Fluorescent PET (Photoinduced Electron Transfer) Sensors with Targeting/Anchoring Modules as Molecular Versions of Submarine Periscopes for Mapping Membrane-Bounded Protons

The two families of fluorescent PET (photoinduced electron transfer) sensors (1-9) show that the effective proton density near the surface of several micelle membranes changes over 2-3 orders of magnitude as the microlocation of the sensor (with respect to the membrane) is altered via hydrophobic tuning.

Recognition of O6MeG lesions by MGMT and mismatch repair proficiency may be a prerequisite for low-dose radiation hypersensitivity

Low-dose hyper-radiosensitivity (HRS) is the phenomenon whereby cells exposed to radiation doses of less than approximately 0.5 Gy exhibit increased cell killing relative to that predicted from back-extrapolating high-dose survival data using a linear-quadratic model. While the exact mechanism remains to be elucidated, the involvement of several molecular repair pathways has been documented. These processes in turn are also associated with the response of cells to O6-methylguanine (O6MeG) lesions. We propose a model in which the level of low-dose cell killing is determined by the efficiency of both pre-replicative repair by the DNA repair enzyme O6-methylguanine methyltransferase (MGMT) and post-replicative repair by the DNA mismatch repair (MMR) system. We therefore hypothesized that the response of cells to low doses of radiation is dependent on the expression status of MGMT and MMR proteins. MMR (MSH2, MSH6, MLH1, PMS1, PMS2) and MGMT protein expression signatures were determined in a panel of normal (PWR1E, RWPE1) and malignant (22RV1, DU145, PC3) prostate cell lines and correlated with clonogenic survival and cell cycle analysis. PC3 and RWPE1 cells (HRS positive) were associated with MGMT and MMR proficiency, whereas HRS negative cell lines lacked expression of at least one (MGMT or MMR) protein. MGMT inactivation had no significant effect on cell survival. These results indicate a possible role for MMR-dependent processing of damage produced by low doses of radiation.

Efficient Algorithms for Answering the m-Closest Keywords Query

As an important type of spatial keyword query, the m-closest keywords (mCK) query finds a group of objects such that they cover all query keywords and have the smallest diameter, which is defined as the largest distance between any pair of objects in the group. The query is useful in many applications such as detecting locations of web resources. However, the existing work does not study the intractability of this problem and only provides exact algorithms, which are computationally expensive.

In this paper, we prove that the problem of answering mCK queries is NP-hard. We first devise a greedy algorithm that has an approximation ratio of 2. Then, we observe that an mCK query can be approximately answered by finding the circle with the smallest diameter that encloses a group of objects together covering all query keywords. We prove that the group enclosed in the circle can answer the mCK query with an approximation ratio of 2 over 3. Based on this, we develop an algorithm for finding such a circle exactly, which has a high time complexity. To improve efficiency, we propose another two algorithms that find such a circle approximately, with a ratio of 2 over √3 + ε. Finally, we propose an exact algorithm that utilizes the group found by the 2 over √3 + ε)-approximation algorithm to obtain the optimal group. We conduct extensive experiments using real-life datasets. The experimental results offer insights into both efficiency and accuracy of the proposed approximation algorithms, and the results also demonstrate that our exact algorithm outperforms the best known algorithm by an order of magnitude.