48572 Federal Register / Vol. 74, No. 183 / Wednesday, September 23, 2009 / Notices 

Philippine and is currently being 

commercialized in the US by Epeius 

Biotechnologies. 

Inventor: Bruce A. Shapiro (NCI). 

Publications: 

1. E Bindewald, C Grunewald, B 

Boyle, M O’Connor, BA Shapiro. 

Computational strategies for the 

automated design of RNA nanoscale 

structures from building blocks using 

NanoTiler. J Mol Graph Model. 2008 

Oct;27(3):299–308. 

2. B Shapiro, E Bindewald, W 

Kasprzak, Y Yingling. (E Gazit, F 

Nussinov, eds.) Protocols for the In 

silico Design of RNA Nanostructures. In: 

Nanostructure Design Methods and 

Protocols. Totowa, NJ: Humana Press; 

2008. p. 93–115. 

3. HM Martinez, JV Maizel Jr, BA 

Shapiro. RNA2D3D: a program for 

generating, viewing, and comparing 3- 

dimensional models of RNA. J Biomol 

Struct Dyn. 2008 Jun;25(6):669–683. 

4. I Severcan, C Geary, L Jaeger, E 

Bindewald, W Kasprzak, B Shapiro. (G 

Alterovitz, M Ramoni, R Benson, eds.) 

Computational and Experimental RNA 

Nanoparticle Design. In: Automation in 

Genomics and Proteomics: An 

Engineering Case-Based Approach. 

Hoboken: Wiley Publishing; 2009. 

5. E Bindewald, R Hayes, YG 

Yingling, W Kasprzak, BA Shapiro. 

RNAJunction: a database of RNA 

junctions and kissing loops for threedimensional structural analysis and 

nanodesign. Nucleic Acids Res. 2008 

Jan;36:D392–397. 

6. YG Yingling and BA Shapiro. 

Computational design of an RNA 

hexagonal nanoring and an RNA 

nanotube. Nano Lett. 2007 

Aug;7(8):2328–2334. 

7. BA Shapiro and YG Yingling. PCT 

Application No. PCT/US2007/13027 

filed 31 May 2007, which published as 

WO 2008/039254 on 03 Apr 2008, and 

U.S. Patent Application No. 12/227,955 

filed 02 Dec 2008; both entitled ‘‘RNA 

Hexagonal Ring and RNA Nanotube.’’ 

Patent Status: U.S. Provisional 

Application No. 61,187,495 filed 16 Jun 

2009 (HHS Reference No. E–059–2009/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contacts: Uri Reichman, 

Ph.D., MBA; 301–435–4616; 

UR7a@nih.gov; John Stansberry, Ph.D.; 

301–435–5236; js852e@nih.gov 

Collaborative Research Opportunity: 

The National Cancer Institute’s 

Nanobiology Program is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize RNA nanostructures. 

Please contact John D. Hewes, Ph.D. at 

301–435–3121 or hewesj@mail.nih.gov 

for more information. 

Bactericidal Peptides From Avian 

Leukocyte Ribonuclease A–2 

Description of Invention: These 

bactericidal polypeptides offer a novel 

alternative to conventional antibiotics 

that are used to treat and prevent 

bacterial infections. As infectioncausing bacteria continue to develop 

antibiotic resistance to first line 

antibiotics there will always be a need 

for new antibiotic alternatives. 

Additionally, a greater understanding of 

the specific cytoxic activity of RNase A 

ribonucleases, their functional domains, 

and their roles in promoting antipathogen host defense may provide 

insight into new therapeutic agents. 

This invention includes a novel 

RNase A ribonuclease from chicken 

leukocytes and polypeptides that have 

bactericidal activities against both gram 

positive and gram negative bacteria, 

including such pathogens as Escherichia 

coli, Salmonella spp., and 

Staphylococcus. 

Applications: 

• Polypeptides exhibiting 

bactericidal, bacteriostatic, and 

ribonuclease activity. 

• Pharmaceutical compositions 

comprising the bactericidal 

polypeptides. 

• Methods for treating bacterial 

infections. 

Development Status: Early stage. 

Market: With the increase in 

antibiotic and antibacterial drug 

resistance, the market for alternatives is 

growing. 

Inventors: Helene F. Rosenberg et al. 

(NIAID). 

Related Publication: T Nitto, KD Dyer, 

M Czapiga, HF Rosenberg. Evolution 

and function of leukocyte RNase A 

ribonucleases of the avian species, 

Gallus gallus. J Biol Chem. 2006 Sep 

1;281(35):25622–25634. 

Patent Status: U.S. Patent Application 

No. 12/438,700 filed 24 Feb 2009, 

claiming priority to 24 Aug 2006 (HHS 

Reference No. E–281–2006/0–US–03) 

Licensing Status: Available for 

licensing. 

Licensing Contact: RC Tang JD LLM; 

301–435–5031; tangrc@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIAID Laboratory of Allergic 

Diseases is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize this technology. Please 

contact William Ronnenberg, NIAID 

Office of Technology Development, at 

301–451–3522 or 

wronnenberg@niaid.nih.gov for more 

information. 

Dated: September 17, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–22975 Filed 9–22–09; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2009–N–0440] 

Availability of Grant Funds for the 

Support of Cooperative Agreement 

Award to Georgetown University 

Entitled: Genome Wide Methylation 

Arrays for Detecting Markers of 

Increased Susceptibility to Mammary 

Cancer Caused by In-Utero Exposures 

to Endocrine Disruptors (U01) 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA), Center for 

Veterinary Medicine (CVM), and Office 

of New Animal Drugs (ONADE) is 

announcing the availability of grant 

funds for the support of a sole source, 

cooperative agreement award to 

Georgetown University, Lombardi 

Cancer Research Center and Department 

of Oncology entitled: ‘‘Genome Wide 

Methylation Arrays for Detection 

Markers of Increased Susceptibility to 

Mammary Cancer Caused by In-Utero 

Exposures to Endocrine Disruptors 

(U01).’’ The main purpose of this study 

is to help gain an understanding of the 

extent to which exposures to endocrine 

disruptors early in life increase later 

susceptibility to developing breast 

cancer by inducing heritable epigenetic 

changes in transcription factors, which 

are linked to increased breast cancer 

risk. The study is subject to the 

requirements of the Federal Food, Drug, 

and Cosmetic Act (the act) (21 U.S.C. 

331, et seq.) regulations issued under it 

and applicable Department of Health 

and Human Services statutes and 

regulations. 

DATES: Important dates are as follows: 

1. The application due date is 30 days 

from the publication in the Federal 

Register. 

2. The anticipated start date is 

September 2009. 

FOR FURTHER INFORMATION CONTACT: 

Peer Review/Administrative Contact: 

Michelle Fuller, Center for 

mstockstill on DSKH9S0YB1PROD with NOTICES

Federal Register / Vol. 74, No. 183 / Wednesday, September 23, 2009 / Notices 48573 

Veterinary Medicine (HFV–10), 

Food and Drug Administration, 

7519 Standish Pl., Rockville, MD 

20855, 240–276–9736, FAX: 240– 

276–9744, email:michelle.fuller@fda.hhs.gov. 

Scientific Contact: M. Cecilia Aguila, 

Center for Veterinary Medicine 

(HFV–153), Food and Drug 

Administration, 7500 Standish Pl. 

(rm. E478), Rockville, MD 20855, 

240–276–8125, FAX: 240–276– 

8116, e-mail: 

Cecilia.aguila@fda.hhs.gov. 

For more information on this funding 

opportunity announcement (FOA), and 

to obtain detailed requirements, please 

refer to the full FOA located at http:// 

www.fda.gov/cvm. 

SUPPLEMENTARY INFORMATION: 

I. Funding Opportunity Description 

Request for Application: RFA FD09–020 

Catalog of Federal Domestic Assistance 

Number: 93.103 

A. Background 

More than 80,000 chemicals are 

registered for use in commerce in the 

United States and an estimated 2,000 

new chemicals are introduced annually. 

These chemicals are used or present as 

contaminants in everyday items such as: 

Foods, personal care products, 

prescription drugs, household cleaners, 

and lawn care products (National 

Toxicology Program, 2002). Scientists 

are continually learning more about 

how these compounds interact with the 

body and the long-term impact of these 

interactions on our health. For example, 

many synthetic chemicals have been 

identified as known or suspected EDCs 

(endocrine disruptors), including DES 

(diethylstilbesterol), BPA (bisphenol A), 

and GEN (genistein). The long-term 

impact of these chemicals on human 

health is still largely unknown, 

particularly when the exposure levels 

are relatively low and do not cause any 

apparent toxic effects. EDCs may have 

estrogenic, antiestrogenic, androgenic, 

and/or anti-androgenic actions and /or 

they may disrupt adrenal and/or thyroid 

functions, too. 

The endocrine system participates in 

many important functions of an 

organism, such as sexual differentiation 

before birth, sexual maturation during 

puberty, reproduction in adulthood, 

growth, metabolism, digestion, 

cardiovascular and immune functions, 

and excretion. Hormones are implicated 

in the etiology of certain cancers of 

hormone-dependent tissues, such as 

those of the breast, uterus, and prostate 

gland. Environmentally released manmade chemicals are suspected of being 

responsible for numerous adverse 

effects on the endocrine function in 

wildlife species as well as in humans. 

EDCs may be harmful to human 

health following fetal exposure. This 

likely relates to epigenetic changes in 

gene methylation patterns occurring 

during gametogenesis and embryonic 

development. During these periods, 

most of our genes are demethylated, 

followed by remethylation; the timing 

and pattern of remethylation depends 

on the tissue lineage, intrauterine 

environment, and maternal nutrition 

and other exposures. Several genes have 

been identified whose expression is 

epigenetically altered in adult tissues in 

animals that have been exposed in utero 

to environmental contaminants with 

endocrine disrupting activity. Therefore, 

we hypothesize that in utero EDC 

exposures increase hypomethylation of 

genes, including those that regulate 

mammary stem cell behavior. 

It is increasingly evident that many 

diseases, including breast cancer, may 

originate during fetal life. Experimental 

findings and limited human data show 

that maternal exposures during 

pregnancy to synthetic estrogens such as 

DES or endocrine disruptors present in 

food may precipitate mammary gland 

development and increase breast cancer 

risk. To date, traditional toxicity tests 

such as the 2-year rodent bioassay have 

been the bases for most regulatory 

decisions regarding the carcinogenic 

potential of chemicals in the food. The 

agency recommends an in utero 

exposure in these bioassays for direct 

food and color additives. Therefore, 

only a limited number of chemicals 

have been studied by this approach. 

Additionally, these in vivo toxicology 

studies are not routinely used to predict 

the effects of in utero exposures on later 

susceptibility to various diseases. 

B. Research Objectives 

The main purpose of the this study is 

to help gain an understanding of the 

extent to which exposures to endocrine 

disruptors early in life increase later 

susceptibility to developing breast 

cancer by inducing heritable epigenetic 

changes in transcription factors, which 

are linked to increased breast cancer 

risk. This will be accomplished, first, by 

exposing pregnant rodents to estrogen 

and estrogen-like endocrine disruptors 

at doses previously found to increase 

mammary cancer among offspring. 

Focus will be on the resulting 

hypomethylated genes that express high 

levels of transcription factors, which 

regulate proliferation, apoptosis, and 

differentiation of mammary epithelial 

cells. Second, humans will be exposed 

to maternal diet containing plantderived compounds with hormonal 

activity during pregnancy to determine 

if the diet induces epigenetic changes 

among daughters in the same 

transcription factors identified in 

rodents. Third, the study will utilize 

genetically modified animal models to 

determine if the epigenetic changes 

identified in global methylation arrays 

are causally linked to an increased 

susceptibility to developing mammary 

cancer in vivo. 

The data from this study will be used 

to develop the Prenatal Endocrine 

Disruption and Mammary Tumor 

Susceptibility assay (PEDMATS), which 

will provide a novel approach for 

predicting the safety of chemicals with 

endocrine activity. Consequently, the 

agency will benefit from the proposed 

study, which combines mechanismfocused toxicology studies and modern 

molecular biology tools, and addresses 

the question of the cellular target of 

breast cancer initiation; i.e., mammary 

stem and progenitor cells. PEDMATS 

would help the agency to predict the 

potential breast cancer risk for 

chemicals that have been identified as 

having, or that may have, endocrine 

activity, and for which there are no 

valid rodent carcinogenicity bioassays. 

Another valuable feature of this 

approach is the potential that the 

PEDMATS studies can be integrated 

into the current reproductive and 

developmental toxicity assessment 

battery used to evaluate the safety of 

new drugs. 

C. Eligibility Information 

Georgetown University is uniquely 

qualified to conduct this research. It has 

the expertise to study genetic markers in 

breast cancer in animal models and 

humans. Importantly, Georgetown 

University has expertise and proven 

ability in identifying genes affected in 

breast cancer. The data analysis is a 

critical component of the hybridization 

array experiments and poses a number 

of challenges due to the large amount of 

data generated even in a single 

experiment. Sophisticated, statistically 

principled data mining tools should be 

used. These state-of-the-art clustering 

pattern analyses use standard Finite 

Normal Mixture models and 

probabilistic component subspaces, 

multimodal clusters being automatically 

identified using Akaide information 

criterion and minimal information 

analysis. Georgetown University, 

Lombardi Cancer Center recently 

developed a simple approach for the 

exploration of limited gene expression 

data sets. To reduce dimensionality, a 

simple univariate statistical analysis (ttest) to compare gene expression data is 

mstockstill on DSKH9S0YB1PROD with NOTICES

48574 Federal Register / Vol. 74, No. 183 / Wednesday, September 23, 2009 / Notices 

used. The reduced dimensional data set 

is visualized in three dimensions using 

these novel algorithms. These visualized 

algorithms derive the first three 

principal components from Fisher’s 

matrix and project the multidimensional 

data into three dimensional gene 

expression data space. Exploration of 

the reduced dimensional data set allows 

for the identification of discriminant 

genes that are either assembled into a 

predictive neural network, and/ or 

selected for functional studies. These 

approaches have proved useful in recent 

studies conducted by Dr. HilakiviClarke (Georgetown University, 

Lombardi Cancer Center) in identifying 

genes affected by timing of dietary 

exposures on breast cancer risk and are 

the preferred approaches for this study. 

Georgetown University, Lombardi 

Cancer Research Center Animal Core 

Facility has an AAALAC (Association 

for Assessment and Accreditation of 

Laboratory Animal Care) accredited 

animal facility where the animals can be 

housed. Georgetown can provide the 

software, hardware, and sophisticated, 

statistically principled data mining 

tools. In addition, Georgetown 

University is already collaborating in an 

on-going women study in Finland 

measuring hormone and adipokine 

levels from blood samples. 

This is a sole source award to 

Lombardi Comprehensive Cancer Center 

and Department of Oncology, 

Georgetown University, Washington, 

DC. 

II. Award Information/Funds Available 

Awards are made under the 

authorization of section 301 of the 

Public Health Service Act (PHS Act) (42 

U.S.C. 241), as amended, and under 

Federal regulations at 42 CFR part 52 

and 45 CFR parts 74 and 92. 

A. Award Amount 

The total amount CVM expects to 

award is $100,400 in the first year and 

$104,400 in the second year for a total 

award of $204,800; total award amount 

includes direct and indirect costs. 

B. Length of Support 

The project period will be from 

September 2009 to August 31, 2011. The 

first budget period will be from 

September 2009 to August 31, 2010. 

The second year award will depend 

on the availability of funds and 

recipient approved performance. 

III. Paper Application, Registration, 

and Submission Information 

To submit a paper application in 

response to this FOA, applicants should 

first review the full announcement 

located at http://www.fda.gpo/cvm. 

Persons interested in applying for a 

grant may obtain application forms and 

instructions at http://grants.nih.gov/ 

grants/forms.htm. For all paper 

application submissions, the following 

steps are required: 

• Step 1: Obtain a Dun and Bradstreet 

(DUNS) Number 

• Step 2: Register With Central 

Contractor Registration (CCR) 

• Step 3: Register With Electronic 

Research Administration (eRA) 

Commons 

Steps 1 (DUNS Number) and 2 (CCR), 

in detail, can be found at http:// 

www07.grants.gov/applicants/ 

organization_registration.jsp. Step 3 

(eRA Commons), in detail, can be found 

at https://commons.era.nih.gov/ 

commons/registration/registration

Instructions.jsp. 

After you have followed these steps, 

submit paper applications to the Grants 

Management Contact at the following 

address: 

Gladys M. Bohler, Division of 

Acquisition Support and Grants (HFA– 

500), Food and Drug Administration, 

5630 Fishers Lane, rm. 2105, Rockville, 

MD 20857, 301–827–7168, FAX: 301– 

827–7101, e-mail: 

gladys.bohler@fda.hhs.gov. 

Dated: September 17, 2009. 

David Horowitz, 

Assistant Commissioner for Policy. 

[FR Doc. E9–22848 Filed 9–22–09; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute of Dental & 

Craniofacial Research; Notice of 

Closed Meeting 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended (5 U.S.C. App.), notice is 

hereby given of the following meeting. 

The meeting will be closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 

as amended. The grant applications and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable material, 

and personal information concerning 

individuals associated with the grant 

applications, the disclosure of which 

would constitute a clearly unwarranted 

invasion of personal privacy. 

Name of Committee: National Institute of 

Dental and Craniofacial Research Special 

Emphasis Panel; Review of R34 Clinical Trial 

Pilot Applications PAR–08–195 and R01 PA– 

07–070 Applications. 

Date: October 30, 2009. 

Time: 10:30 a.m. to 1:30 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, One 

Democracy Plaza, 6701 Democracy 

Boulevard, Bethesda, MD 20892, (Telephone 

Conference Call). 

Contact Person: Rebecca Wagenaar Miller, 

PhD, Scientific Review Officer, Scientific 

Review Branch, National Inst of Dental & 

Craniofacial Research, National Institutes of 

Health, 6701 Democracy, Rm 666, Bethesda, 

MD 20892, 301–594–0652, 

rwagenaa@mail.nih.gov. 

Catalogue of Federal Domestic Assistance 

Program Nos. 93.121, Oral Diseases and 

Disorders Research, National Institutes of 

Health, HHS) 

Dated: September 16, 2009. 

Jennifer Spaeth, 

Director, Office of Federal Advisory 

Committee Policy. 

[FR Doc. E9–22969 Filed 9–22–09; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute of Allergy and 

Infectious Diseases; Notice of Closed 

Meeting 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended (5 U.S.C. App.), notice is 

hereby given of the following meeting. 

The meeting will be closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 

as amended. The grant applications and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable material, 

and personal information concerning 

individuals associated with the grant 

applications, the disclosure of which 

would constitute a clearly unwarranted 

invasion of personal privacy. 

Name of Committee: Microbiology, 

Infectious Diseases and AIDS Initial Review 

Group; Microbiology and Infectious Diseases 

Research Committee. 

Date: October 6, 2009. 

Time: 8 a.m. to 5 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: The Legacy, 1775 Rockville Pike, 

Rockville, MD 20852. 

Contact Person: Michelle M. Timmerman, 

PhD, Scientific Review Officer, Scientific 

Review Program, DEA/NIAID/NIH/DHHS, 

Room 2217, 6700B Rockledge Drive, MSC– 

7616, Bethesda, MD 20892–7616. 301–451– 

4573. timmermanm@niaid.nih.gov. 

This notice is being published less than 15 

days prior to the meeting due to the timing 

mstockstill on DSKH9S0YB1PROD with NOTICES