Characterization of Jak, STAT, and Src interactions in Head and Neck Squamous Cell Carcinoma

Recurrence of Head and Neck Squamous Cell Carcinoma (HNSCC) is common; thus, it is essential to improve the effectiveness and reduce toxicity of current treatments. Proteins in the Src/Jak/STAT pathway represent potential therapeutic targets, as this pathway is hyperactive in HNSCC and it has roles in cell migration, metastasis, proliferation, survival, and angiogenesis. During short-term Src inhibition, Janus kinase (Jak) 2, and signal transducer and activator of transcription (STAT) 3 and STAT5 are dephosphorylated and inactivated. Following sustained Src inhibition, STAT5 remains inactive, but Jak2 and STAT3 are reactivated following their early inhibition. To further characterize the mechanism of this novel feedback pathway we performed several experiments to look at the interactions between Src, Jak2, STAT5 and STAT3. We attempted to develop a non-radioactive kinase assay using purified recombinant Jak2 and Src proteins, but found that phospho-tyrosine antibodies were non-specifically binding to purified recombinant proteins. We then performed in vitro kinase assays (IVKAs) using purified recombinant Jak2, Src, STAT3, and STAT5 proteins with and without Src and Jak2 pharmacologic inhibitors. We also examined the interactions of these proteins in intact HNSCC cells. We found that recombinant Jak2, STAT3, and STAT5 are direct substrates of Src and that recombinant Src, STAT3, and STAT5 are direct substrates of Jak2 in the IVKA. To our knowledge, the finding that Src is a Jak substrate is novel and has not been shown before. In intact HNSCC cells we find that STAT3 can be reactivated despite continuous Src inhibition and that STAT5 continues to be inhibited despite Jak2 reactivation. Also, Jak2 inhibition did not affect Src or STAT5 activity but it did cause STAT3 inhibition. We hypothesized that the differences between the intact cells and the IVKA assays were due to a potential need for binding partners in intact HNSCC cells. One potential binding partner that we examined is the epidermal growth factor receptor (EGFR). We found that EGFR activation caused increased activation of Src and STAT5 but not Jak2. Our results demonstrate that although STAT3 and STAT5 are capable of being Src and Jak2 substrates, in intact HNSCC cells Src predominantly regulates STAT5 and Jak2 regulates STAT3. Regulation of STAT5 by Src may involve interactions between Src and EGFR. This knowledge along with future studies will better define the mechanisms of STAT regulation in HNSCC cells and ultimately result in an ideal combination of therapeutic agents for HNSCC

Adaptive Digital Scan Variable Pixels

The square and rectangular shape of the pixels in the digital images for sensing and display purposes introduces several inaccuracies in the representation of digital images. The major disadvantage of square pixel shapes is the inability to accurately capture and display the details in the objects having variable orientations to edges, shapes and regions. This effect can be observed by the inaccurate representation of diagonal edges in low resolution square pixel images. This paper explores a less investigated idea of using variable shaped pixels for improving visual quality of image scans without increasing the square pixel resolution. The proposed adaptive filtering technique reports an improvement in image PSNR.Comment: 4th International Conference on Advances in Computing, Communications and Informatics, August, 201

Traumatic hyphaema following successive vacuum and forceps-assisted delivery

Hyphaema can cause corneal staining and is a potential risk for glaucoma. We report a case of a neonate with isolated traumatic hyphaema following a prolonged delivery with the consecutive use of vacuum and forceps. A review the literature discusses reports of ophthalmic injuries associated with assisted vaginal deliveries.peer-reviewe

Energy Information Systems: From the Basement to the Boardroom

A significant buildings energy reduction opportunity exists in the office sector, given that this market segment typically is an early adopter of new technology. There is a rising trend towards smart and connected offices through the internet of things (IoT) that provides new opportunities for operational efficiency and environmental sustainability practices. Leading commercial real estate companies have begun to shift from individual building automation systems (BAS) to partially integrated and automated systems such as energy information systems (EIS). In both the United States and India, organizations are seeking operational excellence, enhanced tenant relationships, and topline growth. Hence it is imperative to engage the executives with decision-making power, by tapping into their interest in sustainability, corporate social responsibility, and innovation. This expansion of interest can enable data-driven decisions, strong energy investments, and deeper energy benefits, and would drive innovation in this field. However, none of this would be possible without robust, consistent building energy information to provide visibility across all the levels of decision making, i.e. from the basement where the facilities staff take operational action to the boardroom where the executives make investment decisions. Price, security, and ease of use remain barriers to the adoption and pervasive use of promising EIS technologies in commercial office buildings. We believe that these barriers can be addressed through the development of ready, simplified, consistent, commercially available, low-cost EIS-in-a-box packages, that have a pre-defined set of hardware components and software features and functionality that are pertinent to a particular building sector. These simplified, sector-specific EIS packages can help to obviate the need for customization, and enhance ease of use, thereby enabling scale-up, in order to facilitate building energy savings. The EIS-in-a-box are adaptable in both U.S. and Indian office buildings, and potentially beyond these two countries

Linkage to care following home-based HIV counseling and testing: a mixed methods study in rural South Africa

Thesis (D.P.H.)--Boston UniversityBackground: The mandate for scale up of home-based HIV counseling and testing (HBHCT) is strong. To maximize the benefits of testing, prompt linkage to care and treatment for HIV-positive clients is essential. Timely linkage can lead to decreased morbidity and mortality, as well as increased quality of life and life expectancy. Early treatment initiation can also reduce HIV transmission to uninfected partners. While data exists on the transition to care from mobile and facility-based HIV testing, less is known about the transition from HBHCT. Methods: A mixed methods study was conducted among a sample of 492 HIV-positive HBHCT clients in rural South Africa to: 1) determine the rate of linkage from HBHCT to facility-based services; and 2) identify factors that influence linkage. Clients were followed up to assess linkage to care, defined as providing a blood sample for a facility-based CD4 count. Using data from a cross-sectional survey conducted among a subsample of 196 clients 6-153 days after testing, Cox regression was performed to determine factors associated with linkage. To further explore potential barriers and facilitating factors, in-depth interviews were conducted with 30 clients who were purposively selected based on timely versus delayed care seeking. Results: Among 359 HIV-positive HBHCT clients, 62.1% (95% CI: 55.7% - 68.5%) linked to care within 3 months. For those who did not link promptly, barriers occurred at all levels: individual, relationships, community, and health systems. Delayed care seeking was influenced by poor psychological responses to the diagnosis; challenges surrounding disclosure and limited social support; lack of time, opportunity, and financial resources; and internalized negative experiences with the healthcare system. Often, barriers interacted and were subtly reinforced by stigma. Women and youth may be particularly vulnerable to these barriers. Conclusion: The findings highlight important gaps in our understanding, and provide the basis for policy and programmatic recommendations. Key recommendations include: 1) including HBHCT and monitoring of linkage to care in the role of community health workers; 2) offering tailored counseling and motivational interviewing; 3) conducting short-term intensive community-based support groups; 4) offering mobile point-of-care CD4 counts; and 5) piloting and evaluating community based nurse-initiated treatment

Detours admitting short paths

Finding shortest paths between two vertices in a weighted graph is a well explored problem and several efficient algorithms for solving it have been reported. We propose a new variation of this problem which we call the Detour Admitting Shortest Path Problem (DASPP).We present an efficient algorithm for solving DASPP. This is the first algorithm that constructs a shortest path such that each edge of the shortest path admits a detour with no more than k−hops. This algorithm has important applications in transportation networks. We also present implementation issues for the detour admitting shortest path algorithm