An analysis of the Supramolecular NanoStamping technology for its market potential based upon a review of DNA microarray intellectual property

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2006.Includes bibliographical references (leaf 38).Supramolecular NanoStamping is a novel printing method for exploiting the supramolecular interactions between organic and biological molecules. This technology is advantageous because of the ability to transfer a massive amount of chemical and spatial information, its high resolution, the growth of masters used multiple times and the versatility of initial master fabrication. The technology may be used to make DNA microarrays which are an essential tool to genomic research assisting in gene expression and genotyping. This paper explores the potential of bring Supramolecular NanoStamping technology to the microarray market. An in depth analysis of the current patent landscape of DNA microarrays is conducted to recognize the various competitors and the coverage of their patents. In addition, a better understanding of the landscape was achieved by assessing the major litigation that has occurred in the field. By engaging in a thorough intellectual property analysis, the commercialization potential of Supramolecular NanoStamping technology was realized through a licensing model.by Kathy H. Li.M.Eng

Characterizing physiological and symptomatic variation in menstrual cycles using self-tracked mobile health data

The menstrual cycle is a key indicator of overall health for women of reproductive age. Previously, menstruation was primarily studied through survey results; however, as menstrual tracking mobile apps become more widely adopted, they provide an increasingly large, content-rich source of menstrual health experiences and behaviors over time. By exploring a database of user-tracked observations from the Clue app by BioWink of over 378,000 users and 4.9 million natural cycles, we show that self-reported menstrual tracker data can reveal statistically significant relationships between per-person cycle length variability and self-reported qualitative symptoms. A concern for self-tracked data is that they reflect not only physiological behaviors, but also the engagement dynamics of app users. To mitigate such potential artifacts, we develop a procedure to exclude cycles lacking user engagement, thereby allowing us to better distinguish true menstrual patterns from tracking anomalies. We uncover that women located at different ends of the menstrual variability spectrum, based on the consistency of their cycle length statistics, exhibit statistically significant differences in their cycle characteristics and symptom tracking patterns. We also find that cycle and period length statistics are stationary over the app usage timeline across the variability spectrum. The symptoms that we identify as showing statistically significant association with timing data can be useful to clinicians and users for predicting cycle variability from symptoms or as potential health indicators for conditions like endometriosis. Our findings showcase the potential of longitudinal, high-resolution self-tracked data to improve understanding of menstruation and women's health as a whole.Comment: The Supplementary Information for this work, as well as the code required for data pre-processing and producing results is available in https://github.com/iurteaga/menstrual_cycle_analysi

Independent Planning System and Public Administration in Metropolitan Development: Agglomeration Strategies of Greater Chaoshan in Southern China

This paper examines independent planning system as a means of public administration in regional economic development. It proposes a new strategy based on the theories of public administrative resources, to agglomerate and unify the cities of Shantou, Jieyang, and Chaozhou into a new administrative entity as a metropolis with the status of independent planning and the preferred policies of a Special Economic Region to lead regional development. The optimal allocation of public administrative resources has played a key role in the fundamental economic development in China in recent years. The new administrative system of large cities (metropolises) with independent planning has become an innovative format to utilize the renewable soft resources of administration, which in fact is a new attempt to reform the economic system by the Chinese government. The greater Chaoshan area needs to be agglomerated and unified to further develop the regional economy with the implementation of independent planning system. The current research conducted from a practical and political point of view is of significant value to the overall planning and strategic layout of the economic and social development of the whole eastern Guangdong region

AMG 837: A Novel GPR40/FFA1 Agonist that Enhances Insulin Secretion and Lowers Glucose Levels in Rodents

Agonists of GPR40 (FFA1) have been proposed as a means to treat type 2 diabetes. Through lead optimization of a high throughput screening hit, we have identified a novel GPR40 agonist called AMG 837. The objective of these studies was to understand the preclinical pharmacological properties of AMG 837. The activity of AMG 837 on GPR40 was characterized through GTPγS binding, inositol phosphate accumulation and Ca2+ flux assays. Activity of AMG 837 on insulin release was assessed on isolated primary mouse islets. To determine the anti-diabetic activity of AMG 837 in vivo, we tested AMG 837 using a glucose tolerance test in normal Sprague-Dawley rats and obese Zucker fatty rats. AMG 837 was a potent partial agonist in the calcium flux assay on the GPR40 receptor and potentiated glucose stimulated insulin secretion in vitro and in vivo. Acute administration of AMG 837 lowered glucose excursions and increased glucose stimulated insulin secretion during glucose tolerance tests in both normal and Zucker fatty rats. The improvement in glucose excursions persisted following daily dosing of AMG 837 for 21-days in Zucker fatty rats. Preclinical studies demonstrated that AMG 837 was a potent GPR40 partial agonist which lowered post-prandial glucose levels. These studies support the potential utility of AMG 837 for the treatment of type 2 diabetes

Role of RPL39 in Metaplastic Breast Cancer

Background: Metaplastic breast cancer is one of the most therapeutically challenging forms of breast cancer because of its highly heterogeneous and chemoresistant nature. We have previously demonstrated that ribosomal protein L39 (RPL39) and its gain-of-function mutation A14V have oncogenic activity in triple-negative breast cancer and this activity may be mediated through inducible nitric oxide synthase (iNOS). The function of RPL39 and A14V in other breast cancer subtypes is currently unknown. The objective of this study was to determine the role and mechanism of action of RPL39 in metaplastic breast cancer. Methods: Both competitive allele-specific and droplet digital polymerase chain reaction were used to determine the RPL39 A14V mutation rate in metaplastic breast cancer patient samples. The impact of RPL39 and iNOS expression on patient overall survival was estimated using the Kaplan-Meier method. Co-immunoprecipitation and immunoblot analyses were used for mechanistic evaluation of RPL39. Results: The RPL39 A14V mutation rate was 97.5% (39/40 tumor samples). High RPL39 (hazard ratio = 0.71, 95% confidence interval = 0.55 to 0.91, P = .006) and iNOS expression (P = .003) were associated with reduced patient overall survival. iNOS inhibition with the pan-NOS inhibitor NG-methyl-L-arginine acetate decreased in vitro proliferation and migration, in vivo tumor growth in both BCM-4664 and BCM-3807 patient-derived xenograft models (P = .04 and P = .02, respectively), and in vitro and in vivo chemoresistance. Mechanistically, RPL39 mediated its cancer-promoting actions through iNOS signaling, which was driven by the RNA editing enzyme adenosine deaminase acting on RNA 1. Conclusion: NOS inhibitors and RNA editing modulators may offer novel treatment options for metaplastic breast cancer

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

Molecular Basis of NDM-1, a New Antibiotic Resistance Determinant

The New Delhi Metallo-β-lactamase (NDM-1) was first reported in 2009 in a Swedish patient. A recent study reported that Klebsiella pneumonia NDM-1 positive strain or Escherichia coli NDM-1 positive strain was highly resistant to all antibiotics tested except tigecycline and colistin. These can no longer be relied on to treat infections and therefore, NDM-1 now becomes potentially a major global health threat

Rare loss of function variants in candidate genes and risk of colorectal cancer

Although ~ 25% of colorectal cancer or polyp (CRC/P) cases show familial aggregation, current germline genetic testing identifies a causal genotype in the 16 major genes associated with high penetrance CRC/P in only 20% of these cases. As there are likely other genes underlying heritable CRC/P, we evaluated the association of variation at novel loci with CRC/P. We evaluated 158 a priori selected candidate genes by comparing the number of rare potentially disruptive variants (PDVs) found in 84 CRC/P cases without an identified CRC/P risk-associated variant and 2440 controls. We repeated this analysis using an additional 73 CRC/P cases. We also compared the frequency of PDVs in select genes among CRC/P cases with two publicly available data sets. We found a significant enrichment of PDVs in cases vs. controls: 20% of cases vs. 11.5% of controls with ≥ 1 PDV (OR = 1.9, p = 0.01) in the original set of cases. Among the second cohort of CRC/P cases, 18% had a PDV, significantly different from 11.5% (p = 0.02). Logistic regression, adjusting for ancestry and multiple testing, indicated association between CRC/P and PDVs in NTHL1 (p = 0.0001), BRCA2 (p = 0.01) and BRIP1 (p = 0.04). However, there was no significant difference in the frequency of PDVs at each of these genes between all 157 CRC/P cases and two publicly available data sets. These results suggest an increased presence of PDVs in CRC/P cases and support further investigation of the association of NTHL1, BRCA2 and BRIP1 variation with CRC/P

Daily Dosing of Rifapentine Cures Tuberculosis in Three Months or Less in the Murine Model

Eric Nuermberger and colleagues found that after two months of treatment, mice with lung cultures positive for tuberculosis that received daily doses of rifapentine- and moxifloxacin-containing regimens converted to negative lung cultures. This finding could make possible the development of shorter treatment regimens for humans