First On-Sky High Contrast Imaging with an Apodizing Phase Plate

We present the first astronomical observations obtained with an Apodizing Phase Plate (APP). The plate is designed to suppress the stellar diffraction pattern by 5 magnitudes from 2-9 lambda/D over a 180 degree region. Stellar images were obtained in the M' band (4.85 microns) at the MMTO 6.5m telescope, with adaptive wavefront correction made with a deformable secondary mirror designed for low thermal background observations. The measured PSF shows a halo intensity of 0.1% of the stellar peak at 2 lambda/D (0.36 arcsec), tapering off as r^{-5/3} out to radius 9 lambda/D. Such a profile is consistent with residual errors predicted for servo lag in the AO system. We project a 5 sigma contrast limit, set by residual atmospheric fluctuations, of 10.2 magnitudes at 0.36 arcsec separation for a one hour exposure. This can be realised if static and quasi-static aberrations are removed by differential imaging, and is close to the sensitivity level set by thermal background photon noise for target stars with M'>3. The advantage of using the phase plate is the removal of speckle noise caused by the residuals in the diffraction pattern that remain after PSF subtraction. The APP gives higher sensitivity over the range 2-5 lambda/D compared to direct imaging techniques.Comment: 22 pages, 5 figures, 1 table, ApJ accepte

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Pheromone trail following in the antLasius niger: high accuracy and variability but no effect of task state

The use of pheromone trails in ant colony organization is an important model for understanding collective decision-making and complex adaptive systems. The ant Lasius niger L. (Hymenoptera: Fomicidae) is one of the main model organisms used for such studies. Key to understanding pheromone trail use by ants is knowing how well trails are followed. The results of a previous study suggest that L. niger trail following is poor, with between 60% and 70% accuracy at a T bifurcation. It is hypothesized that the true trail following accuracy is higher, and that the low accuracy reported previously is the result of a methodological error. Specifically, it is hypothesized that 'task state' (i.e. what the ants 'thought they were doing') affected pheromone following accuracy. In the present study, the task state of the ants is set experimentally to one of three states: scouting (completely naive), recruited (having information that food has been found, but not where it is) and shuttling (having a strong memory of the location of a food source). Trail following accuracy is tested for each group. Trail following is found to be more accurate than previously reported: 83%, 82% and 74% correct decisions for scouts, recruits and shuttlers, respectively. However, the difference between the three groups is not significant. Importantly, very high inter-trial variation is reported both in the present study and in experiments from other research groups. This variation is unexplainable by trail strengths or colony-level differences, and is highlighted as an important factor when experimentally measuring trail following

Brain areas consistently linked to individual differences in perceptual decision-making in younger as well as older adults before and after training

Perceptual decision-making performance depends on several cognitive and neural processes. Here, we fit Ratcliff's diffusion model to accuracy data and reaction-time distributions from one numerical and one verbal two-choice perceptual-decision task to deconstruct these performance measures into the rate of evidence accumulation (i.e., drift rate), response criterion setting (i.e., boundary separation), and peripheral aspects of performance (i.e., nondecision time). These theoretical processes are then related to individual differences in brain activation by means of multiple regression. The sample consisted of 24 younger and 15 older adults performing the task in fMRI before and after 100 daily 1-hr behavioral training sessions in a multitude of cognitive tasks. Results showed that individual differences in boundary separation were related to striatal activity, whereas differences in drift rate were related to activity in the inferior parietal lobe. These associations were not significantly modified by adult age or perceptual expertise. We conclude that the striatum is involved in regulating response thresholds, whereas the inferior parietal lobe might represent decision-making evidence related to letters and numbers

Escherichia coli MutL and the Vsr repair

endonucleas

Is Thymidine Glycol Containing DNA a Substrate of <i>E. coli</i> DNA Mismatch Repair System?

<div><p>The DNA <u>m</u>is<u>m</u>atch <u>r</u>epair (MMR) system plays a crucial role in the prevention of replication errors and in the correction of some oxidative damages of DNA bases. In the present work the most abundant oxidized pyrimidine lesion, 5,6-dihydro-5,6-dihydroxythymidine (thymidine glycol, Tg) was tested for being recognized and processed by the E. coli MMR system, namely complex of MutS, MutL and MutH proteins. In a partially reconstituted MMR system with MutS-MutL-MutH proteins, G/Tg and A/Tg containing plasmids failed to provoke the incision of DNA. Tg residue in the 30-mer DNA duplex destabilized double helix due to stacking disruption with neighboring bases. However, such local structural changes are not important for <i>E. coli</i> MMR system to recognize this lesion. A lack of repair of Tg containing DNA could be due to a failure of MutS (a first acting protein of MMR system) to interact with modified DNA in a proper way. It was shown that Tg in DNA does not affect on ATPase activity of MutS. On the other hand, MutS binding affinities to DNA containing Tg in G/Tg and A/Tg pairs are lower than to DNA with a G/T mismatch and similar to canonical DNA. Peculiarities of MutS interaction with DNA was monitored by Förster resonance energy transfer (FRET) and fluorescence anisotropy. Binding of MutS to Tg containing DNAs did not result in the formation of characteristic DNA kink. Nevertheless, MutS homodimer orientation on Tg-DNA is similar to that in the case of G/T-DNA. In contrast to G/T-DNA, neither G/Tg- nor A/Tg-DNA was able to stimulate ADP release from MutS better than canonical DNA. Thus, Tg residue in DNA is unlikely to be recognized or processed by the <i>E.</i> coli MMR system. Probably, the MutS transformation to active “sliding clamp” conformation on Tg-DNA is problematic.</p></div