Neoadjuvant Therapy for Ovarian Cancer Using BioglycogenTM Nanoparticles SBIR Grant Proposal

Project Summary Technical Abstract This Small Business Innovation Research Phase I project, presented by Talamo Inc., is to test an ovarian cancer therapeutic delivery system, comprised of a nanoscale biocompatible vesicle that carries a bioactive small interfering RNA molecule (siRNA), in vivio in mice. The siRNA has shown to reduce the expression of an enzyme (Sod2) that is highly expressed in multiple ovarian cancer types. The reduced expression of Sod2 will allow the tumor to become increasingly susceptible to chemotherapy agents, while simultaneously diminishing tumor progression. Research has proved that the nanoscale vesicle is non-toxic and in combination with siRNA effectively reduced Sod2 expression, in vitro, in ovarian cancer cells. Based upon these findings Talamo, Inc. plans to move forward to in vivo mice testing. It is necessary to prove that the nanoscale vesicle system is effective in inhibiting Sod2 expression and is also non-toxic in mice. The funds from phase I of this Small Business Innovation Research (SBIR) grant will allow Talamo, Inc. to proceed with in vivo mice testing. The anticipated results are that the mice given the therapy will have smaller tumors and lower Sod2 levels than the control group. Commercialization Abstract This neoadjuvant therapy has great commercial potential. Ovarian cancer is the deadliest of the gynecologic cancers. There will be 14,030 deaths in 2013 from ovarian cancer and ranks as the 10th most common cancer among women. This therapy would be administered to a patient as soon as she was diagnosed with ovarian cancer. Immediate therapy would slow the tumor progression and increase sensitivity to chemotherapy agents. This would allow physicians more time to proactively treat or to remove the tumors. Thus, the survival rates of patients with clear cell carcinoma will increase. Talamo Inc. has established conditional collaboration with Bristol-Myers Squibb, if the nanoscale delivery system is proven to be non-toxic and effective at inhibiting Sod2 in mice. Thus, it is imperative for Talamo, Inc. to be awarded this SBIR Phase I grant in order to fund in vivo mice testing. If the results from the in vivo mice testing prove favorable, Bristol-Myers Squibb will fund Phase 1 FDA clinical trials in conjunction with the $1,000,000 SBIR Phase II award. Once this therapy has been brought to market, after passing Phase 1-3 FDA clinical trials, Talamo Inc. will use its profits to fund future R&D for nanoscale delivery wesicles to be used to treat other cancers that also exhibit high levels of Sod2

Reliable Peer-to-Peer Access for Italian Citizens to Digital Government Services on the Internet

In the delivery of e-government services to citizens it should be clear that the viewpoint cannot simply be the standard one of client-supplier commonly used to provide services on the Internet. In a modern society it has rather to be the peer-to-peer approach which is typical of democracies, where institutions are equal to citizens in front of the law. But this is not yet a widely accepted standpoint in digital government efforts going on in many advanced countries in the world. Italian government, in its ever increasing effort to provide citizens with easier access to online government services, has instead adopted and is pursuing this symmetric approach, which is going to represent a fundamental tool in the ongoing march towards e-democracy. In this paper we describe the organizations involved in the process and the Information Technology (IT) infrastructure enabling the effective management of the whole process while ensuring the mandatory security functions in a democratic manner. Organizational complexity lies in the distribution of responsibilities for the management of people’s personal data among the more than 8000 Italian Municipalities and the need of keeping a centralized control on all processes dealing with identity of people. Technical complexity stems from the need of efficiently supporting this distribution of responsibilities while ensuring, at the same time, interoperability of IT-based systems independent of technical choices of the organizations involved, and fulfillment of privacy constraints. The IT architecture defined for this purpose features a clear separation between security services, provided at an infrastructure level, and application services, exposed on the Internet as Web Services

Algorithms for the on-line travelling salesman

In this paper the problem of efficiently serving a sequence of requests presented in an on-line fashion located at points of a metric space is considered. We call this problem the On-Line Travelling Salesman Problem (OLTSP). It has a variety of relevant applications in logistics and robotics. We consider two versions of the problem. In the first one the server is not required to return to the departure point after all presented requests have been served. For this problem we derive a lower bound on the competitive ratio of 2 on the real line. Besides, a 2.5-competitive algorithm for a wide class of metric spaces, and a 7/3-competitive algorithm for the real line are provided. For the other version of the problem, in which returning to the departure point is required, we present an optimal 2-competitive algorithm for the above mentioned general class of metric spaces. If in this case the metric space is the real line we present a 1.75-competitive algorithm that compares with a \approx 1.64 lower bound

Saving old bones: A non-destructive method for bone collagen prescreening

Bone collagen is an important material for radiocarbon, paleodietary, and paleoproteomic analyses, but it degrades over time, making such analyses more difficult with older material. Collagen preservation between and within archaeological sites is also variable, so that much time, effort, and money can go into the preparation and initial analysis of samples that will not yield meaningful results. To avoid this, various methods are employed to prescreen bone for collagen preservation (e.g., %N, microporosity, and FTIR spectroscopic analyses), but these are often destructive and/or require exportation for analysis. Here, we explore near-infrared spectroscopy as a tool for gauging the collagen content of ground and whole bone from about 500 to 45,000 years ago. We show that a portable spectrometer’s ability to quantify collagen content and classify specimens by preservation status is comparable to that of other popular prescreening methods. Moreover, near-infrared spectroscopy is non-destructive and spectra can be acquired in a few seconds

The footprint of a historical paleoearthquake: the sixth-century-CE event in the European western Southern Alps

Low-deformation regions are characterized by long earthquake recurrence intervals. Here, it is fundamental to extend back the record of past events as much as possible to properly assess seismic hazards. Evidence from single sites or proxies may be not compelling, whereas we obtain a more substantial picture from the integration of paleo-and archeoseismic evidence at multiple sites, eventually supplemented with historical chronicles. In the city of Como (N Italy), we perform stratigraphic and sedimentological analyses on the sedimentary sequences at Via Manzoni and we document earthquake archeological effects at the Roman baths by means of structure from motion and field surveys. Radiocarbon dating and chronological constraints from the archeological site allow us to bracket the time of occurrence of the deformations to the sixth century AD. We interpret the observed deformations as due to earthquake ground shaking and provide constraints on the lower threshold for the triggering of such evidence. We move toward a regional view to infer possible relevant seismic sources by exploiting a dataset of published paleoseismic evidence in Swiss and N Italy lakes. We performan inverse grid search to identify the magnitude and location of an earthquake that can explain all the positive and negative evidence consistent with the time interval of the event dated at Como. Ou rresults show that an earthquake (minimum Mw 6.32) with epicenter located at the border between Italy and Switzerland may account for all the observed effects; a similar event in the sixth century AD has not been documented so far by historical sources. Our study calls for the need to refine the characterization of the local seismic hazard, especially considering that this region seems unprepared to face the effects of an earthquake size similar to the one inferred for the sixth-century-ADevent

Reuse of building components. Assessment system to support decisions in indoor re-layout interventions.

Compared to other industrial fields, the construction sector, although encouraged by a framework of international policies that push towards spreading circular economy principles, still needs to adopt new ‘closed cycle’ resource management models. Among the barriers that hinder this transition is the limited availability of tools and methods to determine the overall outcomes of circularity actions. Although metrics to evaluate the degree of circularity of processes and products are currently available, tools that allow the evaluation of the environmental benefits achievable through the reuse of products and systems have yet to be widespread. The paper proposes a simplified method for quantifying the environmental benefits that can derive from the reuse practices of building components in building re-layout projects

COGNITIVE THEORY OF CATEGORIZATION, AS EXEMPLIFIED ON JAPANESE MATERIAL

Nakon uvodnog utvrđivanja teorijske razlike između tradicionalnog aristotelovskog i suvremenog kognitivnog poimanja procesa ljudske kategorizacije, te navođenja prednosti kognitivnog pristupa, autor u ovome radu na primjerima iz japanskoga jezika oprimjeruje mentalne procese prisutne u oblikovanju konceptualnih kategorija koje su preslikane na jezični materijal. Na primjerima se japanskih brojača objašnjavaju procesi koji uključuju konceptualnu metaforu i metonimiju, konvencionalne mentalne slike, transformaciju slike u shemu (shematizacija), višestruko temeljenu motivaciju te pojavu lančanog vezivanja (značenjski lanci). Također se primjerom konceptualne kategorije ja u japanskome jeziku prikazuje sposobnost utjecaja društva i kulture da nametnu značenjski okvir unutar kojega će se određena kategorija upotrebljavati.After an introduction to theoretical distinctions between traditional Aristotelian and contemporary cognitive approach to the process of human categorization, and a demonstration of the advantages of the cognitive approach, the paper goes on to discuss Japanese data which exemplify mental processes underlying the formation of conceptual categories and their mapping onto linguistic structures. Japanese classifiers are discussed in the context of cognitive phenomena such as conceptual metaphor and metonymy, conventional mental images, imageschema transformation, multiple motivation, and the phenomenon of chaining structures. The final section discusses the conceptual category self in Japanese, specifically the ability of society and culture to impose a meaning frame within which a given category will be used