Delivery actuator for a transcervical sterilization device

The use of delivery systems in the human body for positioning and deploying implants, such as closure devices, dilation balloons, stents, coils and sterilization devices, are gaining more importance to preclude surgical incisions and general anesthesia. The majorities of the non-surgical medical devices are delivered in a low profile into human body form and subsequently require specialized operations for their deployment and release. An analogous procedure for permanent female sterilization is the transcervical approach that does not require either general anesthesia or surgical incision and uses a normal body passage. The objective of this paper is to detail the design, development and verification of an ergonomic actuator for a medical application. In particular, this actuator is designed for the deployment and release of an implant to achieve instant permanent female sterilization via the transcervical approach. This implant is deployed under hysteroscopic visualization and requires a sequence of rotary and linear operations for its deployment and release. More specifically, this manually operated actuator is a hand held device designed to transmit the required forces in a particular sequence to effect both implant deployment and release at a target location. In order to design the actuator and to investigate its mechanical behavior, a three-dimensional (3D) Computer Aided Design (CAD) model was developed and Finite Element Method (FEM) was used for simulations and optimization. Actuator validation was performed following a number of successful bench-top in-air deployments and in-vitro deployments in animal tissue and explanted human uteri. During these deployments it was observed that the actuator applied the required forces to the implant resulting in successful deployment. Initial results suggest that this actuator can be used single handedly during the deployment phase. The ongoing enhancement of this actuator is moving towards “first-in- man” clinical trials

Pactamycin Inspired Drug Discovery: A Synthetic and Chemoenzymatic Approach

Pactamycin, first reported in 1962, is a potent antitumor antibiotic produced by the soil bacterium Streptomyces pactum. Structurally, it contains a cyclopentitol core unit, a 3-aminoacetophenone (3AAP), a 6-methylsalicylic acid (6-MSA), and a N,N-dimethyl urea. The aminocyclopentitol ring is derived from glucose, possibly via N-acetyl glucosamine (GlcNAc), the 3-aminoacetophenone (3AAP) moiety is derived from 3-aminobenzoic acid (3ABA), and the 6-MSA moiety is produced from acetate by an iterative type I polyketide synthase. Despite some knowledge of its biosynthetic origin, details of the mode of formation of this unique natural product are still elusive. Using genetic, chemical complementation, and biochemical studies we demon-strate that 3ABA is processed by a set of discrete polyketide synthase proteins, i.e. an AMP-forming acyl-CoA synthetase (PtmS), an acyl carrier protein (ACP) (PtmI), and a -ketoacyl-ACP synthase (PtmK), to give 3-[3-aminophenyl]3-oxopropionyl-ACP, which is then glycosylated by a broad spectrum N-glycosyltransferase, PtmJ (Chapter 2). This is the first example of glycosylation of an ACP-bound polyketide intermediate in natural product biosynthesis. Additionally, we demonstrate that PtmO is a hydrolase that is re-sponsible for the release of the glycosylated -ketoacid product from the ACP, and the free -ketoacid product subsequently undergoes non-enzymatic decarboxylation. In addition to the β-ketoacyl-ACP synthase gene ptmK, the pactamycin biosyn-thetic gene cluster also contains a gene (ptmR) that encodes a β-ketoacyl-acyl carrier protein (β-ketoacyl-ACP) synthase (KAS) III. KAS III catalyzes the first step in fatty acid biosynthesis, involving a Claisen condensation of the acetyl-CoA starter unit with the first extender unit, malonyl-ACP, to form acetoacetyl-ACP. KAS III-like proteins have also been reported to catalyze acyltransferase reactions using coenzyme A esters or discrete ACP-bound substrates. Through in vivo and in vitro characterizations of the KAS III-like protein PtmR, we discovered that this enzyme directly transfers a 6-methylsalicylyl moi-ety from an iterative type I polyketide synthase (PtmQ) to the aminocyclopentitol unit in pactamycin biosynthesis (Chapter 3). PtmR is highly promiscuous, recognizing a wide array of S-acyl-N-acetylcysteamines as substrates to produce a suite of pactamycin de-rivatives with diverse alkyl and aromatic features. The results suggest that KAS III-like proteins may be used as versatile tools for modifications of complex natural products for drug discovery. The pronounced biological activity displayed by pactamycin spans across all three phylogenetic domains. Unfortunately the indiscriminate cytotoxicity of pactamycin towards mammalian cells has suppressed its development toward therapeutic appli-cation. Nevertheless, we believe pactamycin is a wellspring of promising biological activity that is waiting to be harnessed. Our previous work demonstrated, through biosynthetic manipulations, production of new pactamycin analogs with pronounced antimalarial activity, lacking significant antibacterial activity, and are about 10–30 times less toxic than pactamycin toward mammalian cells. Furthermore, we have developed a chemoenzymatic process using the promiscuous KAS III-like protein PtmR to produce new pactamycin analogs. Continuing our efforts to draw further on the bountiful activity of the aminocycli-tol core of pactamycin, we have taken a third approach by synthesizing the core amino-cyclopentitol ring which could open up a diverse library of biologically active com-pounds. In Chapter 4, we describe an efficient, modular, and asymmetric synthesis of several aminocyclopentitol compounds resembling the pactamycin pharmacophore be-lieved responsible for its biological activity. The outlined synthesis work has generated four promising biologically active compounds, two of which display modest activity against Gram-positive bacteria, whereas the other two compounds exhibit potent anti-cancer activity against A375 melanoma cells

Presentation: NADDI 2015: Crowdsourcing DDI Development: New Features from the CED2AR Project

Ben Perry (Cornell/NCRN) presents joint work with Venkata Kambhampaty, Kyle Brumsted, Lars Vilhuber, & William C. Block at NADDI 2015.Recent years have shown the power of user-sourced information evidenced by the success of Wikipedia and its many emulators. This sort of unstructured discussion is currently not feasible as a part of the otherwise successful metadata repositories. Creating and augmenting metadata is a labor-intensive endeavor. Harnessing collective knowledge from actual data users can supplement officially generated metadata. As part of our Comprehensive Extensible Data Documentation and Access Repository (CED2AR) infrastructure, we demonstrate a prototype of crowdsourced DDI, using DDI-C and supplemental XML. The system allows for any number of network connected instances (web or desktop deployments) of the CED2AR DDI editor to concurrently create and modify metadata. The backend transparently handles changes, and frontend has the ability to separate official edits (by designated curators of the data and the metadata) from crowd-sourced content. We briefly discuss offline edit contributions as well. CED2AR uses DDI-C and supplemental XML together with Git for a very portable and lightweight implementation. This distributed network implementation allows for large scale metadata curation without the need for a hardware intensive computing environment, and can leverage existing cloud services, such as Github or Bitbucket

NCRN Meeting Spring 2016: Crowdsourcing Metadata – Challenges and Outlook

Presented at the NCRN Meeting Spring 2016 in Washington DC on May 9-10, 2016; see http://www.ncrn.info/event/ncrn-spring-2016-meetingRecent years have shown the power of user-sourced information evidenced by the success of Wikipedia and its many emulators. This sort of unstructured discussion is currently not feasible as a part of the otherwise successful metadata repositories. Creating and augmenting metadata is a labor-intensive endeavor. Harnessing collective knowledge from actual data users can supplement officially generated metadata. As part of our Comprehensive Extensible Data Documentation and Access Repository (CED²AR) infrastructure, we demonstrate a prototype of crowdsourced DDI on actual codebooks. While the system itself is more general, the demonstrated implementation relies on a set of linked deployments of the basic software on web servers. The backend transparently handles changes, and frontend has the ability to separate official edits (by designated curators of the data and the metadata) from crowd-sourced content. The implementation allows a data curator, such as a statistical agency, to collect and incorporate improvements suggested by knowledgeable users in a structured way.NSF Grant 1507241 (NCRN Coordinating Office) and 1131848 (to Cornell University

Collaborative Editing of DDI Metadata: The Latest from the CED2AR Project

Benjamin Perry's presentation on "Collaborative Editing and Versioning of DDI Metadata: The Latest from Cornell's NCRN CED²AR Software" at the 6th Annual European DDI User Conference in London, 12/02/2014

ncrncornell/ced2ar: 2.10.0

Installation For server installation: ced2ar.war is the server binary BaseX.war is the server database template ced2ardata2ddi.war is an optional server binary for the ced2ardata2ddi service. ced2ardata2ddi.war files are located at ced2ardata2ddi/releases. redeploy_ced2ar_v2.sh is a script used to backup some config files before redeploying ced2ar-web.war. For desktop installation, see previous release. New Features and Issues New features and issues only come from github: GitHub - The public site where users of the system can post Issues. Jira has been phased out. This is the last release that will refer to JIRA. JIRA - Phased out. The restricted site used by the development team to track work related to CED2AR development. New Features The following high level features have been added in this release: CED2AR v2 has been Dockerized! You can now implement a standalone docker configuration. See: README.md A new page has been added to generate PDF files from codebooks. See: #46, The CED2AR Configuration Files More information on how to set up the various ways CED2AR can be configured has been added. See: #35, #36, The CED2AR Configuration Files Resolved Issues The following issues were fixed in this release. They are listed below. github Issues #32 - Ability to edit stdyDscr/citation/titlStmt if necessary #35 - Provide some example configuration files #36 - Improve documentation of configuration properties #42 - The wiki.ncrn server is missing the "official version" line and link. #43 - ced2ar-web-beans.xml: Replace 2 hard coded property values with property names. #46 - Zero byte pdf problem jira Issues New Feature CDR-230 - Develop docker-based approach for running V2 CDR-231 - Create BaseX container CDR-245 - Create CED2AR container CDR-246 - Create means of changing config CDR-252 - Add ced2ardata2ddi service CDR-251 - Volume mount data directories Issue CDR-255 - Document API ingest/export feature for v