Extensions to the e-algorithm for fault detection in combinational logic cicuits

This thesis deals with the detection of stuck-at type faults in combinational circuits. Two different ways are presented of modifying the E-algorithm for generating fault detection test sets of a combinational network

Synthesis of Cortistatin Alkaloids and a Versatile Synthesis of Isoquinolines

The cortistatins are a recently identified class of marine natural products that were found to exhibit potent and selective inhibition of human umbilical vein endothelial cells (HUVECs), making them promising leads for the development of anti-angiogenic drugs. In our synthesis, we envisioned that natural cortistatins and unnatural analogs could be prepared by late-stage introduction of isoquinolines to 17-keto precursors, and that these differentially substituted precursors could all be derived from a common key intermediate 112. We developed a robust synthetic route to prepare gram quantities of key intermediate 112 starting from readily available benzylzinc reagent 116 and enol triflate 117. Key intermediate 112 was next converted to cortistatin precursors 108, 109, 110, and 111 in three to eight steps, representing each of the four natural cortistatin ABC-ring substitution patterns. Subsequently, a generally applicable method was developed to introduce the isoquinoline moiety. After complexation to N,N,N',N'-tetramethylethylenediamine (TMEDA), 7-lithio-isoquinoline added to 17-keto precursors to provide the corresponding 1,2-addition products; the resulting tertiary alcohols underwent radical deoxygenation via their trifluoroacetates to afford the desired (17S)-products. This organolithium-addition-deoxygenation sequence provided cortistatins A (1, on a 20-mg scale), J (9), K (10), and L (11) in good overall yields. We also synthesized cortistatin primary amines (176 and 186) and used them to prepare several cortistatin based affinity reagents. By employing these reagents in pull-down experiments, we identified a 55-kD membrane kinase as a putative protein target of cortistatins. We wanted to prepare cortistatin analogs with isoquinoline modifications due to the importance of this ring for the biological activity of cortistatins. This led us to develop a novel and versatile synthesis of substituted isoquinolines. In our method, lithiated o-tolualdehyde tert-butylimines were condensed with different nitriles to generate eneamido anion intermediates, which were trapped in situ with various electrophiles at the C4-position, affording a wide range of substituted isoquinolines. Further diversification was achieved by modification of the work-up conditions and by subsequent transformations.Chemistry and Chemical Biolog

Temperature-heat uncertainty relation for quantum thermometry

We investigate the resource theory for temperature estimation. We demonstrate that it is the fluctuation of heat that fundamentally determines temperature precision through the temperature-heat uncertainty relation. Specifically, we find that heat is divided into trajectory heat and correlation heat, which are associated with the heat exchange along thermometer's evolution path and the correlation between the thermometer and the sample, respectively. Based on two type of thermometers, we show that both of these heat terms are resources for enhancing temperature precision. Additionally, we demonstrate that the temperature-heat uncertainty relation is consistent with the well known temperature-energy uncertainty relation in thermodynamics. By clearly distinguishing the resources for enhancing estimation precision, our findings not only explain why various quantum features are crucial for accurate temperature sensing but also provide valuable insights for designing ultrahigh-sensitive quantum thermometers.Comment: 6 pages, 1 figur

Synthesis of Cortistatins A, J, K, and L

The cortistatins are a recently identified class of marine natural products characterized by an unusual steroidal skeleton and have been found to inhibit differentially the proliferation of various mammalian cells in culture by an unknown mechanism. We describe a comprehensive route for the synthesis of cortistatins from a common precursor, which in turn is assembled from two fragments of similar structural complexity. Cortistatins A and J, and for the first time, K and L, have been synthesized in parallel processes from like intermediates prepared from a single compound. With the identification of facile laboratory transformations linking intermediates in the cortistatin L synthetic series with corresponding intermediates to cortistatins A and J, we have been led to speculate that somewhat related paths might occur in nature, offering potential sequencing and chemical detail for cortistatin biosynthetic pathways.Chemistry and Chemical Biolog

Quantum Control in Open and Periodically Driven Systems

Quantum technology resorts to efficient utilization of quantum resources to realize technique innovation. The systems are controlled such that their states follow the desired manners to realize different quantum protocols. However, the decoherence caused by the system-environment interactions causes the states deviating from the desired manners. How to protect quantum resources under the coexistence of active control and passive decoherence is of significance. Recent studies have revealed that the decoherence is determined by the feature of the system-environment energy spectrum: Accompanying the formation of bound states in the energy spectrum, the decoherence can be suppressed. It supplies a guideline to control decoherence. Such idea can be generalized to systems under periodic driving. By virtue of manipulating Floquet bound states in the quasienergy spectrum, coherent control via periodic driving dubbed as Floquet engineering has become a versatile tool not only in controlling decoherence, but also in artificially synthesizing exotic topological phases. We will review the progress on quantum control in open and periodically driven systems. Special attention will be paid to the distinguished role played by the bound states and their controllability via periodic driving in suppressing decoherence and generating novel topological phases.Comment: A review articl

Ab initio MCDHF calculations of the In and Tl electron affinities and their isotope shifts

We report multiconfiguration Dirac-Hartree-Fock and relativistic configuration interaction calculations on the Thallium (Tl) electron affinity, as well as on the excited energy levels arising from the ground configuration of Tl$^-$. The results are compared with the available experimental values and further validated by extending the study to its homologous, lighter element, Indium (In), belonging to Group 13 (III.A) of the periodic table. The calculated electron affinities of In and Tl, 383.4 and 322.8 meV, agree with the latest measurements by within 1\%. Three bound states $^3P_{0,1,2}$ are confirmed in the $5s^25p^2$ configuration of In$^-$ while only the ground state $^3P_{0}$ is bound in the $6s^26p^2$ configuration of Tl$^-$. The isotope shifts on the In and Tl electron affinities are also estimated. The E2/M1 intraconfiguration radiative transition rates within 5s^25p^2 \; ^3P_{0,1,2} of In$^-$ are used to calculate the radiative lifetimes of the metastable $^3P_{1,2}$ levels

miR-15a and miR-16-1 inhibit the proliferation of leukemic cells by down-regulating WT1 protein level

<p>Abstract</p> <p>Background</p> <p>miR-15a and miR-16-1(miR-15a/16-1) have been implicated as tumor suppressors in chronic lymphocytic leukemia, multiple myeloma, and acute myeloid leukemic cells. However the mechanism of inhibiting the proliferation of leukemic cells is poorly understood.</p> <p>Methods</p> <p>K562 and HL-60 cells were transfected with pRS-15/16 or pRS-E, cell growth were measured by CCK-8 assay and direct cell count. Meanwhile WT1 protein and mRNA level were measured by Western blotting and quantitative real-time PCR.</p> <p>Results</p> <p>In this study we found that over-expression of miR-15a/16-1 significantly inhibited K562 and HL-60 cells proliferation. Enforced expression of miR-15a/16-1 in K562 and HL-60 cells significantly reduced the protein level of WT1 but not affected the mRNA level. However enforced expression of miR-15a/16-1 can not reduce the activity of a luciferase reporter carrying the 3'-untranslated region(3'UTR) of WT1. Silencing of WT1 by specific siRNA suppressed leukemic cells proliferation resembling that of miR-15a/16-1 over-expression. Anti-miR-15a/16-1 oligonucleotides (AMO) reversed the expression of WT1 in K562 and HL-60 cells. Finally, we found a significant inverse correlation between miR-15a or miR-16-1 expression and WT1 protein levels in primary acute myeloid leukemia (AML) blasts and normal controls.</p> <p>Conclusions</p> <p>These data suggest that miR-15a/16-1 may function as a tumor suppressor to regulate leukemic cell proliferation potentially by down-regulating the WT1 oncogene. However WT1 is not directly targeted by miR-15a/16-1 through miRNA-mRNA base pairing, therefore more study are required to understand the mechanism by which miR-15a/16-1 downregulate WT1.</p

Formulation and In Vitro Evaluation of Ethosomes as Vesicular Carrier for Enhanced Topical Delivery of Isotretinoin

Purpose: The purpose of the present research was to evaluate the ability of ethosomes for topical delivery of isotretinoin. The ethosomal vesicles were prepared with various concentrations of lecithin and ethanol by using hot method. The ethosomal based isotretinoin gel (GEL-ES) was compared to that of marketed formulations isotretinoin (GEL-MF) by using hydrophobic hydroxyl propyl methyl cellulose as gel base. The physicochemical and stability of ethosomal based isotretinoin and a marketed gel (control) were evaluated for organoleptic properties, drug entrapment, drug content uniformity and in vitro drug release and skin permeation studies. F2 ethosomal vesicles containing 2%w/w lecithin and 30%w/w ethanol was found to have shown the best entrapment percentage (99.21%) and also showed suitable physicochemical characteristics for topical administration. Physical stability studies were also conducted for 45 days at 4°C and 25°C. GEL-ES and GEL-MF were applied to rat skin and penetration was assessed by Franz diffusion cells. In vitro release studies showed that less than 10% of isotretinoin reached the receptor compartment compared to GEL-MF till 8 h. On comparing F2 and F4 gel formulations, F2 gel has shown better controlled release by in vitro drug release and in vitro skin permeation profile than F4 gel. However, the in vitro skin permeation was increased with the addition of enhancers. From the experimental data, it may be concluded that the ethosomal vesicles and enhancers increased the skin permeation and depot formation of drug in the skin

Demonstration of Adiabatic Variational Quantum Computing with a Superconducting Quantum Coprocessor

Adiabatic quantum computing enables the preparation of many-body ground states. This is key for applications in chemistry, materials science, and beyond. Realisation poses major experimental challenges: Direct analog implementation requires complex Hamiltonian engineering, while the digitised version needs deep quantum gate circuits. To bypass these obstacles, we suggest an adiabatic variational hybrid algorithm, which employs short quantum circuits and provides a systematic quantum adiabatic optimisation of the circuit parameters. The quantum adiabatic theorem promises not only the ground state but also that the excited eigenstates can be found. We report the first experimental demonstration that many-body eigenstates can be efficiently prepared by an adiabatic variational algorithm assisted with a multi-qubit superconducting coprocessor. We track the real-time evolution of the ground and exited states of transverse-field Ising spins with a fidelity up that can reach about 99%.Comment: 12 pages, 4 figure