Tests for comparing images based on randomization and permutation methods

Tests comparing image sets can play a critical role in PET research, providing a yes-no answer to the question "Are two image sets different?" The statistical goal is to determine how often observed differences would occur by chance alone. We examined randomization methods to provide several omnibus test for PET images and compared these tests with two currently used methods. In the first series of analyses, normally distributed image data were simulated fulfilling the requirements of standard statistical tests. These analyses generated power estimates and compared the various test statistics under optimal conditions. Varying whether the standard deviations were local or pooled estimates provided an assessment of a distinguishing feature between the SPM and Montreal methods. In a second series of analyses, we more closely simulated current PET acquisition and analysis techniques. Finally, PET images from normal subjects were used as an example of randomization. Randomization proved to be a highly flexible and powerful statistical procedure. Furthermore, the randomization test does not require extensive and unrealistic statistical assumptions made by standard procedures currently in use.     

Targeting CD10 on B-Cell Leukemia Using the Universal CAR T-Cell Platform (UniCAR)

Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies.     

A 16-Mb MRAM featuring bootstrapped write drivers

A 16-Mb magnetic random access memory (MRAM) is demonstrated in 0.18-/spl mu/m three-Cu-level CMOS with a three-level MRAM process adder. The chip, the highest density MRAM reported to date, utilizes a 1.42/spl mu/m/sup 2/ 1-transistor 1-magnetic tunnel junction (1T1MTJ) cell, measures 79 mm/sup 2/ and features a /spl times/16 asynchronous SRAM-like interface. The paper describes the cell, architecture, and circuit techniques unique to multi-Mb MRAM design, including a novel bootstrapped write driver circuit. Hardware results are presented.     

A high-speed 128-kb MRAM core for future universal memory applications

A 128-kb magnetic random access memory (MRAM) test chip has been fabricated utilizing, for the first time, a 0.18-/spl mu/m V/sub DD/=1.8 V logic process technology with Cu metallization. The presented design uses a 1.4-/spl mu/m/sup 2/ one-transistor/one-magnetic tunnel junction (1T1MTJ) cell and features a symmetrical high-speed sensing architecture using complementary reference cells and configurable load devices. Extrapolations from test chip measurements and circuit assessments predict a 5-ns random array read access time and random write operations with <5-ns write pulse width.     

Nido-Hydroborate-Based Electrolytes for All-Solid-State Lithium Batteries

Hydroborate-based solid electrolytes have recently been successfully employed in high voltage, room temperature all-solid-state sodium batteries. The transfer to analogous lithium systems has failed up to now due to the lower conductivity of the corresponding lithium compounds and their high cost. Here LiB₁₁H₁₄ nido-hydroborate as a cost-effective building block and its high-purity synthesis is introduced. The crystal structures of anhydrous LiB₁₁H₁₄ as well as of LiB₁₁H₁₄-based mixed-anion solid electrolytes are solved and high ionic conductivities of 1.1 × 10⁻⁴ S cm⁻¹ for Li₂(B₁₁H₁₄)(CB₁₁H₁₂) and 1.1 × 10⁻³ S cm⁻¹ for Li₃(B₁₁H₁₄)(CB₉H₁₀)₂ are obtained, respectively. LiB₁₁H₁₄ exhibits an oxidative stability limit of 2.6 V versus Li⁺/Li and the proposed decomposition products are discussed based on density functional theory calculations. Strategies are discussed to improve the stability of these compounds by modifying the chemical structure of the nido-hydroborate cage. Galvanostatic cycling in symmetric cells with two lithium metal electrodes shows a small overpotential increase from 22.5 to 30 mV after 620 h (up to 0.5 mAh cm⁻²), demonstrating that the electrolyte is compatible with metallic anodes. Finally, the Li₂(B₁₁H₁₄)(CB₁₁H₁₂)  electrolyte is employed in a proof-of-concept half cell with a TiS₂ cathode with a capacity retention of 82% after 150 cycles at C/5.     

The effect of heat treatment on the microfibrillar network of poly(p-phenylene benzobisthiazole)

Materials exhibiting exceptional mechanical properties can be fabricated from rigid polymers. In a spinning process, an oriented solution is solidified by the action of a nonsolvent, which induces crystallization of an oriented rigid polymer. Drying and heat treatment result in the final material having the desired properties. The effect of heat treatment on the morphology of poly(p-phenylene benzobisthiazole) (PBZT) films was studied by measurements of small-angle X-ray scattering (SAXS) and wide-angle X-ray diffraction (WAXD). Films were formed by coagulation in water. The wet films were dried with supercritical CO₂ to maintain an open network structure. Coagulation in water resulted in formation of microfibrils having diameter of ∼9 nm. Heat-treatment at 600°C caused significant coalescence of microfibrils. The crystallite size was increased by heat treatment from a value that is smaller than the microfibrillar diameter indicating defects in chain packing, to a value comparable to the microfibrillar diameter.     

Biocompatibility of Lithium Disilicate and Zirconium Oxide Ceramics with Different Surface Topographies for Dental Implant Abutments

Gingivafibroblasts were cultured on lithium disilicate, on zirconia dioxide, and on titanium with two different surface roughnesses (0.2 µm and 0.07 µm); Proliferation (MTT), Living/Dead staining, cytotoxicity (LDH), proliferation (FGF2), and inflammation (TNFα) were analyzed after 1 day and 21 days. Furthermore, alteration in cell morphology (SEM) was analyzed. The statistical analysis was performed by a Kruskal–Wallis test. The level of significance was set at p < 0.05. There were no distinct differences in cellular behavior between the tested roughness. There were slight differences between tested materials. Cells grown on zirconia dioxide showed higher cytotoxic effects. Cells grown on lithium disilicate showed less expression of TNFα compared to those grown on zirconia dioxide or titanium. These effects persisted only during the first time span. The results indicate that the two tested high-strength ceramics and surface properties are biologically suitable for transmucosal implant components. The findings may help clinicians to choose the most appropriate biomaterial as well as the most appropriate surface treatment to use in accordance with specific clinical dental applications.     

Efficient phage display of intracellularly folded proteins mediated by the TAT pathway

Phage display with filamentous phages is widely applied and well developed, yet proteins requiring a cytoplasmic environment for correct folding still defy attempts at functional display. To extend applicability of phage display, we employed the twin-arginine translocation (TAT) pathway to incorporate proteins fused to the C-terminal domain of the geneIII protein into phage particles. We investigated functionality and display level of fluorescent proteins depending on the translocation pathway, which was the TAT, general secretory (SEC) or signal recognition particle (SRP) pathway mediated by the TorA, PelB or DsbA signal sequences, respectively. Importantly, for green fluorescent protein, yellow fluorescent protein and cyan fluorescent protein, only TAT, but not SEC or SRP, translocation led to fluorescence of purified phage particles, although all three proteins could be displayed regardless of the translocation pathway. In contrast, the monomeric red fluorescent protein mCherry was functionally displayed regardless of the translocation pathway. Hence, correct folding and fluorophor formation of mCherry is not limited to the cytosol. Furthermore, we successfully displayed firefly luciferase as well as an 83 kDa argonaute protein, both containing free cysteines. This demonstrates broad applicability of the TAT-mediated phagemid system for the display of proteins requiring cytoplasmic factors for correct folding and should prove useful for the display of proteins requiring incorporation of co-factors or oligomerization to gain function.     

Knowledge‐Based Conceptual Synthesis of Industrial‐Scale Downstream Processes for Biochemical Products

A generic, knowledge‐based guideline assisting downstream process synthesis for biochemical products is presented. It offers process designers a structured process design methodology supporting them in capturing potentially relevant information, which might be beyond their expertise. The guideline is based on heuristic knowledge which was collected, structured in a generic way, and clearly represented. The generation of alternative downstream routes as starting points for experiments, simulation, and cost calculation is hereby accelerated. The application of the guideline is demonstrated on the example of penicillin V downstream processing from fermentation broth.