivals this March.

A cultural convoy of about 40 to 50 Israeli techies, musicians and filmmakers — calling themselves I: Made in Israel — will be attending this year’s conference. This is the second time Israeli representatives have come to the conference, but their presence this year will be three times as large as last time.

The Consulate General of Israel in Houston is working with Wyatt Brand on the South By initiative.

David Wyatt, owner of Wyatt, said he looks forward to raising the profile of the film, music and technology that’s happening in Israel — particularly its energetic, metropolitan city of Tel Aviv. One challenge for them: The arts and culture of Israel is often overshadowed by political news or religious and historical reference, Wyatt said.

“We are telling the story of the creative life and talent that’s in places like Tel Aviv,” Wyatt said. “It’s about getting people excited about the [arts] and then making the association that it’s from Israel.”

Wyatt Brand, a communications and branding firm that specializes in working with culture and arts organizations, said gaining Israel as a client has been a great affirmation for the agency.

Media & Marketing


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Red Bull leaves Austin boot maker with unpaid bill

Red Bull has left one Austin boot maker with an unpaid bill for a pair of custom-made boots for Formula 1 driver Sebastian Vettle.

Noel Escobar, owner of Texas Custom Boots, told German newspaper Bild that he worked through the night to make the boots for Red Bull, but no one came to pick them up.

“Red Bull owes me $2,150,” Escobar told the paper.

The energy drink company told the newspaper it had to cancel the order at short notice, but is happy to pay the bill.

Click here to see a photo of the boots on Bild's website.

Follow us on Twitter @MyABJ, on Google+ and on Facebook.


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Investor buys three Dayton buildings

A New Carlisle investor is boosting his local holdings. Garrett Gernon recently bought three downtown Dayton buildings on East Third Street.

Tammy Tumblison, a realtor with Dayton Commercial Realty, on March 26 sold the building at 131 and 133 E. Third St. and the two buildings at 135, 137 and 139 E. Third St. to Gernon for $450,000. The buildings previously were owned by North Third Holding LLC and are at Third and St. Clair streets.

Gernon, who owns various properties in the Dayton area, purchased the sites as an investment opportunity, Tumblison said. Gernon declined to comment.

The deals signify a burgeoning investment landscape across Dayton. Both local and out-of-state buyers have recently inked deals for Dayton investment properties.

The 131 and 133 E. Third St. building — a 15,900-square-foot building — houses Cachet G, a clothing store, on the ground floor and 18 studio apartments, seven of which are occupied. The other two buildings, each of which is 2,200 square feet, formerly housed Santana’s Cafe.

Since Tumblison took on the listings in April 2010, more than 2,500 people have toured the buildings and a dozen have made offers, she estimates. However, despite the interest, the deals fell through because the potential buyers couldn’t get financing for the buildings, which require renovation.


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Colorado stocks: Kodiak Oil, Ciber up 6%; Guaranty Bancorp up 5%

The Dow and Nasdaq scored gains Tuesday. In Colorado, Kodiak Oil, Ciber and Guaranty Bancorp were among the biggest actively traded gainers.

The Dow Jones Industrial Average finished the trading day at 11,105.85, up 44.73 points (0.4 percent). It was the blue-chip index's second straight gain.

The S&P 500 closed at 1,172.87, up 10.6 points (0.91 percent).

The Nasdaq Composite finished at 2,532.15, up 37.06 points (1.49 percent).

Among actively traded Colorado-based stocks, Kodiak Oil & Gas Corp. (KOG) led the day’s gainers percentagewise, up 6.18 percent (35 cents) to close at $6.01.

Other Colorado gainers:

Ciber Inc. (CBR) — Up 5.81 percent (18 cents) to $3.28.

• Guaranty Bancorp (GBNK) — Up 5.45 percent (6 cents) to $1.16.

Advanced Energy Industries Inc. (AEIS) — Up 5.41 percent (51 cents) to $9.94.

National CineMedia Inc. (NCMI) — Up 5.15 percent (66 cents) to $13.47.

Janus Capital Group Inc. (JNS) — Up 5.07 percent (33 cents) to $6.84.

Among actively traded Colorado-based stocks that declined on the day was M.D.C. Holdings Inc. (MDC), down 2.44 percent (43 cents) to close at $17.20.

Other Colorado decliners:

Evergreen Energy Inc. (EEE) — Down 0.91 percent (1 cent) to $1.09.


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Joe Blattner on YPO: "People had my back"

Joe Blattner learned about the Young Presidents Organization while he was enrolled in a program at Carnegie Mellon University’s Donald H. Jones Center for Entrepreneurship in 1994. Blattner, then 40, was head of the advertising agency Blattner Brunner. (He left the agency, now known as Brunner Inc., in 2003). He so enjoyed learning from fellow entrepreneurs that the opportunity to do the same with top executives intrigued him. He not only wound up joining YPO’s Pittsburgh chapter, but when he reached the age of 50 — the cut-off point for YPO — he was happy to “graduate” to its sibling entity, the World Presidents Organization.

Now running three companies, Class-G LP, COMPackage and Joe Blattner Consulting, he remains supportive of YPO and was instrumental in helping the Business Times coordinate a roundtable of seven local company chiefs, all current YPO members, who discussed multiple aspects of leadership in the April 25-May 1 issue. Blattner shared his thoughts and experiences in the following Q&A:

How did you come to join YPO?

I met (Genco CEO) Herb Shear through the Don Jones program. He was my sponsor. It was a very hush-hush group and they were reverse-selective. I knew about YPO but not enough about it. I joined because I wanted to learn from people who knew stuff I didn’t know. YPO isn’t about networking, but it’s a fabulous network. It’s not about hobnobbing with customers. but it’s a fabulous place for customers. You’re not allowed to solicit fellow members. It’s about education and there are so many environments where you learn — there are the chapter meetings, seminars, forums, university and specialty groups. And it’s an organization of peers. In my 10 years there, every year I went to a four-day conference which was always held somewhere incredible and different. There’d be spectacular education sessions in the morning and spectacular networking in the afternoon.


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Company Profile

News from The Business Journals

Mar 19, 2015, 6:45 am  EDT Morning Edition Triangle Business Journal

Raleigh's 10 best restaurants, according to The Culture Trip

Choosing 10 had to have been difficult. See if you agree with the travel website's list.

Aug 18, 2014, 7:57 am  EDT Real Estate Inc. Triangle Business Journal

18 Seaboard renegotiating lease at Seaboard Station

Jason Smith's 18 Seaboard restaurant was one of the first tenants to open in 2006 in the redeveloped Shops at Seaboard Station in downtown Raleigh, but his lease there is set to expire soon.

Oct 30, 2013, 2:32 pm  EDT Triangle Business Journal

Getting an early start on holiday shopping? Downtown Raleigh now has its own gift card

More than 80 retailers and restaurants in downtown Raleigh are combining their retail power this holiday season with the first-ever Downtown Raleigh g ...

Aug 27, 2013, 8:58 am  EDT Triangle BizBlog Triangle Business Journal

Raleigh's 18 Seaboard chef plans new eatery in Durham

Jason Smith, the celebrated chef-proprieter of 18 Seaboard in downtown Raleigh, has started to settle on plans for his third restaurant in the Triangl ...

Apr 18, 2011, 3:29 pm  EDT Triangle Business Journal

Wake Tech Culinary Arts Showcase

Wake Technical Community College last week hosted the Wake Tech Culinary Arts Showcase, which took center stage at the Raleigh Convention Center, with ...

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Josh Voegtli
New Hire November 12, 2012

Josh Voegtli

Controller at Guarantee Electrical Co.

Josh Voegtli, CPA (resident of South St. Louis County, 63129), has joined Guarantee Electrical Co. as controller. Voegtli assumes responsibility for the financial control of company assets and cultivates the firm’s banking, bonding and insurance relationships. More information is online at

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S. M. Wilson & Co.

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Bala Nibhanupudi
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Adam Williams

Adam Williams

Turnip Truck

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Autism Society of Colorado

Sponsor Nick Mattingly

Nick Mattingly

Switcher Studio


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Nasdaq threatens to delist Famous Dave's

Nasdaq threatened to boot Famous Dave's of America Inc. from the securities exchange following the resignation of two board members, the Minnetonka-based BBQ chain disclosed in a regulatory filing.

Richard Monfort and Lisa Kro resigned from the Famous Dave's (Nasdaq: DAVE) board of directors last month.

Their departures left the company with only two independent directors serving on the board's audit committee, one short of the three independent committee members required for listing on the securities exchange, according to a Wednesday filing with the Securities and Exchange Commission.

Famous Dave's alerted Nasdaq to its noncompliance last week. Nasdaq gave the company until its next annual shareholders' meeting to add another independent director to the committee. The most recent annual meeting was May 6.

Famous Dave's said it "intends to appoint another director who meets the applicable independence requirements to its audit committee and expects to regain compliance."

The board's chairman resigned earlier this month, following the chief financial officer, its president and chief operating officer, and the company's previous CEO out the door of 2014. Former McDonald's executive Ed Rensi is now the CEO of Famous Dave's.

RELATED: Famous Dave's will pay severance to one ex-CEO but not the other


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Okay, so your site is pretty. You’ve gotten your branding and images all perked up and the aesthetics look pleasing to your focus groups and testing has shown that yes, your value proposition is succinct and believeable. But no clicks. Huh?

It’s a stage I think that many many SMBs go thru and that stage can be headed ‘little usablity’ and yes, we see at least 50% of our potential SEO clients coming to us and being “stuck” in that rut. Pretty site, but is it visitor friendly or usable? And the answer is usually no, it’s anything but.

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Last week we highlighted some of the new features that’s been added to our new 6.0 release. You can read about the complete set of features in this blog article What’s new in BizTalk360 v6.0. We are extremely delighted to announce the immediate availability of v6.0, you can download and try it on your own [...]

The post BizTalk360 Version 6.0 is released appeared first on BizTalk360 Blog.

Blog Post by: Saravana Kumar


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December 20, 2012

Positivity: A Teenager’s Life-Saving Decision

Filed under: Health Care,Life-Based News,Positivity — Tom @ 6:00 am

from Corsica, South Dakota:

Published: December 14, 2012, 6:06 PM

A Corsica teenager will be honored on a Rose Parade float. Andrea Cleveland died after a car crash last fall but thanks to her organ donations, she helped save five people’s lives.

That action is now representing the Upper Midwest on the Donate Life Float in the Tournament of Roses Parade.

Andrea was a fun-loving, outgoing 16-year-old.

“When she walked in the room, she lit up the room,” Andrea’s father, Jeff Cleveland, said.

But on November 1, 2011, the Corsica teenager lost control of her car on a rural road. She later died at the hospital.

“It took days, maybe weeks for me to realize that she’s actually gone. Every day I’d wait for her to come running down the steps, hearing her footsteps running down to get ready for school,” Andrea’s mother, Marlene Cleveland, said.

One thing that has helped the family heal is the fact that Andrea was an organ donor. Because of that, she was able to save the lives of five people. She also helped others.

“Many people also received tissue grafts from the gifts Andrea gave. She also was able to donate corneas to two people to restore sight,” LifeSource CEO Susan Gunderson said.

The family has met two of the people Andrea helped save: 29-year-old Meleah and two-year-old Keegan.

“It really helped us at Christmas time to know, yah, we’re grieving. I don’t know how we’re going to get through Christmas but then we see the picture of Keegan. Andrea saved this little boy’s life,” Jeff said.

“When they came in the room, I just picked up little Keegan and started hugging and holding him. It’s like holding or hugging Andrea again. I could feel her presence,” Marlene said. …

Go here for the rest of the story.

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Birmingham 24

Birmingham 24

Draughtsman: [Dawson, Robert]

Medium: Pen and ink on paper

Date: 1814

Shelfmark: OSD 256

Item number: 24

Length: 46

Width: 30

Genre: Map

Map scale ratio: 2'' : 1 Mile (1 : 31680)

This drawing is attributed to Robert Dawson. Different shades of green are employed to distinguish different land uses, and darker tones to describe the bold undulation of the landscape. Birmingham is depicted top left, at the centre of a network of toll roads and canals. Prominently featured on the plan is the Grand Junction Canal. This waterway was at the heart of the Industrial Revolution in this region at the beginning of the 19th century, carrying raw materials to mills and industrial centres, and finished goods to markets throughout Britain.

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