Obligations of Contracts: Intent and Distortion

<p><b>Introduction:</b> Treosulfan is an alkylating agent that is used for the treatment of ovarian cancer and for conditioning prior to stem cell transplantation. It is a prodrug that is activated non-enzymatically to two active epoxides.</p> <p><b>Objectives:</b> To optimize a protocol for both <i>in vivo</i> samples handling and <i>in vitro</i> drug preparation. Treosulfan stability was tested in biological fluids at different conditions as well as for its cytotoxicity on cell lines.</p> <p><b>Results:</b> Plasma samples can be safely frozen for a short period up to 8 h, however; for longer periods, samples should be acidified. Urine samples and cell culture media can be safely frozen regardless their pH. For <i>in vitro</i> investigations, incubation of treosulfan at 37 °C for 24 h activated 100% of the drug. Whole blood acidification should be avoided for the risk of hemolysis. Finally; treosulfan cytotoxicity on HL-60 cells has increased following pre-incubation for 24 h at 37 °C compared to K562 cell line.</p> <p><b>Conclusion:</b> The stability profiling of treosulfan provided a valuable reference for handling of biological samples for both <i>in vivo</i> and <i>in vitro</i> studies. These results can be utilized for further investigations concerning the drug kinetics and dynamics in addition to the development of new pharmaceutical formulations.</p

Adapting Differential Privacy in Scenarios

Privacy leakage events have been increasingly frequent recently. Your DOB, home address, workplace, household composition, race, shopping and movie preferences, and other sensitive information can be easily compromised without your awareness. Differential Privacy is a provable robustness approach to address those privacy issues. This thesis proposed three Differential Privacy methods to protect location data and census data. First method can protect your accurate home address while maintaining its South East position to the CBD. Second method can protect COVID infected patients’ home addresses and meanwhile preserve the distribution of those cases for epidemiological study. Third method protect census data.</p

Visualization.mp4

This video shows the multi-focus images captured when moving the camera

Orthogonal designs and complementary sequences: constructions and applications for wireless communication

Problems concerned with the algebraic structure and existence of orthogonal designs and complementary sequences with zero aperiodic autocorrelation have long been of interest in combinatorics, coding theory and applied statistics. Over the last few decades, due to an increased demand for wireless services, new technologies have had to be considered since traditional methods are reaching their technical or financial limits. This has motivated the study of new applications of algebraic structures for wireless communications to improve system performance. For example, space-time block codes (STB Cs) from orthogonal designs for multiple-input multiple-output (M IM O) wireless systems have received a lot of attention due to their inherent orthogonality, which guarantees a full transmit diversity and a simple linear decoding. The objective of this research is to investigate the construction of orthogonal designs and complementary sequences in terms of wireless communication applications. One thread of this thesis is the introduction of amicable orthogonal designs over the real and quaternion domain in the context of STB Cs from orthogonal designs. Another part is the study of Golay complementary sequences and their applications as orthogonal spreading sequences for direct sequence code division multiple access (D S-CD M A) systems. We address the following problems in this thesis: ² The current complex orthogonal STB Cs for more than two antennas are not delay optimal or full rate, and even contain many z eros, which will impede their practical implementation. We first introduce some new complex orthogonal codes of order eight with fewer wasted time slots compared to conventional codes. Furthermore, for those complex STB Cs constructed from amicable orthogonal designs containing z eros and irrational numbers in their coefficient matrices, we use the representation theory of Cliord algebras to improve the form of complex orthogonal STB Cs. B y applying this proposed method, we can construct square, maximum rate complex codes with less z eros and no irrational numbers, e.g. transmitted symbols are equally dispersed through transmit antennas. ² However, given any arbitrary order and type, many amicable orthogonal designs are left undecided, since they cannot be constructed using current techniques. We thus introduce the concept of orthogonal designs equivalence. By searching all the equivalence classes of orthogonal designs we find new amicable orthogonal designs of order eight. In addition, some undecided cases can be concluded with non-existence after searching all the equivalence classes of an orthogonal design with the same order and type. We then summarize all the existence and non-existence results of amicable orthogonal designs with order eight. ² Motivated by the success of space-time block codes from orthogonal designs, we also discuss the construction of amicable orthogonal designs over the quaternion domain (AOD Q ) for their possible applications as space-time-polarization block codes, since the additional polarization diversity can be modelled by means of quaternions. We construct some new AOD Q s using the Kronecker product with real amicable orthogonal designs or real weighing matrices from an amicable family. ² Complementary pairs and orthogonal spreading sequences constructed on the basis of complementary sequences have long been studied for channel separation in D S-CD M A systems. H owever, it is hard to generate sequences with both good autocorrelation and cross-correlation properties so as to achieve a good interference performance. We derive a new class of quadri-phase orthogonal spreading sequences from small mutually orthogonal (M O) complementary sets. We then apply a sequence modification method based on choosing a diag- onal H -equivalent matrix to optimize the correlation properties of sequences. The modifed sequences exhibit a reasonable compromise between autocorrela- tion and cross-correlation characteristics, and, as shown through simulations, lead to good performance when used in an asynchronous multi-user CD M A system

Pharmacological targeting of p53 pathway alterations in tumors

The p53 tumor suppressor plays an important role in cell fate decisions upon diverse stress conditions. In response to stress, p53 functions as a transcription factor, activating transcription of a variety of its target genes responsible for several cellular responses, most importantly cell cycle arrest and apoptosis. The p53 gene is one of the most frequently mutated genes in cancer. Dysfunction of the p53 protein due to gene mutations has been observed in ca 50% of all known human cancers. In the other half of human tumors, p53 is not functional due to extensive degradation by MDM2 or HPVE6/E6AP. Inactivation of p53 is essential for tumor survival, therefore the strategy aimed at restoring its functions is a promising approach for cancer treatment.Previously identified small molecule RITA has been shown to rescue p53 functions in tumor cells where it protects p53 from MDM2-mediated degradation. RITA reactivates p53 and triggers apoptosis in tumor cells while it does not affect normal cells. Here, we address the questions whether RITA can rescue p53 function upon its inactivation in HPV-E6 and point mutations in the p53 gene.Cervical cancer is one of the most common cancer types in women worldwide. It is causally linked to infection by the human papilloma virus whose E6 oncoprotein hijacks a cellular E3 ligase, E6AP (E6-associated protein), and targets p53 for degradation. Here, we show that RITA can reduce the interaction between p53 and E6AP, thereby reactivating p53 in cervical carcinoma cells. RITA rescued p53 s transcriptional functions and induced apoptosis in a p53-dependent manner. Importantly, RITA suppressed growth of cervical carcinoma xenografts in vivo.We found that small molecule RITA rescued the function of various p53 mutants in tumor cell lines of different origin. RITA triggered p53-dependent growth suppression in cells that harbor mutant p53 and induced apoptosis. Similar to its effects in wild-type p53 expressing cells, RITA restored mutant p53 s transcriptional activity. Thus, RITA can rescue the function of both wild-type and mutant p53.Notably, we found that 53BP1, an important mediator of DNA damage response, plays a critical role in the tumor-specific effects of RITA. Furthermore, we found that 53BP1 interacts with and stabilizes both wild-type and mutant p53 in tumor cells. 53BP1 regulates p53 stability upon DNA damage or oncogenic stress but not in untransformed cells. This suggests that 53BP1 confers tumor-selective p53 stabilization. However, depending on the p53 status, 53BP1 might function as an tumor suppressor in cells with wild-type p53, or as an oncogene when it stabilizes mutant p53.In conclusion, our findings show that RITA has specificity towards tumor cells expressing wild-type or mutant p53, and can serve as a lead compound for future development of target-specific anti-cancer drugs.List of scientific papersI. Zhao CY, Szekely L, Bao W, Selivanova G (2010). "Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradation." Cancer Res 70(8): 3372-81. https://doi.org/10.1158/0008-5472.CAN-09-2787 II. Zhao Y, Grinkevich VV, Nikulenkov F, Bao W, Selivanova, G (2010). "Rescue of the apoptotic-inducing function of mutant p53 by small molecule RITA." Cell Cycle. [Accepted] https://pubmed.ncbi.nlm.nih.gov/20436301III. Bao W, Nikulenkov F, Zhao Y, Spinnler C, Bartek J, Selivanova G (2010). "Crucial role f 53BP1 in the stabilization of wild-type and mutant p53 upon oncogene activation." [Manuscript]</p

Stability of the motor under different control methods.

Stability of the motor under different control methods.</p

Tracking error of four motors under traditional SMC.

Tracking error of four motors under traditional SMC.</p

SSE performance of motors 2, 3 and 4 under two SMC.

SSE performance of motors 2, 3 and 4 under two SMC.</p

Output speed of four motors under traditional SMC.

Output speed of four motors under traditional SMC.</p

Structure of improved DCC for MPMMS.

The synchronous control system of multi-permanent magnet motor has the characteristics of many parameter variables and mutual coupling. The use of sliding mode control to optimize the parameters in the multi-permanent magnet motor system not only ensures the stability of the system operation, but also improves the control accuracy of the system, which is of great importance in practical applications. Based on this background, the study combines the new adaptive integral sliding mode control (NAISMC) with the improved sliding-mode disturbance observer (SMDO) and uses it for the multi-permanent magnet synchronous motor (MPMSM). In NAISMC, the controller updates and adjusts the parameters of the controller using an adaptive algorithm according to the state of the system and the error signals, which further improves the stability and robustness of the system. SMDO utilizes the principle of the sliding-mode observer to estimate the disturbance of the system, and eliminates the effect of the disturbance on the system by introducing a compensation term. The sliding mode observer calculates the disturbance estimate by comparing the difference between the actual and the estimated outputs. The disturbance estimate is finally used to generate the corresponding compensation signal to eliminate or minimize the effect of the disturbance on the system. NAISMC is combined with SMDO and used in the deviation coupling control of MPMSM. The study established a simulation experiment environment in MATLAB, set the simulation time to 0.4s, and the rated speed of the motor to 1000r/min. The improved sliding mode control scheme is tested, and the results show that the motor output speed, tracking error and electromagnetic torque variation under the improved sliding mode control scheme are smaller than those under the traditional sliding mode control scheme. Under the same simulation conditions, the multi-motor speed synchronization error under the improved sliding mode control scheme is around 0r/min, and its error value is close to 0, so the control effect is higher. In conclusion, the optimization scheme proposed in this study can effectively improve the stability and control accuracy of the multi-motor system.</div