Small Molecule Receptor Binding Inhibitors with In Vivo Efficacy against Botulinum Neurotoxin Serotypes A and E

Botulinum neurotoxins (BoNTs) are the most poisonous substances in nature. Currently, the only therapy for botulism is antitoxin. This therapy suffers from several limitations and hence new therapeutic strategies are desired. One of the limitations in discovering BoNT inhibitors is the absence of an in vitro assay that correlates with toxin neutralization in vivo. In this work, a high-throughput screening assay for receptor-binding inhibitors against BoNT/A was developed. The assay is composed of two chimeric proteins: a receptor-simulating protein, consisting of the fourth luminal loop of synaptic vesicle protein 2C fused to glutathione-S-transferase, and a toxin-simulating protein, consisting of the receptor-binding domain of BoNT/A fused to beta-galactosidase. The assay was applied to screen the LOPAC1280 compound library. Seven selected compounds were evaluated in mice exposed to a lethal dose of BoNT/A. The compound aurintricarboxylic acid (ATA) conferred 92% protection, whereas significant delayed time to death (p < 0.005) was observed for three additional compounds. Remarkably, ATA was also fully protective in mice challenged with a lethal dose of BoNT/E, which also uses the SV2 receptor. This study demonstrates that receptor-binding inhibitors have the potential to serve as next generation therapeutics for botulism, and therefore the assay developed may facilitate discovery of new anti-BoNT countermeasures.     

Studying different dimensions of amylose–long chain fatty acid complexes: Molecular, nano and micro level characteristics

Recently amylose inclusion complexes, or V-amylose, have drawn much attention as a possible vehicle for the nanoencapsulation of unsaturated fatty acids. This study aimed to study three different structural strata of V-amylose, the molecular attributes using XRD, DSC and ¹³C CP/MAS NMR and the nanostructures using SAXS. Using these methods it was noted that decreased degree of fatty acid unsaturation induces the formation of more organized and well defined structures. Specifically, calculations based on SAXS data show that regardless of the crystallization temperature saturated SA yields the highest values for parameters like average crystalline lamellar thickness (φ = 0.26) and characteristic particle dimension (R_g = 9.6). SEM shows this trend extends even into the microscopic level. Overall, this study shows that in the case of long chain fatty acids, increased fatty acid unsaturation impairs the structure of amylose inclusion complexes.     

A 70 nm 16 Gb 16-Level-Cell NAND flash Memory

A 16 Gb 16-level-cell (16LC) NAND flash memory using 70 nm design rule has been developed . This 16LC NAND flash memory can store 4 bits in a cell which enabled double bit density comparing to 4-level-cell (4LC) NAND flash, and quadruple bit density comparing to single-bit (SLC) NAND flash memory with the same design rule. New programming method suppresses the floating gate coupling effect and enabled the narrow distribution for 16LC. The cache-program function can be achievable without any additional latches. Optimization of programming sequence achieves 0.62 MB/s programming throughput. This 16-level NAND flash memory technology reduces the cost per bit and improves the memory density even more.     

Medical applications of infrared transmitting silver halide fibers

It is clear that infrared transmitting fibers of high quality, with many uses in IR optical systems, can be fabricated from silver halide crystals. The process requires ultrapure starting material and control of extrusion parameters such as temperature and pressure. Under laboratory conditions, fibers have been produced that are usefully transparent from 2-25 μm and have a loss coefficient of less than O.2 dB/m at 10.6 μm. These fibers are flexible, and can be repeatedly bent into small radii circles without loss of transmission. The material is nontoxic, insoluble in water, and has an adequate shelf life. It is also of low cost and can be considered as a "disposable" if necessary. Lengths of several meters have been extruded, and with larger preforms and couplers, length is not a limitation. Further, much is now known of the optical and mechanical properties, and the possibility of laser-fibers is envisaged. These MIR fibers will be useful in many medical procedures, such as laser surgery, noncontact fiber-optic thermometry, and fiber-optic spectrometry. Fiber-optic medical tools based on MIR fibers will be used for diagnosis, therapy, and surgery in minimally invasive systems     

The Pros and Cons of Temporally Near and Distant Action.

The present research demonstrated that in considering an action, considerations against (con) the action tend to be subordinate to considerations in favor of (pro) the action in that cons are considered only if the level of pros is sufficient, whereas pros are considered independent of the level of cons (Studies 1A and IB). The authors therefore concluded that pros constitute a higher construal level than cons and predict, on the basis of temporal construal processes (Y. Trope & N. Liberman. 2003). that pros would be more salient in making decisions for the more distant future, whereas the reverse should hold for cons. As predicted, participants generated more pros and fewer cons toward new exam procedures (Study 2), public policies (Study 3), and personal and interpersonal behaviors (Studies 4-6) that were expected to take place in the more distant future. This research also examined the limiting conditions and the evaluative consequences of these shifts. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

On the Limitations of Universally Composable Two-Party Computation Without Set-Up Assumptions

The recently proposed universally composable security framework for analyzing security of cryptographic protocols provides very strong security guarantees. In particular, a protocol proven secure in this framework is guaranteed to maintain its security even when run concurrently with arbitrary other protocols. It has been shown that if a majority of the parties are honest, then universally composable protocols exist for essentially any cryptographic task in the plain model (i.e., with no set-up assumptions beyond that of authenticated communication). When honest majority is not guaranteed, general feasibility results are known only when given a trusted set-up, such as in the common reference string model. Only little was known regarding the existence of universally composable protocols in the plain model without honest majority, and in particular regarding the important special case of two-party protocols. We study the feasibility of universally composable two-party function evaluation in the plain model. Our results show that in this setting, very few functions can be securely computed in the framework of universal composability. We demonstrate this by providing broad impossibility results that apply to large classes of deterministic and probabilistic functions. For some of these classes, we also present full characterizations of what can and cannot be securely realized in the framework of universal composability. Specifically, our characterizations are for the classes of deterministic functions in which (a) both parties receive the same output, (b) only one party receives output, and (c) only one party has input.     

Success on a practical driver's license test with and without the presence of another testee

The present study examined whether performance in practical driving tests differed when individuals were tested with and without the presence of another testee. In addition, this study examined whether such differences were dependent on the sex of the tested person, on that of the observer testee, and on the order of tests. It was found that for both males and females, a greater proportion of drivers who were tested alone passed the test as compared to drivers who were tested in pairs. Additionally, proportionately more males than females passed the driving test. Only for males was performance also dependent on the gender of the other tested individual. A greater proportion of males who were tested with an accompanying female passed the test than males who were tested with an accompanying male. These results are discussed in relation to social facilitation, gender differences in driving performance, and differences in testing procedures.     

On-line predictive model for disassembly process planning adaptation

This paper presents an on-line predictive model for disassembly process adaptation. The prediction enables a planner to adapt the process plan based on the condition of the product (e.g., degree of rustiness, deformation) during process execution. This model tries to correlate the product physical condition, used as an explanatory variable, with the component value and disassembly cost, the response variables. The core of the approach is based on an inference engine that used a kernel regression. A simple methodology for integrating the predictive planner in a disassembly system is presented and exemplified by a case study of the disassembly of a ratio.     

A Bis-Zn2+-Pyridyl-Salen-Type Complex Conjugated to the ATP Aptamer: An ATPase-Mimicking Nucleoapzyme

Catalytic nucleic acids consisting of a bis-Zn²⁺-pyridyl-salen-type ([di-Zn^II 3,5 bis(pyridinylimino) benzoic acid]) complex conjugated to the ATP aptamer act as ATPase-mimicking catalysts (nucleoapzymes). Direct linking of the Zn²⁺ complex to the 3′- or 5′-end of the aptamer (nucleoapzymes I and II) or its conjugation to the 3′- or 5′-end of the aptamer through bis-thymidine spacers (nucleoapzymes III and IV) provided a set of nucleoapzymes exhibiting variable catalytic activities. Whereas the separated bis-Zn²⁺-pyridyl-salen-type catalyst and the ATP aptamer do not show any noticeable catalytic activity, the 3′-catalyst-modified nucleoapzyme (nucleoapzyme IV) and, specifically, the nucleoapzyme consisting of the catalyst linked to the 3′-position through the spacer (nucleoapzyme III) reveal enhanced catalytic features in relation to the analogous nucleoapzyme substituted at the 5′-position (k_cat=4.37 and 6.88 min⁻¹, respectively). Evaluation of the binding properties of ATP to the different nucleoapzyme and complementary molecular dynamics simulations suggest that the distance separating the active site from the substrate linked to the aptamer binding site controls the catalytic activities of the different nucleoapzymes.     

Conservative Visibility and Strong Occlusion for Viewspace Partitioning of Densely Occluded Scenes

Computing the visibility of out-door scenes is often much harder than of in-door scenes. A typical urban scene, for example, is densely occluded, and it is effective to precompute its visibility space, since from a given point only a small fraction of the scene is visible. The difficulty is that although the majority of objects are hidden, some parts might be visible at a distance in an arbitrary location, and it is not clear how to detect them quickly. In this paper we present a method to partition the viewspace into cells containing a conservative superset of the visible objects. For a given cell the method tests the visibility of all the objects in the scene. For each object it searches for a strong occluder which guarantees that the object is not visible from any point within the cell. We show analytically that in a densely occluded scene, the vast majority of objects are strongly occluded, and the overhead of using conservative visibility (rather than visibility) is small. These results are further supported by our experimental results. We also analyze the cost of the method and discuss its effectiveness.