New Perspectives in Reducing Amyloid Aggregation and Toxicity

One of the fundamental biochemical characteristics of Alzheimer′s Disease (AD) is the intercellular accumulation of amyloid beta (Aβ) peptide plaques in the brain. Although there is not yet a cure for AD, major efforts have been made to identify antiamyloidogenic agents and therapeutic strategies to treat this disease and related conditions. Our group focuses on inhibiting the aggregation and toxicity of Aβ using two distinct approaches. The first involves covalently attaching the sequence-derived core amyloidogenic amino acid fragment KLVFF to the surfaces of serum albumin microspheres. These particles bind soluble Aβ with high affinity, inhibit its aggregation, reduce its toxicity, and decrease the inflammation induced by its aggregates. Microsphere-bound Aβ stimulates microglia and is phagocytosed via a different mechanism from that used for Aβ removal, so enabling its clearance even by defective cells. Our second approach utilizes self-assembled cyclic D,L-α-peptides as conformational mimics of the amyloid fibril architecture that inhibit the aggregation and cytotoxicity of Aβ. Here, we review these strategies and their mechanisms of action.     

复混肥料中硼含量测定方法的改进

本文提出了复混肥料中微量元素硼的化学分析方法,采用甘露醇强化硼酸后滴定的方法,其测定结果与推荐性国标相符,可以用来指导生产。     

Membrane-induced step in the activation of Sendai virus fusion protein

Peptides derived from conserved heptad-repeat regions of several viruses have been shown recently to inhibit virus-cell fusion. To find out their possible role in the fusion process, two biologically active heptad-repeat segments of the fusion protein (F) of Sendai virus, SV-150 (residues 150-186), and SV-473 (residues 473-495) were synthesized, fluorescently labeled and spectroscopically characterized for their structure and organization in solution and within the membrane. SV-150 was found to be 50-fold less active than SV-473 in inhibiting Sendai virus-cell fusion. Circular dichroism (CD) spectroscopy revealed that in aqueous solution, the peptides are self-associated and adopt low alpha-helical structure. However, when the two peptides are mixed together, their alpha-helical content significantly increases. Fluorescence studies, CD, and polarized attenuated total reflection infrared (ATR-FTIR) spectroscopy showed that both peptides, alone or as a complex, bind strongly to negatively charged and zwitterionic phospholipid membranes, dissociate therein into alpha-helical monomers, but do not perturb the lipid packing of the membrane. The ability of the peptides to interact with each other in solution may be correlated with antiviral activity, whereas their ability to interact with the membrane, together with their location near the fusion peptide and the transmembrane domain, suggests a revision to the currently accepted model for viral-induced membrane fusion. In the revised model, in the sequence of events associated with viral entry, the two heptad-repeat sequences may assist in bringing the viral and cellular membranes closer, thus facilitating membrane fusion.     

Electromagnetic impedance tomography (EMIT): a new method for impedance imaging

We propose a new impedance imaging method, electromagnetic impedance tomography (EMIT), in which the boundary electric potential measurements in electrical impedance tomography (EIT) are augmented by measurements of the exterior magnetic field induced by the currents excited in the object by the standard EIT procedures. These magnetic measurements can be obtained reliably and inexpensively by simple pickup coils located around the imaged cross section. We derive expressions for the forward problem and for the Jacobian of the measurements, and propose an iterative reconstruction algorithm using a squared error cost function. The performance of EMIT and EIT is compared in numerical simulations using a finite-element model for the conductivity distribution of several phantoms. Evaluation of the rank and condition of the Jacobian demonstrates that the additional magnetic measurements provided by a few pickup coils in EMIT turn an underdetermined EIT problem into a well-posed one with reasonable condition, or significantly improve the conditioning of the EIT problem when it is already fully determined. Reconstructions of various phantoms reveal that EMIT provides particularly significant visual and quantitative improvement (threefold to tenfold reduction in the root-mean-squared error) in the sensitivity at the center of the object, which is the area most difficult to image using EIT.     

Learning Changing Concepts by Exploiting the Structure of Change

This paper examines learning problems in which the target function is allowed to change. The learner sees a sequence of random examples, labelled according to a sequence of functions, and must provide an accurate estimate of the target function sequence. We consider a variety of restrictions on how the target function is allowed to change, including infrequent but arbitrary changes, sequences that correspond to slow walks on a graph whose nodes are functions, and changes that are small on average, as measured by the probability of disagreements between consecutive functions. We first study estimation, in which the learner sees a batch of examples and is then required to give an accurate estimate of the function sequence. Our results provide bounds on the sample complexity and allowable drift rate for these problems. We also study prediction, in which the learner must produce online a hypothesis after each labelled example and the average misclassification probability over this hypothesis sequence should be small. Using a deterministic analysis in a general metric space setting, we provide a technique for constructing a successful prediction algorithm, given a successful estimation algorithm. This leads to sample complexity and drift rate bounds for the prediction of changing concepts.     

Diagnostic criteria for latex allergy

The author has made an observation which seems to illustrate his proposition perfectly. A patient who was the victim of many acute episodes of rhino-conjunctivitis and severe Quincke's oedema has found benefit from two specialised assessments which established a diagnosis of allergy only to latex. The key to this diagnosis rested on unusual reasoning based on a search for a sufficiently "virulent" allergen to be responsible for the severity of the clinical signs. This idea and recent understanding of crossed allergy materials should aid detection of subjects who are allergic to natural latex.     

Elementary approximation algorithms for prize collecting Steiner tree problems

This paper deals with approximation algorithms for the prize collecting generalized Steiner forest problem, defined as follows. The input is an undirected graph G=(V,E), a collection T={T₁,…,T_k}, each a subset of V of size at least 2, a weight function , and a penalty function . The goal is to find a forest F that minimizes the cost of the edges of F plus the penalties paid for subsets T_i whose vertices are not all connected by F. Our main result is a -approximation for the prize collecting generalized Steiner forest problem, where n2 is the number of vertices in the graph. This obviously implies the same approximation for the special case called the prize collecting Steiner forest problem (all subsets T_i are of size 2). The approximation algorithm is obtained by applying the local ratio method, and is much simpler than the best known combinatorial algorithm for this problem.Our approach gives a -approximation for the prize collecting Steiner tree problem (all subsets T_i are of size 2 and there is some root vertex r that belongs to all of them). This latter algorithm is in fact the local ratio version of the primal-dual algorithm of Goemans and Williamson [M.X. Goemans, D.P. Williamson, A general approximation technique for constrained forest problems, SIAM Journal on Computing 24 (2) (April 1995) 296–317]. Another special case of our main algorithm is Bar-Yehuda's local ratio -approximation for the generalized Steiner forest problem (all the penalties are infinity) [R. Bar-Yehuda, One for the price of two: a unified approach for approximating covering problems, Algorithmica 27 (2) (June 2000) 131–144]. Thus, an important contribution of this paper is in providing a natural generalization of the framework presented by Goemans and Williamson, and later by Bar-Yehuda.     

Effects of three cellulose gums on the texture profile and sensory properties of low fat frankfurters

Composition, textural, viscoelastic, hydration, colour, and sensory attributes of regular and low fat pork/beef frankfurters with and without cellulose gums (carboxymethyl cellulose (CMC) and two types of microcrystalline cellulose (MCC-I and II)) were investigated. Fat was replaced with water in the low fat products. Moisture loss during cooking was reduced in low fat products from 10 to 6% because of the addition of CMC; however, both MCC increased moisture loss by 12–15%. CMC addition also increased the amount of free water. The high fat product was lighter (higher 'L') than the reduced fat frankfurters; gums did not appreciably change the colour. The viscoelastic properties (relaxation time, elastic moduli) were unaffected by the changes in fat level. Product hardness, brittleness, gumminess and chewiness increased with the decrease in fat level. MCC-II improved the textural properties of the low fat product to those of the high fat product. Sensory panel results indicated a decrease in tenderness with low fat and this was not improved by MCC-II. Overall, acceptability scores indicated that all the products (high and low fat) were acceptable.     

Binding Energies of Aromatic 1:1 Hetero-Clusters in a Supersonic Jet

Methods used to experimentally estimate the binding energies of van der Waals clusters containing an aromatic molecule are surveyed. These include microwave and infrared absorption spectroscopies, single and two photon ionization, dispersed fluorescence, and stimulated emission pumping. The problems encountered in the application of these methods are briefly discussed, and prospects for the firm establishment of the binding energies are assessed. Although the present database is too small for firm conclusions, methods based on dispersed fluorescence (i.e., probing the excited state surface) tend to yield lower values for argon adducts than those based on ionization, probing the ground state, or ionic surfaces. A mechanism that may account for this tendency is proposed, and further experiments are proposed to test it.     

Two phase biomass air-steam gasification model for fluidized bed reactors: Part II—model sensitivity

A sensitivity analysis was performed on the two phase biomass gasification model developed by Sadaka et al. (Biomass Bioenergy) to test its response to variations in three operating parameters (fluidization velocity, steam flow rate and biomass to steam ratio). The model performance criteria included bed temperature, gas compositions, higher heating value and gas production rate. The results showed that the model was sensitive to changes in all operating parameters. The temperatures of the reactor were more influenced by changes in the steam flow rate than those of fluidization velocity and biomass to steam ratio. The steam flow rate has the most effect on the mole fractions of CH₄, and CO₂ followed by the biomass to steam ratio and then the fluidization velocity. In the case of H₂, and CO the biomass to steam ratio has the most effect on their mole fractions followed by the steam flow rate and then fluidization velocity. The fluidization velocity has the most effect on the mole fraction of N₂. The biomass to steam ratio has the most effect on the gas higher heating value and the gas production rate.